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.

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

    First draft prepared by Dr. J. Risher and Dr. H. Choudhury,
    US Environmental Protection Agency,
    Cincinnati, Ohio, USA

    World Health Orgnization
    Geneva, 1991

         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
    Organization. The main objective of the IPCS is to carry out and
    disseminate evaluations of the effects of chemicals on human health
    and the quality of the environment. Supporting activities include
    the development of epidemiological, experimental laboratory, and
    risk-assessment methods that could produce internationally
    comparable results, and the development of manpower in the field of
    toxicology. Other activities carried out by the IPCS include the
    development of know-how for coping with chemical accidents,
    coordination of laboratory testing and epidemiological studies, and
    promotion of research on the mechanisms of the biological action of

    WHO Library Cataloguing in Publication Data


        (Environmental health criteria ; 121)

        1.Aldicarb - adverse effects 2.Aldicarb - toxicity 3.Environmental
        exposure 4.Environmental pollutants       I.Series

        ISBN 92 4 157121 7        (NLM Classification: WA 240)
        ISSN 0250-863X

         The World Health Organization welcomes requests for permission
    to reproduce or translate its publications, in part or in full.
    Applications and enquiries should be addressed to the Office of
    Publications, World Health Organization, Geneva, Switzerland, which
    will be glad to provide the latest information on any changes made
    to the text, plans for new editions, and reprints and translations
    already available.

    (c) World Health Organization 1991

         Publications of the World Health Organization enjoy copyright
    protection in accordance with the provisions of Protocol 2 of the
    Universal Copyright Convention. All rights reserved.

         The designations employed and the presentation of the material
    in this publication do not imply the expression of any opinion
    whatsoever on the part of the Secretariat of the World Health
    Organization concerning the legal status of any country, territory,
    city or area or of its authorities, or concerning the delimitation
    of its frontiers or boundaries.

         The mention of specific companies or of certain manufacturers'
    products does not imply that they are endorsed or recommended by the
    World Health Organization in preference to others of a similar
    nature that are not mentioned. Errors and omissions excepted, the
    names of proprietary products are distinguished by initial capital



    1. SUMMARY

         1.1. Identity, properties, and analytical methods
         1.2. Uses, sources, and levels of exposure
         1.3. Kinetics and metabolism
         1.4. Studies on experimental animals
         1.5. Effects on humans


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


         3.1. Natural occurrence
         3.2. Anthropogenic sources
              3.2.1. Production levels, processes, and uses
               production figures


         4.1. Transport and distribution between media
              4.1.1. Air
              4.1.2. Water and soil
              4.1.3. Vegetation and wildlife
         4.2. Biotransformation
         4.3. Interaction with other physical, chemical or biological
              4.3.1. Soil microorganisms


         5.1. Environmental levels
              5.1.1. Air
              5.1.2. Water
              5.1.3. Food and feed
         5.2. General population exposure
         5.3. Occupational exposure during manufacture, formulation
              or use


         6.1. Absorption
         6.2. Distribution
         6.3. Metabolic transformation
         6.4. Elimination and excretion in expired air, faeces, and


         7.1. Single exposure
         7.2. Short-term exposure
         7.3. Skin and eye irritation; sensitization
         7.4. Long-term exposure
         7.5. Reproduction, embryotoxicity, and teratogenicity
         7.6. Mutagenicity and related end-points
         7.7. Carcinogenicity
         7.8. Other special studies
         7.9. Factors modifying toxicity; toxicity of metabolites
         7.10. Mechanisms of toxicity - mode of action


         8.1. General population exposure
              8.1.1. Acute toxicity; poisoning incidents
              8.1.2. Human studies
              8.1.3. Epidemiological studies
         8.2. Occupational exposure
              8.2.1. Acute toxicity; poisoning incidents
              8.2.2. Effects of short- and long-term exposure;
                        epidemiological studies


         9.1. Microorganisms
         9.2. Aquatic organisms
         9.3. Terrestrial organisms
         9.4. Population and ecosystem effects


         10.1. Evaluation of human health risks
              10.1.1. Exposure levels
                General population
                Occupational exposure
              10.1.2. Toxic effects
              10.1.3. Risk evaluation
         10.2. Evaluation of effects on the environment


         11.1. Conclusions
              11.1.1. General population
              11.1.2. Occupational exposure
              11.1.3. Environmental effects
         11.2. Recommendations














    Dr I. Boyer, The Mitre Corporation, McLean, Virginia, USA

    Dr G. Burin, Health Effects Division, Office of Pesticide
         Programs, US Environmental Protection Agency, Washington, DC, USA
          (Joint Rapporteur)

    Dr S. Dobson, Institute of Terrestrial Ecology, Monks Wood
         Experimental Station, Abbots Ripton, Huntingdon, United Kingdom
          (Vice Chairman)

    Professor W. J. Hayes, Jr., School of Medicine, Vanderbilt
         University, Nashville, Tennessee, USA  (Chairman)

    Professor F. Kaloyanova, Institute of Hygiene and
         Occupational Health, Medical Academy, Sofia, Bulgaria

    Dr S. K. Kashyap, National Institute of Occupational
         Health, Indian Council of Medical Research, Meghani Nagar,
         Ahmedabad, India

    Dr H. P. Misra, University Center for Toxicology, Virginia
         Polytechnic Institute and State University, Blacksburg, Virginia,

    Mr D. Renshaw, Department of Health, Hannibal House,
         London, United Kingdom

    Dr J. Withey, Environmental & Occupational Toxicology
         Division, Environmental Health Center, Tunney's Pasture, Ottawa,
         Ontario, Canada

    Dr Shou-zheng Xue, School of Public Health, Shanghai
         Medical University, Shanghai, China

     Representatives of other organizations

    Dr L. Hodges, International Group of National Associations
         of Manufacturers of Agrochemical Products (GIFAP), Brussels,

    Dr J. M. Charles, International Group of National
         Associations of Manufacturers of Agrochemical Products (GIFAP),
         Brussels, Belgium


    Dr B. H. Chen, International Programme on Chemical Safety,
         World Health Organization, Geneva, Switzerland  (Secretary)

    Dr H. Choudhury, Environmental Criteria and Assessment
         Office, US Environmental Protection Agency, Cincinnati, Ohio, USA
          (Joint Rapporteur)

    Dr P. G. Jenkins, International Programme on Chemical
         Safety, World Health Organization, Geneva, Switzerland


         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 monographs, readers are kindly requested to communicate any
    errors that may have occurred to the Manager of the International
    Programme on Chemical Safety, World Health Organization, Geneva,
    Switzerland, in order that they may be included in corrigenda, which
    will appear in subsequent volumes.

                                   *  *  *

         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


         A WHO Task Group on Environmental Health Criteria for Aldicarb
    met in Cincinnati, USA, from 6 to 10 August 1990. Dr C. DeRosa opened
    the meeting on behalf of the US Environmental Protection Agency. Dr
    B.H. Chen of the International Programme on Chemical Safety (IPCS)
    welcomed the participants on behalf of the Manager, IPCS, and the
    three IPCS cooperating organizations (UNEP/ILO/ WHO). The Task Group
    reviewed and revised the draft criteria monograph and made an
    evaluation of the risks for human health and the environment from
    exposure to aldicarb.

         The first draft of this monograph was prepared by Dr J. Risher
    and Dr H. Choudhury of the US Environmental Protection Agency. The
    second draft was prepared by Dr H. Choudhury incorporating comments
    received following the circulation of the first draft to the IPCS
    Contact Points for Environmental Health Criteria documents. During the
    Task Group meeting all the participants contributed to review the
    large amount of information submitted by Rhône-Poulenc, and undertook
    a substantial revision of the second draft. Dr B.H. Chen and Dr P.G.
    Jenkins, both members of the IPCS Central Unit, were responsible for
    the overall scientific content and technical editing, respectively.

         The efforts of all who helped in the preparation and finalization
    of the document are gratefully acknowledged. The Secretariat wishes to
    thank Dr S. Dobson and Dr G. Burin for the significant contributions
    and revisions of the draft document during the meeting.

         Financial support for the meeting was provided by the US
    Environmental Protection Agency, Cincinnati, USA.


         ADI       acceptable daily intake

         ai        active ingredient

         CHO       Chinese hamster ovary

         FAD       flavin adenine dinucleotide

         FPD       flame photometric detector

         GC        gas chromatography

         GPC       gel permeation chromatography

         HPLC      high-performance liquid chromatography

         LC        liquid chromatography

         MATC      maximum acceptable toxic concentration

         MS        mass spectroscopy

         NADPH     reduced nicotinamide adenine dinucleotide phosphate

         NOEL      no-observed-effect level

         TLC       thin-layer chromatography

         UV        ultraviolet

    1.  SUMMARY

    1.1  Identity, properties, and analytical methods

         Aldicarb is a carbamate ester. It is a white crystal-line solid,
    moderately soluble in water, and susceptible to oxidation and
    hydrolytic reactions.

         Several different analytical methods, including thin-layer
    chromatography, gas chromatography (electron capture, flame
    ionization, etc.), and liquid chromatography, are available. The
    currently preferred method for analysing aldicarb and its major
    decomposition products is high-performance liquid chromatography with
    post-column derivatization and fluorescence detectors.

    1.2  Uses, sources, and levels of exposure

         Aldicarb is a systemic pesticide that is applied to the soil to
    control certain insects, mites, and nematodes.  The soil application
    includes a wide range of crops, such as bananas, cotton, coffee,
    maize, onions, citrus fruits, beans (dried), pecans, potatoes,
    peanuts, soybeans, sugar beets, sugar cane, sweet potatoes, sorghum,
    tobacco, as well as ornamental plants and tree nurseries. Exposure of
    the general population to aldicarb and its toxic metabolites (the
    sulfoxide and sulfone) occurs mainly through food. The ingestion of
    contaminated food has led to poisoning incidents from aldicarb and its
    toxic metabolites (the sulfoxide and sulfone).

         Due to the high acute toxicity of aldicarb, both inhalation and
    skin contact under occupational exposure conditions may be dangerous
    for workers if preventive measures are inadequate. There have been a
    few incidents of accidental exposure of workers due to improper use or
    lack of protective measures.

         Aldicarb is oxidized fairly rapidly to the sulfoxide, 48%
    conversion of parent compound to sulfoxide occurring within 7 days
    after application to certain types of soils. It is oxidized much more
    slowly to the sulfone. Hydrolysis of the carbamate ester group, which
    inactivates the pesticide, is ph dependent, half-lives in distilled
    water varying from a few minutes at a pH of > 12 to 560 days at a pH
    of 6.0. Half-lives in surface soils are approximately 0.5 to 3 months
    and in the saturated zone from 0.4 to 36 months Aldicarb hydrolyses
    somewhat more slowly than either the sulfoxide or the sulfone.
    Laboratory measurement of the biotic and abiotic breakdown of aldicarb
    have yielded very variable results and have led to extrapolations
    radically different from field observation. Field data on the
    breakdown products of aldicarb furnish more reliable estimates of its

         Sandy soils with low organic matter content allow the greatest
    leaching, particularly where the water table is high. Drainage
    aquifers and local shallow wells have been contaminated with aldicarb
    sulfoxide and sulfone; levels have generally ranged between 1 and
    50µg/litre, although an occasional level of approximately 500 µg/litre
    has been recorded.

         As aldicarb is systemic in plants, residues may occur in foods.
    Residue levels greater than 1 mg/kg have been reported in raw
    potatoes. In the USA, where the tolerance limit for potatoes is 1
    mg/kg, residue levels of up to 0.82 mg/kg have been reported from
    controlled field trials using application rates recommended by the
    manufacturer. An upper 95th percentile level of 0.43 mg/kg has been
    estimated from field trial data, and upper 95th percentile levels of
    up to 0.0677 mg/kg in raw potatoes have been determined from a
    market-basket survey.

    1.3  Kinetics and metabolism

         Aldicarb is efficiently absorbed from the gastrointestinal tract
    and, to a lesser extent, through the skin. It could be readily
    absorbed by the respiratory tract if dust were present. It distributes
    to all tissues, including those of the developing rat fetus. It is
    metabolically transformed to the sulfoxide and the sulfone (both of
    which are toxic), and is detoxified by hydrolysis to oximes and
    nitriles. The excretion of aldicarb and its metabolites is rapid and
    primarily via the urine. A minor part is also subject to biliary
    elimination and, consequently, to enterohepatic recycling. Aldicarb
    does not accumulate in the body as a result of long-term exposure. The
    inhibition of cholinesterase activity  in vitro by aldicarb is
    spontaneously reversible, the half-life being 30-40 min.

    1.4  Studies on experimental animals

         Aldicarb is a potent inhibitor of cholinesterases and has a high
    acute toxicity. Recovery from its cholinergic effects is spontaneous
    and complete within 6 h, unless death intervenes. There is no
    substantial evidence to indicate that aldicarb is teratogenic,
    mutagenic, carcinogenic, or immunotoxic.

         Birds and small mammals have been killed as a result of ingesting
    aldicarb granules not fully incorporated into the soil as recommended.
    In laboratory tests, aldicarb is acutely toxic to aquatic organisms.
    There is no indication, however, that effects would occur in the

    1.5  Effects on humans

         The inhibition of acetylcholinesterase at the nervous synapse and
    myoneural junction is the only recognized effect of aldicarb in humans
    and is similar to the action of organophosphates. The carbamyolated
    enzyme is unstable, and spontaneous reactivation is relatively rapid
    compared with that of a phosphorylated enzyme. Non-fatal poisoning in
    man is rapidly reversible. Recovery is aided by the administration of


    2.1  Identity

         Common name:   Aldicarb

         Chemical structure:

                          CH3           O
                          '             "
                   CH3S - C - CH = N - OCNHCH3

         Molecular formula:  C7H14N2O2S

         Synonyms and        Aldicarb (English); Aldicarbe (French);
         common trade        Carbanolate; ENT 27 093; 2-methyl-2-
         names:              (methylthio)propanal
                              O-[(methylamino)-carbonyl]oxime (C.A.);
                              O-methyl-carbamoyloxime (IUPAC);
                             NCI-CO8640; OMS-771; Propanal,
                              O-((methylamino)carbonyl)oxime; Temic;
                             Temik; Temik G; Temik M; Temik LD; Sentry;
                             Temik 5G; Temik 10G; Temik 15G; Temik 150G;
                             Union Carbide UC 21 149.

         CAS registry
         number              116-06-3

         RTECS no.           UE2275000.

    2.2  Physical and chemical properties

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

         Aldicarb, for which the IUPAC name is
    2-methyl-2-(methylthio)propionaldehyde  O-methylcarbamoyloxime, is an
    oxime carbamate insecticide that was introduced in 1965 by the Union
    Carbide Corporation under the code number UC 21 149 and the trade name
    Temik (Worthing & Walker, 1987).

         Takusagawa & Jacobson (1977) reported that the molecular
    structure of the aldicarb crystal, as determined by single-crystal
    X-ray diffraction techniques, consists of an orthorhombic unit cell
    with eight molecules per cell. The C-O single bond length in the
    carbamate group was reported to be significantly greater than in
    carboxylic acid esters. This supports the theory that interaction with
    acetylcholinesterase involves disruption of this bond.

         Aldicarb has two geometrical isomers as shown below:


         The commercial product is a mixture of these two isomers. It is
    not certain which isomer is the more active.

    2.3  Conversion factors

    In air at 25 °C and 101.3 kPa (760 mmHg): 

                   1 ppm (v/v) = 7.78 mg/m3

                   1 mg/m3 = 0.129 ppm (v/v).

    2.4  Analytical methods

         The methods for analysing aldicarb include thin-layer
    chromatography (Knaak et al., 1966a,b; Metcalf et al., 1966), liquid
    chromatography (LC) (Wright et al., 1982), ultraviolet detection
    (Sparacino et al., 1973), post-column derivatization and fluorometric
    detection (Moye et al., 1977; Krause, 1979), and gas chromatography
    (GC) with various detectors. These include the Hall detector (Galoux
    et al., 1979), mass spectrometry (Muszkat & Aharonson, 1983), flame
    ionization detection (Knaak et al., 1966a,b), and esterification and
    electron capture detection (Moye, 1975). A multiple residue method
    exists for detecting  N-methylcarbamate insecticide in grapes and
    potatoes. It involves separation by reverse phase liquid
    chromatography and detection by a post-column fluorometric technique
    (AOAC, 1990).

        Table 1. Some physical and chemical properties of aldicarba
    Relative molecular mass:           190.3

    Form:                              colourless crystals (odourless or slight
                                       sulfurous smell)

    Melting point:                     100 °C

    Boiling point:                     unknown; decomposes above 100 °C

    Vapour pressure (25 °C):           13 mPa (1 x 10-4 mmHg)

    Relative density (25 °C):          1.195

    Solubility (20 °C):                6 g/litre of water; 40% in acetone;
                                       35% in chloroform; 10% in toluene

    Properties:                        heat sensitive, relatively unstable
                                       chemical; stable in acidic media but 
                                       decomposes rapidly in alkaline media;
                                       non-corrosive to metal; non-flammable;
                                       oxidizing agents rapidly convert it to
                                       the sulfoxide and slowly to the sulfone

    Impurities                         dimethylamine; 2-methyl-2-(methylthio)
                                       propionitrile; 2-methyl-2-(2-methyl-
                                       thiopropylenaminoxy) propinaldehyde
                                        O-  (methylcarbamoyl) oxime;
                                       2-methyl-2-(methylthio) propionaldehyde

    Log octanol/water partition        1.359

    a  From: Kuhr & Dorough (1976), Worthing & Walker (1987), and FAO/WHO (1980).
         Because of aldicarb's thermal lability, it degrades rapidly in
    the injection port or on the column during GC analysis. Thus, short
    columns have been used to facilitate more rapid analyses and prevent
    thermal degradation (Riva & Carisano, 1969). A major drawback to using
    GC methods is that aldicarb degrades to aldicarb nitrile during GC;
    this degradation may also occur in the environment (US EPA, 1984).
    During GC analysis by conventional-length columns, aldicarb nitrile
    interferes with aldicarb analysis, thus necessitating a time-consuming
    clean-up procedure. Furthermore, aldicarb nitrile cannot be detected
    by LC with UV detection since absorption does not occur in the UV
    range (US EPA, 1984). The post-column fluorometric technique used in
    LC requires hydrolysis of the analyte, with the formation of
    methylamine, which reacts with  o-phthalaldehyde to form a
    fluorophore. Since aldicarb nitrile does not hydrolyse to form
    methylamine, it cannot be detected (Krause, 1985a).

         US EPA (1984) reported that high-performance liquid
    chromatography (HPLC) can be used to determine
     N-methyl-carbamoyloximes and  N-methylcarbamates in drinking-water.
    With this method, the water sample is filtered and a 400-µl aliquot is
    injected into a reverse-phase HPLC column. Compounds are separated by
    using gradient elution chromatography. After elution from the column,
    the compounds are hydrolysed with sodium hydroxide. The methylamine
    formed during hydrolysis reacts with  o-phthalaldehyde (OPA) to form
    a fluorescent derivative, which is detected with a fluorescence
    detector. The estimated detection limit for this method is 1.3 µg

         Reding (1987) suggested that samples be kept chilled, acidified
    with hydrochloric acid to pH 3, and dechlorinated with sodium
    thiosulfate. Other procedures used were the same as those described in
    the previous paragraph.

         In a collaborative study, Krause (1985a,b) reported an LC
    multi-residue method for determining the residues of
     N-methylcarbamate insecticides in crops. The average recovery for 11
    carbamates (which included aldicarb and aldicarb sulfone) from 14
    crops was 99%, with a coefficient of variation of 8% (fortification
    levels of 0.03-1.8 mg/kg), and for aldicarb sulfoxide, a very polar
    metabolite, was 55% and 57% at levels of 0.95 and 1.0 mg/kg,
    respectively. Methanol and a mechanical ultrasonic homogenizer were
    used to extract the carbamates. Water-soluble plant co-extractives and
    non-polar plant lipid materials were removed from the carbamate
    residues by liquid-liquid partitioning. Additional crop co-extractives
    (carotenes, chlorophylls) were removed with a Nuchar S-N-silanized
    Celite column. The carbamate residues were then separated on a
    reverse-phase LC column, using acetonitrile-water gradient mobile
    phase. Eluted residues were detected by an in-line post-column
    fluorometric detection technique. Six laboratories participated in

    this collaborative study.  Each laboratory determined all the
    carbamates at two levels (0.05 and 0.5 mg/kg) in blind duplicate
    samples of grapes and potatoes. Repeatability coefficients of
    variation and reproducibility coefficients of variation for all
    carbamates in the two crops averaged 4.7 and 8.7%, respectively. The
    estimated limit of quantification was 0.01 mg/kg.

         Ting & Kho (1986) discussed a rapid analytical method using HPLC.
    They modified their previous method (Ting et al., 1984) by using a
    25-cm CH-Cyclohexyl column instead of the 15-cm C-18 column. This
    modification resulted in the separation of the interference peak found
    in watermelon co-extractives. The separation of the interference peak
    and the aldicarb sulfoxide peak was made possible by the additional 10
    cm in the length of the column and the higher polarity of the
    CH-Cyclohexyl. Acetonitrile and methanol were used in the extraction
    and derivatization procedure before the HPLC determination. Water
    melons fortified with aldicarb sulfoxide at 0.1, 0.2, and 0.4 mg/kg
    showed a mean recovery of 74-76%.

         Chaput (1988) described a simplified method for determining seven
     N-methylcarbamates (aldicarb, carbaryl, carbofuran, methiocarb,
    methomyl, oxamyl, and propoxur) and three related metabolites
    (aldicarb sulfoxide, aldicarb sulfone, and 3-hydroxy-carbofuran) in
    fruits and vegetables. Residues are extracted from crops with
    methanol, and co-extractives are then separated by gel permeation
    chromatography (GPC) or GPC with on-line Nuchar-Celite clean-up for
    crops with high chlorophyll and/or carotene content (e.g., cabbage and
    broccoli). Carbamates are separated on a reverse-phase liquid
    chromatography column, using a methanol-water gradient mobile phase.
    Separation is followed by post-column hydrolysis to yield methylamine
    and by the formation of a flurophore with  o-phthalaldehyde and
    2-mercaptoethanol prior to fluorescence detection. Recovery data were
    obtained by fortifying five different crops (apples, broccoli,
    cabbages, cauliflower, and potatoes) at 0.05 and 0.5 mg/kg. Recoveries
    averaged 93% at both fortification levels, except in the case of the
    very polar aldicarb sulfoxide for which recoveries averaged around 52%
    at both levels. The coefficient of variation of the method at both
    levels was < 5% and the limit of detection, defined as five times the
    baseline noise, varied between 5 and 10 µg/kg, depending on the

         The International Register of Potentially Toxic Chemicals (IRPTC,
    1989) reported a GLC-FPD method for aldicarb analysis in foodstuffs.
    The limit of quantification was 0.01-0.03 mg/kg with a recovery rate
    of 76-125%. In this method, the acetone/dichloromethane-extracted
    sample is evaporated to dryness and the residue is dissolved in a
    buffered solution of potassium permanganate in water in order to
    oxidize the thioether pesticide and its sulfoxide metabolite to the
    corresponding sulfone. Aldicarb sulfone is then extracted with
    dichloromethane and the extract is evaporated to dryness. The residue
    is dissolved in acetone and the solution is analysed by GC-FPD using
    a pyrex column filled with 5% ov-225 on chromosorb W-HP, 150-180 U
    (the column temperature is 175 °C and the carrier gas is nitrogen with
    a flow rate of 60 ml/min).


    3.1  Natural occurrence

         Aldicarb is a synthetic insecticide; there are no natural sources
    of this ester.

    3.2  Anthropogenic sources

    3.2.1  Production levels, processes, and uses

         Aldicarb is a systemic pesticide used to control certain insects,
    mites, and nematodes. It is applied below the soil surface (either
    placed directly into the seed furrow or banded in the row) to be
    absorbed by the plant roots. Owing to the potential for dermal
    absorption of carbamate insecticides (Maibach et al., 1971), aldicarb
    is produced only in a granular form. The commercial formulation,
    Temik, is available as Temik 5G, Temik 10G, and Temik 15G, which
    contain 50, 100, and 150 g aldicarb/kg dry weight, respectively. The
    metabolite aldicarb sulfone is also used as a pesticide under the
    common name aldoxycarb. Aldicarb is usually applied to the soil in the
    form of Temik 5G, 10G, or 15G granules at rates of 0.56-5.6 kg ai/ha.
    Soil moisture is essential for its release from the granules, and
    uptake by plants is rapid. Plant protection can last up to 12 weeks
    (Worthing & Walker, 1987), but actual insecticidal activity may vary
    from 2 to 15 weeks, depending on the organism involved and on the
    application method (Hopkins & Taft, 1965; Cowan et al., 1966; Davis et
    al., 1966; Ridgway et al., 1966). The effective life of this
    insecticide will vary, depending on the type of soil, the soil
    moisture, the soil temperature, the rainfall and irrigation
    conditions, and the presence of soil micro-organisms.

         Aldicarb is approved for use on a variety of crops, which include
    bananas, cotton plants, citrus fruits, coffee, maize, onions, sugar
    beet, sugar cane, potatoes, sweet potatoes, peanuts, pecans, beans
    (dried), soybeans, and ornamental plants (FAO/WHO 1980; Berg, 1981).
    Its use in the home and garden has been proscribed by the

         Since aldicarb is used in a granular form, this reduces the
    handling hazards, as water is necessary for the active ingredient to
    be released. Respirators and protective clothing should, however, be
    used in certain field application settings (Lee & Ransdell, 1984).  World production figures

         In the USA, a total of 725 tonnes was sold domestically for
    commercial use in 1974 (SRI, 1984).

         The US EPA (1985) estimated that aldicarb production from 1979 to
    1981 ranged from 1360 to 2130 tonnes/year. In 1988, the US EPA
    estimated that between 2359 and 2586 tonnes of aldicarb were applied
    annually in the USA (US EPA, 1988a). More recent world production
    figures are not available.  Manufacturing processes

         Aldicarb is produced in solution by the reaction of methyl
    isocyanate with 2-methyl-2-(methylthio)propanal-doxime (Payne et al.,
    1966). During normal production, loss to the environment is not


    4.1  Transport and distribution between media

         The fate and transport of aldicarb and its decomposition products
    in various types of soil have been studied extensively under
    laboratory and field conditions. Owing to the physical properties of
    aldicarb such as its low vapour pressure, its commercial granular
    form, and its application beneath the surface of the soil, the vapour
    hazard of aldicarb is low. Thus the fate of aldicarb in the atmosphere
    has not received much attention. Similarly, its fate in surface water
    has not been extensively studied. However, the rates and mechanisms of
    the hydrolysis of aldicarb have been studied in the laboratory in some

    4.1.1  Air

         No studies on the stability or migration of aldicarb in the air
    over or near treated fields have been reported.  Laboratory migration
    studies with radiolabelled aldicarb in various soil types showed a
    loss of the applied substrate. This loss could not be explained unless
    aldicarb or its decomposition products had been transferred to the
    vapour phase (Coppedge et al., 1977). When 34 mg of 14C-aldicarb
    granules was applied 38 mm below the surface of a column of soil
    contained in a 63 x 128 mm poly-propylene tube, about 43% of the
    radiolabel was collected in the atmosphere above the column.
    Additional experiments showed that the transfer of radioactivity to
    the surrounding atmosphere was inversely proportional to the depth of
    application in the soil.  When 14C- and 35S-labelled aldicarb were
    used separately in similar experiments, only the experiments in which
    the 14C-labelled compound was used led to a transfer of
    radioactivity to the surrounding atmosphere, thus showing that the
    volatile compound was a carbon-containing breakdown product rather
    than aldicarb  per se.

         In a subsequent study with aldicarb using 14C at the
     S-methyl,  N-methyl, and tertiary carbon, Richey et al. (1977)
    reported that 83% of the radiolabel was recovered as carbon dioxide
    from a column of soil. The rate of degradation depended on the
    characteristics of the soil, e.g., pH and humidity.

         Supak et al. (1977) reported that when aldicarb (1 mg/g) was
    applied to clay soil and placed in a volatilizer, its volatilization
    was very limited. The authors stated that the possibility of aldicarb
    causing an air contamination hazard when it is applied in the field is
    negligible since it is applied at a rate of only 1.1-3.4 kg/ha and is
    inserted to 5-10 cm below the soil surface.

    4.1.2  Water and soil

         There have been numerous studies on aldicarb, under field and
    laboratory conditions, to investigate its movement through soil and
    water, persistence, and degradation. While earlier studies suggested
    that aldicarb degraded readily in soil and did not leach, later
    identification of residues in wells indicated that persistence could
    be longer than predicted and that mobility was greater. Laboratory
    studies have given variable results and the only totally reliable data
    are from full-scale field studies.

         In one of the few studies conducted with natural water (Quraishi,
    1972), rain overflow and seepage water were collected from ditches
    near untreated fields, filtered, and then treated with aldicarb at a
    concentration of 100 mg/litre. Solutions were stored in ambient
    lighting at temperatures ranging from 16 to 20 °C. It took 46 weeks
    for the aldicarb concentration to decrease to 0.37 mg/litre.

         Following an extensive study under laboratory-controlled
    conditions, Given & Dierberg (1985) reported that the hydrolysis of
    aldicarb was dependent on pH. They found that the apparent first-order
    hydrolysis rate over the pH range 6-8 and at 20 °C was relatively slow
    (Table 2). Above pH 8 the increase in the hydrolysis rate showed a
    first-order dependence on hydroxide ion concentration. The authors
    stated that these studies probably represented a "worst-case"
    situation with respect to the persistence of aldicarb in water, since
    other means of aldicarb removal or decomposition (e.g.,
    volatilization, adsorption, leaching, and plant and microbial uptake)
    had been prevented.

         Hansen & Spiegel (1983) showed that aldicarb hydrolyses at much
    slower rates than aldicarb sulfoxide and aldicarb sulfone. Since
    aldicarb oxidizes fairly rapidly to the sulfoxide and at a slower rate
    to the sulfone, and subsequent hydrolysis of the oxidation products
    usually occurs, aldicarb does not persist in the aerobic environment.

         In his review, de Haan (1988) discussed leaching of aldicarb to
    surface water in the Netherlands. Some of the factors favourable to
    leaching are weak soil binding, high rainfall, irrigation practices,
    and low transformation rates of the oxidation products of aldicarb.

         Aharonson et al. (1987) reported that hydrolysis of aldicarb is
    one of the abiotic chemical reactions that is linked to the detection
    of the pesticide in the ground water. The hydrolysis half-life at pH
    7 and 15 °C has been estimated by these authors to be as long as
    50-500 weeks.

        Table 2. Apparent first-order rate constant (k), half-life (t´), and
    coefficient of variation of the regression line (r2) for aldicarb
    hydrolysis at 20 °C in pH-buffered distilled watera

    pH          Period     k (day-1)b          t´b               r2
                (days)                         (days)

    3.95        89         5.3 x 10-3            131           0.86

    6.02        89         1.2 x 10-3            559           0.90

    7.96        89         2.1 x 10-3            324           0.62

    8.85        89         1.3 x 10-3             55           0.98

    9.85        15         1.2 x 10-1              6           1.00

    a  Adapted from Given & Dierberg (1985).
    b  Rates and resulting half-life values for pH 6-8 represent
       only estimates since the slopes of the log percentage
       remaining versus time regression lines were probably not
       significantly different from zero.

             The products of aldicarb hydrolysis at 15 °C under alkaline
    conditions (pH 12.9 and 13.4) are aldicarb oxime, methylamine, and
    carbonate (Lemley & Zhong, 1983). The half-lives of hydrolysis at
    these two pHs are 4.0 and 1.3 min, respectively. Other hydrolysis
    data, determined at pH 8.5 and 8.2, yielded rates with half-lives of
    43 and 69 days, respectively (Hansen & Spiegel, 1983; Krause, 1985a).
    Lemley et al. (1988) reported that at pH values of 5-8 the sorption of
    aldicarb, aldicarb sulfoxide, and aldicarb sulfone decreases as the
    temperature increases from 15 to 35 °C.

         Andrawes et al. (1967) applied the pesticide at the recommended
    rate of 3.4 kg/ha to potato fields and found that < 0.5% of the
    original dose remained at the end of a 90-day period. In fallow soil,
    decomposition of aldicarb to its sulfoxide and sulfone was rapid, >
    50% of the administered compound dissipating within 7 days after
    application. Peak concentrations of the aldicarb sulfoxide (8.24
    mg/kg) and aldicarb sulfone (0.8 mg/kg) were reached at day 14 after
    the application.

         Ou et al. (1986) investigated the degradation and metabolism of
    14C-aldicarb in soils under aerobic and anaerobic conditions. They
    found that under aerobic conditions, aldicarb rapidly disappeared and
    aldicarb sulfoxide was rapidly formed; the latter in turn was slowly
    oxidized to aldicarb sulfone. The sulfoxide was the principal
    metabolite in soils under strictly aerobic conditions. Although the

    parent compound aldicarb persisted considerably longer in anaerobic
    soils, anaerobic half-lives for total toxic residue (aldicarb,
    aldicarb sulfoxide, and aldicarb sulfone) in subsurface soils were
    significantly shorter than under aerobic conditions.

         A number of factors, including soil texture and type, soil
    organic content, soil moisture levels, time, and temperature, affect
    the rate of aldicarb degradations (Coppedge et al., 1967; Bull, 1968;
    Bull et al., 1970; Andrawes et al., 1971a; Suspak et al., 1977). Bull
    et al.  (1970) reported that soil pH had no significant effect on the
    breakdown of aldicarb, but Supak et al. (1977) noted an increase in
    the rate of degradation when the pH was lowered.

         Lightfoot & Thorne (1987) investigated the degradation of
    aldicarb, aldicarb sulfoxide, and aldicarb sulfone in the laboratory
    using distilled water, water extracted from soil, and water with soil
    particles (Table 3). Degradation of all three compounds was greatest
    in the uppermost "plough" layer of the soil profile and much higher in
    the presence of soil particulates. Even after sterilization of the
    soil, degradation was fast in this layer, indicating that the effect
    of particulate matter is not entirely microbial. Degradation continued
    in the saturated zone (ground water) at a slower rate (particularly
    for the sulfoxide and sulfone). A further series of experiments
    investigated the degradation of mixtures of aldicarb sulfoxide and
    sulfone in soil and water from the saturated zone of two soil types
    (Table 4). The half-life was longer in the acidic Harrellsville soil
    than the alkaline Livingston soil. As in the case of laboratory
    experiments, the presence of particulates considerably increased the
    rate of degradation of the carbamates. Investigation of many variables
    in the laboratory led the authors to conclude that pH, temperature,
    redox potential, and perhaps the presence of trace substances can all
    affect degradation rates. They believed that laboratory
    experimentation could not provide definitive results without the
    identification of critical variables and that field observation was a
    more reliable indicator of aldicarb degradation

        Table 3.  Degradation rates for aldicarb, aldicarb sulfoxide,
              and aldicarb sulfonea
                                                  Half-life at 25 °C (days)b

                                       Aldicarb                 Total carbamatesc

    Plough-layer soil
         sterilized                   2.5 (2.3-2.6)              10 (7-16)
         unsterilized                 1.0 (0.9-1.1)              44 (39-50)

    Soil water
         sterilized                  1679 (1056-4064)          1924 (1133-6370)
         unsterilized                 156 (143-176)             175 (158-195)

    Distilled water (no buffers)      671 (507-994)             697 (518-1064)

    Saturated zone soil and water
         sterilized                    15 (14-16)                16 (15-18)
         unsterilized                  37 (33-42)               123 (115-132)

    a    From: Lightfoot & Thorne (1987).
    b    Values in parentheses represent 95% confidence intervals.
    c    Aldicarb, aldicarb sulfoxide, and aldicarb sulfone.
    pH measurements
         sterilized soil water: 6.6-7.0 for 238 days;
         4.8-5.0 at day 368 unsterilized soil water: 6.6-6.7 for 56
         days; 4.2-4.4 at day 238, 3.2 at day 368 distilled water:
         7.3-7.5 for 238 days, 6.2-6.8 at day 368 saturated zone soil
         and water: 4.1-4.5 throughout entire study.
         Coppedge et al. (1977) studied the movement and persistence of
    aldicarb in four different types of soil in laboratory and field
    settings using a radiolabelled substrate. Samples of clay, loam,
    "muck" (soil with high organic content), and sand were packed in
    polypropylene columns (63 x 128 mm), saturated with water, and
    maintained at 25 °C throughout the study. Radiolabelled aldicarb
    granules (34 mg) were applied to each column at a point 38 mm below
    the soil surface. Water was then applied to each soil column at a rate
    of 2.5 cm/week for the next 7 weeks. The water eluted through the
    columns was collected and analysed for radiolabel. At the end of the
    7-week period, the soil was removed in layers 25 mm thick and analysed
    for residual radiolabel. The results of this study are shown in Tables
    5 and 6. The radiolabel (< 1%) in the loam and clay soils remained in
    the upper layers of the column, close to where it had been applied. In
    the sand, the residual radiolabel (2-3%) passed through to the lower

    parts of the column. A much higher percentage (5-6%)  of the
    radiolabel was retained in the muck soil column and was evenly
    distributed along the column. The radiolabel leached into the water
    eluted from the sand was 8-10 times greater than that from the other
    soil types. The nature of the decomposition products (ultimately shown
    to be carbon dioxide) resulted in some loss to the atmosphere
    surrounding the soils. The data in Table 6 indicate that most of the
    radioactivity retained in clay and loam soils represented aldicarb,
    sulfoxide whereas that in sand largely represented the parent
    compound. Greater leaching through sand decreased loss to the
    atmosphere by degradation to carbon dioxide.

         Coppedge et al. (1977) also studied the persistence  of aldicarb
    using field lysimeters. Aldicarb (34 mg), labelled with 35S, was
    added to columns (63 x 128 mm) containing Lufkin fine sandy loam soil
    at a point 76 mm below the surface. The contents were moistened with
    water and then buried in the same type of soil at a depth where the
    insecticide granules were 152 mm below the surface.  The experiment
    lasted for 7 weeks and rain was the only other source of moisture. The
    column recovered 3 days after the application yielded 71% of the
    radiolabel, while the column recovered at the end of 7 weeks yielded
    only 0.9%. This suggested an approximate half-life for the aldicarb of
    < 1 week, and the label distribution suggested an upward movement
    through volatilization of the decomposition products. The authors
    therefore concluded that there was little danger that aldicarb would
    move into the underground water supply in this type of soil.

         Bowman (1988) studied the mobility and persistence of aldicarb
    using field lysimeters containing cores (diameter, 15 cm; length, 70
    cm) of Plainfield sand. Half of the cores received only rainfall,
    while the remainder received rainfall plus simulated rainfall (50.8
    mm) on the second and eighth days after treatment, followed by
    simulated irrigation for the duration of the study. The results of
    this study indicated that under normal rainfall about 9% of the
    applied aldicarb leached out of the soil cores as sulfoxide or
    sulfone, whereas, in cores receiving supplementary watering, up to 64%
    of applied aldicarb appeared in the effluent principally as sulfoxide
    or sulfone.

        Table 4.  Degradation rates for aldicarb sulfoxide and aldicarb sulfone mixtures in groundwater degradation mechanism studiesa
                                                      Sterilized (25 °C)                         Unsterilized (25 °C)
    Soil type and medium
                                               Half-lifeb                pHc              Half-lifeb                   pHc

    Harrellsville, NC
         saturated zone soil and water                                                    137 (117-165)                5

    Harrellsville, NC (first set)
         saturated zone soil and water          378 (287-550)           4.3              1910 (1170-5180)              4.2
         coarse-filtered water                 1100 (760-1970)          4.6            > 2000                          4.6
         fine-filtered water                 > 2000                     4.6            > 2000                          4.2

    Livingston, CA (original data)
         saturated zone soil and water                                                    8 (7-10)                     7

    Livingston, CA
         saturated zone soil and water          1.3 (1.2-1.4)           9.0               7.5 (6.9-8.1)                8.4
         coarse-filtered water                 19 (17-22)               7.7               6.0 (5.7-6.3)                8.3

    a    From: Lightfoot & Thorne (1987).
    b    Half-life (days) for carbamate residues.  Values in parentheses represent 95% confidence intervals.  Since the experiments
         were conducted for only 1 year, half-life estimates greater than about 600 days are not as reliable as other estimates. 
         Half-lives longer than about 2000 days could not be determined.
    c    Approximate average value during experiment.

    Table 5.  Distribution and persistence of 14C-aldicarb equivalents in soil columnsa,b


                                  Percentage of total dose in the various layers                        Percentage of total dose

    Soil type                                                           Total    Unextractable  In leached
                      0-25 c    25-50      50-75     75-100   100-128  extracted  residue from     water d      Recovered        Lost
                                                                      from soil     soil

    Houston clay       0.4       0.1       0.1        T         T        0.6       2.5           12.5           15.6           84.4

    Lufkin loam        1.2       0.3       0.1       0.1        T        1.7       3.0            3.9            8.6           91.4

    Coarse sand         T         T        0.2       0.5       2.0       2.7       0.2           84.0           86.9           13.1

    Muck               8.7       5.3       8.5       5.6       4.8      32.9       7.1            3.5           43.5           56.5


    a    From: Coppedge et al. (1977).
    b    Results are the average from triplicate samples. Trace amounts (T) = < 0.1% of total dose.
    c    Layers are indicated by the distance (in mm) from the surface.
    d    Water that passed through the columns after the weekly addition of moisture.

    Table 6. 14C-labelled aldicarb and metabolites in water eluted through soil columnsa,b

                                                Percentage of total dose recovered at indicated days after treatment

    Soil type and compounds       3         10        16        23        29        35        41        47        53


         aldicarb                                    0.5       0.2                 T         0
         sulfoxide                                   3.2       1.9                 0.4       0.2
     sulfone                                         0         T                   T         0
     other metabolites                               0.7       0.6                 0.3       0.2

    Total                       0        3.2        4.4       2.7       0.8       0.7       0.4       0.3       0
    Accumulative total       0        3.2        7.6      10.3      11.1      11.8      12.2      12.5      12.5

         aldicarb                                    7.3      31.5                 5.0       5.4       2.3
         sulfoxide                                   0.9       2.6                 1.6       2.0       2.1
         sulfone                                     0         0                   0         0         0
          other metabolites                          0.2       1.9                 0.4       0.5       1.1

    Total                       0        3.5        8.4      36.0       9.2       7.0       7.9       5.5       6.7
    Accumulative total       0        3.5       11.9      47.9      57.1      64.1      72.0      77.5      84.0

    Table 6 (contd). 14C-labelled aldicarb and metabolites in water eluted through soil columnsa,b

                                                Percentage of total dose recovered at indicated days after treatment

    Soil type and compounds       3         10        16        23        29        35        41        47        53

         aldicarb                                    T                   T                   T         0
         sulfoxide                                   0.9       0.3       0.2       0.3       0.2       0.3
         sulfone                                     0         0                   T         T
         other metabolites                           0.2       T         0.2       T         0.1       0.2

    Total                        0        0.7       1.1       0.3       0.4       0.3       0.3       0.5       0.3
    Accumulative total        0        0.7       1.8       2.1       2.5       2.8       3.1       3.6       3.9

         aldicarb                                              T
         sulfoxide                                             0.1
         sulfone                                               0
         other metabolites                                     0.2

    Total                        0        0.2       0.6       0.9       0.9       0.3       0.1       0.3       0.3
    Accumulative total        0        0.2       0.8       1.7       2.6       2.9       3.0       3.3       3.6

    a    From: Coppedge et al. (1977).
    b    Results are the average from triplicate samples. Trace amounts (T) = < 0.1% of total dose.  Where a "total" value is given
          without values for each component, the volume of samples was insufficient for individual analyses.
         Andrawes et al. (1971a) studied the fate of radio-labelled
    aldicarb ( S-methyl-14C-Temik) in potato fields. The initial soil
    concentration was 13.1 mg/kg, which fell to 25.6 and 9.5% of the
    applied amount after 7 and 90 days, respectively. Samples taken as
    early as 30 min after the application showed that 12.7% of the
    aldicarb had already been converted to aldicarb sufoxide. By day 7 it
    had increased to 48%. In fallow soil, aldicarb was applied as an
    acetone/water solution at the same level as that used in the planted
    field. The dissipation of 14C residues occurred at a relatively slow
    rate for the first 2 weeks and then at a faster rate. The breakdown
    products in both the fallow and planted fields were essentially the

         LaFrance et al. (1988) studied the adsorption characteristics of
    aldicarb on loamy sand and its mobility through a water-saturated
    column in the presence of dissolved organic matter. The results of
    these studies suggested that aldicarb does not undergo appreciable
    complexation with dissolved humic materials found in the interstitial
    water of the unsaturated zones. Thus the presence of dissolved humic
    substances in the soil interstitial water should not markedly affect
    the transport of the pesticide towards the water table.

         Woodham et al. (1973a) studied the lateral movement of aldicarb
    in sandy loam soil. They applied the granular commercial formulation
    of the pesticide (Temik 10G) to irrigated and non-irrigated fields at
    a rate of 16.8 kg/ha and placed it 15-20 cm to the side of cotton
    seedlings and 12.5-15 cm deep. Soil samples were collected throughout
    the growing season from a depth of 15 cm, from the bottom of a creek
    adjacent to a treated field, and from sites 0.40 and 1.61 km
    downstream. The aldicarb used in this study was found to have a short
    residence time. Levels in the treated field fell to 15% within one
    month. Only 8% remained after 47 days. No residues were found after 4
    months and no aldicarb was detected either between rows or in the bed
    of the creek that collected water drainage.  The authors concluded
    that aldicarb was translocated into crop plants and weeds but that
    there would be no carry-over of aldicarb or its metabolites from one
    growing season to another (Woodham et al., 1973b). The results of
    studies by Andrawes et al. (1971a) and Maitlen & Powell (1982) agree
    with the observations of Woodham and his colleagues. Gonzalez & Weaver
    (1986) failed to detect aldicarb or its breakdown products in run-off
    water from a field treated with aldicarb in California, USA.

         The method and timing of application can also affect the
    migration and degradation of aldicarb (Jones et al., 1986). Aldicarb
    was applied in-furrow during the planting of potatoes and as a
    top-dressing at crop emergence. At the end of the growing season the
    residues from the first application were found primarily in the top
    0.6 m of soil, and the residues from the emergence application were
    found primarily in the top 0.3 m of soil.

         In a three-year Wisconsin potato field study (sandy plain),
    Fathulla et al. (1988) monitored aldicarb residues in the saturated
    zone ground water under fluctuating conditions of temperature, pH, and
    total hardness. Soils were well drained sands, loamy sands or sandy
    loams (with 1 to 2% organic matter). The water table was high with a
    depth to the saturated zone of between 1.3 and 4.6 m. Sampling wells
    were bored to a maximum of 7.5 m for groundwater sampling. Rothschild
    et al. (1982) had found all residues of aldicarb (and its breakdown
    products) within the upper 1.5 m of the ground water in the same area
    in an earlier study. This is consistent with the views of both groups
    of authors that movement of aldicarb will occur in these aquifers. The
    report of Fathulla et al. (1988) indicated that detection and
    persistence of aldicarb in the ground water were dependent on
    alkalinity and temperature. Movement of aldicarb was lateral as well
    as vertical and the authors emphasized the importance of seasonal
    changes in water table depth and precipitation as factors influencing
    movement. Degradation by microorganisms in the upper layers of the
    soil and ground water was noted and identified as a major factor in
    the short-term fate of the aldicarb. Hegg et al. (1988) measured the
    movement and degradation of aldicarb in a loamy sand soil in South
    Carolina, USA, and found that it degraded at a rate corresponding to
    a half-life of 9 days with essentially no residues present 4 months
    after application. This was a faster loss of aldicarb from the soil
    than in comparable studies in neighbouring areas. Using the
    unsaturated plant root zone model (PRZM) with rainfall records from 15
    years, aldicarb residues were predicted to be limited to the upper 1.5
    m, regardless of year-to-year variations in rainfall.

         Pacenka et al. (1987) sampled both soil cores and ground water
    from sites on Long Island (New York, USA), where earlier surveys had
    suggested contamination of wells with aldicarb and its breakdown
    products (the sulfone and sulfoxide). Three study areas were chosen
    with shallow (3 m), medium (10 m), and deep (30 m) water tables. All
    were overlain with sandy soils. Soil cores, driven to the depth of the
    water table, were taken from a field where aldicarb had been applied
    to potatoes and from surrounding areas. Ground water was sampled from
    188 wells of varying depth and at different distances from the
    aldicarb source.  Results indicated that the residence time of
    aldicarb (including the sulfone and sulfoxide) in the soil depended on
    the depth of the water table and, hence, the overlying unsaturated
    zone. In the shallow and medium depth water table sites, all aldicarb
    residues had disappeared within 3 years of the last use of the
    compound. In deeper unsaturated layers, aldicarb residues were present
    at increasing concentrations in soil water from 10 m down to the water
    table at 30 m. The uppermost 10 m was free of residues. Analysis of
    the groundwater samples showed lateral movement of residues extending
    from 120 m to 270 m "downstream" of the source in a single year. It
    was calculated that the relatively shallow aquifer in the area (which
    lay over a deeper aquifer capped by an impervious layer of clay) would

    flush residues from the area completely within 100 years and lead to
    concentrations below the drinking-water guideline level (New York) of
    7 µg/litre being attained between 1987 and 2010 (depending on
    assumptions for dispersion and degradation). Pacenka et al. (1987)
    revised this figure downwards on the basis of their more extensive
    field observations, although no firm figure could be advanced.

         Studies in other geographical areas of the USA, including those
    showing some residues of aldicarb or the sulfoxide and sulfone in
    wells, have demonstrated a shorter residence time and more rapid
    degradation than in the Long Island study (Jones et al., 1986; Wyman
    et al., 1987; Jones, 1986, 1987). In these studies there was little
    lateral movement of the ground water in the saturated zone. Water
    table levels in these areas were generally high and much of the
    sampling of the ground water was in the top 4-5 m of the saturated
    zone. Much greater lateral movement of ground water in the Florida
    Ridge area at a shallower depth than similar movement in Long Island
    also shifted the aldicarb residues away from the treated area.
    However, degradation was sufficiently fast in these soils to reduce
    the chance of contamination of wells used for drinking-water. An
    impervious layer 6 m down would prevent deeper contamination in this
    area (Jones et al., 1987a).

         A review of well and groundwater monitoring of aldicarb residues
    throughout the USA has been published by Lorber et al. (1989, 1990),
    which indicates geographical areas at greatest risk of water
    contamination and local restrictions on the use of aldicarb.

    4.1.3  Vegetation and wildlife

         The uptake of aldicarb and its residues by food crops and plants
    has been reported in several studies (Andrawes et al., 1974; Maitlen
    & Powell, 1982). Residue levels in plants and crops grown in
    aldicarb-treated soil are given in Table 7. Of the many varieties and
    species of birds and mammals studied, only the oriole had aldicarb
    residues (0.07 mg aldicarb equivalents per kg) in its tissues (Woodham
    et al., 1973b).

         In a study by Iwata et al. (1977), aldicarb was applied to the
    soil in orange groves at rates of 2.8, 5.6, 11.2, and 22.4 kg ai/ha.
    Residues found on day 118 after application in the soil were 0.03,
    0.16, 0.20, and 0.42 mg/kg, respectively. On day 193, samples were
    taken from the pulp of oranges grown in soil that had been given the
    highest amount (22.4 kg ai/ha) of aldicarb. The residues in these
    samples ranged from 0.02-0.03 mg/kg.

         After aldicarb was applied to the leaves of young cotton plants
    under field conditions, it was not translocated to other parts of the
    plant to any great extent (Bull, 1968). Two weeks after application, 

    93% of the recovered radiolabel was found at the application site. The
    remainder was spread evenly throughout the plant, including the roots
    and fruit.

    4.2  Biotransformation

         In plants, aldicarb is metabolized by processes involving
    oxidation to the sulfoxide and sulfone, as well as by hydrolysis to
    the corresponding oximes and, ultimately, to the nitrile.

         There have been several studies on the metabolism of aldicarb by
    the cotton plant. Metcalf et al. (1966) found that aldicarb was
    completely converted within 4-9 days to the sulfoxide, which was then
    hydrolysed to the oxime. The subsequent oxidation of the sulfoxide to
    the sulfone occurred more slowly and was found to lead to
    bioaccumulation in aged residues (Coppedge et al., 1967).

         When aldicarb (10 µl of an aqueous solution containing 10µg
    aldicarb) was applied to the leaves of cotton plants, 7.1% of the
    administered dose was converted to the sulfoxide within 15 min. Two
    days later there was no residual aldicarb in or on the plant tissues,
    and the principal metabolite (78.4% of the initial dose) was the
    sulfoxide. After 8 days, 7.4% of the initial dose was found as the
    sulfone while the nitrile sulfoxide and an unidentified metabolite
    were the final products of decomposition (Bull, 1968).

    4.3  Interaction with other physical, chemical or biological factors

    4.3.1  Soil microorganisms

         Kuseske et al. (1974) studied the degradation of aldicarb under
    aerobic and anaerobic conditions and found that degradation was much
    slower under anaerobic conditions. Jones (1976) studied the metabolism
    of aldicarb by five common soil fungi. The potential for aldicarb
    detoxification by these fungi (in decreasing order) was as follows:
     Gliocladium catenulatum > Penicillium multicolor = Cunninghamella
     elegans > Rhizoctonia sp. > Trichoderma harzianum . The major
    organosoluble metabolites were identified as aldicarb sulfoxide, the
    oxime sulfoxide, the nitrile sulfoxide, and smaller amounts of the
    corresponding sulfones, indicating that the metabolic pathways were
    similar to those found in higher plants and animals.

         Spurr & Sousa (1966, 1974) tested the effects of aldicarb and its
    metabolites on pathogenic and saprophytic microorganisms and found
    that some of the microorganisms appeared to use aldicarb as a carbon
    source. The various bacteria and fungi used in these tests showed no
    growth inhibition when aldicarb was added at levels up to 20 times
    those usually used in field conditions.

        Table 7. Residues (in mg/kg) of aldicarb and its sulfoxide and sulfone metabolites found in various
    crops grown in aldicarb-treated soila,b

    Replicate           Potato         Potato         Alfalfa        Alfalfa        Mint      Mustard        Radish    Radish
    no.                 leavesc        leaves         (transplanted) (seeded)       foliage   greens         tops      roots
                        (70)d          (408)          (456)          (456)          (408)     (408)          (408)     (408)

    3.4 kg ai/ha application

         1               7.65           0.52           0.14           0.16          0.02       ND             0.08     ND
         2               7.93           0.15           ND             0.04          0.01       O.03           0.07     ND
         3               8.11           1.34           0.09           0.05          0.05       0.08           0.05     ND
         4               8.74           1.27           0.24           0.14          0.10
         5               9.60           1.03           0.13           0.24          0.06

    Average              8.41           0.66           0.12           0.13          0.05       0.04           0.07     ND

    15.0 kg ai/ha application

         1              19.30           0.69           0.89           0.89          0.64       ND             0.27      0.04
         2              14.90           1.10           0.34           1.47          0.92       0.26           0.27      0.05
         3              20.80           1.12           0.43           0.26          0.37       0.40           0.18      0.03
         4              19.40           0.50           0.76           0.61          0.23
         5              22.60           1.96           1.37           8.37          1.55

    Average             19.40           1.07           0.76           2.32          0.74       0.22           0.24      0.04

    a    From: Maitlen & Powell (1982).
    b    Residues in this table were determined by oxidizing the aldicarb, aldicarb sufoxide, and aldicarb sulfone and then
          determining them as one combined compound, aldicarb sulfone.  ND = none detected; the lower limit of reliable detection for
          these samples was < 5.0 ng/aliquot analysed or < 0.02 mg/kg.
    c    These samples are from the crop of 1979.  All others are from the crop of 1980.
    d    Figures in parentheses are the interval in days between treatment of soil and sampling of plants.


    5.1  Environmental levels

    5.1.1  Air

         Since aldicarb is applied in granular form to the soil surface,
    it reaches the atmosphere only by upward migration and by
    volatilization. Thus, it is not transported to the atmosphere to any
    great extent and so is not expected to contribute a significant health
    threat from this source. In a volatilization study (Supak et al.,
    1977), a special apparatus was designed to determine the volatility of
    aldicarb from the soil. The air eluted from the apparatus after it had
    passed over soil samples containing dispersed aldicarb was analysed by
    the method of Maitlen et al. (1970). This method allowed the
    quantitative analysis of aldicarb and its two oxidation products, the
    sulfoxide and sulfone, both of which are toxic. Nontoxic decomposition
    products, such as the sulfoxide and sulfone oximes, both of which
    interfere with the determination of aldicarb sulfone by this method,
    were removed by LC.  When aldicarb was mixed with soil to a
    concentration of 1 mg/kg, only 2µg of aldicarb volatilized over the
    first 9 days of the experiment and subsequent losses increased to a
    steady-state rate of approximately 1µg/day. According to the authors,
    this rate of volatilization was almost negligible and not high enough
    to cause a potential health hazard.

    5.1.2  Water

         Run-off to surface water and leaching to aquifers used as sources
    of water for human consumption have been investigated. Aldicarb
    residues have been found in drinking-water wells in New York
    (Wilkinson et al., 1983; Varma et al., 1983), Wisconsin (Rothschild et
    al., 1982), and Florida (Miller et al., 1985). The US EPA groundwater
    team reported that they had found groundwater residues in 22 states
    (US EPA, 1988b). In Canada, water samples taken from private wells
    showed contamination with aldicarb up to 6.0 µg/litre; ground water
    from Quebec (maximum of 28 µg/litre) and Ontario (maximum of 1.1
    µg/litre) also contained detectable levels (Hiebsch, 1988).

         Prince Edward Island, Canada, is wholly dependent upon ground
    water from a highly permeable sandstone aquifer for domestic,
    agricultural, and industrial use. Priddle et al.  (1989) reported that
    12% of monitored wells exceeded the Canadian drinking-water guideline
    of 9µg/litre for aldicarb. The maximum level detected was 15 µg/litre.

         Following extensive agricultural use of aldicarb and as a result
    of a combination of environmental and hydro-logical conditions on
    eastern Long Island, New York, in 1978 the insecticide

    and its metabolites had leached into groundwater aquifers that
    constitute the major source of drinking-water for local inhabitants.
    In December 1978, detectable levels of aldicarb were found in 20 of 31
    water sources; similar results were obtained in the following June.
    When both private and community wells located near potato farms were
    sampled in August 1979, analyses revealed detectable levels of
    aldicarb in potable water.  In March 1980, the Department of Health
    Services in Suffolk County, New York, undertook an extensive sampling
    programme that included nearly 8000 wells. Union Carbide performed the
    analyses, with the New York Department of Health serving as the
    quality control arm. Levels of aldicarb ranging from trace amounts to
    > 400 µg/litre were detected in 27% of the wells sampled. Baier &
    Moran (1981)  reported that of 7802 wells sampled, 5745 (73.6%) did
    not have detectable concentrations of aldicarb, 1025 (13.1%) had
    concentrations in excess of the 7 µg/litre guideline of the New York
    State Department of Health, and the remaining 1032 (13.3%) had trace
    amounts of this insecticide.

         Aldicarb has been found at levels of 1-50 µg/litre in the ground
    water of the USA (Cohen et al., 1986; de Hann, 1988).

         The contamination of the Long Island (New York) aquifer by
    aldicarb at levels of up to 500 µg/litre (in one well) was attributed
    by Marshall (1985) to a combination of circumstances (high rainfall,
    coarse sandy soil, low soil temperatures, and a shallow water table)
    that favoured leaching. There have been some predictions that this
    undesirable situation would persist for only a year or two, but also
    some suggestions that wells could remain contaminated for up to a
    century. Marshall (1985) also voiced concern that under anaerobic
    conditions in cool climates, such as those in northern regions, the
    breakdown of aldicarb and its residues would be a much slower process.
    Contamination would also be favoured by heavy usage of Temik.

         During 1982, aldicarb was identified in several wells in the
    state of Florida (Miller et al., 1985). The state Commission of
    Agriculture and Consumer Services subsequently banned the use of Temik
    on citrus crops in 1983. A University of Florida task force was
    appointed to sample the 10 largest drinking-water systems that
    obtained water from groundwater sources in 35 counties. Neither
    aldicarb nor its oxidative sulfoxide or sulfone metabolites were
    detected in any of the almost 400 samples collected.

         During the application season of 1984 (January to April), 2040
    tonnes of aldicarb was used on citrus fruits at a rate of 5.6 kg ai/ha
    in more than 30 counties in Florida. No residues were detected in
    samples taken from community water systems, but trace amounts of
    aldicarb, aldicarb sulfoxide, and aldicarb sulfone were found in the

    Calloosahatchee River from which Lee County draws its drinking-water.
    (However, no residues were found in finished drinking-water in Lee
    County). The authors stated that the persistence of aldicarb and its
    metabolites in shallow ground water may also contaminate
    drinking-water. The results of a monitoring study by the Union Carbide
    Corporation (UCC) showed that in shallow ground water aldicarb can
    move further from its application point than originally predicted.

    5.1.3  Food and feed

         Residues have been detected on a variety of crops for which
    aldicarb is used (see section 3.2.1). In the USA, aldicarb
    intoxication from eating contaminated watermelons has been reported in
    California (Jackson et al., 1986) and in Oregon (Green et al., 1987),
    and two episodes of poisoning from eating aldicarb-contaminated
    cucumbers have been reported in Nebraska (Goes et al., 1980).
    Store-bought cucumbers, grown hydroponically, were found to contain
    between 7 and 10 mg aldicarb/kg (Aaronson et al., 1980). It should be
    noted that aldicarb is not approved for use on these crops.

         Laski & Vannelli (1984) reported the results of a survey of
    potatoes grown in New York State in 1982. Fifty samples, each
    consisting of 9 kg, were collected after harvest from four areas. In
    each of these areas, except one (Long Island), aldicarb was applied at
    rates of 14 to 22 kg/ha at planting stage. Samples were analysed for
    aldicarb, aldicarb sulfoxide, and aldicarb sulfone by the method of
    Krause (1980). Over 50% (23 out of 43) of potato samples obtained from
    areas where aldicarb was applied were positive for aldicarb sulfoxide
    (trace to 0.48 mg/kg)  and/or sulfone (trace to 0.20 mg/kg), but
    aldicarb itself was not detected. No residues were found in any of the
    7 samples from Long Island. The maximum concentrations were detected
    in samples from the North Eastern location, where there is sandy soil.
    Potatoes with the maximum concentration (0.48 mg/kg) were found to
    contain two and a half times higher concentrations (1.2 mg/kg) when
    reanalysed by a more sensitive method (Union Carbide, 1983). The
    investigators suggested that soil type and climatic conditions
    influenced residues in the crops.

         When Krause (1985b) analysed aldicarb and its oxidative
    metabolites in "market basket" potatoes, he detected levels of
    aldicarb sulfone ranging from < 0.01 to 0.18 mg/kg and of aldicarb
    sulfoxide from < 0.01 to 0.61 mg/kg.  All 39 samples collected
    between 1980 and 1983 contained residues of aldicarb or its

         Potato samples collected from farms in the north-central part of
    New York, where soil is of the wet muck type, contained lower aldicarb
    residues than did the rocky-sandy soil type found in the north-eastern
    part of the state, even though application rates were the same in both
    areas. These lower residue levels were the result of aldicarb
    decomposition associated with moisture. Cairns et al. (1984) described
    the persistence of aldicarb in fresh potatoes.

         Peterson & Gregorio (1988) reported upper 95 percentile residue
    levels of 0.0677 mg/kg in raw potatoes (tolerance = 1 mg/kg), 0.0658
    mg/kg in fresh bananas (tolerance = 0.3 mg/kg), and 0.0212 mg/kg in
    grapefruit (tolerance = 0.3 mg/kg) in a market basket survey conducted
    in the USA (national food survey). These authors also reported a
    maximum residue level of 0.82 mg/kg in raw potatoes obtained in
    controlled field trials, as well as upper 95 percentile residue levels
    as high as 0.43 mg/kg in raw potatoes, 0.12 mg/kg in bananas, and 0.17
    mg/kg in citrus products, estimated from the distribution of residue
    levels obtained in field trials.

    5.2  General population exposure

         The general population may be exposed to aldicarb and its
    residues primarily through the ingestion of food containing aldicarb
    and from contaminated water, as discussed in sections 5.1.2, 5.1.3.,
    and section 8. The largest documented episode of foodborne pesticide
    poisoning in North American history occurred in July 1985. This
    resulted from the consumption of Californian watermelons contaminated
    with up to 3.3 mg/kg of aldicarb sulfoxide (Ting & Kho, 1986).

         Hirsch et al. (1987) reported 140 cases of poisoning incidences
    in the Vancouver area of British Columbia, Canada. A review of the
    onset of symptoms and food consumed suggested illness associated with
    eating cucumbers contaminated with aldicarb. Analytical investigations
    confirmed that the cucumbers from one producer contained residues of
    total aldicarb up to 26 mg/kg.

         Petersen & Gregorio (1988) reported the results of a
    comprehensive analysis of aldicarb data from controlled field residue
    studies and provided estimates of the upper 95 percentile of residues
    in foods in the USA. The analysis showed that daily exposure at the
    upper 95 percentile consumption rate for aldicarb-treated commodities
    containing the estimated upper 95 percentile aldicarb residue levels
    would be approximately one-quarter of the daily exposure calculated by
    assuming that all of the aldicarb-treated commodities contained
    residues at the tolerance levels (e.g., 1.77 µg/kg per day versus 6.38
    µg/kg per day for the USA population). In addition, Petersen &
    Gregorio (1988) presented the results of a statistically designed 

    national food survey on the five commodities that were estimated to 
    be responsible for more than 90% of the dietary exposure to aldicarb 
    residues in the USA (bananas, white potatoes, sweet potatoes, oranges, 
    and grapefruit). Daily exposure to aldicarb at the 95 percentile 
    consumption rate for aldicarb-treated commodities containing the 
    95 percentile aldicarb residue levels, as estimated from the national 
    food survey, would be approximately 6% of the daily exposure calculated 
    by assuming aldicarb residue levels at the tolerance levels 
    (e.g. 0.40 µg/kg body weight per day versus 6.38 µg/kg per day for the 
    USA population).

         The highest daily exposure estimated from the results of the
    national food survey was 0.89 µg/kg per day for non-nursing infants
    and children (1-6 years of age).

         A US EPA survey indicated that the vast majority of wells
    contained levels of aldicarb residues less than 10 µg/litre and noted
    that heat treatment of water used in cooking would result in aldicarb
    residues no higher than 5 µg/litre (Cohen et al., 1986).

         Accidental leaks of several gases at a plant producing aldicarb
    in Institute, West Virginia, USA, required 135 people to be the
    hospitalized (Marshall, 1985).

    5.3  Occupational exposure during manufacture, formulation or use

         The dangers of inadequate safety precautions and improper dress
    and handling procedures are discussed in section 8. People involved in
    the manufacture and field application of aldicarb are potentially at
    higher risk than the general population (Doull et al., 1980) and
    should always take proper safety precautions.


    6.1  Absorption

         A number of studies on various mammalian and non-mammalian
    species have shown that aldicarb, as well as its sulfoxide and sulfone
    metabolites, is absorbed readily and almost completely from the
    gastrointestinal tract (Knaak et al., 1966a,b; Andrawes et al., 1967;
    Dorough & Ivie, 1968; Dorough et al., 1970; Hicks et al., 1972; Cambon
    et al., 1979). Andrawes et al. (1967) reported that the uptake of
    aldicarb and aldicarb sulfoxide from the gastro-intestinal tract of
    the rat was rapid and efficient. They recovered 80-90% of the
    radiolabel in the urine during the first 24 h after administration.
    Their observation was substantiated by Knaak et al. (1966a,b), who
    also recovered > 90% of the administered oral dose in rats.

         Cambon et al. (1979) reported the rapid uptake of aldicarb in
    pregnant rats. The rats showed overt signs of depression of
    cholinesterase activity < 5 min after they were given single oral
    doses of aldicarb ranging from 0.001 to 0.10 mg/kg. At all dose
    levels, acetylcholin-esterase activity was significantly decreased in
    fetal blood, brain, and liver 1 h after dosing.

         Dorough et al. (1970) recovered 92% of the doses (0.006-0.52
    mg/kg per day) of aldicarb and aldicarb sulfone in the urine of
    lactating Holstein cows dosed during a 14-day period. Dorough & Ivie
    (1968) found that > 90% of a single dose of 0.1 mg/kg administered
    orally to lactating Jersey cows was absorbed and excreted in the
    urine. In laying hens, oral doses of aldicarb and aldicarb sulfone
    were administered in a 21-day short-term feeding study and in a single
    capsule dose study, respectively. In the short-term feeding study,
    80-85% of each daily dose was excreted in the faeces during the
    following 24 h, while 90% of the total dose consumed was excreted
    within one week after the cessation of aldicarb intake. In the single
    dose study, 90% of the single oral dose was excreted within 10 days
    (Hicks et al., 1972).

         Feldman & Maibach (1970) reported the relatively efficient dermal
    uptake of carbamate insecticides in man (73.9% of a dermally applied
    dose of carbaryl was absorbed over a period of 5 days compared with
    10% for five other representative pesticides). The percutaneous uptake
    of aldicarb in water or in toluene has also been demonstrated
    qualitatively in rabbits (Kuhr & Dorough, 1976; Martin & Worthing,
    1977) and in rats (Gaines, 1969).

    6.2  Distribution

         The rapid depression of acetylcholinesterase activity in fetal
    and maternal blood and tissues observed after the oral administration
    of aldicarb to pregnant rats demonstrated that aldicarb or its toxic
    metabolites (the sulfoxide and sulfone) are distributed to the tissues
    by the systemic circulation (Cambon et al., 1979, 1980). The
    quantitative distribution of radiolabelled aldicarb and its
    metabolites in the tissues of female rats, given a single oral dose of
    0.4 mg aldicarb/kg, is shown in Table 8 (Andrawes et al., 1967).
    Aldicarb and its residues appeared to be distributed among the various
    tissues examined with no tendency to be sequestered or accumulated in
    any one tissue, since animals killed from 5 to 11 days after dosing
    had no detectable radiolabelled residues.

         Aldicarb and its metabolites were found to be concentrated in the
    livers of cows fed 0.12, 0.6, or 1.2 mg aldicarb/kg diet for up to 14
    days (Dorough et al., 1970).  Levels of the radiolabel in muscle, fat,
    and bone were low or below the detection levels. In a previous study,
    Dorough & Ivie (1968) found that 3% of the radiolabel was excreted in
    the milk of a lactating cow after a single oral dose of 0.1 mg/kg.

         Hicks et al. (1972) conducted a study in which single oral doses
    (0.7 mg/kg) of aldicarb or a 1:1 molar ratio of aldicarb and aldicarb
    sulfone were administered to laying hens. The radiolabel equivalents
    were greatest in the liver and kidneys for the first 24 h, much lower
    levels being found in fat and muscle. In a second study,
    aldicarb/aldicarb sulfone was administered at 0.1, 1.0, or 20 mg/kg
    diet for 21 days. Distribution to the tissues after this multiple
    dosing regimen was similar to that after the single dose, the highest
    residue levels appearing in the liver and kidneys.

        Table 8. Total aldicarb equivalents (mg/kg) in tissues of rats treated
             orally with 35  S-aldicarba

                                      Time period (days after dosing)b

                                Day 1              Day 2              Day 3             Day 4
                             W        D         W         D        W         D       W        D
    Heart                   0.12     0.44      0.09      0.32    0.08       0.29    0.11     0.38

    Kidneys                 0.16     0.56      0.08      0.25    0.06       0.16    0.07     0.21

    Brain                   0.11     0.35      0.02      0.08    0.08       0.25    0.05     0.19

    Lungs                   0.15     0.60      0.02      0.48    0.04       0.14    0.06     1.19

    Spleen                  0.27     1.08      0.04      0.12    0.10       0.37    0.05     0.17

    Liver                   0.16     0.28      0.07      0.22    0.07       0.21    0.05     0.14

    Leg muscle              0.16     0.61      0.02      0.07    0.05       0.20    0.04     0.12

    Fat                     0.23     0.72      0.11      0.12    0.09       0.11    0.03     0.04

    Bone                    0.11     0.15      0.09      0.13    0.06       0.08    0.02     0.04

    Stomach                 0.19     0.64      0.07      0.26    0.08       0.29    0.06     0.19

    Stomach contents        0.18     0.94      0.14      1.05    0.10       0.65    0.03     0.09

    Small intestine         0.18     0.74      0.13      0.45    0.10       0.30    0.06     0.16

    Small intestine         0.25     1.20      0.19      1.03    0.08       0.49    0.06     0.24

    Table 8 cont'd. Total aldicarb equivalents (mg/kg) in tissues of rats treated
            orally with 35  S-aldicarba
                                      Time period (days after dosing)b

                              Day 1               Day 2             Day 3             Day 4
                          W          D         W        D        W         D       W        D

    Large intestine       0.15       0.66      0.12     0.54    0.08       0.27    0.13     0.30

    Large intestine       0.18       0.67      0.05     0.24    0.09       0.39    0.04     0.16

    Blood                 0.16       0.74      0.14     0.18    0.08       0.21    0.05     0.17

    a     From: Andrawes et al. (1967).
    b     W = wet weight; D = dry weight.

    6.3  Metabolic transformation

         Carbamates undergo a limited number of  in vivo reactions:
    oxidation, reduction, hydrolysis, and conjugation (Ryan, 1971). In
    animals, the enzymes involved in these processes are found in the
    microsomal fraction of the liver homogenate. In the case of aldicarb,
    both oxidation of the sulfur to the sulfoxide and sulfone and
    hydrolysis of the carbamate ester group are involved (Andrawes et al.,
    1967). Although the hydrolysis reaction destroys insecticidal
    activity, both the sulfoxide and sulfone are active anticholinesterase
    agents (Andrawes et al., 1967; Bull et al., 1967; NAS, 1977). The
    metabolic pathways for aldicarb in the rat are shown in Fig. 1
    (Wilkinson et al., 1983). The metabolism of aldicarb in animals
    usually results in the formation of the sulfoxide, sulfone, oxime
    sulfoxide, oxime sulfone, nitrile sulfoxide, nitrile sulfone, and at
    least five other metabolites (Knaak et al., 1966a,b; Dorough et al.,
    1970). Aldicarb metabolites formed by incubation with liver microsomal
    enzymes are similar to the metabolites formed in plants and insects
    (Oonnithan & Casida, 1967). The rapid conversion to the sulfoxide and
    sulfone has been demonstrated in plants (Metcalf et al., 1966;
    Coppedge et al., 1967) and animals (Andrawes et al., 1967; Dorough &
    Ivie, 1968).

          In vitro studies by Oonnithan & Casida (1967) showed that the
    first stage in the metabolism of aldicarb involves the microsomal
    reduced nicotinamide adenine dinucleotide phosphate (NADPH) system to
    form the sulfoxide, but that the subsequent oxidation to the sulfone
    derivative occurs only to a small extent. Andrawes et al. (1967)
    confirmed these findings and showed that in the presence of the NADPH
    cofactor the production of metabolites increases by a factor of 15.
    The same authors also demonstrated that the principal urinary
    metabolites in the rat consist of hydrolytic products with only a
    small amount of carbamate. In studies with pig liver enzymes, Hajjar
    & Hodgson (1982) concluded that, under aerobic conditions and in the
    presence of NADPH, the FAD-dependent monooxygenase is responsible for
    the observed oxidation of the thio-ether in the primary metabolic
    step. The same authors found that sulfoxidation is enhanced rather
    than inhibited by  n-octylamine, a known inhibitor of cyto-chrome
    P-450-dependent oxygenation.

    6.4  Elimination and excretion in expired air, faeces, and urine

         Most studies on the elimination and excretion of aldicarb and its
    metabolites have used the radiolabelled compound. No kinetic
    coefficients have been reported, although studies in which rats (Knaak
    et al., 1966a,b; Andrawes et al., 1967; Dorough & Ivie, 1968; Marshall
    & Dorough, 1979), cows (Dorough & Ivie, 1968; Dorough et al., 1970),
    and chickens (Hicks et al., 1972) were used gave some information
    about the clearance rates, mechanisms, and routes of excretion. In all
    species, the principal excretion route for aldicarb and its

    metabolites (> 90%) is via the urine. A small amount of aldicarb and
    its metabolic products is excreted via the faeces (which is in part
    due to biliary excretion), or is exhaled as carbon dioxide.

         The total excretion of  S-methyl-C14-,  tert-butyl-C14-,
    and  N-methyl-C14-labelled aldicarb by rats after oral dosing was
    investigated by Knaak et al. (1966a). Within 24 h, the total excretion
    of the  S-methyl,  tert-butyl, and  N-methyl labels was
    approximately 90, 90, and 60%, respectively. For the  S-methyl- and
     tert-butyl-labelled compounds, > 90% was excreted via the urine and
    only 1.1% of the radiolabel was excreted as carbon dioxide. In a study
    on rats dosed orally with aldicarb (labelled in a different position
    and with different radioisotopes), Andrawes et al. (1967) showed that
    > 80% of the applied dose (labelled with 14C) was excreted over 24
    days, while 6.6% was excreted in the faeces within 4 days.

         The biliary excretion of aldicarb and its metabolites was studied
    by Marshall & Dorough (1979) in rats with cannulated bile ducts. A
    single oral dose of 14C-thiomethyl aldicarb (0.1 mg/kg) in 0.2 ml of
    vegetable oil was given by intubation, and urine, bile, and faeces
    were collected over the next 72 h. Biliary excretion accounted for
    2.6, 9.5, 22.9, 28.1, and 28.6% of the administered dose at 3, 6, 12,
    24, and 48 h after dosing, respectively. More than 64% was excreted in
    the urine over the 48-h period, and < 1% was recovered from the

         In a study by Dorough & Ivie (1968), 83% of an oral dose of 0.1
    mg/kg given to a lactating cow was recovered in the urine within 24 h,
    this increasing to 90% over 22.5 days. Only 2.85% of the radiolabel
    was recovered in the faeces within 8 days after dosing. All samples of
    milk taken from 3 h to 22.5 days after dosing contained the radiolabel
    and accounted for 3.02% of the administered dose.

         Hicks et al. (1972) dosed laying hens with 35S-aldicarb or with
    a 1:1 molar ratio of 14C-aldicarb and 14C-aldicarb sulfone. The
    dose (0.7 mg/kg) was administered orally in a gelatin capsule. In both
    cases, the label was excreted rapidly; 75% of the radiolabel was
    recovered in the faeces within 24 h and > 80% was recovered within 48
    h. Repeated dosing, twice a day for 21 days, resulted in a similar
    pattern of excretion, 80-85% of the daily dose being excreted in the
    faeces within 24 h after the administration of each dose.


    FIGURE 1


    7.1  Single exposure

         The acute oral and dermal toxicity of aldicarb has been studied
    in several species (Table 9). Oral LD50 values appear to be fairly
    consistent (0.3-0.9 mg/kg body weight in the rat) and not dependent on
    the carrier vehicle. Oral administration of the granular formulation
    of aldicarb gives LD50 values proportional to the active ingredient
    content (Carpenter & Smyth, 1965). The oral LD50 values for aldicarb
    sulfoxide and sulfone in rats are 0.88 mg/kg body weight and 25.0
    mg/kg body weight, respectively (Weil, 1968). Dermal LD50 values
    vary with the mode of application and the carrier vehicle used.
    Several acute dermal toxicity studies using different carrier vehicles
    have been reported. The dermal 24-h LD50 in rabbits for a single
    application of aldicarb in water was 32 mg/kg body weight (West &
    Carpenter, 1966).  However, when aldicarb was tested in propylene
    glycol, the observed dermal LD50 was 5 mg/kg body weight (Striegel
    & Carpenter, 1962). A dermal LD50 of 141 mg/kg body weight was
    reported in a 4-h exposure study on rabbits using dry Temik 10G
    formulation. On the basis of results of acute oral and dermal toxicity
    studies, aldicarb should be labelled as extremely hazardous (WHO,

         Carpenter & Smyth (1965) reported 100% mortality within 5 min
    when rats, mice, and guinea-pigs were exposed to aldicarb dust at a
    concentration of 200 mg/m3. The rats and mice were more sensitive
    than the guinea-pigs. Rats survived a dust concentration of 6.7
    mg/m3 for 15 min, but five out of six died after 30 min. All rats
    survived for 8 h when exposed to a saturated vapour concentration.
    Rats were also less sensitive to aerosol concentrations than to
    similar concentrations of the dust. Two of six rats survived an 8-h
    exposure to an aerosol concentration of 7.6 mg/m3. Weil & Carpenter
    (1970)  determined an LD50 of 0.44 mg/kg body weight in rats by the
    intraperitoneal route.

        Table 9.  Acute toxicity of aldicarb and its formulation products

    Compound       Route of       Vehicle             Species  LD50                  Reference
                   adminis                                     (mg/kg body
                   tration                                     weight)a
    Technical      oral                               rat           0.93           Martin & Worthing
    aldicarb                                                                       (1977)

                   oral           peanut oil          rat        M: 0.8            Gaines (1969)
                                                                 F: 0.65

                   oral           corn oil            rat        M: 0.09           Carpenter & Smyth

                   oral           corn oil            rat        F: 1.0            Weiden et al. (1965)

                   oral           not specified       mouse         0.3            Black et al. (1973)

                   skin           xylene              rat        M: 3.0            Gaines (1969)
                                                                 F: 2.5

                   skin           not specified       rabbit        5.0            Weiden et al. (1965)

                   skin           propylene glycol    rabbit        5.0            Striegel & Carpenter
                                  (5%)                                             (1962)

    Temik 10G      oral           not specified       rat           7.7            Weil (1973)

                   dermal         water               rat         400              Carpenter & Smyth
                   (4 h)                                                           (1965)

                   dermal         none                rat         200              Carpenter & Smyth


    Table 9 cont'd.  Acute toxicity of aldicarb and its formulation products

    Compound       Route of ad-      Vehicle             Species  LD50               Reference
                   ministration                                   (mg/kg body

                   dermal            none                rat         850            Weil (1973)

                   dermal            water (50%)         rabbit       32            West & Carpenter

                   dermal            dimethyl            rabbit       12.5          West & Carpenter
                   (4 h)             phthalate                                      (1966)

                   dermal            toluene (5%)        rabbit        3.5          West & Carpenter
                   (4 h)                                                            (1966)

    a    M = male; F = female.

         Trutter (1989a) investigated the clinical effects and the effect
    on plasma cholinesterase and erythrocyte acetylcholinesterase of a
    single feeding of aldicarb residues (about 83.4% sulfoxide and 16.6%
    sulfone). These residues were contained in a watermelon grown under
    experimental conditions, aldicarb having been applied to the soil at
    intervals beginning at the time of planting. Water-melon with a
    residue concentration of 4.9 mg/kg was fed to three male and three
    female cynomolgus monkeys at a dosage that provided a residue intake
    of 0.005 mg/kg body weight. Additional groups of three male and three
    female monkeys received untreated water-melon (20 g/kg body weight).
    The test monkeys received supplemental untreated water-melon so that
    their total intake of the fruit was the same as that of the controls.
    Cholinesterase activity was measured 16, 9, and 3 days before and
    immediately before the test. Peak inhibition of plasma cholinesterase
    (31-46%) occurred 1 h after treatment. It was only slightly less at 2
    h but was absent at 4 h after feeding. Observations continued at
    intervals for 24 h. No inhibition of erythrocyte cholinesterase and no
    clinical effects occurred (Trutter, 1989a).

         A similar study with identical numbers of cynomolgus monkeys was
    conducted using treated bananas. The total residue level (0.25-0.29
    mg/kg) in six bananas was less than that in the water-melon, and the
    average distribution of metabolites was different (91.8% sulfoxide and
    8.2% sulfone). The dosage of aldicarb metabolites for the test monkeys
    was 0.005 mg/kg body weight and the banana intake for both test and
    control animals was 20 g/kg body weight. Inhibition of cholinesterase
    was similar in male and female test monkeys, averaging 23% one hour
    after dosing, increasing to 33% by the second hour, and decreasing to
    24% by the fourth hour. No inhibition of erythrocyte cholinesterase
    and no clinical effects occurred (Trutter, 1989b).

    7.2  Short-term exposure

         Short-term studies have been conducted in several species with
    aldicarb and its principal metabolites (the sulfoxide and sulfone)
    both alone and in combination.

         In studies by Weil & Carpenter (1968b,c), male and female rats
    were fed daily doses of aldicarb sulfoxide (0, 0.125, 0.25, 0.5, and
    1.0 mg/kg body weight) or aldicarb sulfone (0, 0.2, 0.6, 1.8, 5.4, and
    16.2 mg/kg body weight) in the diet for 3 and 6 months.
    Acetylcholinesterase activities were depressed at the three highest
    levels of each compound, and this was accompanied by some growth
    retardation. No mortality or pathological effects (gross or
    microscopic) were observed. In an earlier study, Weil & Carpenter
    (1963) fed male and female rats daily with 0, 0.02, 0.10, or 0.50 mg
    aldicarb/kg for 93 days. Plasma cholinesterase activity was depressed
    in both males and females but erythrocyte cholinesterase activity was
    depressed only in males. Male and female rats fed doses of either 

    aldicarb sulfoxide or the sulfone (0.4, 1.0, 2.5, or 5.0 mg/kg body
    weight per day) for 7 days tolerated the lowest dose level of the
    sulfoxide with no effects on body or organ weight (Nycum & Carpenter,
    1970). There was no evidence of plasma, erythrocyte or brain
    cholinesterase inhibition at that dose level. However, these
    parameters were significantly affected at all higher dose levels. 
    Aldicarb sulfone caused a significant decrease in brain, plasma, and
    erythrocyte cholinesterase activity at the highest dose level in rats
    of both sexes. Reduction in brain cholinesterase activity also
    occurred at the two intermediate dose levels for the sulfone in female
    rats only.

         In a 13-week feeding study (NCI, 1979), there was 100% mortality
    in rats exposed to 100 or 320 mg aldicarb/kg and body weight loss at
    80 mg/kg in male rats.

         DePass et al. (1985) exposed 8-week-old male and female Wistar
    rats (10 of each sex per group) to a 1:1 mixture of aldicarb sulfoxide
    and aldicarb sulfone in their drinking-water for 29 days. Their study
    was based on a report by Wilkinson et al. (1983) that residues of
    aldicarb in drinking-water consist essentially of a 1:1 mixture of the
    sulfoxide and sulfone. The drinking-water levels were 0, 0.075, 0.30,
    1.20, 4.80, and 19.20 mg/litre (0-1.67 mg/kg body weight per day for
    males and 0-1.94 mg/kg body weight per day for females). The authors
    concluded that 4.8 mg/litre (470µg/kg body weight per day) was the
    no-observed-effect level (NOEL), based on erythrocyte
    acetylcholinesterase and plasma cholinesterase inhibition observed at
    the highest dose level.

         Short-term dermal studies were conducted in which Temik 10G (with
    10% ai) was applied with wetted gauze to the abraded skin of male
    albino rabbits for 6 h/day for 15 days (Carpenter & Smyth, 1966). Dose
    levels of 0.05, 0.10, and 0.20 g/kg body weight were applied daily,
    and weight gain, food consumption, organ weights, cholinesterase
    activity, and the histopathology of several tissues were examined.
    Only plasma cholinesterase activity levels and weight gain at dose
    levels of 0.1 and 0.2 g/kg per day were significantly altered.

         In a 2-year study on beagle dogs, aldicarb was administered in
    the diet at dose levels of 0, 0.025, 0.05, and 0.10 mg/kg body weight
    per day (Weil & Carpenter, 1966).  The same parameters as those
    monitored in the rat study conducted by these authors were
    investigated in this study, but none were significantly different from
    controls. The authors concluded that the NOEL for rats and dogs was at
    least 0.10 mg/kg body weight per day, since this was the highest level

         In a study by Hamada (1988), male and female beagle dogs were fed
    for one year a diet containing 0, 1, 2, 5 or 10 mg technical aldicarb
    per kg to provide approximately 0, 0.025, 0.05, 0.13, or 0.25 mg/kg
    body weight per day. No dogs died during the study, and there were no

    effects on body weight, food and water consumption, organ weights, or
    on haematological, ophthalmological, histopathological, and gross
    pathological parameters. However, statistically significant increases,
    compared to controls, in the combined incidence of soft stools, mucoid
    stools, and diarrhoea were found in all groups treated with 0.05 mg/kg
    per day or more, as well as in females treated with 0.025 mg/kg per
    day. No statistically significant decrease in erythrocyte or brain
    cholinesterase was found in groups treated with 0.025 or 0.05 mg/kg
    body weight per day.  However, plasma cholinesterase was inhibited in
    male dogs treated with 0.05 mg/kg body weight per day or more
    throughout the observation period of this study (weeks  5-52). In
    addition, plasma cholinesterase was inhibited at the conclusion of the
    study (week 52) in male dogs treated with 0.025 mg/kg body weight per
    day. The author noted that plasma cholinesterase activity in the male
    dogs treated with 0.025 mg/kg body weight per day was subsequently
    determined to be within historical control values, and that the
    statistically significant increase in soft stools and related effects
    in females treated with 0.025 mg/kg body weight per day could be
    attributable to an unusually high incidence of mucoid stools in one
    dog during the last half of the experiment. The author concluded that
    the NOEL in this study was 1 mg/kg (0.025 mg/kg body weight per day).

         In a short-term study, Dorough et al. (1970) dosed lactating
    Holstein cows with Temik (10% ai) at 0.042 mg ai/kg body weight per
    day in their diet for 10 days and, in a second experiment, with a
    mixture of aldicarb and aldicarb sulfone (Temik equivalents of 0.006,
    0.027, and 0.052 mg/kg body weight per day) for a period of 14 days.
    Although no alteration in blood cholinesterase activity levels or
    other clinical effects were noted, aldicarb sulfoxide and sulfone were
    detected in tissues. Milk production, feed consumption, and amount of
    excreta were unaltered.

    7.3  Skin and eye irritation; sensitization

         Pozzani & Carpenter (1968) observed that aldicarb (0.7 mg/kg body
    weight) in saline injected intradermally into male guinea-pigs had no
    sensitizing properties.

         In male albino rabbits, application of aldicarb as a solution in
    propylene glycol on covered clipped skin did not produce any
    irritation. Instillation of 0.1 ml of a 25% suspension of aldicarb in
    propylene glycol or 1 mg of dry compound did not cause corneal
    irritation (Striegel & Carpenter, 1962).

         The administration of 25 mg of aldicarb (Temik 5G)  into the
    conjunctival sac of rabbits resulted in conjunctival irritation, which
    lasted for 24 h, in all the six test albino rabbits (Myers et al.,

         In a study by Myers et al. (1982), the application of 500 mg
    Temik 5G, moistened in saline solution, did not produce primary skin
    irritation in rabbits. Similarly percutaneous administration to
    abraded skin did not cause focal skin irritation.

         Separate tests using aldicarb (75% wettable powder)  and
    technical aldicarb in saline resulted in no sensitization response in
    male albino guinea-pigs following intradermal injections (Pozzani &
    Carpenter, 1968).

    7.4  Long-term exposure

         In a study by Weil & Carpenter (1972), male and female rats were
    fed aldicarb (0.3 mg/kg body weight per day), aldicarb sulfoxide (0.3
    or 0.6 mg/kg body weight per day), aldicarb sulfone (0.6 or 2.4 mg/kg
    body weight/day), or a 1:1 mixture of the sulfoxide plus sulfone (0.6
    or 1.2 mg/kg body weight per day) for 2 years. No effects were
    observed at the low dose level with any of the treatments. At the high
    dose level (except in the case of the sulfone), there was increased
    mortality within the first 30 days and a reduction in plasma
    cholinesterase activity, as well as decreased weight gain in the
    males. The NOEL values determined for aldicarb, aldicarb sulfoxide,
    aldicarb sulfone, and a 1:1 aldicarb sulfoxide/aldicarb sulfone
    mixture were 0.3, 0.3, 2.4, and 0.6 mg/kg body weight per day,

         When male and female rats were fed diets containing aldicarb
    (0.005, 0.025, 0.05, or 0.1 mg/kg body weight per day) for 2 years,
    there were no effects on food consumption, mortality, lifespan,
    incidence of infection, liver and kidney weight, haematocrit,
    incidence of neoplasms and pathological lesions, or on plasma, brain,
    and erythrocyte cholinesterase levels (Weil & Carpenter, 1965).

    7.5  Reproduction, embryotoxicity, and teratogenicity

         Proctor et al. (1976) studied the effects of several methyl
    carbamate and organophosphate insecticides on teratogenicity and
    chicken embryo nicotinamide adenine dinucleotide (NAD) levels. Fertile
    White Leghorn eggs (45-55 g) were used for the test. After the eggs
    were incubated at 37 °C and 73% relative humidity for 4 or 5 days, 1
    mg of aldicarb in a 30-µl methoxytriglycol solution was injected into
    the yolk and the injection hole on the shell was then sealed with
    paraffin wax. On day 12 after injection, some of the embryos were
    removed and the NAD levels were examined. On day 19 after injection,
    the remaining embryos (at least 10) were examined. NAD levels were
    similar to those of controls. There were no terato-genic effects
    (straight legs, abnormal feathers, or wry neck) in any of the embryos
    exposed to aldicarb.

         In a study by Weil & Carpenter (1964), pregnant rats were fed
    with doses of 0, 0.04, 0.20, and 1.0 mg aldicarb per kg body weight
    per day. One group was fed throughout the pregnancy and until the pups
    were weaned, a second group was fed from the day of appearance of the
    vaginal plug until the 7th day of gestation, and a third group
    received aldicarb between days 5 and 15 of gestation.  Although the
    highest dose administered was near the reported LD50 for rats, no
    significant effects on fertility, viability of offspring, lactation or
    other parameters were observed.

         In a teratology study, Harlan-Wistar rats were fed aldicarb
    sulfone in their diets at dosages of 0.6, 2.4 or 9.6 mg/kg body weight
    per day, administered either during the first 20 days of gestation,
    during day 6 to day 15 of gestation, or during day 7 to day 9 of
    gestation. No treatment-related teratogenicity occurred as a result of
    any of the treatment regimes at any of the levels of exposure to the
    sulfone (Woodside et al., 1977).

         Groups of 16 pregnant Dutch Belted rabbits were given doses of 0,
    0.1, 0.25 or 0.50 mg aldicarb/kg body weight per day by gavage on days
    7-27 of gestation (IRDC, 1983). Fetuses were then removed by Caesarean
    section. One spontaneous abortion was reported in each group given
    0.25 or 0.50 mg/kg body weight per day. Although the number of viable
    fetuses and total implantation values were lower in all treatment
    groups than those in controls, they fell within historical control
    ranges and no significant differences were recorded.

         Developmental toxicity of aldicarb has been evaluated by Tyl &
    Neeper-Bradley (1988). Four groups of pregnant CD Sprague-Dawley rats,
    25 in each group, were administered aldicarb (0.125, 0.25 or 0.5 mg/kg
    body weight per day) in water solution by gavage from gestation days
    6 to 15. There were three treatment-related maternal deaths in the
    high-dose group on day 7 of gestation (second day of administration).
    Maternal toxicity at that dose level was indicated by reduced body
    weight and food consumption and cholinergic signs. Body weight and
    food consumption were also reduced in the rats given 0.25 mg/kg body
    weight per day. The NOEL for maternal toxicity was 0.125 mg/kg body
    weight per day. Litter weight was significantly reduced at 0.5 mg/kg
    body weight per day. Fetotoxicity was indicated by body weight
    reduction, increased skeletal variation, retarded ossification, and
    ecchymosis on the trunk. No embryotoxicity was observed. An increased
    incidence of dilation of the cerebral lateral ventricle was observed
    at the highest dose level. However, due to the very high baseline
    control value for such changes found in pooled historical review, this
    increase was not considered to be significant.

         In a 3-generation reproductive study on rats conducted by Weil &
    Carpenter (1964), aldicarb was incorporated into the diet of the
    parent generation at levels of 0.05 or 0.10 mg/kg body weight per day
    for 84 days before mating. Similar doses were fed to the subsequent
    F2 and F3 generations. No effects were noted.

         In a further 3-generation reproductive toxicity study, Weil &
    Carpenter (1974a) fed Harlan-Wistar rats aldicarb in their diet at
    dosages of 0.2, 0.3 or 0.7 mg/kg body weight per day. No consistent
    treatment-related effects were observed in any of the parameters

         A 3-generation reproductive toxicity study was performed on
    Harlan-Wistar rats that were fed aldicarb sulfone in their diets at
    levels adjusted to give dosages of 0.6, 2.4, and 9.6 mg/kg body weight
    per day (Woodside et al., 1977). Apart from occasional reductions in
    maternal body weight gain at the medium and high dosage levels, there
    were no treatment-related adverse effects on any of the parameters

         Cambon et al. (1979) tested three carbamate insecticides
    (aldicarb, carbaferran, and primicarb) on acetyl-cholinesterase
    activity in tissues from pregnant Sprague-Dawley rats and fetuses.
    Aldicarb was administered by gastric intubation (0.001, 0.01 or 0.1
    mg/kg body weight) to the pregnant animals (eight per group) on day 18
    of gestation, and acetylcholinesterase activity was measured in
    maternal and fetal whole blood. Signs of poisoning occurred in animals
    about 5 min after the administration of the medium and high doses.
    There was significant inhibition of acetylcholinesterase in most
    maternal and fetal tissues, and its activity in maternal and fetal
    blood and liver was still lower than the control activity 24 h after
    treatment at the medium and high dose levels.

    7.6  Mutagenicity and related end-points

         Ercegovich & Rashid (1973) evaluated the mutagenicity of aldicarb
    in an Ames-type test using five strains of  Salmonella  typhimurium 
    (identity of strains not stated). Aldicarb was found to be weakly
    mutagenic in the absence of a metabolic activation system.

         Based on the results of four different laboratories that tested
    aldicarb for mutagenicity in  S. typhimurium (TA98, TA100, TA1535,
    TA1537, and TA1538) and  E. coli (WP2  uvrA ), both with and without
    metabolic activation, Dunkel et al. (1985) reported that aldicarb did
    not produce a mutagenic response in any of the bacterial strains

         Rashid & Mumma (1986), reported that "technical grade aldicarb"
    (500 µg/plate) induced DNA damage in  S. typhimurium (TA1538). It did
    not, however, have any lethal effect on the DNA-repair proficient
    strain of  S. typhimurium (TA1978). No DNA-damage was caused in  E.
    coli strains K-12 and WP2.

         An  in vitro gene mutation assay in L5178Y mouse lymphoma cells
    gave inconclusive results for aldicarb in the absence of metabolic
    activation, but aldicarb caused mutations in the presence of S9 mix
    from Aroclor 1254- induced F-344 rat liver (Myhr & Caspary, 1988). In
    an identical experiment performed at a different laboratory  (Mitchell
    et al., 1988), aldicarb was shown to be mutagenic in both the presence
    and absence of induced S9 mix.

         When aldicarb was tested  in vitro in the CHO/HGPRT mammalian
    cell forward gene mutation assay, there was no evidence of
    mutagenicity either in the presence or absence of S9 mix from Aroclor
    1254-induced male Sprague-Dawley rat livers (Stankowski et al., 1985).

         Blevins et al. (1977) found no evidence of DNA damage in human
    skin fibroblasts exposed  in vitro to aldicarb.

         No evidence that aldicarb caused any unscheduled DNA synthesis in
    primary cultures of hepatocytes from male F- 344 rats was detected by
    Godek et al. (1984).

         Aldicarb caused increases in the numbers of chromatid and
    chromosome breaks in human peripheral lymphocytes exposed  in vitro
    (Cid & Matos, 1987). This effect was greater in the presence of S9
    mix from phenobarbital-induced livers of male Sprague-Dawley rats than
    in its absence.

         When Cid & Matos (1984) studied the effects of aldicarb on human
    lymphocytes  in vitro , they found that it caused a significant
    increase in sister chromatid exchanges (SCE). Slightly higher SCE
    values were found in the presence of S9 liver homogenate fractions
    than in its absence.

         The  in vivo clastogenicity of aldicarb in bone marrow has been
    investigated in rats and mice via the intraperitoneal route. Sharaf et
    al. (1982) treated male albino rats (strain not stated) with
    injections of aldicarb (0.00121, 0.00666 or 0.0121 mg/kg body weight)
    dissolved in a 1:1 water/acetone vehicle. One group of animals served
    as a control, a second group received one injection per day for 5
    days, and a third group received one injection only. Increases in
    structural and numerical aberrations were observed in bone marrow
    cells in all groups of treated animals. Structural chromosomal
    aberrations consisted of chromatid breaks or deletions, chromatid
    gaps, centromeric attenuation, and (in the case of repeated exposure
    only) centric fusions. Numerical aberrations were mainly due to
    endomitosis, although there was also some evidence of increased
    polyploidy. In mice, however, there was no evidence of any effect on
    chromosomal aberration frequencies in bone marrow cells following a
    single intraperitoneal injection of aldicarb (93.5% pure; 0.010 or
    0.001 mg/kg body weight). In addition, no effects were seen when five
    daily doses of 0.010 mg/kg body weight were given (Cimmino et al.,

         Dominant lethal studies have been performed using Harlan-Wistar
    rats (from the F2 generation of multi-generation studies) that had
    been treated with aldicarb (Weil & Carpenter, 1974a) or aldicarb
    sulfone (Woodside et al., 1977) given in the diet at dosages of 0.2,
    0.3, and 0.7 mg/kg (aldicarb) and 0.6, 2.4, and 9.6 mg/kg (aldicarb
    sulfone). The treated males were then mated with untreated virgin
    females. The results of the studies gave no indication of an increased
    incidence of dominant lethal mutations in rats treated orally with
    aldicarb or aldicarb sulfone.

         Although some of the mutagenicity tests performed on aldicarb
    gave positive results, the results of the various  in vitro and  in
     vivo tests, when considered together, indicate that aldicarb is not
    an win vivow mutagen.

         The mutagenic potential of  N-nitroso aldicarb has also been
    investigated. A bacterial spot test conducted with Salmonella
    typhimurium his- G46 gave a weakly positive result (Seiler, 1977).
    Blevins et al. (1977) investigated the interaction of  N-nitroso
    aldicarb with DNA in  in vitro human skin fibroblasts and found
    numerous single-strand breaks in the DNA of all the
    nitroso-derivative-treated cells but not in the DNA from cells treated
    with aldicarb itself. Cid et al. (1988) found that
     N-nitroso-aldicarb caused an increase in the number of sister
    chromatid exchanges in human lymphocytes in vitro.

    7.7  Carcinogenicity

         Weil (1968) reported a skin-painting study of male mice in which
    a 0.125% solution of aldicarb was applied to the hair-free skin on the
    backs of animals twice a week for up to 28 months. There were no
    substantial differences with respect to the incidence of tumours. Two
    growths, a haemangioma and a thymoma, were noted in the animals
    administered aldicarb. These internal growths were not accompanied by
    cutaneous papillomas or carcinomas and were considered to be
    spontaneous growths unrelated to any incidence of malignancy
    (Wilkinson et al., 1983).

         In a study by Weil & Carpenter (1974b), aldicarb was dissolved in
    acetone prior to mixing with the diet, and dietary levels of 0.1, 0.3
    or 0.7 mg/kg body weight were administered to groups of 50 male CD-1
    mice for 18 months.  Two control groups of 50 mice were used in
    addition to a group of untreated mice from which one animal was killed
    for comparison purposes each time a mouse in the aldicarb-treated
    groups died during the experimental period. There was no
    treatment-related effect on mortality. Furthermore, there were no
    treatment-related effects on the incidence of any tumour type at any
    site or on the total incidence of tumours.

         In a study by Woodside et al. (1977), groups of CD-1 mice (50 of
    each sex per group) were administered aldicarb sulfone (0, 0.15, 0.6,
    2.4 or 9.6 mg/kg body weight) in the food for 18 months. Observations
    included mortality, food consumption, and body weight determinations,
    and gross and microscopic examinations were performed on all mice.
    Body weight changes were sporadic and exhibited no trends.
    Histological changes were not statistically different from those in
    controls at any dose level for either sex.

         In a 2-year feeding study on rats, Weil & Carpenter (1965, 1972)
    reported no significant tumour increases in rats fed aldicarb (0.005,
    0.025, 0.05, 0.10, or 0.30 mg/kg body weight per day) or its sulfoxide
    and sulfone. In an NCI (1979) bioassay, male and female F-344 rats and
    B6C3F1 mice were given technical aldicarb (2 or 6 mg/kg body weight)
    in their diet for 103 weeks. No treatment-related tumours were
    observed in either species.

         Quarles et al. (1979) performed a series of experiments to
    examine the transforming and tumorigenic activity of aldicarb and its
    nitroso derivative. Pregnant hamsters were given intraperitoneal
    injections of aldicarb (0.1 or 0.5 mg/kg) or nitroso-aldicarb (2
    mg/kg) on day 10 of gestation. Fetal cell cultures were prepared and
    plated on agar on day 13 of gestation. To test for tumorigenicity, 1
    x 106 cells were injected subcutaneously into adult nude mice.
    Aldicarb was found to be inactive and did not induce either
    morphological transformations or cells that grew in agar, whereas
    nitroso-aldicarb induced morphological transformations that were
    tumorigenic in nude mice.

         Weekly administration by oral gavage of  N-nitroso-aldicarb
    (nine doses of 10 mg/kg body weight or two doses of 20 mg/kg body
    weight) to groups of 12 female Sprague-Dawley rats resulted in the
    development, by the end of their natural lives, of forestomach
    carcinomas in two of the rats from each treated group, compared with
    none in control animals (Lijinsky & Schmahl, 1978). The nitroso
    derivative of aldicarb may be formed in the laboratory when aldicarb
    is in the presence of nitrite under the pH and temperature conditions
    of the human stomach (Elespuru & Lijinsky, 1973; Lijinsky & Schmahl,

    7.8  Other special studies

         Farage-Elawar (1988) studied the functional consequences of
    dosing six-day-old chicks orally with 0.2 mg aldicarb/kg body weight
    per day for seven days. Both acetylcholinesterase and neuropathy
    target esterase levels were determined during treatment and on days 1,
    3, 6, 10, 20, 30, and 40 after treatment. Measurements of motor
    function consisted of analysis of the gait at the same times. Six days
    after the last treatment there was a significant weight reduction with
    no recovery to the control weight. There were significant alterations

    in three parameters of gait starting on post-treatment day 1 and
    lasting until day 40. Aldicarb reduced the acetylcholin-esterase
    levels significantly only 24 h after the first day of treatment, with
    recovery to control levels thereafter. There were no significant
    alterations in neuropathy target esterase levels at any time. The
    authors concluded that motor function changes in the young chick can
    be seen in the absence of alterations in acetylcholinesterase levels.

         Olsen et al. (1987) conducted studies using low concentrations of
    aldicarb (0, 1, 10, 100 or 1000 wµwg per litre) in the drinking-water
    of inbred Swiss Webster mice for 34 days and measured the splenic
    plaque-forming cells (PFC) response to sheep red blood cells. The mean
    PFC count in the 1-µg/litre group was significantly less than in the
    control group after 34 days. The authors stated that aldicarb
    exhibited immunomodulatory capability.

         Thomas et al. (1987) conducted experiments similar to Olson et
    al. (1987), but used both Swiss Webster and B6C3F1 mice. The mean
    PFC counts at 0.1 µg/litre were lower than the controls; at 1.0
    µg/litre they exceeded the controls; and at 10µg/litre they were lower
    than the controls. With B6C3F1 mice PFC counts exceeded control
    values at both 100 and 1000µg/litre, whereas in the case of Swiss
    Webster mice they were similar to control values at 100µg/litre but
    lower at 1000µg/litre. The authors concluded that aldicarb at
    environmentally relevant exposure concentrations is not immunotoxic in

         Shirazi et al. (1990) studied the immunomodulation response of
    mice to low levels of aldicarb in drinking-water (0.01 to
    1000µg/litre). Compared to the mean PFC values of the control group,
    the mean values of treated groups indicated a stimulatory effect for
    30- and 60-day tests and an inhibitory effect for 90- and 180-days
    tests. However, when the data were reanalysed using the distribution
    of the relative PFC counts, a consistently inhibitory response was
    observed. The authors concluded that the dose-response relationships
    indicated a polyphasic and inhibitory response.

         Selvan et al. (1989) observed that aldicarb selectively affected
    macrophage-mediated cytotoxicity of tumor target cells without
    affecting the cytotoxicity mediated by natural killer cells. However,
    no dose-response relationship was found.

         Dean et al. (1990) investigated the effect of aldicarb on
    syngenic mixed lymphocyte reaction (SMLR). In this reaction CD4+
    T-helper cells (autoreactive T cells) respond to syngenic Ia molecules
    expressed on C3H mouse macrophages. The authors reported that
    intraperitoneal treatment (0.1 ml per mouse of a solution containing
    0.1 to 1000µg aldicarb per litre) suppressed the SMLR by selectively
    decreasing the stimulatory activity of macrophages without affecting
    directly the responsiveness of autoreactive T cells.

         A significant suppression of macrophage-mediated cytotoxicity of
    tumor cells was observed in C3H mice that received seven daily doses
    of 0.1 to 10µg aldicarb per kg. The authors concluded that aldicarb
    may selectively affect the macrophage function but not directly affect
    other components of the immune response.

         Thomas & Ratajczak (1988) reported that when aldicarb was
    administered in the drinking-water (0.1, 1.0, 10, 100 or 1000µg/litre)
     ad libitum for 34 consecutive days to both Swiss Webster and
    B6C3F1 hybrid female mice, there were no effects in either strain on
    body weight, organ weight, circulatory white blood cells or
    microscopic pathology of the thymus, spleen, liver, kidneys or lymph
    nodes.  In vivo host resistance to infectious viral challenge was
    unaffected by aldicarb treatment. Aldicarb was found to have no effect
    in either strain on the number of antibody-forming cells in the spleen
    or on the amount of circulating antibody in the blood. The capacity of
    B and T lymphocytes to respond to nonspecific mitogens was unaltered,
    as was the ability of T lymphocytes to recognize genetically different
    cell types in a mixed lymphocyte culture (MLC). It was concluded that
    aldicarb in drinking-water had no effect on any measured immunological

         Thomas et al. (1990) exposed adult female B6C3F1 mice to
    drinking-water containing 1.0, 10 or 100µg aldicarb per litre or to
    distilled drinking-water alone for 34 consecutive days. The impact of
    aldicarb exposure on the ability of splenic natural killer cells and
    specifically sensitized cytotoxic T lymphocytes to lyse YAC-1 lymphoma
    target cells and P 815 tumor cells was evaluated. The percentages and
    absolute numbers of total T cells, T-suppressor, T-helper, and B cells
    was also measured. The authors concluded that the absence of
    statistically significant effects on any of these parameters indicated
    that aldicarb treatment did not adversely affect the immune system of

    7.9  Factors modifying toxicity; toxicity of metabolites

         Of the metabolites that have been identified, only the sulfoxide
    and sulfone have a mechanism of toxicity similar to aldicarb (as a
    cholinesterase inhibitor in a carbamylation reaction). The sulfoxide
    appears to be equally toxic and the sulfone considerably less toxic
    than aldicarb in acute and long-term tests (Weil, 1968; Weil &
    Carpenter, 1972).

    7.10  Mechanisms of toxicity - mode of action

         Aldicarb and acetylcholine exhibit very close structural

               CH3       O              CH3        O
               '         "              '          "
    CH3S - C - CH = N - OCNHCH3   CH3 - N - CH2CH2OCCH3
               '                        '
               CH3                      CH3

               Aldicarb                 Acetylcholine

         The mechanism of toxic action of aldicarb and its metabolites
    (sulfoxide and sulfone) involves their reaction with cholinesterase
    enzymes. In particular, the carbamylation of acetylcholinesterase
    interferes with hydrolysis of acetylcholine at synaptic and myoneural
    junctions. This adversely affects neural transmission (Carpenter &
    Smyth, 1965; Weil & Carpenter, 1968a,b,c, 1970; Dorough, 1970).
    Various cholinesterase enzymes have been identified in the plasma, red
    blood cells, liver, and brain (Kuhr & Dorough, 1976; Cambon et al.,
    1980). The function of plasma cholinesterase is not fully understood,
    but it is considered to play no role in cholinergic transmission. 
    Acetylcholinesterase in erythrocytes reflects the acetylcholinesterase
    activity in the nerve synapses. Since acetylcholinesterase in
    erythrocytes and in nerve synapses are considered to be biochemically
    identical, erythrocyte cholinesterase activity may be taken as an
    indicator of the biochemical effect of anti-cholinesterase pesticides
    (WHO, 1990a).

         Carbamates, like organophosphates, inhibit esterases
    (serine-esterases and/or beta-esterases) (WHO, 1986). Although the
    inhibition of serine-esterases other than acetylcholinesterase is not
    significant for the toxicity of the compound, it may have significance
    for the potentiation of toxicity of other compounds after long-term
    low level exposure (Sakai & Matsumara, 1968, 1971; Aldridge & Magos
    1978). The site of carbamylation of the enzyme is the hydroxyl moiety
    of the serine amino acid.  The rate of reactivation of the
    carbamylated enzyme to acetylcholinesterase is relatively rapid
    compared to that of the enzyme phosphorylated by an organophosphorus
    pesticide. Thus the inhibition of acetylcholinesterase by carbamate
    pesticides is rapid and reversible. The chemistry of carbamate
    pesticides is such that no aging reaction is possible, as occurs with
    the phosphorylated enzyme. In order to permit an evaluation of
    cholinesterase inhibition by carbamates  in vivo , special care is
    required. Carbamate cholinesterase inhibition studies should utilize
    minimal dilution during the preparation of the assay, minimal
    incubation times, and minimal time between blood sampling and assay
    (WHO, 1990a).


    8.1  General population exposure

         The symptoms that have been reported for accidental or
    occupational poisoning and controlled human exposure to aldicarb are
    cholinergic and subside spontaneously, usually within 6 h, unless
    death intervenes. Clinical symptoms and signs include dizziness,
    salivation, excessive sweating, nausea, epigastric cramps, vomiting,
    diarrhoea, bronchial secretion, blurred vision, non-reactive
    contracted pupils, dyspnoea, and muscular fasciculations. The
    intensity of these symptoms varies with the extent of exposure.

    8.1.1  Acute toxicity; poisoning incidents

         The first reported case of accidental poisoning occurred in 1966
    when aldicarb was being used as an experimental pesticide (Hayes,
    1982). The wife of an experimental scientist used a small amount of a
    10% granular formulation to treat the soil around a rose bush.
    Twenty-four days later she ate a sprig of mint from a plant growing
    nearby, which consisted of the terminal 4-6 leaves and the stem.
    Thirty minutes later she vomited and had diarrhoea and involuntary
    urination. On admission to the hospital, she was found to have
    pinpoint pupils, muscle fasciculations, and difficulty in breathing.
    Maximal signs were observed 2 h after onset. She was given 1 mg of
    atropine with no observable effect. About 15 min later she was given
    2 mg atropine and had transient opening of the pupils. A further 2 mg
    atropine was followed by sustained opening of the pupils and gradual
    improvement in the patient's condition. Three-and-a-half hours after
    onset, she was resting comfortably and had no further signs or
    symptoms. It was estimated that she had eaten between 0.5 and 1.0 g of
    mint. Feeding 3.0 g of this mint to a rabbit resulted in its death
    within 2 h; 2.4 g caused severe symptoms in a second rabbit.

         Two minor incidents of aldicarb poisoning with moderately severe
    symptoms occurred after hydroponically grown cucumbers were eaten
    (CDC, 1979; Goes et al., 1980; Hayes, 1982). Although carbamates had
    been used in both cases, there were no data on the aldicarb content of
    the cucumbers in the first case. Levels of 6.6-10.7 mg aldicarb/kg
    were found in the second case (the hydroponic nutrient solution
    contained 1.8 mg aldicarb/litre). The symptoms lasted only 4.5-6.0 h,
    and recovery from cholinergic symptoms occurred without specific
    treatment (Aaronson et al., 1979).

         Aldicarb food poisoning from contaminated melons was reported in
    California, USA, in 1985. Of the 1358 cases reported, 692 were
    classified as probable. The melons were tested for aldicarb

    sulfoxide, and 10 (4%) of the 250 tests were positive. The most severe
    signs and symptoms included loss of consciousness and cardiac
    arrhythmia. Six deaths and two stillbirths were reported but no
    analyses for aldicarb sulfoxide were reported (Jackson et al., 1986;
    Ting & Kho, 1986).

         Goldman et al. (1990a) analysed the same epidemic in California
    in 1985. According to their result, 1376 cases of illness within
    California were reported to the California Department of Health
    Services of which 77% were classified as being probably or possible
    carbamate-related illnesses. Seventeen individuals required

         An outbreak of illness caused by aldicarb-contaminated
    water-melons was reported in Oregon, USA, in 1985. About 264 cases of
    poisoning were reported and 61 definite cases were confirmed. The
    levels of residue in the water-melons ranged from 0.01 mg/kg (limit of
    detection) to 6.3 mg/kg. (Green et al., 1987).

         Goldman et al. (1990b) reviewed three outbreaks of poisoning due
    to aldicarb-contaminated water-melons or cucumbers in California
    between 1985 and 1988, and one outbreak due to contaminated cucumbers
    in England. Estimated dosages of aldicarb sulfoxide that caused the
    illnesses ranged between 0.0011 and 0.06 mg/kg body weight and most
    were well below the 0.025 mg/kg for subclinical whole blood
    cholinesterase depression.

         Ramasamy (1976) reported an incident in which a 7-month-old
    female baby ate some aldicarb powder. Recovery was complete after she
    was given a total dose of 105.6 mg atropine.

    8.1.2  Human studies

         An experimental study was carried out on 12 men already involved
    in the study of aldicarb and, therefore, familiar with its effects.
    Four volunteers in each of three groups took aldicarb (99.2% purity;
    dissolved in drinking-water) at concentrations of 0.025, 0.05, or 0.10
    mg/kg body weight. Blood was collected for cholinesterase measurement
    at 18 h and 1 h before ingestion of aldicarb and at 1, 2, 4, and 6 h
    after ingestion. The samples of whole blood were analysed by the
    radiometric method for whole blood, which has the advantage of
    involving minimal dilution of the blood and a maximum of only 3 min
    from the time the sample is taken until the chemical reaction is
    complete (the period of storage of the samples until the radioactivity
    in them is measured has no effect on the result). The compound
    hydrolysed is acetylcholine and not, as in many methods, a substitute.
    Urine samples were collected at 1, 2, 4, and 6 h after ingestion.
    Analysis was by gas chromatography after all metabolites had been
    oxidized to aldicarb sulfone. The highest dosage chosen was that
    already found to be a no-observed-effect level in a 2-year rat feeding
    study. This was done even though it was recognized that some symptoms

    might occur if ingestion occupied less than 1 min rather than 24 h as
    in the rat. Signs and symptoms did, in fact, occur at the highest
    dosage and included nausea and vomiting, pinpoint non-reactive pupils,
    malaise, weakness, epigastric pain, air hunger and yawning, sweating
    of the hands, forearms and forehead, salivation, and slurred speech.
    The authors stated that none of the signs and symptoms were severe and
    they required no treatment. Cholinesterase activity was depressed in
    proportion to the dosage. Based on the individual 18-h pre-dosing
    samples, the average level 1 h after ingestion was reduced to 53.3,
    38.8, and 34.6% of normal at 0.025, 0.05, and 0.1 mg/kg, respectively.
    At the highest dosage, the activity was further decreased (28.1% of
    normal) in the 2-h sample, but it was elevated at the two lower
    dosages. At 4 h it was elevated in all groups but by 6 h it had almost
    returned to normal. Urinary excretion of metabolites was proportional
    to dosage; the total recovery varied from 3.4 to 10.7% during the 8 h
    (Haines, 1971).

         In a separate test of volunteers, one man took a dosage of 0.26
    mg/kg body weight in the form of Temik 10G granules. He became ill and
    took atropine. The carbamate concentration was greatest in a urine
    sample collected 4.5 h after ingestion, but total recovery of aldicarb
    was only 8.1% in 24 h (Cope & Romine, 1973).

    8.1.3  Epidemiological studies

         After aldicarb had been detected in well-water samples in Suffolk
    County, New York, Varma et al. (1983) conducted a preliminary mail
    survey of families who had consumed water from these wells in 1981.
    The 1500 subjects had consumed water that contained from 8 to over 64
    µg aldicarb/litre. They were asked to report any symptoms of 20
    general health problems and the outcome of all pregnancies. A list of
    25 randomly arranged neurological symptoms was also included. The
    response rate (20%) was poor. No conclusive evidence of the
    association of health problems with aldicarb exposure was obtained
    from this study (for which there were no controls), although there
    appeared to be an association between some neurological
    symptoms/syndromes and the concentration of aldicarb in the well
    water. The rate of spontaneous abortions was also high among women who
    consumed water from wells that contained the highest aldicarb
    concentrations (66 µg/litre or more).

         In a cross-sectional study of exposed and unexposed residents of
    Portage County, Wisconsin, Fiore et al. (1986) reported the effects of
    chronic ingestion of ground water contaminated with levels of aldicarb
    (< 61 µg per litre) on the immune function of 50 women aged 18 to 70
    with no known underlying reason for immunodysfunction. Of these
    exposed women, 23 consumed water from a source with detectable levels
    of aldicarb, while 27 unexposed women consumed water from a source
    with no detectable level of aldicarb. Exposed women showed an elevated
    stimulation assay response to Candida antigen, an increase in the

    number of T8 cells, and a decrease in the ratio of T4:T8 cells as
    compared with unexposed women. Although the results of this study are
    of interest, the T lymphocyte data fall within the normal range
    indicated by Martin et al. (1985). The Candida response data are also
    within normal limits that have been routinely observed at the
    University of Wisconsin Medical Center. The results of this study,
    because of the presence of other contaminants, present no evidence for
    a causal relationship between consumption of water contaminated with
    aldicarb and alteration of immunological parameters.

    8.2  Occupational exposure

    8.2.1  Acute toxicity; poisoning incidents

         Peoples et al. (1978) reported on occupational exposure to
    aldicarb in California during the period 1974-1976. They reviewed 38
    illnesses, 31 of which were systemic, that were directly related to
    occupational aldicarb (Temik) exposure. There were four cases of
    contact dermatitis and one case of eye irritation in which dust from
    Temik granules was blown directly into the eye causing chemical

         Lee & Ransdell (1984) reported the death of a 20-year-old farm
    worker who was run over by a tractor after he had been handling Temik
    15G. Tissue samples taken at autopsy revealed an estimated body burden
    of 18.2 mg aldicarb (0.275 mg/kg). This level is nearly 3 times higher
    than that known to produce cholinergic symptoms in humans, and the
    authors considered that pesticide intoxication contributed to the
    worker's death.

         Sexton (1966) reported the incapacitation of a foreman working in
    an aldicarb mechanical bagging operation. Symptoms of cholinesterase
    depression lasted longer than 6 h, but he returned to work the next
    day. Griffith & Duncan (1985) surveyed Florida citrus fruit growers
    over a 12-month period for aldicarb-related poisonings. Only one case,
    that of a certified applicator who required hospitalization for
    cholinergic symptoms, was directly related to the aldicarb exposure.

         Aldicarb is one of the most potent and acutely toxic pesticides
    in use. In most cases, excessive occupational exposure to aldicarb has
    been due either to its improper application or to the improper use of
    protective equipment. Its formulation as granules and its application
    to the subsoil as a systemic pesticide have been recommended by the
    manufacturer to reduce the hazards (SR1, 1984).

    8.2.2  Effects of short- and long-term exposure; epidemiological

         No controlled occupational exposure or epidemiological      
    studies have been reported.


    9.1  Microorganisms

         Some aspects of the effects of microorganisms on aldicarb have
    been discussed in section 4.3.1. In the study by Kuseske et al.
    (1974), application rates of 5 and 500 ppm of a commercial formulation
    of aldicarb (100 g/kg ai) caused a decrease in the population of
    microflora for the first 16 days and then stimulated the population
    growth, in proportion to the application rate, over the next 14 days.
    The microorganisms used in this study were  Actinomycetes,
    Nitrosomonas europaea , and  Nitrobacter agilis . When 5 ppm of the
    insecticide was applied, depletion of  Nitrosomonas resulted in
    complete inhibition of the conversion of the ammonium ion to nitrite.
    The oxidative capability of five common soil fungi (Jones, 1976) is
    discussed in section 4.3.1. Spurr & Sousa (1966, 1967) found no
    inhibition of bacterial or fungal growth by aldicarb. Indeed, in the
    case of  Rhizoctonia solani (a plant pathogen and soil saprophyte),
    the addition of aldicarb to the medium doubled its growth rate. The
    authors concluded that microorganisms probably used aldicarb as a
    carbon source.

    9.2  Aquatic organisms

         The acute toxicity of aldicarb to freshwater aquatic organisms
    varies greatly. The 96-h LC50 values for different species of fish
    range between 52 and 2420 µg per litre at different temperatures and
    water hardness (Table 10). Aquatic molluses are very insensitive to
    the effects of aldicarb (Singh & Agarwal, 1981). For the adult water
    flea,  Daphnia laevis , the sulfoxide is more toxic than aldicarb by
    a factor of two and the sulfone less toxic by a factor of five to six
    (Foran et al., 1985). For the bluegill sunfish,  Lepomis  macrochirus
    , the toxicity of aldicarb and the sulfoxide is comparable, but the
    sulfone is less toxic (Clarkson, 1968b). For estuarine and marine
    organisms, acute lethality is less variable with 96-h  LC50 values
    ranging between 13 and 170µg/litre for all species tested (Table 10).
    Pant & Kumar (1981) studied the acute toxicity of aldicarb to the
    Himalayan lake teleost  Barbus  conchonius in both hard and soft
    water. Temperatures varied from 14 to 22 °C during the experiment, and
    the tests were carried out under static conditions. Results indicated
    that the toxicity of aldicarb to  B. conchonius was considerably
    greater in soft water (Table 10). Mortality data showed that
    concentrations of 1.5 mg/litre in soft water and 6.0 mg/litre in hard
    water resulted in 100% mortality within 96 h.

        Table 10.  Acute toxicity (LC50) of aldicarb to freshwater, estuarine, and marine organismsa
    Organism      Age/size    Stat/   M/ Temperature  Hardness     pH   Compound    Duration   Concentration   Reference
                              flow    N     (°C)      (mg/litre)                               (ug/litre)

    Water flea    adult       stat    M    21         58          6.9      A         48 h      209 (175-265)   Foran et al. (1985)
     laevis)                          M    21         58          6.9      AX        48 h      103 (36-142)    Foran et al. (1985)
                                      M    21         58          6.9      AN        48 h      1124 (993-1320) Foran et al. (1985)
                  (1-3                                                     A                   70 (61-84)      Foran et al. (1985)
                  days old)
                                                                           AX                  84 (73-95)      Foran et al. (1985)
                                                                           AN                  910 (821-1099)  Foran et al. (1985)
    Water flea
     (Daphnia                                                              A         48 h      410             US EPA (1988a)

    Water snail   adult       stat                                         A         24 h      30 000          Singh & Agarwal (1981)
     acuminata)                                                                      96 h      11 500          Singh & Agarwal (1981)
                                                                                    240 h      7500            Singh & Agarwal (1981)
    Water snail   adult       stat                                         A         96 h      175 000         Singh & Agarwal (1981)
     (Pila                                                                          240 h      78 000          Singh & Agarwal (1981)

    Bluegill      1.3 g       stat         24         44          7.4      A         24 h      103 (66-161)    Mayer & Ellersieck
    sunfish                                                                                                    (1986)
     macro-       1.3 g       stat         24         44          7.4      A         96 h      52 (34-79)      Mayer & Ellersieck
     chirus)                                                                                                   (1986)
                  3.9 g       stat         18         44          7.4      A         24 h      160 (130-214)   Mayer & Ellersieck

    Table 10 (contd). Acute toxicity (LC50) of aldicarb to freshwater, estuarine, and marine organismsa
    Organism      Age/size    Stat/   M/ Temperature  Hardness     pH   Compound    Duration   Concentration   Reference
                              flow    N     (°C)      (mg/litre)                               (ug/litre)
                  3.9 g       stat         18         44          7.4      A         96 h      71 (54-93)      Mayer & Ellersieck
                  5.0 g       stat                                         A         72 h      100             Clarkson (1968b)
                  5.0 g       stat                                         AX        72 h      4000            Clarkson (1968b)
                  5.0 g       stat                                         AN        72 h      64 000          Clarkson (1968b)

    Rainbow       0.5 g       stat         12         44          7.4      A         24 h      1000 (727-      Mayer & Ellersieck
    trout                                                                                      1376)           (1986)
     (Salmo       0.5 g       stat         12         44          7.4      A         96 h      560 (394-796)   Mayer & Ellersieck
     gairdneri)                                                                                                (1986)
                  2.7 g       stat         18         44          7.4      A         24 h      780 (592-1027)  Mayer & Ellersieck
                  2.7 g       stat         18         44          7.4      A         96 h      660 (472-921)   Mayer & Ellersieck
     conchonius   4.8 cm      stat         14-22      319         7.4      A         48 h      8990 (4265-     Pant & Kumar (1981)
                                                                                               18 586)
                  4.8 cm      stat         14-22      319         7.4      A         96 h      2420 (2280-     Pant & Kumar (1981)
                  4.8 cm      stat         14-22      61          7.2      A         48 h      3296 (1116-     Pant & Kumar (1981)
                  4.8 cm      stat         14-22      61          7.2      A         96 h      459 (445-521)   Pant & Kumar (1981)

    Table 10 (contd). Acute toxicity (LC50) of aldicarb to freshwater, estuarine, and marine organismsa
    Organism      Age/size    Stat/   M/ Temperature  Hardness     pH   Compound    Duration   Concentration   Reference
                              flow    N     (°C)      (mg/litre)                               (ug/litre)
    Estuarine & marine

    Alga                      stat    N    20         30                   A         96 h      > 50 000b       Mayer (1987)

    Mysid shrimp  juvenile    stat    N    25         20                   A         96 h      13 (10-15)      Mayer (1987)
     (Mysidopsis  (1 day
     bahia)       old)
                  adult       flow    M    22         28                   A         96 h      16 (13-20)      Mayer (1987)

    Pink shrimp   adult       flow    M    22         29                   A         96 h      12 (7.5-18)     Mayer (1987)

    White shrimp  juvenile    stat    N    25         20                   A         96 h      72 (65-82)      Mayer (1987)

    Eastern       embryo      stat    N    25         20                   A         48 h      8800c           Mayer (1987)
    oyster                                                                                     (1400-56 000)

    Sheepshead    juvenile    stat    N    25         20                   A         96 h      170 (100-320)   Mayer (1987)
     (Cyprinodon  (28 days
     variegatus)   old)
                  adult       flow    M    28         28                   A         96 h      41 (55-72)      Mayer (1987)

    Table 10 (contd). Acute toxicity (LC50) of aldicarb to freshwater, estuarine, and marine organismsa
    Organism      Age/size    Stat/   M/ Temperature  Hardness     pH   Compound    Duration   Concentration   Reference
                              flow    N     (°C)      (mg/litre)                               (ug/litre)
    Pinfish       adult       flow    M    22         30                   A         96 h      80 (43-150)     Mayer (1987)

    Spot          adult       stat    N    25         20                   A         96 h      200 (120-290)   Mayer (1987)

    Snook         juvenile    stat    N    26-30      35                   A         48 h      100             Landau & Tucker (1984)
     undecima-    (0.23 g)

    a   M = measured concentration; N = nominal concentration; stat = static conditions; flow = flow-through conditions; 
    A = aldicarb; AX = aldicarb sulfoxide; AN = aldicarb sulfone.   b LC50 for growth.   c  LC50 for metamorphosis.

         Landau & Tucker (1984) exposed eggs of the estuarine snook
     (Centropomus undecimalis) from 2 to 3 h after fertilization to
    various aldicarb concentrations. Larvae were more sensitive than eggs
    to aldicarb. Mortality over 14 to 25 h was 0, 17, 22, and 30% of
    embryos and 0, 83, 78, and 70% of larvae at 0.025, 0.1, 0.25, and 0.5
    mg per litre, respectively.

         Pickering & Gilliam (1982) exposed eggs and newly hatched larvae
    of the freshwater fathead minnow to aldicarb at 20, 38, 78, 156, and
    340 µg/litre and monitored hatching and growth of juveniles over 30
    days. None of the aldicarb concentrations affected embryo survival and
    only the two highest levels reduced larval-juvenile survival (by 58%
    and 80%, respectively) over 30 days. Growth of surviving young was
    reduced significantly only at the highest exposure concentration.
    Based on the acute maximum acceptable toxic concentration (MATC) of 78
    to 156 µg per litre, the authors calculated a chronic MATC of 110 µg

    9.3  Terrestrial organisms

         Haque & Ebing (1983) conducted a 14-day laboratory toxicity test
    of aldicarb using the earthworms  Lumbricus terrestris and  Eisenia
    foetida as test species. The pesticide was homogeneously incorporated
    into the test soil substrates. The authors noted a species-specific
    variation in toxicity,  L. terrestris showing an LC50 of 530
    (490-565) and  E. foetida of 65 (58-75) mg/kg dry soil substrate.

         The acute oral LD50 for birds has been found to vary between
    0.8 and 5.3 mg/kg body weight, while the dietary toxicity ranged from
    approximately 250 to 800 mg/kg diet (Table 11). West & Carpenter
    (1965) reported that the oral LD50 for White Leghorn cockerels was
    9 mg/kg body weight (i.e. 10 times that of rats). Symptoms of aldicarb
    poisoning in chickens were excessive salivation, dyspnoea, stiffness,
    and twitching of leg, wing, and pectoral muscles (Schlinke, 1970).
    When 28-day-old Japanese quail ( Coturnix coturnix japonica ) were
    given analytical grade aldicarb in corn oil solution (in gelatin
    capsules) at a dose of 30 mg/kg body weight (i.e. 3 times the LD50),
    all birds died within 3 h (Martin et al., 1981). Balcomb et al. (1984)
    measured the acute oral toxicity of aldicarb to two species of song
    bird (house sparrow and redwinged blackbird) (Table 11). When birds
    were dosed with varying numbers of aldicarb granules (Temik 15G), 40%
    of blackbirds given a single granule died, and 80% of those given 5
    granules died. In a study on the redwinged blackbird, technical and
    granular (Temik 15G) aldicarb yielded similar LD50 values. However,
    the oral LD50 of granular aldicarb for sparrows was 3.8 mg/kg body
    weight whereas that for technical aldicarb was 0.8 mg/kg/body weight.
    Hill & Camardese (1981) reported that dietary LC50 values in young
    Japanese quail  (Coturnix coturnix japonica) increased with the age of
    the bird, the increase being reasonably predictable between 7 and 21
    days of age. Five-day dietary LC50 values were 247, 355, 542, and
    786 mg/kg diet at ages 1, 7, 14, and 21 days, respectively.

         In studies by Schlinke (1970) on the toxic effects of aldicarb
    and other nematocides in chickens, groups of five White Leghorn
    chickens, 6-7 weeks old, were given oral doses of 1.0, 2.5 or 5 mg
    aldicarb/kg per day. Individual doses were administered in gelatin
    capsules or by an aqueous oral drench for 10 days. Groups of six to
    eight chickens were used simultaneously as controls. Body weight gain
    and mortality were determined. In the low-dose group, a slight
    decrease in the percentage body weight gain (44% treated versus 49%
    controls) was observed, but no adverse effects were reported at this
    level. Body weight gain for the chickens given 2.5 mg/kg was 30%
    versus 40% in controls. In addition one chicken died after receiving
    a single dose of the compound and a second died after receiving three
    consecutive daily doses. In the high-dose groups (5 mg/kg per day),
    one chicken died after receiving a single dose (day 1 of
    administration), one after the second dose, and the remaining three
    chickens died after the third dose (day 3).

         Farage-Elawar et al. (1988) compared the sensitivity of young and
    adult chickens to aldicarb and carbaryl. Brain, liver, and plasma
    cholinesterase levels were measured and histological examinations were
    conducted. Adult chickens showed no changes in any of the parameters
    measured. Brain acetylcholinesterase, plasma cholinesterase, plasma
    carboxylesterase, and liver cholinesterase were all inhibited in young
    chickens, but there were no histological changes or alterations in
    neurotoxic esterase or liver carboxylesterase in the young birds.

         In a study by Belal et al. (1983), aldicarb was administered in
    the feed of 1-week-old chickens at a dietary level of 1 mg/kg. After
    11 days of treatment, the mortality rate was 27%. Blood cholinesterase
    activity levels were reduced by 74.3% during this treatment period.

         Spierenburg et al. (1985) reported that six cows became ill and
    two died after the accidental spill of Temik in a pasture. Chemical
    analyses for aldicarb in the rumen of one of the dead animals revealed
    the presence of aldicarb at a concentration above the lethal dose.
    Examination for aldicarb residues showed the meat and organs to be
    unfit for human consumption.

         Schafer & Bowles (1985) found the approximate acute oral LD50
    of aldicarb for the deermouse  Peromyscus maniculatus to be 1-6 mg/kg
    body weight.

        Table 11.  Oral and dietary toxicity of aldicarb to birds

    Species                       Age            Exposurea      Parameter      Concentration       Reference
    House sparrow                 adult          oral           LD50              0.8              Balcomb et al. (1984)
     (Passer domesticus)

    Redwinged blackbird           adult          oral           LD50              1.8              Balcomb et al. (1984)
     (Agelaius phoenicus)

    Grackle                                      oral           LD50              0.8               d
     (Quiscalus quiscula)

    Starling                                     oral           LD50              4.2               d
     (Sturnus vulgaris)

    Pigeon                                       oral           LD50              3.2               d
     (Columba liviavar.)

    California quail              10 months      oral           LD50           M: 2.6 (2-3.4)      Hudson et al. (1984)
     (Loportyx californica)                                                    F: 4.7 (3.3-6.6)

    Table 11 (contd).

    Species                       Age            Exposurea      Parameter      Concentration       Reference
    Bobwhite quail                mature         oral           LD50              2.8              Clarkson & Rowe
     (Colinus virginianus)                                                                         (1970)

    Pheasant                      3-4 months     oral           LD50            5.3 (3.9-7.4)      Hudson et al. (1984)
     (Phasianus colchicus)

    Pheasant                      10 days        diet           LC50            > 300              Hill et al. (1975)
     (Phasianus colchicus)

    Japanese quail                14 days        diet           LC50            387 (336-445)      Hill & Camardese
     (C. coturnix japonica)                                                                        (1986)

    Mallard duck                  5 days         diet           LC50            594 (507-695)      Hill et al. (1975)
     (Anas platyrhynchos)         10 days        diet           LC50            < 1000c

    a   Oral dosing consisted of a single capsular dose.  Dietary dosing consisted of 5 days feeding on a contaminated diet followed
         by a 2-day observation period.
    b   LD50   = lethal dose for 50% of animals, expressed as mg/kg body weight.  LC50   = lethal concentration for 50% of animals,
         expressed as mg/kg diet. M = male; F = female.
    c   There was 70% mortality at 1000 mg/kg.
    d   Letter by E.W. Schafer, Jr, dated 28 April 1975: Summary of three data sheets on avian toxicity. Union Carbide Agricultural
         Products Company.

    9.4  Population and ecosystem effects

         No studies have revealed effects at the population level
    resulting from the recommended use of the pesticide aldicarb, nor has
    significant introduction of aldicarb or its metabolites into the food
    chain been reported in the limited information available (Woodham et
    al., 1973b).

         Of 48 bobwhite quail  (Colinus virginianus) penned in treated
    fields (34 kg/ha), only one died as a result of ingesting Temik 10G
    granules. No effects were seen on the body weight of the test birds
    compared to controls (Clarkson et al., 1968). In a second study,
    Clarkson (1968a) misapplied Temik 10G to fields by surface broadcast
    or "spilled" it in one corner of the pen as a small heap of granules.
    No deaths of bobwhite quail were seen in the broadcast application,
    but the birds consumed "spilled" granules and died. Chickens refused
    to eat "spilled" granules even when hungry. Further studies were
    reviewed by Clarkson et al. (1969) who concluded that broadcast Temik
    10G granules could be toxic to bobwhite quail in the field under
    conditions of confinement and food stress. Incorporation of the
    granules into the soil and/or irrigation reduced or eliminated the
    potential hazard.

         In a study in which Woodham et al. (1973b) examined total toxic
    aldicarb residues in weeds, grasses, and wild-life in Texas after the
    soil was treated with aldicarb, no evidence of mortality among mammal
    or bird populations was observed in treated or adjacent areas. Of the
    small mammals, coyotes, and birds examined, only one bird had
    detectable levels of aldicarb residues (an oriole with a concentration
    level of 0.07 mg/kg). In all, 8 mammals and 14 birds were sampled.

         Bunyan et al. (1981) conducted an extensive field trial with
    sampling of invertebrates, birds, and small mammals around fields of
    sugar beet treated in furrow with aldicarb granules (10% ai) at 1.12
    kg aldicarb per ha. A dead partridge and high levels of residues in
    blackbirds and two small mammals trapped within the treated field
    indicated to the authors that the most significant hazard of aldicarb
    was from direct ingestion of non-incorporated granules by ground
    feeders soon after application. A secondary hazard involved
    aldicarb-poisoned earthworms that came to the surface of the soil
    particularly in wet conditions. Moribund worms containing residues
    were found 2-6 days after drilling. Low residues of aldicarb were
    found in herbivores eating young plants that had systemically absorbed
    aldicarb. Residues and reduced esterase activity in brain were found
    in a number of bird species feeding on the ground, indicating that
    exposure to aldicarb can be widespread in the case of granular

         The death of 600 songbirds, poisoned following the surface
    application of Temik granules without incorporation into the soil was
    reported by Baron & Merrian (1988).


    10.1  Evaluation of human health risks

         Aldicarb is an extremely hazardous pesticide. The human health
    risk arises mainly from the improper use of aldicarb and a failure to
    use protective equipment during its manufacture, formulation, and
    application. Aldicarb may contaminate food and drinking-water. The
    effects of excessive exposure are acute and reversible. Although the
    cholinergic effects may be severe and incapacitating and require
    hospitalization, seldom have they been fatal.

    10.1.1  Exposure levels  General population

         The main possible sources for general population exposure are
    food and water.

         Some data are available in the USA to estimate daily dietary
    intake of aldicarb (see section 5.2). Extensive data show that
    residues in most harvested crops are generally low and do not exceed
    the maximum residue limits if aldicarb is used according to good
    agricultural practice and recommended pre-harvesting periods are
    followed. However, even in this case, levels up to 1 mg/kg, and
    occasionally more, have been found in potatoes.

         High levels of aldicarb have been discovered in some food crops
    treated illegally with aldicarb. One poisoning incident occurred after
    the consumption of hydroponically grown cucumbers with levels of
    6.6-10.7 mg aldicarb/kg. Two incidences of poisoning were reported in
    the USA from contaminated watermelons where aldicarb levels ranged
    from < 0.01 to 6.3 mg/kg. However, there is no certainty that this
    range reflected the actual exposure.

         Contamination of ground water by aldicarb has occurred. About 12%
    of wells monitored in some regions of Canada exceeded 9 µg/litre. Of
    7802 wells sampled in New York State, USA, in an area of aldicarb use
    on potatoes, 5745 (73.6%) had no detectable residues, 1032 (13.3%) had
    trace amounts; and 1025 (13.1%) had concentrations greater than 7

         A nationwide survey of 15 000 private wells in the  USA showed
    levels of aldicarb in the water between 1 and 50 µg/litre in
    approximately one-third of the positive samples. Occasional levels of
    500 µg/litre in ground water have been reported in test bores.  Occupational exposure

         Air concentrations of aldicarb during agricultural application
    are minimized by the granular form of the product. However, some
    operations, such as the loading process, may be hazardous if adequate
    individual protection is not taken. Over-exposure to aldicarb leading
    to a tissue level of 0.275 mg/kg contributed to the death of a young
    worker loading formulated aldicarb. The main route of occupational
    exposure is through the skin, especially when workers do not follow
    recommended precautions and neglect the use of protective equipment.

    10.1.2  Toxic effects

         The effects or manifestations of aldicarb toxicity and its
    metabolites (sulfoxide and sulfones) result from its inhibitory action
    on acetylcholinesterase. The inhibition of cholinesterase is
    reversible. The clinical signs and symptoms, depending upon the
    magnitude and severity of exposure, include headache, dizziness,
    anxiety, excessive sweating, salivation, lacrimation, increased
    bronchial secretions, vomiting, diarrhoea, abdominal cramps, muscle
    fasciculations, and pinpoint pupils. There is no substantial evidence
    of carcinogenicity, mutagenicity, teratogenicity or immunotoxicity.

         In human subjects, a single oral administration of 0.025 mg
    aldicarb/kg body weight produced significant inhibition of whole blood
    cholinesterase activity, but no symptoms. A dosage of 0.10 mg/kg body
    weight led to cholinergic signs and symptoms and a dosage of 0.26
    mg/kg body weight resulted in acute intoxication that needed

    10.1.3  Risk evaluation

         The risks from an extremely hazardous chemical can be evaluated
    only in terms of different kinds of exposure and only in terms of the
    safety measures available and the degree of certainty of their use.

         By far the greatest risk from aldicarb is to those who
    manufacture, formulate and use it. Aldicarb is manufactured in a
    closed system. The use of aldicarb in granular form reduces the
    generation of dust and the risk from occupational exposure. There have
    been a few accidents associated with the formulation and use, but each
    was the result of one or more clear violations of safety rules (see
    section 8.2.1). However, although aldicarb is used in granules, there
    can be a hazard to applicators if they do not follow all recommended

         The sources of aldicarb residues in food include the legal
    application of aldicarb to soil in which crops for which aldicarb use
    has been approved are grown, as well as the illegal or improper use of
    aldicarb. There is no evidence of a health risk from aldicarb in food
    to the general population at recommended application rates and
    employing current techniques. However, a substantial hazard exists
    when aldicarb is used on non-approved crops, as indicated by reports
    of several poisoning episodes. On the other hand, soil application
    rates and tolerances for aldicarb residues have been set for approved
    aldicarb use to protect the general population. The success of these
    measures is suggested by the observation that no reports have been
    found of adverse health effects attributable to aldicarb exposure from
    commodities where aldicarb was used properly. The limited
    market-basket survey data suggest that exposure to aldicarb will
    probably not exceed 1 µg/kg body weight per day in the USA. This is
    well below the acceptable daily intake (ADI) established by the Joint
    FAO/WHO Meeting on Pesticide Residues (FAO/WHO, 1983).

         Aldicarb has not been found in public water supplies derived from
    deep aquifers or surface waters, and thus there is no anticipated risk
    from aldicarb in water obtained from these sources. Aldicarb water
    contamination has been reported in ground water, generally at levels
    of 1-50 µg/litre in the USA with occasional findings of up to 500
    µg/litre. However, most wells sampled in contaminated areas have
    undetectable or trace amounts of aldicarb or its metabolites. Reduced
    contamination of ground water has resulted from the restriction of use
    in sandy soils.

         Assuming an average daily water consumption of 2 litres and an
    average body weight of 60 kg, the exposure of people consuming water
    from locally contaminated shallow wells containing between 1 and 50
    µg/litre would result in an exposure to metabolites of aldicarb
    ranging from 0.033 to 1.7 µg/kg body weight per day. A well containing
    water contaminated with aldicarb at a level of 500 µg/litre would
    result in an exposure of 17 µg per kg body weight per day. The most
    appropriate available study for the assessment of drinking-water risk
    is a study in which aldicarb sulfoxide and sulfone were administered
    to rats in drinking-water. The no-observed-effect-level for
    acetylcholinesterase inhibition in this study was 480 µg/kg body
    weight per day. The estimated exposure from contaminated ground water
    is therefore well below this level.

    10.2  Evaluation of effects on the environment

         With full incorporation of aldicarb granules into soil at a depth
    of 5 cm, as recommended by the manufacturer, there is minimal hazard
    to birds and small mammals. Non-target soil invertebrates,

    such as earthworms, can be killed when aldicarb is used at recommended
    application rates. Kills of up to 600 songbirds have been reported
    from misapplication of the granules on the soil surface, since birds
    can die after ingesting a single granule.  Small mammals would be
    similarly at risk from surface-broadcast aldicarb.

         There is no indication that aquatic organisms have been killed
    from aldicarb poisoning despite its relatively high potential
    toxicity. Aldicarb could contaminate drainage ditches when used in
    areas where periodic torrential rainfall is likely, causing
    substantial run-off of both water and surface soil. However, this is
    unlikely to kill fish or aquatic invertebrates.


    11.1  Conclusions

    11.1.1  General population

         Aldicarb is a highly toxic pesticide.

         Accidental poisoning and a controlled laboratory study resulted
    in cholinergic symptoms that included the following: malaise, blurred
    vision, muscle weakness in arms and legs, epigastric cramping pain,
    excessive sweating, nausea, vomiting, non-reactive contracted pupils,
    dizziness, dyspnoea, air hunger, diarrhoea, and muscle fasiculation.
    The symptoms disappeared spontaneously within 6 h. The highest oral
    dose that produced no observable symptoms in a human study was 0.05
    mg/kg body weight, although there was significant transient
    whole-blood cholinesterase inhibition at this level.

         The primary mechanism of aldicarb toxicity is
    acetylcholinesterase inhibition. It is accepted that carbamate
    insecticides interfere with the ability of acetylcholinesterase to
    break down the chemical transmitter acetylcholine at synaptic and
    myoneural junctions. The same mechanism of action is evident in both
    target and non-target organisms. There is no substantial evidence of
    carcinogenicity, mutagenicity, teratogenicity, or immunotoxicity.

    11.1.2  Occupational exposure

         Intoxication and poisoning due to occupational exposure are known
    to have occurred as a result of a neglect of recommended safety

    11.1.3  Environmental effects

         Aldicarb will not cause effects on organisms in the environment
    at the population level. Incidents of kills of individual birds and
    small mammals will occur where granules are not fully incorporated
    into the soil. Aquatic organisms are not at risk from aldicarb.

    11.2  Recommendations for protection of human health and the

    a)   The handling and application of aldicarb should be undertaken by
         trained applicators.

    b)   The agricultural use of aldicarb should be restricted to
         situations where less hazardous substitutes are unavailable.

    c)   Manufacturing of aldicarb is a hazardous process with   possible
         risk of exposure to toxic chemicals. Safety systems should be
         adequate to prevent leaks and discharges.

    d)   To minimize or eliminate exposure of terrestrial vertebrates to
         aldicarb, granules should be fully incorporated into soil to a
         depth of 5 cm, as recommended by the manufacturer.


    a)   Additional pharmacokinetic studies, including uptake studies
         following dermal application, are needed to allow physiologically
         based pharmacokinetic modelling.

    b)   A case of intoxication resulting from the consumption of
         aldicarb-containing mint demonstrated effects at what appeared to
         be an unusually low dosage. A study of treated mint might reveal
         a previously unknown metabolite or other factors relevant to this
         poisoning episode.

    c)   Studies of the immunological effects of aldicarb are
         inconclusive. Additional studies are needed to examine more
         thoroughly the effects of aldicarb on the immune system.

    d)   A reproduction study in the rat is needed to investigate concerns
         of fetal susceptibility. One such study is underway.


         The Joint FAO/WHO Expert Committee on Pesticide Residues (JMPR)
    recommended an ADI of 1 µg/kg (FAO/WHO, 1980). In 1982, JMPR revised
    the ADI upward to 5 µg per kg body weight per day. Aldicarb is
    classified as an extremely hazardous pesticide (WHO, 1990b).


     H.W., GIBBSONS, G., & STOESZ, P.A. (1979) Suspected carbamate
    intoxications - Nebraska. Morb. Mortal. wkly Rep., 28: 133-134.

    AARONSON, M.J., TESSARI, J.D., SAVAGE, E.P., & GOES, E.A. (1980) 
    Determination of aldicarb sulfone in hydroponically grown cucumbers.
    J. food Saf., 2: 171-181.

    KEARNEY, P.C., OTTO, S., ROBERTS, T.R., & VONK, J.W. (1987) Potential
    contamination of groundwater by pesticides. Pure appl. Chem., 59(10):

    ALDRIDGE, W.N. & MAGOS, L. (1978) Carbamates, thiocarbamates, and
    dithio-carbamates, Luxembourg, Commission of the European Communities.

    ANDRAWES, N.R., DOROUGH, H.W., & LINDQUIST, D.A. (1967) Degradation
    and elimination of Temik in rats. J. econ. Entomol., 60: 979-987.

    ANDRAWES, N.R., BAGLEY, W.P., & HERRETT, R.A. (1971a) Fate and
    carryover properties of Temik aldicarb pesticide
    [2-methyl-2-(methylthio)propionaldehyde O-(methylcarbamoyl)oxime] in
    soil. J. agric. food Chem., 19: 727-730.

    ANDRAWES, N.R., BAGLEY, W.P., & HERRETT, R.A. (1971b) Metabolism of
    2-methyl-2-(methylthio)propionaldehyde O-(methylcarbamoyl)oxime (Temik
    aldicarb pesticide) in potato plants. J. agric. food Chem., 19:

    ANDRAWES, N.R., ROMINE R.R., & BAGLEY, W.P. (1974) Metabolism and
    residues  of Temik aldicarb pesticide in cotton foliage and seed under
    field conditions. J. agric. food Chem., 21: 379-386.

    AOAC (1990) 985.23.  N-Methylcarbamate insecticide and metabolite
    residues: Liquid chromatographic method. In: Helrich, K., ed. Official
    methods of analysis, Arlington, Virginia, Association of Official
    Analytical Chemists, pp. 292-294.

    BAIER, J. & MORAN, D. (1981) Status report on aldicarb contamination
    of ground water as of September 1981, Suffolk County Department of
    Health Services.

    BALCOMB, R., STEVENS, R., & BOWEN, C. (1984) Toxicity of 16 granular
    insecticides to wild-caught songbirds. Bull. environ. Contam.
    Toxicol., 33:  302-307.

    BARON, R.L. & MARRIAM, T. (1988) Toxicology of aldicarb. Rev. environ. 
    Contam. Toxicol. 105: 1-69.

    BELAL, M., RIAD, S., EL-HUSSEINY, O., & AWAAD, M. (1983) The toxicity
    of some insecticides to Fayoumi chicks. Egypt. J. anim. Prod., 22:

    BERG, G.L., ed. (1981) Farm chemicals handbook, Willoughby, Ohio,
    Meister Publishing Co., p. C326.

    BLACK, A.L., CHIU, Y.C., FAHMY, M.A.H., & FUKUTO, T.R. (1973)
    Selective toxicity of N-sulfenylated derivatives of insecticidal
    methylcarbamate esters. J. agric. food Chem., 21: 747-751.

    BLEVINS, D., LIJINSKY, W., & REGAN, J.D. (1977) Nitrosated
    methylcarbamate insecticides: Effect on the DNA of human cells. Mutat.
    Res., 44: 1-7.

    BOWMAN, B.W. (1988) Mobility and persistence of metolachlor and
    aldicarb in field lysimeters. J. environ. Qual., 17(4): 689-694.

    BULL, D.L. (1968) Metabolism of UC-21149
    [2-methyl-2-(methylthio)propionaldehyde O-(methylcarbamoyl)oxime] in
    cotton plants and soil in the field. J.  econ. Entomol., 61:

    BULL, D.L., LINDQUIST, D.A., & COPPEDGE, J.R. (1967) Metabolism of
    2-methyl- 2(methylthio)propionaldehyde O-(methylcarbamoyl)oxime in
    insects. J. agric.  food Chem., 15: 610- 616.

    BULL, D.L., STOKES, R.A., COPPEDGE, J.R., & RIDGWAY, R.L. (1970)
    Further studies of the fate of aldicarb in soil. J. econ. Entomol.,
    63: 1283- 1289.

    (1981) An intensive field trial and a multi-site surveillance exercise
    on the use of aldicarb to investigate methods for the assessment of
    possible environmental hazards presented by new pesticides. Agro
    Ecosyst., 7: 239-262.

    CAIRNS, T., SIEGMUND, E.G., & SAVAGE, T.S. (1984) Persistence and
    metabolism of aldicarb in fresh potatoes. Bull. environ. Contam.
    Toxicol., 32: 274-281.

    CAMBON, C., DECLUME, C., & DERACHE, R. (1979) Effect of the
    insecticidal carbamate derivatives (carbofuran, primicarb, aldicarb)
    in the activity of acetylcholinesterase in tissues from pregnant rats
    and fetuses. Toxicol. appl. Pharmacol., 49: 203-208.

    CAMBON, C., DECLUME, C., & DERACHE, R. (1980) Foetal and maternal rat
    brain acetylcholinesterase: Isoenzymes changes following insecticidal
    carbamate derivatives poisoning. Arch. Toxicol., 45: 257-262.

    CARPENTER, C.P. & SMYTH, H.F. (1965) Recapitulation of pharmacodynamic
    and acute toxicity studies on Temik (Unpublished Mellon Institute
    Report No. 28- 78).

    CARPENTER, C.P. & SMYTH, H.F. (1966) Temik 10G. 15-Day dermal
    applications to rabbits (Unpublished Mellon Institute Report No.

    CDC (CENTERS FOR DISEASE CONTROL) (1979) Epidemiologic notes and
    reports: Suspected carbamate intoxications - Nebraska. Morb. Mortal.
    wkly  Rep., 28: 133-134.

    CHAPUT, D. (1988) Simplified multiresidue method for liquid
    chromatographic determination of  N-methyl carbamate insecticides in
    fruit and vegetables J.  Assoc. Off. Anal. Chem., 71(3): 542-546.

    CID, M.G. & MATOS, E. (1984) Induction of sister-chromatid exchanges
    in cultered human lymphocytes by aldicarb, a carbamate pesticide.
    Mutat. Res., 138: 175-179.

    CID, M.G. & MATOS, E. (1987) Chromosomal aberrations in cultured human
    lymphocytes treated with aldicarb, a carbamate pesticide. Mutat. Res.,
    191: 99-103.

    CID, M.G., LORIA, D., & MATOS, E. (1988) Nitroso-aldicarb induces
    sister-chromatid exchanges in human lymphocytes in vitro. Mutat. Res.,
    204: 665-668.

    CIMINO, M.C., GALLOWAY, S.M., & IVETT, J.L. (1984) Mutagenesis
    evaluation  of aldicarb technical 93.43% in the mouse bone marrow
    cytogenetic assay (Study conducted for Union Carbide Corporation,
    submitted to WHO).

    CLARKSON, V.A. (1968a) Field evaluations of the toxic hazard of
    misapplied Temik formulations to Bobwhite quail and chickens (Study
    conducted for Union Carbide Corporation, submitted to WHO).

    CLARKSON, V.A. (1968b) Toxicity of Temik, Temik sulfoxide and Temik
    sulfone to Bluegill sunfish (Study conducted for Union Carbide
    Corporation, submitted to WHO).

    CLARKSON, V.A. & ROWE, B.K. (1970) Field evaluations of the toxic
    hazard of Temik formulations 10G, 10GV, 10GC and 10GV134 to Bobwhite
    quail (Study conducted for Union Carbide Corporation, submitted to

    CLARKSON, V.A., ROWE, B.K., & HENSLEY, W.H. (1968) Field evaluation of
    the toxic hazard of Temik to Bobwhite quail (Unpublished Union Carbide
    Corporation study, submitted to WHO).

    CLARKSON, V.A., ROWE, B.K., & HENSLEY, W.H. (1969) Report on
    additional field tests with Temik 10G aldicarb pesticide on the
    potential hazard to Bobwhite quail (Study conducted for Union Carbide
    Corporation, submitted to WHO).

    COHEN, S.Z., EIDEN, C., & LORBER, M.B. (1986) Monitoring groundwater
    for pesticides. In: Garner, W.Y., ed. Evaluation of pesticides in
    groundwater, Washington, DC, American Chemical Society, pp. 170-196
    (ACS Symposium Series 315).

    COPE, R.W. & ROMINE, R.R. (1973) Temik 10G aldicarb pesticide: Results
    of aldicarb ingestion and exposure studies with humans and results of
    monitoring human exposure in working environments (Unpublished Union
    Carbide study, Project No. 111A13, 116A16, File No. 18269).

    Fate of 2-methyl-2-(methylthio)propionaldehyde
    O-(methylcarbamoyl)oxime (Temik) in cotton plants and soil. J. agric.
    food Chem., 15: 902-910.

    COPPEDGE, J.R., BULL, D.L., & RIDGWAY, R.L. (1977) Movement and
    persistence of aldicarb in certain soils. Arch. environ. Contam.
    Toxicol., 5: 129-141.

    W.C., Jr, & DUDLEY, R.F. (1966) Systemic insecticides for control of
    cotton insects. J. econ. Entomol., 59: 958.

    DAVIS, J.W., WATKINS, W.C., Jr, COWAN, C.B., Jr, RIDGWAY, R.L., &
    LINDQUIST, D.A. (1966) Control of several cotton pests with systemic
    insecticides. J. econ. Entomol., 59: 159.

    P.S. (1990) Aldicarb treatment inhibits the stimulatory activity of
    macrophages without affecting the T-cell responses in the syngeneic
    mixed lymphocyte reaction. Int. J. Immunopharmacol., 12: 337-348.

    DE HAAN, F.A.M. (1988) Effects of agricultural practices on the
    physical, chemical and biological properties of soils: Part III.
    Chemical degradation of soil as the results of the use of mineral
    fertilizers and pesticides: Aspects of soil quality evaluation. Neth.
    J. agric. Sci., 36: 211-235.

    DEPASS, L.R., WEAVER, E.V., & MIRRO, E.J. (1985) Aldicarb sulfoxide/
    aldicarb sulfone mixture in drinking water of rats: Effects on growth
    and acetylcholinesterase activity. J. Toxicol. environ. Health, 16:

    DOROUGH, H.W. & IVIE, G.W. (1968) Temik-S35 metabolism in a lactating
    cow.  J. agric. food Chem., 16: 460-464.

    DOROUGH, H.W., DAVIS, R.B., & IVIE, G.W. (1970) Fate of
    Temik-carbon-14 in lactating cows during a 14-day feeding period. J.
    agric. food Chem., 18: 135- 142.

    DOULL, J., KLAASSEN, C.D., & AMDUR, M.O., ed. (1980) Casarett &
    Doull's toxicology: the basic science of poisons, 2nd ed., New York,
    MacMillan Publishing Co., pp. 374-379.

    MORTEIMANS, K., ROSENKRANZ, S., & SIMMON, V.F. (1985) Reproducibility
    of microbial mutagenicity assays: II. Testing of carcinogens and
    noncarcino-gens in  S. typhimurium and  E. coli. Environ. Mutagen.,
    7: 1-248.

    ELESPURU, R.K. & LIJINSKY, W. (1973) The formation of carcinogenic
    nitroso compounds from nitrite and some types of agricultural
    chemicals. Food Cosmet.  Toxicol., 11: 807-817.

    ERCEGOVICH, C.D. & RASHID, K.A. (1973) Mutagenesis induced in mutant
    strains of Salmonella typhimurium by pesticides. Abstracts of papers,
    Washington, DC, American Chemical Society, p. 43.

    FAO/WHO (1980) Pesticide residues in food. 1979 Report of the 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,
    Food and Agriculture Organization of the United Nations (Plant
    Production and Protection Paper 20).

    FAO/WHO (1983) Pesticide residues in food. 1982 Report of the 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,
    Food and Agriculture Organization of the United Nations (FAO Plant
    Production and Protection Paper 46).

    FARAGE-ELAWAR, M. (1988) Toxicity of aldicarb in young chicks.
    Neurotoxicol. Teratol., 10: 549-554.

    FARAGE-ELAWAR, M., EHRICH, M.F., & MISRA, H.P. (1988) Effects of
    multiple oral doses of two carbamate insecticides on esterae levels in
    young and adult chickens. Pestic. Biochem. Physiol., 32: 262-268.

    FATHULLA, R.N., JONES, F.A., HARKIN, J.M., & CHESTERS, G. (1988)   
    Distribution and persistence of aldicarb residues in the
    sand-and-gravel aquifer of central Wisconsin. 1. Relationship between
    aldicarb residue concentration and groundwater chemistry. Adv.
    environ. Modelling, 13: 59-84.

    FELDMAN, R.J. & MAIBACH, H.I. (1970) Pesticide percutaneous
    penetration in man. J. invest. Dermatol., 54: 435.

    J.E., NORDSTROM, D., HANRAHAN, L., & BELLUCK, D. (1986) Chronic
    exposure to aldicarb-contaminated ground water and human immune
    function. Environ. Res., 41: 633-645.

    FORAN, J.A., GERMUSKA, P.J., & DELFINO, J.J. (1985) Acute toxicity of
    aldicarb, aldicarb sulfoxide and aldicarb sulfone to  daphnia  laevis.
    Bull. environ. Contam. Toxicol., 35: 546-550.

    GAINES, T.B. (1969) Acute toxicity of pesticides. Toxicol. appl.
    Pharmacol., 14: 515-534.

    GALOUX, M., VAN DAMME, J.C., BARNES, A., & POTVIN, J. (1979) GLC
    determination of aldicarb sulfoxide and aldicarb in soils and water
    using a Hall electrolytic conductivity detector. Chem. Abstr., 91: 164

    GIVEN, C.J. & DIERBERG, F.E. (1985) Effect of pH on the rate of
    aldicarb hydrolysis. Bull. environ. Contam. Toxicol., 34: 627-633.

    GODEK, E.G., NAISMITH, R.W., & MATTHEWS, R.J. (1984) Rat hepatocyte
    primary culture/DNA repair test (Study conducted for Union Carbide
    Corporation, submitted to WHO).

    WHEELER, H.W. (1980) Suspected foodborne carbamate pesticide
    intoxications associated with ingestion of hydroponic cucumbers. Am.
    J. Epidemiol., 111: 254- 259.

    STRATTON, J., WALLER, K., JACKSON, R.J., & KIZER, K.W. (1990a) 
    Pesticide food poisoning from contaminated watermelons in California,
    1985. Arch. environ. Health, 45(4): 229-236.

    GOLDMAN, L.R., BELLER, M., & JACKSON, R.J. (1990b) Aldicarb food
    poisonings in California, 1985-1988: Toxicity estimates for humans.
    Arch. environ. Health, 45(3): 141-147.

    GONZALEZ, D.A. & WEAVER, D.J. (1986) Monitoring concentrations of
    aldicarb and its breakdown products in irrigation water runoff and
    soil from agricultural fields in Kern Country 1985, Sacramento,
    California Department of Food and Agriculture, Environmental
    Monitoring and Pesticide Management, pp. 1-9 (Unpublished report).

    J.M. (1987) An outbreak of watermelon-borne pesticide toxicity. Am. J.
    public Health, 77:  1431-1434.

    GRIFFITH, J. & DUNCAN, R.C. (1985) Grower reported pesticide
    poisonings among Florida citrus fieldworkers. J. environ. Sci. Health,
    B20: 61-72.

    HAINES, R.G. (1971) Ingestion of aldicarb by human volunteers: A
    controlled study of the effect of aldicarb on man, Terryton, NY, Union
    Carbide Corporation (Unpublished report with addendum).

    HAJJAR, N.P. & HODGSON, E. (1982) Sulfoxidation of
    thioether-containing pesticides by the
    flavin-adenine-dinucleotide-dependent monooxygenase of pig liver
    microsomes. Biochem. Pharmacol., 31: 745-752.

    HAMADA, N.N. (1988) One-year chronic oral toxicity study in beagle
    dogs with aldicarb technical (Study conducted for Rhône-Poulenc AG
    Company, submitted to WHO).

    HANSEN, J.L. & SPIEGEL, M.H. (1983) Hydrolysis studies of aldicarb,
    aldicarb sulfoxide and aldicarb sulfone. Environ. Toxicol. Chem., 2:

    HAQUE, A. & EBING, W. (1983) [Toxicity determination of pesticides to
    earthworms in the soil.] Z. Pflanzenkr. Pflanzenschutz, 90: 395-408
    (Abstract) (in German).

    HAYES, W.J. (1982) Pesticides studied in man, Baltimore, Maryland,
    Williams & Wilkins Publishers, pp. 447-462.

    HEGG, R.O., SHELLY, W.H., JONE, R.L., & ROMINE, R.R. (1988) Movement
    and degradation of aldicarb residues in South Carolina loamy sand
    soil. Agric.  Ecosyst. Environ., 20: 303-315.

    HICKS, B.W., DOROUGH, H.W., & MEHENDALE, H.M. (1972) Metabolism of
    aldicarb pesticide in laying hens. J. agric. food Chem., 20: 151-156.

    HIEBSCH, S. (1988) The occurence of 35 pesticides in Canadian drinking
    water and surface water, Ottawa, Canada, Environmental Health
    Directorate, Department of National Health and Welfare.

    HILL, E.F. & CAMARDESE, M.B. (1981) Subacute toxicity testing with
    young birds:  Response in relation to age and interest variability in
    LC50 estimates. In: Lamb, D.W. & Kenaga, E.E., ed. Proceedings of
    the Conference on Avian and Mammalian Toxicology, Philadelphia,
    American Society for Testing and Material, pp. 41-65 (Abstract) (STP

    HILL, E.F. & CAMARDESE, M.B. (1986) Lethal dietary toxicities of
    environmental contaminants and pesticides to Coturnix, Washington, DC,
    US Department of Interior, Fish and Wildlife Service, 23 pp (Technical
    Report No. 2).

    HILL, E.F., HEALTH, R.G., SPANN, J.W., & WILLIAM, J.D. (1975) Lethal
    dietary toxicities of environmental pollutants to birds, Washington,
    DC, US Department of Interior, Fish and Wildlife Service, 8 pp
    (Special Report No. 191).

    B.C. (1987) Report of illness caused by aldicarb-contaminated
    cucumbers. Food Addit. Contam., 5: 155-160.

    HOPKINS, A.R. & TAFT, H.M. (1965) Control of certain cotton pests with
    a new systemic insecticide, UC-21149. J. econ. Entomol., 58: 746-749.

    HUDSON, R.H., TUCKER, R.K., & HAEGELE, M.A. (1984) Handbook of
    toxicity of pesticides to wildlife, Washington, DC, US Department of
    Interior, Fish and Wildlife Service (Resource Publication No. 153).

    Teratology study in rabbits, Institute, West Virginia, Union Carbide

    IRPTC (1989) IRPTC data profile on aldicarb, Geneva, International
    Register of Potentially Toxic Chemicals, United Nations Environment
    Programme (Report No. OR 2134).

    F.A. (1977) Aldicarb residues in oranges, citrus by-products, orange
    leaves and soil after an aldicarb soil application in an orange grove.
    J. agric. food Chem., 25: 933.

    EPSTEIN, D., NEUTRA, R.R., KELTER, A., & KIZER, K.W. (1986) Aldicarb
    food poisoning from contaminated melons - California. Morb. Mortal.
    wkly Rep., 35: 255-257.

    JONES, A.S. (1976) Metabolism of aldicarb by five soil fungi. J.
    agric. food Chem., 24: 115-177.

    JONES, R.L. (1986) Field, laboratory and modelling studies on the
    degradation and transport of aldicarb residues in soil and
    groundwater. In: Garner, W.Y., ed. Evaluation of pesticides in
    groundwater, Washington, DC, American Chemical Society, pp. 197-218
    (ACS Symposium Series 315).

    JONES, R.L. (1987) Central California studies on the degradation and
    movement of aldicarb residues. J. Contam. Hydrol., 1: 287-298.

    JONES, R.L., ROURKE, R.V., & HANSEN, J.L. (1986) Effect of application
    methods on movement and degradation of aldicarb residues in Maine
    potato fields. Environ. Toxicol. Chem., 5: 167-173.

    JONES, R.L., HORNSBY, A.G., RAO, P.S., & ANDERSON, M.P. (1987a)
    Movement and degradation of aldicarb residues in the saturated zone
    under citrus groves on the Florida ridge. J. Contam. Hydrol., 1:

    JONES, R.L., KIRKLAND, S.D., & CHANCEY, E.L. (1987b) Measurement of
    the environmental fate of aldicarb residues in a Nebraska sand Hills
    soil. Appl. agric. Res., 2: 177-182.

    KNAAK, J.B., TALLANT, M.J., & SULLIVAN L.J. (1966a) The metabolism of
    2-methyl-2-(methylthio)propionaldehyde O-(methylcarbamoyl)oxime in the
    rat. J. agric. food Chem., 14: 573-578.

    KNAAK, J.B., TALLANT, M.J., BARTLEY, W.J., & SULLIVAN, L.J. (1966b) 
    Metabolism of carbaryl in the rat, guinea pig and man. J. agric. food
    Chem., 13(6): 537-543.

    KRAUSE, R.T. (1979) Resolution, sensitivity and selectivity of an HPLC
    post-column fluorometric labelling technique for determination of
    carbamate insecticides. J. Chromatogr., 185(1): 615-624.

    KRAUSE, R.T. (1980) Resolution, sensitivity and selectivity of
    HPLC-post column fluorometric labelling technique for determination of
    carbamate insecticides Chem. Abstr., 92: 141601.

    KRAUSE, R.T. (1985a) Liquid chromatographic determination of N-
    methylcarbamate insecticides and metabolites in crops. I.
    Collaborative study. J. Assoc. Off. Anal. Chem., 68(4): 726-733.

    KRAUSE, R.T. (1985b) Liquid chromatographic determination of N-
    methylcarbamate insecticides and metabolites in crops. II. Analytical
    characteristics and residue findings. J. Assoc. Off. Anal. Chem.,
    68(4): 734- 741.

    KUHR, R.J. & DOROUGH, H.W. (1976) Carbamate insecticides: Chemistry,
    biochemistry, and toxicology, Cleveland, Ohio, CRC Press, Inc., pp.
    2-6, 103- 112, 187-190, 211-213, 219-229.

    KUSESKE, D.W., FUNK, B.R., & SCHULTZ, J.T. (1974) Effects and
    persistence of Baygon (propoxur) and Temik (aldicarb) insecticides in
    soil. Plant Soil, 41:  255-269.

    J.P. (1988) Sorption of the pesticide aldicarb by soil: Its mobility
    through a saturated medium in the presence of dissolved organic
    matter. Water Pollut. Res. J. Can., 23(2): 253-269.

    LANDAU, M. & TUCKER, J.W. (1984) Acute toxicity of EDB and Aldicarb to
    young of two estuarine fish species. Bull. environ. Contam. Toxicol.,
    33: 127-132.

    LASKI, R.R. & VANNELLI, J.J. (1984) Survey of potatoes grown in New
    York state for aldicarb residues. Bull. environ. Contam. Toxicol., 32:

    LEE, M.H. & RANSDELL, J.F. (1984) A farmworker death due to pesticide
    toxicity: a case report. J. Toxicol. environ. Health, 14: 239-246.

    LEMLEY, A.T. & ZHONG, W.Z. (1983) Kinetics of aqueous base and acid
    hydrolysis of aldicarb, aldicarb sulfoxide and aldicarb sulfone. J.
    environ.  Sci. Health, B18: 189-206.

    LEMLEY, A.T., WAGNET, R.T., & ZHONG, W.Z. (1988) Sorption and
    degradation of aldicarb and its oxidation products in a soil-water
    flow system as a function of pH and temperature. J. environ. Qual.,
    17(3): 408-414.

    LIGHTFOOT, E.N. & THORNE, P.S. (1987) Laboratory studies on mechanisms
    for the degradation of aldicarb, aldicarb sulfoxide and aldicarb
    sulfone Environ. Toxicol. Chem., 6: 337-394.

    LIJINSKY, W. & SCHMAHL, D. (1978) Carcinogenicity of N-nitroso
    derivatives of N-methylcarbamate insecticides in rats. Ecotoxicol.
    environ. Saf., 2: 413-419. 

    Focus: A national evaluation of the leaching potential of aldicarb:
    Part I - An integrated assessment methodology. Groundwater monit.
    Rep., Fall 1989: 109- 125.

    LORBER, M., COHEN, S. & DEBUCHANNE (1990) Focus: A national evaluation
    of the leaching potential of aldicarb: Part II - An evaluation of
    groundwater monitoring data. Groundwater monit. Rep., Winter 1990:

    MAIBACH, H.I., FELDMAN, R.J., MILBY, T.H., & SERAT, W.F. (1971)
    Regional variation in percutaneous penetration in man. Arch. environ.
    Health, 23: 208- 211.

    MAITLEN, J.C. & POWELL, D.M. (1982) Persistence of aldicarb in soil
    relative to the carry-over of residues into crops. J. agric. food
    Chem., 30: 589-592.

    (1970) Aldicarb residues in apples, pears, sugarbeets and cottonseed,
    performance in apples and pears, Washington, DC, US Department of
    Agriculture, Agricultural Research Service (Report AR5-33-135).

    MARSHALL, E. (1985) The rise and decline of Temik. Science, 229:

    MARSHALL, T.C. & DOROUGH, H.W. (1979) Biliary excretion of carbamate
    insecticides in the rat. Pestic. Biochem. Physiol., 11: 56-63.

    MARTIN, A.D., NORMAN, G., STANLEY, P.I., & WESTLAKE, G.E. (1981) Use
    of reactivation techniques for the differential diagnosis of
    organophosphorus and carbamate pesticide poisoning in birds. Bull.
    environ. Contam. Toxicol., 26:  775-780.

    R., MUIRHEAD, K., HORAN, P., & GRAINICK, H. (1985) Normal human blood
    density gradient lymphocytes subset analysis. 1. An interlaboratory
    flow cytometric comparison of 85 normal adults. Am. J. Hematol., 20:

    MARTIN, H. & WORTHING, C.R., ed. (1977) Pesticide manual, Croydon,
    British Crop Protection Council, p. 6.

    MAYER, F.L. (1987) Acute toxicity handbook of chemicals to estuarine
    organisms, Gulf Breeze, Florida, US Environmental Protection Agency,
    Environmental Research Laboratory, 14 pp (Unpublished report).

    MAYER, F.L. & ELLERSIECK, M.R. (1986) Manual of acute toxicity:
    interpretation and data base for 410 chemicals and 66 species of
    freshwater animals, Washington, DC, US Department of Interior, Fish
    and Wildlife Service, 9 pp (Report No. 160).

    REYNOLDS, H.T., & OSMAN, M.F. (1966) Metabolism of
    2-methyl-2-(methylthio)-propianaldehyde O-(methylcarbamoyl)oxime in
    plant and insect. J. agric. food Chem., 14: 579-584.

    D.P. (1985) Peer Review Committee Report - The Florida Temik study:
    Groundwater monitoring, Las Vegas, NV, US Environmental Protection
    Agency (Final report) (EMSL/ORD).

    MITCHELL, A., RUDD, C.J., & CASPARY, W.J. (1988) Evaluation of L5178Y
    mouse lymphoma cell mutagenesis assay: intralaboratory results for
    sixty-three coded chemicals tested at SRI International Environ. mol.
    Mutagen., 12: 37-102.

    MOYE, H.A. (1975) Esters of sulfonic acids as derivatives for the gas
    chromatographic analysis of carbamate pesticides. J. agric. food
    Chem., 23(3): 415-418.

    MOYE, H.A. & MILES, C.J. (1988) Aldicarb contamination of groundwater
    Rev. environ. Contam. Toxicol., 105: 99-146.

    MOYE, H.A., SCHERER, S.J., & ST. JOHN, P.A. (1977) Dynamic fluorogenic
    labeling of pesticides for HPLC: Detection of N-methyl carbamates with
    o-phthaladehyde. Anal. Lett., 10(3): 1049-1073.

    MUSZKAT, L. & AHARONSON, N. (1983) GC/CI/MS analysis of aldicarb,
    butocar-boxim and their metabolites. J. chromatogr. Sci., 21: 411-414.

    MYERS, R.C., WEIL, C.S., & FRANK, F.R. (1982) Temik 5G (Corn Cob
    Grits). Percutaneous toxicity and skin irritancy study, Export,
    Pennsylvania, Union Carbide Bushy Run Research Center, 12 pp
    (Unpublished Project Report No. 45-88, submitted to WHO by
    Rhône-Poulenc Co.).

    MYERS, R.C., DEPASS, L.R., & FRANK, F.R. (1983) Temik 5G (Corn Cob
    Grit).  Acute peroral toxicity and eye irritancy study, Export,
    Pennsylvania, Union Carbide Bushy Run Research Center, 10pp
    (Unpublished Project Report No. 46-100, submitted to WHO by
    Rhône-Poulenc Co.).

    MYHR, B.C. & CASPARY, W.J. (1988) Evaluation of the L5178Y mouse
    lymphoma cell mutagenesis assay: Intralaboratory results for
    sixty-three coded chemicals tested at Litton Bionetics, Inc. Environ.
    mol. Mutagen., 12: 103-194.

    NAS (1986) Drinking water and health, Washington, DC, National Academy
    of Sciences, Vol. 6, pp. 13-19.

    NCI (1979) Bioassay of aldicarb for possible carcinogencity, Bethesda,
    Maryland, National Cancer Institute (Report NCI-CG-TR-136).

    NYCUM, J.S. & CARPENTER, C. (1970) Summary with respect to guideline
    PR70-15 (Unpublished Mellon Institute Report No. 31-48).

    W.P., BINNING, L.K., BIDGOOD, R.C., & NORDHEIM, E.V. (1987) Aldicarb
    immunomodulation in mice: An inverse dose-response to parts per
    billion levels in drinking water. Arch. environ. Contam. Toxicol., 16:

    OONNITHAN, E.S. & CASIDA, J.E. (1967) Oxidation of methyl- and
    dimethyl-carbamate insecticide chemicals by microsomal enzymes and
    anticholinesterase activity of the metabolites. J. agric. food Chem.,
    16: 29-44.

    W.B. (1986) Aerobic and anaerobic degradation of aldicarb in
    asceptically collected soils. J. environ. Qual., 15: 356-363.

    H.B.F. (1987) Changing aldicarb residue levels in soil and
    groundwater, Eastern Long Island, New York, J. environ. Hydrol., 2:

    PANT, S.C. & KUMAR, S. (1981) Toxicity of Temik for a freshwater
    teleost, wBarbus conchoniusHamilton. Experientia (Basel), 37:

    PAYNE, L.K., STANSBUR, H.A., & WEIDEN, M.H.J. (1966). Synthesis and
    insecticidal properties of some cholinergic trisubstituted acetaldehye
    O-(methylcarbamoyl)oximes. J. agric. food Chem., 14: 356-365.

    PEOPLES, S.A., MADDY, K.T., & SMITH, C.R. (1978) Occupational exposure
    to Temik (aldicarb) as reported by California physicians for
    1974-1976. Vet. hum. Toxicol., 20(5): 321- 324.

    PETERSON, B. & GREGORIO, C.A. (1988) Aldicarb acute dietary exposure
    analysis (Unpublished report prepared for Rhône-Poulenc Co.).

    PICKERING, D.J. & GILLIAM, W.T. (1982) Toxicity of aldicarb and
    fonofos to the early-life stage of the fathead minnow. Arch. environ.
    Contam. Toxicol., 11: 699-702.

    POZZANI, U.C. & CARPENTER, C.P. (1968) Sensitizing potential in guinea
    pigs as determined by a modified Lansteiner test (Unpublished Mellon
    Institute Report No. 31-143).

    PRIDDLE, M.W., JACKSON, R.E., & MUTCH, J.P. (1989) Contamination of
    the sandstone aquifer of Prince Edward Island, Canada, by aldicarb and
    nitrogen residues Groundwater monit. Rep., Fall 1989: 134-140.

    PROCTOR, N.H., MOSCIONI, A.D., & CASIDA, J.E. (1976) Chicken embryo
    NAD levels lowered by teratogenic organophosphorus and methylcarbamate
    insecticides. Biochem. Pharmacol., 25: 757-762.

    QUARLES, J.M., SEGA, M.W., SCHENLEY, C.K., & LIJINSKY, W. (1979) 
    Transformation of hamster fetal cells by nitrosated pesticides in a
    transplacental assay. Cancer Res., 39: 4525-4533.

    QURAISHI, M.S. (1972) Edaphic and water relationships of aldicarb and
    its metabolites. Can. Entomol., 104: 1191-1196.

    RAMASAMY, P. (1976) Carbamate insecticide poisoning. Med. J. Malaysia,
    31:  150-152.

    RASHID, K.A. & MUMMA, R.O. (1986) Screening pesticides for their
    ability to damage bacterial DNA. J. environ. Sci. Health, B21(4):

    REDING, R. (1987) Chromatographic monitoring methods for organic
    contaminants under the Safe Drinking Water Act. J. chromatogr. Sci.,
    25: 338-343.

    RICHEY, F.A., BARTLEY, W.J., & SHEETS, K.P. (1977) Laboratory studies
    on the degradation of the pesticide aldicarb in soils. J. agric. food
    Chem., 25: 47- 51.

    B.G., & BARIOLA, L.A. (1966) Systemic insecticides for control of
     Lygus hesperus Knight on cotton. J. econ. Entomol., 59: 1017.

    RIVA, M. & CARISANO, A. (1969) Compact dual-channel flame ionization
    and thermionic detector for high-specificity chromatographic analysis.
    J. Chromatogr., 42: 464.

    ROTHSCHILD, E.R., MANSER, R.J., & ANDERSON, M.P. (1982) Investigation
    of aldicarb in ground water in selected areas of the central sand
    plain of Wisconsin. Groundwater, 20: 437-445.

    RYAN, A.J. (1971) The metabolism of pesticidal carbamates. CRC crit.
    Rev.  Toxicol., 1: 33-54.

    SAKAI, K. & MATSUMURA, F. (1968) Esterases of mouse brain active in
    hydrolysing organophosphate and carbamate insecticides. J. agric. food
    Chem., 16(5): 803-807.

    SAKAI, K. & MATSUMURA, F. (1971) Degradation of certain
    organophosphate and carbamate insecticides by human brain esterases.
    Toxicol. appl. Pharmacol., 19(4): 660-666.

    SCHAFER, E.W., Jr & BOWLES, W.A., Jr (1985) Acute oral toxicity and
    repellency of 933 chemicals to house and deer mice. Arch. environ.
    Contam.  Toxicol., 14: 119-129.

    SCHLINKE, J.C. (1970) Toxicologic effects of five soil nematocides in
    chickens. J. Am. Vet. Med. Assoc., 31: 119-121.

    SEILER, J.P. (1977) Nitrosation win vitrow by sodium nitrate, and
    mutagenicity of nitrogenous pesticides Mutat. Res., 48: 225-236.

    M. (1989) Aldicarb suppresses macrophage but not natural killer (NK)
    cell-mediated cytotoxicity of tumor cells. Bull. environ. Contam.
    Toxicol., 43: 676-682.

    SEXTON, W.F. (1966) Report on aldicarb. EPA Pesticide Petition No.
    9F0798, Section C., submitted to US Environmental Protection Agency,
    Washington, DC.

    E.A. (1982) Effect of aldicarb (Temik), a carbamate insecticide, on
    chromosomes of the laboratory rat. Egypt. J. Genet. Cytol., 11(2):

    Analysis of risk from exposure to aldicarb using immune response of
    nonuniform population of mice. Arch. environ. Contam. Toxicol., 19:

    SINGH, O. & AGARWAL, R.A. (1981) Toxicity of certain pesticides to two
    economic species of snails in northern India. J. econ. Entomol., 74:

    SPARACINO, C.M., PELLIZARRI, E.D., COOK, C.E., & WALL, M.W. (1973) 
    Reexamination of the GC determination of ý-d-propoxyphene. J.
    Chromatogr., 77(2): 413-418.

    (1985) [A case of aldicarb intoxication in cattle.] Tijdschr.
    Diergeneeskd., 110: 555-558 (in Dutch with English abstract).

    SPURR, H.W., Jr & SOUSA, A.A. (1966) Pathogenicidal activity of a new
    carbamoyloxime insecticide. Plant Dis. Rep., 50: 424-425.

    SPURR, H.W., Jr & SOUSA, A.A. (1967) Effects of aldicarb as a systemic
    fungicide. Chem. Abstr., 67: 10927 (116136m).

    SPURR, H.W., Jr & SOUSA, A.A. (1974) Potential interactions of
    aldicarb and its metabolites on nontarget organisms in the
    environment. J. environ. Qual., 3: 130-133.

    SRI (1984) Chemical economics handbook, Menlo Park, California,
    Stanford Research Institute, Chemical Information Service.

    STANKOWSKI, L.F., NAISMITH, R.W., & MATTHEWS, R.J. (1985)  Mammalian
    cell forward gene mutation assay (Study conducted for Union Carbide
    Corporation, submitted to WHO).

    STRIEGEL, J.A. & CARPENTER, C.P. (1962) Range finding tests on
    Compound 21149 (Unpublished Mellon Institute Report No. 25-53).

    SUPAK, J.R., SWOBODA, A.R., & DIXON, J.B. (1977) Volatilization and
    degradation losses of aldicarb from soils. J. environ. Qual., 6:

    TAKUSAGAWA, F. & JACOBSON, R.A. (1977) Crystal and molecular structure
    of carbamate insecticides. 2. Aldicarb. J. agric. food Chem., 25:

    THOMAS, P.T., & RATAJCZAK, H.V. (1988) Assessment of carbamate
    pesticide immunotoxicity. Toxicol. ind. Health, 4(3): 381-390.

    KETELS, K.V., & BARBERA, P.W. (1987) Evaluation of host resistance and
    immunity in mice exposed to the carbamate pesticide aldicarb. Fundam.
    appl. Toxicol., 9: 82-89.

    (1990) Aldicarb immunotoxicity: Functional analysis of cell- mediated
    immunity and quantitation of lymphocyte subpopulations. Fundam. appl.
    Toxicol., 15: 221-230.

    TING, K.C. & KHO, P.K. (1986) High performance liquid chromatographic
    method for the determination of aldicarb sulfoxide in watermelon.
    Bull. environ.  Contam. Toxicol., 37: 192-198.

    (1984) High performance liquid chromatographic method for
    determination of six N-methylcarbamates in vegetables and fruits.
    Bull. environ. Contam. Toxicol., 33: 538-547.

    TRUTTER, J.A. (1989a) Acute oral toxicity study in cynomolgus monkeys
    of aldicarb sulfoxide/sulfone residues in watermelons (Unpublished
    Union Carbide Corporation study, submitted to WHO).

    TRUTTER, J.A. (1989b) Acute oral toxicity study in cynomolgus monkeys
    of aldicarb sulfoxide/sulfone residues in bananas (Unpublished Union
    Carbide Corporation study, submitted to WHO).

    TYL, R.W. & NEEPER-BRADLEY, T.L. (1988) Developmental toxicity
    evaluation of aldicarb administered by gavage to CD rats (Study
    conducted for Rhône-Poulenc Co., submitted to WHO).

    UNION CARBIDE (1983) Temik aldicarb pesticide: A scientific assessment
    (Unpublished study submitted by Union Carbide to US EPA).

    US EPA (1984) Method 531. Measurement of N-methylcarbamoyloximes and
    N-methylcarbamates in drinking water by direct aqueous injection HPLC
    with post column derivatization, Cincinnati, Ohio, US Environmental
    Protection Agency, Environmental Monitoring and Support Laboratory.

    US EPA (1985) Risk assessment of potential Temik contamination of
    drinking water in Florida, Cincinnati, Ohio, US Environmental
    Protection Agency, Environmental Criteria and Assessment Office.

    US EPA (1986) Reference dose for aldicarb, Cincinnati, Ohio, US
    Environmental Protection Agency, Environmental Criteria and Assessment
    Office (Prepared for US EPA, Office of Solid Waste, Washington).

    US EPA (1988a) Aldicarb special review technical support document.
    Washington, DC, US Environmental Protection Agency, Office of
    Pesticides and Toxic Substances.

    US EPA (1988b) Pesticides in groundwater. Data base 1988 interim
    report,  Washington, DC, US Environmental Protection Agency, Office of
    Pesticide Programs, Environmental Fate and Groundwater Branch.

    US EPA (1989) Protection of environment. Aldicarb tolerance for
    residues. Fed. Reg., 40: 324 180.269.

    VARMA, A.O., ZAKI, M., & STERMAN, A.B. (1983) Results of a preliminary
    survey, Stony Brook, New York, State University of New York, School of

    WEIDEN, M.H.J., MOOREFIELD, H.H., & PAYNE, L.K. (1965)
    O-(methyl-carbomyl)-oximes: A class of carbamate insecticides -
    Acarides. J. econ. Entomol., 58: 154-155.

    WEIL, C.S. (1968) EPA Pesticide Petition No. 9F0798 (Unpublished
    Mellon Institute Report No. 31-48).

    WEIL, C.S. (1973) Miscellaneous toxicity studies (Unpublished Mellon
    Institute Report No. 35-41).

    WEIL, C.S. & CARPENTER, C.P. (1963) Results of three months of
    inclusion of Compound 21149 in the diet of rats (Unpublished Mellon
    Institute Report No. 26-47, Section C).

    WEIL, C.S. & CARPENTER, C.P. (1964) Results of a three-generation
    reproduction study on rats fed Compound 21149 in their diet
    (Unpublished Mellon Institute Report No. 27-158).

    WEIL, C.S. & CARPENTER, C.P. (1965) Two-year feeding of Compound 21149
    in the diet of rats (Unpublished Mellon Institute Report No. 28-123).

    WEIL, C.S. & CARPENTER, C.P. (1966) Two-year feeding of Compound 21149
    in the diet of dogs (Unpublished Mellon Institute Report No. 29-5).

    WEIL, C.S. & CARPENTER, C.P. (1968a) Temik 10G. Acute and fourteen-day
    dermal applications to rabbits (Unpublished Mellon Institute Report
    No. 31-137).

    WEIL, C.S. & CARPENTER, C.P. (1968b) Temik sulfoxide. Results of
    feeding in the diet of rats for six months and dogs for three months
    (Unpublished Mellon Institute Report No. 31-141).

    WEIL, C.S. & CARPENTER, C.P. (1968c) Temik sulfone. Results of feeding
    in the diet of rats for six months and dogs for three months
    (Unpublished Mellon Institute Report No. 31-142).

    WEIL, C.S. & CARPENTER, C.P. (1970) Temik and other materials.
    Miscellaneous single dose peroral and parenteral LD50 assays and
    some joint action studies (Mellon Institute Report No. 33-7. Amendment
    to EPA Pesticide Petition No.  9F0798).

    WEIL, C.S. & CARPENTER, C.P. (1972) Aldicarb (A), aldicarb sulfoxide
    (ASO), aldicarb sulfone (ASO2) and a 1:1 mixture of ASO:ASO2. Two-year
    feeding in the diet of rats (Unpublished Mellon Institute Report No.

    WEIL, C.S. & CARPENTER, C.P. (1974a) Aldicarb. Inclusion in the diet
    of rats for three generations and a dominant lethal mutagenesis test
    (Unpublished Mellon Institute Report 37-90).

    WEIL, C.S. & CARPENTER, C.P. (1974b). Aldicarb. 18-Month feeding in
    the diet of mice, Study II (Unpublished Mellon Institute Report

    WEST, J.S. & CARPENTER, C.P. (1965) The single dose peroral toxicity
    of Compounds 20299, 21149, 19786 and 20047A for white leghorn
    cockerels (Unpublished Mellon Institute Report No. 28-30).

    WEST, J.S. & CARPENTER, C.P. (1966) Miscellaneous acute toxicity data
    (Unpublished Mellon Institute Report No. 28-140).

    WHO (1986) Environmental Health Criteria 64: Carbamate pesticides: a
    general introduction, Geneva, World Health Organization, 137 pp.

    WHO (1990a) Environmental Health Criteria 104: Principles for the
    toxicological assessment of pesticide residues in food, Geneva, World
    Health Organization, 117 pp.

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

    A toxicological evaluation of aldicarb and its metabolites in relation
    to the potential human health impact of aldicarb residues in Long
    Island ground water, Ithaca, New York, Cornell University, Committee
    from the Institute for Comparative and Environmental Toxicology
    (Unpublished report).

    Total toxic aldicarb residues in soil, cotton seed, and cotton lint
    following a soil treatment with the insecticide on the Texas High
    Plains. J. agric. food Chem., 21: 303-307.

    WOODHAM, D.W., REEVES, R.G., & EDWARDS, R.R. (1973b) Total toxic
    aldicarb residues in weeds, grasses, and wildlife from the Texas High
    Plains following a soil treatment with insecticide. J. agric. food
    Chem., 21: 604-607.

    WOODSIDE, M.D., WEIL, C.S., & COX, E.F. (1977) Inclusion in the diet
    of rats for three generations (aldicarb sulfone), dominant lethal
    mutagenesis and teratology studies (Unpublished Mellon Institute
    Report No. 419, submitted to WHO by Union Carbide Corporation).

    WORTHING, C.R. & WALKER, S.B. (1987) The pesticide manual: a world
    compendium, 8th ed., London, British Crop Protection Council.

    WRIGHT, L.H., JACKSON, M.D., & LEWIS, R.G. (1982) Determination of
    aldicarb residues in water by combined high performance liquid
    chromatography/mass spectrometry. Bull. environ. Contam. Toxicol., 28:

    WYMAN, J.A., JONES, R.L., JOSE, M., CURWEN, D., & HANSEN, J.L. (1987) 
    Environmental fate studies of aldicarb and aldoxycarb applications to
    Wisconsin potatoes. J. Contam. Hydrol., 2: 61-72.


    1.  Identité, propriétés et méthodes d'analyse

         L'aldicarbe est un ester carbamique. Il se présente sous la forme
    d'un solide cristallin blanc, modérément soluble dans l'eau, sensible
    à l'oxydation et à l'hydrolyse.

         Plusieurs méthodes d'analyse sont utilisables, notamment la
    chromatographie en couche mince, la chromatographie en phase gazeuse
    (capture d'électrons, ionisation de flamme, etc.) et la
    chromatographie en phase liquide.  Actuellement la méthode de choix
    pour le dosage de l'aldicarbe et de ses principaux produits de
    décomposition est la chromatographie en phase liquide à haute
    performance avec formation de dérivés après passage sur colonne et
    détection par fluorescence.

    2.  Usages, sources et niveaux d'exposition

         L'aldicarbe est un pesticide endothérapique que l'on applique
    dans le sol pour détruire certains insectes, acariens et nématodes.
    Les récoltes concernées sont très diverses: bananes, coton, café,
    maïs, oignons, agrumes, haricots (secs), noix de pécan, pommes de
    terre, arachide, soja, betteraves sucrières, canne à sucre, patates
    douces, sorgho, tabac ainsi que les plantes ornementales et les
    pépinières. L'exposition de la population générale à l'aldicarbe et à
    ses métabolites toxiques (le sulfoxyde et la sulfone) intervient
    principalement par l'intermédiaire des aliments. C'est ainsi que
    l'ingestion de produits alimentaires contaminés a entraîné des cas
    d'intoxication par l'aldicarbe ou ses métabolites toxiques (sulfoxyde
    et sulfone).

         En raison de la forte toxicité aiguë de l'aldicarbe, l'inhalation
    et le contact cutané avec cette substance, dans des conditions
    d'exposition professionnelle, peuvent être dangereuses pour les
    travailleurs en l'absence de mesures de prévention. On dénombre
    quelques cas d'exposition accidentelle de travailleurs qui
    s'expliquent par des erreurs de manipulation ou l'absence de mesures
    de protection.

         L'aldicarbe s'oxyde rapidement en sulfoxyde, le taux de
    conversion étant de 48% en l'espace de sept jours après application
    sur certains types de sol. L'oxydation en sulfone est beaucoup plus
    lente. L'hydrolyse du groupement ester carbamique, qui inactive le
    pesticide, dépend du pH, la demi-vie dans l'eau distillée allant de
    quelques minutes à pH > 12 à 560 jours à pH 6,0. Dans le sol de
    surface, la demi-vie varie d'environ 0,5 à trois mois et dans la zone
    saturée, de 0,4 à 36 mois. L'aldicarbe s'hydrolyse un peu plus
    lentement que le sulfoxyde ou la sulfone. L'étude en laboratoire de la
    décomposition biotique et abiotique de l'aldicarbe a fourni des

    résultats très variables qui ont donné lieu à des extrapolations
    radicalement différentes sur la base d'observations en situation
    réelle. En ce qui concerne les produits de dégradation de l'aldicarbe,
    ce sont les données obtenues sur le terrain qui permettent les
    hypothèses les plus fiables quant à la destinée de ce pesticide.

         Les terrains sablonneux à faible teneur en matières organiques
    permettent un lessivage maximal, en particulier lorsque la nappe
    phréatique est haute. Des nappes de drainage et des puits de faible
    profondeur ont été contaminés par du sulfoxyde et de la sulfone
    d'aldicarbe; les concentrations étaient généralement comprises entre
    1 et 50 µg/litre, avec une fois une teneur d'environ 500 µg/litre.

         L'aldicarbe étant un pesticide endothérapique, il peut laisser
    des résidus dans les aliments. On a fait état de résidus dépassant 1
    mg/kg dans des pommes de terre crues. Aux Etats-Unis d'Amérique, où la
    limite de tolérance pour les pommes de terre est de 1 mg/kg, on a
    signalé des teneurs en résidus allant jusqu'à 0,82 mg/kg à la suite
    d'essais contrôlés sur le terrain aux doses d'emploi recommandées par
    le fabriquant. Les données obtenues ont permis de fixer le 95ème
    percentile à 0,43 mg/kg, cette valeur atteignant 0,0677 mg/kg dans les
    pommes de terre crues lors d'une enquête basée sur le panier de la

    3.  Cinétique et métabolisme

         L'aldicarbe est bien résorbé au niveau des voies digestives et
    dans une moindre mesure, au niveau de la peau. Présent sous la forme
    de poussière, il pourrait être très facilement absorbé dans les voies
    respiratoires. Il se distribue dans l'ensemble des tissus et notamment
    dans ceux du foetus de rat en développement. Il subit ensuite une
    transformation métabolique en sulfoxyde et en sulfone, qui sont tous
    deux toxiques, puis une détoxification par hydrolyse en oximes et en
    nitriles. L'excrétion de l'aldicarbe et de ses métabolites s'effectue
    rapidement, principalement par la voie urinaire. Il est également
    excrété en faible proportion dans la bile et subit donc un recyclage
    entérohépatique. L'aldicarbe ne s'accumule pas dans l'organisme par
    suite d'une exposition de longue durée.  In vitro , l'inhibition de
    la cholinestérase par l'aldicarbe est spontanément réversible, avec
    une demi-vie de 30 à 40 minutes.

    4.  Etudes sur les animaux d'expérience

         L'aldicarbe est un puissant inhibiteur de cholinestérases et
    présente une forte toxicité aiguë. Si l'animal ne meurt pas, les
    effets cholinergiques disparaissent spontanément et complètement en
    six heures. Rien n'indique que l'aldicarbe soit tératogène, mutagène,
    cancérogène ou immunotoxique.

         Des oiseaux et de petits mammifères sont morts après ingestion de
    granulés d'aldicarbe qui n'étaient pas complètement incorporés au sol
    conformément aux recommandations d'emploi. Au laboratoire, l'aldicarbe
    se révèle doté d'une forte toxicité aiguë pour les organismes
    aquatiques. Rien n'indique toutefois que ces effets se produiraient
    sur le terrain.

    5.  Effets sur l'homme

         L'inhibition de l'acétylcholinestérase au niveau de la synapse
    nerveuse et de la plaque motrice est le seul effet qui ait été dûment
    observé chez l'homme et il est analogue à celui qu'exercent les
    organophosphorés. L'enzyme carbamylée est instable et elle se réactive
    spontanément assez vite par comparaison avec l'enzyme phosphorylée.
    Lorsqu'elle n'est pas mortelle, l'intoxication est rapidement
    réversible chez l'homme. La réactivation est facilitée par
    l'administration d'atropine.


    1.  Evaluation des risques pour la santé humaine

         L'aldicarbe est un pesticide extrêmement dangereux. Pour l'homme,
    les risques découlent principalement d'erreurs de manipulation et de
    la non-utilisation de matériel protecteur au cours de la fabrication,
    de la formulation et de l'épandage. L'aldicarbe peut contaminer les
    denrées alimentaires et l'eau de boisson. Les effets d'une
    surexposition sont aigus mais réversibles. Les effets cholinergiques
    peuvent être graves, incapacitants et nécessiter une hospitalisation,
    mais ils sont rarement mortels.

    1.1  Niveaux d'exposition

    1.1.1  Population générale

         Les principales sources d'exposition de la population générale
    sont les denrées alimentaires et l'eau.

         Il existe aux Etats-Unis un certain nombre de données qui
    permettent d'estimer l'apport alimentaire journalier d'aldicarbe (voir
    section 5.2). De nombreuses données montrent que les résidus présents
    dans la plupart des produits après récolte sont généralement peu
    abondants et ne dépassent pas en tout cas les limites maximales de
    résidus, dans la mesure où l'aldicarbe est utilisé conformément aux
    bonnes pratiques agricoles pendant les périodes recommandées avant la
    récolte. Toutefois, même dans ce dernier cas, on trouve des
    concentrations dans les pommes de terre pouvant aller jusqu'à 1 mg/kg
    et parfois plus.

         On a découvert de fortes concentrations d'aldicarbe dans
    certaines cultures vivrières traitées illégalement avec ce produit. Un
    cas d'intoxication s'est produit après consommation de concombres
    obtenus par culture hydroponique, à des concentrations de 6,6 à 10,7
    mg d'aldicarbe par kg. Deux autres cas d'intoxication ont été signalés
    aux Etats-Unis par suite de la consommation de pastèques contaminées,
    la teneur en aldicarbe allant de < 0,01 à 6,3 mg/kg. Toutefois il
    n'est pas certain que ces valeurs correspondent à l'exposition réelle.

         Il y a eu des cas de contamination des eaux souterraines par de
    l'aldicarbe. Dans certaines régions du Canada, environ 12% des puits
    contrôlés en contiennent plus de 9 µg/litre. Sur 7802 puits soumis à
    des prélèvements dans l'Etat de New York aux Etats-Unis, dans un
    secteur où l'on épandait de l'aldicarbe sur des pommes de terre, 5745
    (73,6%) ne présentaient aucun résidu décelable, 1032 (13,3%) en
    contenaient des traces et 1025 (13,1%) présentaient une teneur
    supérieure à 7µg/litre.

         Aux Etats-Unis, on a constaté à la suite d'une enquête portant
    sur l'eau de 15 000 puits privés, que celle-ci contenait entre 1 et 50
    µg/litre d'aldicarbe dans environ un tiers des cas. Occasionnellement,
    on a relevé lors de forages de contrôle, des concentrations de 500
    mg/litre dans les eaux souterraines.

    1.1.2  Exposition professionnelle

         Lorsqu'on effectue des épandages à des fins agricoles, on peut
    réduire les concentrations atmosphériques d'aldicarbe en utilisant le
    produit sous forme de granulés. Toutefois certaines opérations, comme
    le chargement, demeurent dangereuses si des mesures de protection
    individuelle suffisantes ne sont pas prises. Un jeune ouvrier qui
    travaillait au chargement d'une formulation d'aldicarbe est décédé par
    suite d'une surexposition à ce produit qui avait conduit une
    concentration tissulaire de 0,275 mg/kg. La principale voie
    d'exposition professionnelle est la voie cutanée, en particulier
    lorsque les ouvriers ne respectent pas les précautions d'emploi et
    omettent d'utiliser un équipement protecteur.

    1.2  Effets toxiques

         Les effets ou manifestations toxiques de l'aldicarbe et de ses
    métabolites (sulfoxyde et sulfone) proviennent de leur action
    inhibitrice sur l'acétylcholinestérase. Cette inhibition est
    réversible. Les symptômes, qui dépendent de l'ampleur et de la gravité
    de l'exposition, sont les suivants: maux de tête, sensation
    vertigineuse, anxiété, sueur profuse, salivation, lacrymation,
    hypersécrétions bronchiques, vomissements, diarrhées, coliques,
    fibrillation musculaire et myosis. Rien n'indique que le produit soit
    cancérogène, mutagène, tératogène ou immunotoxique.

         Chez l'homme, l'administration par voie orale d'une seule dose de
    0,025 mg d'aldicarbe par kg de poids corporel a produit une inhibition
    sensible de l'activité cholinestérasique du sang total, qui est
    toutefois restée asymptomatique. A la dose de 0,10 mg/kg de poids
    corporel, sont apparus des symptômes cholinergiques et à celle de 0,26
    mg/kg une intoxication aiguë nécessitant un traitement.

    1.3  Evaluation du risque

         Les risques découlant de l'utilisation d'une substance chimique
    extrêmement dangereuse ne peuvent s'évaluer qu'en fonction des
    différents types d'exposition, ainsi que des mesures de sécurité qu'on
    peut mettre en oeuvre et du degré de certitude qu'on a de leur
    utilisation effective.

         Ce sont les personnes qui fabriquent, formulent et utilisent
    l'aldicarbe qui sont de loin les plus exposées au risque. La
    fabrication s'effectue en vase clos. L'emploi de l'aldicarbe sous
    forme de granulés réduit la formation de poussière et le risque
    d'exposition professionnelle. Quelques accidents se sont produits lors
    des opérations de formulation et d'épandage mais dans chaque cas il y
    avait eu, à une ou plusieurs reprises, violation indiscutable des
    règles de sécurité (voir section 8.2.1). Toutefois, même utilisé en
    granulés, l'aldicarbe peut être dangereux pour les ouvriers chargés de
    l'épandage s'ils n'observent pas les précautions recommandées.

         Des résidus d'aldicarbe peuvent être présents dans les denrées
    alimentaires par suite de l'application en toute légalité de ce
    produit sur des récoltes pour lesquelles on en a autorisé l'emploi,
    ainsi d'ailleurs qu'en raison d'une utilisation illicite ou
    défectueuse de ce produit. Rien ne permet de penser que la population
    générale courre un risque dû à la présence d'aldicarbe dans les
    produits alimentaires lorsque cette substance est appliquée aux doses
    recommandées et selon les techniques actuelles. Toutefois il existe un
    risque non négligeable si l'on répand de l'aldicarbe sur des cultures
    pour lesquelles il n'est pas autorisé ainsi que le montrent un certain
    nombre de cas d'intoxication. D'ailleurs, on a établi des limites et
    des tolérances pour les taux d'application sur le sol dans les cas où
    l'emploi d'aldicarbe est autorisé afin de protéger la population dans
    son ensemble. Ces mesures ont été couronnées de succès puisqu'on ne
    signale pas de cas d'effets nocifs dus à une exposition à l'aldicarbe
    par suite de la consommation de denrées traitées correctement au moyen
    de ce produit. Des enquêtes sur le panier de la ménagère ont fourni
    des données limitées qui montrent que l'exposition à l'aldicarbe ne
    dépasse probablement pas aux Etats-Unis 1 µg/kg de poids corporel et
    par jour. Cette valeur est très inférieure à la dose journalière
    admissible (DJA), fixée lors de la Réunion conjointe FAO/OMS sur les
    résidus de pesticides (FAO/OMS, 1983).

         On n'a pas retrouvé d'aldicarbe dans l'eau d'adduction provenant
    de nappes profondes ou d'eau de surface et il n'y a donc pas lieu de
    craindre un risque d'intoxication par l'aldicarbe qui aurait cette
    origine. On a signalé des cas de contamination d'eau souterraine par
    de l'aldicarbe, en général à des doses de 1 à 50 µg/litre aux
    Etats-Unis, avec parfois des teneurs allant jusqu'à 500 µg par litre.
    Toutefois, la plupart des puits qui ont été contrôlés dans les zones
    contaminées ne contenaient tout au plus que des traces d'aldicarbe ou
    de ses métabolites. Les restrictions imposées à l'utilisation de
    l'aldicarbe sur les sols sableux ont permis de réduire la
    contamination des eaux souterraines.

         Si l'on admet que la consommation d'eau est en moyenne de 2
    litres par jour pour un poids corporel moyen de 60 kg, on peut en
    déduire que l'exposition des personnes qui consommeraient de l'eau

    provenant de puits peu profonds contaminés par de l'aldicarbe à des
    teneurs allant de 1 à 50 µg/litre, serait de 0,033 à 1,7 µg/kg de
    métabolites par jour. Un puits dont l'eau serait contaminée à la dose
    de 500 µg/litre entraînerait une exposition de 17 µg/kg de poids
    corporel et par jour. La meilleure étude relative au risque de
    contamination par consommation d'eau de boisson a été effectuée sur
    des rats qui recevaient de l'aldicarbe sous forme de sulfoxyde et de
    sulfone dans leur eau de boisson. La dose sans effet observable sur
    l'acétylcholinestérase mesurée dans cette étude était de 480 µg/kg de
    poids corporel et par jour. On voit donc que l'exposition qui
    résulterait de la consommation d'eau de source contaminée se situe
    bien endessous de cette valeur.

    2.  Evaluation des effets sur l'environnement

         Lorsque les granulés d'aldicarbe sont convenablement enfouis dans
    le sol jusqu'à une profondeur de 5 cm, comme le recommande le
    fabricant, le danger est minime pour les oiseaux et les petits
    mammifères. Aux doses d'emploi recommandées, l'aldicarbe peut être
    mortel pour certains invertébrés terricoles non visés comme les
    lombrics. Jusqu'à 600 oiseaux chanteurs ont été détruits par suite
    d'applications défectueuses d'aldicarbe sur le sol; en effet les
    oiseaux peuvent mourir après ingestion d'un seul granulé. Les petits
    mammifères courent un risque analogue en cas d'épandage d'aldicarbe à
    la surface du sol.

         Rien n'indique que des organismes aquatiques aient été détruits
    par suite d'intoxications à l'aldicarbe malgré la très forte toxicité
    potentielle de ce produit. L'aldicarbe pourrait contaminer les fossés
    de drainage lorsqu'on l'applique dans des secteurs où il y a risque de
    pluies torrentielles périodiques et par voie de conséquence,
    possibilité de ruissellement et d'entraînement des particules du sol.
    Toutefois il est peu probable que des poissons et des invertébrés
    aquatiques soient détruits de cette manière.


    1.  Conclusions

    1.1  Population générale

         L'aldicarbe est un pesticide hautement toxique.

         A l'occasion d'intoxications accidentelles et lors d'une étude
    contrôlée en laboratoire, on a observé des symptômes de type
    cholinergique parmi lesquels: malaise général, vision trouble,
    faiblesse musculaire dans les bras et les jambes, crampes
    épigrastriques, sueur profuse, nausées, vomissements, pupilles
    contractées aréactives, sensation vertigineuse, dyspnée, respiration
    de Kussmaul, diarrhée et fibrillation musculaire. Ces symptômes ont
    disparu spontanément en l'espace de six heures. La dose orale la plus
    forte sans effet observable mesurée lors d'une étude sur l'homme se
    situait à 0,05 mg/kg de poids corporel. Toutefois, on a tout de même
    observé à cette dose une inhibition passagère mais sensible de la
    cholinestérase du sang total.

         Le mécanisme essentiel de l'intoxication par l'aldicarbe consiste
    en une inhibition de l'acétylcholinestérase. On admet que les
    carbamates insecticides abolissent la capacité de
    l'acétylcholinestérase à dégrader l'acétylcholine, qui joue le rôle de
    médiateur chimique au niveau de la synapse et de la plaque motrice. On
    observe le même mode d'action chez les organismes visés ou non visés.
    Rien n'indique que l'aldicarbe soit cancérogène, mutagène, tératogène
    ou immunotoxique.

    1.2  Exposition professionnelle

         On connaît des cas d'intoxication professionnelle par suite de
    négligences dans l'observation des mesures de sécurité.

    1.3  Effets sur l'environnement

         L'aldicarbe ne représente aucune menace pour les divers
    organismes qui peuplent l'environnement. Il peut cependant y avoir des
    cas de mortalité individuelle d'oiseaux ou de petits mammifères
    lorsque les granulés ne sont pas convenablement enfouis dans le sol.
    Les organismes aquatiques ne courent aucun risque.

    2.  Recommandations en vue de la protection de la santé humaine et de

    a)   La manipulation et l'épandage de l'aldicarbe doivent être confiés
         à des personnes convenablement formées.

    b)   L'utilisation d'aldicarbe à des fins agricoles doit être limitée
         aux cas où il n'existe pas de produits de remplacement moins

    c)   La fabrication de l'aldicarbe comporte des risques d'exposition
         à des substances chimiques toxiques. Les systèmes de sécurité
         doivent empêcher toute fuite ou décharge accidentelle.

    d)   Pour réduire au minimum ou éliminer l'exposition des vertébrés à
         l'aldicarbe, il faut que les granulés soient bien enfouis dans le
         sol jusqu'à une profondeur de 5 cm, ainsi que le recommande le


    a)   Des études pharmacocinétiques - comportant notamment une étude de
         la fixation du produit après application cutanée - sont
         nécessaires pour permettre une modélisation pharmacocinétique
         fondée sur des données physiologiques.

    b)   Dans un cas d'intoxication résultant de la consommation de menthe
         contenant de l'aldicarbe, on a observé des effets à une dose
         anormalement faible. L'étude de la menthe traitée par l'aldicarbe
         pourrait révéler l'existence d'un métabolite encore inconnu
         susceptible d'expliquer ce phénomène.

    c)   Les études concernant les effets immunologiques ne sont pas
         concluantes. Des travaux supplémentaires sont nécessaires pour
         approfondir la nature des effets exercés sur le système

    d)   Une étude de reproduction sur le rat est nécessaire pour voir
         s'il y a lieu de craindre une sensibilité du foetus. Une étude de
         ce genre est en cours.


    1.  Identidad, propiedades y métodos analíticos

         El aldicarb es un éster de carbamato. Se trata de un sólido
    cristalino blanco, moderadamente hidrosoluble y susceptible de
    oxidación y de reacciones hidrolíticas.

         Existen varios métodos analíticos, entre los que se cuentan la
    cromatografía en capa fina, la cromatografía de gases (captura
    electrónica, ionización de llama, etc.), y la cromatografía en fase
    líquida. Actualmente, el método preferido de análisis del aldicarb y
    de sus principales productos de descomposición es la cromatografía en
    fase líquida de elevado rendimiento con derivación postcolumnar y
    detectores de fluorescencia.

    2.  Usos, fuentes y niveles de exposición

         El aldicarb es un plaguicida sistémico que se aplica al suelo
    para combatir ciertos insectos, ácaros y nematodos. Este tipo de
    aplicación se hace en una gran variedad de cultivos, como la banana,
    el algodón, el café, el maíz, la cebolla, los cítricos, las legumbres
    (secas), la pacana, la papa, el cacahuete, la soja, la remolacha
    azucarera, la caña de azúcar, la batata camote, y el sorgo, así como
    en plantas ornamentales y en viveros de árboles. La exposición de la
    población general al aldicarb y sus metabolitos tóxicos (el sulfóxido
    y la sulfona) tiene lugar principalmente por vía alimentaria. La
    ingestión de alimentos contaminados ha ocasionado casos de
    intoxicación por aldicarb y sus metabolitos tóxicos (el sulfóxido y la

         Dada la elevada toxicidad aguda del aldicarb, tanto la inhalación
    como el contacto cutáneo en condiciones de exposición profesional
    pueden resultar peligrosos para los trabajadores si las medidas
    preventivas son insuficientes. Se han producido algunos incidentes de
    exposición accidental de trabajadores debidos al uso inadecuado o a la
    ausencia de medidas de protección.

         El aldicarb se oxida con relativa rapidez para dar el sulfóxido;
    a los 7 días de la aplicación a ciertos tipos de suelo se produce la
    conversión del 48% del compuesto original en sulfóxido. La oxidación
    sulfona es mucho más lenta. La hidrólisis del grupo éster del
    carbamato, que inactiva al plaguicida, depende del pH; la semivida en
    agua destilada varía entre algunos minutos en un pH > 12 y 560 días
    en un pH de 6,0. Las semividas en los suelos de superficie son de
    aproximadamente 0,5 a 3 meses y en la zona saturada de 0,4 a 36 meses.
    El aldicarb se hidroliza un poco más despacio que el sulfóxido o la
    sulfona. La medida en el laboratorio de la degradación biótica y
    abiótica del aldicarb ha producido resultados sumamente variables y ha
    llevado a extrapolaciones que difieren radicalmente de las
    observaciones sobre el terreno. Los

    datos obtenidos en el terreno sobre los productos de la degradación
    del aldicarb proporcionan estimaciones más fiables de su evolución

         Los suelos arenosos con bajo contenido de materia orgánica son
    los que más favorecen la lixiviación, en particular allí donde el
    nivel freático es alto. Algunos acuíferos de drenaje y pozos locales
    poco profundos se han contaminado con sulfóxido y sulfona de aldicarb;
    en general, los niveles han variado entre 1 y 50 µg por litro, aunque
    en una ocasión se registró un nivel de aproximadamente 500 µg/litro.

         Como el aldicarb tiene acción sistémica en las plantas, pueden
    aparecer residuos en los alimentos. Se han notificado niveles de
    residuos superiores a 1 mg/kg en papas crudas. En los EE.UU., donde el
    límite de tolerancia para las papas es de 1 mg/kg, se han comunicado
    niveles de residuos de hasta 0,82 mg/kg en ensayos controlados sobre
    el terreno con los regímenes de aplicación recomendados por el
    fabricante. A partir de los datos obtenidos en los ensayos sobre el
    terreno se ha calculado un nivel máximo del 95° percentilo de 0,43
    mg/kg; en una encuesta sobre la cesta de la compra se han determinado
    niveles máximos del 95° percentilo de hasta 0,0677 mg/kg en papas

    3.  Cinética y metabolismo

         El aldicarb es absorbido con facilidad a partir del tracto
    gastrointestinal y, en menor medida, a través de la piel. Se
    absorbería fácilmente en el tracto respiratorio si hubiera polvo. Se
    distribuye a todos los tejidos, inclusive los del feto de rata en
    desarrollo. Se transforma metabólicamente en el sulfóxido y la sulfona
    (los cuales son tóxicos), y es detoxificado por hidrólisis dando
    oximas y nitrilos. La excreción del aldicarb y de sus metabolitos es
    rápida y se produce principalmente por la orina. Una pequeña parte
    puede ser objeto de eliminación por vía biliar y, en consecuencia, de
    reciclaje enterohepático. El aldicarb no se acumula en el organismo
    como resultado de la exposición a largo plazo. La inhibición  in vitro
    de la actividad de la colinesterasa por el aldicarb es
    espontáneamente reversible; la semivida es de 30-40 minutos.

    4.  Estudios en animales de experimentación

         El aldicarb es un potente inhibidor de las colinesterasas y tiene
    una elevada toxicidad aguda. Sus efectos colinérgicos revierten de
    modo espontáneo y completo al cabo de 6 horas a menos que entretanto
    sobrevenga la muerte. No se dispone de pruebas bastantes que indiquen
    que el aldicarb sea teratogénico, mutagénico, carcinogénico o

         Se han producido muertes de aves y pequeños mamíferos por la
    ingestión de gránulos de aldicarb no incorporados plenamente al suelo
    como se recomienda. En pruebas de laboratorio, el aldicarb ha
    demostrado ser sumamente tóxico para los organismos acuáticos. Nada
    indica, no obstante, que esos efectos se produzcan sobre el terreno. 

    5.  Efectos en el ser humano

         La inhibición de la acetilcolinesterasa en la sinapsis nerviosa
    y la unión neuromuscular es el único efecto reconocido del aldicarb en
    el hombre y se asemeja a la acción de los organofosfatos. La enzima
    carbamiolada es inestable y la reactivación espontánea es
    relativamente rápida en comparación con la de una enzima fosforilada.
    La intoxicación no mortal en el hombre es rápidamente reversible. La
    recuperación se acelera mediante la administración de atropina.


    1.  Evaluación de los riesgos para la salud humana

         El aldicarb es un plaguicida sumamente peligroso. El riesgo para
    la salud humana se debe principalmente a su uso incorrecto y a la no
    utilización de equipo de protección durante su fabricación,
    elaboración y aplicación. El aldicarb puede contaminar los alimentos
    y el agua de bebida. Los efectos de la exposición excesiva son agudos
    y reversibles. Aunque los efectos colinérgicos pueden ser graves y
    discapacitantes y exigen la hospitalización de la persona afectada, en
    muy raros casos han sido mortales.

    1.1  Niveles de exposición

    1.1.1  Población general

         Las principales fuentes posibles de exposición para la población
    general son los alimentos y el agua.

         En los EE.UU. se dispone de algunos datos para calcular la
    ingesta diaria de aldicarb (véase la sección 5.2). Muchos datos
    demuestran que, en la mayoría de los cultivos cosechados, los residuos
    suelen aparecer en pequeñas cantidades y no sobrepasan los límites
    máximos para residuos cuando la sustancia se usa siguiendo prácticas
    agrícolas correctas y se respetan los periodos de precosecha
    recomendados. No obstante, incluso en ese caso, se han encontrado en
    las papas niveles de hasta 1 mg/kg, y en ocasiones superiores.

         En algunos cultivos tratados ilegalmente con aldicarb se han
    descubierto niveles elevados de esa sustancia. Se produjo un caso de
    intoxicación tras el consumo de pepinos cultivados hidropónicamente
    con niveles de 6,6-10,7 mg de aldicarb/kg. En los EE.UU. se
    notificaron dos casos de intoxicación por sandías contaminadas en las
    que los niveles de aldicarb se encontraban entre < 0,01 y 6,3 mg/kg.
    No obstante, no puede asegurarse que este margen refleje la verdadera

         Se ha producido algún caso de contaminación de aguas subterráneas
    con aldicarb. Alrededor del 12% de los pozos examinados en algunas
    regiones del Canadá excedieron los 9 µg/litro. De 7802 pozos
    muestreados en el Estado de Nueva York (EE.UU.), en una zona en la que
    se tratan las papas con aldicarb, 5745 (73,6%) no tenían residuos
    detectables, 1032 (13,3%) tenían cantidades mínimas y 1025 (13,1%)
    tenían concentraciones superiores a 7 µg/litro.

         En una encuesta a escala nacional de 15 000 pozos privados en los
    Estados Unidos de América se observaron niveles de aldicarb en el agua
    de 1 a 50 µg/litro en aproximadamente un tercio de las muestras
    positivas. En perforaciones experimentales se han comunicado niveles
    ocasionales de 500 µg/litro en aguas subterráneas.

    1.1.2  Exposición profesional

         Las concentraciones de aldicarb en la atmósfera durante la
    aplicación agrícola quedan reducidas al mínimo por la forma granular
    del producto. No obstante, algunas operaciones, como el proceso de
    carga, pueden ser peli-grosas si no se adoptan las medidas apropiada
    de protección individual. La exposición excesiva al aldicarb, que
    ocasionó un nivel tisular de 0,275 mg/kg, contribuyó a la muerte de un
    joven obrero que cargaba preparaciones de aldicarb. La principal vía
    de exposición profesional es a través de la piel, especialmente cuando
    los trabajadores no adoptan las precauciones recomendadas ni usan
    equipo de protección.

    1.2  Efectos tóxicos

         Los efectos o manifestaciones de la toxicidad del aldicarb y sus
    metabolitos (sulfóxido y sulfonas) se deben a su acción inhibitoria de
    la acetilcolinesterasa. La inhibición de la colinesterasa es
    reversible. Entre los signos y síntomas clínicos, según la magnitud y
    la gravedad de la exposición, figuran: dolor de cabeza, mareo,
    ansiedad, transpiración excesiva, salivación, secreción de lagrimas,
    aumento de las secreciones bronquiales, vómitos, diarrea, calambres
    abdominales, fasciculaciones musculares y pupilas contraídas. No
    existen pruebas importantes de carcinogenicidad, mutagenicidad,
    teratogenicidad o inmunotoxicidad.

         En sujetos humanos, la administración única por vía oral de 0,025
    mg de aldicarb/kg de peso corporal produjo una inhibición
    significativa de la actividad de la colinesterasa en sangre entera,
    aunque sin síntomas. Con dosis de 0,10 mg/kg de peso corporal se
    produjeron signos y síntomas colinérgicos y con una dosis de 0,26
    mg/kg de peso corporal se produjo una intoxicación aguda que exigió 

    1.3  Evaluación del riesgo

         Los riesgos que representa una sustancia química sumamente
    peligrosa sólo pueden evaluarse en función de los distintos tipos de
    exposición y sólo en función de las medidas de seguridad disponibles
    y el grado de certeza de que se usan.

         Con diferencia, el grupo más expuesto al riesgo del aldicarb está
    formado por los que lo fabrican, lo elaboran y lo usan. El aldicarb se
    fabrica en un sistema cerrado. El uso del aldicarb en forma granular
    reduce la formación de polvo y el riesgo de exposición profesional. Se
    han producido algunos accidentes asociados a la elaboración y el uso,
    pero en todos los casos se debieron a una o varias transgresiones
    claras de las normas de seguridad (véase la sección 8.2.1). No
    obstante, aunque el aldicarb se usa en forma granular, puede
    representar un riesgo para las personas que lo aplican si no se
    adoptan todas las precauciones recomendadas.

         Las fuentes de residuos de aldicarb en los alimentos comprenden
    la aplicación de acuerdo con la ley a los suelos en los que se
    cultivan cosechas para las que se ha aprobado el uso de aldicarb, y no
    sólo el uso ilícito o indebido de esa sustancia. No hay pruebas de que
    la salud de la población general corra riesgos debidos al aldicarb
    presente en los alimentos en los niveles de aplicación recomendados y
    con las técnicas actuales. No obstante, existe un riesgo importante
    cuando el aldicarb se usa en cultivos no aprobados, como lo indican
    los informes de varios casos de intoxicación. Por otro lado, se han
    establecido regímenes de aplicación en el suelo y límites de
    tolerancia para los residuos de aldicarb en los usos aprobados de la
    sustancia a fin de proteger a la población general. El éxito de estas
    medidas viene indicado por la observación de que no se han notificado
    efectos adversos para la salud que puedan atribuirse a la exposición
    al aldicarb a partir de productos básicos en los que la sustancia se
    usó debidamente. Los limitados datos obtenidos en la encuesta sobre la
    cesta de la compra sugieren que la exposición al aldicarb
    probablemente no excederá 1 µg/kg de peso corporal al día en los
    EE.UU. Esto se encuentra muy por debajo de la ingesta diaria admisible
    (IDA), establecida en la Reunión Conjunta FAO/OMS sobre Residuos de
    Plaguicidas (FAO/WHO, 1983).

         No se ha encontrado aldicarb en los canales públicos de agua
    procedentes de acuíferos profundos o aguas de superficie, por lo que
    no se prevé riesgo alguno debido al aldicarb en las aguas de esa
    procedencia. Se han comunicado casos de contaminación por aldicarb en
    aguas subterráneas, generalmente con niveles de 1-50 µg/litro en los
    EE.UU. y con casos excepcionales de hasta 500 µg por litro. No
    obstante, la mayoría de los pozos muestreados en zonas contaminadas
    tienen cantidades indetectables o indicios de aldicarb o sus
    metabolitos. La restricción del uso de la sustancia en suelos arenosos
    ha reducido la contaminación de las aguas subterráneas.

         Suponiendo un consumo diario medio de agua de 2 litros y un peso
    corporal medio de 60 kg, las personas que consumen agua de pozos poco
    profundos contaminados localmente que contienen entre 1 y 50 µg/litro
    estarian sometidas a una exposición a los metabolitos de aldicarb de 

    entre 0,033 y 1,7 µg/kg de peso corporal al día. Un pozo de agua 
    contaminada con aldicarb a un nivel de 500 µg por litro daria lugar 
    a una exposición de 17 µg/kg de peso corporal al día. El estudio
    más apropiado que se conoce para la evaluación del riesgo en el agua
    de bebida es un estudio en el que se administraron sulfóxido y sulfona
    de aldicarb a ratas en el agua de bebida. En ese estudio, el nivel de
    no observación de efectos en la inhibición de la acetilcolinesterasa
    fue de 480 µg/kg de peso corporal al día. La exposición estimada por
    consumo de agua subterránea contaminada está, por lo tanto, muy por
    debajo de ese nivel.

    2.  Evaluación de los efectos en el medio ambiente

         La plena incorporación de los gránulos de aldicarb al suelo a una
    profundidad de 5 cm, tal y como recomienda el fabricante, representa
    un riesgo mínimo para las aves y los pequeños mamíferos. Los
    invertebrados del suelo que no se pretende destruir con la sustancia,
    como las lombrices, pueden morir cuando se usa el aldicarb de
    acuerdocon los regímenes de aplicación recomendados. Se han comunicado
    casos de hasta 600 muertes de aves canoras debidas a la aplicación
    indebida de los gránulos en la superficie del suelo, ya que los
    pájaros pueden morir por la ingestión de un solo gránulo. La
    aplicación superficial del aldicarb expone a los pequeños mamíferos a
    un riesgo similar.

         No se tienen pruebas de que hayan muerto organismos acuáticos por
    intoxicación con aldicarb a pesar de su toxicidad potencial
    relativamente elevada. El aldicarb puede contaminar las zanjas de
    drenaje cuando se usa en zonas de lluvias torrenciales periódicas, que
    provocan una intensa escorrentía del agua y el suelo de la superficie.
    No obstante, es poco probable que con ello mueran peces o
    invertebrados acuáticos.


    1.  Conclusiones

    1.1  Población general

         El aldicarb es un plaguicida sumamente tóxico.

         La intoxicación accidental y un estudio controlado en el
    laboratorio dieron lugar a síntomas colinérgicos entre los que
    figuraron los siguientes: malestar, visión borrosa, debilidad muscular
    en los brazos y las piernas, calambres epigástricos dolorosos,
    transpiración excesiva, náuseas, vómitos, pupilas contraídas no
    reactivas, mareos, disnea, hambre de aire, diarrea y fasciculación
    muscular. Los síntomas desaparecieron espontáneamente al cabo de seis
    horas. La dosis oral más elevada que produjo síntomas no observables
    en un estudio en el ser humano fue de 0,05 mg/kg de peso corporal,
    aunque se produjo una significativa inhibición transitoria de la
    colinesterasa de sangre entera con ese nivel.

         El mecanismo primario de la toxicidad del aldicarb es la
    inhibición de la acetilcolinesterasa. Comúnmente se acepta que los
    insecticidas con carbamato interfieren con la capacidad de la
    acetilcolinesterasa de degradar el transmisor químico acetilcolina en
    las uniones sinápticas y neuromusculares. El mismo mecanismo de acción
    se manifiesta en los organismos que se prentende combatir y en los
    demás. No hay pruebas sustanciales de carcinogenicidad, mutagenicidad,
    teratogenicidad o inmunotoxicidad.

    1.2  Exposición profesional

         Se han producido casos de intoxicación y envenenamiento debidos
    a la exposición profesional por no adoptarse las precauciones

    1.3  Efectos en el medio ambiente

         El aldicarb no ejerce efecto alguno en los organismos del medio
    ambiente en el nivel de población. Pueden producirse casos de muerte
    de aves y pequeños mamíferos aislados cuando los gránulos no se
    incorporan plenamente al suelo. Los organismos acuáticos no están
    expuestos al riesgo del aldicarb.

    2.  Recomendaciones para la protección de la salud humana y del medio

    a)   La manipulación y la aplicación del aldicarb debe ser llevada a
         cabo por personal adiestrado.

    b)   El uso del aldicarb en la agricultura debe limitarse a aquellos
         casos en los que no se disponga de sustitutos menos peligrosos.

    c)   La fabricación del aldicarb es un proceso peligroso que entraña
         el posible riesgo de exposición a sustancias químicas tóxicas.
         Los sistemas de seguridad deben ser suficientes para impedir los
         derrames y vertidos.

    d)   Para reducir al mínimo o eliminar la exposición de los  
         vertebrados terrestres al aldicarb, los gránulos deben quedar
         plenamente incorporados al suelo a una profundidad de 5 cm, tal
         y como recomienda el fabricante.


    a)   Se necesitan más estudios farmacocinéticos, inclusive   estudios
         de asimilación tras la aplicación por vía cutánea, que permitan
         la formulación de modelos farma-cocinéticos de base fisiológica.

    b)   En un caso de intoxicación debida al consumo de menta que
         contenía aldicarb se observaron efectos con una dosis
         aparentemente muy reducida. El estudio de la menta tratada puede
         revelar la existencia de un metabolito desconocido o de otros
         factores que hayan intervenido en ese caso de intoxicación.

    c)   Los estudios sobre los efectos inmunológicos del aldicarb no han
         dado resultados concluyentes. Es necesario hacer nuevos estudios
         para examinar más a fondo los efectos del aldicarb en el sistema

    d)   Es preciso llevar a cabo un estudio de reproducción en la rata
         para investigar aspectos relacionados con la susceptibilidad
         fetal. Hay un estudio de ese tipo en marcha.

    See Also:
       Toxicological Abbreviations
       Aldicarb (HSG 64, 1991)
       Aldicarb (ICSC)
       Aldicarb (Pesticide residues in food: 1979 evaluations)
       Aldicarb (Pesticide residues in food: 1982 evaluations)
       Aldicarb (Pesticide residues in food: 1992 evaluations Part II Toxicology)
       Aldicarb (IARC Summary & Evaluation, Volume 53, 1991)