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    INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY


    ENVIRONMENTAL HEALTH CRITERIA 133





    FENITROTHION









    This report contains the collective views of an international group of
    experts and does not necessarily represent the decisions or the stated
    policy of the United Nations Environment Programme, the International
    Labour Organisation, or the World Health Organization.

    First draft prepared by Dr. J. Sekizawa
    (National Institute of Hygienic Sciences, Japan)
    and Dr. M. Eto (Kyushu University, Japan) with
    the assistance of Dr. J. Miyamoto and
    Dr. M. Matsuo (Sumitomo Chemical Company)

    Published under the joint sponsorship of
    the United Nations Environment Programme,
    the International Labour Organisation,
    and the World Health Organization

    World Health Orgnization
    Geneva, 1992


         The International Programme on Chemical Safety (IPCS) is a
    joint venture of the United Nations Environment Programme, the
    International Labour Organisation, and the World Health
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    development of know-how for coping with chemical accidents,
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    promotion of research on the mechanisms of the biological action of
    chemicals.

    WHO Library Cataloguing in Publication Data

    Fenitrothion.

        (Environmental health criteria ; 133)

        1.Fenitrothion - adverse effects   2.Fenitrothion - toxicity
        3.Environmental exposure   I.Series

        ISBN 92 4 157133 0        (NLM Classification: WA 240)
        ISSN 0250-863X

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    letters.

    CONTENTS

         ENVIRONMENTAL HEALTH CRITERIA FOR FENITROTHION

    1. SUMMARY AND EVALUATION, CONCLUSIONS AND RECOMMENDATIONS

         1.1. Summary and evaluation
              1.1.1. Exposure
              1.1.2. Uptake, metabolism, and excretion
              1.1.3. Effects on organisms in the environment
              1.1.4. Effects on experimental animals and
                         in vitro test systems
              1.1.5. Effects on human beings
         1.2. Conclusions
         1.3. Recommendations

    2. IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS

         2.1. Identity
         2.2. Physical and chemical properties
         2.3. Conversion factors
         2.4. Analytical methods

    3. SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

         3.1. Natural occurrence
         3.2. Man-made sources
              3.2.1. Production
              3.2.2. Uses

    4. ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

         4.1. Transport and distribution between media
         4.2. Abiotic and biotic transformation
              4.2.1. Abiotic transformation
                   4.2.1.1   Thermal degradation
                   4.2.1.2   Photolysis in air
                   4.2.1.3   Hydrolysis and photolysis
                             in water
                   4.2.1.4   Photolysis on soil
              4.2.2. Biotransformation
                   4.2.2.1   Biodegradation in soil
                   4.2.2.2   Biodegradation and bioaccumulation
                             in organisms
                   4.2.2.3   Abiotic and biological
                             degradation in/on plants

    5. ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

         5.1. Environmental levels
              5.1.1. Air
              5.1.2. Water
              5.1.3. Soil
              5.1.4. Food
         5.2. Human exposure
              5.2.1. Food

    6. KINETICS AND METABOLISM

         6.1. Absorption, distribution, metabolic
              transformation, elimination, and excretion
         6.2. Retention and turnover

    7. EFFECTS ON EXPERIMENTAL ANIMALS AND  IN VITRO TEST SYSTEMS

         7.1. Single exposure
         7.2. Skin and eye irritation; skin sensitization
              7.2.1. Skin and eye irritation
              7.2.2. Skin sensitization
         7.3. Short-term studies
              7.3.1. Rat
              7.3.2. Dog
              7.3.3. Rabbit
              7.3.4. Guinea-pig
         7.4. Long-term and carinogenicity studies
         7.5. Reproductive effects, embryotoxicity, and
              teratogenicity
              7.5.1. Reproductive effects
              7.5.2. Embryotoxicity and teratogenicity
         7.6. Mutagenicity
         7.7. Neurotoxicity
         7.8. Effects on hepatic enzymes
         7.9. Effects on hormonal balance
         7.10. Toxicity of metabolites and the S-isomer
         7.11. Factors modifying toxicity
         7.12. Mechanism of toxicity - mode of action
              7.12.1. Mode of action
              7.12.2. Selective toxicity
              7.12.3. Potentiation of toxicity of
                        other chemicals

    8. EFFECTS ON MAN

         8.1. General population exposure
              8.1.1. Acute toxicity
              8.1.2. Poisoning incidents

              8.1.3. Contact dermatitis
              8.1.4. Possible links with Reye's syndrome
         8.2. Occupational exposure

    9. EFFECTS ON ORGANISMS IN THE ENVIRONMENT

         9.1. Microorganisms and algae
         9.2. Aquatic organisms
              9.2.1. Fish
              9.2.2. Invertebrates
              9.2.3. Amphibians and arthropods
         9.3. Terrestrial organisms
              9.3.1. Terrestrial invertebrates
              9.3.2. Birds
              9.3.3. Mammals

    10. PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

    REFERENCES

    ANNEX I. TREATMENT OF ORGANOPHOSPHATE INSECTICIDE POISONING IN MAN

    ANNEX II. NO-OBSERVED-EFFECT LEVELS IN PLASMA, RED BLOOD CELLS, AND
              BRAIN ChE, IN ANIMALS TREATED WITH FENITROTHION

    RESUME ET EVALUATION, CONCLUSIONS ET RECOMMANDATIONS

    RESUMEN Y EVALUACION, CONCLUSIONES ET RECOMENDACIONES
    

    WHO TASK GROUP ON ENVIRONMENTAL HEALTH CRITERIA FOR TRICHLORFON
    AND FENITROTHION


    Members

    Dr   V. Benes, Department of Toxicology and Reference Laboratory,
         Institute of Hygiene and Epidemiology, Prague, Czech and Slovak
         Federal Republic

    Dr   C. Carrington, Division of Toxicological Review and Evaluation,
         Food and Drug Administration, Washington, DC, USA  (Joint
         Rapporteur)

    Dr   W. Dedek, Department of Chemical Toxicology, Academy of 
         Sciences, Leipzig, Germany

    Dr   S. Dobson, Institute of Terrestrial Ecology, Monks Wood 
         Experimental Station, Huntingdon, United Kingdom

    Dr   D.J. Ecobichon, Department of Pharmacology and  Therapeutics,
         McGill University, Montreal, Canada

    Dr   M. Eto, Department of Agricultural Chemistry, Kyushu 
         University, Fukuoka-shi, Japan  (Vice-Chairman)

    Dr   Bo Holmstedt, Department of Toxicology, Karolinska Institute,
         Stockholm, Sweden

    Dr   S.K. Kashyap, National Institute of Occupational Health, 
         Ahmedabad, India

    Dr   J. Miyamoto, Takarazuka Research Centre, Hyogo, Japan

    Dr   H. Spencer, United States Environmental Protection Agency, 
         Washington, DC, USA (Chairman)

    Dr   M. Takeda, National Institute of Hygienic Sciences, Tokyo, 
         Japan

    Observers

    Dr   M. Matsuo, Biochemistry and Toxicology Laboratory, Sumitomo
         Chemical Co. Ltd, Osaka-shi, Japan (representing GIFAP)

    Secretariat

    Dr   K.W. Jager, IPCS, World Health Organization, Geneva, 
         Switzerland  (Secretary)

    Dr   J. Sekizawa, National Institute of Hygienic Sciences, Tokyo, 
         Japan  (Joint Rapporteur)

    NOTE TO READERS OF THE CRITERIA DOCUMENTS

         Every effort has been made to present information in the
    criteria documents as accurately as possible without unduly delaying
    their publication. In the interest of all users of the Environmental
    Health Criteria documents, readers are kindly requested to
    communicate any errors that may have occurred to the Director of the
    International Programme on Chemical Safety, World Health
    Organization, Geneva, Switzerland, in order that they may be
    included in corrigenda.

                                  *   *   *

         A detailed data profile and a legal file can be obtained from
    the International Register of Potentially Toxic Chemicals, Palais
    des Nations, 1211 Geneva 10, Switzerland (Telephone No. 7988400 or
    7985850).

    ENVIRONMENTAL HEALTH CRITERIA FOR FENITROTHION

         A WHO Task Group on Environmental Health Criteria for
    Trichlorfon and Fenitrothion met at the World Health Organization,
    Geneva, from 10 to 14 December 1990. Dr K.W. Jager, IPCS, welcomed
    the participants on behalf of Dr M. Mercier, Manager of the IPCS,
    and the three IPCS cooperating organizations (UNEP/ILO/WHO). The
    Group reviewed and revised the draft and made an evaluation of the
    risks for human health and the environment from exposure to
    fenitrothion.

         The first draft was prepared by Dr J. Sekizawa of the National
    Institute of Hygienic Sciences of Japan in collaboration with Dr J.
    Miyamoto and Dr M. Matsuo of Sumitomo Chemical Company, and Dr M.
    Eto of Kyushu University. Dr J. Sekizawa also prepared the second
    draft, incorporating comments received following circulation of the
    first drafts to the IPCS contact points for Environmental Health
    Criteria.

         Dr K.W. Jager of the IPCS Central Unit was responsible for the
    scientific content and Mrs M.O. Head of Oxford for the editing.

         The fact that Sumitomo Chemical Company Limited, Japan
    (trichlorfon and fenitrothion) and Bayer AG, Germany (trichlorfon)
    made available to the IPCS and the Task Group their proprietary
    toxicological information on the products under discussion is
    gratefully acknowledged. This allowed the Task Group to make its
    evaluation on the basis of more complete data.

         The efforts of all who helped in the preparation and
    finalization of the document are gratefully acknowledged.

    1. SUMMARY AND EVALUATION, CONCLUSIONS AND RECOMMENDATIONS

    1.1  Summary and evaluation

    1.1.1  Exposure

         Fenitrothion is an organophosphorus insecticide that has been
    in use since 1959. It is used in agriculture to control insects on
    rice, cereals, fruits, vegetables, stored grains, and cotton. It is
    also used to control insects in forests and for fly, mosquito, and
    cockroach control in public health programmes. It is formulated as
    emulsifiable concentrates, ultra-low-volume concentrates, powders,
    granules, dusts, oil-based sprays, and in combination with other
    pesticides. Between 15 000 and 20 000 tons of fenitrothion are
    produced per year.

         Fenitrothion enters the air by volatilization from contaminated
    surfaces and may drift beyond the intended target area during
    spraying. It leaches very slowly from most soils, but some run-off
    can be expected.

         Fenitrothion is degraded by photolysis and hydrolysis. In the
    presence of ultraviolet radiation (UVR) or sunlight, the half-life
    of fenitrothion in water is less than 24 h. The presence of
    micro-flora may also accelerate degradation. In the absence of
    sunlight or microbial contamination, fenitrothion is stable in
    water. In soil, biodegradation is the primary route of degradation,
    though photolysis may also play a role.

         Airborne concentrations of fenitrothion may be as high as 5
    µg/m3 directly after spraying, but may decrease markedly with time
    and distance from the application site. Levels in water may be as
    high as 20 µg/litre, but decrease rapidly.

         Bioconcentration factors for fenitrothion with continuing
    exposure have been estimated to range from 20 to 450 for a number of
    different aquatic species.

         Levels of fenitrothion residues in fruits, vegetables, and
    cereal grains may range from 0.001 to 9.5 mg/kg immediately after
    treatment, but decline rapidly, with a half-life of 1-2 days.

    1.1.2  Uptake, metabolism, and excretion

         Fenitrothion is rapidly absorbed from the intestinal tract of
    experimental animals and distributed to various body tissues. The
    half-life for the dermal absorption of fenitrothion in the monkey
    was 15-17 h. Fenitrothion has been shown to be metabolized through
    the major pathways of  O-demethylation and by cleavage of the
    P-O-aryl bond. The nitro group of fenitrothion is reduced by
    intestinal microorganisms, in ruminants only. The major route of

    elimination is via the urine, most of the metabolites being
    eliminated within 2-4 days in the rat, guinea-pig, mouse, and dog. 
    The major metabolites reported are demethyl fenitrothion, demethyl
    fenitrooxon, dimethylphosphorothioic acid and dimethyl phosphoric
    acid, and 3-methyl-4-nitrophenol and its conjugates. Differences in
    the composition of metabolites found among most laboratory test
    animals and between sexes of the same species appear to be mainly
    quantitative in nature. Only rabbits appear to excrete fenitrooxon
    and aminofenitrooxon in small, though quantifiable, amounts in the
    urine.

         Evidence from studies on rabbits and dogs showed preferential
    deposition of fenitrothion in the adipose tissue.

         Residues found in the milk of cows following exposure to
    fenitrothion were not detected two days later.

         Though fenitrothion is readily absorbed via the oral route, it
    is rapidly metabolized and excreted and is unlikely to remain in the
    body for any prolonged period.

    1.1.3  Effects on organisms in the environment

         The concentrations of fenitrothion that are likely to be found
    in the environment do not have any effects on microorganisms in soil
    or water.

         Fenitrothion is highly toxic for aquatic invertebrates in both
    freshwater and seawater with LC50 values of a few µg/litre for
    most species tested. The no-observed-effect level (NOEL) for
    Daphnia, in 48-h tests, was < 2 µg/litre; in life-cycle tests, a
    maximum acceptable toxicant concentration (MATC) of 0.14 µg per
    litre was established. Field observations and studies on
    experimental ponds have shown effects on populations of
    invertebrates. However, most of the changes observed were temporary,
    even at concentrations considerably higher than those likely to
    occur after recommended usage.

         Fish are less sensitive to fenitrothion than invertebrates and
    show 96-h LC50 values in the range of 1.7-10 mg/litre. The most
    sensitive life stage is the early larva. Long-term studies have
    established a MATC at, or above, 0.1 mg/litre for 2 species of
    freshwater fish. Field studies after application of fenitrothion to
    forests showed no effects on wild populations of fish or on the
    survival of caged test fish with measured water concentrations of
    fenitrothion of up to 0.019 mg/litre. Repeated application of
    fenitrothion to forests had no effect on fish populations.

         In laboratory tests, freshwater molluscs showed LC50 values
    in the range 1.2 to 15 mg/litre. No field effects were seen after
    forest spraying at 140 g/ha.

         Fenitrothion is highly toxic for bees (topical LD50,
    0.03-0.04 µg/bee). Field effects have been reported with high
    numbers of honey bees and other species killed locally. However, the
    total numbers killed represented only a small percentage of the hive
    population.

         Acute oral LD50 values for birds range between 25 and 1190
    mg/kg body weight and most 8-day dietary LC50s exceeded 5000 mg/kg
    diet. NOEL values for reproduction were 10 mg/kg body weight for the
    quail and 100 mg/kg body weight for the mallard. Song-bird deaths
    occurred soon after application of fenitrothion at a rate of 280
    g/ha and were markedly increased at 560 g/ha for species living in
    the forest canopy. After spraying at 420 g/ha followed by 210 g/ha a
    few days later, the reproductive success of White-throated Sparrows
    was reduced. In many studies, song-birds showed inhibition of ChE
    soon after the fenitrothion spraying of forests.

         Field observations have not revealed any effects of
    fenitrothion on populations of wild small mammals.

    1.1.4  Effects on experimental animals and  in vitro test systems

         Fenitrothion is an organophosphate and causes cholinesterase
    activity depression in plasma, red blood cells, and brain and liver
    tissues. It is metabolized to fenitrooxon, which is more acutely
    toxic. Its toxicity may be potentiated by some other organophosphate
    compounds.

         Fenitrothion is an insecticide of moderate toxicity with oral
    LD50 values in rats and mice ranging from 330 to 1416 mg/kg body
    weight. Acute dermal toxicity in rodents ranged from 890 mg/kg body
    weight to more than 2500 mg/kg body weight.

         Fenitrothion is only minimally irritating to the eyes and is
    nonirritating to the skin. The chemical showed dermal sensitizing
    potential in one of two studies on guinea-pigs.

         Fenitrothion has been tested in short-term studies on rats,
    dogs, guinea-pigs, and rabbits and in long-term carcinogenicity
    studies on rats and mice. In short-term studies on rats and dogs,
    the no-observed-adverse-effect levels (NOAELs), based on brain-ChE
    activity, were, respectively, 10 mg/kg diet and 50 mg/kg diet.

         Long-term studies on rats and mice indicated a NOAEL (based on
    brain ChE activity) of 10 mg/kg diet.

         No carcinogenic effects were found in any of the long-term
    studies reported.

         Fenitrothion was not mutagenic in  in vitro and  in vivo
    studies.

         Fenitrothion has not been found to be teratogenic at doses of
    up to 30 mg/kg body weight in rabbits and up to 25 mg/kg body weight
    in rats. Dose levels exceeding 8 mg/kg body weight were maternally
    toxic.

         Developing young rats exhibited behavioural deficits
    post-natally following  in utero exposure. A NOEL for this effect
    was established at 5 mg/kg body weight per day.

         Multigeneration reproduction studies on rats did not indicate
    any morphological effects. A NOAEL of 120 mg/kg diet, based on
    reproductive parameters, was demonstrated in these studies.

         Delayed neurotoxicity has not been reported as a result of
    exposure to fenitrothion.

    1.1.5  Effects on human beings

         Administration of fenitrothion as a single oral dose of 0.042-
    0.33 mg/kg body weight and in repeated doses of 0.04-0.08 mg/kg body
    weight to human volunteers did not cause inhibition in plasma and
    erythrocyte ChE. The urinary excretion of a metabolite,
    3-methyl-4-nitrophenol, was complete within 24 h.

         Several cases of poisoning have occurred. The signs and
    symptoms of poisoning were those of parasympathic stimulation. In a
    few cases, the toxic manifestations were delayed in onset and
    recurred for up to a few months. It has been suggested that the slow
    release of the insecticide from adipose tissue can give rise to a
    protracted clinical course or late symptoms of intoxication. In some
    cases, contact dermatitis has been attributed to exposure to this
    insecticide. There is no evidence of delayed neurotoxicity or of an
    association with Reye's syndrome following exposure to fenitrothion.

         Within WHO programmes, fenitrothion has been used in a few
    countries for indoor residual spraying for malaria control
    (application dose: 2.0 g of active ingredient/m2). No evidence of
    toxicity was noted in thousands of inhabitants observed, with the
    exception of one study in which less than 2% inhabitants reported
    mild complaints. However, approximately 25% of spray operators
    showed up to 50% inhibition of whole blood ChE activity. Following

    aerial application of a 50% EC formulation, some workers developed
    symptoms of poisoning and decreased whole blood ChE activity within
    48 h. Occupational exposure for a period of over 5 years of male
    workers in a production plant and female workers in the packaging
    unit produced clinical signs and symptoms of poisoning in 15% of
    male and 33% of female workers. The measured air concentration of
    fenitrothion in the workplace ranged between 0.028 and 0.118
    mg/m3.

    1.2  Conclusions

    *    Fenitrothion is a moderately toxic organophosphorus ester 
         insecticide. However, over-exposure from handling during 
         manufacture or use and accidental or intentional ingestion may 
         cause serious poisoning.

    *    Exposure of the general population, resulting mainly from 
         agricultural and forestry practices and public health 
         programmes, should not constitute a health hazard.

    *    With good work practices, hygienic measures, and safety 
         precautions, fenitrothion is unlikely to present a hazard for 
         those occupationally exposed.

    *    Despite its high toxicity for non-target arthropods,
         fenitrothion has been extensively used for pest control with
         few, or no, adverse effects on populations in the environment.

    1.3  Recommendations

    *    For the health and welfare of workers and the general
         population, the handling and application of fenitrothion should
         only be entrusted to competently supervised and well-trained
         operators who will follow adequate safety measures and use
         fenitrothion according to good application practices.

    *    The manufacture, formulation, use, and disposal of fenitrothion
         should be carefully managed to minimize contamination of the
         environment, particularly surface waters.

    *    Regularly exposed workers should receive periodic health 
         evaluations.

    *    Application rates of fenitrothion should be limited, to avoid 
         effects on non-target arthropods. The insecticide should never 
         be sprayed over water bodies or streams.

    2.  IDENTITY, PHYSICAL AND CHEMICAL PROPERTIES, ANALYTICAL METHODS

         Fenitrothion was first prepared in Czechoslovakia in 1956
    (Drabek, Truchlik, 1957). Later, it was prepared independently by
    Sumitomo Chemical Co. and by Bayer A.G. in 1959 and later by
    American Cyanamid Co.

         Its basic insecticidal activity was described by Nishizawa et
    al. (1961).

    2.1  Identity

    Primary constituent

    Chemical formula:   C9H12NO5PS

    Chemical structure:

    CHEMICAL STRUCTURE

    Relative molecular mass: 277.25

    Common name:             fenitrothion

    CAS chemical name:        O,O-dimethyl  O-(3-methyl
                             -4-nitro-phenyl) phosphorothioate

    IUPAC name:               O,O-dimethyl  O-(4-nitro-m-tolyl)
                             phosphorothioate

    RTECS Registry number:   TG0350000

    CAS Registry number:     122-14-5

    Synonyms:                Accothion, Agrothion, Bayer 41831, Bayer S
                             5660, Cytel, Dybar, Fenitox, MEP,
                             Novathion, Nuvanol, Cyfen, Sumitomo 1102A

    Technical product (FAO/WHO, 1988b)

    Major trade names:       Metathion, Novathion, Sumithion, Folithion

    Purity:                  > 93% (Sumithion)

    Impurities:               O,O-dimethyl  O-3-nitro- m-tolyl-
                             phosphorothioate   < 1.5%
                              O-methyl  O,O-bis(4-nitro- m-tolyl)
                             phosphorothioate   < 2.5%
                              O-methyl  S-methyl
                              O-(4-nitro- m-tolyl)
                             phosphorothioate(S-isomer)  < 0.8%
                              O,O-dimethyl  O-2-nitro- m-tolyl
                             phosphorothioate    < 3.0%
                              O,O-dimethyl  O-6-nitro- m-tolyl
                             phosphorothioate    < 2.5%
                              O,O-dimethyl  O-2,4-dinitro- m-tolyl
                             phosphorothioate    < 2.0%
                              O,O-dimethyl  O-4,6-dinitro- m-tolyl
                             phosphorothioate    < 1.5%
                             3-methyl-4-nitrophenol    < 0.5%

    Isomeric composition:     S-isomer, < 0.8%

    2.2  Physical and chemical properties

         Some physical and chemical properties of Fenitrothion are given
    in Table 1.

    2.3  Conversion factors

         1 ppm = 11.5 mg/m3 (at 20 °C)
         1 mg/m3 = 0.087 ppm.

    2.4  Analytical methods

         Methods for the determination of fenitrothion in foods,
    environmental samples, technical products, and formulations are
    summarized in Tables 2 and 3. The common procedure for determining
    residues in foods and environmental media consists of (1)
    extraction, (2) partition, (3) chromatographic separation
    (clean-up), and (4) qualitative and quantitative analysis using
    analytical instruments.

         Fenitrothion levels in technical products and formulations are
    usually determined by the diazo method, the colorimetric method, or
    gas-liquid chromatography. The common procedure consists of: (1)
    dissolution or extraction, (2) separation of impurities and (3)
    determination. Granules should be pulverized before analysis.

         The joint FAO/WHO Codex Alimentarius Commission has given
    recommendations for the methods of analysis to be used for the
    determination of fenitrothion residues (FAO/WHO, 1989d).

    
    Table 1. Some physical and chemical properties of fenitrothiona
                                                                                  

    Physical state                liquid
                                                                                  

    Colour                        yellow-brown

    Odour                         chemical odour

    Melting point                 0.3 °C

    Boiling point                 140-145 °C (decomp.)/0.1 mmHg

    Flash point                   157 °C

    Vapour pressure               18 mPa at 20 °C; 6 x 10-6 mmHg at 20 °C

                                   25              25
    Density                       d    1.32-1.34; d    1.3227
                                   25              4

    n-Octanol/water partition
     coefficient (log P)          3.16

    Solubility in water           14 mg/litre at 30 °C

    Solubility in organic         freely soluble in alcohols, esters,
     solvents                     ketones, and aromatic hydrocarbons;
                                  > 1000 g/kg dichloromethane, methanol,
                                  xylene; 193 g/kg propan-2-ol; 42 g/kg 
                                  hexane at 20-25 °C

    Stability                     hydrolysed by alkali: half-life
                                  4.5 h in 0.01 N NaOH at 30 °C
                                  decomposed by heat: 145 °C
                                                                                  

    a    From: Martin & Worthing (1981); Worthing & Walker (1983);
         Meister et al. (1985);  Moody et al. (1987a).

    

    
    Table 2.  Analytical methods for the determination of fenitrothion in food and environmental samples
                                                                                                                                              

    Sample                          Sample preparation                      Determination GLC             MDCc     Recovery (%),    Reference
                    Extraction      Partition      Clean-up   Elution       or HPLC conditions;           (mg/kg)  (fortification
                    solvent                        column                   detectora, column,                     level, mg/kg)
                                                                            temperature, RTb
                                                                                                                                              

    Residue analysis

    apple, orange   acetone         ESd            florisil   acetone/      GC: FTD, NPD, FPD, 2%         0.1      95-96 (0.1)      Ferreira &
    peach, grape                    /2%Na2SO4                 hexane        DC-200 + 3% OF-1, 1.5%                 86-97 (0.2)      Fernandes
    tomato,                         /n-hexane                 (4/96)        OV-17 + 1.95% OF-1, 10%                88-102 (0.5)     (1980)
    cabbage                                                                 DC-200                                 86-98 (1.0)
                                                                                                                   94-95 (2.0)

    chinese         methanol/       benzene                                 GC: FPD, 3% OV-1,                      89 (0.5)         Talekar
    cabbage         acetone/                                                10% DC-200                                              et al.
                    benzene                                                                                                         (1977)
                    (Soxhlet)

    onion           acetonitrile                   Amberlite  methanol      GC: FPD, 4% OV-1, 200 °C               99 (0.5)         Iwata
                    CH2Cl2/                        XAD-8      benzene                                                               et al.
                    benzene (1:4)                  charcoal                                                                         (1981)

    apple,lettuce   acetone         ESd            florisil   benzene       GC: ECD                       0.1      70-102           Möllhoff
    carrot,onion                    /CH3Cl3                                 5% SE-30, 190 °C, 6.3 min              64-89 (0.5)      (1967)
    tomato,potato                                                           5% OF-1, 190 °C, 5.6 min               88-114 (1.0)
                                                                            5% DC-200, 190 °C, 3.4 min
                                                                            5% E-301, 190 °C, 2.9 min

                                                                                                                                              

    Table 2 (contd).
                                                                                                                                              

    Sample                          Sample preparation        Determination GLC                           MDCc     Recovery (%),    Reference
                    Extraction      Partition      Clean-up   Elution       or HPLC conditions;           (mg/kg)  (fortification
                    solvent                        column                   detectora, column,                     level, mg/kg)
                                                                            temperature, RTb
                                                                                                                                              

    orange,potato   ethyl           acetonitrile/  florisil   petroleum sp/ GC:NPD,                       0.001                     Mestres
                    acetate         petroleum                 ethyl                                                                 et al.
                    CH2Cl2          spirit                    ether or                                                              (1974)
                    (4:1)                                     ethyl
                    acetate

    peach           acetone         water/         charcoal+  CH2Cl2        GC:NPD                                                  Ambrus et al.
    potato          CH2Cl2          MgO                                     3% OV-22; 3% OV-101;                                    (1981)
                                                                            1.95% SP-2401/1.5%

                    acetone         alumina N      hexane                   SP-2250; 3% NPGS;
                                                                            3% SE-30 on 100-120
                                                                            mesh Gas-Chrom Q
                    acetone         silica gel     benzene
                                    5% water

    apple           acetonitrile    ESd                                     HPLC: UV (280 nm)             0.03     81-87 (0.5)      Funch (1981)
    salad           2% Nacl                                                 Radpak A with ODS
                    /CH2Cl2

    unpolished      n-hexane        I. n-hexane    charcoal/  acetone/      GC: FPD                                                 Aoki et al.
    rice            (Soxhlet)       /CH3CN         avicel     n-hexane      10% DC-200 + 15%                       76 (0.4)         (1975)
                                                   (1/10)     (50/50)
    wheat                                                                   OF-1, 180 °C, 7.9 min
    buck wheat                      II. CH3CN                               2% DEGS + 0.5% H3PO4,         0.0007   92 (0.4)
    string bean                     /5% NaCl/                               180 °C, 10.2 min
    soybean                         benzene                                 10% DC-200 + 15%              0.0008   79-101 (0.4)
    pear                                                                    OV-17, 190 °C, 9.4 min

                                                                                                                                              

    Table 2 (contd).
                                                                                                                                              

    Sample                          Sample preparation                      Determination GLC             MDCc     Recovery (%),    Reference
                    Extraction      Partition      Clean-up   Elution       or HPLC conditions;           (mg/kg)  (fortification
                    solvent                        column                   detectora, column,                     level, mg/kg)
                                                                            temperature, RTb
                                                                                                                                              

    water melon     acetone         ESd                                     GC-MS                         0.1      91-102 (0.5)     Kobayashi
    tomato                          NaCl/                                   5% OV-1, 150 °C                                         et al.
                                    n-hexane                                                                                        (1979)

    wheat grain     methanol                                                GC: AFI, FPD, 5%              0.1      86 (0.5)         Smart
                                                                            OV-17 + Epikote 1001                   94 (1.0)         (1980)

    apple           methanol/                                               GC: FTD                       0.005    80-97 (0.1)      Takimoto &
    strawberry      CH3CN/CHCl3                                             10% DC-200 + 20% OF-1,                 97 (0.2)         Miyamoto
    pear, tomato                                                            210 °C                                                  (1976b)
    cucumber

    potato          methanol/                      florisil   benzene/      GC: FTD, 10% DC-200           0.005    96 (0.01)        Takimoto &
                    CH3CN/CHCl3                               ethyl         + 20% OF-1, 210 °C                                      Miyamoto
                                                              acetate                                                               (1976b)
                                                              (10/1)

    soybean         methanol/       CH3CN/         silica     benzene                                     0.005    98 (0.2, 0.02)   Takimoto &
    (fresh)         CH3CN/          n-hexane       gel        OF-1, 210 °C                                                          Miyamoto
                    CH3Cl3                                                                                                          (1976b)

    green tea       CH3CN/          CH3CN/         florisil   benzene/                                    0.005    90-93 (0.02)     Takimoto &
    rice grain      benzene         n-hexane                  ethyl                                                92-98 (0.5)      Miyamoto
                                                              acetate/                                             (1976b)
                                                              (10/1)

                                                                                                                                              

    Table 2 (contd).
                                                                                                                                              

    Sample                          Sample preparation                      Determination GLC             MDCc     Recovery (%),    Reference
                    Extraction      Partition      Clean-up   Elution       or HPLC conditions;           (mg/kg)  (fortification
                    solvent                        column                   detectora, column,                     level, mg/kg)
                                                                            temperature, RTb
                                                                                                                                              

    milk            methanol/       CH3CN/                                                                0.005    89 (0.1)         Takimoto &
                    CH3CN/          n-hexane                                                                                        Miyamoto
                    CHCl3                                                                                                           (1976b)

    butter          hexane          I. hexane/                              GC: ECD, 5% DC-200,           0.02     95               Gajduskova
                                    CH3CN                                                                 180 °C                    (1974)
                                    II. aq.
                                    Na2SO4
                                    CH3CN/
                                    CH2Cl2

    milk            acetone         I. acetone     silica     benzene       GC: FPD, 10% DC-200,          0.001    96 (0.5),        Bowman &
                                    CH2Cl2         gel                                                                              Bcraza
                                    II. hexane/    (20% H2O)  180 °C 2.9 min                                       94 (0.05)        (1969)
                                    CH3CN

    meat            ethanol/        CH3CN/         TLC        benzene/      GC: FTD, 10% DC-200           0.005    95 (0.1),        Takimoto &
                    benzene         n-hexane                  ethyl         + 20% OF-1                             86 (0.2)         Miyamoto
                                                              acetate                                                               (1976b)
                                                              (4/1)

    lettuce,        petroleum-      petroleum-     TLC        methanol      Spectrophotometry             0.05-    89-115           Kovac &
    apple           ether           ether          (A12O3)                  400 nm, after hydrolysis               0.1 (0.25-1)     Sohler
    cherries                        +CH3CN(1:1)               (NaOH+                                                                (1965)
    plums                                                     H2O2)                                                                 Cerna &
    kohlrabi                                                                                                                        Benes
    cauliflower                                                                                                                     (1972)

                                                                                                                                              

    Table 2 (contd).
                                                                                                                                              

    Sample                          Sample preparation                      Determination GLC             MDCc     Recovery (%),    Reference
                    Extraction      Partition      Clean-up   Elution       or HPLC conditions;           (mg/kg)  (fortification
                    solvent                        column                   detectora, column,                     level, mg/kg)
                                                                            temperature, RTb
                                                                                                                                              

    cabbage
    citrus,         acetone         ESd            silica     hexane/       TLC 3% OV-225                 ng                        Gardner
    potato                          CH3CCl3        gel        acetone       170-240 °C                    0.05     94 (0.5)         (1971)
                                                              (9/1)                                                                 Martindale
                                                                                                                                    (1988)

    Environmental analysis

    water                           amberlite                 ethyl         HPLC: UV (245 nm) RP-8        0.001    94 (0.05-        Volpe &
                                    XAD-4                     acetate       CH3CN/H2O (50/50)                                       Mallet
                                                                                                                                    (1981)
    water                           amberlite                 CH2Cl2 or     GC: FPD, 3.6% OV-101                   90 (0.05-        Volpe &
                                    XAD-4 or 7                ethyl         + 5% OV-210                            0.005)           Mallet
                                                              acetate                                                               (1980)

    drinking-                       amberlite                 acetone/      GC: NPD, -MS, 3%              0.001    104 (0.1),       LeBel
    water                           XAD-2                     hexane        OV-17                                  96 (0.01)        et al.
                                                              (15/85)                                                               (1979)

    water                           amberlite                 ethyl         GC: FPD, 4% OV-101 +          0.001    91.5 (0.01)      Mallet
                                                              acetate                                                               et al.
                                    XAD-2                                   6% OV-210, 195 °C                                       (1978)

    water           uBondapak                                               HPLC: UV (280                 0.005    95.6 (0.737)     Takaku
                    Phenyl                                                  uBondapak Phenyl H2O/                                   et al.
                                                                            CH3CN (100/0-0/100)                                     (1979a)

                                                                                                                                              

    Table 2 (contd).
                                                                                                                                              

    Sample                          Sample preparation                      Determination GLC             MDCc     Recovery (%),    Reference
                    Extraction      Partition      Clean-up   Elution       or HPLC conditions;           (mg/kg)  (fortification
                    solvent                        column                   detectora, column,                     level, mg/kg)
                                                                            temperature, RTb
                                                                                                                                              

    water           petroleum                                               GC: FPD, 5% SE-30, 180 °C              98-102           Grift &
                    ether                                                   5% DC-200, 180 °C                      (0.005-0.0005)   Lockhart
                                                                                                                                    (1974)

    pasture         CH3CN/          CH3CN/         florisil   benzene/      GC: FTD, 10% DC-200 +         0.005    95 (0.1)         Takimoto &
                                                              ethyl
    grass           benzene         n-hexane                  acetate       20% OF-1, 210 °C                                        Miyamoto
                                                                                                                                    (1976b)

    corn            methanol/                      silica     benzene       GC: FPD, 10% DC-200,          0.002    99-100 (5)       Bowman &
                                                   gel                                                                              Bcraza
    grass           CHCl3                          (20% H2O)                180 °C, 2.9 min                        98-99 (0.5)      (1969)
                                                                                                                   97-98 (0.05)

    jack pine       ethyl                          I.carbon/  benzene       GC: NPD, 6% SE-30 +           96-100   (0.2)            McNeil
    foliage         acetate                        celite                   4% OF-1, 225 °C                                         et al.
                                                                                                                                    (1979)
                                                   (1/6) II.  60%
                                                   florisil   benzene
                                                   Si600      in hexane

    water           n-hexane                                                GC: FPD, 11% OV-17 +          0.00001  100-108          Ripley
                                                                            OF-1 3.6% OV-101, 225 °C               (0.01-0.0001)    et al.
                                                                                                                                    (1974)

                                                                                                                                              

    Table 2 (contd).
                                                                                                                                              

    Sample                          Sample preparation                      Determination GLC             MDCc     Recovery (%),    Reference
                    Extraction      Partition      Clean-up   Elution       or HPLC conditions;           (mg/kg)  (fortification
                    solvent                        column                   detectora, column,                     level, mg/kg)
                                                                            temperature, RTb
                                                                                                                                              

    fish            ethyl           ESd            florisil   benzene/      GC: FPD                       0.05     93-110           Grift &
                                                              ethyl                                                                 Lockhart
                    acetate         CH3CN                     acetate       5% DC-200, 180 °C                                       (1974)
    sediment                        /hexane                                 5% SE-30, 180 °C              0.05     88-102 (5-0.1)

    bivalve         ethyl                          bio-       CH2Cl2/       GC: FPD, -MS, 3% OV-          0.0009   94.4 (10-0.01)   Sergeant
                    acetate                        beads,     cyclohexane   101, 180 °C, 11% OV-17/                                 et al.
                    (Soxhlet)                      SX-3                     OF-1, 200 °C                                            (1979)
                                                   (50/50)

    soil            acetonitrile                   Amberlite  ethyl         GC: FPD, 3.6% OV-17           +0.05    98-112 (0.5)     Hache
                                                   XAD-2      acetate                                                               et al.
    chicken liver                                                           5% OV-210, 210 °C                                       (1981)
    wine, clam
    pine needle

    soil            acetone         acetone        florisil   benzene       GC: ECD                       0.1      58-100 (0.1)     Möllhoff
                                    /CHCl3                                  5% SE-30, 190 °C, 6.3 min              76-98 (0.5)      (1967)
                                                                            5% QF-1, 190 °C, 5.6 min               98-122 (1.0)
                                                                            5% DC-200, 190 °C, 3.4 min
                                                                            5% E-301, 190 °C, 2.9 min

                                                                                                                                              

    Table 2 (contd).
                                                                                                                                              

    Sample                          Sample preparation                      Determination GLC             MDCc     Recovery (%),    Reference
                    Extraction      Partition      Clean-up   Elution       or HPLC conditions;           (mg/kg)  (fortification
                    solvent                        column                   detectora, column,                     level, mg/kg)
                                                                            temperature, RTb
                                                                                                                                              

    Ambient air

    vapour          trapped on 10% OV-101 on chromosorb                     GC: FPD, 3% OV-1,             5 x                       Krzymien
    aerosol         W packed in a glass tube and                            205 °C                        10-12                     (1979)
                    thermally released and carried to GC column

    aerosol         consecutive plates of cascade                                                         5 x      100 (30)         Krzymien
                    impactor, plates washed                                                               10-12                     (1979)
                    with n-hexane, n-hexane solution
                    injected into GC
                                                                                                                                              

    a    Detectors for GC (FPD = flame photometric detector; FTD = flame thermionic detector; ECD = electron capture detector;
         NPD = NP specific detector; AFI = alkali flame ionization detector), MS = mass spectrometry.
    b    RT = Retention time.
    c    MDC = minimum detectable concentration.
    d    ES = extraction solvent.

    

    
    Table 3.  Analytical methods for fenitrothion in technical products and formulationsa
                                                                                               

    Sample             Sample preparation                       Determination
                                                                                               

    Diazo method

    TG and EC          dissolution (ether)                      reduction (Zn-acetic acid)
                       partition (ether/1% Na2CO3)              titration (NaNO2)
                                                                end-point (potentiometer or
                                                                iodide-starch paper)

    Colorimetric method

    TG and EC          dissolution (methanol)                   addition (1% Na2CO3)
                                                                determination (free NMC);

    WP and dust        extraction (methanol)                    400 nm hydrolysis (5N KOH)
                                                                determination (total NMC);
    Granule            pulverization extraction (methanol)      400 nm

    TLC-UV method

    TG and EC          dissolution (CHCl3)                      determination; 271 nm
                       TLC (benzene/diethyl ether=19/1)

    WP                 extraction (methanol)
                       TLC (benzene/diethyl ether=19/1)

    Dust               extraction (CHCl3)
                       TLC (benzene/diethyl ether=19/1)

    Granule            pulverization extraction (CHCl3)
                       TLC (benzene/diethyl ether=19/1)

    TLC-phosphorus method

    TG and EC          dissolution (CHCl3)   TLC                digestion (H2SO4 and HNO3)
                                                                colouring (ammonium metavanadate

    WP                 extraction (methanol) TLC                and ammonium molybdate)
                                                                determination;

    Dust               extraction (CHCl3)   TLC                 420 nm

                                                                                               

    Table 3. (cont'd).
                                                                                               

    Sample             Sample preparation                       Determination
                                                                                               

    Granule            pulverization extraction (CHCl3) TLC

    GC method

    TG and EC          dissolution (IS solution)                GC: FID
                                                                2% DC-QF-1, 170 °C

    WP and dust        extraction (IS solution) centrifuge

    Granule            pulverization extraction (IS solution)
                       centrifuge
                                                                                               

    a    From: Takimoto et al. (1975).
         TG = technical grade; EC = emulsifiable concentrate; WP = water-dispersible
         powder; NMC = 3-methyl-4-nitrophenol; IS = internal standard (dibutyl
         sebacate);
         GC = gas-liquid chromatography.

    
    3.  SOURCES OF HUMAN AND ENVIRONMENTAL EXPOSURE

    3.1  Natural occurrence

         Fenitrothion is not a natural product.

    3.2  Man-made sources

    3.2.1  Production

         The global production volume is not available. However, the
    global manufacturing capacity has been estimated to be between 15
    000 and 20 000 tonnes. Production figures in Japan (a major
    manufacturing country) are 5346 tonnes in 1982 increasing up to
    about 10 000 tonnes in 1988 (Japan Plant Protection Association,
    1984, 1986, 1988, 1989). Production in India was reported to be 400
    tonnes in 1978, 350 tonnes in 1979, and 100 tonnes in 1980
    (Battelle, 1982). Production in Czechoslovakia in 1989 was 964
    tonnes (Benes, personal communication).

         Fenitrothion is formulated as an emulsifiable concentrate
    (50%), an ultra-low-volume concentrate, flowable (20%), a wettable
    powder (40%), granules (3%), dust (3%), an oil-based liquid spray
    alone or in combination with other pesticides, e.g., trichlorfon,
    malathion; BPMC; fenvalerate (insecticide), tetramethrin (house-hold
    insecticide); IBP, phthalide, thiophanate-methyl (fungicide).

    3.2.2  Uses

         Fenitrothion is mainly used in agriculture for controlling
    chewing and sucking insects on rice, cereals, fruits, vegetables,
    stored grains, cotton, and in forest areas. It is also used for the
    control of flies, mosquitos, and cockroaches in public health
    programmes and/or indoor use.

    4.  ENVIRONMENTAL TRANSPORT, DISTRIBUTION, AND TRANSFORMATION

    4.1  Transport and distribution between media

         Several studies were performed to elucidate the mechanism of
    the apparent rapid disappearance of fenitrothion from the water
    phase after the field spraying of fenitrothion formulation. The
    processes most likely to explain the phenomena include sorption by
    the sediments, photolysis, microbial degradation, hydrolysis, and
    volatilization.

         Marshall & Roberts (1977) discounted volatilization as a major
    pathway for the disappearance on the basis of the calculated
    half-life of 93 days obtained in a 1-m water column, designed as a
    simple model for small, well-mixed lentic systems with compartments
    representing the major pools, i.e., the water, the hydrosol, and the
    suspended solids, which include both biotic and abiotic material.

         Maguire & Hale (1980) studied the kinetics of fenitrothion
    distribution and transformation in water and sediment, both
    experimentally and after field spraying (see section 5.1.2 for
    results after field spraying). Laboratory experiments demonstrated
    that volatilization of fenitrothion from true solutions (5 mg/litre)
    in distilled water followed first-order kinetics and that the
    half-life of disappearance at 20 °C was estimated to be 64 ± 5 days. 
    The fact that the half-life was considerably longer (> 180 days) in
    the presence of 5 mg fulvic acid/litre indicated that the rate would
    be considerably reduced in natural waters too. In contrast with
    this, the volatilization of fenitrothion that had been sprayed on
    the surface of water appeared to be a very fast process in the
    laboratory (half-life = 18 min for volatilization from the surface
    of water). Surface volatilization was suggested to play a
    significant role in the dissipation of fenitrothion from a small
    pond after spraying the formulation.

         Metcalf et al. (1980) also reported the significance of
    volatilization in the disappearance of fenitrothion in a lake by
    taking account of the effects of winds and water currents on natural
    water bodies in experiments using various rates of aeration.
    Observed half-lives of fenitrothion in Palfrey Lake and Brook in
    Southwestern New Brunswick (water temperature: 11 °C, average pH
    value in the lake: 6.7) were 6.3 days (bottom) - 7.2 days (surface)
    and 0.9 days, respectively.

         In a laboratory leaching study, 14C fenitrothion and its
    degradation products hardly moved with water in 3 loam soils,
    whereas, in Muko sand containing 0.2% clay and less than 0.1%
    organic matter, about 15% of the applied 14C was eluted from the
    soil column. Preincubation of the fenitrothion in sandy soil for 60

    days before leaching decreased the degree of mobility. In the
    effluent from sandy soil, a trace amount of fenitrothion (0-0.1%)
    together with water-soluble products, such as
    3-methyl-4-nitro-phenol [9]1 (0.6%) and amino-fenitrothion [13]
    (11.3%), were detected (Takimoto et al., 1976, see Fig. 3).

         Baarschers et al. (1983) examined the adsorption of
    fenitrothion and 3-methyl-4-nitrophenol [9] in water-soil suspension
    systems, using 4 different soils and 1 sediment as adsorbents. The
    Freundlich k values were 15.5-354.8 for fenitrothion and 2.1-147.8
    for 3-methyl-4-nitrophenol [9]. Both of the k values increased when
    the organic matter content increased from 0.9 to 33.1%. The
    adsorption characteristics of fenitrothion may be correlated with
    the lower degree of mobility in the leaching study.

    4.2  Abiotic and biotic transformation

    4.2.1  Abiotic transformation

    4.2.1.1  Thermal degradation

         Tsuji et al. (1980) examined the mechanisms of thermal
    degradation of fenitrothion in air and found that 3 major exothermic
    steps were involved (Fig. 1). The first step was formation of
    fenitrooxon [1], and S-methyl fenitrothion [8] with evolution of
    sulfur dioxide at 150-160 °C.

         The second step was formation of fenitrooxon [1], S-methyl
    O,O-bis(3-methyl-4-nitrophenyl) phosphorothioate [11] and
    polymetaphosphate [12] with evolution of dimethyl sulfide from
    S-methyl fenitrothion [8] at 210-235 °C. The third step was
    carbonization of the phenolic ring of [12] and gas evolution from
    [11] at 270-285 °C. In a nitrogen atmosphere, the first step did not
    take place and only the other two steps were involved. S-methyl
    fenitrothion was produced by heating fenitrothion up to 193 °C.

         The thermal degradation of fenitrothion in a closed system was
    more rapid than that in an open system. Maeda et al. (1982) proposed
    that dimethyl sulfide, which was evolved during thermal degradation
    of S-methyl fenitrothion [8], catalysed isomerization of
    fenitrothion to [8]. In fact, addition of 0.4-1.6% of dimethyl
    sulfide in a closed system enhanced the degradation of fenitrothion.
    Although metal salts, such as zinc, aluminum, ferric chloride, and
    stannic chloride, also accelerated isomerization of fenitrothion,
    calcium dodecylbenzene sulfonate (surfactant) showed no effect.

                  

    1 Chemical structures in Fig. 1-7 are referred to giving the
      numbers in brackets.

    FIGURE 1

    4.2.1.2  Photolysis in air

         Addison (1981) examined the photolysis of fenitrothion by UV
    radiation (200-400 nm) from a xenon lamp in the vapour phase
    (10-15 mg/50-1 reaction chamber) at about 85-90 °C, and computed the
    half-life of disappearance to be 61 ± 11 min and 24 ± 3 min in the
    absence or presence of ozone (0.7-0.9 ± 1 mg/m3), respectively.

         Brewer et al. (1974) also studied the vapour phase photolysis
    of fenitrothion at 313 nm UV radiation, and detected
    3-methyl-4-nitrophenol [9] and an unidentified product as primary
    photo-products (Fig. 2).

    4.2.1.3  Hydrolysis and photolysis in water

         Fenitrothion underwent hydrolysis in the absence of light
    through a pH-independent process below pH 7 and a base-catalysed
    process above pH 10, while both processes occurred between pH 7 and
    pH 10. The half-lives of fenitrothion within the pH range of 5-9
    (normally found in natural water) were about 200-630 days at 15 °C,
    17-61 days at 30 °C, and 4-8 days at 45 °C. The predominant
    hydrolysis products were 3-methyl-4-nitrophe-nol [9] above pH 10 and
    demethylated fenitrothion [7] below pH 8 (Fig. 2; Mikami et al.,
    1985a).

         [Phenyl-14C]-fenitrothion was dissolved at 1.0 mg/litre in
    aqueous buffer solutions at pH values of 5, 7, and 9 and kept at 25
    ± 1 °C in the dark for 30 days, free from microbial contamination.
    Fenitrothion was less stable at pH 9 with a half-life of 100-101
    days, compared with those of 180-186 days and 191-200 days at pH 7
    and pH 5, respectively. Cleavage of the P-O-methyl linkage to form
    demethylated fenitrothion [7] was predominant at pH 5 and pH 7,
    while at pH 9 cleavage of the P-O-aryl linkage to form
    3-methyl-4-nitrophenol [9] was the major hydrolytic path-way (Ito
    et al., 1988).

          Greenhalgh et al. (1980) and Aly & Badawy (1982) demonstrated
    that hydrolysis of fenitrothion follows pseudo-first-order kinetics,
    yielding mainly the phenol [9] at alkaline pH and the demethylated
    form [7] under acidic conditions.

         The rate of hydrolysis of fenitrothion may be accelerated
    through the addition of peroxide ion (1.7 x 10-4 mol/litre),
    particularly under alkaline conditions, since energies of activation
    were reduced to 7.8 kcal/mol for peroxide hydrolysis from
    16.3 kcal/mol for alkaline hydrolysis (Desmarchelier, 1987).

    FIGURE 2

         The photostability of fenitrothion in water is dependent on
    both pH and energy of UVR or sunlight (Miyamoto, 1977a).
    Fenitrothion rapidly decomposed in distilled water under sunlight
    and in pH 7 and pH 9 solutions at ambient temperatures, but was
    considerably more stable at pH 3. The half-life of fenitrothion was
    10, 50, 20, and 6 h, respectively, in distilled water and in
    solutions at pH 3, pH 7, and pH 9. Fenitrothion decomposed nearly 8
    times faster at pH 9 than at pH 3.

         Mikami et al. (1985a) determined the quantum yield of the
    photodecomposition reaction of fenitrothion in distilled water (8.0
    x 10-4) and calculated that the half-life of photolysis by
    sunlight at the 40° north latitude was 7.6, 6.8, 11.3, and 17.0 h in
    spring, summer, autumn and winter, respectively. The actual
    half-life in autumn in Takarazuka, Japan, at a latitude of 35°
    north, was 12 h, agreeing with the above calculation.
    Photode-composition of fenitrothion in sterile lake water and sea
    water was also rapid and the half-life in both these solutions was
    less than 1.1 days.

         Fenitrothion degraded fairly rapidly under sunlight to form
    CO2; 14C ring-labelled fenitrothion released 39.4, 40.4, and
    45.0% CO2 in 32 days in distilled water, in a buffer solution (pH
    7), and in sterilized sea water (pH 7.8), respectively (Mikami et
    al., 1985a).

         [Phenyl-14C]-fenitrothion was dissolved at 1.0 mg/litre in
    aqueous acetate buffer (pH 5.0), free from microbial contamination
    and irradiated with artificial sunlight (wave length > 290 nm,
    xenon arc lamp), for 30 days (10 h/day irradiation) at 25 ± 1 °C. 
    Fenitrothion was degraded rather rapidly with a half-life of
    3.33-3.65 days (70.8-140.9 days under dark conditions).
    Photo-degradation reactions were oxidation of the aryl methyl group
    to a carboxyl group to form compound [3] (a main product, 8.0-12.4%
    in 14 days), oxidation of the P=S group to P=O group, cleavage of
    the P-O-CH3 or P-O-aryl linkage, and further decomposition to
    14CO2 (41.2-42.0%) during 30 days (Katagi et al., 1988).

         Kanazawa (1977) demonstrated that fenitrothion (20 µg/litre)
    degraded to 8% of the original concentration under greenhouse
    conditions and only to 55% in the absence of light, in sea water,
    over 2 weeks.

         Fenitrothion (about 0.1 mg/litre) degraded in sea waters
    collected from various coasts of Japan to 44-62% and 63-94%, with
    and without sediments, respectively, after 2 weeks in the absence of
    sunlight and aeration (Environment Agency of Japan, 1978).

         The effects of several factors on the persistence of
    fenitrothion in sea water were examined using the experimental
    design with an L16 orthogonal layout (Kodama & Kuwatsuka, 1980).
    The persistence of fenitrothion was affected mainly by water quality
    (river water or sea water) and sunlight (exposed or unexposed), but
    also partially by temperature; it was not affected by the presence
    of suspended solid or vaporization. After 72 h, the persistence of
    fenitrothion in sea water was 56-97% of the original concentration
    under varying conditions, while that in river water was 1-28%. When
    river water was boiled, the rate of disappearance of fenitrothion
    was the same as that in sea water, indicating that microbial
    degradation was one of the most important contributing factors.

         The photodegradation of fenitrothion (1 mg/litre) in sea water
    collected along 3 different coastlines of Japan was very rapid with
    a half-life of about 3 h, twice as fast as that in distilled water
    (Takimoto et al., 1980).

         A microcosm study using distilled, estuarine, and lake water
    revealed that the ionic complement and/or microflora content of
    estuarine water contributed more to the degradation of fenitrothion
    than the pH. Sunlight irradiation in the static lake/bay models
    decomposed 80% of fenitrothion to polar products within 6 h
    (Weinberger et al., 1982a).

         Twenty-one out of at least 50 radioactive photoproducts of
    14C ring-labelled fenitrothion in water at various pHs were
    identified.  The major photoproducts were O,O-dimethyl
    O-(3-carboxy-4-nitrophenyl) phosphorothioate [3] in distilled
    water and in buffer solutions at pH 3 and 7. A dimeric compound [5]
    composed of [3] and the corresponding amino analogue [4] was more
    predominantly formed in buffer solutions at pH 7 and 9, in natural
    river (pH 7.4) and sea (pH 7.8) water. On prolonged irradiation with
    sunlight, these photoproducts decreased to less than 4% of the
    initial concentration with concomitant increases in carbon dioxide
    (21.5-45%) and the unextractable residues (29.3-51.4%) consisting of
    polymeric humic acids. Demethylated products [6,7] and hydrolysis
    products at the P-O-aryl linkage, such as 3-methyl-4-nitrophenol
    [9], were of minor importance, independent of pH values.  S-Methyl
    fenitrothion [8] was occasionally detected in trace amounts (Mikami
    et al., 1985a).

         The UV irradiation of fenitrothion in oxygenated hexane
    solution produced fenitrooxon [1] and  O,O-dimethyl
     O-(3-formyl-4-nitrophenyl)phosphorothioate [2] (Greenhalgh &
    Marshall, 1976). However, these photochemical reactions might not
    play a major role in the environmental photochemistry of
    fenitrothion in water.

    4.2.1.4  Photolysis on soil

         When fenitrothion was applied to thin-layer plates with a 2 mm
    thickness of 7 different types of soil and exposed to sunlight, it
    took 50-150 days for the 90% disappearance of fenitrothion from the
    soils (Miyamoto, 1977a). No clear correlation existed between the
    rate of disappearance of fenitrothion and the physical and chemical
    parameters of the soils.  S-Methyl fenitrothion and
    aminofenitrothion similarly applied to the soil decreased much more
    rapidly than fenitrothion. The order of stability was fenitrothion
    >  S-methyl fenitrothion > aminofenitrothion. Under dark
    conditions, decomposition of these 3 compounds proceeded more
    slowly, the range of stability among them being the same as that
    observed under irradiated conditions. At most, 10% of the applied
    chemical was lost, probably by evaporation, from the soil after 14
    days. Fenitrothion was degraded on the soil surface mainly by
    oxidation of the P = S to the P = O group and cleavage of the P-O-
    aryl linkage.

         The rapid photodecomposition of fenitrothion on soil surfaces
    was also demonstrated by Mikami et al. (1985a). Unlike photolysis in
    water, the principal products were fenitrooxon [1] and
    3-methyl-4-nitrophenol [9], amounting to 3.6-9.4% and 20.4-23.1% of
    the applied  14C, respectively, after 12 days.

         A photolysis study was conducted with
    [phenyl- 14C]-fenitrothion applied on the surface of soil at a rate
    of 23.4 µg/cm2. The samples were continuously irradiated (290 nm)
    using an artificial light source (xenon arc lamp) over 30 days, the
    soil temperature being maintained at 25 ± 1 °C throughout the
    experiment. The rate constant and the half-life of photolysis were
    determined to be 0.00814/day and 85 days, respectively, while under
    dark conditions these were 0.0038/day and 182 days. Degradation
    products identified included fenitrooxon [1] (2.0% at day 30),
    demethyl fenitrothion [7] (2.1%) and 3-methyl-4-nitrophenol [9]
    (3.0%) (Dykes & Carpenter, 1988).

         Sunlight irradiation of fenitrooxon [1], 3-methyl-4-nitrophenol
    [9], or carboxy-fenitrothion [3] on silica gel TLC plates resulted
    in degradation and polymerization to humic acids, with half-lives of
    3.9, 4.3, and 1.8 days, respectively (Ohkawa et al., 1974).

    4.2.2  Biotransformation

    4.2.2.1  Biodegradation in soil

         The degradation pathways of fenitrothion in soils are shown in
    Fig. 3.

         When fenitrothion was incorporated at 10 mg/kg (on a dry-weight
    basis) in soils with various physical and chemical properties, and
    kept at 25 °C in the dark, under upland or submerged conditions, the
    adsorption and decomposition of fenitrothion were quite variable,
    depending on the properties of the soils and on the incubation
    conditions (Takimoto et al., 1976; Miyamoto, 1977a). The half-life
    of fenitrothion was 12-28 days under upland conditions, and 4-20
    days under submerged conditions. However, no direct relationship was
    observed between the decomposition of fenitrothion in soil and any
    of the physical or chemical properties measured, namely clay
    content, organic matter content, ion exchange capacity, and pH.
    Under upland conditions, 3-methyl-4-nitrophenol [9] was formed at an
    early stage of incubation, amounting to 10-20% of the applied
    radioactivity ( m-methyl position). Levels of
    3-methyl-4-nitrophenol decreased with longer incubation. Another
    major decomposition product was radioactive carbon dioxide, which
    amounted to approximately 40% of the initial fenitrothion after 60
    days. No aminofenitrothion [13] was detected.

         On the other hand, under submerged conditions,
    3-methyl-4-nitrophenol [9] and carbon dioxide were minor products.
    The major decomposition product was aminofenitrothion [13], its
    formation being parallel to the decrease in fenitrothion. The
    maximum amounts of aminofenitrothion were 18-66% of the initial
    fenitrothion. Aminofenitrothion tended to disappear slowly on longer
    incubation.

         In soils, 14C-ring-labelled fenitrothion (10 mg/kg) degraded
    at 25 °C in the dark with a half-life of 2-5 days under upland and
    submerged conditions; after 8-26 weeks, levels declined to less than
    0.1 mg/kg. After one year, the carbon dioxide evolved amounted to
    60-70% of the initial radiocarbon under upland conditions and to
    23-40% under submerged conditions, while the remaining radiocarbon
    was mostly incorporated into the organic matter fractions of the
    soil. When the soils containing the bound residues of the
    radiocarbon were mixed with fresh soil, the release of radioactive
    carbon dioxide was accelerated. Under upland conditions, degradation
    of 3-methyl-4-nitrophenol [9] was more rapid than that of
    fenitrothion (Mikami et al., 1985b).

         Adhya et al. (1981a) also found that fenitrothion was degraded
    primarily by reduction of the nitro group to aminofenitrothion in
    flooded soil with lower redox potentials. Sterilization of the
    prereduced flooded soil samples by autoclaving prevented the rapid
    decomposition of fenitrothion in soil.

    FIGURE 3

         Aminofenitrothion was further degraded to demethyl
    amino-fenitrothion [14] in typical flooded acid sulfate soils from
    Kerala, India. Dealkylation also occurred in low sulfate soils under
    submerged conditions, when supplemented with extraneous sulfate
    (e.g., ammonium sulfate or ferrous sulfate). Hydrogen sulfide,
    evolved as an end product of the anaerobic metabolism of sulfate,
    catalysed the dealkylation of aminofenitrothion (Adhya et al.,
    1981b).

         Fenitrothion was stable when incubated in soil suspensions
    containing streptomycin, cycloheximide, and mineral salts. However,
    it decomposed rapidly when the soil suspension was added to a
    culture medium suitable for fungal or bacterial growth (Takimoto et
    al., 1976). The major decomposition product in the culture was
    aminofenitrothion [13], the content of which reached 40-65%, and a
    maximum 60-80% when formylamino-[15] and acetylamino- fenitrothion
    [16] were combined. Demethyl fenitrothion [7] and
    3-methyl-4-nitrophenol [9] were detected among other products. The
    dominant species of microorganisms (Fusarium and Bacillus species),
    isolated from the above soils, metabolized fenitrothion well.

         When ring-labelled fenitrothion (7.4 mg/kg) was incubated with
    two kinds of forest soils collected from the State of Maine, USA,
    the half-life of fenitrothion at 30 °C was about 3 days. In 50 days,
    94-97% of the fenitrothion had been decomposed yielding 35%
    radioactive carbon dioxide, 5-7% 3-methyl-4-nitrophenol [9], 4%
    3-methyl-4-nitroanisole [17], and approximately 50% of soil- bound
    radioactivity (Spillner et al., 1979a).

         It has been reported (National Research Council of Canada,
    1975) that several species of soil and water bacteria, including
     Bacillus  subtilis, Escherichia coli, E. freundii, Pseudomonas
    reptilovora, and  P. aeruginosa, can metabolize or inactivate
    fenitrothion.

         The fungus  Trichoderma viride can also hydrolyse fenitrothion
    and fenitrooxon, and the hydrolysed product,
    3-methyl-4-nitro-phenol, is co-metabolized by this fungus
    (Baarschers & Heitland, 1986).

          Flavobacterium sp. ATCC 27551, isolated from paddy field,
    hydrolysed fenitrothion to yield 3-methyl-4-nitrophenol [9] in
    culture solutions containing mineral salts (Adhya et al., 1981c).

         A crude cell extract from a mixed bacterial culture growing on
    parathion also hydrolysed fenitrothion to yield
    3-methyl-4-nitro-phenol [9]. The chemical hydrolysis of fenitrothion
    was 3-5 times slower than that of parathion. However, the rate of
    enzymatic hydrolysis was 24-205 times faster than that of chemical
    hydroly-sis by 0.1 N sodium hydroxide at 40 °C (Munnecke, 1976).

         Liu et al. (1981) studied the biodegradability of fenitrothion
    using a mixed-culture of microorganisms from activated sludge, soil,
    and sediments, under aerobic and anaerobic conditions. Fenitrothion
    was more readily degraded under anaerobic co-metabolic conditions
    (half-time = 1.0 day) than under aerobic conditions (half-time = 5.5
    days). When fenitrothion was applied to the medium as the sole
    source of carbon, its stability was greater under aerobic
    conditions, 77% of the initial dose being recovered after 164 h
    incubation.

    4.2.2.2  Biodegradation and bioaccumulation in organisms

    a) Aquatic organisms

         The accumulation and partitioning of fenitrothion residues
    among different tissues and organs in wild trout were investigated
    following 2 applications of the compound to a lake (280 g a.i./ha
    with a 9-day interval). Fenitrothion residues accumulated fairly
    rapidly in the tissues of both brook trout and lake trout. Peak
    levels of fenitrothion were reached 2-4 days after the first
    application (in lake trout, fat: 280 µg/kg, muscle: 96.8 µg/kg,
    intestine: 96.3 µg/kg, liver: 16.1 µg/kg, ovary: 48.2 µg/kg) and 8
    days after the second application (in lake trout, fat: 665 µg/kg,
    muscle: 133 µg/kg, intestine: 114 µg/kg, liver: 39.6 µg/kg). These
    levels were many times higher than those in the surrounding waters
    of Lac Ste-Anne. Fenitrothion residues continued to persist in lake
    trout tissues (but not in the tissues of brook trout) up to at least
    8 days after the second application, even though the residues in the
    water had declined to non-detectable levels 4 days earlier (Holmes
    et al., 1984).

         When exposed to running water containing 0.1 or 0.02 mg
    fenitrothion/litre, both underyearling rainbow trout ( Salmo
     gairdneri) and southern top-mouthed minnow ( Pseudorasbora parva)
    rapidly absorbed the chemical (Takimoto & Miyamoto, 1976a). The
    fenitrothion concentration in the fish reached a maximum after 1-3
    days of exposure, and then remained virtually constant. The
    bioaccumulation ratio did not increase on longer exposure and was
    more or less independent of the fenitrothion concentration in water.
    The ratio was similar in the 2 fish species, being approximately
    250, 230, and 200 (at its maximum) in underyearling trout, yearling
    trout, and minnow, respectively.  Once the fish were transferred
    from fenitrothion-containing water to fresh water, the levels of
    fenitrothion in the fish decreased rapidly to about 0.01 mg/kg in 5
    days. None of the fish species exhibited noticeable signs of
    intoxication during the exposure period. In another study, the
    bioaccumulation ratio for the fresh-water species, top-mouthed
    minnow, was 246 (Kanazawa, 1981).

         Killifish (Oryzias latipes) took up fenitrothion in a flow
    system with bioaccumulation ratios at different developmental stages
    of: 115 in embryos, 173 in yolk sac fry, 88 in postlarval stages,
    441 in juveniles, 520 in adult males, 540 in adult females, and 224
    in eggs produced from fenitrothion-exposed adults (Takimoto et al.,
    1984a). However, the half-lives of disappearance of the compound in
    clean water were less than 2 days, independent of fat content.

         Similar results were reported with southern top-mouthed minnows
    in a static aquarium test; the fenitrothion concentration in water
    at 23 °C decreased from 0.81 mg/litre to 0.002 mg/litre in 28 days,
    while the observed maximum concentration of fenitrothion in the fish
    (162 mg/kg on the 4th day) decreased to 4.9 mg/kg after 28 days
    (Kanazawa, 1975).

         With respect to the distribution and metabolism of
    fenitrothion, autoradiograms of rainbow trout exposed to labelled
    fenitrothion under static water conditions for 6 h revealed that the
    concentration of radiocarbon was highest in the gall bladder and
    intestines; after 24 h, the radiocarbon was present in every tissue,
    except the brain and heart. Twenty-four hours after the transfer of
    the fish to fresh water, most of the radioactivity in the tissues
    had disappeared. Only the gall bladder, intestines, and pyloric
    caeca still contained an appreciable amount of the radiocarbon.
    Intact fenitrothion accounted for 90% of the absorbed radioactivity
    in fish. The remaining 10% comprised fenitrooxon [1], demethyl
    fenitrothion [7], 3-methyl-4-nitrophenol [9], and its glucuronide
    [27]. In water, the percentage of these degradation products
    increased with time and amounted to 25% of the radioactivity.
    Because fenitrothion is stable in water under the experimental
    conditions, the degradation products are presumably derived from
    fish metabolism (Takimoto & Miyamoto, 1976a) (see Fig. 4).

         All developmental stages of killifish metabolized fenitrothion
    mainly to 3-methyl-4-nitrophenyl-ß-glucuronide [27] (comprising
    20-40% of 14C), except the embryo, which had the lowest metabolic
    activity. Yolk sac fry contained the highest concentration (28%) of
    demethyl fenitrothion [7]. Fenitrooxon [1] and demethyl fenitrooxon
    [20] were present in small amounts, at the most, 0.5%. These
    metabolites and the intact fenitrothion were eliminated into the
    surrounding water, when the fish were transferred to fresh water
    (Takimoto et al., 1984a).

         Absorption of [methyl-14C]-fenitrothion at 0.1 mg/litre in
    running water to a similar plateau level in the killifish (Oryzias
    latipes) was more rapid at 25 °C than at 15 °C; the bioaccumulation
    ratios of fenitrothion were 235 and 339, respectively. Water of
    higher salinity (2.3%) resulted in slightly higher accumulation

    ratios of fenitrothion in both killifish (303) and mullet, Mugil
    cephalus (179), than fresh water (235 and 30, respectively), but the
    half-lives were independent of temperature and salinity, with values
    of 0.24-0.36 day. Fenitrothion was metabolized, primarily through
    hydrolysis, to [9] by the killifish, demethylation to demethyl
    fenitrothion [7] by the mullet, and conjugation of the liberated
    phenol with glucuronic acid [27] by both species.  Although the
    metabolism of the compound in both fish was not affected by the
    different salinities and temperatures, the glucuronide conjugate was
    more directly excreted into water under conditions of lower
    temperature and higher salinity. 14C-labelled compounds were
    distributed primarily to the gall bladder, as shown by whole-body
    radioautography (Takimoto et al., 1987a).

         Bluegill sunfish (Lepomis macrochirus) was exposed to
    [phenyl-14C] - fenitrothion or non-radiolabelled fenitrothion in a
    flow-through system at concentrations of 0.049 mg/litre and 0.043
    mg/litre, respectively, for a 28-day exposure period. The
    concentrations of labelled and non-labelled fenitrothion in whole
    fish reached an equilibrium on days 1-3 of exposure at levels of 5.4
    and 1.3 mg/litre, respectively. Mean bioconcentration factors for
    labelled and non-labelled fenitrothion during the uptake period were
    respectively 111 and 29 for whole fish, 26 and 10 for the edible
    portion, and 279 and 36 for the non-edible portion. When the exposed
    fish were transferred to running fresh water, the concentrations of
    labelled and non-labelled fenitrothion in the fish decreased
    rapidly, with biological half-lives of less than 1 day in both the
    edible and non-edible portions of the fish. A non-linear
    2-compartment, kinetic modelling computer programme estimated 81.9
    and 111 as the uptake rate constants (K1), 0.69 and 3.72 as the
    depuration rate constants (K2), and 118 and 30 as the
    bioconcentration factors (BCF) for labelled and non-labelled
    fenitrothion, respectively. Fenitrothion was metabolized through the
    oxidation of P=S to P=O, demethylation of the P-O-alkyl linkage,
    cleavage of the P-O-aryl linkage, and conjugation of the phenol with
    glucuronic acid. The major metabolites were demethylfenitrothion [7]
    and 3-methyl-4-nitrophenyl-ß-glucuronide [27], amounting to 29-40%
    and 11-15% of the recovered 14C from the whole fish, respectively
    (Ohshima et al., 1988).

         Freshwater teleosts ( Tilapia mossambica; body weight, 5-9 g;
    length, 5-7 cm) were exposed to 200 mg fenitrothion/kg body weight
    for 24 h. Fenitrothion and its metabolites, extracted from the
    liver, kidney, and brain, were separated and identified using HPLC
    and preparative silica gel TLC. The metabolites extracted from the
    liver were identiied as fenitrooxon,  N-acetylaminofenitrothion
    [16], and fenitrothion. The metabolites from the kidney were
    identified as demethyl- N-acetylaminofenitrooxon [37]. The
    metabolites from the brain were identified as 3-methyl-4-nitrophenol
    [9] and demethyl- N-acetylamino-fenitrooxon [37] (Anjum & Qadri,
    1986).

    FIGURE 4

         McLeese et al. (1979) reported that accumulation ratios of
    fenitrothion were independent of the exposure levels, and were
    19-35, 78-130, and 9, in marine clam (Mya arenaria), mussel (Mytilus
    edulis), and freshwater clam (Anodonta cataractae), respectively.

         When freshwater snails ( Cipangopaludina japonica and Physa
     acuta) were exposed to 0.1 mg [methyl-14C]-fenitrothion/litre in
    a dynamic flow system, the concentrations of fenitrothion and
    14C-label in the body reached equilibrium on day one of exposure. 
    The maximum bioaccumulation ratios of fenitrothion were 18 and 53 in
     C. japonica and  P. acuta, respectively. These snails metabolized
    the compound primarily by demethylation to [7], hydrolysis to [9],
    and reduction to [13], and [14]. The liberated phenol moiety was
    conjugated with sulfate [26] in  C. japonica and mainly with
    glucose [18] in  P. acuta. When the snails were transferred to a
    freshwater stream, fenitrothion and its metabolites were rapidly
    eliminated, and the half-life of the parent compound was less than
    0.5 days in both snails. In  P. acute, fenitrothion and its
    decomposition products were mainly distributed in the liver as shown
    by whole-body radioautography (Takimoto et al., 1987b).

         When the waterflea  Daphnia pulex and the shrimp  Palaemon
     paucidens were exposed to 1.0 µg [methyl-14C]-fenitrothion/litre
    in a flow-through system, the concentrations of fenitrothion and
    14C-label in the body reached equilibrium (on day one of exposure)
    and the maximum bioaccumulation ratios of fenitrothion were 71 and 6
    in the daphnia and shrimp, respectively. These crustaceans primarily
    metabolized the compound through oxidation of P = S to P = O to form
    compound [1], hydrolysis of P-O-aryl linkage to form compound [9],
    and demethylation to give compounds [7] and [20]. The liberated
    phenol was conjugated with sulfate to form compound [26] in  D.
    pulex and with glucose to form compound [18] in the shrimp. When
    the organisms were transferred to a freshwater stream, fenitrothion
    and its metabolites were rapidly eliminated from their bodies, and
    the half-life of the parent compound was less than 0.2 day in both
    species (Takimoto et al., 1987c) (see Fig. 4).

         The uptake rate of radiolabelled fenitrothion by the blue crab
    (Callinectes sapides) increased with temperature and salinity. The
    highest concentrations of radioactivity were found in the
    hepato-pancreas and stomach. The blue crab can metabolize
    fenitrothion to produce fenitrooxon, aminofenitrothion,
    3-methyl-4-nitrophe-nol, 3-methyl-4-aminophenol, demethyl
    fenitrothion, demethyl fenitrooxon, and glycoside and sulfate
    conjugates of the phenols (Johnston & Corbett, 1986).

         Aquatic plants were collected and analysed after the aerial
    application of fenitrothion (280 g/ha) in Manitoba, Canada, (Moody
    et al., 1978); the fenitrothion residues present in surface-
    dwelling duckweed, obtained from stagnant water, disappeared rapidly
    from 1.44 mg/kg after 1 h to 0.03 mg/kg after 192 h, while the
    submerged hornwort, also from stagnant water, contained rather
    persistent, but low, residues of fenitrothion ranging from 0.12 to
    0.15 mg/kg after 192 h. No fenitrothion was detected in the
    submerged flowering rush in running water.

          Chlorella pyrenoidosa exposed to 10 mg radioactive
    fenitrothion per litre rapidly took up the compound and the 14C
    level reached equilibrium after 4 h with a bioaccumulation ratio of
    417. On transfer to fresh water, the fenitrothion in the chlorella
    was rapidly desorbed (Weinberger et al., 1982b). Other algae
    ( Chlamydomonas reinhardii and  Euglena gracilis) showed less
    bioaccumulation of fenitrothion. The aquatic macrophyte,  Elodea
    densa, showed a bioaccumulation ratio of 24-76 (Weinberger et al.,
    1982b).

         Three types of algae,  Chlorella vulgaris, Nitzschia
    closterium, and  Anabaena flos-aquae, also rapidly absorbed
    fenitrothion with maximum bioaccumulation ratios of 44, 105, and 53,
    respectively (Kikuchi et al., 1984). Only A. flos-aquae (blue-green
    algae) actively degraded fenitrothion. When transferred to a
    fenitrothion-free medium, these algae released fenitrothion, as well
    as its metabolites, with half-lives of the compounds of less than 1
    day, except in the case of A. flos-aquae when the half-life was 2.6
    days (see Fig. 4).

         Bioaccumulation ratios for fenitrothion in 2 species of
    blue-green algae (Anabaena sp. and Aulosira fertilissima) were
    reported to be 42-347 and 136-784, respectively, when exposed to 1,
    5, or 10 mg/litre (Lal et al., 1987).

         In a field test in which fenitrothion was sprayed twice at 210
    g/ha, to give a maximum concentration of 0.9 µg/litre in surface
    water and 0.42 µg/litre in subsurface water (3 m depth),
    phyto-planktons and zooplanktons contained maximum levels of 0.05
    and 0.014 µg fenitrothion/litre, respectively, the concentrations
    decreasing with time (Lakshminarayama & Bouque, 1980).

    b) Birds

         When male Hubbert chickens were intubated with fenitrothion at a 
    dose of 10 mg/kg, twice every other week, for 2-8 weeks, the residue
    levels in the brain, blood, liver, and adipose tissue were less than
    0.071 mg fenitrothion equivalent/kg wet tissue. None of the tissues
    retained any significant amounts of fenitrothion or its metabolites,
    and no tendency towards bioaccumulation was observed (Trottier &
    Jankowska, 1980).

         White Leghorn hens, dosed with 2 mg fenitrothion/kg body weight
    for 7 consecutive days, discharged 95% of the radioactivity in the
    excreta within 6 h following the last administration. The
    radioactivity in the hen egg-white decreased sharply after the last
    dosage, with the highest concentration (0.02 mg/kg) recorded on the
    third day of administration. The egg yolk showed a maximum
    radiocarbon level of 0.10 mg/kg (fenitrothion, 0.006 mg/kg), 1 day
    after the last dose, followed by a decline to 0.02 mg/kg after 1
    week (Mihara et al., 1979).

         After oral administration of ring-labelled 14C fenitrothion
    at 5 mg/kg body weight to female Japanese quails, 99% of the
    radio-carbon was eliminated during the first 24 h (Miyamoto, 1977a).

         When [phenyl-14C]-fenitrothion was administered orally to
    Japanese quails in a single dose of 5 mg/kg body weight or to White
    Leghorn hens at a daily dose of 2 mg/kg body weight for 7 days,
    97-99% of the radiocarbon was eliminated in the mixture of urine and
    faeces within one day. The radioactivity in the eggs was, at most,
    0.2% of the parent compound (0.055 mg/kg). More than 18 metabolites
    were found in the excreta. The major metabolites were
    3-methyl-4-nitrophenol [9] and its sulfate conjugate [26], which
    accounted for 70.5% of the dose in quails and 50.8% in hens.
    Demethylfenitrothion [7] and demethylfenitrooxon [20] were found as
    minor metabolites; several  m-methyl oxidation products were also
    detected.  In vitro studies revealed that the oxidation activity of
    hen, quail, pheasant, and duck liver enzymes at the  m-methyl group
    of fenitrooxon was higher than that of mammalian liver enzymes,
    though the avian enzymes had extremely low  O-demethylase activity
    (Mihara et al., 1979) (see Fig. 5).

    c) Terrestrial organisms

         Lactating Japanese Sannen goats were treated orally with
    [phenyl-14C]-fenitrothion at 0.5 mg/kg body weight per day for 7
    days. One day after treatment, no residues of intact fenitrothion
    were found in the organs and tissues, but a small amount of
    aminofenitrothion [13] was detected in the digestive tracts (rumen,
    omasum, and large intestine). The administered radiocarbon was
    essentially quantitatively eliminated during the week following
    treatment; 50% of the dose was recovered in the urine, 44%, in
    faeces, and 0.1%, in the milk with a maximum concentration of 0.011
    mg/litre. The major metabolites in the urine, faeces, and milk were
    aminofenitrothion [13] and   O-methyl  O-hydrogen
     O-(3-methyl-4-acetyl-aminophenyl) phosphate [37], and
     O,O-dimethyl  O-(3-methyl-4-sulfo-aminophenyl) phosphorothioate
     (N-sulfo-aminofenitrothion) [38], respectively. No intact
    fenitrothion or fenitrooxon was found in the milk, urine, or faeces
    (Mihara et al., 1978) (see Fig. 6).

    FIGURE 5

         When 30 calves (1-1.5 years old, average weight, 243 kg) were
    confined on a pasture sprayed with 378 g fenitrothion/ha (initial
    residue on grass, 11.8 mg/kg), the meat and fat contained about 0.01
    mg fenitrothion residues/kg on the first day. No fenitrothion
    residues were found in the meat from the third day on, and only
    0.004-0.007 mg fenitrothion/kg was found in the fat on the third
    day; these amounts decreased to almost control levels by the seventh
    day (Miyamoto & Sato, 1969).

         Silage prepared from corn treated with 1.1, 2.2, or 3.4 kg
    fenitrothion/ha was fed to lactating Jersey cattle for 8 weeks. 
    Although traces (0.001-0.005 mg/kg) of aminofenitrothion [13] were
    found in the milk of cows fed 3.4 kg fenitrothion/ha silage, no
    residues (< 0.001 mg/kg) were found in the milk of cows that had
    consumed the silage treated at lower levels (Leuck et al., 1971).

         Jersey cows, administered 3 mg fenitrothion/kg body weight for
    7 consecutive days, produced milk containing fenitrothion and
    aminofenitrothion [13] levels of up to 0.002 and 0.003 mg/kg,
    respectively. However, levels were undetectable within 2 days of the
    last dose (Miyamoto et al., 1967).

         Johnson & Bowman (1972) reported that neither fenitrothion nor
    its metabolites were detected in the milk of lactating Jersey cows,
    7 days after being fed (for 28 days) a diet containing the pesticide
    at a concentration of 1.84 mg/kg.

         Topical application of a lethal dose of fenitrothion to spruce
    budworm ( Choristoneura fumiferana) resulted in the formation of
    3-methyl-4-nitrophenol (2-17%) and desmethyl fenitrothion (2-4%).
    Trace levels (1-2% of the applied dose) of fenitrooxon were also
    detected (Sundaram, 1988).

    4.2.2.3  Abiotic and biological degradation in/on plants

         The photolysis and metabolic pathways of fenitrothion in plants
    are illustrated in Fig. 7.

         One half the amount of fenitrothion applied at 12 mg/kg to rice
    plants at the preheading stage was lost by evaporation and only 10%
    was left on the plant surface after 24 h, 50% penetrating into
    tissues (Miyamoto & Sato, 1969). Although fenitrooxon [1] was
    detected at 0.01-0.86 mg/kg in leaf sheaths and blades (not in
    harvested grains), it disappeared faster than fenitrothion.

         The half-lives of fenitrothion were 1-3 days on, and in,
    fenitrothion-treated apples (approx. 4.5 mg/kg) growing on the tree
    under natural conditions, with fenitrooxon [1] (0.005 mg/kg) and
     S-methyl fenitrothion [8] (approx. 0.005 mg/kg), on the fruit and
    demethyl fenitrothion [7] (0.012 mg/kg), 3-methyl-4-nitro-phenol

    [9] (0.024 mg/kg), and its glucose conjugate [18] in the fruit after
    21 days (Hosokawa & Miyamoto, 1974). It was concluded that the fruit
    metabolized the penetrating fenitrothion gradually to
    3-methyl-4-nitrophenol [9], and further to the glucose conjugate
    (e.g., [18]) in the tissues; this was combined with the
    disappearance of fenitrothion on the fruit surface through
    photodecomposition and volatilization.

         A number of residue data are available on various feed plants
    (Sumitomo, 1969; Takimoto & Miyamoto, 1976b). Coastal Bermuda grass
    and corn treated with fenitrothion at 1, 2, and 3 kg/ha were
    analysed for residues of the parent compound and some metabolites
    (Leuck & Bowman, 1969); the residues of fenitrothion diminished
    rapidly to approximately one hundredth of the initial levels after
    14 days. The fenitrooxon [1] contents were low, declining more
    rapidly, and none was detected after 21 days. While the amounts of
    3-methyl-4-nitrophenol [9] were highest in the 1- and 7-day samples,
    the total residues on both crops diminished to less than 1 mg/kg in
    28 days.

         Under operational spraying (280 g/ha) for the control of
    budworm, fenitrothion deposits (2-4 mg/kg, wet weight) on the
    foliage of red and white spruce and balsam fir decreased by about
    50% within 4 days, and 70-85% within two weeks. In some cases, about
    10% of the initial deposit (0.05-0.5 mg/kg) persisted for most of
    the year following spraying (Yule & Duffy, 1972).

         To monitor the persistence of fenitrothion in the Canadian
    forest, LaPierre (1985) measured residues in leaves. Immediately
    following application (15 min) of fenitrothion to poplar ( Populus
     tremuloidus) and gray birch trees ( Betula  populifolia),
    fenitrothion levels of 22 and 18 mg/kg, respectively, were detected.
    Residue levels decreased to less than 1 mg/kg and 0.1 mg/kg,
    respectively, within 30 and 120 days. No fenitrooxon was detected in
    any of the samples. The observation, made by McNeil & McLeod (1977),
    indicating that sawfly populations were depressed by persistent
    fenitrothion residues in jack pine foliage apparently supported the
    persistence of fenitrothion within leaf tissues. However, it may be
    that, in this case, the fenitrothion was rather persistent because
    of the special circumstances (in micro sink).

         A complete disappearance of fenitrothion from spruce foliage
    was observed, within 45 days, following operational spraying with
    280 g/ha. The hardwood species within mixed forests, such as red
    maple, appeared to collect 3-4 times higher deposits on their
    foliage when exposed to the same operational spraying (National
    Research Council of Canada, 1975), but the residues decreased
    rapidly.

    FIGURE 6

    FIGURE 7

         During environmental surveillance of aerial spraying of
    fenitrothion, carried out from 1979 to 1982 in Quebec, the
    insecticide concentrations were measured in foliage samples taken
    from 1 to 4 h after spraying, when residue levels were likely to
    have peaked. Over the 4 years studied, the median residue level of
    fenitrothion found in balsam fir foliage was 3.81 mg/kg (dry
    weight), with a maximum concentration of 111 mg/kg. On conifer
    foliage, feni-trothion had a half-life of 2-4 days; 70-95% of the
    residue dissipated in less than 2 weeks (Morin et al., 1986).

         Takimoto et al. (1978) examined the stability of fenitrothion
    (6 and 15 mg/kg) in stored rice grains. The insecticide decomposed
    after 12 months to 22.0-26.3% and 64.7-65% of the initial dose at 30
    and 15 °C, respectively. The major metabolites in rice grains were
    demethyl fenitrothion [7] and 3-methyl-4-nitrophenol [9], which
    amounted to 10.0-19.2% and 16.0-38.0% of the dose, respectively. In
    addition, trace amounts of  S-methyl fenitrothion [8],  S-methyl
    demethyl fenitrothion [21], fenitrooxon [1], demethyl fenitrooxon
    [20], 3-hydroxymethyl-4-nitrophenol [22], 3-methyl-4-nitroanisole
    [17], 1,2-dihydroxy-4-methyl-5-nitro-benzene [23], and
    1,2-dimethoxy-4-methyl-5-nitrobenzene [24] were detected (see Fig.
    7). Fenitrothion and its degradation products were distributed in
    the outer portions of the endosperm and at 100 µm in depth from the
    surface of rice grains stored for 12 months, as determined by
    whole-body autoradiography. On cooking, the unpolished rice grains
    treated with fenitrothion yielded 3-methyl-4-nitrophenol [9] and
    demethyl fenitrothion [7] as primary degradation products.

         Abdel-Kader & Webster (1980) and Abdel-Kader et al. (1982)
    studied the stability of fenitrothion (8 mg/kg) in stored wheat. 
    Very little (< 3%) breakdown of the insecticide residue occurred on
    wheat stored at -35 or -20 °C for 72 weeks. However, fenitrothion
    residues decreased as the temperature increased. After 72 weeks, 18,
    35, 56, 90, 96% of the initial deposit had degraded in wheat stored
    at -5, 5, 10, 20, at 20 °C respectively. The major metabolites in
    wheat stored at 20 °C for 12 months were demethyl fenitrothion [7],
    3-methyl-4-nitrophenol [9], and dimethyl phosphorothioic acid [19]
    (Fig. 7), as determined by GLC. Concentrations of demethyl
    fenitrothion [7] and dimethyl phosphorothioic acid [19], which were
    highest (2.01 and 0.55 mg/kg, respectively) after 6 months storage,
    decreased to 0.98 and 0.21 mg/kg, respectively, at the end of
    storage. The residue level of 3-methyl-4-nitrophenol [9] gradually
    increased to 0.96 mg/kg after 12 months. No fenitrooxon [1] or
     S-methyl fenitrothion [8] was detected throughout the experimental
    period (Abdel-Kader & Webster, 1982).

         When labelled fenitrothion was applied to bean leaves at a rate
    of 84.5 µg/12.5 cm2, 26 and 64% of the radioactivity was lost by
    volatilization after 1 and 3 days, respectively. The decrease of the
    parent compound was rapid, both on and in the leaf.


    After 12 days, the major products remaining on the bean leaves were
    fenitrooxon [1] (0.1%), carboxy-fenitrothion [3] (0.1%), and
    3-carboxy-4-nitrophenol [10] (0.1%) (Ohkawa et al., 1974).

         The residues of fenitrothion in coastal Bermudagrass and corn
    diminished to less than 0.13 mg/kg in 28 days, with half-lives of
    less than 1 day, following a spray of the emulsifiable concentrate
    at 1, 2, or 3 kg a.i./ha. The major metabolite was
    3-methyl-4-nitrophenol [9], with smaller amounts of fenitrooxon [1].
    After 28 days, the residues had declined to less than 1 mg/kg for
    all 3 rates of application (Leuck & Bowman, 1969).

         In leaves of shrubbery ( Maesa japonica) sprayed twice with
    fenitrothion at 735 g/ha, fenitrothion was detected at 78.3 mg/kg on
    the day of application, but 99% had disappeared within a week. 
    Although fenitrooxon [1] was detected at levels of 0.1-0.3% of
    fenitrothion in the leaves, it disappeared after strong rainfall,
    35-37 days after application. Fenitrothion was detected in grasses,
    and the upper and lower layers of the soil, at levels of 0.1, 0.01,
    and 0.001 mg/kg, respectively, 144 days after application (Ohmae et
    al., 1981).

         Hallett et al. (1973) observed the transport of fenitrothion to
    the embryo, and its metabolism in seed tissues, when pine seeds were
    germinated for up to 54 days in an aqueous solution or suspension of
    fenitrothion (10 or 1000 mg/litre). Laboratory studies of
    fenitrothion on seeds of eastern white pine demonstrated penetration
    and accumulation of the parent compound, its oxon, and the
     S-methyl metabolites in the embryo and perisperm. This appeared to
    alter the amino acid metabolism in the seed but did not affect the
    later growth of seedlings (Hallett et al., 1974). No significant
    differences in germination and growth were reported between the
    seeds of white pine from areas sprayed at 140-280 g/ha and from
    unsprayed (control) areas (Pomber et al., 1974).

         Similarly, the seeds of white pine, white spruce, and yellow
    birch readily absorbed fenitrothion when germinated for up to 21
    days in an aqueous solution or suspension of fenitrothion (10 or
    1000 mg/litre). Fenitrooxon [1], demethyl fenitrothion [7], and
     S-methyl fenitrothion [8] were detected as primary metabolites in
    all 3 species. The highest concentrations of [1], [7], and [8] were
    1.4-75 mg/kg, 10-37 mg/kg, and 1-8 mg/kg, respectively. Hallett et
    al. (1977) proposed that the formation of S-methyl fenitrothion [8]
    resulted from the alkylation of demethyl fenitrothion by excess
    fenitrothion in the conifer seeds. It is probable that [8] will be
    formed in plants via the non-enzymatic alkylation reaction, if the
    concentrations of fenitrothion and [7] are extremely high.  However,
    formation of [7] will be extremely low or negligible, when
    fenitrothion is used at the recommended dosage.

         Sundaram & Prasad (1975) established the uptake and
    transportation of fenitrothion in young spruce trees by growing the
    plants in a nutrient solution containing the insecticide. However,
    when fenitrothion was applied to the needles of spruce and fir
    trees, which are the part of the tree most exposed to the
    insecticide during spraying, the foliar penetration of fenitrothion
    was found to be extremely small. Furthermore, less than 0.1% of the
    fenitrothion that had penetrated was translocated laterally and
    upward to the untreated parts of the foliage. The amounts found in
    the stems and roots were also negligible (Sundaram et al., 1975).

         On the other hand, Moody et al. (1977) using an
    autoradiographic technique, suggested the systemic potential of
    fenitrothion applied to 4-year-old seedlings of balsam fir and, to a
    lesser extent, white spruce, and jackpine.

         Prasad & Moody (1976) also found that, mainly because of
    volatilization, 70% of the applied fenitrothion was lost one day
    after treatment, though low levels of the insecticide (0.48 mg/kg
    after 21 days) persisted in conifer tissues.

         When labelled fenitrothion was applied to the leaves of
    Japanese cypress at about 300 µg per leaf, approximately 70-80% of
    the applied dose disappeared, mainly through evaporation, within 24
    h. The major metabolites in the treated leaves were demethyl
    fenitrothion [7], 3-methyl-4-nitrophenol [9] (approx. 2-10 µg), and
    its glucoside conjugate [18] (Tabata & Okubo, 1980).

         Immediately following the application of fenitrothion to poplar
    ( Populus tremuloidus) and birch trees ( Betula populifolia),
    levels of 22 and 18 mg/kg, respectively, were detected. Residue
    levels dropped to under 1 mg/kg within 30 days of treatment, and
    under 0.1 mg/kg by 120 days. The oxygen analogue, fenitrooxon, was
    not detected in any of the samples (La Pierre, 1985).

    5.  ENVIRONMENTAL LEVELS AND HUMAN EXPOSURE

    5.1  Environmental levels

    5.1.1  Air

         In the 1980 spray programme in Canada, fenitrothion was
    detected occasionally in air, the maximum concentration being 12
    ng/m3 (Mallet, 1980), when the compound was sprayed at 140-280
    g/ha.

         Collaborative field studies were initiated in 1978 in Canada to
    obtain relevant information concerning long-range pesticide drift
    during the aerial spraying of fenitrothion in forest pest control,
    using a surrogate (tris(2-ethylhexyl)phosphate) (Crabbe et al.,
    1980a). At approximately 7.5 km downwind of the spray, the peak
    treetop concentration of the drifting cloud varied from 1.4 ng/litre
    in relatively neutral conditions to 5.0 ng/litre in the most stable
    conditions. The fraction of the tracer material still airborne, 7.5
    km from the spray line, was 6 and 16% for the neutral and most
    stable environmental tests, respectively.

         In 1980, a study was conducted to measure the atmospheric
    fenitrothion exposure levels at breathing height near aerial
    forestry spray operations (Crabbe et al., 1980b). The results
    revealed an aerial concentration (or dosage) of 40 ng/min per litre1
    at the spray line (flight path of aircraft) falling to an average of
    8 ng/min per litre, 700 m from the spray line, in the first hour
    after delivery. During the first hour after spraying, 30% of the
    material collected in the samplers was vapour and the rest, aerosol.
    Droplets of approx. 4.0 µm diameter contributed most to the mass of
    drifting spray cloud at 500 m, about 15% of the airborne aerosol
    mass consisting of droplets larger than 25 µm in diameter. The peak
    aerosol concentration at chest height underneath the sprayed swath
    of forest was approximately 15 ng/litre. One result of considerable
    interest was the degree of volatilization of fenitrothion from an
    early morning spray, which resulted in a sustained vapour plume
    during the afternoon with a concentration

                  
    1  The value nanograms/min per litre represents the time
       integrated aerial concentration of fenitrothion consisting of
       the mean aerosol cloud concentration of agent (nanograms per
       litre) divided by the residence time (minutes) of the cloud. 

    of 25 ng/litre at the spray line, falling to approximately 1.0
    ng/litre 100 m downwind of the swath at an ambient temperature of
    20-25 °C. The vapour plume persisted throughout the day and, in a
    10-h period following spraying, was estimated to contribute up to
    0.4 µg/person of respirable fenitrothion.

         A pesticide residue survey was conducted in relation to the
    1980 spruce budworm spray programme (210 g a.i./ha applied twice
    with a 3-day interval) in New Brunswick, Canada. Fenitrothion was
    detected occasionally in the air, the maximum level being 1.2
    µg/m3. Amino-fenitrothion was sometimes present in the air at a
    maximum level of 12.0 µg/m3 (Mallet & Volpe, 1982).

         A chemical residue survey was undertaken to determine the
    extent of the deposition and persistence of fenitrothion in the
    environment in relation to the 1981 spruce budworm spray programme
    (210 g a.i./ha applied twice with a 7-day interval) in New
    Brunswick, Canada. Fenitrothion was only detected twice in the air
    at levels of 0.08 and 0.04 µg/m3 (Mallet & Cassista, 1984).

         When a 1.0% emulsion of fenitrothion was applied to a 61.2 m3
    room (3.7 ± 0.3 g a.i./room) at 23.5-25.4 °C, using a compressed air
    sprayer, the airborne concentrations of fenitrothion on days 0 and 3
    after application were 3.3 µg/m3 and 0.5 µg/m3, respectively
    (Wright et al., 1981).

    5.1.2  Water

         In actual field spraying in Canada, concentrations of
    fenitrothion in stream waters varied greatly, depending on the spray
    history and the weather. Spraying at 210 g/ha resulted in measurable
    concentrations (> 0.03 µg/litre) in streams as far as 4 km from the
    sprayed area. However, at 140-210 g/ha, most peak concentrations
    were lower than 15 µg/litre and diminished very rapidly in
    fast-flowing streams. Disappearance was still faster when a rain
    storm followed spray application (Eidt & Sundaram, 1975).

         High peak concentrations of fenitrothion were recorded in a few
    cases, e.g., 64 µg/litre in flowing stream water approximately 1 h
    after completion of spraying, and 75.5 µg/litre in stagnant water
    some 17 h after spraying at 140-280 g/ha (Lockhart et al., 1977).
    Fenitrothion concentrations usually dropped to less than 1 µg/litre
    within a few days in forest streams and beaver ponds after
    experimental and operational applications of 140-280 g/ha by
    aircraft (Flannagan, 1973; Peterson & Zitko, 1974; Sundaram, 1974;
    Eidt & Sundaram, 1975), and no measurable traces of fenitrothion
    have been found in water longer than 40 days after spraying.
    According to Symons (1977), the fenitrothion concentration in water
    immediately after aerial spray at 140-280 g/ha in Canada seldom
    exceeded 15 µg/litre.

         One hour after the first application of fenitrothion (280 g
    a.i./ha, applied twice with a 9-day interval) to a lake,
    fenitrothion residues in the water were concentrated near the
    surface (0.80-0.90 µg/litre), with small amounts (0.06 µg/litre) at
    the bottom. Six hours later, residues were fairly evenly distributed
    throughout the water column (0.91-1.49 µg/litre). Residue levels, 97
    h after treatment, were similar at all depths at 0.41-0.46 µg per
    litre, but declined rapidly in the next 48 h to < 0.01-0.06
    µg/litre. Similar results were obtained after the second application
    (Holmes et al., 1984).

         Sundaram (1973) also reported that concentrations of
    fenitrothion in aqueous systems diminished rapidly by dilution and
    by physicochemical and microbial degradation to low levels (0.03
    µg/litre) within a period of 40 days. The half-lives were found to
    be short, ranging from 0.25 to 3.5 days.

         In the 1980 spruce budworm spray programme in Canada,
    fenitrothion was usually detected in water in the immediate vicinity
    of the sprayed sites. The maximum level was 20.0 µg/litre and
    persistence was usually limited to a few days. Aminofenitrothion
    [13] was also found at a maximum of 8.0 µg/litre (Mallet, 1980;
    Mallet & Volpe, 1982).

         Water, suspended solids, and sediment samples were collected
    from a small pond in a spruce-fir forest in New Brunswick, Canada,
    before and after spraying with a fenitrothion formulation. When an
    11% fenitrothion formulation was sprayed on a pond at 1500 g/ha, the
    initial fenitrothion concentrations in the surface microlayer,
    subsurface water, and suspended solids (0.25-0.67 h after spraying)
    were 1.5, 0.015, and 1.9 µg/litre, respectively (Maguire & Hale,
    1980). Thereafter, the fenitrothion disappeared exponentially with
    half-lives of 0.34, 9.8, 1.8, and 3.2 h in the surface microlayer,
    subsurface water, sediment, and suspended solids, respectively.
    Residue levels declined rapidly to below detectable levels, 2 days
    after spraying. The degradation products, 3-methyl-4-nitrophenol [9]
    in water and aminofenitrothion [13] in sediment persisted for less
    than 2 and 4 days, respectively. The concentration of fenitrothion
    in rainwater during spraying (140-280 g/ha) in Canada was 77
    µg/litre in the sprayed area, 17 out of 43 samples in the
    neighbouring areas contained levels ranging from a trace to 1.1
    µg/litre, while levels were less than 0.01 µg/litre in other regions
    (Pearce et al., 1979a). No residues of fenitrooxon [1],
    aminofenitrothion [13], or  S-methyl fenitrothion [8] were
    detected, even in the sprayed area (less than 0.05 µg/litre).

         In the 1981 spruce budworm spray programme in Canada, the
    amounts of fenitrothion residues detected in water were low (maximum
    1.30 µg/litre) and post-spray samples did not contain detectable
    amounts (less than 0.01 µg/litre) of fenitrothion. Small amounts of
    aminofenitrothion [13] (0.1 µg/litre) were detected in some samples
    (Mallet & Cassista, 1984).


         In Quebec, environmental surveillance was performed in the
    sprayed areas after aerial spraying, carried out from 1979 to 1982. 
    The insecticide concentrations were measured in foliage and water
    samples taken from 1 to 4 h after spraying, when residue levels were
    likely to peak. In lentic water, the median residue level was 5.82
    µg fenitrothion/litre, with a maximum level of 1114 µg/litre. In
    lotic water, the median concentration was 2.84 µg fenitrothion per
    litre, with a maximum level of 127 µg/litre. In aquatic
    environments, fenitrothion residues disappeared rapidly. Levels of
    less than 1.0 µg/litre were found 2-8 days after spraying at 140-280
    g a.i./ha (Morin et al., 1986).

         Fenitrothion levels in a mountain stream increased to 20 µg per
    litre, 6-9 h after spraying, and then decreased to below 1 µg/litre
    within 24 h (Hatakeyama et al., 1990).

    5.1.3  Soil

         When operationally sprayed twice at 735 g/ha (Japan),
    fenitrothion levels reached a maximum of 0.13-0.23 mg/kg in soil
    under shrubbery after 1-8 days and then diminished with half-lives
    of 2-4 days. Aminofenitrothion [13] was detected at maximum levels
    of 1.5-6.5 µg/kg, but only shortly after spraying. Little
    contamination with fenitrothion due to drift was observed (a maximum
    of 0.01 µg/m2 per min, 1 h later) in areas that were 1.5 or 3.0 km
    from the application site (Ohmae et al., 1981).

         Yule & Duffy (1972) found that an operationally applied dosage
    of fenitrothion (280 g/ha) produced a deposit of up to 0.04 mg/kg
    (average depth 15 cm) in forest soil, and that the initial deposit
    was too small to investigate degradation pathways. Sundaram (1974)
    found a similar pattern of loss of fenitrothion from the soil after
    5 years of repeated annual applications at a rate of 210-350 g/ha in
    Canada; the insecticide content in the soil samples ranged from
    traces to 0.1 mg/kg and disappeared within 45 days. No measurable
    amounts of the breakdown products were found. Despite consecutive
    annual spraying for up to 5 years at 210-350 g/ha in New Brunswick,
    Canada, there was no evidence of build-up (< 0.005 mg/kg) in the
    soil (Yule, 1974).

         In the 1981 sprucce budworm spray programme in Canada, foilage
    and soil litter collected after the second spray application
    contained fenitrothion at levels of 0.2-0.5 and 0.06-0.14 mg/kg,
    respectively; post-spray samples collected 2 weeks later contained
    similar levels of fenitrothion. No residual fenitrothion was
    detected in sediment (Mallet & Cassista, 1984).

    5.1.4  Food

         Fenitrothion is used for the pre-harvest treatment of a variety
    of crops, such as fruits, vegetables, rice, cereals, soybeans and
    coffee, at the rate of 0.5-2.0 kg a.i./ha. The initial

    residue levels on fruits, vegetables, rice, and cereals were
    relatively high (0.001-9.5 mg/kg), but declined rapidly with a
    half-life of 1-2 days (FAO/WHO, 1970, 1975b).

         A survey of pesticide residues in crops (total number of
    samples: 697) collected in the Tokyo Metropolitan Central Vegetable
    and Fruit Market was carried out from April 1984 to March 1989. Low
    fenitrothion residues (0.01-0.06 mg/kg) were found in only a few
    samples (Nagayama et al., 1986, 1987, 1988, 1989).

         Fenitrothion (EC) was applied 3 times to peach at a rate of 2.0
    kg a.i./ha in Japan. The residue levels in peach (pulp) were
    0.03-0.07 mg/kg, 7 days after application and decreased to
    0.005-0.015 mg/kg after 13-15 days. Peach peel contained most of the
    residues (1.1-1.6 mg/kg), 7 days after application, but the levels
    decreased to 0.3-0.6 mg/kg in 15 days.

         Lettuce, plums, and apples were treated once with 0.2%
    fenitrothion (EC) at a rate of 0.8 kg. a.i./ha. No increase in
    3-methyl-4-nitrophenol indicating the hydrolysis of fenitrothion
    residues was observed during 8 days following treatment. Levels of
    3-methyl-4-nitrophenol did not exceed 10% of the fenitrothion
    residues (Cerna & Benes, 1972).

         Strawberries were treated twice with fenitrothion (EC) at a
    rate of 1.0 kg a.i./ha; the residue levels were 0.02-0.03 mg/kg and
    0.005-0.007 mg/kg, 7 and 15 days after treatment, respectively
    (FAO/WHO, 1975b). Following 3 applications of fenitrothion to
    tomatoes, a residue of 1.32 mg/kg was detected on the same day as
    the final application (Kannan & Jayarnama, 1981). The residue level
    dropped to 0.07 mg/kg, one day later, but there was very little
    further reduction in fenitrothion levels over a further 2-week
    period.

         Fenitrothion (as EC, dust, or WP) was applied to rice plants in
    Japan at rates of 0.5-1 kg a.i./ha at various time intervals (3-5
    times/season) before harvest. Over 120 samples of harvested rice
    were analysed for residues of the parent compound. The average
    residue levels ranged from negligible (0.001 mg/kg) to 0.1 mg/kg
    with a maximum level of 0.3 mg/kg, 11-20 days after the final
    application, and 0.001 mg/kg, 41-67 days after treatment (Sumitomo
    Chemical Co. Ltd, 1969).

         A variety of fenitrothion formulations were applied 1-7 times
    to rice crops pre-harvest at intervals ranging from 14 to 120 days.
    Most of the samples of hulled rice did not contain any residues at
    harvest (limit of determination 0.001 mg/kg), but a few contained
    low levels (maximum level 0.025 mg/kg) (FAO/WHO, 1978b).

         Fenitrothion is also used in the post-harvest treatment of
    stored grain. When grains with a moisture content of 12-13% were
    treated with fenitrothion at 15 mg/kg (18 mg/kg for brown rice), the
    residues decreased after 3 and 6 month at 25 °C to 6.8 mg/kg and 3.1
    mg/kg, respectively, in barley, 6.9 mg/kg and 4.2 mg/kg in oats, 6.2
    mg/kg and 3.5 mg/kg in rice, 11.5 mg/kg and 8.0 mg/kg in brown rice,
    and to 10 mg/kg and 7.5 mg/kg in polished rice. The rates of
    decrease of fenitrothion in/on grains in storage can be predicted
    accurately from the temperature, relative humidity, and dosage level
    (FAO/WHO, 1978b).

         When grains were subjected to milling, processing, preparation,
    and cooking, there was a significant loss of fenitrothion.
    Fenitrothion was deposited on the epidermis and removed with bran
    during the milling process, so that the residue level on bran was
    from 2 to 2.5 times higher than that on whole wheat and about 7
    times higher than that on husked (brown) rice. After milling, the
    residue of fenitrothion in white flour was about 10% or less of the
    residue in the raw wheat. The residue in the white bread prepared
    from the white flour was reduced to 1-2% of the residue in the raw
    wheat. In case of wholemeal bread, however, 20-25% of the initial
    concentration remained after baking. The residue of fenitrothion in
    rice was decreased to 4.1 and 1.8% of the initial residue during
    husking and milling, respectively. The residue in polished rice was
    also decreased to 30% of original concentration. The concentration
    of fenitrothion in oats, rice in husk, husked rice, and polished
    rice decreased to 30-60% of the initial concentration after boiling.
    The malting process removed substantially all of the fenitrothion
    residue on raw barley. During the processing of oats for the
    production of rolled oats and groats, more than 95% of the residues
    on the raw oats were removed (FAO/WHO, 1977).

         In the United Kingdom, fenitrothion was found in home-produced
    and imported wheat at levels of up to 0.2-0.9 mg/kg in 1982 (MAFF,
    1986). During the period of 1984-88, residues of fenitrothion were
    found in haricot and mung beans at levels of up to 0.1 mg/kg, but
    residues in several other pulses did not exceed 0.05 mg/kg. In
    retail wheat products, fenitrothion was found at levels of up to
    0.05 mg/kg in white bread, 0.3 mg/kg in brown bread, 0.5 mg/kg in
    bran, and 0.02 mg/kg in cereal-based infant foods, but was not
    detected in breakfast cereals, wheatgerm products, brown rice, rye
    products, and processed oats, the level of detection being 0.01-0.1
    mg/kg, depending on the commodity and the year of survey (MAFF,
    1989).

    5.2  Human exposure

    5.2.1  Food

         In the USA, average fenitrothion residues of 0.0001 mg/kg were
    detected in grains and cereal products in 1979-80, and the average
    intake for an adult from this source was calculated to be 0.0608
    µg/day (or 0.001 µg/kg body weight per day) in 1980 (Gartrell et
    al., 1985a). For the infant and toddler, maximum daily intakes were
    estimated to be < 0.001 µg/kg body weight per day and 0.002 µg/kg
    body weight per day, respectively, during 1977-80 (Gartrell et al.,
    1985b).

    6.  KINETICS AND METABOLISM

         The metabolic pathways of fenitrothion in mammals are shown in
    Fig. 8.1

    6.1  Absorption, distribution, metabolic transformation,
         elimination, and excretion

         32P-fenitrothion administered orally at doses of 15 and 500
    mg/kg to rats and guinea-pigs, respectively, was readily absorbed
    from the gastrointestinal tract and distributed among various
    tissues. The concentrations of 32P in the blood of rats reached a
    maximum (15.5 µg/g) 1-3 h after treatment, and diminished to below
    detectable levels within 4 days (Miyamoto et al., 1963a).

         Following intravenous injection of 32P-fenitrothion in rats
    or guinea-pigs at a dose of 15 or 40 mg/kg, fenitrothion disappeared
    equally rapidly from the blood and tissues (Miyamoto, 1964a, 1969).
    The radioactivity (32P) was mostly excreted within 2-4 days into
    the urine (85-97%), up to 10% being eliminated in the faeces,
    accounting for nearly 100% recovery of the dose. The metabolites in
    excreta were demethyl fenitrothion [7], demethyl fenitrooxon [20],
    dimethylphosphorothioic acid [19], and dimethylphosphoric acid [25].
    Fenitrooxon [1] was detected only after intravenous administration
    of a large amount of fenitrothion and not after oral administration
    (Miyamoto et al., 1963a; Miyamoto, 1964a).

         Hollingworth et al. (1967a) studied the metabolism of
    fenitrothion in white mice. 32P-fenitrothion administered orally
    to mice at a dose of 3, 17, 200, or 850 mg/kg was rapidly eliminated
    in the urine and faeces with a recovery of > 90% 72 h after
    treatment.  The isolated metabolites indicated that both the
    P-O-alkyl and P-O-aryl bonds of fenitrothion and fenitrooxon [1]
    were cleaved. No evidence was obtained indicating that the nitro
    group was reduced to form aminofenitrothion [13] or that the ring
    methyl group was oxidized. At the lower dose (17 mg/kg), demethyl
    fenitrothion [7], demethyl fenitrooxon [20], dimethylphosphorothioic
    acid [19], and dimethylphosphoric acid [25] were the major
    metabolites. At the 200 mg/kg body weight dose, the amounts of
    dimethylphosphorothioic acid [19] and dimethylphosphoic acid [25]
    decreased, and demethyl fenitrothion [7] increased.

                  

    1  Chemical structures in Fig. 1 to 8 are referred to according to
       numbers in the brackets.

    FIGURE 8

          m-Methyl-14C-fenitrothion, administered orally at a dose of
    15 mg/kg to Wistar rats, ICR mice, native Japanese rabbits, and
    Beagle dogs, was readily absorbed from the gastrointestinal tract
    and distributed to various tissues with maximum concentrations of
    0.093 mg/kg (rats) - 0.144 mg/kg (dogs) after 1-3 h of the
    treatment, and the radiocarbon was rapidly and completely
    eliminated, mainly in the urine of rats (89-95%), mice (> 90%),
    rabbits (86-94%), and dogs (88%) (Miyamoto et al., 1976b).
    Examination of 11 rat tissues, including fat and muscle, revealed
    that the concentrations of fenitrothion ranged from 0.004 mg/kg to
    less than 0.001 mg/kg (except in fat-0.034 mg/kg), 24 h after
    administration. Whole body autoradiography also indicated the rapid
    disappearance of the radiocarbon from the tissues of mice. The
    cumulative patterns of elimination were essentially the same among
    these animals when radioactive fenitrothion was given at 15 mg/kg
    body weight. Similar patterns were obtained in rats when
    fenitrothion was administered at 105 mg/kg body weight or 15 mg/kg
    body weight after a total of 5 pretreatments with non-radioactive
    fenitrothion at 15 mg/kg body weight every other day. Thin-layer
    chromatographic analysis of the urinary metabolites showed the
    absence of intact fenitrothion and the presence of as many as 18
    metabolites, of which 17 (92-99% of radioactivity) were identified.
    The differences in the composition of the metabolites among these
    animal species and between males and females of the same species
    were mostly quantitative. The percentage of the metabolites
    retaining the P-O-aryl linkage varied with animal species, ranging
    from 8.6% (rabbits) to more than 56.9% (dogs). Most of these
    metabolites were demethylated products [7,20] at the O-methyl
    position. Rats and mice tended to eliminate greater amounts (15-26%)
    of demethyl fenitrooxon [20] than rabbits and dogs (2-6%).
    3-Methyl-4-nitrophenol [9], free or as conjugates with sulfuric acid
    [26] or glucuronic acid [27], constituted another group of major
    metabolites. Approximately 50-75% of the urinary radioactivity was
    accounted for by these three metabolites ([9] [26] [27]), except in
    dogs (36%). The urinary activity in rabbits (64-75%) exceeded that
    in other animal species (50-60%). A trace amount of the oxidized
    phenols (0.5-2%) [10,22] was present in rats and rabbits. Rabbits
    were exceptional in excreting fenitrooxon [1] and animofenitrothion
    [13], though in small amounts (0.1-3.7%). The urine of rabbits and,
    to a lesser extent, of rats contained several minor metabolites
    derived from aminofenitrothion [13] or from 3-methyl-4-aminophenol
    [28]. The minor products totalled approximately 15% of the excreted
    radiocarbon in rabbits and about 12% in rats. A few metabolites had
    unique structures resulting from the reduction of the nitro group
    and oxidation of the  m-methyl group [29]. An appreciable amount of
    the excreted metabolites from the 4 animal species was in the form
    of conjugates. It appeared that rabbits were most active in this
    regard, and dogs least active. In the 4 species treated, higher
    amounts of sulfate conjugates than glucuronides were excreted. Thus,
    fenitrothion was

    metabolized through two major pathways, via O-demethylation and via
    cleavage of the P-O-aryl bond. Neither  S-(3-methyl-4-nitrophenyl)
    glutathione mediated by glutathione  S-aryltransferase nor ring
    hydroxylation products have been positively demonstrated (Miyamoto
    et al., 1976b).

         Although reduction of the nitro group in the fenitrothion
    molecule, presumably by intestinal microorganisms, was a minor
    metabolic pathway in the above 4 animal species, it was the major
    metabolic pathway in ruminants. In fact, a study of female goats
    revealed that most of the urinary and faecal metabolites of
    fenitrothion were amino derivatives [13,14,30] and were formed most
    probably in rumen fluid (Mihara et al., 1978).

         The metabolism of fenitrothion in Wistar rats with hepatic
    lesions induced experimentally by dietary administration of
    diaminodiphenyl-methane (DDM), by feeding a low protein-high fat
    diet (LPHF), or by intramuscular treatment with carbon
    tetrachloride, was also investigated. The  in vitro rates of
    degradation of fenitrothion were significantly reduced in all
    preparations from livers with induced hepatic lesions, with the
    greatest reduction produced by LPHF followed by carbon
    tetra-chloride and DDM. The rate of degradation of fenitrothion and
    fenitrooxon [1] was less severely affected than the rate of
    activation of fenitrothion, because of the greater activity of
    glutathione  S-alkyltransferase (Miyamoto et al., 1977a). However,
    the cumulative excretion patterns of radiocarbon were not altered by
    these three hepatic lesions after oral administration to the injured
    rats of either 15 or 50 mg  14C-fenitrothion/kg body weight, or 15
    mg/kg body weight of the compound after pretreatment with approx.
    2.8 mg/kg body weight per day of nonactive fenitrothion for 4 weeks.
    Moreover, the injured rats metabolized fenitrothion equally as well
    in vivo, as the control animals, even though the pathway yielding
    demethyl fenitrothion [7] predominated. Higher or short-term doses
    of fenitrothion tended to reduce the metabolic differences observed
    between the injured and the control animals (Miyamoto et al.,
    1977b). These results indicated that even very severe hepatic
    lesions, such as those described here, hardly influenced the in vivo
    detoxification of fenitrothion and the excretion of its metabolites.
    The results also indicated that there was not much possibility of
    retention or storage of the parent compound and/or its toxic
    metabolites in the mammalian body under such unfavourable
    conditions.

         The dermal penetration of 14C-ring-labelled fenitrothion and
    aminocarb was determined in male, rhesus monkeys and male,
    Sprague-Dawley rats. In monkeys, 49 ± 4% of the fenitrothion
    (urinary excretion half-life = 14 h) was absorbed from the

    forehead, while 21 ± 10% of the fenitrothion (half-life = 17 h) was
    absorbed from the ventral forearm. Monkey forehead was 2.3 times
    more permeable than the forearm. In rats, 84 ± 12% of the
    fenitrothion (half-life = 20 h) was absorbed from the middorsal
    region (Moody & Franklin, 1987).

         The presence of N,N-diethyl-m-toluamide (DEET), used as an
    insect repellent by workers spraying fenitrothion, increased the
    absorption of 14C fenitrothion through rat skin (32% DEET; 15%
    control with acetone) and monkey skin (9.7% DEET; 3.2% control)
    (Moody et al., 1987b).

    6.2  Retention and turnover

         To evaluate the possible retention of fenitrothion residues in
    animal tissues, methyl-14C-fenitrothion was administered orally to
    male Wistar rats at 15 mg/kg body weight per day for 7 days, and
    then at 30 mg/kg body weight per day for a further 3 days. A
    measurable amount (0.09 mg/kg) of fenitrothion was found in
    abdominal fat and athe level increased (2.4 mg/kg) at the later
    staes of administration. This amount, however, tended to disappear
    quite rapidly on cessation of the administration (Miyamoto, 1977c).

         Following administration of 10 or 3 mg fenitrothion/kg body
    weight per day to male native Japanese rabbits for 6 months, blood,
    skeletal muscle, and abdominal fat were analysed by gas
    chromatography for fenitrothion and fenitrooxon. In most cases,
    blood and muscle did not contain any detectable amounts of either
    compound (detection limit for fenitrothion 0.005 or 0.002 mg/kg, and
    that of fenitrooxon, 0.01 mg/kg). Averages of 0.131 mg
    fenitrothion/kg (0.243 mg/kg maximum) and of 0.045 mg/kg were
    measured in the fat of rabbits dosed at 10 and 3 mg/kg body weight
    per day, respectively, while muscle contained a maximum of 0.006 mg
    fenitrothion/kg. No fenitrooxon was detected (Miyamoto et al.,
    1976a).

         Three male beagle dogs were treated orally with 5 mg
    fenitrothion/kg body weight per day, 6 days per week, for 10 months.
    After termination of the treatment, only the fat contained trace
    amounts of fenitrothion (maximum of 0.160 mg/kg) (Tomita et al.,
    1974).

    7.  EFFECTS ON EXPERIMENTAL ANIMALS AND  IN VITRO TEST SYSTEMS

         A more complete treatise on the effects of organophosphorus
    insecticides in general, especially their short- and long-term
    effects on the nervous system, can be found in Environmental Health
    Criteria 63: Organophosphorus insecticides - A general introduction
    (WHO, 1986).

         No-observed-effect levels on the ChE in the plasma,
    erythrocytes, and brain of animals treated with fenitrothion under
    various conditions are summarized in Annex II.

    7.1  Single exposure

         As with other organophosphorus insecticides, a large dose of
    fenitrothion produces toxic signs and symptoms in various animals by
    the inhibition of acetylcholinesterase (AChE) in the nervous system,
    with the consequent accumulation of excessive levels of
    acetylcholine. The major toxic signs in experimental animals are
    salivation, tremor, exophthalmos, urinary incontinence,
    piloerection, and dyspnoea, which are similar to the toxic signs
    elicited by other organophosphorus insecticides (Namba, 1971).

         The acute toxicity of fenitrothion varies according to the
    species of the test animal, its sex, the route and method of
    administration and/or the solvent used, as shown in Table 4. The
    acute oral LD50s in mammals range from 330 mg/kg in the rat to
    1850 mg/kg in the guinea-pig, the dermal LD50s range from
    890 mg/kg in the rat to > 2500 mg/kg in the mouse.

         Groups of 8 male and 8 female Sprague-Dawley rats were exposed
    to fenitrothion mists dissolved in a mixture of deodorized kerosene
    and xylene (particles mostly less than 3 µ in diameter) to assess
    inhalation toxicity at aerial concentrations of 10, 70, and 186
    mg/m3 for 2, 4, or 8 h. No significant toxic signs were observed
    in the rats exposed to an aerial concentration of 10 mg/m3 for 2
    and 4 h. With longer exposure and/or higher fenitrothion
    concentrations, toxic symptoms developed including salivation,
    urinary incontinence, tremor, lacrimation, muscular fibrillation,
    and dyspnoea, and, after 8 h exposure to 186 mg fenitrothion/m3, 2
    out of 8 males died. A transient body weight decrease was observed
    after 8 h exposure to 10 and 70 mg fenitrothion/m3. A marked body
    weight decrease was observed at a concentration of 186 mg/m3. The
    LC50 value for fenitrothion in rats exposed for 8 h, was estimated
    to be more than 186 mg/m3 (Kohda & Kadota, 1979).


    
    Table 4.  Acute toxicity of fenitrothion
                                                                                                                                              

    Animal          Strain              Sex            Route         LD50 (mg/kg)   Vehicle              Reference
                                                                                                                                              

    Mouse                               male           oral          1336                                Carshalton (1964)
                                        female         oral          1416
                    dd                  male           oral          1030           10%Tween 80 aq.      Miyamoto & Kadota (1972)
                    dd                  female         oral          1040           10%Tween 80 aq.
                    dd                  male           dermal        > 2500         Undiluted            Kadota et al. (1972)
                                        female         dermal        > 2500         Undiluted

    Rat             Sherman             male           oral          740            Peanut oil           Gaines (1969)
                    Sherman             female         oral          570            Peanut oil
                    Sprague-Dawley      male           oral          330            10%Tween 80 aq.      Miyamoto & Kadota (1972)
                    Sprague-Dawley      female         oral          800            10%Tween 80 aq.
                    Wistar              male           oral          940                                 Benes & Cerna (1970)
                    Wistar              female         oral          600
                    Sprague-Dawley      male           dermal        890            Undiluted            Kadota et al. (1972)
                    Sprague-Dawley      female         dermal        1200           Undiluted

    Guinea-pig                          male           oral          500                                 DuBois & Puchala (1960)
                                                       oral          1850           Sorpol 2001          Miyamoto et al. (1963b)

    Dog             Beagle              male/          oral          > 681          Gelatin capsule      Mastalski (1971b)
                                        female

    Hen             White Leghorn                      oral          500            10%Tween 80 aq.      Kadota et al. (1975b)

                                                                                                                                              

    

        The pulmonary toxicity of fenitrothion was evaluated following
    a single exposure of caged rats (n = 160) placed in a field
    oversprayed by aircraft during an operational forest treatment.
    Depending on the position of the cages, the air concentrations of
    fenitrothion measured in the first 30 min after spraying, were 6.19
    and 33.2 µg/m3. Plasma pseudocholinesterase activity and pulmonary
    alveoli ultrastructure were used as indices of fenitrothion
    exposure. Although a few signs of toxic lung injury were observed on
    days 3 and 7, there were no cholinergic signs or effects on
    pseudocholinesterase activity within 12 h in exposed animals,
    compared with controls. The alveolar toxic reaction was limited to
    small and discrete foci, and was entirely reversible within a period
    of 2 months (Coulombe et al., 1986).

        Rat lungs were examined with light and electron microscopes,
    3-60 days after exposure to fenitrothion. Groups of 9 male,
    Sprague-Dawley rats were exposed by a "nose-only" apparatus for 1 h
    to an aerosol of fenitrothion (15%) mixed with non aromatic
    hydrocarbon solvent and oil diluent at 2 or 500 mg/m3. Only minor
    modifications of lung alveolar tissue were observed after exposure
    to the higher concentration. At 3 days, discrete foci of mild
    inflammation were detected, including interstitial oedema, cellular
    infiltration, and an increased number of alveolar macrophages. At 7
    days, signs of irritation were diminished, and, at 21 and 60 days,
    alveolar tissues were essentially normal.  Exposure to the lower
    concentration induced more limited changes at 3 days; no
    modification was seen at later examinations. It was considered that
    a single exposure to this fenitrothion mixture at 500 mg/m3 did
    not present a serious hazard to the lung (Chevalier et al., 1984).
    Alveolar irritation was also seen in the solvent- exposed control
    animals.

        When Holstein milk cows and sheep (male) were administered
    fenitrothion orally at 500 and 770 mg/kg body weight, respectively,
    they showed signs of poisoning, such as paralysis of the hindlegs
    and salivation, but gradually recovered 4 h after treatment (Namba
    et al., 1966). Pigs given a single oral dose of 310 mg/kg body
    weight showed typical signs of ChE inhibition, but the toxic signs
    disappeared within 48 h. When cows and sheep were given fenitrothion
    at 3 mg/kg body weight per day, for 90 and 60 days, respectively,
    the ChE activity in the plasma decreased in both species early in
    the test period, but recovered fully after 30 days.

    7.2  Skin and eye irritation; skin sensitization

    7.2.1  Skin and eye irritation

        One tenth ml of fenitrothion (technical) was applied to one eye
    of 9 male, New Zealand White rabbits. The untreated eye served as a
    control. The treated eyes of 6 animals remained unwashed. The

    treated eyes of the other 3 animals were flushed for 1 min with
    about 300 ml lukewarm water, 30 seconds after application. Slight
    hyperaemia in the conjunctiva was observed 1 h after application in
    the unwashed eyes. This change had disappeared 48 h after
    application. No irritating reactions were induced in any washed
    eyes. The irritating potency of fenitrothion in eyes was judged to
    be minimal for the unwashed group, and negative for the washed group
    (Hara & Suzuki, 1981).

        A half ml of fenitrothion (technical) on a 1 x 1 inch lint
    patch was applied to abraded and intact parts of the back skin of 6
    New Zealand White rabbits. No irritating reactions, such as erythema
    and oedema, were noticed in the animals. The irritating potency of
    the material was estimated to be negative (Hara & Suzuki, 1981).

    7.2.2  Skin sensitization

        The Landsteiner-Draize test with fenitrothion (technical) was
    conducted on 6 male, Hartley guinea-pigs using
    2,4-dinitrochloro-benzene (DNCB) as a positive control, to examine
    possible skin sensitization activity. Fenitrothion dissolved in corn
    oil at concentrations of 1 or 5% was applied intradermally every
    other day, 10 times. The animals were treated for a challenge with
    intradermal injection and dermal application 2 weeks after the last
    sensitizing treatment. Allergic reactions were not observed in any
    animals treated with fenitrothion, while reactions, such as swelling
    and hyperaemia, were clearly noticed in the animals treated with
    DNCB. It was concluded that fenitrothion (technical) was not a skin
    sensitizer (Kohda et al., 1972).

        The maximization test was undertaken to study the allergenicity
    of fenitrothion. Ten young adult, female, Hartley guinea-pigs
    weighing from 300 to 500 g were studied, induction and challenge
    being undertaken according to the original method. The
    concentrations of the compounds for the induction were 5 and 25% for
    intradermal and topical treatment, respectively. Challenge
    concentrations of 0.05% showed the potential for allergenicity in
    this test (Matsushita et al., 1985).

    7.3  Short-term studies

    7.3.1  Rat

        Male rats were given daily oral doses of 13 mg fenitrothion/kg
    body weight for 28 days. Erythrocyte ChE activity was severely
    depressed, but recovered 30 days after withdrawal of fenitrothion
    (Kimmerle, 1962a).

        Oral administration of fenitrothion at 7.25 or 14.5 mg/kg body
    weight per day to male, Wistar rats (5/group) for 28 days resulted
    in increases in plasma corticosterone and glucose levels, 7 days
    after the start of treatment, and in the relative adrenal weight, 2
    weeks after the start of treatment (Yamamoto et al., 1982b).

        Groups of 36 male, CD rats received technical fenitrothion by
    oral gavage (2.5, 5.0, 10.0, or 20.0 mg/kg per day) for 30
    consecutive days. No significant treatment-related changes were
    observed by serum biochemistry or by light microscopy of liver.
    However, a dose-dependent decrease was noted in the brain, plasma,
    and erythrocyte ChEs as well as tissue esterase activities. Eight
    out of 36 animals died at the 20.0 mg/kg level (Trottier et al.,
    1980).

        Male rats were fed 5, 10, or 20 mg fenitrothion/kg diet for 5
    weeks. The activity of brain and erythrocyte ChE was normal in the 5
    mg/kg group, whereas the 10 mg/kg group showed a slight depression
    of erythrocyte ChE activity after 5 weeks and recovery 2 weeks after
    withdrawal. The 20 mg/kg group showed some depression of activity in
    both erythrocyte and brain ChE and the recovery in brain ChE
    remained incomplete 2 weeks after withdrawal (Carshalton, 1964).

        The neurobehavioural effects were examined in male,
    Sprague-Dawley rats (6/group) of fenitrothion administered orally at
    doses of 10, 20, or 40 mg/kg body weight, daily, for a period of 40
    days.  At the 2 higher doses, mortality was more than 50%, while
    only one animal died at a dose of 10 mg/kg. Toxic signs, such as
    cholinergic signs, loss of reflexes, and changes in motor activity
    and indices of ataxia, were observed markedly at the 2 higher doses,
    and slightly at the lowest dose. However, these effects tended to
    recover gradually later in the study (Rondeau et al., 1981).

        Groups of male, Wistar rats (16 or 17 in number) were fed 0,
    32, 63, 125, 250, or 500 mg fenitrothion/kg diet for 90 days.
    Mortality, food intake, growth, general behaviour, urinalysis,
    average organ weights, and histopathology in the groups fed 32, 63,
    125, and 250 mg/kg diet were comparable to those in the controls.
    All animals fed 500 mg/kg diet showed clinical signs of
    anticholinesterase poisoning and there were minimal toxic signs in 4
    animals in the 250 mg/kg diet group. In the 500 mg/kg group, the
    average weights of the testes and brain were increased in comparison
    with those of the control group. On monthly interim sacrifice of 4
    rats from each group, the cholinesterase (ChE) activity of plasma,
    erythrocyte, brain cortex, liver, and kidney showed a dose-dependent
    depression, the lowest activity being in the brain. The ChE activity
    in the 32 and 63 mg/kg diet groups generally increased by day 60 of
    feeding to a level within the normal limits (Misu et al., 1966).

        Fenitrothion (60% water miscible concentrate) was given to
    groups of 12 Wistar rats/sex at dose levels of 0, 20, 92.8, 430.7,
    or 2000 mg/kg diet in the feed or 0, 10, 46.4, 215, or 1000 mg/litre
    in drinking-water, for 90 days. The levels causing no appreciable
    effect on the ChE activity of plasma, erythrocyte, and whole blood
    were 20 mg/kg diet and 10 mg/litre drinking-water. The above
    mentioned levels and 92.8 mg/kg diet and 46.4 mg/litre and 215
    mg/litre in drinking-water did not cause any effects on food or
    water intake, weight gain, average organ weights, haemogram, and
    blood biochemistry. However, 92.8 mg fenitrothion/kg diet and 46.4
    mg/litre in the drinking-water moderately depressed the activities
    of whole blood and erythrocyte ChE and had a more marked depressive
    effect on plasma ChE. The ChE activity recovered between 30-40 days
    after withdrawal of fenitrothion.  The levels of 430 mg/kg diet and
    1000 mg/litre drinking-water caused a depression in body weight gain
    (Cooper, 1966).

        Two groups of male rats (20 each) were dosed by stomach tube
    with fenitrothion (50% formulation) at 10 mg/kg or 11 mg/kg body
    weight, for 6 days per week, over 6 months. During the first weeks,
    the rats showed a temporary deterioration in general condition and
    loss of weight. Haematology and urinalysis during the study and
    gross and microscopic pathology at its termination did not reveal
    any abnormalities (Klimmer, 1961).

        Groups of rats (15 males and 15 females) were fed fenitrothion
    at 0, 10, 30, or 150 mg/kg diet for 6 months. In all groups, growth,
    food and water consumption, mortality, blood and urinalysis, and
    blood biochemistry were comparable with those of the controls. The
    ChE activities in the brain, erythrocytes, and plasma were depressed
    in both sexes in the 150 mg/kg diet group and in females in the 30
    mg/kg diet group. In the 10 mg/kg diet group, only the plasma ChE of
    females was depressed. Absolute and relative organ weights were
    within normal limits. No histopathological changes were found in the
    organs examined. Based on brain acetylcholinesterase inhibition, a
    NOAEL of 10 mg/kg diet was concluded (Kadota et al., 1975a).

        Groups of 8 male and 8 female rats were fed diets containing 0,
    10, 50, or 250 mg fenitrothion/kg for 34 weeks. In another test,
    groups of 16 rats of each sex were fed fenitrothion at 0, 5, 25, or
    125 mg/kg diet over the same period. The feeding of fenitrothion at
    250 mg/kg diet resulted in a decrease in body weight gain in
    females. In the 125 mg/kg diet group, a lower relative weight of
    spleen was found in both sexes. The ChE activities in both the
    plasma and erythrocytes, measured at intervals, showed a
    dose-dependent decrease in all test groups, except for males at 5
    mg/kg diet whose plasma ChE activity was not suppressed. In females,
    the depression was slight. The ChE activity in the brain was
    decreased only in the 250 mg/kg diet group (Benes & Cerna, 1970).

        Groups of 9 and 10 male Sprague-Dawley rats were fed 0, 25,
    100, or 400 mg fenitrothion/kg diet for 63 weeks. A positive control
    group was fed 800 mg malathion/kg. At the 400 mg/kg level of
    fenitrothion, body weight gain was decreased and only a few animals
    survived the 63-week period. At this level, there was also a 100%
    depression of erythrocyte ChE. At the 100 mg/kg level, a slight ChE
    depression (10-30%) occurred in the brain and a moderate depression
    (30-65%) in the erythrocyte and plasma. At 25 mg/kg diet,
    fenitrothion had a slight effect on plasma ChE activity, but did not
    cause any effects on other parameters (food intake, body weight
    gain, brain and erythrocyte ChE) evaluated (Ueda & Nishimura, 1966).

        Groups of male, Wistar rats (60/group with 120 controls) were
    administered fenitrothion, by gavage, at 0, 0.5, 1, 5, or 10 mg/kg
    body weight per day, for 12 months. Each month, 10 controls and 5
    rats from each group were sacrificed. After 12 months,
    administration was stopped and survivors were held for an additional
    2 months to monitor recovery from the biological effects of the
    treatment. No changes attributable to treatment with fenitrothion
    were observed in haematology or blood biochemistry, except in
    esterase activities. Marked reductions in hepatic ChE, and brain and
    erythrocyte AchE activities, observed at doses of 5 and 10 mg/kg
    body weight per day, within 1 month of treatment, persisted for the
    duration of the treatment. Two months after treatment was
    terminated, the esterase activities in all treated rats were
    comparable to those in the controls. Little change was measured at
    0.5 and 1 mg/kg per day (Ecobichon et al., 1980).

        Groups of Wistar rats (26 males and 27 females) were fed a diet
    containing 0, 1, 5, or 25 mg fenitrothion/kg for one year. No
    significant changes were observed in body weight, food and water
    intake, organ weights, or histopathology. The ChE activity in the
    brain, liver, and erythrocytes was reduced at 5 and 25 mg/kg diet
    during the first month but then recovered (Kanoh et al., 1982).

        A nose-only inhalation toxicity study of fenitrothion was
    conducted on Sprague-Dawley rats (Breckenridge et al., 1982). Groups
    of 10 male and 10 female rats (20/sex for the controls) were exposed
    to fenitrothion 11% emulsifier mixture at chamber concentrations of
    0, 6.7, 20, or 60 mg/m3, for 2 h/day, for 30 consecutive days. ChE
    activity in the plasma, erythrocytes, and brain was inhibited in the
    60 mg/m3 males and in all the treated females, except those in the
    6.7 and 20 mg/m3 groups, in which the erythrocyte ChE activity was
    not affected. Hepatic and renal carboxyesterases were inhibited in
    the 60 mg/m3 male group and the 20 and 60 mg/m3 female groups.
    These enzyme activities had returned to normal values 30 days after
    treatment. Suppression of the brain ChE activity in the 60 mg/m3
    female group persisted. Haematological, urinary, blood biochemical,
    and histopathological studies did not reveal any deleterious effects
    of fenitrothion.

        Durham et al. (1982) reported a short-term study of
    fenitrothion (11% emulsifiable concentrate) in the absence or
    presence of Atlox 3409F (emulsifier) and Dowanol TPM (cosolvent).
    Forty-five male, Sprague-Dawley rats were assigned to each of the
    treated and control groups. No changes in the haematological, serum
    biochemical parameters or in tissue morphology were observed in rats
    treated with fenitrothion at doses of 1, 5, 10, or 20 mg a.i./kg.
    The emulsifier and co-solvent did not substantially enhance or
    reduce the toxicity of fenitrothion.

    7.3.2  Dog

        Groups of dogs (1 male and 1 female) were given daily oral
    doses (by capsule) of 0, 2, 9, or 40 mg fenitrothion/kg body weight
    for 98 days. Body weights, blood biochemistry, ChE levels, and
    haematology were checked at intervals. At the 2 mg/kg level,
    fenitrothion did not produce any effects on the parameters examined.
    At 9 mg/kg, a slight depression after 60 days and, at 40 mg/kg, a
    moderate depression after 29 days occurred in whole blood, plasma,
    and erythrocyte ChE activity. At 40 mg/kg, there were also marked
    toxic signs typical of cholinergic stimulation, and the dogs in this
    group were sacrificed before the end of 98-day period (Cooper,
    1966).

        Groups of dogs (6 males and 6 females) were fed fenitrothion at
    levels of 0, 30, 100, or 200 mg/kg diet for two years. Body weights,
    blood biochemistry, and plasma, erythrocyte, and brain ChE
    activities were monitored, together with histopathological
    examination. The only adverse effect was a reduction in the ChE
    activities. Depression of plasma ChE activity was apparent in all
    groups, while erythrocyte enzyme activity was unaffected in the 30
    mg/kg group, when the treated and control animals were compared. The
    brain ChE activity was decreased only after ingestion of 200 mg/kg
    (Mastalski et al., 1973).

        Groups of Beagle dogs (6 males and 6 females) were fed
    fenitrothion at dose levels of 0, 5, 10, or 50 mg/kg diet for one
    year. The only treatment-associated change was a depression of ChE
    activity. At 50 mg/kg diet, plasma ChE was depressed in both sexes,
    and erythrocyte ChE was slightly depressed in the males only.
    However, brain ChE was not depressed at any levels.  The
    no-observed-effect level was 10 mg/kg or 50 mg/kg diet, based on the
    effects on erythrocyte or brain ChE, respectively (Griggs et al.,
    1984).

        A group of 3 male Beagle dogs was given fenitrothion in
    capsules at 5 mg/kg body weight per day, for 6 days a week, over 10
    months. A marked depression of plasma and erythrocyte ChE activities
    was observed compared with the control group (2 animals). However,
    no appreciable accumulation of the compound was noted in the blood,
    fat tissue, or liver (Tomita et al., 1974).

        Groups of Beagle dogs (2 females) were treated orally with 
    fenitrothion at dose levels of 0 or 2 mg/kg body weight per day (by
    capsule) for one year. A marked depression of plasma and erythrocyte
    ChE activities was observed 2 weeks after initiation of treatment.
    No changes attributable to treatment with fenitrothion were found in
    haematology, blood biochemistry, or ophthalmology (Ogata, 1972).

    7.3.3  Rabbit

        When groups of male Japanese albino rabbits (15 animals per
    group) were administered fenitrothion at 0, 3, or 10 mg/kg body
    weight per day in the diet for 6 months, a significant depression of
    the plasma and erythrocyte ChE activities was observed in both
    treated groups. At the higher dosage, depression of the brain ChE
    was also found. However, no noteworthy changes, either biochemical
    or histochemical, were observed in musculi rectus medialis ChE, and
    the fine structure of the neuromuscular junctions of the tissue was
    essentially normal when examined using an electron microscope. No
    other adverse effects were observed in behaviour, mortality,
    haematology, clinical biochemistry, organ weights, or histopathology
    of major organs and tissues (Miyamoto et al., 1976a).

    7.3.4  Guinea-pig

        Treatment of male guinea-pigs with 5 or 10 mg fenitrothion/kg
    ip for 30 days resulted in a dose-dependent increase in
    acetylcholine levels in the heart, decreased heart rate, and
    hypocalcaemia (Anand et al., 1989).

        Active sensitization toxicity by inhalation of fenitrothion
    (technical) or fenitrothion 22% emulsifiable concentrate (EC) was
    examined in 10-15 male and female Hartley guinea-pigs using
    bacterial alpha amylase as a positive control material. Fenitrothion
    (technical) suspended in 10% Tween 80 aqueous solution and the
    undiluted EC formulation were sprayed daily for 120 min for 7 days.
    The air concentrations of fenitrothion were 226 and 628 mg a.i./m3
    in the chamber where the technical sample was sprayed, and 360 and
    1048 mg a.i./m3 in the chamber where the EC formulation was
    sprayed. Animals inhaling the material at the higher air
    concentration of the EC formulation showed salivation from the third
    day. The cholinesterase activities in the brain, packed red cells,
    and plasma were severely inhibited in treated animals at the
    completion of the sensitization period. The animals were challenged
    7 days after the last sensitizing inhalation, but signs of allergic
    asthma were not observed in any animals treated with fenitrothion.
    In contrast, animals treated with bacterial alpha amylase showed
    severe allergic signs of asthma. It was concluded that fenitrothion
    did not cause allergic asthma (Okuno et al., 1977).

    7.4  Long-term and carcinogenicity studies

        Groups of Wistar rats (15 males and 15 females) were fed diets
    containing fenitrothion at levels of 0, 2.5, 5, or 10 mg/kg for 92
    weeks, to investigate the effects of fenitrothion on ChE activities. 
    The ChE activity in the blood was measured after 2, 4, 6, 8, 12, 16,
    20, 24, 42, 68, and 92 weeks. In the 5 mg/kg group (equivalent to
    0.27 mg/kg body weight per day), a 20-25% decrease in plasma ChE
    activity in the males during the first 16 weeks and a 20-35%
    decrease in the females during 12 weeks were recorded. The activity,
    however, recovered during the remaining test period. In the 10 mg/kg
    group, the plasma activity decreased during the first 8 weeks by
    30-40% in males and 40-50% in females. The activity, however,
    gradually returned to normal during the next 8 weeks. The activity
    of erythrocyte ChE was decreased by 20-30% in both sexes during the
    first 6 weeks at 10 mg/kg and then recovered fully. The brain ChE
    activity, determined at the end of the test period, was not affected
    by fenitrothion at any dose level. The no-observed-effect level in
    this study was 5 mg/kg diet (0.27 mg/kg body weight per day in males
    or 0.28 mg/kg body weight per day in females) (Kadota et al.,
    1975a).

        Three groups of Charles-River albino rats (50 males and 50
    females) were administered fenitrothion at levels of 10, 30, or 100
    mg/kg diet (corresponding to 0.5, 1.5, and 5 mg/kg body weight) for
    a period of 104 weeks, with 60 females and 60 males as controls.
    These animals were derived from the F1a generation of a
    reproduction study (see section 7.5.1). Ten rats of each sex and
    group were sacrificed after one year and all the surviving animals
    at 104 weeks. The body weights of males and females at 100 mg/kg
    were lower than those of the controls from the start of the test and
    remained so in males until 52 weeks, but at the end of the test no
    significant differences were seen. Food consumption at 52 weeks was
    lower for the middle- and high-level males, but normal for low-level
    males and all the females. The mortality rate in the treated females
    was comparable with that in the control females, while, in males,
    the mortality rate was significantly higher than the controls only
    in the lowest-dose group. Blood and urine analyses were normal while
    ChE activity showed a dose-dependent decrease among the test rats.
    Significant depressions in ChE activities in the plasma were
    recorded at all 3 dosage levels (F1a being affected from the
    beginning), but erythrocyte ChE depression and brain ChE depression
    occurred only at the 30 and 100 mg/kg levels in both sexes.
    Statistical analysis of the probabilities of tumour incidence did
    not reveal any differences between the controls and the animals
    treated with 10 or 100 mg/kg. There was a decrease in the
    probability of benign tumours in males treated with 30 mg/kg and an
    increase in pituitary adenoma incidence in the 30

    mg/kg females; however, since this was not observed at the 100 mg/kg
    level, it was not considered related to treatment. Absolute and
    relative organ weights and gross and histopathology did not reveal
    any dose-dependent changes (Rutter & Nelson, 1974).

        In a study by Rutter & Banas (1975), groups of ICR Swiss mice
    (200 animals/sex) were fed a diet containing 0, 30, 100, or 200 mg
    fenitrothion/kg for 78 weeks (18 months). No observable effects
    attributable to the compound were detected on body weight gain, food
    intake, mortality, or ophthalmological and gross/histopathological
    findings. It was concluded that fenitrothion is not carcinogenic in
    mice fed up to 200 mg/kg diet for 18 months.

        Groups of B6C3F1 mice (100 males and 100 females) were
    administered fenitrothion at levels of 0, 3, 10, 100, or 1000 mg/kg
    diet. Each group of mice was divided into 2 subgroups (main and
    satellite groups) comprising 50 mice of each sex. The main groups
    were maintained on the control or test diets until death, or for a
    maximum of 104 weeks. The satellite groups were used for interim
    sacrifices. Throughout the administration period, no
    treatment-related abnormal symptoms were observed, nor were there
    any significant differences in the survival rates between control
    and treated groups. Decreases in body weight gain, food consumption,
    and water intake were observed at the 1000 mg/kg level in both
    sexes. Urinalysis, ophthalmology, and haematology did not reveal any
    treatment-related effects. Significant depression of ChE activity
    occurred in plasma at the 3 highest levels, while, in erythrocytes
    and brain, the depression occurred at 100 and 1000 mg/kg levels in
    both sexes. The blood biochemical examination revealed an elevation
    of total cholesterol values in both sexes in the 100 and 1000 mg/kg
    groups and a decrease in glucose levels in both sexes in the 1000
    mg/kg group. Some other biochemical changes were observed
    transiently in the 1000 mg/kg group. The incidence of alopoecia was
    decreased at the final sacrifice of 1000 mg/kg females. Brain
    weights were increased in both sexes in the 1000 mg/kg group.
    Histopathological examination revealed that calcification of brain
    parenchyma in both sexes in the 1000 mg/kg group, and hair
    follicular atrophy in 1000 mg/kg females were less frequent than in
    the controls. No treatment-related increase was observed in the
    incidence of any neoplastic changes. The level causing no
    toxicological effect was concluded to be 10 mg/kg diet, based on the
    depression of brain ChE (Tamano et al., 1990).

    7.5  Reproductive effects, embryotoxicity, and teratogenicity

    7.5.1  Reproductive effects

        A 2-litter, 3-generation, reproduction study on Charles River
    albino rats was carried out with 15 males and 30 females per test
    group (20 males and 40 females for control) administered dietary

    levels of 0, 10, 30, and 150 mg fenitrothion/kg. After the first
    filial generation (F1a), the highest dose level was reduced to 100
    mg/kg. Fertility, gestation, lactation, and live birth indices were
    compared. Administration of 150 or 100 mg fenitrothion/kg in the
    diet caused weight reduction in the parental animals in the P0 and
    P1 generations and suppressed lactation indices through all
    generations. The highest dose group also showed a higher incidence
    of cannibalism and smallness at weaning, whereas all litters seemed
    normal at birth. No dose-dependent malformations or
    histopathological changes were seen (Rutter & Voelker, 1974).

        Crl: CD(R)(SD)BR male and female rats (30 animals/group) were
    exposed to technical fenitrothion (94.6% pure) in the feed for 2
    generations (2 litters in the first generation and 1 litter in the
    second generation) at dietary levels of 0, 10, 40, or 120 mg/kg. A
    dose-dependent, statistically significant decrease in body weight
    gain and absolute and relative feed consumption occurred in males
    and females given 120 mg/kg diet. Body weights and body weight gains
    were significantly affected at 40 mg/kg diet in the P1 generation
    female rats during lactation, and in the F1a generation male rats
    during post-cohabitation. Absolute feed consumption values were
    significantly affected at 40 mg/kg diet in the F1a generation
    female rats. There was no compound-related effect on reproductive
    performance in either the P1 or F1a generations at levels of up
    to 120 mg/kg diet. The body weights of pups were significantly
    reduced in litters of both generations at 120 mg/kg diet and
    mortality was significantly increased in the P1 generation, F1a
    and F1b litters, and the F1a generation and F2 litters, at 120
    mg/kg diet. There were no treatment-related histomorphological
    changes in the male and female F0 and F1 generation rats at up to
    120 mg/kg diet (Hoberman, 1990).

        Groups of 10 male and 20 female rats were fed a diet containing
    0, 10, 40, or 80 mg technical fenitrothion/kg in a 4-generation,
    2-litter, reproduction study. The following parameters were
    monitored: body weight and food consumption of parent animals and
    indices of fertility, gestation, live birth, 24-h survival, 5-day
    survival, and lactation; gross pathology of all pups, organ weights,
    and histopathological examination of F4b weanlings; cholinesterase
    activity in whole blood in males of F2a (aged 15 weeks) and in all
    weanlings of F4b (aged 4 weeks). Fertility, gestation, and live
    birth indices were normal in all groups, whereas the 24-h and 5-day
    survival indices were reduced in one or both litters of the 80 mg/kg
    group in almost all generations. The lactation index was reduced in
    all generations in the 40 and 80 mg/kg groups. The mean litter size
    was smaller in all but 5 test litters, but this was without any
    clear dose-dependence. However, the lowest number of pups was found
    in 6 out of 8 litters in the 80

    mg/kg group.  The mean weight of the pups at birth and at 21 days of
    age was normal, whereas the growth of the parent animals was
    slightly decreased in the 80 mg/kg group. Plasma and erythrocyte
    cholinesterase activity was decreased in relation to the dose and
    length of exposure; in the 10 mg/kg group, the decrease was not
    significant. Organ weights and gross pathological examination did
    not reveal any abnormalities (Benes et al., 1974).

        Fenitrothion fed to 10 female rats and male rats at 200 mg/kg
    diet before mating, and during the gestation period, in a
    one-generation reproduction study did not affect the reproductive
    indices, such as fertility, gestation, and live birth indices. 
    Moreover, it was revealed that fenitrothion did not have any
    estrogenic activity, according to the mouse uterine weight assay
    (Gowda & Sastry, 1979).

    7.5.2  Embryotoxicity and teratogenicity

        Groups of female albino rabbits were inseminated (gestation day
    0) and during gestation days 6-18 were dosed with 0, 0.3, or 1 mg
    fenitrothion/kg per day in gelatine capsules. A positive control
    group given 37.5 mg thalidomide/kg per day was included. The
    compound did not induce any effects on the does or on the number of
    implantation sites, early or late resorption sites, number of dead
    or live young, or aborted fetuses. In the thalidomide group,
    approximately 10% of the fetuses showed external malformations,
    while none were seen in the other groups. No effects related to the
    administration of fenitrothion were seen on examination for internal
    or skeletal deformities (Ladd et al., 1971).

        Fenitrothion (technical grade, 96.6% purity) was dissolved in
    corn oil and administered orally to 14-16 pregnant rabbits (New
    Zealand White) during the period of organogenesis (gestation days
    7-19) at dose levels of 0, 3, 10, or 30 mg/kg body weight per day. 
    There were no treatment-related effects on pregnancy rate, fetal
    viability, fetal sex ratio, or mean fetal body weight values. 
    Implantation efficiency was slightly lower at 30 mg/kg body weight
    per day compared with the controls. There were no dose-related
    increases in the incidences of external, visceral, or skeletal
    malformations at any dose level (Morseth et al., 1986).

        Groups of 25 or 27 pregnant mice (ICR) were administered
    fenitrothion orally at dose levels of 0, 20, 70, or 200 mg/kg per
    day during gestation days 7-12. Groups of 23-26 pregnant SD rats
    were also dosed orally with fenitrothion at levels of 0, 2, 7, or 20
    mg/kg per day during gestation days 9-14. No embryotoxic or
    teratogenic effects were observed in mice or rats at any of these
    dose levels (Miyamoto et al., 1975).

        Fenitrothion (technical grade, 96.9% purity) was dissolved in
    corn oil and administered orally to 20-24 pregnant Sprague-Dawley
    rats during the period of organogenesis (gestation days 6-15) at
    dose levels of 0, 3, 8, or 25 mg/kg body weight per day. There were
    no adverse effects on pregnancy rates, mean implantation efficiency,
    fetal viability, fetal sex ratio, or mean fetal body weights. The
    frequency and the distribution of fetal malformation findings did
    not indicate a teratogenic response at any dose level. Maternal
    toxicity, as evidenced by body weight decrease and clinical
    observations (tremors), was indicated at a dose of 25 mg/kg body
    weight per day (Morseth et al., 1987).

        Prenatal administration of fenitrothion (50% EC) to CFY rats at
    5, 10, or 15 mg/kg body weight by oral gavage from days 7 to 15 of
    gestation resulted in dose-related decreases in open field activity
    and motor coordination in the offspring of animals treated at the
    two highest dose levels. Long-lasting alterations in the acquisition
    and extinction of a conditioned escape response, as well as
    increased social interactions were observed in the adult offspring.
    The results indicated a no-observed-effect level of 5 mg/kg
    (Lehotzky et al., 1989).

        Fenitrothion (97.6% purity, 0.1% of 3-methyl-4-nitrophenol) was
    administered to groups of 20 pregnant Wistar rats in sunflower oil,
    by gavage, at single daily doses of 0, 2, 8, 16, or 24 mg/kg body
    weight during days 6-15 of gestation. On day 20 of gestation, the
    rats were sacrificed and the numbers of viable and dead fetuses,
    resorptions, implantations, and corpora lutea were recorded. Fetuses
    were subjected to external and internal (skeletal and soft tissue)
    examination. Fenitrothion was not found to be teratogenic in this
    study at any dose. At doses exceeding 8 mg/kg per day, fenitrothion
    was maternally toxic (Benes & Tejnorova, 1986).

    7.6  Mutagenicity

        Fenitrothion was examined using a variety of mutagenicity tests
    including  in vitro and  in vivo gene mutation, DNA damage/repair,
    and chromosomal aberration assays (see Table 5). Most of the tests
    showed that fenitrothion was not mutagenic, but some of the tests
    gave weakly positive results: Ames tests with  S. typhimurium TA100
    (Kawachi, 1978; Moriya et al., 1983; Hara et al., 1989), sister
    chromatid exchange (SCE) assays (Kawachi, 1978) and chromosomal
    aberration tests (Kawachi, 1978). However, more recent studies
    showed that fenitrothion was negative in gene mutation assays with
     S.  typhimurium TA100 NR, a nitro-reductase-deficient strain of
    TA100, and in mammalian cells, V79 Chinese hamster lung cells.
    Mutagenicity in  S. typhimurium TA100 was considered attributable
    to the nitro-reductase inherent to bacteria (Hara et al., 1989). An
    SCE test in cultured mouse embryo cells showed a negative result for
    clastogenic potential

    (Suzuki & Miyamoto, 1980);  in vitro and  in  vivo chromosomal
    aberration tests in the rat, mouse, and Chinese hamster test systems
    also gave negative results (Hara & Suzuki, 1982a,b; Hara et al.,
    1988).

        When CFLP mice were given 3-methyl-4-nitrophenol (25 mg/kg),
    intraperitoneally, once a week for 10 weeks, the numbers of
    chromosome gaps in bone marrow were significantly increased (Nehez
    et al., 1985).

    7.7  Neurotoxicity

        Seven hens protected against acute anti-cholinesterase effects
    with atropine and 2-pyridine aldoxime methiodide (2-PAM) were given
    an oral dose of 250 mg fenitrothion/kg body weight and 3 other hens
    were given 500 mg/kg. Two of the 500 mg/kg group died within 1-2
    days, while the remaining 8 hens did not show any signs of paralysis
    during the observation period of 6 weeks (Kimmerle, 1962b).

        Groups of 6 adult White Leghorn hens were given single oral
    doses of fenitrothion at 250, 500, or 1000 mg/kg body weight.
    Tri- O-cresyl phosphate (TOCP, 300 mg/kg) was used as a positive
    control. Toxic signs, which lasted 4-10 days, occurred in all
    groups. One half of the hens in the middle dosage group and all
    those in the highest fenitrothion group died within 24-48 h of
    treatment. No delayed paralysis of the legs occurred in the
    survivors in any dose group or at any time during the 5-week
    observation period, while all TOCP dosed animals developed paralysis
    within 3 weeks. The sciatic nerve in all the surviving hens given
    fenitrothion was normal (Kadota et al., 1975b).

        Sixteen adult White Leghorn hens received 500 mg
    fenitrothion/kg orally and were protected against intoxication by
    atropine and 2-PAM; this treatment was repeated 3 weeks later. TOCP
    was used as a positive control. Five hens died 2 days after the
    first treatment with fenitrothion and none after the second; the
    survivors showed toxic signs of cholinesterase inhibition. No
    paralysis was observed and histopathological findings in the sciatic
    nerves were normal (Kadota et al., 1975b).

        Groups of 8 adult, White Leghorn hens were given 16.7 or 33.7
    mg fenitrothion/kg per day, 6 days/week, over 4 weeks and then
    observed for another 3 weeks. Slight toxic signs were seen in both
    groups during the administration period. One hen in the higher
    dosage group died on the 5th day of dosing. Body weights were
    decreased in both groups, but the decrease in the lower dosage group
    was transient. No delayed leg paralysis or histopathological changes
    in the sciatic nerve or spinal cord were recorded (Kadota et al.,
    1975b).


    
    Table 5.  Mutagenicity tests on fenitrothion
                                                                                                                                              

    Tests                   Strains                    Dose levels             Metabolic      Results        Reference
                                                                               activation
                                                                                                                                              

    Gene mutation tests

    Microorganism test      E. coli  K12               13.2, 132 µg/ml                          -            Suzuki et al. (1974)
                            Coli-phage lambda          13.2, 132 µg/ml                          -
                            1847 sus E-h+

                            S. typhimurium
                            TA1535                     10, 100, 1000,              +            -            Suzuki & Miyamoto (1976)
                            10 000 µg/plate                                        -            -
                            TA1537                                                 +            -
                                                                                   -            -
                            TA1538                                                 +            -
                                                                                   -            -

                            S. typhimurium
                            TA98                       500,750,1000,               +            -            Kawachi (1978)
                            2500 µg/plate                                          -            -
                            TA100                                                  +       + (weakly)
                                                                                   -       + (weakly)
                            TA1537                                                 +            -
                                                                                   -            -

                            S. typhimurium
                            TA100                      < 5000 µg/plate             +            +            Moriya et al. (1983)
                                                                                   -            +
                            TA98                                                   +            -
                                                                                   -            -
                                                                                                                                              

    Table 5 (contd).
                                                                                                                                              

    Tests                   Strains                    Dose levels             Metabolic      Results        Reference
                                                                               activation
                                                                                                                                              

                            TA1535                                                 +            -
                                                                                   -            -
                            TA1537                                                 +            -
                                                                                   -            -
                            TA1538                                                 +            -
                                                                                   -            -

                            E. coli                                                +            -
                            WP2 hcr                                                -            -

                            S. typhimurium
                            TA98                       100, 200, 500, 1000,        +            -            Hara et al. (1989)
                                                       2000, 5000 µg/plate         -            -
                            TA1535                                                 +            -
                                                                                   -            -
                            TA1537                                                 +            -
                                                                                   -            -
                            TA100                                                  +       + (weakly)
                                                                                   -       + (weakly)
                            TA100NR                                                +            -
                                                                                   -            -
                            TA100 1,8-DNP6                                         +       + (weakly)
                                                                                   -            -

                            E. coli
                            WP2uvrA                                                +            -
                                                                                   -            -
                                                                                                                                              

    Table 5 (contd).
                                                                                                                                              

    Tests                   Strains                    Dose levels             Metabolic      Results        Reference
                                                                               activation
                                                                                                                                              

    Host-mediated assay     ICR mouse

                            S. typhimurium  G46        100, 200 mg/kg body                      -            Suzuki & Miyamoto (1976)
                                                       weight; oral, im/ip
                                                       (mouse)

    Mammalian cell test     Chinese hamster            0.01, 0.03, 0.1,            +            -            Hara et al. (1989)
                            lung cells V79             0.3 mmol/litre              -            -

    DNA-Damage and repair tests

    Rec-assay               B. subtilis                up to 20 µlitre             +            -            Shirasu et al. (1979)
                            H17/M45                                                -            -

    Sister chromatid        Human embryonic cells      5 x 10-4 (mol/litre)                 2.6 times        Kawachi (1978)
                                                                                             higher
    exchange (SCE)          HE2144                                                          SCE than
                                                                                             control
                            Chinese hamster cells      1 x 10-3 (mol/litre)
                            Don-6

                            ICR mouse embryo cells     10-5, 5 x 10-5,             +            -            Suzuki & Miyamoto (1980)
                                                       10-4 (mol/litre)            -            -

    Unscheduled DNA         SD rat hepatocyte          300 mg/kg body                           -            Kawamoto et al. (1989)
    synthesis (UDS)                                    weight, oral)
    in vivo/in vitro

                                                                                                                                              

    Table 5 (contd).
                                                                                                                                              

    Tests                   Strains                    Dose levels             Metabolic      Results        Reference
                                                                               activation
                                                                                                                                              

    Chromosomal aberration tests

    Chromosomal aberration  Wistar rat F2b (male)      80 mg/kg diet                            -            Benes et al. (1975)
                            F3b (male)                 80 mg/kg diet                            -

                            Chinese hamster lung       0.1 mg/ml                               21%           Kawachi (1978)
                            cells                                                          aberration

                            Chinese hamster ovary      0.075, 0.15, 0.3 mg/ml      +            -            Hara et al. (1988)
                            cells-K1                   0.003, 0.01, 0.03 mg/ml     -            -

                            Long-Evans rat             400, 800, 1000 mg/kg                + (weakly)        Kawachi (1978)
                                                       body weight, oral;
                                                       20, 40 mg/kg body                   + (weakly)
                                                       weight, oral, x 5 days

                            ICR mouse (male)           200, 400, 800 mg/kg                      -            Hara & Suzuki (1982a)
                                                       body weight, ip

                            SD rat (male)              100, 200, 400 mg/kg,                     -            Hara & Suzuki (1982b)
                                                       oral, 20, 40, 80 mg/kg,                  -
                                                       oral, x 5 days

                            Wistar rat (male)          15, 30, 60 mg/kg body                    -            Malhi & Grover (1987)
                                                       weight, ip, x 5 days

                            Q mouse (male)             1000 mg/kg body                          -            Degraeve et al. (1984)
                                                       weight, ip
                                                                                                                                              

    Table 5 (contd).
                                                                                                                                              

    Tests                   Strains                    Dose levels             Metabolic      Results        Reference
                                                                               activation
                                                                                                                                              

    Micronucleus test

                            ICR mouse (male)           200, 400, 800 mg/kg                      -            Hara & Suzuki (1982c)
                                                       body weight, ip

                            ddy mouse (male)           200, 400, 800 mg/kg                      -            Hayashi et al. (1988)
                                                       body weight, ip
                                                       100, 300, 600 mg/kg body                 -
                                                       weight, ip, x 4 days

                            Wistar rat (male)          75, 165, 330 mg/kg                       -            Grover & Malhi (1985)
                                                       body weight, ip

    Dominant lethal test    Wistar rat F2b             10, 40, 80 mg/kg diet                    -            Benes et al. (1975)
                            F4b                        10, 40, 80 mg/kg diet                    -

                            ICR mouse                  20, 200 mg/kg body                       -            Kohda & Kadota (1975)
                                                       weight, oral, x 5 days

                            SD rat                     2, 7, 20 mg/kg body                      -
                                                       weight, oral, x 5 days

                            Q mouse                    1000 mg/kg body                          -            Degraeve et al. (1984)
                                                       weight, ip

    Others                  S. cerevisiae              0.3% in DMSO per plate                   -            Yadav et al. (1982)

                            D. melanogaster            50, 150 mg/kg diet                       -            Velazquez et al. (1987)
                                                                                                                                              

    

        The inhibitory activities of fenitrothion against neuropathy
    target esterase (neurotoxic esterase, NTE) and acetylcholinesterase
    (AChE) in the hen (White Leghorn) brain were examined. Oral
    treatment with 500 mg fenitrothion/kg resulted in significant (80%)
    inhibition of AChE, but not of NTE (less than 10%) (Ohkawa et al.,
    1980).

        The potential of a single, toxic dose of fenitrothion to elicit
    delayed neurotoxicity in adult White Leghorn hens (5 per group) was
    compared with the effects produced following similar treatment with
    the known neurotoxin, tri-O-cresyl phosphate (TOCP). Hens receiving
    single oral doses of either fenitrothion (500 mg/kg) or TOCP (500
    mg/kg) were assessed for toxicity by measuring biochemical (brain
    and spinal cord AChE and NTE), physiological (motor function) and
    morphological parameters of the brain, spinal cord, and sciatic
    nerve 24 h, and 7, 14, 28, 42, and 56 days after treatment. At 24 h,
    fenitrothion caused a marked inhibition of neuronal AChE. No
    alteration in NTE activity was found in any fenitrothion-treated
    hens. A characteristic, central-peripheral, distal axonopathy was
    observed following treatment with TOCP, mild signs appeared 7-14
    days after treatment and increased in severity up to 28 days after
    treatment, concomitant with morphological changes primarily in the
    sciatic nerve and spinal cord.  Minimal morphological changes were
    elicited by fenitrothion at this dosage, but the tissues appeared
    morphologically similar to those seen in vehicle-treated control
    hens. The results demonstrated that fenitrothion was not neuropathic
    in the classic manner of TOCP (Durham & Ecobichon, 1986).

    7.8  Effects on hepatic enzymes

        Groups of male and female Wistar rats (4 animals each) were
    kept on a diet containing fenitrothion at 150 mg/kg or
    3-methyl-4-nitrophenol at 500 or 1500 mg/kg, and the effects on
    hepatic oxidative phosphorylation and mixed function oxidases were
    studied. Respiratory control ratios of mitochondria were normal,
    adenosine triphosphatase (ATPase) activity was normal, and no
    differences were found between the treated and control groups. A
    slight decrease in the adenosine diphosphate:oxygen ratio was
    observed in females fed 1500 mg nitrophenol/kg. However, the
    difference was not regarded as statistically significant. Thus, rat
    hepatic mitochondrial respiration systems do not seem to be affected
    by administration of fenitrothion or 3-methyl-4-nitrophenol.
    Similarly, these chemicals did not affect hepatic microsomal mixed
    function oxygenase activities (Hosokawa & Miyamoto, 1975).

        Uchiyama et al. (1975) reported that intraperitoneal injection
    of 25 mg fenitrothion/kg to male ddY mice inhibited aminopyrine
     N-demethylation and aniline hydroxylation activities in the liver
    by about 50%.

        Yamamoto et al. (1982a) reported that a single oral
    administration of about 13 mg fenitrothion/kg (5 µmol/rat) or
    repeated oral administration of about 1.3 mg/kg per day (0.5
    µmol/rat per day) for 10 days to 4 or 5 Wistar rats did not affect
    aminopyrine  N-demethylase activity and cytochrome P-450 content,
    or inhibit the dearylation or desulfuration of fenitrothion.

        Groups of 5-7 weanling male Wistar rats received 50 mg
    fenitrothion/kg body weight per day dissolved in peanut oil, by
    gavage, for 5 consecutive days. Overt signs of toxicity were
    observed within 30 min of receiving the third dose. Severely
    affected animals were sacrificed for analysis of tissue esterase
    activities and insecticide residues and to assess the influence of
    the insecticide on hepatic microsomal mono-oxygenase activity. Daily
    treatment was terminated after 5 days and the survivors were
    sacrificed at intervals to assess the recovery of activity of
    esterases in the tissues. Fenitrothion caused a significant
    reduction in liver and body weights, a marked increase in
    pentobarbital sleeping time, and a marked reduction in hepatic
    microsomal mono-oxygenase ( p-nitroanisole  O-demethylase, aniline
    hydroxylase) activities. Marked inhibition of plasma
    pseudocholinesterase, hepatic and renal non-specific
    carboxyesterase, and erythrocyte and brain acetylcholinesterase
    occurred. Recovery from 5 such daily doses was slow for all tissue
    esterases with the exception of plasma cholinesterase, which
    returned to 78% of control activity values within 5 days. Activities
    of the other tissue esterases were 20-50% of normal at 5 days, and
    only 70-90% of normal 16 days after the final dose (Ecobichon &
    Zelt, 1979).

        A single oral dose of 250 mg fenitrothion/kg resulted in a
    slight decrease in a number of biochemical indices of liver function
    in rats, including mitochondrial ATPase activity, cytochrome P-450
    content, aniline hydroxylase activity, and aminopyrine
     N-demethylase activity (Mihara et al., 1981). A dose of 25 mg/kg
    also had a slight effect on P-450 content and xenobiotic metabolism,
    while 5 mg/kg did not have any significant effects. The magnitude of
    the effects was greater in females than in males.

        Intraperitoneal doses of 50 or 500 mg fenitrothion/kg,
    administered to mice, depleted hepatic glutathione levels and
    inhibited microsomal aniline hydroxylase and paranitroanisole
     O-demethylase activities (Ginsberg et al., 1982).

    7.9  Effects on hormonal balance

        Osicka-Koprowska et al. (1987) reported a significant elevation
    in plasma corticosterone levels in rats given a single oral dose or
    260 mg fenitrothion/kg. Levels returned to control values within 12
    h. Adrenal ascorbic acid content was also

    significantly decreased between 1 and 5 h after dosing. The authors
    attributed the changes to hypersecretion of ACTH. After daily dosing
    with fenitrothion at 13 mg/kg for 14 days, there was no significant
    difference in circulating corticoseterone levels between the
    controls and treated animals. There was a significant decrease in
    14C derived from injected (ip) 14C-corticosterone in the
    hypothalamus, adrenals, blood, liver, and muscle, but not in the
    pituitary gland, at the end of the dosing period and 30 min after
    injection of the label.

    7.10  Toxicity of metabolites and the S-isomer

        The acute toxicity of fenitrooxon, a metabolite of
    fenitrothion, is greater than that of the parent compound.
    3-Methyl-4-nitro-phenol, another metabolite, is less toxic
    (Table 6).

        The intraperitoneal toxicity of fenitrothion metabolites and
    their related compounds was tested in mice. 3-Hydroxymethyl and
    3-formyl derivatives of fenitrothion and fenitrooxon were more toxic
    than fenitrothion and fenitrooxon, respectively. Fifteen other
    compounds tested, including aminofenitrothion, demethyl
    fenitrothion, and demethyl fenitrooxon, were much less toxic than
    the parent compound (Miyamoto et al., 1978).

        The acute oral toxicity of the  S-methyl-isomer ( O-methyl
     S-methyl  O-(3-methyl-4-nitrophenyl) phosphorothioate) in rats
    and mice is approximately twice that of fenitrothion (e.g., LD50
    in mice: 550 and 1400 mg/kg, respectively) and the signs of
    poisoning are typical of the muscarinic and nicotinic actions of
    acetylcholine, as seen with fenitrothion (Kovacicova et al., 1973;
    Rosival et al., 1974). The  S-isomer, when injected
    intraperitoneally, is 7-9 times more toxic in mice than fenitrothion
    (Miyamoto, 1977a).

        The bimolecular inhibition constant of  S-methyl fenitrothion
    on rat brain acetylcholinesterase is about 1000 times greater than
    that of fenitrothion (Thompson et al., 1989).

    7.11  Factors modifying toxicity

        The best therapy in rats against severe poisoning with a 100%
    lethal dose of fenitrothion was confirmed to be repeated and
    combined treatment with atropine and 2-PAM, resulting in a 90%
    survival ratio and considerable alleviation of toxic signs
    (Matsubara & Horikoshi, 1983).

    
    Table 6.  Acute toxicity of metabolites
                                                                                               

    Compound            Animal               Route      LD50        Reference
                        (strain)                        (mg/kg)
                                                                                               

    Fenitrooxon

                        Mouse                oral       90          Miyamoto et al. (1963b);
                                                                    Miyamoto (1969)

                        Mouse                oral       120         Hollingworth et al. (1967b)
                        (Swiss White)

                        Rat                  oral       24          Miyamoto et al. (1963b);
                                                                    Miyamoto (1969)

                                             iv         3.3         Miyamoto et al. (1963b);
                                                                    Miyamoto (1969)

                        Guinea-pig           oral       221         Miyamoto et al. (1963b);
                                                                    Miyamoto (1969)

                                             iv         32          Miyamoto et al. (1963b);
                                                                    Miyamoto (1969)

                        Dog (Beagle)         oral       > 68.1      Mastalski et al. (1971)

                        Hen                  oral       35          Kadota et al. (1975b)
                        (White Leghorn)

    3-Methyl-4-
     nitrophenol        Rat
                        (Male) (Wistar)      oral       2300        Sumitomo (1971)
                        (Female) (Wistar)    oral       1200        Sumitomo (1971)

                        Dog (Beagle)         oral       > 680       Mastalski (1971a)

                                                                                               
    
        The effects of adrenalectomy (Adx), SKF 525-A, phenobarbital
    (PB), and diethyl maleate (DEM) on the acute toxicity of
    fenitrothion were investigated in male Wistar rats. PB administered
    (ip) at 60 mg/kg per day for 3 days, did not exert any effect on the
    toxicity of fenitrothion (100 mg/kg) given orally 24 h after the
    last injection of PB. In adrenalectomized and SKF 525-A-pretreated
    rats, the toxicity of fenitrothion was lower than in the controls.
    Fenitrothion toxicity was increased by administration of DEM at (1
    ml/kg), which depletes hepatic glutathione (GSH) levels. In
     in vitro experiments, the rates of fenitrothion decomposition
    and fenitrooxon formation by microsomes were markedly affected by
    PB, SKF 525-A, and Adx. The decomposition of fenitrooxon by the
    microsomal fraction and GSH-dependent decomposition of fenitrooxon
    by the soluble fraction were not affected by PB, SKF 525-A, and
    Adx pretreatment. The GSH-dependent decomposition of fenitrothion
    and fenitrooxon was increased by the addition of GSH to the incubation
    mixture. It was considered that the GSH-dependent metabolic pathway
    plays an important role in the detoxification of fenitrothion
    (Yamamoto et al., 1983a).

    7.12  Mechanism of toxicity - mode of action

    7.12.1  Mode of action

        Fenitrothion is not a strong inhibitor of AChE  in vitro, but
    is much more so  in vivo. The compound is converted in the animal
    body to the active esterase inhibitor, fenitrooxon [ O,O-dimethyl
     O-(3-methyl-4-nitrophenyl)phosphate], by the action of microsomal
    mixed function monooxygenase in liver and other tissues (Miyamoto et
    al., 1963b; Miyamoto, 1964a).

        Plasma ChE is the enzyme most susceptible to acute and
    short-term administration of fenitrothion in rats, guinea-pigs,
    dogs, rabbits, and humans (Miyamoto et al., 1963b; FAO/WHO, 1975b). 
    Brain AChE in rabbits is less inhibited by fenitrothion (Miyamoto et
    al., 1976a).

    7.12.2  Selective toxicity

        Hollingworth et al. (1967a,b) and Hollingworth (1969) concluded
    that dealkylation was an important factor among the many that
    contribute to the lower mammalian toxicity of fenitrothion compared
    with that of methylparathion. For example, the cholinesterase
    inhibition of fenitrooxon is less, the activation by conversion of
    P=S to P=O, slower, the translocation of fenitrothion more rapid,
    and the detoxification rate of fenitrothion, higher. Comparison of
    metabolites, at equitoxic doses in white mice (i.e., 17 mg
    methylparathion/kg and 850 mg fenitrothion/kg) showed that
    demethylation is the major detoxification path for fenitrothion at
    high doses (200-850 mg/kg), but not for methylparathion. However,
    inherently, demethylation of both compounds proceeds in a similar

    way (Miyamoto et al., 1968) and both fenitrothion and
    methylparathion are metabolized at a similar rate  in vivo 
    (Miyamoto, 1964a, 1969). On the basis of these findings, Miyamoto
    (1969) concluded that the relatively poorer penetration of
    fenitrooxon into the brain (Miyamoto, 1964b) explained the
    selectively lower toxicity of fenitrothion rather than the
    dealkylation detoxification mechanism. Similar conclusions were
    reached by Kuroiwa & Yamamoto (1977).

        The mechanisms for the lower toxicity of fenitrothion compared
    with methylparathion were investigated in male Wistar rats. The
    difference in acute toxicity between fenitrothion and
    methylparathion could be because of the more rapid decomposition of
    fenitrothion and fenitrooxon in rat liver compared with that of
    methylparathion and methylparaoxon. In particular, the decomposition
    of fenitrothion by hepatic microsomes was accelerated by increasing
    the insecticide concentration. The oxygen analogues of both
    insecticides, fenitrooxon and methylparaxon, were not detected in
    the brain after administration of the parent compounds. It was
    considered that the lower toxicity of fenitrothion compared with
    that of methylparathion could be due to the greater rate of
    decomposition of fenitrothion to its less toxic metabolites rather
    than to the different rates of penetration of the oxygen analogues
    into the brain (Yamamoto et al., 1983b).

    7.12.3  Potentiation of toxicity of other chemicals

        Female rats were administered ip a combination of fenitrothion
    and parathion, malathion, diazinon, or carbaryl. No potentiation was
    demonstrated. However, a marked potentiation (increased mortality)
    was observed when male and female Sprague-Dawley rats were given
    single oral doses of fenitrothion and phosphamidon. In female rats,
    potentiation occurred only with mixtures containing relatively low
    concentrations of fenitrothion (Dubois & Kinoshita, 1963; Braid &
    Nix, 1968).

        The effects of a combination of fenitrothion with malathion in
    male rats were more than additive. The potentiation was most
    pronounced (half of the expected LD50) with a combination rate of
    1:1. No potentiation was observed with other tested
    organophosphates, i.e., bromophos, amidithion, and trichlorfon
    (Benes & Cerna, 1970).

        Hladka et al. (1974) noted that a single dose of a mixture of
    fenitrothion and malathion caused a significant increase in
    fenitrooxon but not fenitrothion levels in the blood and muscles of
    female Wistar rats.

 

       Fenitrothion at a subtoxic oral dose (100 mg/kg body weight; 4
    h pretreatment or 1000 mg/kg diet for one week) potentiated the
    acute oral toxicity of 2-sec-butylphenyl methylcarbamate (BPMC) in
    male ICR mice. Through several  in vivo and  in vitro studies, it
    was suggested that competitive inhibition of BPMC metabolism in the
    liver by fenitrothion played, in part, a role in the inhibition of
    BPMC detoxication, resulting in the potentiation of its toxicity
    (Takahashi et al., 1984, 1987; Tsuda et al., 1984).

        The same effects were investigated in female Beagle dogs. Oral
    co-administration of fenitrothion (100 mg/kg) doubled the duration
    of symptoms of BPMC (50 mg/kg) (5 h). The plasma level of BPMC in
    the eliminating phase was increased by the co-administration and
    began to decrease after 6 h, while ChE inhibition continued for 8 h.
    Pretreatment with fenitrothion at 5 mg/kg per day, for 7 days,
    caused one death in 3 dogs after the administration of BPMC (100
    mg/kg), while the same dose of BPMC without pretreatment did not
    cause any deaths. The pretreatment with fenitrothion increased the
    duration of the toxic symptoms of BPMC 2.5-fold. The time course of
    the toxic symptoms was correlated with the plasma concentration of
    BPMC (Miyaoka et al., 1983).

    8.  EFFECTS ON MAN

    8.1  General population exposure

    8.1.1  Acute toxicity

        Fenitrothion was given to a total of 24 human volunteers in
    single oral doses of 0.042-0.33 mg/kg body weight or 2.5-20 mg per
    person. The excretion of a metabolite, 3-methyl-4-nitrophenol, in
    the urine was almost complete within 24 h, and ranged from about 70%
    of the dose (0.042 mg/kg) to about 50% (0.33 mg/kg). Neither plasma
    nor erythrocyte cholinesterase (ChE) activities were depressed below
    normal, except in one person given 0.33 mg/kg, whose plasma ChE
    activity was about 65% of the pretest level after 6 and 24 h. When
    repeated doses of 0.04-0.08 mg/kg were given to 5 individuals, 4
    times at 24-h intervals, most of the metabolites appeared in the
    urine within 12 h of administration. After receiving the third and
    fourth doses, there was a trend towards a rise in erythrocyte ChE
    activity (Nosal & Hladka, 1968; Hladka et al., 1977).

    8.1.2  Poisoning incidents

        Several cases of acute fenitrothion poisoning, a few of them
    lethal, have been described in the literature. These were either
    accidental, intentional (suicide), or due to gross neglect of safety
    precautions. A review of these cases is given by Hayes & Lawes
    (1991).

        In all cases, the onset of poisoning was rapid, early signs and
    symptoms being exhaustion, headache, weakness, confusion, vomiting,
    abdominal pain, excessive sweating, and salivation. The pupils were
    small. Difficulty in breathing may be experienced, due to either
    congestion of the lungs or weakness of the respiratory muscles. In
    severe cases of poisoning, muscle spasms, unconsciousness, and
    convulsions may develop and death may result from respiratory
    failure.

        In atypical cases, symptoms of poisoning may be observed for a
    more prolonged period and up to 8 months after exposure. It has been
    suggested that fenitrothion can be stored in human fat tissue and
    then released under stress conditions (Ecobichon et al., 1977).

        An attempted suicide using a large quantity of fenitrothion was
    treated successfully by 2-PAM, atropine, and glutathione with
    artificial respiration. The case was characterized by delay in the
    onset of severe signs of intoxication (the 3rd day after
    hospitalization) and relatively prolonged poisoning (the 70th day
    after hospitalization), as evidenced by electroencephalogram and
    inhibition of ChE. It was reported that the patient (56-year-old
    female) had been suffering from diabetes, which presumably caused

    delayed biotransformation of fenitrothion to fenitrooxon or delayed
    absorption of the compound from the intestines, resulting in the
    delay in the onset of symptoms and prolonged poisoning. However, no
    evidence leading to this presumption was seen in the study
    (Tsukimoto et al., 1981).

        A case of delayed neurotoxicity of late onset has been reported
    in a 70-year-old female who ingested 40 ml of 50% Fenitrothion EC.
    At first, no toxic symptoms were apparent. However, 48 h after
    ingestion, certain signs became apparent. An impediment in
    consciousness was observed. Fasciculation and muscular weakness were
    noted, while plasma and urinary levels of 3-methyl-4-nitro-phenol
    reached a maximum. Neither atropine sulfate nor 2-PAM was effective.
    For 3 weeks, the patient required ventilatory support, and
    consequently her muscle strength and neurological status gradually
    recovered with falling of the phenol level (Sakamoto et al., 1984).
    The late symptoms reported by Sakamoto et al. (1984) are not those
    of the organophosphorus ester-induced delayed neurotoxicity (OPIDN)
    reported for some other organo-phosphorus compounds (Martinez
    Chuecos & Sole Violan, 1985).

        A 56-year-old male attempted suicide by the ingestion of about
    60 ml of 50% fenitrothion emulsion. Five hours later, combined
    haemoperfusion and haemodialysis (HP-HD) treatment was performed for
    60 min and, subsequently, the symptoms gradually improved. Four days
    after ingestion, cholinergic symptoms recurred. Immediate HP-HD
    treatment was of no use and the patient died 6 days after ingestion
    of fenitrothion. Analysis of the organ and tissue distribution of
    fenitrothion revealed that the highest concentration of fenitrothion
    was found in fat (59.0 mg/kg wet weight, more than 10 times the
    concentrations in other organs). It was suggested that a slow
    release of the pesticide from adipose tissue can give rise to a
    protracted clinical course or late symptoms of intoxication (Yoshida
    et al., 1987).

    8.1.3  Contact dermatitis

        An analysis of 202 patients with contact dermatitis caused by
    organophosphorus insecticides was undertaken. The organophosphorus
    insecticides presumably attributing to the dermatitis were
    dichlorvos, salithion, fenitrothion, leptophos, cyanophos,
    amidothion, diazinon, and malathion. The dermatitis was located on
    the fingers, face, forearms, neck and nape. About one quarter
    (25.2%) of the cases with dermatitis had complications with symptoms
    of acute poisoning by these compounds. The prognosis of the
    dermatitis was relatively good; 44.1% of the cases healed but 23.8%
    of the patients were incompletely cured (Matsushita et al., 1985).

    8.1.4  Possible links with Reye's syndrome

        Concerns have been raised about the possible association
    between the aerial spraying of forests with fenitrothion
    formulations and the incidence of Reye's Syndrome, an encephalopathy
    complicated by hepatic damage, occurring primarily in children up to
    18 years of age and linked to viral infections (Reye et al., 1963;
    Ruben et al., 1976; Corey et al., 1976).

        Crocker et al. (1976a) reported that patients from a
    fenitrothion-sprayed area had reduced plasma ChE and erythrocyte
    AChE activities compared with those in children living in an
    unsprayed region. However, Pollack et al. (1977) confirmed that,
    while the serum ChE of Reye's patients was lower, the difference was
    not significant. No correlation between aerial spraying and the
    incidence of Reye's Syndrome was established in epidemio-logical
    studies conducted in New Brunswick, Canada, and Maine, USA
    (Schneider, 1976; Spitzer, 1982; Wood & Bogdan, 1986).  Attention
    was focused on the potential of various emulsifiers and co-solvents
    used in oil- and water-based formulations of fenitrothion to enhance
    virus-induced lethality in neonatal mice or to promote viral growth
    in cell cultures (Crocker et al., 1974, 1976b).  However, in a
    neonatal animal model, the infection of neonatal mice by influenza
    virus was not potentiated by any emulsifiers in fenitrothion
    formulations (Menna, 1985). Similarly, in an  in vitro cell culture
    system, the growth of the virus was not enhanced by co-incubation
    with various concentrations of fenitrothion, in the presence or
    absence of a wide range of emulsifiers, co-solvents and diluents,
    commonly used in aerial spraying formulations (Brookman et al.,
    1984).

    8.2  Occupational exposure

        In a WHO (1973) programme, 3 different water-dispersible powder
    formulations of fenitrothion were applied indoors as a residual
    spray with the aim of depositing 2 g active ingredient/m2 on the
    wall. The first three rounds of spraying lasted for approximately
    six, 5-day, working weeks and the fourth round lasted for 8 weeks. A
    slight to moderate depression of cholinesterase (ChE) activity was
    observed in most of the spraymen towards the end of the spraying
    rounds. Except for one case of headache, no other complaints
    attributable to insecticide exposure were recorded during a total of
    2000 man-days of spraying. No complaints were received from the 20
    000 inhabitants whose houses had been sprayed repeatedly. However,
    no ChE activity determinations were performed.

        During 30-days indoor spraying of fenitrothion (2 g/m2) for
    malaria control in Southern Iran in August 1971, a group of 28 pest
    control operators and 925 inhabitants were monitored with respect to
    their health and ChE activity. Clinical investigations and ChE

    tests on 840 workers showed 42 cases of clinical symptoms, most of
    which were very slight and subsided after the workers had showered
    and rested (2-3 h). Out of 20 spraymen, 8 showed decreased ChE
    levels, and one individual preparing the spray mixture showed a
    significant depression of the enzyme activity, which was reactivated
    after an appropriate treatment. Among 925 inhabitants, only 15 cases
    of very mild complaints, namely dizziness and nausea, were reported.
    While fenitrothion was characterized as a pesticide that is safe for
    the inhabitants in a subtropical region during dry and hot seasons,
    further investigations were recommended on the toxic effects on
    operators under tropical conditions (Motabar et al., 1972).

        In a field spraying operation in a village in southern Nigeria
    using a 5% spray of fenitrothion, 18 villagers examined one week
    later did not show any clinical symptoms of toxicity or plasma ChE
    depression. The ChE levels in the 3 spraymen examined on the first,
    second, and sixth days after spraying were also not depressed
    compared with pre-spraying levels (Vandekar, 1965).

        In another field spraying operation in northern Nigeria, 10 000
    huts, in which about 16 500 people lived, were sprayed. Field test
    ChE determinations on whole blood did not show any appreciable
    differences in the ChE levels of 535 villagers tested before
    spraying and 299 villagers tested 5-30 days after spraying. After
    one week of intensive spraying, 5 out of 20 spraymen developed a 50%
    depression of ChE, which returned to a stable level after a period
    of rest. One sprayman developed symptoms of intoxication that lasted
    only a few hours and disappeared without treatment (Wilford et al.,
    1965).

        The health was monitored of workers employed in forest spraying
    operations using fenitrothion, in New Brunswick, and plasma and
    erythrocyte ChE activities, measured. There were no instances of ChE
    activity fluctuating beyond the accepted range or of suspected
    poisoning resulting from occupational exposure to this insecticide
    (Braid & McCarthy, 1977).

        Moderate poisoning of 25 workers was reported in Czechoslovakia
    (Kalas, 1978; Hayes, 1982), where a formulation containing 50%
    fenitrothion was applied by aircraft during a strong wind. Onset of
    poisoning developed 2.5-6 h after inhalation and the symptoms were
    typical. Whole blood ChE activity was decreased by 48%. Recovery
    required 3 days of treatment with atropine.

        In the Haitian malaria control programme, depressed whole blood
    cholinesterase activity (< 50% of normal) was detected rapidly
    prior to the development of serious symptoms. Evidence of
    fenitrothion over-exposure appeared in spraymen early in the first
    spray cycle, and was associated with faulty protective clothing and
    failure to follow strictly the recommended safety measures at work.

    After these deficiencies were corrected, insecticide application
    continued without serious incidents or interruption of the
    programme. It was recommended that training and monitoring
    programmes should be instituted whenever organophosphate pesticides
    are used as residual sprays for malaria control (Warren et al.,
    1985a). Similar observations were made in another study undertaken
    in Pakistan and Haiti (Miller & Shah, 1982).

        Cholinesterase activity was significantly reduced at the end of
    the working week in 3 out of 28 fenitrothion workers in Haiti. 
    Urinary levels of 3-methyl-4-nitrophenol in the spraymen ranged from
    2.2 to 25.2 mg/litre. In fenitrothion workers who had no direct
    contact with spraying (weighers and supervisors), the cholinesterase
    activity remained > 75% of the normal control value, and the
    urinary 3-methyl-4-nitrophenol levels were relatively low. The
    cholinesterase levels improved and the urinary excretion of
    metabolites decreased after 2 days of rest from the spraying
    operations. In the residents of the sprayed houses, low
    concentrations of 3-methyl-4-nitrophenol were detected in the urine,
    1 day after spraying, and measurable, but reduced, levels were still
    present after 7 days. In all these cases, the cholinesterase
    activity remained > 75% of the normal control value (Warren et
    al., 1985b).

        In an epidemiological study on the effects of fenitrothion on
    occupationally exposed male workers in the production department and
    female workers in the packing room during a 5-year period, the
    results of clinical examinations pointed to parasympathetic
    stimulation and disposition to hypotonia. Neurological and
    psychiatric findings revealed a low-grade pseudoneurasthenic
    syndrome in 33% of females and in 15% of males. The results of
    psychodiagnostic tests after exposure to fenitrothion and its
    intermediate products showed partial deterioration of retention,
    impairment of visuomotor coordination of movements in tapping,
    impaired orientation readiness, prolonged average time in
    decision-making, and prolonged average reaction time for complex
    sensorimotor responses. The following effects on biochemical
    parameters after exposure to fenitrothion should be mentioned:
    inhibition of cholinesterase in the blood, increase of glutamate
    pyruvate transaminase, increase of isoenzyme lactate dehydro-genase
    (LDH-5), and changes in protein fractions, all of which were
    statistically significant (P < 0.001). The values of
    3-methyl-4-nitrophenol excreted in the urine of males after the
    exposure to fenitrothion averaged 5.61 mg/litre, compared with an
    average value of 1.54 mg 3-methyl-4-nitrophenol/litre before
    exposure.  The average values of 3-methyl-4-nitrophenol excreted in
    the urine of females involved in bottling fenitrothion were 4.0 mg
    3-methyl-4-nitrophenol before exposure and 6.58 mg
    3-methyl-4-nitrophenol/litre of urine after exposure. The
    concentrations of fenitrothion in the air of the workplace ranged
    from 0.028 to 0.118 mg/m3. From the values of the

    3-methyl-4-nitrophenol excreted in the urine of the exposed workers
    and of volunteers, to whom fenitrothion was administered in doses of
    2.5-20 mg, it could be judged that the exposed male workers received
    approxi-mately 15 mg of fenitrothion per capita a day and the
    exposed female workers received 20 mg or more per capita a day
    (Liska et al., 1982).

        The introduction of the ultra-low-volume application of the
    organophosphate pesticide fenitrothion in grain terminals presented
    a risk to workers of skin contact with a high concentration. Blood
    testing, by the Ellman method, of a group of 5 grain terminal
    workers engaged in grain treatment showed a lowering of mean
    erythrocyte cholinesterase activity to 23 units/g Hb (normal value
    28-40) with a range of 16-29. The probable cause was identified as
    percutaneous absorption of fenitrothion through ungloved hands
    exposed to clean blocked drip feed nozzles. Modification of work
    practices was followed by a rise of mean erythrocyte ChE activity to
    33.6 units/g Hb (range 32-36) during the following grain treatment
    season. Erythrocyte ChE activity measured during the intervening
    winter season, i.e., during a non-exposure period, showed a mean of
    33.3 units/g Hb (range 23-40) (Gun et al., 1988).

    9.  EFFECTS ON ORGANISMS IN THE ENVIRONMENT

    9.1  Microorganisms and algae

        Salonius (1972) reported that a 12-month incubation of forest
    soils with massive doses of fenitrothion emulsion at the rate of 48
    mg/pot, equivalent to approximately 112 kg/ha, based on surface area
    of the soil, did not alter the population or respiration of the soil
    microflora.

        No effects of fenitrothion were observed on the growth of 6
    species of fungi responsible for the decomposition of organic
    detritus in streams and swamp water containing 15, 150, or 1500 µg
    fenitrothion/litre for up to 3 months (Eidt, 1978).

        In Maine (USA), viable populations of bacteria, yeasts, fungi,
    and actinomycetes were monitored in forest leaf litter treated with
    fenitrothion at 1 mg/kg (Spillner et al., 1979a); fenitrothion
    treatment did not appear to affect microbial populations or
    respiration in the forest litter. Furthermore, fenitrothion (1 or 5
    mg/kg) did not have any effects on cellulose-degrading organisms
    (Spillner et al., 1979b).

        Total numbers of bacteria and the nitrification activity in the
    soil were not affected by a 5-year application of fenitrothion 50%
    EC diluted 1000 times at 125 ml/m2 (Nishio & Kusano, 1978). No
    effects on urease and glucanase were observed when fenitrothion was
    incorporated into silt loam soil at field rates (0.70-2.11 kg
    a.i./ha) (Burns & Lethbridge, 1981).

        Mandoul et al. (1968) reported that a concentration of 5 mg
    fenitrothion/litre did not affect microplankton in a freshwater
    environment. They stated that 2 applications of fenitrothion at 140
    g/ha would not approach 5 mg/litre, even assuming that all of the
    material reached the lakes or streams.

        Growth inhibition tests were carried out using 3 species of
    algae, and EC50 values were determined to be 4-9 mg/litre for diatom
    and blue-green algae, and more than 100 mg/litre for green algae
    (Kikuchi et al., 1984) (Table 7).

    9.2  Aquatic organisms

    9.2.1  Fish

        Toxicity data of fenitrothion on aquatic non-target organisms
    are summarized in Table 7. Fenitrothion is moderately toxic for fish
    species with LC50 values of more than 1 mg/litre.


    
    Table 7.  Toxicity of fenitrothion for aquatic non-target organismsa
                                                                                                                                              

    Species                       Size          Parameters         Toxicity       Formulation    Temperature         Reference
                                                                   (mg/litre)                       (°C)
                                                                                                                                              

    Microorganisms

    Activated sewage sludge                     4-h growth EC50    450                           22 ± 2           Kwasniewska et al. (1980)
    sediment soil

    Algae

    (Chlorella vulgaris)          F             growth EC50        100            T              23 ± 2           Kikuchi et al. (1984)

    (Nitzschia closterium)        F             growth EC50        3.9            T              23 ± 2           Kikuchi et al. (1984)

    (Anabaena flos-aquae)         F             growth EC50        8.6            T              23 ± 2           Kikuchi et al. (1984)

    Mollusca

    (Pila globosa)                F 30 ± 2 g    72-h LC50          1.2            T              29 ± 2           Madhu et al. (1982)

    (Phya acuta)                  F             48-h LC50          15             EC                              Hashimoto & Nishiuchi (1981)

    Red snail                     F             48-h LC50          8.5            EC                              Hashimoto & Nishiuchi (1981)
    (Indoplanorbis exustus)

    Marsh snail                   F             48-h LC50          6.0            EC                              Hashimoto & Nishiuchi (1981)
    (Semisulcospira libertina)

    Eastern oyster                M juvenile    96-h EC50          0.450          T              27               Mayer (1987)
    (Crassostrea virginica)                     growth
                                                                                                                                              

    Table 7 (contd).
                                                                                                                                              

    Species                       Size          Parameters         Toxicity       Formulation    Temperature           Reference
                                                                   (mg/litre)                    (°C)
                                                                                                                                              

    Crustacean

    Lobster                       M  larva      96-h               approx.        T              15               Mcleese (1974)
                                                                   0.001
    (Homarus americanus)          adult         96-h LC50          approx.        T              15               Mcleese (1974)
                                                                   0.001

    Prawn                         M  nauplius   24-h LC50          1.9            T              23-25            Hirayama & Tamanoi (1980)
    (Penaeus japonicus)           postlarva     24-h LC50          0.0005-        T              23-25
                                                                   0.0009

    Crab                          M  zoea       24-h LC50          0.005-0.008    T              23-26            Hirayama & Tamanoi (1980)
    (Portunus trituberculatus)    megalopa      24-h LC50          0.0002-        T              23-26
                                                                   0.0005
                                  young         24-h LC50          0.003          T              23-26

    Blue crab                     M 8.5-        96-h LC50          0.0086         T              22               Johnston & Corbett (1985)
    (Callinectes sapidus)         11.0 cm

    Brown shrimp                  M juvenile    96-h LC50          0.0015         T              29               Mayer (1987)
    (Panaeus aztecus)

    Water fleas
    (Daphnia pulex)               F adult       3-h LC50           0.050          T              24-26            Hashimoto & Nishiuchi (1981)
    (Daphnia magna)               adult         48-h LC50          0.0086         T              20 ± 2           Forbis (1987)
                                  adult/young   21-day MATC        0.00014        T              20 ± 2           Burgess (1988)
    (Moina macrocopa)             F adult       3-h LC50           0.050          T              24-26            Hashimoto & Nishiuchi (1981)

    Mite

    (Hydrachna trilobata viets)   F             48-h LC50          0.074          T              28 ± 3           Nair (1981)
                                                                                                                                              

    Table 7 (contd).
                                                                                                                                              

    Species                       Size          Parameters         Toxicity       Formulation    Temperature           Reference
                                                                   (mg/litre)                    (°C)
                                                                                                                                              

    Arthropod Insects

    Caddisfly larva               F             96-h LC50          11             T              5                Symons & Metcalf (1978)
    (Brachycentrus numberosus)

    Scud                          M             96-h LC50          0.01           T              18               Swain & Ivanikiw (1976)
    (Gammarus pseudolimnaeus)                   96-h LC50          0.0043-        T              12               Woodward & Mauck (1980)
                                                                   0.0088

    Stonefly naiad
    (Peleronarcys californica)    F             96-h LC50          0.004          T              16               Swain
    & Ivanikiw (1976)
    (Pteronarcella badia)                       96-h LC50          0.0051-        T              12               Woodward & Mauck (1980)
                                                                   0.0072

    Mayfly larva                  F 9.3 mm,     48-h LC50          0.0032         EC             25               Nishiuchi (1981)
    (Cloeon dipterum)             5.6 mg

    Dragon fly larva              F 2.3 cm,     48-h LC50          0.055          EC             25               Nishiuchi (1981)
    (Orthetrum albistylum         0.62 g
    speciosum) 

    (Sigara substriata)           F 5.9 mm,     48-h LC50          0.023          EC             25               Nishiuchi (1981)
                                  6.1 mg

    (Micronecta sedula)           F 3.2 mm,     48-h LC50          0.058          EC             25               Nishiuchi (1981)
                                  1.8 mg

    (Sympetrum frequens)          F 2.1 mm,     48-h LC50          0.050          EC             25               Nishiuchi (1981)
    (larva)                       0.56 g

                                                                                                                                              

    Table 7 (contd).
                                                                                                                                              

    Species                       Size          Parameters         Toxicity       Formulation    Temperature           Reference
                                                                   (mg/litre)                    (°C)
                                                                                                                                              

    (Eretes sticticus)            1.5 cm,       48-h LC50          0.062          EC             25               Nishiuchi (1981)
                                  0.20 g

    Amphibian

    Clawed toad                   embryo        24-h LC50          10             T              18               Elliott-Feeley &
    (Xenopus laevis)                            24-h EC50          4.2            T              18               Armstrong (1982)
                                                24-h LC50          10             T              25
                                                24-h EC50          0.37           T              25
                                                24-h LC50          0.33           T              30
                                                24-h EC50          0.17           T              30

    (Bufo b. japonics)            tadpole       48-h LC50          9.0            EC                              Hashimoto & Nishiuchi (1981)

    (Microhyla ornatas)           embryo        96-h LC50          3.21           T                               Pawar & Katdare (1984)
                                  tadpole       96-h LC50          1.14           T

    Freshwater fish

    Carp                          5.1 cm        48-h LC50          8.2            T              25 ± 1           Hashimoto & Nishiuchi (1981)
    (Cyprinus carpio)             7-9 cm        72-h LC50          2.3            50% EC         28- 32           Toor & Kaur (1974)
                                  eyed egg      24-h LC50          3.5            EC             25 ± 2           Hashimoto et al. (1982)
                                  sac fry       24-h LC50          1.5            EC             25 ± 2           Hashimoto et al. (1982)
                                  floating fry  24-h LC50          1.7-4.0        EC             25 ± 2           Hashimoto et al. (1982)
                                  6.0 cm,       oral LD50          10 mg/kg       T              20 ± 22          Hashimoto & Fukami (1969)
                                  2.5 g
                                                                                                                                              

    Table 7 (contd).
                                                                                                                                              

    Species                       Size          Parameters         Toxicity       Formulation    Temperature           Reference
                                                                   (mg/litre)                    (°C)
                                                                                                                                              

    Killifish                                   48-h LC50          7.0            T              25 ± 1           Hashimoto & Nishiuchi (1981)
    (Oryzias latipes)             embryo        96-h LC50          10             T              25 ± 1           Takimoto et al. (1984b)
                                  yolk sac      96-h LC50          6.94           T              25 ± 1           Takimoto et al. (1984b)
                                  fray
                                  postlarva     96-h LC50          2.36           T              25 ± 1           Takimoto et al. (1984b)
                                  juvenile      96-h LC50          3.54-4.66      T              25 ± 1           Takimoto et al. (1984b)
                                  adult         96-h LC50          3.70           T              25 ± 1           Takimoto et al. (1984b)

    Rainbow trout                 fingerling    96-h LC50          2.0            T              15               Klaverkamp et al. (1977)
    (Salmo gairdneri)             9.2 ±
                                  0.1 cm,
                                  10.35 ±
                                  0.78 g
                                  egg/fry       60-days post-      0.12           T              10 ± 1           Cohle (1988)
                                                hatch MATC

    Brook trout                                 96-h LC50          1.7            T              12               Swain & Ivanikiw (1976)
    (Salvelinus fontinalis)                     96-h LC50          2.1            40% EC         7                Swain & Ivanikiw (1976)
                                                96-h LC50          2.2            40% EC         12               Swain & Ivanikiw (1976)
                                                96-h LC50          1.8            40% EC         17               Swain & Ivanikiw (1976)
                                  15-21 cm      No effect on       10 mg/kg       T              15 ± 2           Wildish & Lister (1977)
                                  (42-120 g)    growth             food
                                  8.3-12.6 cm   Effect on          0.50           T              15               Peterson (1974)
                                                critical
                                                swimming
                                                velocity

    Cutthroat                     118 mm, 20 g  96-h LC50          2.57-2.88      T              12               Woodward & Mauck (1980)
    (Salmo clarki)                              96-h LC50          2.88           87%            EC               12
                                                96-h LC50          2.70           87%            EC               7
                                                                                                                                              

    Table 7 (contd).
                                                                                                                                              

    Species                       Size          Parameters         Toxicity       Formulation    Temperature           Reference
                                                                   (mg/litre)                    (°C)
                                                                                                                                              

    Gold fish                     2-3 g, 4-5    24-h LC50          4.5            pure           25 ± 2           Gras (1966)
    (Carassius auratus)                                                           product

    Goldfish                      9-11 cm       48-h LC50          3.4            T              25               Hashimoto & Nishiuchi (1981)
    (Carassius auratus)                         threshhold for     approx. 0.01   T              15               Scherer (1975)
                                                avoidance

    Eel (Anguilla anguilla)       2 g, 10 cm    24-h LC50          3.2            pure           25 ±             Gras (1966)
                                                                                  product

    Gambusia                      0.25-0.60 g   24-h LC50          2.6            pure           25 ±             Gras (1966)
    (Gambusia affinis)                                                            product

    Fathead minnow                embryo-larva  31 days            0.13-0.30      T              23.8 ± 1         Kleiner et al. (1984)
    (Pimephales promelas)                       MATC

    Pond loach                                  48-h LC50          4.8            T              25 ± 1           Hashimoto & Nishiuchi (1981)
    (Misqurnus anquilicaudatus)

    (Acheilognathus moriokae      5.5-6.0 cm,   72-h LC50          5.0            T              25               Nishiuchi (1977)
                                  1.2-1.4 g

    (Channa gachua)               116 mm, 18 g  96-h LC50          12.2           50% EC         24 ± 2           Verma et al. (1978a)

    (Saccobranchus fossilis)      135 mm, 25 g  96-h LC50          12.5           50% EC                          Verma et al. (1978b)
                                  50-75 mm,     96-h LC50          12.6           50% EC         18 ± 2           Verma et al. (1982)
                                  5-10 g

    (Mystus cavasius)             6-8 cm        96-h LC50          3.3            T              28 ± 2           Murty et al. (1983)
                                                                                                                                              

    Table 7 (contd).
                                                                                                                                              

    Species                       Size          Parameters         Toxicity       Formulation    Temperature           Reference
                                                                   (mg/litre)                    (°C)
                                                                                                                                              

    (Labeo rohita)                118 mm, 20 g  96-h LC50          4.63           50% EC                          Verma et al. (1977)
                                  3-4.4 cm      96-h LC50          2.8            T              28 ± 2           Murty et al. (1983)
                                  4.5-5.9 cm    96-h LC50          4.1            T              28 ± 2           Murty et al. (1983)
                                  6-8 cm        96-h LC50          4.6            T              28 ± 2           Murty et al. (1983)

    (Aplocheilus latipes)                       24-h LC50          4.5            T              25               Shim & Self (1973)

    (Zacco platypus)                            24-h LC50          7.4            T              25               Shim & Self (1973)

    (Puntius ticto)               50-68 mm,     96-h LC50          5.8            50% EC         11-29            Bhatia (1971)
                                  1.6-5.1 g

    Seawater fish

    Japanese striped knifejaw     egg-prelarva  24-h LC50          2.4-4.2        50% EC         22 ± 0.1         Seikai (1982)
    (Oplegnathus fasciatus)       postlarva     24-h LC50          0.145          50% EC         22 ± 0.1         Seikai (1982)
                                  postlarva-    24-h LC50          1.25-2.35      50% EC         22 ± 0.1         Seikai (1982)
                                  juvenile

    Agohaze (Chasmichthus         0.02-0.06 g   96-h LC50          1.1            50% EC         15               Hirose et al. (1979)
    dolichognathus d.)                          96-h LC50          1.7            50% EC         20               Hirose et al. (1979)

    Sheepshead minnow             juvenile      48-h LC50          > 1.0          T              9                Mayer (1987)
    (Cyprinodon variegatus)

                                                24-h EC50          0.17           T              30
                                                                                                                                              

    a    EC = Emulsifiable concentrate; F = Freshwater; M = Marine; MATC = Maximum Acceptable Toxicant
         Concentration; NEC = No effect concentration; T = Technical ingredient.

    

        In studies on the relative toxicity of fenitrothion in
    different developmental stages of fish, postlarvae of killifish
    (Takimoto et al., 1984b), and Japanese striped knifejaw (Seikai,
    1982) and the sac fry of carp (Hashimoto et al., 1982) were most
    susceptible with LC50 values of 2.36, 0.145, and 1.5 mg/litre,
    respectively.

        Oral administration of fenitrothion to carp showed a high
    LD50 value (more than 10 mg/kg) (Hashimoto & Fukami, 1969),
    whereas the 4-week, no-effect, dietary concentration was 1 mg/kg
    food (Wildish & Lister, 1973).

        Ingestion of contaminated, aquatic or terrestrial insects by
    salmonids is extremely unlikely to cause lethal or sublethal effects
    in the fish. Behavioural changes did not occur in laboratory studies
    until brook trout ingested 3000 times more fenitrothion than the
    3.19 mg/kg found in poisoned insects in treatment areas (Wildish &
    Lister, 1973).

        Exposure of young Atlantic salmon to 0.1 or 1 mg fenitrothion
    per litre for 15-16 h caused a 20 or 50% reduction in numbers of
    fish holding territories, respectively. Recovery of the parr from
    the above effects appeared to be complete in 3 weeks. Feeding and
    swimming behaviours returned to normal within 24-48 h (Symons,
    1973). After exposure to 1.0 mg fenitrothion/litre for 24 h,
    Atlantic salmon parr were more vulnerable than unexposed fish to
    predation by large brook trout; fenitrothion at 0.1 mg/litre did not
    have any noticeable effects on vulnerability (Hatfield & Anderson,
    1972).

        Juvenile Atlantic salmon exposed to 6.7 µg fenitrothion/litre
    for 7 days showed a decrease in the reaction distance to prey, but
    no significant decrease in the efficiency of the salmon's attack
    sequence (Morgan & Kiceniuk, 1990).

        The movement of goldfish was dependent on the fenitrothion
    concentration in water, the threshold level being about 0.01
    mg/litre (Scherer, 1975).

        Long-term studies revealed that the no-observed-effect level or
    maximum acceptable toxicant concentration (MATC) was at 0.1 mg/litre
    and above 0.1 mg/litre, respectively, in fathead minnows in a 31-day
    early life stage test (Kleiner et al., 1984) and in guppies in a
    2-month reproduction test (Yasuno et al., 1980).

        Exposure of freshwater murrel ( Channa punctatus) to a
    subtoxic concentration of 1.5 mg fenitrothion 50% EC/litre resulted
    in a reduction in protein-bound iodine levels after 60, but not 30,
    days exposure (Saxena & Mani, 1985a). On day 120 of exposure,
    effects on male and female reproductive function were observed, such
    as reductions in testicular and ovarian weight, growth rates

    of spermatocytes and oocytes, and the numbers of sperm and ova (Mani
    & Saxena, 1985; Saxena & Mani, 1985b, 1987). However, it is not
    clear whether such effects were derived from fenitrothion or other
    EC components.

        Pregnant female guppies were exposed to 10 mg
    fenitrothion/litre for 4 h, 5, 10, or 15 days before the next
    parturition. Half of the females gave premature birth when exposed 5
    or 10 days before parturition, and only 32 or 63%, respectively, of
    the eggs were delivered alive. The females exposed to the
    fenitrothion 15 days before parturition had normal births and only
    9.4% of the offspring were stillborn. The body lengths of the young
    produced by the females after exposure were significantly shorter
    than those produced before exposure in all the studies (Yasuno et
    al., 1980). In a study by Miyashita (1984), exposure of pregnant
    guppies ( Poecilia reticulata) to 10 mg/litre for 4 h at various
    stages of gestation resulted in a reduction in the body lengths of
    the offspring at birth.

        Rainbow trout ( Salmo gairdneri) were exposed to fenitrothion
    in a flow-through, early life stage, toxicity study at
    concentrations of 0, 0.025, 0.046, 0.088, 0.17, or 0.35 mg/litre,
    for 60-days after hatching at 10 ± 1 °C. Survival and growth of fry
    showed that the maximum acceptable toxicant concentration (MATC)
    limits were 0.088-0.17 mg/litre and that the point estimate MATC
    value was 0.12 mg fenitrothion/litre (Cohle, 1988).

        There were no direct lethal effects on wild and caged salmonid
    fish after forest spraying with fenitrothion at dosages varying from
    double sprays of 140 g/ha to single sprays of up to 280 g/ha in
    Newfoundland, Canada (Hatfield & Riche, 1970).

        Studies of the effects on wild salmon of fenitrothion sprays in
    New Brunswick, Canada, from 1966 to 1969 revealed no mortality in
    streams at spray levels of up to 560 g/ha (MacDonald & Penney,
    1969). Studies in Manitoba, Canada, on stream-caged rainbow trout
    exposed to a spray of 280 g fenitrothion/ha did not show any
    significant biochemical changes, including changes in brain and
    serum ChE activities. In the 24-h period after spraying,
    fenitrothion residues in whole fish averaged 0.5 mg/kg wet weight.
    Peak residue values in the fish were as high as 1.84 mg/kg wet
    weight but declined to less than 0.02 mg/kg wet weight in 4 days. 
    Lockhart et al. (1973) concluded that no long-term toxic effects
    would be expected among the caged fish.

        In the 1979 aerial spraying programme in Canada,
    concentrations of fenitrothion of up to 0.64 µg/litre were detected
    in stream water in the spray block within 40 h; no
    insecticide-related deaths of caged fish or abnormal fish behaviour
    occurred (Gillis, 1980).

        In 1979, fenitrothion was sprayed on a Scottish forest at a
    rate of 300 g/ha. The maximum concentration in a river was 18.8 µg
    per litre, 1-2 h after application. There was no evidence that the
    resident fish population was disturbed, and no short-term effects
    were noticeable in caged fish (Morrison & Wells, 1981). Gillis
    (1978) demonstrated, in a 1977 study, that, in an area with a long
    history of perennial treatment with fenitrothion (8 years since
    1969), there were consistently higher numbers of salmon per 100 m of
    stream, but that the density of trout was similar to that in the
    control area. It was concluded that the long history of fenitrothion
    usage in Canadian forests was unlikely to have resulted in depletion
    of the population or biomass of salmon parr trout.

    9.2.2  Invertebrates

        The acute toxicity of fenitrothion for  Daphnia magna was
    assessed using the 48-h static method at 20 ± 2 °C. The 48-h LC50
    value was 8.6 µg/litre (6.8-11 µg/litre) and the no-observed-effect
    level was estimated to be < 2.0 µg/litre after 48 h (Forbis, 1987).

         Daphnia magna was exposed to fenitrothion in a dynamic
    21-day, life cycle, toxicity study at concentrations of 0, 0.029,
    0.042, 0.087, 0.23, or 0.44 µg/litre, at 20 ± 2 °C. Statistical
    analyses of survival, adult mean length, and length in days to first
    brood, showed that the maximum acceptable toxicant concentration
    (MATC) limits were estimated to be 0.087 and 0.23 µg/litre and the
    point estimate MATC value was 0.14 µg/litre (Burgess, 1988).

        Fenitrothion is highly toxic for arthropods, including insect
    larvae, shrimps, crabs, and daphnids. LC50 values for these
    invertebrates are generally at µg/litre levels, except that for
    caddis fly larvae with a value of 11 mg/litre (Table 7).

        Exposure of the freshwater rice-field crab ( Oziotelphusa
    senex  senex) to sublethal concentrations of fenitrothion showed a
    number of effects: limb regeneration was completely inhibited at 0.1
    mg/litre and partially inhibited at 0.01-0.05 mg/litre, during
    continuous 60-days exposure (Reddy et al., 1983a); exposure to 0.04
    mg/litre for 30 days reduced glycolysis and increased
    gluco-neogenesis in the hepatopancreas and muscle (Reddy et al.,
    1982a, 1983b); exposure to 0.1 mg/litre induced inhibition of
    molting and ovarian growth, perhaps by triggering the release of
    molt-inhibiting hormone and gonad-inhibiting hormone (Reddy et al.,
    1982b, 1983c); exposure for 1 day to 0.1 mg/litre produced an
    increase in muscle protease activity and a decrease in the protein
    content, while exposure for 20 days resulted in increases in both
    parameters (Bhagyalakshmi et al., 1983a); continuous exposure for

    20-30 days to higher fenitrothion concentrations of 0.5, 1, or 2
    mg/litre resulted in a decrease in oxygen consumption, an increase
    in haemolymph glucose, and a reduction in carbohydrate metabolism
    rate in the hepatopancreas, with the maximal effect occurring after
    3-7 days of exposure. During the exposure, levels of haemolymph
    glucose and oxygen consumption returned to the control levels,
    accompanied by an increase in carbohydrate metabolism (Bhagyalakshmi
    et al., 1983b, 1984a). Exposure to 1, 2, or 4 mg/litre for 48 h
    resulted in a dose-dependent inhibition of acetylcholinesterase
    activity of the thoracic ganglionic mass, where mean activity levels
    in the treated groups ranged from 30 to 60% of the control values.
    On cessation of exposure, activity levels returned to normal within
    10-15 days (Bhagyalakshmi et al., 1984b).

        Fenitrothion was experimentally added to a stream at a
    concentration of 10 mg/litre, when the predominant and prevalent
    species in the drift samples were shrimps ( Anisogammarus sp.),
    mayfly ( Epeorus ikanonis, and  Baetis sp.), stonefly ( Nemovra
    sp.), and blackfly ( Simulium sp.) larvae. In the course of the
    study,  Simulium sp. increased in density, but  Anisogammarus sp.
    did not recover after 4 months (Yasuno et al., 1981). When
    fenitrothion was applied at 1 mg/litre to a stream, drifting aquatic
    invertebrates including shrimp ( Anisogammarus annandalei),  Baetis
    sp.,  Nemouridae, Epeorus sp.,  Perla quadrata, and  Simulium
    sp., but not caddis fly larvae (Arctopsyche sp.) or crab
    ( Geothelephusa  dehaanii), were affected by the insecticide
    (Hasegawa et al., 1982).

        After treatment of a small lake with 140 g fenitrothion/ha,
    surface populations of zooplankton and phantom midge larvae
     (Chaoborus sp.) were depressed for a short period. No substantial
    impact was found on benthic invertebrates, emerging insects, and
    amphibians in the lake (Kingsbury, 1978).

    9.2.3  Amphibians and arthropods

        Acute toxicity tests revealed that fenitrothion at 0.1 mg/litre
    did not induce any significant effects in amphibian embryos
    ( Xenopus  laevis) (Elliott-Feeley & Armstrong, 1982).

        When the frog embryo  (Microhyla ornata), at the yolk-plug
    stage, was exposed to 1 mg fenitrothion/litre for 96 h, no effects
    were observed on development. Exposure at 3 mg/litre resulted in
    blistering of the body surface and exposure at 5 mg/litre or more
    resulted in abnormal behaviour, curvature of the spine, diminished
    pigmentation, and retarded growth (Pawar & Katdare, 1983, 1984).

        The LC50 value for fenitrothion in tadpoles of Bufo buto
    japonicus was 9.0 mg/litre (Hashimoto & Nishiuchi, 1981). The
    toxicity of fenitrothion in mollusca was low with LC50 values of

    1.2-15 mg/litre in freshwater molluscs and 0.45 mg/litre in eastern
    oyster (Table 7). Fenitrothion residues in frogs, collected near
    stagnant water 1 day after spraying (280 g/ha), ranged from
    0.03-0.17 mg/kg wet weight (Lockhart et al., 1977).

        No effects were observed on amphibians and small mammals in
    Northern Maine, USA, where the forest had been treated twice with
    fenitrothion at the rate of 140 g/ha (USDA, 1976). Large numbers of
    hatching salamander eggs were present throughout the treatment
    period in the silty bottomed pond located in a treatment plot. No
    deaths were observed up to a week after the second spray. When the
    pond was examined approximately 2 months after treatment, it still
    contained many larval salamanders and aquatic invertebrates.

        A stream was treated with fenitrothion at a calculated
    concentration of 73 µg/litre for 2.5 h. The standing crop of benthic
    arthropods decreased, most of the kill consisting of stonefly larvae
    (Leucta sp.). Benthos, including the stonefly larvae, completely
    recovered 50 days after the treatment (Eidt, 1981).

        MacDonald & Penney (1969) studying the effects on aquatic
    insects of fenitrothion, applied twice at a rate of 140 g/ha, found
    that the aquatic insect population remained stable. The results of
    other studies suggested that populations of aquatic insects may be
    reduced following operational spraying with fenitrothion at 140-280
    g/ha (National Research Council of Canada, 1975). Stonefly nymphs,
    in particular, and mayfly nymphs, to a lesser extent, appeared to be
    susceptible to fenitrothion, along with caddis fly larvae.

        Flannagan (1973) reported that within 24 h of spraying at 280
    g/ha in Canada, the drift of chironomid larvae increased by 700-800%
    (total numbers/net). In some instances, Eidt (1975) and Peterson &
    Zitko (1974) observed that the drift returned to normal shortly
    after the pulse of fenitrothion had cleared.

        Fenitrothion was sprayed on a Scottish forest at a rate of 300
    g/ha. The maximum concentration in a river within the sprayed
    region, which was 18.8 µg/litre, fell to 0.5 µg/litre after 24 h.
    Invertebrate drift increased 12-16 h after spraying, but decreased
    to pre-spray levels within 48 h. Caged insects remained alive during
    the 5-day post-spray period (Morrison & Wells, 1981).

        Levels of fenitrothion residues in stream insects would not be
    sufficiently high to cause mortality in fish; 3.19 mg fenitrothion
    per kg was detected in a sample of mayfly nymphs one week after
    spraying with fenitrothion at 280 g/ha, but no residues of
    fenitrothion were found after this date (Kingsbury, 1976).

        An application of fenitrothion at 210 g/ha in Quebec, Canada,
    in 1978, had few or no adverse effects on aquatic invertebrates or
    fish, though a small increase in the drift of mayfly nymphs was
    observed after application (Holmes, 1979).

        In an area with a long history of perennial fenitrothion
    spraying (8 years since 1969), a light depletion of the invertebrate
    population was observed on both drift and benthos in streams after
    each spray, but the invertebrate density stabilized within 1 month
    and was comparable with the control (Gillis, 1978).

        When fenitrothion was dispersed by a helicopter in Japan at a
    rate of 884 g a.i./ha on a paddy field, a peak concentration of 554
    µg/litre was reached immediately after spraying, and the
    concentration of fenitrothion in the paddy field decreased to less
    than 5 µg/litre, 3 days after spray. A crustacean Moina sp., which
    was prevalent in the field, disappeared after fenitrothion spraying,
    but the population recovered to pre-spray levels within 10 days
    (Takaku et al., 1979b).

    9.3  Terrestrial organisms

        The acute and short-term toxicities of fenitrothion for
    terrestrial, non-target organisms are summarized in Table 8.

    9.3.1  Terrestrial invertebrates

        Studies using drop cloths (Leonard, 1971; Kettela & Varty,
    1972; Miller et al., 1973) indicated that large numbers of
     Lepidoptera, sawfly larvae, balsam twig aphids, and perching flies
    (nematocerous  Dipterans, etc.) were killed directly after the
    spraying operation (140 or 210 g/ha), usually within the first 4
    days. Generally, other defoliating insects were reduced in about the
    same proportion as the target species; the larval sawflies were
    affected more severely.

        Various preliminary measurements have been made on the effects
    of fenitrothion on invertebrate fauna (National Research Council of
    Canada, 1975). Populations of ground-inhabiting invertebrates
    declined after two operational applications of 140 and 210 g
    fenitrothion/ha (Carter & Brown, 1973). The densities of predatory
    invertebrates were higher in the 2 years before and the year
    following the application. Thus, while the invertebrate populations
    appeared to be depressed during the years of application, they were
    generally able to recover to the normal levels.

        On the basis of field observations on the long-term effects of
    fenitrothion on non-target arthropods in Canada, Varty (1977)
    concluded that:

    -   The non-target arthropod community on balsam fir was not 
        perceptibly destabilized by perennial or intermittent
        applications at conventional rates (140-210 g/ha) and timing.

    -   A few fir-dwelling insects had become scarcer during the 1970s,
        but the cause-effect was undetermined, and natural fluctuation
        could account for the population decline.

    -   The abundance of predators was related primarily to cycles of 
        preabundance on fir and spruce, and to budworm modification  of
        habits.

    -   Herbivore populations tended to be depressed by budworm 
        competition, but fungivores might be favoured.

    -   The abundance of the two most important species parasitizing 
        spruce budworm larvae persisted, in spite of perennial
        spraying.

    -   Population densities of some species-predatory arthropods in
        the soil community might suffer some setback, but in short-term
        studies recuperation seemed adequate.

    -   Minor-pest eruptions in the 1970s did not appear to be
        triggered by the local disruption of biocontrol mechanisms
        following spraying.

        Fenitrothion is highly toxic for bees (Anderson & Atkins, 1968;
    Okada & Hoshiba, 1970), the LD50 is approximately 0.03-0.13 µg per
    bee (Anderson & Atkins, 1968) (Table 8). However, studies on the
    effects of fenitrothion on colonies of honey-bees indicated that an
    application of 280 g/ha had few long-term effects (National Research
    Council of Canada, 1975). Initially, mortality of adult foraging
    bees was evident. Within 4 days of treatment, the daily adult
    mortality of foraging bees had apparently returned to normal. The
    total detected mortality in excess of controls was about 500 adult
    bees, which was estimated to be about 1% of the total hive
    population. Buckner (National Research Council of Canada, 1975)
    reported that hive activity was unaffected compared with controls,
    and that hive weight and eventual honey yield were almost identical
    in all experimental and control hives. The observed mortality was
    probably restricted to actively foraging worker bees that were
    actually exposed to the spray.


    
    Table 8.  Toxicity of fenitrothion for terrestrial non-target organismsa
                                                                                                                                              

    Species                  Size                  Toxicity                       Formulation    Condition          Reference
                                                                                                                                              

    Birds

    Bobwhite quail           14 days old           LC50  5000 mg/kg diet              T          8-day dietary      Hill et al. (1975)
    (Colinus virginianus)

    Japanese quail           14 days old           LC50  5000 mg/kg                   T          8-day dietary      Hill et al. (1975)
    (Coturnix c japonica)                                diet (no mortality)
                             5 weeks old (M)       LD50  84.85 mg/kg               50% EC            oral           Hattori et al. (1974)
                             5 weeks old (F)       LD50  73.87 mg/kg               50% EC            oral           Hattori et al. (1974)
                             3-6 weeks old (M)     LD50  110 mg/kg                    T              oral           Kadota & Miyamoto (1975)
                             3-6 weeks old (F)     LD50  140 mg/kg                    T              oral           Kadota & Miyamoto (1975)
                             3-6 weeks old         NEL   approx. 5 mg/kg diet         T         4-week dietary      Kadota & Miyamoto (1975)

    Ring-necked pheasant     10 days old           LC50  5000 mg/kg                   T          8-day dietary      Hill et al. (1975)
    (Phasianus colchicus)                                diet (no mortality)

    Mallard duck
    (Anas platyrhynchos)     10 days old           LC50  5000 mg/kg                   T          8-day dietary      Hill et al. (1975)
                                                         diet (no mortality)
                             13-16 weeks old (M)   LD50  1190 mg/kg                   T              oral           Hudson et al. (1979)
                             55-61 weeks old (M)   LD50  504 mg/kg                    T          percutaneous       Hudson et al. (1979)

    Redwinged blackbird
    (Agelaius phoeniceus)                          LD50  25 mg/kg                   oral        Schafer (1972)
                                                                                                                                              

    Table 8 (contd).
                                                                                                                                              

    Species                  Size                  Toxicity                       Formulation    Condition          Reference
                                                                                                                                              

    Pigeon                   250-380 g             LD50  42.24 mg/kg               50% EC            oral           Hattori (1974)
    (Columba livia)

    Grackle
    (Quiscalus quiscula)                           LC50  78 mg/kg diet                T          5-day dietary      Grue (1982)

    Insect

    Honeybee                 7 days old            24-h  LD50 0.13 µg/bee             T             topical         Takeuchi et al. (1980)
    (Apis mellifera)                                                                               32 ± 1 °C

                                                   24-h  LD50 0.03 µg/bee          50% EC           topical         Okada & Hoshiba (1970)
                                                                                                   32 ± 1 °C

                                                   LD90  0.25 µg/bee               60% EC            oral           Clinch & Ross (1970)
                                                                                                     30 °C

    Silkworm                 II-V instar           24-h  LD50                         T             topical         Kashi (1972)
    (Bombyx mori)                                  4.88-18.7 µg/g
                                                                                                                                              

    a    M = Male;  F = Female;  T = Technical ingredient;  EC = Emulsifiable concentrate.

    

        Plowright (1977) demonstrated that fenitrothion, sprayed at a
    dose level of 210 g/ha, was capable of inducing direct mortality in
    caged bumble-bees. Aerially sprayed fenitrothion at 210 g/ha in
    Canada caused 100% mortality in exposed habitats and 47% under dense
    forest canopy, among caged bees  (Bombus sp). Bumble bees foraging
    in sprayed areas suffered significantly higher mortality than in
    unsprayed areas. The abundance of bee species was 3 times less in
    sprayed areas compared with unsprayed areas. Population recovery
    appeared to be complete within a few years (Plowright et al., 1978).

        Plowright & Rodd (1980) further examined the effects of
    fenitrothion in wild bees, and found that fenitrothion sprayed at
    210 g/ha caused high mortality among solitary bees and vespid wasps,
    similar to that in bumble bees (Plowright et al., 1978). Wood (1979)
    found that spraying of fenitrothion over nearby woodland resulted in
    very low counts of native bees; however, the population returned to
    normal levels within 3 years of spraying, with satisfactory
    pollination of blueberry.

        Wild  Bombus sp. queen territories were identified prior to
    treatment and a search was made for these queens after the
    application of fenitrothion (280 g/ha) in Larose Forest, Canada.
    Queens identified prior to a morning spray were again identified 1,
    2, and 3 days after treatment. In this single study, no significant
    effects were indicated (National Research Council of Canada, 1975).

        The low yield of low-bush blueberry was reported to be
    attributable to the mortality of native bees (Kevan, 1975) and lack
    of pollination following aerial fenitrothion spraying to control
    spruce budworm in nearby forests in New Brunswick. However, field
    experiments in 1980 showed that there was no evidence of any harmful
    effects on the blueberry as a result of fenitrothion spraying and
    that the concentration of fenitrothion aerosols found in blueberry
    fields during the 1980 budworm spray programme was estimated to be
    well below the toxic levels for all bee species (Wood, 1980).

        Bee, pollen, and wax samples were collected from forest areas
    that had been sprayed with fenitrothion for budworm control at an
    operational dosage of 140-280 g/ha, over a 3-year period from 1972.
    The level of fenitrothion in bees was low (maximum 2.08 mg/kg)
    initially, and decreased rapidly to trace levels within a week.
    Fenitrothion levels in pollen were very low initially, but declined
    less rapidly than in bees. Accumulations of the insecticide in honey
    and wax samples were negligibly small, but traces seemed to persist
    in the wax for some time (Sundaram, 1975).

        Fenitrothion is toxic for one of the beneficial insects,
    silkworm ( Bombyx mori) larvae. Silkworms were fed mulberry leaves
    that had been treated with fenitrothion at the rate of 100 ml of

    0.0025 or 0.005% fenitrothion solution /kg leaves (equivalent to 2.5
    and 5 mg/kg). The administration during the 5 instar larva stage
    resulted in a reduction in the number of eggs laid, fertility, and
    hatching (Kuribayashi, 1981). At a lower concentration (1 mg/kg), no
    effect was observed on mortality, egg laying, and hatching (Yamanoi,
    1980). Growth after hatching was not affected by fenitrothion
    treatment (Yamanoi, 1981).

        The populations of nematodes, rotifers, and tardigrades in soil
    were not affected after fenitrothion was sprayed on the surface of a
    pasture at a rate of 2.24 kg a.i./ha (Martin & Yeates, 1975).

    9.3.2  Birds

        The acute oral LD50 values of fenitrothion in birds are shown
    in Table 8. The values range from 25 mg/kg (Redwinged blackbird) to
    1190 mg/kg (Mallard duck).

        Except for the grackle with a dietary LD50 of 78 mg/kg,
    values were generally more than 5000 mg/kg diet and, at this dose
    level, no mortality was observed (Hill et al., 1975).

        The effects of fenitrothion on the brain cholinergic system
    were investigated in male Japanese quail (8-14 weeks old).
    Cholinergic signs, such as salivation and convulsions in legs and
    wings, were seen 6-120 min after the administration of fenitrothion
    (250-350 mg/kg). Sixty minutes after an oral dose of fenitrothion
    (300 mg/kg), free acetylcholine increased and acetylcholinesterase
    (AChE) activity decreased to 20% of the control value.  In vitro,
    fenitrothion inhibited AChE activity in brain homogenate with an
    I50 of 10-5 mol/litre (Kobayashi et al., 1983).

        Japanese quail (60 per sex; 20 per sex in the 1.5 mg/kg group)
    received 0, 1.5, 5, 15, or 50 mg fenitrothion/kg in the diet for 4
    weeks. No animals died and no toxic signs were seen; no
    abnormalities in body weight or food consumption were observed. A
    dose-related decrease in blood ChE activity was observed in females
    in the 5 mg/kg group (25%), and in males and females in the 15 mg/kg
    (60%) and 50 mg/kg (85%) groups during the treat-ment period. When
    these animals were fed the control diet again, partial recovery of
    ChE activity occurred within 2 weeks, while the brain ChE activity
    was reduced in females in the 15 mg/kg group (25%) and males and
    females in the 50 mg/kg group (65%). Full recovery of ChE activity
    occurred after 4 weeks. In the 50 mg/kg group, the egg-laying rate
    was decreased, but returned to normal after 3 weeks (Kadota &
    Miyamoto, 1975).

        Reproduction studies on bobwhite quails and mallard ducks
    revealed that short-term feeding of fenitrothion at rates of up to
    10 mg/kg diet (quails) or 100 mg/kg diet (ducks) did not adversely
    affect parental growth and reactions, egg production, egg weight,
    hatchability, and the growth and viability of the young (Miyamoto,
    1977b).

        Adverse effects on bird species were observed occasionally when
    fenitrothion was applied at dosages higher than those commonly used
    for operational applications (National Research Council of Canada,
    1975); above 280 g/ha, mortality was observed in adults that
    inhabited the crown canopy, and, at rates of 560 g/ha or more, adult
    mortality increased markedly. At rates of 210 or 280 g/ha,
    behavioural changes were observed in adults as well as some juvenile
    mortality.

        When fenitrothion was sprayed at 1.7 kg a.i./ha, twice a year,
    for three consecutive years in Japan, Takano & Hijikata (1981) were
    unable to detect impacts on bird diversity, abundance, and
    reproductive success, when 9 species (including the long-tailed tit,
    which is most sensitive to fenitrothion) out of 48 were monitored in
    the forests and fields (55 ha).

        The various effects of fenitrothion on White-throated Sparrows
    in New Brunswick, Canada, were investigated, with the following
    results (Pearce & Busby, 1980):

    -   The parent compound fenitrothion was detected at levels as low 
        as 0.02 to 0.41 mg/kg in the male birds from the spray zone,
        but  none of its metabolites were found. There were no
        correlations  between fenitrothion residue levels and brain ChE
        activity in  sparrows.

    -   Singing frequency, song structure, clutch size, hatching
        success,  and fledging rates were similar in the control and
        experimental  area.

    -   Growth parameters, such as body weight, tarsus length, bill 
        length and width, and wing length, of the nestling birds 
        appeared to be lower in the exposed nestlings than in the 
        controls after fenitrothion spraying at a rate of 210 g
        a.i./ha.

    -   The reproductive success was reduced in the exposed area after 
        repeated spraying of fenitrothion, first at 420 g/ha and
        several  days later at 210 g/ha. The young White-throated
        Sparrows  from 11.6% of the eggs laid fledged in the sprayed
        area,  whereas the young from 58.3% of the eggs laid fledged in
        the  control area.

    -   The main causes of reduced productivity in the sprayed area 
        were the high rate of nest desertion, the occasional death or 
        incapacitation of incubating females, and the high rate of 
        nestling disappearance from nests.

        Eight hours after being exposed to an operational spray of
    fenitrothion at 280 g/ha, the crops and carcasses of caged Japanese
    quail contained 0.045-0.459 mg fenitrothion/kg (wet tissue basis),
    when cages were placed in open locations, and the crops, up to 1.89
    mg/kg, when the cages were placed below the tree canopy (Lockhart et
    al., 1977). However, fenitrothion residues in all samples declined
    sharply to an undetectable level (< 0.02 mg/kg) after 5 days.
    Although these birds suffered a drop in serum ChE activity, they
    were not killed and recovery of enzyme activity was observed 5 days
    after spraying (Lockhart et al., 1977).

        Experimental fenitrothion spraying at the rate of 210-280 g
    a.i./ha was conducted using 2 types of spray hardware (boom and
    nozzle and rotary atomizer) in southwest New Brunswick, Canada. The
    brain ChE activity of the 5 avian species monitored (Tennessee
    Warbler ( Vermivora peregrina), Magnolia Warbler ( Dendroica
    magnolia), Blackburnian Warbler ( D. fusca), Bay-breasted Warbler
    ( D.  castanea), and White-throated Sparrow ( Zonotrichia
    albicollis)) was significantly inhibited compared with that in the
    control birds, and 16-30% of the captive birds showed more than 20%
    inhibition compared with the controls. However, no dead birds or
    abnormal avian behaviour was observed (Busby et al., 1981).

        Brain cholinesterase (ChE) inhibition and fenitrothion residues
    were determined in White-throated Sparrows ( Zonotrichia
    albicollis), exposed to aerial applications of fenitrothion (210 g
    a.i./ha applied twice with a 5-8 day interval) during the breeding
    seasons in 1978 and 1979, in New Brunswick (Canada). Brain ChE
    activity was significantly reduced in birds exposed to the sprays
    (50-66% inhibition) and fenitrothion and metabolite residues were
    detected in all exposed birds (0.08-1.4 mg/kg); however, they did
    not show any consistent correlation with brain ChE activity. An
    acute brain ChE response, manifested as sudden ChE reduction
    followed by gradual recovery, was noted in birds collected after
    spraying with 420 g a.i./ha (Busby et al., 1983).

        A study was conducted to assess the response of selected forest
    songbird species, including the Tennessee Warbler ( Vermivora
     peregrina), Bay-breasted Warbler ( Dendroica castanea), Magnolia
    Warbler ( D. magnolia), and White-throated Sparrow ( Zonotrichia
     albicollis), to aerial ultra ULV fenitrothion (40% content)
    spraying (210 g a.i./ha applied twice with a 6-day interval) through
    measurements of brain cholinesterase (ChE) depression. A slight
    reduction (6-17% less brain ChE activity than in the controls) was
    observed in birds collected on day 2

    after the second spray; birds collected on day 1 of the first spray
    were least affected (0-5% less activity). As a group, the Tennessee
    Warbler, the upper canopy forager and singer, exhibited the highest
    degree of ChE inhibition (6-17% less activity) and the
    White-throated Sparrow, the ground-to-low crown dweller, showed the
    least (0-8%) inhibition (Busby et al., 1987).

        Brain AchE activity in songbirds exposed through experimental
    fenitrothion spraying was monitored in Scotland in 1979 and 1980
    (Hamilton et al., 1981). The brain ChE activity of songbirds was
    significantly inhibited in the first 2 days after spraying of
    fenitrothion at dosages of 300 g/ha in 1979 and 280 g/ha in 1980. 
    However, the enzyme activity in willow warblers ( Phylloscopus
     trochilus) and chaffinches ( Fringilla coelebs) returned to the
    normal levels, 7 and 21 days after spraying, respectively. The
    residues of fenitrothion found in skin and plumage samples taken
    from birds during the first few days after spraying were relatively
    high, but declined rapidly to a low level. The fenitrothion residues
    in viscera samples were very small initially and were not detectable
    a few days after spraying (Hamilton et al., 1981).

        Several publications concerning the possible effects of
    fenitrothion on avian species including: Rushmore (1971), Hill et
    al. (1975), National Research Council of Canada (1975), Paul &
    Vadlamudi (1976), USDA (1976), Buckner & McLeod (1977), Germain
    (1977), Pearce & Peakall (1977), Germain & Morin (1979), and Pearce
    et al. (1979b) are not cited in extenso, because they report
    findings similar to those above.

    9.3.3  Mammals

        Bailey & Swift (1968) classified fenitrothion as moderately
    toxic for mammals.

        Buckner reported that, at operational application rates below
    420 g/ha, fenitrothion spraying did not produce any measurable
    effects on small mammals in Maine (USA). Spraying of fenitrothion at
    recommended rates would not be expected to cause mortality or
    interrupt the breeding cycle of small mammal populations in forests
    (Buckner & Sarrazin, 1975; Varty, 1976; Buckner et al., 1977)
    though, at very high rates, some ill effects have been observed on
    shrew and rodent populations (USDA, 1976). In addition, the
    discriminatory behaviour of mature animals suggested that
    fenitrothion-contaminated food material was rejected and that it was
    a learned process (Buckner et al., 1977).

        When fenitrothion was sprayed twice a year, at the rate of 1200
    g/ha, by helicopter, there was no decrease in either plasma or
    erythrocyte ChE activity in the Japanese wood mouse ( Apodemus
     speciosus) inhabiting the sprayed area (Tabata & Kitahara, 1980).

        The metabolism of fenitrothion in red-backed voles, which
    inhabit the coniferous forests of Canada, did not differ
    substantially from that demonstrated for laboratory strains of mice,
    rats and guinea-pigs. When fenitrothion was administered ip at doses
    of 48.4-2040 mg/kg, it was rapidly metabolized and excreted. No
    accumulation of fenitrothion residues in the body was indicated. The
    metabolic detoxification mechanism in red-backed voles involves the
    cleavage of both the P-O-aryl and P-O-alkyl bonds, the latter being
    more prominent at high dose levels (above 1250 mg/kg) (Tschaplinski
    & Gardner, 1981).

        Thus, the standard programme of forest spraying with the
    insecticide does not appear to have serious ecological consequences
    (Symons, 1977).

    10.  PREVIOUS EVALUATIONS BY INTERNATIONAL BODIES

        Fenitrothion was evaluated by the Joint FAO/WHO Expert
    Committee on Pesticide Residues (JMPR) in 1969, 1974, 1976, 1977,
    1979, 1982, 1983, 1984, 1986, 1987, 1988, and 1989, (FAO/WHO, 1970,
    1975a,b, 1977, 1978a,b, 1980a,b, 1983a,b, 1984a,b, 1985a,b, 1986a,b,
    1987a,b, 1988a,b, 1989a,b,c). In 1988 the JMPR established an
    Acceptable Daily Intake (ADI) for man of 0-0.005 mg/kg body weight.

        This was based on the following levels causing no toxicological
    effects:

    -   Rat:     10 mg/kg in the diet, equivalent to 0.5 mg/kg body
                 weight per day (based on brain acetylcholinesterase
                 inhibition and reproduction).

    -   Dog:     50 mg/kg in the diet, equivalent to 1.25 mg/kg body
                 weight per day.

    -   Man:     0.08 mg/kg body weight per day (highest dose tested).

        The FAO/WHO Codex Committee advised maximum residue limits
    (MRLs) in specified food commodities (FAO/WHO, 1986c; 1990) as
    follows:

         Milks                                        0.002 mg/kg

         Cucumbers, meat, onions, potatoes            0.05 mg/kg

         Cauliflower, cocoa beans, egg plants,
          peppers, soybeans (dry)                     0.1 mg/kg

         Bread (white), leeks, radishes               0.2 mg/kg

         Apples, cabbage, cabbage red, cherries,
          grapes, lettuce, pear, peas, strawberries
          tea (dried, green), tomatoes                0.5 mg/kg

         Peach, rice (polished)                       1 mg/kg

         Citrus fruits, wheat flour (white)
          processed wheat bran                        2 mg/kg

         Wheat flour (whole meal)                     5 mg/kg

         Cereal grains                                10 mg/kg

         Raw wheat bran, rice bran unprocessed        20 mg/kg 

         WHO (1990) classified technical fenitrothion as "moderately
    hazardous" (Class II). WHO issued a data sheet on Fenitrothion (No.
    30) (WHO, 1977).

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    on non-target terrestrial arthropods. In: Proceedings of a Symposium
    on Fenitrothion, Ottawa, National Research Council of Canada, pp.
    344-375 (Publication NRCC No. 16073).

    VELAZQUEZ, A., XAMENA, N., CREUS, A., & MARCOS, R. (1987)
    Mutagenicity studies on fenitrothion in Drosophila. Mutagenesis, 2:
    333-336.

    VERMA, S.R., BANSAL, S.K., & DALELA, R.C. (1977) Bioassay trials
    with a few organic biocides on fresh water fish Laveo rohita. Indian
    J. environ. Health, 19: 107-115.

    VERMA, S.R., BHATNAGAR, M.C., & DALELA, R.C. (1978a) Biocides in
    relation to water pollution. Part 2: Bioassay studies of few
    biocides to a fresh water fish  Channa gachua. Acta hydrochim.
    hydrobiol., 6: 137-144.

    VERMA, S.R., BANSAL, S.K., & DALELA, R.C. (1978b) Toxicity of
    selected organic pesticides to a fresh water teleost fish,
     Saccobranchus  fossilis and its application in controlling water
    pollution. Arch. environ. Contam. Toxicol., 7: 317-323.

    VERMA, S.R., BANSAL, S.K., GUPTA, A.K., PAL, N., TYAGI, A.K.,
    BHATNAGER, M.C., KUMAR, V., & DALELA, R.C. (1982) Bioassay trials
    with twenty three pesticides to a fresh water teleost,
     Saccobranchus  fossilis. Water Res., 16: 525-529.

    VOLPE, G.G. & MALLET, V.N. (1980) Development of an analytical
    method for fenitrothion and five derivatives in water using XAD
    resins and gas-liquid chromatography (GLC). Int. J. environ. anal.
    Chem., 8: 291-301.

    VOLPE, G.G. & MALLET, V.N. (1981) High-performance liquid
    chromatography of fenitrothion and seven derivatives - a study of
    their recovery from water using XAD resins as compared with organic
    solvents. Chromatographia, 14: 333-336.

    WARREN, M.W., RUEBUSH, T.K., II, HOBBS, J.H., HIPPOLYTE, R., & MILLER,
    S.  (1985a) Safety measures associated with the use of organophosphate
    insecticides in the Haitian malaria control programme. Bull. World
    Health Organ., 63(2): 345-351.

    WARREN, M.W., SPENCER, H.C., CHURCHILL, F.C., FRANCOIS, V.J.,
    HIPPOLYTE, R., & STAIGER, M.A. (1985b) Assessment of exposure to
    organophosphate insecticides during spraying in Haiti: monitoring of
    urinary metabolites and blood cholinesterase levels.  Bull. World
    Health Organ., 63(2): 353-360.

    WEINBERGER, P., GREENHALGH, R., SHER, D., & OUELLETTE, M. (1982a) 
    Persistence of formulated fenitrothion in distilled, estuarine, and
    lake water microcosmos in dynamic and static systems. Bull. environ.
    Contam. Toxicol., 28: 484-489.

    WEINBERGER, P., GREENHALGH, R., MOODY, R.P., & BOULTON, B. (1982b)
    Fate of fenitrothion in aquatic microcosmos and the role of aquatic
    plants. Environ. Sci. Technol., 16: 470-473.

    WHO(1973) Fenitrothion. In: Safe use of pesticides. Twentieth report
    of the WHO Expert Committee on Insecticides, Geneva, World Health
    Organization, pp. 18-19 (WHO Technical Report Series No. 513).

    WHO/FAO (1977) Data sheets on pesticides No. 30: Fenitrothion,
    Geneva, World Health Organization, 9 pp (VBC/DS/77.30).

    WHO (1986) Environmental Health Criteria 63: Organophosphorus
    insecticides: A general introduction, Geneva, World Health
    Organization, 181 pp.

    WHO (1990) The WHO recommended classification of pesticides by
    hazard and Guidelines to classification 1990-1991, Geneva, World
    Health Organization (WHO/PCS/90.1).

    WILDISH, D.J. & LISTER, N.A. (1973) Biological effects of
    fenitrothion in the diet of brook trout. Bull. environ. Contam.
    Toxicol., 10: u333-339.

    WILDISH, D.J. & LISTER, N.A. (1977) Effects of dietary fenitrothion
    on growth and hierarchial position in brook trout  (Salvelinus 
     fontinalis). Prog. Fish-Cult., 39: 3-9.

    WILFORD, K., LIETEART, P.E.A., & FOLL, C.V. (1965) Fenitrothion:
    Working paper prepared for an informal meeting of toxicology of
    insecticides, Geneva, World Health Organization, pp. 18-23
    (65/TOX/1).

    WOOD, G.W. (1979) Recuperation of native bee. Population in
    blueberry fields exposed to drift of fenitrothion from forest spray
    operations in New Brunswick. J. econ. Entomol., 72: 36-39.

    WOOD, G.W. (1980) Bee toxicology from fenitrothion aerosol,
    Fredericton, Agriculture Canada Research Station, 60 pp.

    WOOD, R.B., Jr & BOGDAN, G.F. (1986) Reye's syndrome and spruce
    budworm insecticide spraying in Maine, 1978-1982. Am. J. Epidemiol.,
    124: 671-677.

    WOODWARD, D.F. & MAUCK, W.L. (1980) Toxicity of five forest
    insecticides to cutthroat trout and two species of aquatic
    invertebrates. Bull. environ. Contam. Toxicol., 25: 846-853.

    WORTHING, C.R. & WALKER, S.B., ed. (1983) Fenitrothion. In: The
    pesticide manual 7th ed., Croydon, The British Crop Protection
    Council, p. 261.

    WRIGHT, C.G., LEIDY, R.B., & DUPREE, H.E., Jr (1981) Insecticides in
    the ambient air of room following their application for control of
    pest. Bull. environ. Contam. Toxicol., 26: 548-553.

    YADAV, A.S., VASHISHAT, R.K., & KAKAR, S.N. (1982) Testing of
    endosulfan and fenitrothion for genotoxicity in  Saccharomyces
     cerevisiae. Mutat. Res., 105: 403-407.

    YAMAMOTO, T., EGASHIRA, T., YOSHIDA, T., & KUROIWA, Y. (1982a) 
    Comparison of the effect of an equimolar and low dose of
    fenitrothion and methylparathion on their own metabolism in rat
    liver. J. toxicol. Sci., 7: 35-41.

    YAMAMOTO, T., EGASHIRA, T., YOSHIDA, T., & KUROIWA, Y. (1982b)
    Increase of adrenal weight in rats by the repeated administration of
    fenitrothion. Toxicol. Lett., 11: 187-191.

    YAMAMOTO, T., EGASHIRA, T., YOSHIDA, T., & KUROIWA, Y. (1983a)
    Effect of adrenalectomy, pretreatment with SKF 525-A, phenobarbital
    and diethyl-maleate on the acute toxicity of fenitrothion in male
    rats. Arch. Toxicol., 52: 233-242.

    YAMAMOTO, T., EGASHIRA, T., YOSHIDA, T., & KUROIWA, Y. (1983b) 
    Comparative metabolism of fenitrothion and methylparathion in male
    rats. Acta pharmacol. toxicol., 53: 96-102.

    YAMANOI, F. (1980) [Effect of insecticides on the progeny in the
    silkworm,  Bombyx mori. I. Effect of organophosphorus insecticides
    on egg laying and their hatching.] J. Sericult. Sci. Jpn, 49:
    434-439 (in Japanese).

    YAMANOI, F. (1981) [Effect of insecticides on the progeny in the
    silkworm,  Bombyx mori. II. Effect of organophosphorus insecticides
    on the next generation.] J. Sericult. Sci. Jpn, 50: 83-87 (in
    Japanese).

    YASUNO, M., HATAKEYAMA, S., & MIYASHITA, M. (1980) Effect on
    reproduction in Guppy  (Poecilia reticulata) under chronic exposure
    to temephos and fenitrothion. Bull. environ. Contam. Toxicol., 25:
    29-33.

    YASUNO, M., OKITA, J., SAITO, K., NAKAMURA, Y., HATAKEYAMA, S., &
    KASUGA, S. (1981) Effect of fenitrothion on benethic fauna in small
    stream of Mt. Tsukuba, Japan. Jpn. J. Ecol., 31: 237-245.

    YOSHIDA, M., SHIMADA, E., YAMANAKA, H., AOYAMA, Y., YAMAMURA, Y., &
    OWADA, S. (1987) A case of acute poisoning with fenitrothion
    (Sumithion). Hum. Toxicol., 6: 403-406.

    YULE, W.N. (1974) The persistence and fate of fenitrothion
    insecticide in a forest environment II. Accumulation of residues in
    balsam fir foliage. Bull. environ. Contam. Toxicol., 12: 249-252.

    YULE, W.N. & DUFFY, J.R. (1972) The persistence and fate of
    fenitrothion insecticide in a forest environment. Bull. environ.
    Contam. Toxicol., 8: 10-18.

    ANNEX I
    TREATMENT OF ORGANOPHOSPHATE INSECTICIDE POISONING IN MAN

    (From EHC 63: Organophosphorus Insecticides - A General
    Introduction)

         All cases of organophosphorus poisoning should be dealt with as
    an emergency and the patient sent to hospital as quickly as
    possible. Although symptoms may develop rapidly, delay in onset or a
    steady increase in severity may be seen up to 48 h after ingestion
    of some formulated organophosphorus insecticides.

         Extensive descriptions of treatment of poisoning by
    organophosphorus insecticides are given in several major references
    (Kagan, 1977; Taylor, 1980; UK DHSS, 1983; Plestina, 1984) and will
    also be included in the IPCS Health and Safety Guides to be prepared
    for selected organophosphorus insecticides.

         The treatment is based on:

         (a)  minimizing the absorption;

         (b)  general supportive treatment; and

         (c)  specific pharmacological treatment.

    1.1  Minimizing the absorption

         When dermal exposure occurs, decontamination procedures include
    removal of contaminated clothes and washing of the skin with
    alkaline soap or with a sodium bicarbonate solution. Particular care
    should be taken in cleaning the skin area where venepuncture is
    performed. Blood might be contaminated with direct-acting
    organophosphorus esters and, therefore, inaccurate measures of ChE
    inhibition might result. Extensive eye irrigation with water or
    saline should also be performed. In the case of ingestion, vomiting
    might be induced, if the patient is conscious, by the administration
    of ipecacuanha syrup (10-30 ml) followed by 200 ml water. This
    treatment is, however, contraindicated in the case of pesticides
    dissolved in hydrocarbon solvents. Gastric lavage (with addition of
    bicarbonate solution or activated charcoal) can also be performed,
    particularly in unconscious patients, taking care to prevent
    aspiration of fluids into the lungs (i.e., only after a tracheal
    tube has been put into place).

         The volume of fluid introduced into the stomach should be
    recorded and samples of gastric lavage frozen and stored for
    subsequent chemical analysis. If the formulation of the pesticide

    involved is available, it should also be stored for further analysis
    (i.e., detection of toxicologically relevant impurities). A
    purgative can be administered to remove the ingested compound.

    1.2  General supportive treatment

         Artificial respiration (via a tracheal tube) should be started
    at the first sign of respiratory failure and maintained for as long
    as necessary.

         Cautious administration of fluids is advised, as well as
    general supportive and symptomatic pharmacological treatment and
    absolute rest.

    1.3  Specific pharmacological treatment

    1.3.1  Atropine

         Atropine should be given, beginning with 2 mg iv and given at
    15-30-min intervals. The dose and the frequency of atropine
    treatment varies from case to case, but should maintain the patient
    fully atropinized (dilated pupils, dry mouth, skin flushing, etc.). 
    Continuous infusion of atropine may be necessary in extreme cases
    and total daily doses up to several hundred mg may be necessary
    during the first few days of treatment.

    1.3.2  Oxime reactivators

         Cholinesterase reactivators (e.g., pralidoxime, obidoxime)
    specifically restore AChE activity inhibited by organophosphates. 
    This is not the case with enzymes inhibited by carbamates. The
    treatment should begin as soon as possible, because oximes are not
    effective on "aged" phosphorylated ChEs. However, if absorption,
    distribution, and metabolism are thought to be delayed for any
    reasons, oximes can be administered for several days after
    intoxication. Effective treatment with oximes reduces the required
    dose of atropine. Pralidoxime is the most widely available oxime. A
    dose of 1 g pralidoxime can be given either im or iv and repeated
    2-3 times per day or, in extreme cases, more often. If possible,
    blood samples should be taken for AChE determinations before and
    during treatment. Skin should be carefully cleansed before sampling.
    Results of the assays should influence the decision whether to
    continue oxime therapy after the first 2 days.

         There are indications that oxime therapy may possibly have
    beneficial effects on CNS-derived symptoms.

    1.3.3  Diazepam

         Diazepam should be included in the therapy of all but the
    mildest cases. Besides relieving anxiety, it appears to counteract

    some aspects of CNS-derived symptoms that are not affected by
    atropine. Doses of 10 mg sc or iv are appropriate and may be
    repeated as required (Vale & Scott, 1974). Other centrally acting
    drugs and drugs that may depress respiration are not recommended in
    the absence of artificial respiration procedures.

    1.3.4  Notes on the recommended treatment

    1.3.4.1  Effects of atropine and oxime

         The combined effect far exceeds the benefit of either drug
    singly.

    1.3.4.2  Response to atropine

         The response of the eye pupil may be unreliable in cases of
    organophosphorus poisoning. A flushed skin and drying of secretions
    are the best guide to the effectiveness of atropinization. Although
    repeated dosing may well be necessary, excessive doses at any one
    time may cause toxic side-effects. Pulse-rate should not exceed
    120/min.

    1.3.4.3  Persistence of treatment

         Some organophosphorus pesticides are very lipophilic and may be
    taken into, and then released from, fat depots over a period of many
    days. It is therefore quite incorrect to abandon oxime treatment
    after 1-2 days on the supposition that all inhibited enzyme will be
    aged. Ecobichon et al. (1977) noted prompt improvement in both
    condition and blood-ChEs in response to pralidoxime given on the
    11th-15th days after major symptoms of poisoning appeared due to
    extended exposure to fenitrothion (a dimethyl phosphate with a short
    half-life for aging of inhibited AChE).

    1.3.4.4  Dosage of atropine and oxime

         The recommended doses above pertain to exposures, usual for an
    occupational setting, but, in the case of very severe exposure or
    massive ingestion (accidental or deliberate), the therapeutic doses
    may be extended considerably. Warriner et al. (1977) reported the
    case of a patient who drank a large quantity of dicrotophos, in
    error, while drunk. Therapeutic dosages were progressively increased
    up to 6 mg atropine iv every 15 min together with continuous iv
    infusion of pralidoxime chloride at 0.5 g/h for 72 h, from days 3 to
    6 after intoxication. After considerable improvement, the patient
    relapsed and further aggressive therapy was given at a declining
    rate from days 10 to 16 (atropine) and to day 23 (oxime),
    respectively. In total, 92 g of pralidoxime chloride and 3912 mg of
    atropine were given and the patient was discharged on the
    thirty-third day with no apparent sequelae.

    REFERENCES TO ANNEX I

    ECOBICHON, D.J., OZERE, R.L., REID, E., & CROCKER, J.F.S (1977)
    Acute fenitrothion poisoning. Can. Med. Assoc. J., 116: 377-379.

    KAGAN, JU.S. (1977) [Toxicology of organophosphorus pesticides],
    Moscow, Meditsina, pp. 111-121, 219-233, 260-269 (in Russian).

    PLESTINA, R. (1984) Prevention, diagnosis, and treatment of
    insecticide poisoning, Geneva, World Health Organization
    (Unpublished document VBC/84.889).

    TAYLOR, P. (1980) Anticholinesterase agents. In: Goodman, L.S. &
    Gilman, A., ed. The pharmacological basis of therapeutics, 6th ed.,
    New York, Macmillan Publishing Company, pp. 100-119.

    UK DHSS (1983) Pesticide poisoning: notes for the guidance of
    medical practitioners, London, United Kingdom Department of Health
    and Social Security, pp. 41-47.

    VALE, J.A. & SCOTT, G.W. (1974) Organophosphorus poisoning. Guy's
    Hosp. Rep., 123: 13-25.

    WARRINER, R.A., III, NIES, A.S., & HAYES, W.J., Jr (1977)  Severe
    organophosphate poisoning complicated by alcohol and terpentine
    ingestion. Arch. environ. Health, 32: 203-205.



        ANNEX II.  No-observed-effect levels in plasma, red blood cells, and brain ChE, in animals treated with fenitrothion

    ANNEX II.  No-observed-effect levels in plasma, red blood cells, and brain ChE, in animals treated with fenitrothion
                                                                                                                                              

    Study/Dosage                             No-observed-effect levels in mg/kg body weight per day and in (mg/kg diet)a
                                 Sex          Plasma                Red blood cells          Brain               Reference
                                             I        F             I         F            I         F
                                                                                                                                              

    Rat 30 days                  male        2.5      2.5           2.5       2.5         < 2.5     < 2.5        Trottier et al. (1980)
    Gavage 0, 2.5, 5.0, 10.0,    female      2.5      2.5           2.5       2.5         < 2.5     < 2.5
    20.0 (mg/kg body weight)

    Rat 5 weeksb                 male         -        -             -       0.25           -        0.5         Carshalton (1964)
    0, 5, 10, 20 mg/kg diet                                                   (5)                   (10)

    Rat 90 daysb                 male        3.2      3.2          < 1.6      3.2          3.2      12.5         Misu et al. (1966)
    0, 32, 63, 125, 250, 500                (63)     (63)         (< 32)     (63)         (63)      (250)
    mg/kg diet

    Rat 90 days                  male         -      < 1.7           -       < 1.7          -         -          Cooper (1966)
    0, 20, 92.8, 430.7, 2000                        (< 20)                  (< 20)
    mg/kg diet                   female              < 1.9                   < 1.9          -         -
                                                    (< 20)           -      (< 20)

    Rat 90 days                  male         -      < 1.2           -        1.2           -         -          Cooper (1966)
    0, 10, 46.4, 215, 1000                          (< 10)                  (< 10)
    (mg/litre water)             female       -      < 1.3           -        1.3           -         -
                                                    (< 10)                  (< 10)

    Rat 6 months                 male         -       1.8            -        1.8           -        1.8         Sumitomo Chem. Co.
    0, 10, 30, 150 mg/kg diet                        (30)                    (30)                   (30)         (1972)
                                 female       -     < 0.64           -       0.64           -       0.64
                                                    (< 10)                  (< 10)                  (10)
                                                                                                                                              

    Annex II (contd).
                                                                                                                                              

    Study/Dosage                             No-observed-effect levels in mg/kg body weight per day and in (mg/kg diet)a
                                 Sex          Plasma                Red blood cells          Brain               Reference
                                             I        F             I         F            I         F
                                                                                                                                              

    Rat 34 weeksb                male       0.25     0.25         < 0.25    < 0.25          -        6.3         Benes & Cerna (1970)
    0, 10, 50, 150                           (5)      (5)          (< 5)     (< 5)                  (125)
    0, 5, 25, 125 mg/kg diet     female    < 0.25   < 0.25        < 0.25    < 0.25          -        6.3
                                            (< 5)    (< 5)         (< 5)     (< 5)                  (125)

    Rat 63 weeksb                male         -     < 1.25           -       1.25           -       1.25         Ueda & Nishimura (1966)
    0, 25, 100, 400 mg/kg diet                      (< 25)                   (25)                   (25)

    Rat 1 year                   male        1.0      1.0           1.0       1.0          1.0       1.0         Ecobichon et al. (1980)
    Gavage 0, 0.5, 1, 5, 10
    (mg/kg body weight)

    Rat 1 yearb                  male      > 1.25   > 1.25         0.25     > 1.25        0.05     > 1.25        Kanoh et al. (1982)
    0, 1, 5, 25 mg/kg diet                 (> 25)   (> 25)          (5)     (> 25)         (1)     (> 25)
                                 female    > 1.25   > 1.25         0.25     > 1.25        0.25     > 1.25
                                           (> 25)   (> 25)          (5)     (> 25)         (5)     (> 25)

    Rat 30 days                  male         -       20             -        20            -        20          Breckenridge et al. (1982)
    by inhalation 0, 6.7,        female       -     < 6.7            -        20            -       < 6.7
    20, 60 (mg/m3)

    Rat 92 weeksb                male       0.13     > 0.5         0.25      > 0.5          -       > 0.5        Kadota et al. (1975a)
    0, 2.5, 5, 10 mg/kg diet                (2.5)   (> 10)          (5)     (> 10)                 (> 10)
                                 female     0.13     > 0.5         0.25      > 0.5          -       > 0.5
                                            (2.5)   (> 10)          (5)     (> 10)                 (> 10)
                                                                                                                                              

    Annex II (contd).
                                                                                                                                              

    Study/Dosage                             No-observed-effect levels in mg/kg body weight per day and in (mg/kg diet)a
                                 Sex          Plasma                Red blood cells          Brain               Reference
                                             I        F             I         F            I         F
                                                                                                                                              

    Rat 2 yearsb                 male       < 0.5    < 0.5          0.5       0.5          0.5       1.5         Rutter & Nelson (1974)
    0, 10, 30, 100 mg/kg diet              (< 10)   (< 10)         (10)      (10)         (10)      (30)
                                 female     < 0.5    < 0.5          0.5       0.5          0.5       1.5
                                           (< 10)   (< 10)         (10)      (10)         (10)      (30)

    Mouse 2 yearsb               male       0.43     0.43          1.43      1.43         1.43      1.43         Tamano et al. (1990)
    0, 3, 10, 100, 1000                      (3)      (3)          (10)      (10)         (10)      (10)
    mg/kg diet                   female     0.43     0.43          1.43      1.43         1.43      1.43
                                             (3)      (3)          (10)      (10)         (10)      (10)

    Dog 98 days oral by          male/        2        -             2         -            -         -          Cooper (1966)
    capsule 0, 2, 9, 40
    (mg/kg body weight)

    Dog 1 yearb                  male       0.25     0.25          0.25      0.25        > 1.25    > 1.25        Griggs et al. (1984)
    0.5, 10, 50 mg/kg diet       (10)       (10)     (10)          (10)     (> 50)       (> 50)
                                 female     0.25     0.25         > 1.25    > 1.25       > 1.25    > 1.25
                                 (10)       (10)    (> 50)        (> 50)    (> 50)       (> 50)

    Dog 10 months                male         -       < 5            -        < 5           -         -          Tomita et al. (1974)
    oral by capsule
    0, 5 (mg/kg body weight)

    Dog 1 year                   female       -       < 2            -        < 2           -         -          Ogata (1972)
    oral by capsule
    0, 2 (mg/kg body weight)
                                                                                                                                              

    Annex II (contd).
                                                                                                                                              

    Study/Dosage                             No-observed-effect levels in mg/kg body weight per day and in (mg/kg diet)a
                                 Sex          Plasma                Red blood cells          Brain               Reference
                                             I        F             I         F            I         F
                                                                                                                                              

    Dog 2 yearb                  male      < 0.75   < 0.75         0.75      0.75           -        2.5         Mastalski et al. (1973)
    0, 30, 100, 200 mg/kg diet             (< 30)   (< 30)         (30)      (30)         (100)
                                 female    < 0.75   < 0.75         0.75      0.75           -        2.5
                                           (< 30)   (< 30)         (30)      (30)         (100)

    Rabbit 6 months              male         -       <3             -        < 3           -         3          Miyamoto et al. (1976a)
    in diet, 0, 3, 10
    (mg/kg body weight)
                                                                                                                                              

    a    I = Interim sacrifice; F = Final sacrifice.
    b    Calculated by dietary concentration providing that 1 mg/kg body weight per day equals 20, 7, and 40 mg/kg in
         rats, mice, and dogs, respectively.

    

    RESUME ET EVALUATION, CONCLUSIONS ET RECOMMANDATIONS

    1.  Résumé et évaluation

    1.1  Exposition

         Le fénitrothion est un insecticide organophosphoré utilisé
    depuis 1959. On l'emploie en agriculture pour détruire les insectes
    qui s'attaquent au riz, aux céréales, aux fruits, aux légumes, aux
    céréales ensilées et au coton. On l'emploie également pour la
    désinsectisation des forêts ainsi que pour la destruction des
    mouches, des moustiques et des blattes dans le cadre des programmes
    de santé publique. Il se présente sous la forme de concentrés
    émulsionnables, de concentrés à très bas volume, de poudres, de
    granulés, de poudres pour poudrage, de bouillies huileuses ainsi
    qu'en association avec d'autres pesticides. La production de
    fénitrothion oscille entre 15 000 et 20 000 tonnes par an.

         Le fénitrothion pénètre dans l'air par volatilisation à partir
    des surfaces contaminées et peut être entraîné pendant l'épandage
    au-delà de la zone à traiter. Dans la plupart des terrains, il n'est
    éliminé que très lentement par lessivage, néanmoins une certaine
    quantité peut être entraînée par les eaux de ruissellement.

         Le fénitrothion est décomposé par photolyse et hydrolyse. En
    présence de rayonnement UV ou de lumière solaire, la demi-vie du
    fénitrothion dans l'eau est inférieure à 24 heures. La présence
    d'une microflore peut également accélérer la décomposition. En
    l'absence de lumière solaire ou de contamination microbienne, le
    fénitrothion est stable dans l'eau. Dans le sol, il est
    essentiellement dégradé par voie biologique, encore que la photolyse
    puisse jouer un certain rôle.

         La concentration du fénitrothion dans l'air peut atteindre 5
    µg/m3 immédiatement après l'épandage mais elle est susceptible de
    diminuer fortement au cours du temps et en fonction de la distance
    au lieu d'épandage. Dans l'eau, la concentration peut atteindre 20
    µg/litre mais elle diminue rapidement.

         En cas d'exposition continue, on observe des facteurs de
    bioconcentration qui se situent entre 20 à 450 chez un certain
    nombre d'espèces aquatiques.

         Les résidus de fénitrothion dans les fruits, les légumes et les
    céréales peuvent aller de 0,001 à 9,5 mg/kg immédiatement après le
    traitement mais ils diminuent rapidement, leur demi-vie étant de 1 à
    2 jours.

    1.2  Fixation, métabolisme et excrétion

         Le fénitrothion est rapidement résorbé dans les voies
    digestives et se répartit ensuite dans les divers tissus. La
    demi-vie du fénitrothion après absorption percutanée chez le singe a
    été estimée à 15-17 heures. Sa métabolisation s'effectue selon les
    grandes voies d' O-déméthylation ainsi que par clivage de la
    liaison P-O-aryle. Le groupement NO2 est réduit par la microflore
    intestinale, mais seulement chez les ruminants. La principale voie
    d'élimination est la voie urinaire, la plupart des métabolites étant
    excrétés en l'espace de 2 à 4 jours chez le rat, le cobaye, la
    souris et le chien. Les principaux métabolites observés sont le
    déméthyl- fénitrothion, le déméthyl-fénitrooxon, l'acide
    diméthylphosphoro-thioïque et l'acide diméthylphosphorique ainsi que
    le 3-méthyl-4-nitrophénol et ses conjugués. Les différences qui ont
    été observées dans la composition en métabolites entre la plupart
    des animaux de laboratoire et entre les sexes, chez une même espèce,
    semblent être essentiellement d'ordre quantitatif. Seul le lapin
    semble excréter du fénitrooxon et de l'aminofénitrooxon en quantités
    faibles mais néanmoins mesurables, par la voie urinaire.

         Des études portant sur des lapins et des chiens montrent que le
    fénitrothion se dépose préférentiellement dans les tissus adipeux.

         Des résidus qui avaient été décelés dans le lait de vache après
    exposition à du fénitrothion ont disparu dans les deux jours.

         Même s'il est rapidement résorbé après administration orale, le
    fénitrothion est métabolisé et excrété sans délai et il est peu
    probable qu'il demeure dans l'organisme pendant une longue période.

    1.3  Effets sur les êtres vivants dans leur milieu naturel

         A la concentration où on le rencontre vraisemblablement dans
    l'environnement, le fénitrothion n'a aucun effet sur les
    microorganismes présents dans le sol ou dans les eaux.

         Il est extrêmement toxique pour les invertébrés aquatiques
    d'eau douce ou d'eau de mer, la CL50 étant de l'ordre de quelques
    µg/litre pour la plupart des espèces étudiées. La dose sans effet
    observable pour la daphnie, lors d'épreuves à 48 heures, s'est
    révélée < 2 µg/litre; lors de tests portant sur la totalité du
    cycle évolutif, on a fixé à 0,14 µg/litre la concentration maximum
    acceptable de produit toxique. Les observations et études effectuées
    sur le terrain dans des étangs expérimentaux ont révélé l'existence
    d'effets sur les populations d'invertébrés. Toutefois, la plupart
    d'entre eux étaient passagers, même à des concentrations beaucoup
    plus élevées que celles auxquelles donne vraisemblablement lieu
    l'emploi de fénitrothion conformément aux recommandations.

         Les poissons sont moins sensibles au fénitrothion que les
    invertébrés, les valeurs de la CL50 à 96 heures dans leur cas
    allant de 1,7 à 10 mg/litre. Ce sont les jeunes larves qui
    constituent le stade le plus sensible. Des études à long terme ont
    fixé à 0,1 mg/litre ou plus la concentration maximale admissible de
    produit toxique pour deux espèces de poissons d'eau douce. Une étude
    écologique effectuée après l'épandage de fénitrothion sur des forêts
    a montré qu'il n'en résultait aucun effet sur les populations
    sauvages de poissons ou sur la survie des poissons d'expérience
    placés dans des nasses, les concentrations de fénitrothion dans
    l'eau allant jusqu'à 0,019 mg/litre. Des épandages répétés de
    fénitrothion sur des forêts n'ont eu aucun effet sur les poissons.

         Lors d'essais en laboratoire, on a constaté que la CL50 pour
    les mollusques dulçaquicoles allait de 1,2 à 15 mg/litre. Aucun
    effet écologique n'a été constaté après épandage sur des forêts à la
    dose de 140 g/hectare.

         Le fénitrothion est extrêmement toxique pour les abeilles
    (DL50 topique comprise entre 0,03 et 0,04 µg/abeille). Des effets
    écologiques ont été observés qui consistaient essentiellement en une
    mortalité localement élevée chez les abeilles et d'autres espèces.
    Toutefois cette mortalité ne représentait qu'un faible pourcentage
    de la population totale des ruches.

         Pour les oiseaux, les valeurs de la DL50 aiguë par voie orale
    vont de 25 à 1190 mg/kg de poids corporel et, dans la plupart des
    cas, la CL50 alimentaire à huit jours dépasse 5000 mg/kg de
    nourriture. Les valeurs de la dose sans effet observable sur la
    reproduction sont de 10 mg/kg de poids corporel pour la caille et de
    100 mg/kg pour le malard. Après épandage de fénitrothion à la dose
    de 280 g/hectare, on a observé une mortalité parmi les oiseaux
    chanteurs, mortalité qui augmentait sensiblement chez les espèces
    peuplant la canopée lorsque la dose était portée à 500 g/hectare.
    Après épandage à des doses de 420 g/hectare puis de 210 g/hectare
    quelques jours plus tard, le nombre de nichées de pinsons à gorge
    blanche  (Zonotrichia  albicollis) a diminué. Dans de nombreuses
    études, on a constaté, chez les oiseaux chanteurs, une inhibition de
    la cholinestérase peu après l'épandage de fénitrothion dans les
    forêts.

         L'observation sur le terrain n'a pas révélé d'effets sur les
    populations de petits mammifères sauvages.

    1.4  Effets sur les animaux d'expérience et les systèmes d'épreuve
          in vitro

         Le fénitrothion est un organophosphoré qui réduit l'activité de
    la cholinestérase plasmatique, érythrocytaire, cérébrale et

    hépatique. Il est métabolisé en fénitrooxon, composé dont la
    toxicité aiguë est encore plus élevée. La toxicité du fénitrothion
    peut être potentialisée par un certain nombre d'organophosphorés.

         Le fénitrothion est un insecticide modérément toxique dont la
    DL50 par voie orale chez le rat et la souris va de 330 à 1416
    mg/kg de poids corporel. Sa toxicité aiguë par voie dermique chez
    les rongeurs varie de 890 mg/kg de poids corporel à plus de 2500
    mg/kg.

         Le fénitrothion n'est que très peu irritant pour les yeux et
    n'irrite pas la peau. Deux études portant sur des cobayes ont fait
    ressortir une certaine tendance à la sensibilisation cutanée.

         Le fénitrothion a fait l'objet d'études à court terme sur des
    rats, des chiens, des cobayes, des lapins ainsi que d'études de
    cancérogénicité à long terme chez des rats et des souris. Les études
    à court terme sur les rats et les chiens ont permis de fixer
    respectivement à 10 mg/kg de nourriture et 50 mg/kg de nourriture la
    dose sans effet nocif observable, d'après l'activité de la
    cholinestérase cérébrale.

         Les études à long terme sur le rat et la souris ont donné une
    dose sans effet nocif observable, basée sur l'activité de la
    cholinestérase cérébrale, de 10 mg/kg de nourriture.

         Aucune des études à long terme signalées n'a mis en évidence
    d'effets cancérogènes.

         Le fénitrothion ne s'est pas révélé mutagène dans les études
     in  vitro et  in vivo.

         A des doses allant jusqu'à 30 mg/kg de poids corporel chez le
    lapin et jusqu'à 25 mg/kg de poids corporel chez le rat, le
    fénitrothion n'a pas produit d'effets tératogènes. Lorsque la dose
    dépassait 8 mg/kg de poids corporel, le fénitrothion était toxique
    pour la mère.

         Après exposition  in utero, on a observé des déficits
    comportementaux après la naissance chez des ratons en cours de
    développement. La dose sans effet observable sur le comportement a
    été fixée à 5 mg/kg de poids corporel et par jour.

         Des études de reproduction portant sur plusieurs générations de
    rats n'ont pas fait ressortir d'effets morphologiques. Ces études
    ont permis de fixer à 120 mg/kg de nourriture, d'après les
    paramètres génésiques, la dose sans effet nocif observable.

         On a fait état d'une neurotoxicité retardée après exposition au
    fénitrothion.

    1.5  Effets sur l'homme

         Administré à des volontaires humains en dose orale unique de
    0,042 à 0,33 mg/kg de poids corporel puis en doses répétées de 0,04
    à 0,08 mg/kg, le fénitrothion n'a pas entraîné d'inhibition de la
    cholinestérase plasmatique ou érythrocytaire. Un des métabolites, le
    3-méthyl-4-nitrophénol, a été totalement excrété par voie urinaire
    dans les 24 heures.

         Plusieurs cas d'intoxication se sont produits. La
    symptomatologie de l'intoxication par le fénitrothion est celle
    d'une stimulation du parasympathique. Il est arrivé que les
    manifestations toxiques n'apparaissent pas immédiatement mais
    récidivent pendant quelques mois. On a avancé que l'allongement de
    la durée de l'évolution clinique de l'intoxication et l'apparition
    de symptômes tardifs pouvaient s'expliquer par une libération lente
    de l'insecticide à partir du tissu adipeux. Certaines dermatites de
    contact ont été attribuées à une exposition à l'insecticide. Rien
    n'indique qu'une exposition au fénitrothion puisse entraîner une
    neurotoxicité retardée ou l'apparition d'un syndrome de Reye.

         Dans le cadre des programmes de l'OMS, on utilise du
    fénitrothion dans quelques pays pour la lutte antipaludique en
    pulvérisation à effet rémanent à l'intérieur des habitations (dose
    d'emploi: 2,0 gr de matière active par m2). Des observations
    portant sur plusieurs milliers de résidents n'ont fait ressortir
    aucun signe de toxicité à l'exception d'une enquête au cours de
    laquelle 2% des personnes enquêtées se sont plaintes de légers
    symptômes. Toutefois, chez environ 25% des ouvriers pulvériseurs, on
    a observé une inhibition à 50% de l'activité de la cholinestérase du
    sang total. Après épandage par voie aérienne d'un concentré
    émulsionnable à 50%, on a constaté chez un certain nombre de
    travailleurs des symptômes d'intoxication accompagnés d'une
    réduction de l'activité cholinestérasique du sang total en l'espace
    de 48 heures. Des ouvriers et des ouvrières exposés de par leur
    profession pendant cinq ans à du fénitrothion respectivement dans un
    atelier de production et dans une unité de conditionnement ont
    présenté, pour 15% d'entre eux et 33% d'entre elles, des symptômes
    cliniques d'intoxication. La concentration de fénitrothion dans
    l'air des lieux de travail variait entre 0,028 et 0,118 mg/m3.

    2.  Conclusions

    *    Le fénitrothion est un insecticide organophosphoré modéré- ment
         toxique. Toutefois, en cas d'exposition excessive résultant de
         manipulations au cours de la production ou de l'épandage ou
         encore par suite d'une ingestion accidentelle ou
         intentionnelle, il peut s'ensuivre une grave intoxication.

    *    L'exposition de la population générale, qui résulte
         principalement de l'emploi du fénitrothion en agriculture, en
         foresterie et dans les programmes de santé publique, ne devrait
         pas présenter de danger pour la santé.

    *    Moyennant de bonnes pratiques de fabrication et le respect des
         mesures d'hygiène et de sécurité, le fénitrothion ne devrait
         pas présenter de danger pour les personnes qui y sont exposées
         de par leur profession.

    *    Malgré sa forte toxicité pour les arthropodes non visés, le
         fénitrothion est utilisé très largement comme pesticide avec
         des effets indésirables minimaux sur les populations animales
         présentes dans l'environnement.

    3.  Recommandations

    *    Afin de préserver la santé et le bien-être des travailleurs et
         de la population générale, il importe de ne confier la
         manipulation et l'épandage du fénitrothion qu'à des personnes
         expérimentées qui prendront les mesures de sécurité nécessaires
         et procéderont à l'épandage en respectant les règles de bonne
         pratique.

    *    Les opérations de production, de formulation, d'épandage et
         d'élimination du fénitrothion doivent être effectuées avec tout
         le soin nécessaire pour réduire au minimum la contamination de
         l'environnement, et notamment des eaux de surface.

    *    Les travailleurs habituellement exposés doivent subir un examen
         médical périodique.

    *    La dose d'emploi du fénitrothion doit être limitée afin
         d'éviter tout effet sur les arthropodes non visés.
         L'insecticide ne doit jamais être épandu sur des étendues ou
         cours d'eau.

    RESUMEN Y EVALUACION, CONCLUSIONES Y RECOMENDACIONES

    1.  Resumen y evaluación

    1.1  Exposición

         El fenitrotión es un insecticida organofosforado que se viene
    utilizando desde 1959. Se emplea en la agricultura para combatir los
    insectos del arroz, los cereales, las frutas, las hortalizas, el
    grano almacenado y el algodón. Se usa también para luchar contra
    insectos en los bosques, y en programas de salud pública para
    combatir moscas, mosquitos y cucarachas. Se ha formulado como
    concentrado emulsionable, concentrados de volumen muy bajo,
    microgránulos, gránulos, polvo, pulverizadores oleosos y en
    combinación con otros plaguicidas. Cada año se fabrican entre 15 000
    y 20 000 toneladas.

         El fenitrotión se incorpora al aire por volatilización a partir
    de superficies contaminadas y puede ser arrastrado fuera de la zona
    de tratamiento durante el rociamiento. Su lixiviación es muy lenta
    en la mayoría de los suelos, pero es previsible que se produzca
    algún arrastre en el agua.

         Se degrada por fotólisis e hidrólisis. En presencia de la
    radiación ultravioleta o de la luz solar, la semivida del
    fenitrotión en el agua es inferior a 24 horas. La presencia de
    microflora también puede acelerar la degradación. En ausencia de luz
    solar o de contaminación microbiana, es estable en el agua. En el
    suelo, la vía principal de eliminación es la biodegradación, aunque
    la fotólisis también puede influir.

         Las concentraciones de fenitrotión en el aire pueden ser de
    hasta 5 µg/m3 inmediatamente después del rociamiento, pero
    decrecen de manera considerable con el tiempo y la distancia del
    lugar de aplicación. Los niveles en el agua pueden alcanzar valores
    de hasta 20 µg/litro, pero disminuyen con rapidez.

         Los factores de bioconcentración calculados en varias especies
    acuáticas sometidas a una exposición constante al fenitrotión varían
    entre 20 y 450.

         Sus niveles residuales en frutas, hortalizas y grano de
    cereales oscilan entre 0,001 y 9,5 mg/kg inmediatamente después del
    tratamiento, pero decrecen rápidamente, con una semivida de 1 a 2
    días.

    1.2  Ingestión, metabolismo y excreción

         El fenitrotión se absorbe con rapidez del tracto intestinal de
    los animales de experimentación y se distribuye a diversos tejidos
    corporales. La semivida en el caso de la absorción cutánea en el

    mono fue de 15 a 17 horas. Se ha demostrado que su metabolismo se
    realiza a través de las principales vías de demetilación oxidativa y
    por rotura del enlace P-O-arilo. Los microorganismos intestinales
    reducen, sólo en los rumiantes, el grupo nitrogenado del
    fenitrotión. La principal vía de excreción es la orina; la mayor
    parte de los metabolitos se eliminan en un periodo de 2 a 4 días en
    el caso de la rata, el cobayo, el ratón y el perro. Los principales
    metabolitos detectados son el demetilfenitrotión, el
    demetilfenitrooxón, el ácido dimetilfosforotioico, el ácido
    dimetilfosfórico y el 3-metil-4-nitrofenol y sus conjugados. Las
    diferencias en la composición de los metabolitos que se detectan en
    la mayor parte de los animales de laboratorio y entre los dos sexos
    de la misma especie parecen ser principalmente de carácter
    cuantitativo. Sólo los conejos parecen excretar fenitrooxón y
    aminofenitrooxón en cantidades pequeñas, pero cuantificables, con la
    orina.

         En estudios realizados en conejos y perros se ha puesto de
    manifiesto que el fenitrotión se deposita preferentemente en el
    tejido adiposo.

         Los residuos encontrados en la leche de vaca tras la exposición
    no se detectaban dos días más tarde.

         Aunque el fenitrotión se absorbe rápidamente por vía oral, se
    metaboliza y excreta con rapidez y no es probable que permanezca en
    el organismo durante un tiempo prolongado.

    1.3  Efectos en los seres vivos del medio ambiente

         La concentraciones normales de fenitrotión en el medio ambiente
    no tienen efecto alguno en los microorganismos del suelo o del agua.

         El fenitrotión es muy tóxico para los invertebrados acuáticos
    de agua dulce y salada; los valores de la CL50 son de pocos
    µg/litro en la mayoría de las especies analizadas. El nivel sin
    efectos observados (NOEL) determinado en  Daphnia en pruebas de 48
    horas fue < 2 µg/litro; en pruebas del ciclo biológico se
    estableció una concentración tóxica aceptable máxima (MATC) de 0,14
    µg/litro. Las observaciones y los estudios sobre el terreno en
    estanques experimentales han puesto de manifiesto ciertos efectos en
    las poblaciones de invertebrados, si bien la mayor parte de los
    cambios observados fueron transitorios, incluso con concentraciones
    muy superiores a las que cabe esperar tras el uso recomendado.

         Los peces son menos sensibles al fenitrotión que los
    invertebrados y muestran valores de la CL50 a las 96 horas que
    oscilan entre 1,7 y 10 mg/litro. La fase más sensible del ciclo
    biológico es la larva joven. En estudios prolongados se ha

    establecido una MATC igual o superior a 0,1 mg/litro para dos
    especies de peces de agua dulce. Los estudios sobre el terreno tras
    la aplicación de fenitrotión a bosques no demostraron efecto alguno
    en las poblaciones silvestres de peces ni en la supervivencia de
    peces de experimentación en vivero, con concentraciones medidas en
    el agua de 0,019 mg/litro. La aplicación repetida en bosques no tuvo
    efectos en las poblaciones de peces.

         En pruebas de laboratorio, los valores de la CL50 para
    moluscos de agua dulce oscilaban entre 1,2 y 15 mg/litro. No se
    observaron efectos sobre el terreno tras rociar bosques con 140
    g/ha.

          El fenitrotión es muy tóxico para las abejas (DL50 tópica,
    0,03-0,04 µg/abeja). Se han comunicado efectos sobre el terreno, con
    un elevado número de abejas de la miel y de otras especies muertas
    en la zona de aplicación. Sin embargo, el número total de individuos
    muertos representaba solamente un pequeño porcentaje de la población
    de las colmenas.

         Los valores de la DL50 en la toxicidad aguda por vía oral en
    las aves oscilan entre 25 y 1190 mg/kg de peso corporal, y en la
    mayor parte de las dietas de ocho días las CL50 excedieron de 5000
    mg/kg de la dieta. Los valores del NOEL para la reproducción fueron
    de 10 mg/kg de peso corporal en la codorniz y de 100 mg/kg de peso
    corporal en el pato silvestre. Poco después de aplicar fenitrotión
    en una concentración de 280 g/ha, se observaron muertes de pájaros
    cantores y la mortalidad aumentó considerablemente con 560 g/ha para
    las especies que vivían en las copas de los árboles del bosque.
    Después de rociar con una concentración de 420 g/ha y unos días más
    tarde con 210 g/ha, se redujo la reproducción de la especie
    zonotrichia albicollis. En muchos estudios, los pájaros cantores
    mostraron inhibición de la colinesterasa inmediatamente después de
    rociar los bosques con fenitrotión.

         Las observaciones sobre el terreno no han puesto de manifiesto
    efecto alguno del fenitrotión en las poblaciones de pequeños
    mamíferos silvestres.

    1.4  Efectos en los animales de experimentación y en sistemas
         de prueba  in vitro

         El fenitrotión es un organofosfato y reduce la actividad de la
    colinesterasa en el plasma, los eritrocitos y los tejidos cerebral y
    hepático. Se metaboliza a fenitrooxón, con mayor toxicidad aguda.
    Otros compuestos organofosfatados pueden potenciar aún más la
    toxicidad del fenitrotión.

         El fenitrotión es un insecticida de toxicidad moderada, con
    valores de la DL50 por vía oral que oscilan entre 330 y 1416 mg/kg
    de peso corporal en ratas y ratones. La toxicidad aguda cutánea en
    roedores varió desde 890 mg/kg hasta más de 2500 mg/kg de peso
    corporal.

         El fenitrotión apenas irrita los ojos y no irrita la piel. En
    uno de los dos estudios realizados en cobayos, el producto mostró
    cierto potencial de sensibilización dérmica.

         Se ha ensayado el fenitrotión en estudios de corta duración en
    ratas, perros, cobayos y conejos y en estudios prolongados de
    carcinogenicidad en ratas y ratones. En los estudios de corta
    duración realizados en ratas y perros los niveles sin efectos
    adversos observados (NOAEL), basados en la actividad de la
    colinesterasa cerebral, fueron, respectivamente, de 10 mg/kg y 50
    mg/kg de la dieta.

         Los estudios de larga duración en ratas y ratones pusieron de
    manifiesto un NOAEL (basado en la actividad de la colinesterasa
    cerebral) de 10 mg/kg de la dieta.

         No se han encontrado efectos carcinogénicos en ninguno de los
    estudios de larga duración que se han publicado.

         En los estudios  in vitro e  in vivo, el fenitrotión no
    mostró efectos mutagénicos.

         No se han detectado efectos teratogénicos con dosis de
    fenitrotión de hasta 30 mg/kg de peso corporal en conejos y de hasta
    25 mg/kg de peso corporal en ratas. Las dosis superiores a 8 mg/kg
    de peso corporal produjeron toxicidad materna.

         Las ratas jóvenes en fase de crecimiento presentaron problemas
    de comportamiento postnatal tras la exposición  in utero. Para este
    efecto se estableció un NOEL de 5 mg/kg de peso corporal al día.

         En estudios multigeneracionales de reproducción en ratas no se
    detectó ningún efecto morfológico. En estos estudios se puso de
    manifiesto un NOAEL de 120 mg/kg de la dieta, basado en parámetros
    de la reproducción.

         No se ha informado de neurotoxicidad retardada como
    consecuencia de la exposición al fenitrotión.

    1.5  Efectos en el ser humano

         La administración de fenitrotión en una dosis oral única de
    0,042 a 0,33 mg/kg de peso corporal y en dosis repetidas de 0,04 a
    0,08 mg/kg de peso corporal en voluntarios humanos no causó la

    inhibición de la colinesterasa del plasma y los eritrocitos. La
    excreción urinaria del metabolito 3-metil-4-nitrofenol fue completa
    en 24 horas.

         Se han registrado varios casos de intoxicación, con los signos
    y síntomas característicos de la estimulación parasimpática. En
    algunos casos, las manifestaciones tóxicas tardaron en aparecer y se
    repitieron durante unos meses. Se ha sugerido que la liberación
    lenta del insecticida a partir del tejido adiposo puede dar lugar a
    un curso clínico prolongado o a síntomas tardíos de intoxicación. En
    algunos casos, la dermatitis de contacto se ha atribuido a la
    exposición al insecticida. No hay pruebas de neurotoxicidad tardía
    ni de relación con el síndrome de Reye.

         El fenitrotión se ha utilizado en algunos países en programas
    de la OMS para el rociamiento residual de interiores en la lucha
    contra el paludismo (dosis de aplicación: 2,0 g de principio
    activo/m2). No se apreciaron indicios de toxicidad en los miles de
    habitantes observados, a excepción de un estudio en el que se
    presentaron trastornos leves en menos del 2% de los habitantes. Sin
    embargo, alrededor del 25% de los encargados del rociamiento
    mostraron una inhibición de hasta el 50% de la actividad de la
    colinesterasa en sangre total. En las 48 horas posteriores a la
    aplicación aérea de una fórmula de concentrado emulsionable al 50%,
    algunos trabajadores mostraron síntomas de intoxicación y una
    disminución de la actividad de la colinesterasa en sangre total. En
    una fábrica de producción, la exposición profesional durante más de
    5 años de los trabajadores varones y de las mujeres del departamento
    de envasado produjo signos clínicos y síntomas de intoxicación en el
    15% de los hombres y en el 33% de las mujeres. La concentración de
    fenitrotión medida en el aire del lugar de trabajo oscilaba entre
    0,028 y 0,118 mg/m3.

    2.  Conclusiones

    *    El insecticida fenitrotión es un éster organofosforado
         moderadamente tóxico. Sin embargo, la exposición excesiva
         durante su fabricación o uso y la ingestión accidental o
         intencional pueden ocasionar una intoxicación grave.

    *    La exposición de la población general, debida fundamentalmente
         a las prácticas agrícolas y forestales y a los programas de
         salud pública, no representa en principio amenaza alguna para
         la salud.

    *    Con buenas prácticas de trabajo, medidas higiénicas y
         precauciones de seguridad no es probable que el fenitrotión
         represente un riesgo para las personas sujetas a exposición
         profesional.

    *    A pesar de su elevada toxicidad para los artrópodos no
         destinatarios, el fenitrotión se ha utilizado ampliamente en la
         lucha contra las plagas, con pocos efectos adversos o ninguno
         en las poblaciones presentes en el medio ambiente.

    3.  Recomendaciones

    *    Para salvaguardar la salud y el bienestar de los trabajadores y
         de la población general, el manejo y la aplicación del
         fenitrotión sólo se deben encomendar bajo una atenta
         supervisión a personas bien capacitadas que se ajusten a las
         medidas de seguridad adecuadas y utilicen el fenitrotión
         correctamente.

    *    Se cuidarán especialmente la fabricación, la formulación, el
         uso y la eliminación del compuesto, a fin de reducir al mínimo
         la contaminación del medio ambiente, en particular de las aguas
         superficiales.

    *    Los trabajadores regularmente expuestos deben someterse a
         revisiones médicas periódicas.

    *    Se ha de limitar el número de aplicaciones de fenitrotión, para
         evitar los efectos en artrópodos no destinatarios. No se deben
         rociar jamás con este insecticida masas o corrientes de agua.


    See Also:
       Toxicological Abbreviations
       Fenitrothion (HSG 65, 1991)
       Fenitrothion (ICSC)
       Fenitrothion (PDS)
       Fenitrothion (FAO/PL:1969/M/17/1)
       Fenitrothion (WHO Pesticide Residues Series 4)
       Fenitrothion (Pesticide residues in food: 1976 evaluations)
       Fenitrothion (Pesticide residues in food: 1977 evaluations)
       Fenitrothion (Pesticide residues in food: 1979 evaluations)
       Fenitrothion (Pesticide residues in food: 1982 evaluations)
       Fenitrothion (Pesticide residues in food: 1983 evaluations)
       Fenitrothion (Pesticide residues in food: 1984 evaluations)
       Fenitrothion (Pesticide residues in food: 1986 evaluations Part II Toxicology)
       Fenitrothion (Pesticide residues in food: 1988 evaluations Part II Toxicology)
       Fenitrothion (JMPR Evaluations 2000 Part II Toxicological)