IPCS INCHEM Home



    PESTICIDE RESIDUES IN FOOD - 1980


    Sponsored jointly by FAO and WHO






    EVALUATIONS 1980





    Joint meeting of the
    FAO Panel of Experts on Pesticide Residues
    in Food and the Environment
    and the
    WHO Expert Group on Pesticide Residues
    Rome, 6-15 October 1980




    FENTHION

    Explanation

    Fenthion was reviewed for an ADI by the Joint Meeting in 1971,
    1975, 1977 and 1978 (FAO/WHO, 1972, 1976; FAO, 1978, 1979).  A
    temporary ADI was estimated to be 0-0.0005 mg/kg bw based on an
    extensive series of short-term studies and human exposure data
    showing cholinesterase depression to be the most significant
    parameter of exposure and effect.

    Previous Meetings have expressed concern over the lack of long-term
    studies and on the prolonged effects of cholinesterase depression
    noted in animals and man.  The Meetings have requested long-term
    toxicology data and ancillary data to evaluate the safety of food
    residues from agricultural use and to assure that an ADI could be
    estimated.  Additional studies have been received that allow a
    complete evaluation of fenthion to be made.  For this reason, the
    pertinent toxicological data reviewed by previous Meetings and the
    new data are all included in this complete monograph.

    DATA CONSIDERED FOR DERIVATION OF ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Absorption, distribution, and excretion

    The first studies on mammals (rats) were reported by Brady and
    Arthur (1961), who use a 32P-labelled compound.  Within a few hours
    of applying the compound, large amounts of 32P-activity was found
    in the tissues including the bones, evidence that fenthion was
    rapidly absorbed, translocated, and degraded by rats.  Neither
    fenthion nor its oxidative metabolites were stored in tissues even
    when rats received daily doses of 10 mg/kg bw by the
    intraperitoneal route for 10 consecutive days.  At 1.5 hours,
    following a single i.p. injection of 200 mg/kg, the following
    acetonitrile-soluble residues were observed:

    liver     29.5 mg/kg
    muscle     9.6 mg/kg
    skin       6.1 mg/kg
    kidney    16.9 mg/kg
    heart      9.6 mg/kg

    Most tissues from rats treated orally with 100 mg/kg (single dose)
    contained less than 0.01 mg/kg chloroform-soluble residues three
    days after treatment.  Except for the liver (0.2 mg/kg), the blood,
    brain, and fat of these animals contained no detectable
    acetonitrile-solution residues.  The orally treated animals
    eliminated 86% of the activity in the excreta within seven days
    after treatment.  One to 4% of the activity in urine and faeces was
    chloroform-soluble.

    As a result of partial starvation, oxidative metabolism in rabbits
    was increased, as evidenced by greater concentrations of
    fenthion-oxygen analogue in blood.  The peak of radioactive
    substances in blood of normal rabbits following oral or
    subcutaneous administration of 35S fenthion was observed in six to
    nine hours following treatment, while in starved rabbits the peak
    value was obtained one hour after treatment (Begum, 1968).

    Following intraperitoneal administration of 32P-labelled fenthion,
    approximately 75% of the administered dose was recovered within
    three days in rat urine (60%) and faeces 15%).  After oral
    administration, 86% of the dose was excreted in urine (45%) and
    faeces (40%) with the majority excreted in three days (Brady and
    Arthur 1961).  Starvation of rabbits had no effect on elimination
    of fenthion (or metabolites) following oral or subcutaneous acute
    administration (Begum, 1968).

    Avrahami and White (1975) treated two lactating dairy cows with 20%
    fenthion as a topical spot treatment used for the control of lice
    using 32P-labelled fenthion applied at the rate of 9 mg/kg body
    weight. Highest residues of total radioactivity in the blood, milk,
    urine and faeces appeared between the first and second day after
    treatment.  The residues were predominantly water-soluble hydrolysis
    products of fenthion.  The highest daily average level offenthion and
    its organosoluble metabolites in the milk from the two cows was
    approximately 0.1 mg/kg on the first day after treatment.  Of the
    total radioactivity applied to each cow, 45-55% was recovered in the
    urine, 2-2.5% in the faeces and 1.5-2% in the milk over a period of 4
    weeks.

    Johnson and Bowman (1972) administered fenthion to lactating dairy
    cows at the rate of 25, 50 or 100 mg/kg in the total daily ration for
    28 days.  Total residues consisting of fenthion, its sulphoxide and
    sulphone and the sulphoxide and sulphone of the oxygen analogue in the
    milk averaged 0.016, 0.049 and 0.099 mg/kg respectively over the
    period.  Total residues in faeces consisted of fenthion and its
    sulphoxide and averaged from 0.042 to 0.308 mg/kg.  Neither fenthion
    nor its oxygen analogue was found in urine but totals of the
    sulphoxide and sulphone of fenthion and its oxygen analogue averaged
    from 0.43 to 1.05 mg/kg. Seven days after feeding was terminated,
    residues could not be detected in milk, urine or faeces.

    Biotransformation

    Five metabolites were isolated from rat urine and characterized as
    fenthion sulphoxide and sulphone, the oxygen analogue of the parent
    compound, and its corresponding sulphoxide and sulphone derivatives.

    In rabbits, the major urinary metabolites were fenthion-sulphoxide,
    fenthion-O-sulphoxide, and sulphone (Begum, 1968).  The metabolic
    scheme is shown in Figure 1.

    FIGURE 1;V080pr16.BMP

    Knowles and Arthur (1966) applied fenthion dermally to two dairy cows
    each weighing 360 kg at a rate of approximately 13 mg/kg per cow, and
    treated two other lactating cows (each weighing 41O kg) by the
    intramuscular route with approximately 8.5 mg of fenthion/kg per cow.
    In the urine, the peak concentration of radioactive materials occurred
    on the first day following either method of treatment.  The total
    residue of 32P materials from intramuscular treatment decreased from
    33 mg/kg at one day to 1.6 mg/kg by 21 days.  More than 95% of the
    radioactive materials eliminated in the urine consisted of hydrolytic
    products.  The total 32P materials eliminated in the faeces peaked
    two days after both types of treatment.  The cumulative percentage of
    the administered dose was about 4%.  The peak concentration of
    acetonitrile-soluble radioactivity occurred one day after
    intramuscular treatment and three days after dermal treatment.  The
    hair of the two cows treated dermally contained about 2000 mg/kg
    radioactive fenthion equivalents immediately after treatment.
    Chloroform to water partition data indicated that fenthion underwent
    little change on the hair to water-soluble components.  The
    radioactivity in the blood after both types of treatment reached a
    peak during the first 24 hours.  Between 10% and 38% of the 32P
    materials partitioned into chloroform, but no detectable
    chloroform-soluble 32P materials were present in the blood at seven
    days after either treatment.

    Fenthion constituted more than 50% of the non-ionic residues in the
    milk for three days after dermal and seven days after i.m. treatment.
    In the urine, fenthion accounted for only a small percentage of the
    chloroform-soluble radioactivity.  More than 50% of the
    acetonitrile-soluble radioactive materials in the faeces consisted of
    the parent compound.  The remainder was accounted for by the other
    metabolites, just as in urine.  The composition of the hydrolytic
    products was also very similar to that found in urine.  In the tissues
    of the animals slaughtered 14 days after dermal treatment and 21 days
    after i.m. treatment, more than 50% of the radioactive
    acetonitrile-soluble materials was chromatographed as fenthion, but
    oxidation products were also present.

    The biotransformation of fenthion in plants is basically similar to
    that in animals.

    Effects on enzymes and other biochemical parameters

    Fenthion and its metabolites are typical organophosphorous
    anticholinesterase agents.  Typical of this class of agents, the
    oxygen analogue is the most potent enzyme inhibitor of all the
    metabolites, containing a phosphorous triester configuration (Francis
    and Barnes, 1963).  The molar I50 fenthion for rat brain
    cholinesterase is 1.3 × 10-4M (Dubois and Kinoshita, 1964). 
    Clinically and biochemically, a prolonged cholinergic effect follows a
    single dose (recovery of blood and brain enzyme is very slow) (Brady
    and Arthur, 1961).  This effect may be as a result of inhibition of
    cholinesterase by metabolites that are released at different rates

    from storage in the body (Francis and Barnes, 1963), or a possible
    potentiation of its own antiesterase effects by selectively inhibiting
    enzymes responsible for hydrolysis of the phosphate ester (Brady and
    Arthur, 1961). Cholinesterase inhibition cannot be reactivated by
    2-PAM, TMB-4 or P-2-S in vivo, indicating that fenthion may
    inhibit cholinesterase in a manner different from other
    organophosphate esters (Dubois, 1960; Dubois and Kinoshita, 1964;
    Francis and Barnes, 1963).


    TOXICOLOGICAL STUDIES

    Special pharmacological studies

    A daily diet containing 300 mg/kg fenthion was given to 8 groups of
    Donrya rats: a hare's eye group, a cervial sympathectomy group, a
    group given antibiotic eye ointment, a group given atropine eyedrops,
    and groups given subcutaneous injections of pralidoxime, atropine, and
    GSH for about one month.  All rats given fenthion showed typical
    symptoms of organophosphorous intoxication such as nervousness,
    general spasms, diarrhoea, and salivation.  Also ophthalmological
    symptoms, such as eye-ball protrusion, keratoconus, mammiform cornea,
    and cornea turbity were observed.  The described pretreatments did not
    prevent the ocular symptoms (abstract only) (Kawai et al, 1976).

    When fenthion was administered at doses of 0.5 mg/kg orally to rats
    and 1-8 mg/kg intravenously to cats, significant inhibition of heart
    rate and blood pressure were observed.  However, an intravenous dose
    of 0.3 mg/kg to cats produced no significant changes in blood
    pressure, heart rate, or other physiological parameters (Wills et
    al, 1975).

    Special studies on reproduction

    Rat

    Except for a slight growth depression at the highest level, fenthion
    at levels of 0, 3 15 or 75 mg/kg in the diet for three generations
    (two litters per generation) produced no adverse effect on rat
    reproduction (Loser, 1969).  Microscopic examination of the tissues of
    the F3b generation did not reveal any significant abnormality (Spicer,
    1971).

    Mouse

    In a five-generation reproduction study (2 litters per generation),
    two groups of Charles River CD-1 mice consisting of 14 females, 10
    males; and 22 females, 10 males received 0 or 60 mg/kg fenthion,
    respectively, in their drinking water.  In the parameters studied
    (reproductivity performance, lactation, viability, and growth rate of
    pups) the principal effect was a significant increase in pup
    mortality, especially in the 2nd, 3rd, and 4th generations.  The
    highest mortality appeared to be in the first postnatal week. No

    histopathological changes were noted in the liver or kidney.  There
    was no evidence of a teratogenic potential (Budreau and Singh, 1973b).

    Special studies on teratogenicity

    Mouse

    Pregnant Charles River CD-1 mice were injected intraperitoneally with
    single doses of 40, 80 or 160 mg/kg body weight or with multiple doses
    of fenthion at various time periods during organogenesis.  Foetuses
    were removed by caesarean section on days 16 and 18 and visceral and
    skeletal structure examined for abnormalities.  The frequency of
    resorptions and foetal deaths was not affected.  Foetal weights were
    reduced significantly.  Although the number and type of abnormalities
    were increased when compared to the control group, this did not appear
    to be dose-related.  There was no apparent teratogenic effect,
    however, the incidence of resorptions was increased when fenthion was
    injected intraperitoneally for three consecutive days (day 9, 10, 11
    of gestation) at 20 mg/kg (Budreau and Singh, 1973a).

    Rat

    Fenthion was administered orally to groups of female rats for one
    generation (two litters) at dosage levels of 5 mg/kg body weight or 10
    mg/kg body weight from both day 1 through day 7 and day 8 through day
    10 of gestation.  Some animals were sacrificed on day 21 and foetuses
    were removed by caesarean section from these and examined for internal
    and external abnormalities.  No malformations were observed.  The
    incidence of resorptions was increased and weight of foetuses reduced.
    The second progeny from the remaining females were not affected.  In a
    further study, rats were given fenthion at a dosage level of 5 mg/kg
    body weight from day 1 through day 13 of gestation.  There was no
    evidence of teratogenesis.  However, the incidence of foetal
    resorption and abortion was increased.  During the lactation period
    there was an increased mortality and a decrease in the body weight
    gain of the pups.  By day 45 postpartum, surviving newborns had
    recovered normal weight (Fytizas-Danielidou, 1971).

    When preliminary studies indicated that a dose of 100 mg/kg was lethal
    to non-pregnant female rats in 2-4 days and that 30 mg/kg induced
    toxic signs of poisoning, four groups of 20 pregnant rats were dosed
    orally at 0, 1, 3, or 10 mg/kg/day on days 6-15 of pregnancy.  (Day 0
    was the day semen was detected).  At sacrifice (day 20 of gestation),
    implantation rate, numbers of live, dead, and resorbed foetuses,
    litter weight, and placental weights were recorded.  After gross
    examinations were made for skeletal and soft tissue malformations, no
    treatment-related teratogenic effects were noted (Machemer, 1978a).

    Special studies on mutagenicity

    In vivo - mouse

    In a dominant lethal assay, 2 groups of 50 male mice (NMRI-strain)
    were given a single oral dose of 0 or 25 mg/kg bw.  Additionally, a
    third group of mice was treated with 10 mg fenthion/kg bw, because 25
    mg/kg induced toxic effects in the males (drowsiness, ruffled coat,
    and dilated intestines).  The compound was given as a 2% aqueous
    emulsion.

    After injection, each male was caged with an untreated virgin female
    for a period of 4 days.  This procedure was repeated for a total of 12
    matings.

    On day 12-16 of gestation, the females were sacrificed and the number
    of implantations, the live and deal implants (sum of deciduomata, the
    resorptions, and the dead embryos) were counted.

    Except for an increased pre-implantation loss at the dose level of 25
    mg/kg bw in the first two mating periods, no other treatment-related
    effects on fertility, pre- and post-implantation loss were observed
    (Machemer, 1978b).

    In vitro - Microorganisms

    Fenthion was examined for its mutagenic potential using 3 standard
    strains of Salmonella typhimurium (TA-1537, TA-98 and TA-100).
    Fenthion was tested in the presence and absence of an S-9 metabolising
    enzyme fraction obtained from Aroclor 1254-induced rat liver at
    concentrations ranging from 3.15 to 3150 g/plate.  Under all
    conditions, there was no increase in the level of revertant colonies
    above that noted with controls. Both positive and negative acting
    chemicals (MMN and benzo [a]pyrene) were used to assure quality
    control in the test system.  Under this standardised bioassay,
    fenthion was not mutagenic (Oesoh, 1977).

    Special studies on carcinogenicity

    Rat

    Groups of rats (50 male and 50 female, F344 strain rats/group, 25 of
    each sex were used as controls) were fed fenthion at dietary dosage
    levels of 0, 10 or 20 mg/kg for 103 weeks in a carcinogenicity
    bioassay.  The animals were maintained for 1-2 weeks after the dietary
    administration stopped and were then sacrificed for gross and
    microscopic examinations.

    There was no mortality in the study and growth and behaviourial data
    were similar to control values.  Histopathological studies described a
    variety of neoplastic and non-neoplastic lesions common to this strain

    of rat.  Based on the histopathology and statistical evaluation of the
    incidence of tumours, fenthion was not considered to be carcinogenic
    to the rat (NCI, 1979).

    Mice

    Groups of mice (50 male and 50 female, B6C3F1 strain mice/group, 25 of
    each sex were used as controls) were fed fenthion in the diet at
    dosage levels of 0, 10 or 20 mg/kg for 103 weeks.  The animals were
    maintained on control diets for up to 1 week after dietary
    administration stopped.  They were then sacrificed and subjected to
    gross and microscopic examinations.

    During the first 4 months, no effects were noted on behaviour or
    appearance.  Clinical signs of poisoning were noted thereafter (it was
    not indicated at what dosage levels there were clinical signs of
    poisoning).  There were no differences in growth over the entire
    dosage range for the 103 weeks of study.  Survival was not affected by
    fenthion.

    A variety of neoplasms were reported, the majority of which were not
    related to dietary administration of fenthion.  It was reported that
    sarcomas in male mice (but not females) occurred with a greater
    frequency than in controls.  The integument was considered to be the
    primary site for all primary sarcomas, MOS and fibrosarcomas.  In an
    incidence of rhabdomyo-sarcoma, the skeletal muscle within
    subcutaneous tissue was defined as the site of origin. 
    Histologically, differentiation was minimal to moderate among the
    various fibrosarcomas.  The total incidence of skin and subcutaneous
    neoplasms (sarcomas) was dose related (controls 0/25; 10 mg/kg - 7/49;
    20 mg/kg - 8/48) although the response was slight with respect to any
    individual lesion.  Spontaneous rhabdosarcomas are rare in mice and
    the total incidence is an unusual occurrence.  The histopathologic and
    statistical evaluation of the data suggested an increased incidence of
    sarcoma in male mice that may be related to the dietary presence of
    fenthion (MCI, 1979).

    The data were reviewed by the Data Evaluation/Risk Assessment Sub
    Group of the National Cancer Institute Clearinghouse on Environmental
    Carcinogens, who concluded that fenthion was not carcinogenic to rats
    or mice under the conditions of the test.  Although, because of the
    increased incidence of sarcoma of the skin in male mice, fenthion was
    suggested to be sarcomagenic in this sex and strain.

    Special studies on potentiation

    Fenthion potentiates the acute intraperitoneal toxicity of malathion,
    dioxathion, and coumaphos in rats.  Intraperitoneal administration of
    13 other organophosphate or carbamate insecticides did not result in a
    greater than additive effect when administered with fenthion (Dubois
    and Kinoshita, 1964).  Dietary combination of fenthion with coumaphos,
    neither of which alone affected cholinesterase when fed to dogs for
    six weeks, was found to potentiate the anticholinesterase activity of

    serum and red blood cells.  Less evident potentiation was observed
    when fenthion and malathion were fed and when fenthion was fed in
    combination with dioxathion, no potentiation was noted (Doull et al,
    1962).  Fenthion (2 mg/kg) and malthion (100 mg/kg) resulted in
    moderate erythrocyte and serum cholinesterase activity inhibition
    (30-40%).  When fenthion (2 mg/kg) and dioxathion (3 mg/kg) were fed,
    cholinesterase activity was not depressed.  When fenthion (2 mg/kg)
    and coumaphos (2 mg/kg) were fed to dogs, significant inhibition (75%)
    of serum cholinesterase and moderate inhibition (30%) of erythrocyte
    cholinesterase was evident.  Oral administration to rats of a 75:25
    mixture of fenthion and dichlorvos did not result in a greater than
    theoretically additive toxicity (Kimmerle, 1967b).

    In rats, no synergistic effects on the acute oral toxicity was noted
    of fenthion with edifenphos and the active ingredient of Bassa
    (2-sec-butylphenyl N-methylcarbamate) (Thyssen, 1977).

    Special studies on neurotoxicity

    No evidence for delayed neurological disruption in hens was evident
    when fenthion was administered orally at a single dose of 25 mg/kg
    (Kimmerle, 1965a).  When chickens were fed up to 100 mg/kg in the diet
    for 30 days, clinical examination of the animals and histological
    examination of nerve tissues indicated no demyelinating effect from
    fenthion (Kimmerle, 1965b; Dieckmann, 1971).

    Acute toxicity

                                                                                        
                                          LD50
    Animal         Sex     Route       (mg/kg bw)         Reference
                                                                                    

    Mouse          M       Oral           150             Francis & Barnes, 1963
                                          227             Dubois, 1968
                   F                      190             Francis & Barnes, 1963
                                          225             Dubois, 1968
                   F       i.p.           150             Dubois & Kinoshita, 1964
                   M                      125             Dubois & Kinoshita, 1964

    Rat            F       Oral         245-310           Dubois & Kinoshita, 1964;
                                                          Gaines, 1960
                                          615             Francis & Barnes, 1963
                   M                    175-470           Dubois & Kinoshita, 1964;
                                                          Klimmer, 1963; Gaines, 1969;
                                                          Francis & Barnes, 1963
                  M&F   Inhalation   1197 mg/m3 (1 hour)  Thyssen, 1978
                   M       i.p.           325             Dubois & Kinoshita, 1964
                   F                      260             Dubois & Kinoshita, 1964
                   M                      152             Klimmer, 1963
                   M      Dermal        330-650           Gaines, 1969; Klimmer, 1963;
                                                          Francis & Barnes, 1963
                                          1680            Mihail, 1978
                   F                      2830            Mihail, 1978
                   F                    330-500           Dubois & Kinoshita, 1964;
                                                          Gaines, 1969; Francis & 
                                                          Barnes, 1963

    Mouse          F       i.p.         200-240           Budreau & Singh, 1973a

    Guinea Pig     M       Oral          1000             Francis & Barnes, 1963
                                          260             Dubois & Kinoshita, 1964
                                          310             Dubois & Kinoshita, 1964

    Rabbit         M       Oral         150-175           Francis & Barnes, 1963
                          Dermal        150               Klimmer, 1963

    Duck                   Oral           15              Dubois & Doull, 1960
                                         1-2              Keith & Mulla, 1966


    Chicken                               30              Dubois & Doull, 1960
                                          28              Sherman & Ross, 1961
                                         30-40            Francis & Barnes, 1963

    Calf                               Approx. 40         McGrath, 1961
                                                                                    
    
    The signs of poisoning are typical of the central and peripheral
    cholinergic effects of organophosphorus esters with a gradual onset of
    the symptoms.  The symptoms in humans and other animals include
    tremors, lacrimation, salivation, vomiting, diarrhoea, and other signs
    of cholinergic stimulation.

    The rate of absorption through the skin of rabbits is slow.  When
    fenthion was applied to a cotton plug and placed in a rabbit ear for 4
    hours, swelling occurred.  When it was left for 24 hours, mortality
    resulted (Kimmerle, 1960).

    Various solvents used to  dissolve fenthion in combination with water
    or ethanol had no significant effect on the acute oral LD50
    (Kimmerle, 1967a).

    Fenthion is an organophosphorus insecticide of intermediate toxicity
    to mammals, although it displays considerable differences in its
    toxicity to various species, e.g., avian species are very sensitive
    (Keith and Mulla, 1966).

    Acute Toxicity of the Metabolites

                                                                   
                                   LD50
    Compound                 Oral1      i.p.2             I50(M)3
                                                                   

    Fenthion                  220       325           >5 × 10-4
    Fenthion sulphoxide       125       250           4.5 × 10-5
    Fenthion sulphone         125       250           4.7 × 10-4
    Fenthion Oxygen analogue  125        26           2.66 × 10-6
    Fenthion O-Sulphoxide      50        22           4.8 × 10-5
    Fenthion O-Sulphone        30         9           3.2 × 10-5
    4-(methylthio)m-cresol    65004

    4-methyl(thiosulphoxide)
      m-cresol                35004
    4-methyl(thiosulphone)    70004
                                                                   

    1 Male rats - according to Francis and Barnes, 1963
    2 Female rats - according to Dubois and Kinoshita, 1964
    3 I50 = Molar concentration resulting in 50% inhibition of human RBC
    cholinesterase (Francis and Barnes, 1963)
    4 Female rats according to Nelson, 1967


    Antidotes

    A number of antidotes that are commonly used for organophosphorus
    poisoning have been shown to be relatively inactive when used
    following fenthion intoxication.  Studies with atropine, 2-PAM, 
    Toxogonin, P-2-S, and TMB-4 (Dubois and Kinoshita, 1964; Francis and

    Barnes, 1963; Dubois, 1960 and Lorke and Kimmerle, 1969) administered
    alone and in combination showed that these materials did not
    successfully alleviate the parasympathomimetic signs of
    organophosphate poisoning.  When BH-6 (Merck; Darmstadt, Germany) was
    administered three to four times in combination with atropine, the
    LD50 value increased from 250 to 440 mg/kg (Kimmerle, 1963).

    Toxogonin was not effective as a cholinesterase reactivator following
    oral intoxication of dogs by fenthion (Hahn and Henschler, 1969).

    Short-term studies

    Inhalation

    Female rats tolerated a daily one-hour inhalation challenge of 0.163
    mg/l air for 30 days with cholinesterase depression but no mortality.
    At 0.415 mg/l air, all animals were dead within 10 days (Dilley and
    Doull, 1961a).  Following a standard 4-hour exposure, the LC50 for
    fenthion for male and female rats was approximately 1200 and 800
    mg/m3.  Five consecutive 4-hour exposures resulted in an LC50 for
    males of approximately 212 mg/m3 and for females the LC50 was
    between 55 and 212 mg/m3 (Thyssen, 1978).

    Exposure by inhalation daily for nine days, six hours per day at 210
    mg/m3 (initial concentration in a static inhalation chamber),
    resulted in signs of poisoning, but no mortality in cats, guinea pigs,
    rabbits, and rats.  Cholinesterase, which was severely depressed,
    recovered in three weeks (Klimmer, 1963).  Fenthion exhibits a
    relatively low degree of acute mammalian toxicity.  In only one
    instance was a sex difference in susceptibility noted, and this is in
    contrast to the generally noted resistance of males to other
    phosphorothioates (Dubois and Kinoshita, 1964).

    Duck

    Mallard ducks fed 25 mg/kg of fenthion in the diet for six weeks
    became emaciated and could not fly or walk; after two days on normal
    food, recovery was evident.  A dietary level of 5 mg/kg produced no
    adverse clinical reaction (Keith and Mulla, 1966).

    Rat

    Dermal administration of fenthion at 14.5 and 25 mg/kg for 60 days to
    rats resulted in 40% mortality in the higher-dosed group and no
    mortality in the lower-dosed group.  However, blood cholinesterase
    levels were depressed to about 20% of normal at the lower treatment
    level (Dubois, 1961).  Cholinesterase was depressed and mortality was
    absent when fenthion was applied to rats dermally for 12 days at 2.9
    mg/kg (Dubois and Puchala, 1960).

    Rats tolerated daily intraperitoneal administration of 10 mg/kg
    fenthion for 60 days with no mortality.  At 20 mg/kg, 80% of the
    treated animals died within 20 days (Dubois and Kinoshita, 1964).

    Mortality (12 dead of 30 rate tested) occurred following daily oral
    administration of approximately 25 mg/kg (1/10 LD50) for 75 days (6
    days per week).  Signs of poisoning were transient, disappearing
    shortly after dosing (Klimmer, 1963).

    In a preliminary study, male rats were orally administered fenthion
    five days a week for 13 weeks at a dose of 30 mg/kg/day.  Mortality
    occurred in approximately 30% of the rats over the course of the
    experiment and cholinesterase activity was depressed between 80-90% of
    normal.  At the conclusion of the experiment, cholinesterase recovery
    was very slow, up to 40 days (Kimmerle, 1961).

    Rats (22 male and 22 female per group) were fed dietary levels of
    fenthion at 0.25, 0.50, 2.5 or 5.0 mg/kg/day for three months.
    Cholinesterase activity depression was evident at 0.5 mg/kg/ day in
    red blood cells, serum, liver, and heart at all testing intervals.  At
    the lowest feeding level (0.25 mg/kg), the inhibition (approximately
    10-20%) did not progressively increase with time, indicating lack of
    cumulative effects.  Mortality in females was evident at 5.0 mg/kg.
    The animals died manifesting muscarinic and nicotinic effects. 
    Body-weight gain was reduced in males at 0.25 mg/kg and above, while
    in females it was evident only at 2.5 mg/kg.  Behaviourial effects
    were noted (piloerection) at 0.5 mg/kg and above (especially in
    females).

    This effect decreased with time and disappeared by week 7.  Organ
    weights were all distinctly lower than the controls, but as the body
    weight was also reduced, the organ-to-body-weight ratio did not appear
    to be affected.  Histological examination showed the testes to have
    reduced spermatogenesis and atrophic prostate glands were noted at the
    highest feeding levels (2.5 and 5.0 mg/kg).  The ovary was not
    affected (Shimamoto and Hattori, 1969).

    Rats (six groups of 12 male and 12 female) were fed for 16 weeks on
    diets containing 0, 2, 3, 5, 25, or 100 mg/kg.  Cholinesterase
    depression was evident at 25 mg/kg and absent at 5 mg/kg.  No adverse
    effects were noted in food consumption, weight gain, or gross and
    microscopic examination of tissues (Doull et al, 1961).

    Rats (six groups of 25 male and 25 female) were fed for one year on
    diets containing 0, 2, 3, 5, 25 or 100 mg/kg of fenthion.  There was
    no evidence of significant changes in growth rate, food consumption,
    general appearance, and gross or microscopic examination of tissues.
    Survival of male rats at 25 mg/kg was slightly depressed.
    Cholinesterase examinations indicated depression at the 5 mg/kg level
    and above, with 3 mg/kg showing no adverse enzyme effects.  A mild
    extramedullary haematopoiesis was observed in controls and all dosage
    levels, and haemosideresis was evident in the spleen of the rats at
    100 mg/kg levels (Doull et al, 1963a).

    Dog

    Groups of dogs (4 male and 4 female beagle dogs/group) were fed
    fenthion in the diet for two years at dosage levels of 0, 3, or 10
    mg/kg.  A high dose group received 30 mg/kg for 64 weeks, 50 mg/kg for
    2 weeks (weeks 65 to 67) and 60 mg/kg for the remainder of the study
    (weeks 68 to 104).

    There was no mortality in the study and all dogs appeared healthy over
    the course of the study.  When the high-dose level was increased from
    30 to 60 mg/kg, faecal changes were noted, although diarrhoea was not
    observed.  Food consumption was normal except for those animals at the
    60 mg/kg level, where at some time intervals, all the food was not
    consumed at each meal.  There were no ophthalmological changes, and
    most clinical blood chemistry, haematology, and urinalyses parameters
    were unaffected by fenthion.  Cholinesterase depression in both
    plasma, erythrocyte, and brain was observed.  Plasma cholinesterase
    was the most sensitive parameter, being depressed at dietary
    concentrations of 10 mg/kg and above.  Erythrocyte cholinesterase was
    depressed in males at 10 mg/kg and in females in the high dose group
    only.  Brain cholinesterase of both males and females was depressed,
    only at the highest concentration tested.  There were no remarkable
    observations associated with gross or microscopic examinations of
    tissues and organs.  A no-effect level in this study was 3 mg/kg,
    equal to a dietary intake of 0.09 mg/kg body weight for fenthion
    (Hoffmann and Weischer, 1975).

    Dog

    Dogs (four groups of two males and two females per group) were fed
    fenthion at 0, 2, 5 or 50 mg/kg for 12 weeks.  Growth was not affected
    at any dietary level.  Erythrocyte cholinesterase activity was
    depressed at 50 mg/kg while serum cholinesterase was depressed at 5
    mg/kg and above.  Little, if any, depression of the serum
    cholinesterase was evident before five weeks, after which it
    progressively decreased to about 40% inhibition (Doull et al, 1961).

    Dogs (four groups of two males and two females) were fed fenthion at
    0, 2, 5, or 50 mg/kg in the diet for one year.  There was no effect of
    fenthion on food consumption or growth over the test interval.
    Erythrocyte and serum cholinesterase were significantly depressed at
    50 mg/kg with the serum also depressed at 5 mg/kg.  An increase in the
    weight of the spleen, which was not dose dependant, was evident in all
    of the treated animals.

    Microscopic examinations of the tissues showed splenic congestion and
    some decrease in the cellularity of the red pulp was evident at all
    dose levels fed.  Extramedullary haematopoiesis and haemosideresis was
    also observed in the spleen.  Microscopic examination of other tissues
    did not reveal any significant changes (Doull et al, 1963b).

    Monkey

    Four groups of 5 male and 5 female rhesus monkeys received 0, 0.02,
    0.07, or 0.2 mg fenthion/kg body weight, as a freshly prepared
    solution in corn oil, daily by stomach tube for one year.  Animals
    were observed daily for general appearance and body weight and
    ophthalmological examinations were reported monthly.  Clinical
    chemistry, haematology, and urinalyses were performed at 0, 1, 3, 6
    and 12 months.  Plasma and erythrocyte cholinesterase activity was
    measured at 0, 1, 2, 3, and 4 weeks and thereafter monthly.  One
    monkey/sex from the 0 and 0.2 mg/kg groups was sacrificed at 7 months,
    3 weeks.  Brain cholinesterase, absolute and relative organ weights,
    and gross and histopathology analyses were reported.  The plasma
    cholinesterase was depressed in both sexes at 0.2 mg/kg.  Plasma
    cholinesterase depression occurred at 0.07 mg/kg, but was inconsistent
    and minimal.  No adverse effects were noted on any other parameter
    (Coulston et al, 1978).

    Long-term studies

    Rat

    In a 2-year toxicity experiment, 50 male and 50 female rats per group
    were fed a diet containing 0, 3, 15, or 75 mg/kg fenthion.  In the
    control group, 100 males and 100 females were used.

    The rats were weighed weekly during the first 26 weeks and thereafter
    at 14-day intervals.  Food consumption was recorded weekly.  Clinical
    chemistry was performed on 5 male and 5 female rats per group at
    intervals of 1, 3, 6 and 12 months, and on 10 males and females at the
    end of the experiment.  The clinical chemistry included: haematology,
    liver and kidney function tests, urinalysis, blood sugar, and serum
    cholesterol determinations.  Plasma and erythrocyte cholinesterase
    activities were determined after 1, 2, 4, 8, 13, 26, 52, 78 and 105
    weeks.  Brain cholinesterase activity was not measured.  At the end of
    the experiment, the rats were examined macroscopically, the organs
    weighed and studied microscopically.

    Fenthion at 3 and 15 mg/kg did not affect the physical appearance,
    behaviour, growth, and survival rate.  The male rats of the 75 mg/kg
    group had a significantly lower body weight.  A tendency toward
    increased mortality was observed in the 75 mg/kg group in both sexes.
    Haematology, blood chemistry, urinalysis, and gross and microscopic
    pathology revealed no compound-related effects.

    Dietary concentrations of 15 and 75 mg/kg fenthion caused
    dose-dependant depression of plasma and erythrocyte cholinesterase
    activity.  At 3 mg/kg, cholinesterase activity was only slightly
    depressed in the plasma of the females.  A no-effect level for
    fenthion in this study is 3 mg/kg (Bomhard and Loser, 1977).

    OBSERVATIONS IN MAN

    Fenthion has been widely used in many parts of the world for control
    of household pests, mosquitoes, etc.  Cholinesterase studies conducted
    on individuals in areas treated by the World Health Organization for
    malaria eradication have shown that very slight plasma cholinesterase
    depression occurs when exaggerated spray schedules were followed.  The
    plasma cholinesterase levels were depressed for up to six weeks after
    spraying (Elliot and Barnes 1963).  It was also evident that the
    children in the population (less than seven years old) were more
    susceptible to the anticholinesterase effects (Taylor, 1963).  A man
    who ingested two ounces of a fenthion formulation (Entex(R)) recovered
    from severe organophosphorous poisoning after being in critical
    condition for the first six days after poisoning.  Recovery was slow,
    lasting up to 30 days.  22 days after poisoning, the cholinesterase
    activity was still depressed (Pickering, 1966).  In humans, the signs
    of poisoning appear rapidly, beginning with blurred vision, unsteady
    gait, and slurred speech.  After 72 hours of emergency treatment
    following an unknown quantity of fenthion, a man suffered extreme
    respiratory difficulty necessitating artificial ventilation and
    endotracheal intubation.  The patient began to recover only after 11
    days of treatment, which included atropine, PAM, and toxogonin (Dean
    et al,  1967).  In another case, 45 minutes after ingestion of 30 ml
    of a fenthion formulation a man was in a comatose state with pale
    skin, cyanotic mucous membranes, slow regular heart beat, no
    peripheral blood pressure, and no reactions to pain or light
    stimulation on the pupils.  Recovery took six days (von Clarmann and
    Geldmacher-von-Mallinkrodt, 1966).

    The potential dermal and respiratory exposure to fenthion during field
    application by hand gun power spray equipment, back-pack hand pressure
    sprayer, and hand granular dispersal for mosquito control was studied
    over two work seasons (Fytizas-Danielidou, 1971).  Human workers
    exposed to 3.6-12.3 mg/h (dermal) or <0.02-0.09 mg/h (inhalation),
    equivalent to 0.5-1.5 mg/kg/day (dermal) and 0.01-0.05 mg/kg/day
    (inhalation), showed a decrease in plasma, but not erythrocyte
    cholinesterase activity (Wolfe et al,  1974).

    A study was carried out on 150 cases of anticholinesterase insecticide
    poisoning to observe the influence of the type of insecticide used on
    the clinical picture and prognosis.  Of the 150 cases, 32 had consumed
    fenthion, 48 fenitrothion, and 50 malathion.  Twenty did not know
    exactly what agent was consumed.  Paralytic signs were significantly
    more frequent with fenthion than with malthion or fenitrothion (being
    81.2%, 30% and 23% respectively).  These signs occurred later with
    fenthion and lasted longer.  Death occurred significantly more often
    with fenthion (the mortality rate being with fenthion 35.5%, with
    malathion 4%, and with fenitrothion 2.1%).  Pulmonary oedema was most
    common with malathion and not encountered with fenthion.  The
    cholinesterase activity was most marked with fenthion reaching 0 in 18
    of the 27 cases studied (Wadia, et al, 1977).

    A group of male volunteers were administered fenthion orally for
    periods of time up to 4 weeks at dosage levels of 0, 0.04 or 0.07
    mg/kg body weight.  There were no effects reported on physical signs
    or symptoms, haematology, or urinalysis parameters.  With the
    exception of a slight plasma cholinesterase depression noted at the
    high dosage level, no effects were noted on the various clinical
    chemistry parameters (Griffin et al, 1979).

    EVALUATION

    COMMENTS

    The meeting reviewed new data requested by previous meetings and
    considered all of the available information on fenthion.

    Fenthion, an organophosphorus insecticide, is rapidly absorbed,
    metabolised and excreted.  Fenthion does not accumulate in the body.
    In most instances, those metabolites that remain fully esterified are
    more toxic than the parent compound.  Fenthion and its biologically
    active metabolites are anticholinesterase agents and the signs and
    symptoms of poisoning are typical of the cholinergic response.  The
    signs of intoxication from a single oral dose develop slowly and
    persist for a considerable time.  Although there is no explanation for
    the long-lasting cholinesterase depression, slow appearance and
    disappearance of cholinergic signs and lack of appropriate antidote,
    these are of minimal concern in establishing an ADI.  It would however
    be of interest to have such information, which could be of high value
    in cases of acute poisoning.  The cholinergic signs of poisoning are
    not readily alleviated by atropine or by the common oxime
    reactivators.

    Fenthion is not mutagenic in mammalian or microbial test systems.  It
    is not carcinogenic, or teratogenic and does not affect reproduction
    in rodents.  Fenthion does not induce delayed neurotoxicity in hens
    nor is it potentiated by other cholinergic chemicals.

    In extended short-term studies with rats, dogs and monkeys, and in a
    long-term rat study, there were no indications of adverse effects
    other than cholinesterase depression.  Studies of humans exposed
    occupationally or through malaria-control programmes, as well as of
    volunteers ingesting a standardised dose, do not indicate any short-
    or long-term adverse effects except plasma depression and acute
    cholinergic response.

    From the available data no-effect levels in rat, dog and a monkey were
    noted.

    Observations in humans provide additional assurance of the safety of
    the residue level in food.

    Maximum level causing no toxicological effect

    Rat:     3 mg/kg in the diet equivalent to 0.15 mg/kg bw/day.
    Dog:     3 mg/kg in the diet equivalent to 0.09 mg/kg bw/day.
    Monkey:  0.07 mg/kg bw/day
    Man:     0.02 mg/kg bw/day


    Estimate of acceptable daily intake for man

    0-0.001 mg/kg bw


    FURTHER WORK AND INFORMATION

    Desirable

    Studies to elucidate the mechanism of the long-lasting cholinesterase
    inhibition noted in human studies as well as in animal bioassays.


    REFERENCES

    Avrahami, M. and White, D.A. Residues in milk of cows after
    spot-treatment with 32P-fenthion. New Zealand Expte. Agric. 3:
    309-11.

    Begum, A. Effect of diet on metabolism of fenthion in animals. Ph. D.
    thesis, Auburn University, Auburn, Alabama. Dissert. Abstr., Sect. B,
    28: 4165.

    Bomhard, E. and Loser E. Chronic toxicity study on rats. (1977)
    Unpublished report (No. 6769) from the Institut für Toxikologie,
    submitted to the World Health Organization by Bayer AG.

    Brady U.E., Jr. and Arthur, B.W. Metabolism of O,O-dimethyl
    O-[4-(methylthio)-m-tolyl] phosphorothioate by white rats. J. Econ.
    Entomol. 54: 1232-1236.

    Budreau, C.H. and Singh, R.P. Teratogenicity and embryotoxicity of
    demeton and fenthion in CF 1 mouse embryos. Tox. Appl. Pharm. 24:
    325-322.

    Budreau, C.H. and Singh, R.P. Effect of fenthion and dimethoate on
    reproduction in the mouse. Tox. Appl. Pharm. 26: 29-38.

    Bull, D.L. and Stokes, R.A. Metabolism of dimethyl
    p-(methylthio)phenyl phosphate in animals and plants. J. Agr. Food
    Chem. 18: 1134-1138.

    Coulston, F., Rosenblum, I. and Ford, W. A safety evaluation of
    fenthion in rhesus monkeys (Macaca mulatta). (1978) Unpublished
    twelve-month interim report from Albany Medical College of Union
    University, Albany, New York, submitted to the World Health
    Organization by Bayer AG.

    Dean, G., Cozon, J. and Brereton, D. Poisoning by an organophosphorus
    compound. A case report. So. African Med. J., 1017-19.

    Dieckmann, W. Neurotoxizitatsunter-suchungen an
    Huhnern-Histopathologie. (1971) Unpublished report of Farbenfabriken
    Bayer AG, submitted to the World Health Organization by Bayer AG.

    Dilley, J. and Doull, J. Chronic inhalation toxicity of Bayer 29493 to
    rats and mice. (1961a) Unpublished report from Department of
    Pharmacology, University of Chicago, submitted to the World Health
    Organisation by Bayer AG.

    Dilley J. and Doull, J. Acute inhalation toxicity of Bayer 29493 to
    rate and mice. (1961b) Unpublished report from Department of
    Pharmacology University of Chicago, submitted to the World Health
    Organization by Bayer AG.

    Dubois, K.P. The absence of antidote activity by 2-PAM and TMB-4
    against acute poisoning by Bayer 29493. (1960) Unpublished report from
    Department of Pharmacology, University of Chicago, submitted to the
    World Health Organization by Bayer AG.

    Dubois, K.P. Effects of repeated dermal application of Bayer 29493 on
    rats. (1961) Unpublished report from Department of Pharmacology,
    University of Chicago, submitted to the World Health Organization by
    Bayer AG.

    Dubois, K.P. Acute oral toxicity of a sample of Bayer 29493 to female
    rats. (1962) Unpublished report from Department of Pharmacology,
    University of Chicago, submitted to the World Health Organization by
    Bayer AG.

    Dubois, K.P. Comparison of the acute oral toxicity of Bayer 29493 and
    Sumithion to mice. (1968) Unpublished report from Department of
    Pharmacology, University of Chicago, submitted to the World Health
    Organization by Bayer AG.

    Dubois. K.P. and Doull, J. The acute toxicity of Bayer 29493 to
    chickens and ducks. (1960) Unpublished report from Department of
    Pharmacology, University of Chicago, submitted to the World Health
    Organization by Bayer AG.

    Dubois, K.P. and Puchala, E. Influence of Bayer 29493 on the
    cholinesterase activity of the blood of rats. (1960) Unpublished
    report from Department of Pharmacology, University of Chicago,
    submitted to the World Health Organization by Bayer AG.

    Dubois, K.P. and Kinoshita, F. Acute toxicity and anticholinesterase
    action of O,O-dimethyl O-4-(methylthio-m-tolyl phosphorotioate)
    (DMTP;Baytex) and related compounds. Tox. Appl. Pharmacol. 6: 86-95.

    Doull J., Root M. and Cowan, J. Determination of the safe dietary
    level for Bayer 29493 for dogs. (1961) Unpublished report from
    Department of Pharmacology, University of Chicago, submitted to the
    World Health Organization by Bayer AG.

    Doull J., Root, M. and Cowan, J. Effect of adding Bayer 29493 in
    combination with other cholinergic insecticides to the diet of male
    and female dogs. (1962) Unpublished report from Department of
    Pharmacology, University of Chicago, submitted to the World Health
    Organization by Bayer AG.

    Doull, J., Root, M., Cowan, N.J., Vesselinovitch, D., Fitch, F.M. and
    Meskauskas, J. Chronic oral toxicity of Bayer 29493 to male and female
    rats. (1963a) Unpublished report from Department of Pharmacology,
    University of Chicago, submitted to WHO by Bayer AG.

    Doull, J., Root, M., Cowan, J. and Vesselinovitch, D. Chronic oral
    toxicity of Bayer 29493 to male and female dogs. (1963b) Unpublished
    report from Department of Pharmacology, University of Chicago,
    submitted to WHO by Bayer AG.

    Doull, J., Vesselinovitch, D., Fitch, F., Cowan, J., Root, M. and
    Meskauskas, J. The effects of feeding diets containing Bayer 29493 to
    rats for a period of 16 weeks. (1961) Unpublished report from
    Department of Pharmacology, University of Chicago, submitted to WHO by
    Bayer AG.

    Elliot, R. and Barnes, J.M. Organophosphorous insecticides for the
    control of mosquitoes in Nigeria. Bull. Wld. Hlth. Org. 18: 35-54.

    Francis, J.I. and Barnes, J.M. Studies on the mammalian toxicity of
    fenthion. Bull. Wld. Hlth. Org. 29: 205-12.

    Fytizas-Danielidou, R. Effects des pesticides sur la reproduction des
    rats blancs. I. Lebaycide. Fakulteit van de Landbouwweten-schappen.
    23. International Symposium over Fytofarmacie, 4 Mei, 1971.

    Gaines, T.B., Acute toxicity of pesticides, Toxicol. Appl. Pharmacol.
    14: 515-34.

    Griffin, T., Rosenblum, I. and Coulston, F. Safety evaluation of
    fenthion in human volunteers. Final report. (1979) Unpublished report
    from the Institute of Comparative and Human Toxicology and the
    International Center of Environmental Safety, submitted to WHO by
    Bayer AG.

    Hahn, H.L. and Henschler, D. The ability of phosphorylated
    cholinesterase to be reactivated by obidoxime chloride (Toxogonin)
    in vivo. Arch. Toxikol. 24: 147-63.

    Hoffman, K. and Weischer, C.H. Fenthion chronic study on dogs
    (two-year feeding experiment). (1975) Unpublished report from Bayer AG
    Institut für Toxikologie (No. 5737), submitted to WHO by Bayer AG.

    Johnson, J.C. and Bowman, M.C. Responses from cows fed diets
    containing fenthion or fenitrothion, J. Dairy Sci. 55: 777-82.

    Katague, D.B. Determination of fenthion residues in milk by
    electron-capture gas chromatography. (1966) Chemagro Corporation,
    Research Department, Report No. 17, 887, submitted to WHO by Bayer AG.

    Kawai, M., Tojo, K., Miyazawa, S., Maruta, H. and Naito, M.
    Experimental studies on the effects of organophosphorous compounds on
    the eyes. Nat. Def. Med. J. 23(1): 1-10 (abstract).

    Keith, J.O. and Mulla, M.S. Relative toxicity of five
    organophosphorous mosquito larvicides to mallard ducks. J. Wildlife
    Management 30: 553-63.

    Kimmerle, G. Re: Active substance S1752. Unpublished report from
    Farbenfabriken Bayer AG, submitted to WHO by Bayer AG.

    Kimmerle, G. Subchronische oral versuche bei ratten mit
    S-1752-Wirkstoff. (1961) Unpublished report from Farbenfabriken Bayer
    AG submitted to WHO by Bayer AG.

    Kimmerle, G. Produc BH6 and S1752 poisoning. (1963) Unpublished report
    from Farbenfabriken Bayer AG, submitted to WHO by Bayer AG.

    Kimmerle, G. Neurotoxic studies with Bayer 29493. (1965a) Unpublished
    report from Farbenfabriken Bayer AG, submitted to the World Health
    Organization by Bayer AG.

    Kimmerle, G. Neurotoxische untersuch-ungen mit S-1752-Werkstoff.
    (1965b) Unpublished report from Farbenfabriken Bayer AG, submitted to
    the World Health Organization by Bayer AG.

    Kimmerle, G. Langdauernde Inhalationsversuche bei Hunden mit dem
    Baytex-Wirkstoff (S-1752). (1966) Unpublished report from
    Farbenfabriken Bayer AG, submitted to the World Health Organization by
    Bayer AG.

    Kimmerle, G. Abhangigkeit der aduten oralen Toxizitat bei Patten vom
    Lössungmittel. (1967a) Unpublished report from Farbenfabriken Bayer
    AG, submitted to the World Health Organization by Bayer AG.

    Kimmerle, G,. Potenzierung von DDVP und S-1752. (1967b) Unpublished
    report from Farbenfabriken Bayer AG, submitted to the World Health
    Organization by Bayer AG.

    Klimmer, R. Toxicologioal testing of Bayer 29493. (1963) Unpublished
    report from Farbenfabriken Bayer AG, submitted to the World Health
    Organization by Bayer AG.

    Knowles, C.O. and Arthur, B.W. Metabolism of and residues associated
    with dermal and intramuscular application of radio-labelled fenthion
    to dairy cows. J. Econ. Entomol. 59: 1346-52.

    Lorke D. and Kimmerle, G. The action of reactivators in phosphoric
    acid ester poisoning. Arch. Pharmakol. 263: 237-8.

    Löser E. Generations versuche an ratten. (1969) Unpublished report
    from Farbenfabriken Bayer AG, submitted to the World Health
    Organization by Bayer AG.

    Machemer, L. S1752 (Fenthion, Lebaycid-Wirkstoff) Untersuchungen auf
    embryotoxische und teratogene Wirkungen an Ratten nach oraler
    Varabreichung, Rep. No. 7580. (1978a) Unpublished report from Institut
    für Toxikologie, Bayer AG, submitted to the World Health Organization
    by Bayer AG.

    Machemer, L. S1752 (Fenthion, Lebaycid active ingredient) Dominant
    lethal study of male mice to teat for mutagenic effects. Report. No.
    7449. (1978b) Unpublished report from Institut für Toxikologie, Bayer
    AG, submitted to the World Health Organization by Bayer AG.

    McGrath, H.B. Toxicity of Bayer 29493 in calves. (1961) Unpublished
    report from Farbenfabriken Bayer AG, submitted to the World Health
    Organization by Bayer AG.

    Metcalf, R.L., Fukoto, T.R. and Winton M.Y. Chemical and biological
    behaviour of fenthion residues. Bull. Wld. Hlth. Org. 29: 219-226.

    Mihail, F. S1752 Lebayoid active ingredient. Determinations of
    percutaneous toxicity. (1978) Unpublished report from Institut für
    Toxicologie, Bayer AG, submitted to the World Health Organization by
    Bayer AG.

    Möllhoff, E. Determination of trichlorfon and fenthion residues in
    animals of different species. Pestic. Sci. 2: 179-181.

    NCI. Bioassay of fenthion for possible carcinogenicity. National
    Cancer Institute Carcinogenesis Technical Report Series No. 103. U.S.
    Dept. of HEW publication No. (NIH) 79-1353. Bioassay conducted by Gulf
    South Research Institute, New Iberia, Louisiana, under contract to NCI
    and subcontract to Tracor Jitco, Inc., who prepared the final report.

    Nelson, D.L. The acute oral toxicity of three phenolic compounds to
    adult female rats. (1967) Unpublished report from Farbenfabriken Bayer
    AG, submitted to the World Health Organization by Bayer AG.

    Oesch F. Ames test for Lebycid (Fenthion). (1977) Unpublished report
    from Pharmakologisches Institut der Unwersitat Mainz, submitted to the
    World Health Organization by Bayer AG.

    Pickering, E.N. Organic phosphate insecticide poisoning. Can. J. Med.
    Tech., p. 174.

    Sherman, M. and Ross, E. Acute and subacute toxicity of insecticides
    to chicks. Toxicol. Appl. Pharmacol. 3: 512-33.

    Shimamoto, K. and Hattori, K. Chronic feeding of Baytex
    (O,O-dimethyl-o-(4-methylmercapto-3-methyl) phenyl-thiophosphate) in
    rats. Acta Med. Univ. Kyoto, 40: 163-71.

    Spicer, E.J.F. Pathology Report of Bay 29493. Generation study in
    rats. (1971) Unpublished report from Farbenfabriken Bayer AG submitted
    to the World Health Organization by Bayer AG. 

    Taylor, A. Observations on human exposure to the organophosphorus
    insecticide fenthion in Nigeria. Bull. Wld. Hlth. Org. 29: 213-18.

    Thyssen, J. Untersuchungen zur kombinationstoxizität von Edifenphos,
    Fenthion und Bassa-Wirkstoff. Report No. 7176. (1977) Unpublished
    report from Bayer AG Institut für Toxikologie, submitted to the World
    Health Organization by Bayer AG.

    Thyssen, J. S1752. (Lebaycid-Wirkstoff). Akute inhalationstaxizitat.
    Unpublished report from Bayer AG Institut für Toxikologie, submitted
    to the World Health Organization by Bayer AG.

    von Clarmann, M. and Geldmacher-von Mallinckrodt, M. A successfully
    treated case of acute oral poisoning by fenthion and its demonstration
    in the gastric contents and urine.  Arch. Toxik. 22: 2-11.

    Wadia, R.S., Bhirud, R.H., Gulavani, A.V. and Amin, R.B. Neurological
    manifestations of three organophosphate poisons. Indian J. Med. Res.
    66(3): 446-48.

    Wills, J.H., Broblewski, G.E. and Coulston, F. (1975) Unpublished
    status report from Institute of Comparative and Human Toxicology,
    Albany Medical College, Albany, New York, submitted to the World
    Health Organization by Bayer AG.

    Wolfe H.R., Armstrong J.F. and Durham, W.F. Exposure of mosquito
    control workers to fenthion. Mosquito News 34: 263-67.

    


    See Also:
       Toxicological Abbreviations
       Fenthion (ICSC)
       Fenthion (PDS)
       Fenthion (WHO Pesticide Residues Series 1)
       Fenthion (WHO Pesticide Residues Series 5)
       Fenthion (Pesticide residues in food: 1977 evaluations)
       Fenthion (Pesticide residues in food: 1978 evaluations)
       Fenthion (Pesticide residues in food: 1979 evaluations)
       Fenthion (Pesticide residues in food: 1983 evaluations)
       Fenthion (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)
       Fenthion (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)
       Fenthion (Pesticide residues in food: 1997 evaluations Part II Toxicological & Environmental)