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    PESTICIDE RESIDUES IN FOOD - 1979


    Sponsored jointly by FAO and WHO






    EVALUATIONS 1979





    Joint meeting of the
    FAO Panel of Experts on Pesticide Residues
    in Food and the Environment
    and the
    WHO Expert Group on Pesticide Residues
    Geneva, 3-12 December 1979



    ALDICARB

    IDENTITY

    Chemical Name

    2-methyl-2-(methylthio) propionaldehyde O-(methylcarbamoyl) oxime

    Synonyms

    TemikR, UC 21149, OMS 771

    Structural Formula

                             CH3               O   H
                              '                "   '   
                    CH3 - S - C - CH = N - O - C - N - CH3
                              '
                              CH3                  C7H14N2O2S

    Other Information on Identity and Properties

    Molecular weight:   190.3
    State:              White, crystalline solid
    Odor:               Slight sulfurous odor
    M.P.:               98-100C
    S.G.:               1.195 @ 25C
    B.P.:               Decomposes above 100C
    V.P.:               0C 1  10-5 mm Hg
                        25C 1  10-4 mm Hg
                        50C 7  10-4 mm Hg
                        75C 4  10-3 mm Eg

    Stability:          Heat sensitive, relatively unstable chemical;
                        stable in acidic media; unstable, decomposes
                        rapidly in alkaline media.

    Solubility:                     Percent Solubility at:

                             10C      20C       30C       50C

    Water                    0.4       0.6        0.9        1.4
    Acetone                  28        40         43         67
    Benzene                  9                    24         49
    Carbon tetrachloride     2                    5          25
    Chloroform               38        35         44         53
    Methyl isobutyl
    ketone                   13                   24         42
    Toluene                  10        10         12         33
    Ethanol                            25
    Isopropanol                        20

    Vapour Pressure of Aldicarb and Metabolites

                                      V.P. (mm Hg) at:

    Chemical               0C        25C        50C        75C

    Aldicarb             1 x 10-5 1 x 10-4  7 x 10-4  4 x 10-3
    Aldicarb Sulfoxide   1 x 10-5 7 x 10-5  5 x 10-4  2 x 10-3
    Aldicarb Sulfone     8 x 10-6 9 x 10-5  6 x 10-4  3 x 10-3

    Aldicarb in relatively non-volatile and the major toxic metabolites
    are less volatile than aldicarb.

    Purity of Technical Product

    The Meeting noted that the technical product normally contains from
    94.7 to 97.7% aldicarb and considered the likely impurities.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Absorption, Distribution and Excretion

    Aldicarb is readily absorbed, distributed widely in the body and
    excreted rapidly in mammals.   Radiolabeled aldicarb (the 14C
    radiolabel was present in one of three positions in the molecule,
    S-methyl, tert-butyl or N-methyl) was administered orally to male
    rats and residue were analyzed over a 14-day period.  Excretion was
    essentially complete within 4 days (greater than 95% of the
    administered dose).  The major concentrations of metabolites were
    observed to have been excreted within 24 hours of dosing.  Four days
    following acute oral dosing residues were not detected in animal
    tissues (Knaak et al., 1966).  Following oral administration (0.4
    mg/kg), aldicarb was rapidly eliminated predominantly in the urine
    80%) and faeces (5%) within 24 hours.   Low levels of radioactive
    metabolite were noted in a variety of tissues in the first days after
    treatment.  Within four days there were essentially no residues which
    could be suggestive of (selective) storage of residues in the body. 
    By the fifth day following acute treatment, tissues were free of
    detectable residues (Andrawes, et al., 1967).  Aldicarb sulfone, a
    minor carbamate metabolite, was administered orally to rats and also
    found to be rapidly absorbed and excreted in a manner similar to that
    noted with aldicarb.  Within 4 days from 90 to 95% of the orally
    administered dose was excreted predominantly in urine.  In two
    analytical studies, performed at 7 or 11 days after treatment, tissue
    residues were absent (Sullivan, 1968c; Andrawes 1977).

    In dogs, the excretion pattern of aldicarb administered subacutely was
    similar to that noted following acute administration in other species.
    Aldicarb was administered to dogs at a dose of 0.75 mg/dog/day in the
    diet for 20 days. On the 21st day, a single radiolabeled dose of

    aldicarb was administered in the place of the non-radiolabeled
    chemical.  Dogs were thereafter maintained for an additional ten days
    on a diet containing aldicarb.  The daily excretion pattern was
    examined in urine.  Approximately 90% of the recovered urinary
    radioactivity was observed to have been excreted within the first 24
    hours of the administration time of the radio-labelled dose.  Thus,
    the elimination via the urine of aldicarb from dogs equilibrated for
    up to three weeks showed an excretion pattern similar to that noted
    with animals administered aldicarb in a single acute dosage (Sullivan,
    1968a).  A similar urinary excretion pattern was observed when
    aldicarb sulfone (Sullivan, 1968b; Andrawes 1977) and aldicarb nitrile
    (Sullivan and Carpenter, 1974) were orally or dietarily administered
    to lactating dairy cows either alone or in combination with one or
    more aldicarb metabolites.  Following a single acute administration of
    aldicarb, approximately 83% of the dosage was eliminated in the urines
    within 24 hours. A minor quantity of residue was eliminated in the
    faeces and small residues were observed in milk (less than 3% of the
    administered dose was observed in milk over a 5-day interval) (Dorough
    and Ivie, 1968).  Increasing the number of days of treatment from one
    to 14 did not change the magnitude or the elimination pattern of
    aldicarb in milk or excretory products.  Approximately 1% of the
    administered dose was secreted in milk with 95% of the administered
    dose eliminated by the other routes.  Small levels of residues were
    observed in tissues with the liver showing the major terminal residue.
    Continuous exposure of cows to aldicarb in the diet did not
    significantly alter its absorption and excretion patterns (Dorough, et
    al., 1970).  In an additional subchronic study a 1:1 mixture of
    aldicarb sulfoxide and aldicarb sulfone was administered to cows to 32
    to 46 days.  Milk residues were found to be approximately 0.1% of the
    administered aldicarb metabolites.  In these studies there was no
    apparent build-up of residues in milk or animal tissues from
    continuous administration of aldicarb and/or its carbamate metabolites
    (Romine, 1973).

    Aldicarb and/or aldicarb sulfone administered as a single oral dose to
    laying hens was rapidly excreted in the faeces.  Minute quantities of
    terminal residues were observed in eggs on the first day after
    treatment but the residue level declined rapidly.  Tissue residues
    were maximal within 6 hours of treatment after which a rapid decline
    was observed.  Continuous administration of aldicarb for 21 days did
    not change the pattern of rapid excretion or of terminal residues in
    eggs or tissues (Hicks, et al., 1972).

    Biotransformation

    The metabolic fate of aldicarb has been studied in a variety of
    vertebrate and invertebrate species.  Minor biotransformation
    differences have been found to occur with respect to quantities of
    individual metabolites.  The basic metabolic profile of aldicarb in
    all species examined appears to be the same and is shown in figure 1.
    Aldicarb is rapidly oxidized to aldicarb sulfoxide, a relatively
    stable metabolite.  Aldicarb sulfoxide in slowly degraded by both

    oxidative and hydrolytic mechanisms yielding the corresponding
    aldicarb sulfone and sulfoxide oxime.

    In rats, urinary metabolites include aldicarb sulfoxide (40%), the
    sulfoxide oxime (30%) and a variety of more polar, relatively acidic,
    metabolites.  Aldicarb was noted in urine only in trace quantities
    (Knaak, et al., 1966; Andrawes, et al., 1967). Results of in
    vitro studies have shown that aldicarb was completely metabolized
    rapidly through oxidative and/or hydrolytic mechanisms yielding the
    same profile of metabolites noted in Figure 1.  Further studies of the
    metabolic fate of aldicarb sulfoxide and aldicarb sulfone have
    confirmed the metabolic pattern of these components as shown in Figure
    1 (Andrawes et al., 1967; Andrawes, 1977).  Approximately one-half
    of the administered dose of aldicarb sulfoxide was rapidly degraded
    through cleavage of the ester carbonyl and eliminated as hydrolytic
    products in the urine.  Aldicarb sulfone was identified as a very
    minor metabolite following administration of aldicarb sulfoxide.  In
    contrast to the rapid cleavage of the carbamate ester and urinary
    elimination following aldicarb sulfoxide treatment, administration of
    aldicarb sulfone to rats resulted in approximately 80% of the urinary
    metabolites as the unchanged aldicarb sulfone.  Conjugation mechanisms
    for elimination of aldicarb from the body appeared to be minor
    reactions possibly because of the polar nature of the metabolites
    themselves.  Studies using enzyme or acid hydrolysis of polar urinary
    metabolites have resulted in the characterization of the aldicarb,
    alcohol and aldehyde derivatives shown in Figure 1a.  These represent
    a very small portion of the degradation mechanism noted for aldicarb.

    In dogs, the identification of a similar urinary metabolic pattern was
    reported (Sullivan, 1968a).  The major urinary metabolites were
    aldicarb sulfoxide and sulfoxide oxime.  Further characterizations of
    the sulfone, sulfone oxime and nitrile were reported.

    The metabolic fate of aldicarb in dairy animals was reported to be the
    same as those metabolite species detected in urine with the principal
    products being aldicarb sulfoxide, sulfoxide oxime and sulfoxide
    nitrile (Dorough and Ivie, 1968).

    Characterization of aldicarb metabolites in milk of cows fed for 14
    consecutive days showed a slightly different metabolic profile than
    animals receiving an acute single administration of aldicarb.  In
    animals treated for 14 days, the major milk metabolic component was
    found to be aldicarb sulfone and its corresponding nitrile derivative.
    Small quantities of aldicarb sulfoxide and larger quantities of the
    sulfoxide oxime suggested that an increased level of oxidative and/or
    hydrolytic metabolism would be expected following subacute, continuous
    dietary administration as opposed to that pattern noted with the
    single acute exposure (Dorough, et al., 1970).  The metabolic fate
    of aldicarb in hens (Hicks, et al., 1972), insects (Metcalf, et al.,
    1966; Bull, et al., 1967) and plants (Metcalf, et al., 1966)
    appears to follow the same pattern as noted in mammalian species with
    oxidation of the sulfur atom predominating, yielding primarily

    aldicarb sulfoxide and to a lesser extent, aldicarb sulfone which are
    further degraded to the hydrolytic oximes and corresponding nitriles.

    In rats, aldicarb nitrile was rapidly degraded to the sulfoxide
    nitrile.   This was identified as a major component in urine with the
    sulfone nitrile and further degradation products also noted (Sullivan
    and Carpenter, 1974).

    Effects on Enzymes and Other Biochemical Parameters

    As noted with other N-methylcarbamate esters aldicarb in an inhibitor
    of cholinesterase activity (Chin & Sullivan, 1968).  Aldicarb is a
    readily reversible cholinesterase inhibitor and in vitro studies
    have shown that cholinesterase inhibition, induced by aldicarb and its
    oxidative metabolites (aldicarb sulfoxide and aldicarb sulfone) can be
    readily reversed by simple dilution.  Aldicarb sulfoxide in a more
    active cholinesterase  agent than aldicarb or the corresponding
    sulfone.  Aldicarb sulfoxide was 47 and 25 times more effective in
    inhibiting cholinesterase than aldicarb and aldicarb sulfone
    respectively with an insect-enzyme preparation and 23 and 60 times
    more effective respectively when using a red blood cell preparation
    obtained from cows (Bull, et al., 1967; Metcalf, et al., 1966).

    Aldicarb sulfoxide and aldicarb sulfone were administered to rats in
    the diet for periods of time varying from 1 to 56 days after which the
    animals were sacrificed for plasma, erythrocyte and brain
    cholinesterase determinations.  Groups of 5 male and 5 female rats
    were administered aldicarb sulfoxide in the diet at dosage levels of
    0, 0.3 and 1.0 mg/kg/day and aldicarb sulfone was administered at
    dietary levels of 0, 2.4 and 16.2 mg/kg/day.  Animals were sacrificed
    at 1, 3, 7, 14, 28 and 56 days for cholinesterase analyses.  Plasma
    and erythrocyte cholinesterase activity was measured at the first
    three time intervals.  At the last three time intervals, plasma,
    erythrocyte and brain cholinesterase activity was examined.  Over the
    course of the of the growth was recorded routinely.

    There was no mortality and growth, as evidenced by body weight, was
    depressed at the highest dose levels with both the sulfoxide and
    sulfone.  Rats administered aldicarb sulfoxide at 1.0 mg/kg body
    weight had a slight but significant cholinesterase depression during
    the study.  There were no effects noted at 0.3 mg/kg.  Cholinesterase
    depression was marked with the aldicarb sulfone consistently
    throughout the study at the highest dose level, 16.2 mg/kg.  Although
    there were no clinical signs of poisoning and no deaths during the 56
    days of treatment, plasma erythrocyte and brain cholinesterase were
    consistently depressed below control values (Weil and Cox, 1975).

    FIGURE 1

    FIGURE 1a;V079PR02.BMP

    TOXICOLOGICAL STUDIES

    Acute Toxicity

    The acute toxicity of aldicarb and its metabolites has been studied in
    a variety of mammalian species.  A summary of acute toxicity data for
    aldicarb in shown in Table 1 and for the metabolites, in Table 2.

    Antidotal studies

    Following acute oral administration to rats, aldicarb has been shown
    to induce a strong muscarinic action at excretory, bronchial and
    cardiac nerve sites.  A nicotinic effect was also shown to occur at
    myoneural junctions.  The parasympathetic signs of poisoning were
    readily reduced following atropine administration (Johnson and
    Sullivan, 1968a).  Administration of combinations of atropine and
    2-PAM alone, or in combination, showed that while atropine was a more
    effective antidote, 2-PAM was also active (Johnson and Sullivan,
    1968b).  While it has been shown that aldicarb elicits a strong
    muscarinic action as well as nicotinic action at myoneural sites, the
    control of signs of poisoning from both mechanisms appears to be
    somewhat difficult to achieve.  Atropine has been shown to be an
    effective antidote to block the nicotinic effects but decamethonium,
    commonly used to block the nicotinic effects,  has been shown to be
    somewhat ineffective.  Additional studies to influence the nicotinic
    action by such drugs as tubocurare also failed to completely eliminate
    nicotinic activity.  Further studies confirmed the therapeutic effects
    of a variety of oximes (P2S and obidoxime) in reducing the acute toxic
    signs of poisoning associated with aldicarb (Natoff and Reiff, 1973).

    Signs of Poisoning

    Aldicarb is an extremely toxic chemical by any route of
    administration.  Severe anticholinesterase signs of poisoning appear
    almost immediately following poisoning.  These signs of poisoning,
    standard parasympathomimetic responses seen with other carbamates and
    anti-cholinesterase organophosphate esters, include: tremors,
    salivation, lacrimation, urination, diarrhea, convulsions, laboured
    respiration, myosis, piloerection, ataxia, pinpoint pupils and death.



        Table 1. Acute Toxicity - Aldicarb

                                                                                                                                  
    Species        Sex     Route     Vehicle1            LD50                 Reference
                                                         (mg/kg)
                                                                                                                                  

    Rat            M       Oral      Corn oil            0.93                 Striegel and Carpenter, 1962
                   M       Oral      Corn oil            0.67-1.23            Carpenter, 1963; Nycum and Carpenter, 1968b
                   F       Oral      Corn oil            0.62-1.07            Carpenter, 1963; Nycum and Carpenter, 1968b
                   F       Oral      Glycerol formal:    1.0                  WHO, 1966
                                     ethanol (9:1)
                   F       ip        Corn oil            0.71                 Carpenter, 1963
                   M&F     ip        Corn oil            0.44                 Carpenter, 1963
                   M       ip        PEG                 0.37-0.44            Weil and Carpenter, 1970a
                   M       ip        Ethanol             0.57                 Johnson and Carpenter, 1966b
                   M       iv        Water               0.47                 Weil and Carpenter, 1970a
                   F       Dermal    DMP                 3.2-7.0 (24 hr)      WHO, 1966
                   M       Dermal    Dry                 3952 (4 hr)          Weil and Carpenter, 1970b
                           Dermal    Water               38.1-44.9 (24 hr)    Weil and Carpenter, 1968a
    Mouse          M       Oral      Corn oil            0.382                Weil and Carpenter, 1972b
                   M       Oral      Corn oil            0.50                 Weil and Carpenter, 1972c
                   F       Oral      Cotton seed oil     1.5                  Dorough, 1970
                   F       ip        Cotton seed oil     0.3                  Dorough, 1970
    Rabbit         M       Dermal    PEG                 5.0                  Striegel and Carpenter, 1962
                   M&F     Dermal    Water               32-502               West and Carpenter, 1966b; Carpenter and Smyth 1966;
                   M       Dermal    Dry                 141 - >200           Weil and Carpenter, 1968a
    Chicken        M       Oral                          9                    West and Carpenter, 1965,
                                                                                                                                  

    1 PEG = polyethylene glycol
      DMP = dimethyl phthalate

    2  Wettable powder formulation

    Table 2.  Acute Toxicity - Metabolites

                                                                                                                
                                                                      LD50
    Chemical                        Species      Route1              (mg/kg)        Reference
                                                                                                                

    Aldicarb                        Rat          Oral                0.84           West and Carpenter, 1966b
    Aldicarb nitrile                Rat          Oral                570            West and Carpenter, 1966b
    Aldicarb sulfoxide              Rat (M)      Oral (C.O.)         0.49-1.13      Weil and Carpenter, 1970a;
                                                                                    Nycum and Carpenter, 1968b
    Aldicarb sulfone                Rat (M)      Oral (C.O.)         20-25          Weil and Carpenter, 1970a;
                                                                                    Nycum and Carpenter, 1968b
    Aldicarb sulfoxide              Rat (M)      ip (Water)          0.47           Weil and Carpenter, 1970a
    Aldicarb sulfone                Rat (M)      ip (PEG)            21.2           Weil and Carpenter, 1970a
    Aldicarb sulfoxide              Rat (M)      iv (Water)          0.47           Weil and Carpenter, 1970a
    Aldicarb sulfone                Rat (M)      iv (Water)          14.9           Weil and Carpenter, 1970a
    Aldicarb sulfoxide              Rabbit       Dermal (Water)      >20 mg/kg      West and Carpenter, 1969b
    Aldicarb suifone                Rabbit       Dermal (Water)      >20 mg/kg      West and Carpenter, 1969b
    2-Methy]-2-(methyl
    sulfinyl) propanol-1            Rat          Oral                11,000 mg/kg   Weil and Carpenter, 1969d
    Hydroxymethyl aldicarb          Rat          Oral                42.9           Carpenter, 1969
    Aldicarb sulfoxide oxime        Rat (M)      Oral                8060           Nycum and Carpenter, 1968a
    Aldicarb sulfone oxime          Rat (M)      Oral                1590           Nycum and Carpenter, 1968a
    Aldicarb sulfoxide nitrile      Rat (M)      Oral                4000           Nycum and Carpenter, 1968a
    Aldicarb sulfone nitrile        Rat (M)      Oral                350            Nycum and Carpenter, 1968a
                                                                                                                

    1  C.O. = corn oil
       PEG = polyethylene glycol
    


    Special Studies on Acute Toxicity

    Administration of aldicarb to the conjunctival sac of rabbits did not
    produce ocular irritation or corneal damage.  Ocular irritation
    studies were performed at doses that were lethal without indication of
    ocular damage (Striegel and Carpenter, 1962).

    There was no evidence of dermal irritation when aldicarb was applied
    to the shaved, abraded backs of rabbits (Striegel and Carpenter,
    1962).  Penetration of aldicarb through the skin was observed to be
    rapid, especially when the skin was moistened, simulating
    perspiration.  When dry, aldicarb did not penetrate the skin as
    rapidly as evidenced by a substantial increase in toxicity when using
    a wet versus the dry preparation (Carpenter and Smyth, 1965; Weil and
    Carpenter, 1969a).

    There was no indication of a sensitization reaction induced by
    aldicarb.  Male guinea pigs were administered aldicarb by multiple
    subdermal applications (0.7 mg/kg body-weight) and re-administered
    aldicarb three weeks later by a similar interderal administration.
    There was no suggestion of sensitization in any of the animals tested
    (Pozzani and Carpenter, 1968a).

    Aldicarb is extremely toxic when administered by the inhalation route
    (Striegel and Carpenter, 1962).  Exposure of rats, mice and guinea
    pigs to a dust formulation at a concentration of 200 mg/m3 for five
    minutes resulted in the death of all animals.  Exposure of female rats
    to a dust formulation at concentrations of 6.7 mg/m3 for 15 minutes
    was not lethal to any of the animals tested.  When exposed for 30
    minutes, 5 of 6 animals died.  However, aldicarb is not volatile and
    studies on the exposure of rats to aldicarb vapours emanating from
    technical or granular formulations for 8 hours resulted in no
    mortality (Pozzani and Carpenter, 1968b; Carpenter, 1963).

    Groups of male rabbits (5 rabbits/group) were administered
    aldicarb dermally for 15 days with a daily exposure of 6 hours per
    day.  Four groups of rabbits with abraded skin were administered
    aldicarb at dose levels of 0, 5, 10 and 20 mg/kg/day.  Water was added
    periodically during the exposure time to the dressing containing the
    aldicarb treatment, simulating a condition of excess perspiration. 
    One additional group was administered 20 mg/kg per day to intact,
    unbraded skin with no water added to the dressing.  The animals were
    administered aldicarb 5 days per week with a 2-day interval of
    non-treatment.  One 3-day period of no treatment was reported, during
    the third week of the study.

    Those animals treated with aldicarb under a dry condition with
    unabraded skin showed normal weight gains and no apparent effects as a
    result of the treatment.  During the interim where dermal treatment
    was not applied, recovery of growth was extremely rapid, attesting to
    the transient toxic nature of dermally-applied aldicarb.  The
    administration of aldicarb under conditions where the dressing was wet

    and the skin abraded resulted in reduced body-weight reflecting rapid
    absorption and an adverse effect at a dermal dosage of 5 mg/kg. 
    Plasma cholinesterase activity was inhibited at the two highest dose
    levels.  There were no adverse effects on haematology or clinical
    chemical parameters or on gross weights of liver and kidney observed
    at the conclusion of the study.  Microscopic examination of several
    major tissues showed no pathological events to attributable to
    aldicarb (Carpenter and Smyth, 1966).

    In a similar study, application of 10 mg/kg aldicarb and above
    when administered to abraded rat skin in the presence of water, again
    severely depressed body-weight.   The 5 mg/kg dosage also depressed
    body weight, but to a lesser extent.  No deaths were noted over the 14
    day interval.  When administered dry, aldicarb at 20 mg/kg (the
    highest dose level) was without effect (Weil and Carpenter, 1968a).

    Special Study on Behaviour

    The effects of acute administration of aldicarb and aldicarb
    sulfoxide on avoidance behaviour in rats, was compared to a variety of
    other carbamate esters.  Rats were trained and evaluated for their
    ability to avoid electrical shock in standard avoidance behaviour
    tests.  Aldicarb and aldicarb sulfoxide were administered by
    intraperitoneal injection and the rats were evaluated for their
    ability to avoid shocks over a 6-hour period following administration.
    The effects of aldicarb and its sulfoxide were compared with 3 other
    carbamate esters.  The lowest behaviourally effective dose was found
    to be 0.266 mg/kg body weight which, when compared to the acute IP
    LD50 value, was noted to have a smaller ratio of behaviour effects to
    acute LD50 than any of the other carbamates tested.  These data
    suggest that the level of aldicarb needed to produce measurable
    avoidance in greater (closer to a fatal dose and less likely to be
    achieved at the suggested use level) than the chemicals to which it
    was compared.  Additionally, the activity over the 6 hour period was
    seen to rapidly decline again attesting to the transient nature of the
    cholinesterase inhibition (Johnson and Carpenter, 1966b).

    Special Studies on Potentiation

    Aldicarb was administered orally to male rats alone and in combination
    with a series of 8 organophosphate esters or 1 carbamate ester, all
    anticholinesterase agents, to examine the potential interactive or
    additive effect.  Results of the study, using proportions of the acute
    lethal dose of each material alone and in combination with aldicarb,
    showed a simple additive effect with all materials tested.  Aldicarb
    was not found to potentiate the acute oral toxicity of other
    anticholinesterase agents (West and Carpenter, 1966a).

    Further studies were reported on the potential interaction of aldicarb
    with alpha-naphthol, aldicarb sulfoxide with aldicarb sulfone and
    aldicarb sulfone with parathion administered orally and aldicarb with
    alpha-naphthol or with carbaryl administered by the interperitoneal

    route.  In no case were any interactions greater than the predicted
    additive effects (Weil and Carpenter, 1970a).

    Special Studies on Reproduction

    Groups of rats (8 male and 16 female rats per group) were administered
    aldicarb in the diet at concentrations of 0, 0.05 and 0.1 mg/kg body
    weight in their diet for approximately 90 days and mated to initiate a
    3 generation reproduction study.  The offspring from the first
    generation were mated to produce the second generation in the one
    litter per generation reproduction study.  In addition to the
    reproduction indices (fertility, gestation, viability and lactation)
    the F3 generation was maintained for an additional period and tissues
    from these animals were histologically examined at either weaning or
    at 90 days of age.

    In all animal groups, the reproduction indices from the
    aldicarb-tested animals were statistically similar to the mean values
    of the control groups.  Body weights of both male and female pups at
    weaning were statistically similar to control values as were results
    of gross and microscopic examinations of tissues and organs in the F3
    weanling and 90-old animals.  In all three generations, with all
    criteria examined, there were no effects of aldicarb on reproduction
    at a dosage level of 0.1 mg/kg body weight (Weil and Carpenter, 1964).

    Groups of rats (10 male and 20 female per group) were administered
    aldicarb in the diet at dosage levels of 0, 0.2, 0.3 and 0.7 mg/kg
    body weight for 100 days and mated to initiate an additional 3
    generation (1 litter per generation) reproduction study.  A larger
    group was used for the F2 generation (15 male and 25 female rate) as
    male pups of this generation were maintained on aldicarb-diets for 148
    days and subjected to a (modified) dominant lethal (mutagenesis)
    bioassay where they were mated with groups of untreated virgin females
    for a period of 10 weeks.  Each female in the group was mated with 2
    treated males and allowed to maintain pregnancy until day 12 when they
    were sacrificed and examined.

    There was some mortality over the course of the study which was
    associated with lung infection and not as a result of aldicarb in the
    diet.  A significant difference from control values was noted in the
    second generation pups with respect to body weight at the highest dose
    level fed.  At this dose level, body weights of both male and female
    were lower than the control values.  Overall, there were no effects on
    any of the reproduction indices (fertility, gestation, viability or
    lactation).  Gross and microscopic examinations of the parents and
    pups of the high level and control groups showed no effects
    attributable to aldicarb.

    The dietary dominant lethal mutagenesis bioassay showed no statistical
    differences between the aldicarb-treated rats and controls with
    respect to early or late fetal death or any other parameter examined
    (Weil and Carpenter, 1974a).

    Special Studies on Teratogenicity

    Using a test protocol where both the reproductive and teratologic
    potential of aldicarb was evaluated, groups of pregnant rats were
    administered aldicarb in the diet at dosage levels of 0, 0.04, 0.2 and
    1.0 mg/kg body weight.  Five or six females from each of the dietary
    groups were assigned to one of three treatment groups: (1) aldicarb
    administered in the diet throughout pregnancy or until pups were
    weaned; (2) aldicarb administered in the diet from day 0 to day 7 of
    gestation; (3) aldicarb administered in the diet from day 5 to day 15
    of gestation.  Five or six females from each group were sacrificed and
    examined on day 20 of pregnancy and a similar number of females were
    allowed to bear, nurse and wean the pups.

    Qualitative data were recorded with respect to fertility, gestation,
    viability and lactation, the indices of a standard reproduction study.
    There were neither gross manifestations of teratogenesis in any of the
    pups carried by females administered aldicarb at dosage levels of up
    to 1 mg/kg body weight nor was there apparent interference with the
    reproductive process by any of the dosing regimens used in this study.
    The administration of aldicarb at dosage levels up to and including
    1.0 mg/kg body weight had no apparent effect on the growth of pregnant
    females during the course of the study.  There were no anomalies
    observed in the animals sacrificed just prior to term nor in the
    animals undergoing natural birth and allowed to be maintained until
    weaning.  Aldicarb, at levels of 1 mg/kg body weight, administered to
    rats during sensitive stages of gestation, did not induce a
    teratogenic effect (Weil and Carpenter, 1966a).

    Special Studies for Mutagenesis

    Rat-Dominant Lethal Study

    Groups of virgin female rats (15 rats per group) were mated with male
    rats that had been administered aldicarb (in the diet at dose levels
    of 0, 0.2, 0.3 or 0.7 mg/kg body weight) prenatally through gestation,
    through weaning and thereafter for up to 148 days of age.  The males,
    part of a 3-generation reproduction study were mated with virgin
    untreated females at weekly intervals for a total of 10 consecutive
    weeks.  At the initiation of the dominant lethal study, the males were
    fed control diets (having been exposed to aldicarb prenatally and for
    148 days prior to mating).  Each female was mated with 2 treated males
    and allowed to develop for 12 days of gestation.

    At 12 days of gestation each female was sacrificed and examined for
    pregnancy, implantation sites and for viable fetuses.  Data from all
    of the ten mating periods, at all of the dosage levels, were compared
    to control values.  There were no significant differences with respect
    to any of the parameters of mating, pregnancy and fetal deaths at any
    dose levels in the study.  In this slightly modified dominant lethal
    mutagenic study, aldicarb did not induce adverse or mutagenic effects
    in males as evidenced by sperm abnormalities (Weil and Carpenter,
    1974a).

    Special Study on Carcinogenicity

    Mice

    Groups of C3H/HeJ male mice were administered aldicarb, dissolved in
    acetone, dermally 3 times a week for 28 months.  Aldicarb was
    administered by applying a brush full of an acetone solution to the
    shaved back of the mice.  Aldicarb was administered for the first two
    weeks at the rate of 3 times a week using a 0.25% solution in acetone.
    After two weeks this was reduced to a twice-weekly application.  This
    dosing regimen was maintained for two months and further reduced
    thereafter to a concentration of 0.125% which was maintained for the
    remainder of the study.

    While there was some aldicarb-induced mortality noted over the course
    of the study, this mortality was not substantially different from that
    noted with control applications.  There were no substantial
    differences with respect to the incidence or onset of tumors.  Two
    growths, a hemangioma and a thymoma, were  noted in the animals
    administered aldicarb.  Neither of these internal growths was
    accompanied by cutaneous papillomas or carcinomas and were considered
    to be spontaneous growths unrelated to treatment.  Aldicarb,
    administered dermally to this sensitive species, did not induce any
    incidence of malignancy (Weil and Carpenter, 1966b).

    Special Studies on Delayed Neurotoxicity

    Groups of 6 adult chickens were administered aldicarb as a single oral
    dose of 4.5 mg/kg body weight or as daily oral doses of 0, 2.25 or 4.5
    mg/kg body weight for 30 days.  A positive control, treated with 100
    mg of TOCP, was used to produce typical delayed neurotoxic signs of
    poisoning.

    While there was some weight loss, which was correlated with the dose
    of aldicarb administered, the only neurological effects attributable
    to aldicarb were acute signs of poisoning noted in the first two or
    three days of treatment.  Neither ataxia nor hind limb paralysis were
    noted over the course of the study.  Aldicarb does not induce a
    delayed neurotoxic syndrome similar to that induced by certain
    organophosphate esters (Johnson and Carpenter, 1966a).

    Short Term Studies

    Rat-Aldicarb

    Groups of rats (5 male and 5 female rats per group, 6-week old rats)
    were fed aldicarb in the diet for 7 days at dosage levels of 0, 4, 8
    and 16 mg/kg body weight.  Animals were observed for acute signs of
    toxicity and were weighed three times during the course of the week's
    study.

    Mortality was noted predominantly at the highest dose level, at which
    all males and 2 of 5 females died.  One of 5 males also died at the 8

    mg/kg dose level.  There were substantial body weight changes noted at
    all dose levels.  In males, kidney weight was significantly reduced at
    8 mg/kg and liver weight was depressed at the 4 and 8 mg/kg dose
    levels.  In females, both liver and kidney weight was significantly
    depressed at all dose levels in the study (Weil and Carpenter, 1970c).

    Groups of young rats (5 male and 5 female rats per group, 7 weeks of
    age) were fed aldicarb in the diet at dose levels of 0, 0.8, 1.6 and
    3.2 mg/kg body weight for 7 days.  Animals were weighed three times
    during the week and observed for clinical signs of toxicity.  At the
    conclusion of the study, animals were sacrificed and brain, red blood
    cell and plasma cholinesterase activity was measured.

    Growth was depressed during the one week study at dosage levels of 1.6
    mg/kg and above.  There was no apparent mortality in the study
    attributable to aldicarb.  Slight effects were noted on both liver and
    kidney weight.  In males, liver weight and liver to body weight ratios
    were depressed in all treatment groups.  In females, liver weight was
    affected only at the highest dose level, but the liver to body weight
    ratio was reduced at 1.6 mg/kg and above.  Kidney weight was reduced
    in males at all dose levels and in females only at the highest dose
    level.

    Cholinesterase depression, measured on day after the conclusion of
    feeding, was normal at the highest dose level tested with the
    exception of plasma cholinesterase which was slightly reduced at the
    highest level (Weil and Carpenter, 1969b).

    Groups of rats (5 male and 5 female rats per group) were fed diets
    containing aldicarb, at dosage levels of 0, 0.4, 0.8, 1.6 and 3.2
    mg/kg body weight, or aldicarb sulfoxide, at dosage levels of 0, 0.4
    and 0.8 mg/kg body weight, or aldicarb sulfone, at dosage levels of 0,
    0.4, 1.0, 2.5, 5.0 and 20.0 mg/kg body weight, for 7 days.  With
    aldicarb (as with its two major carbamate metabolites) there was a
    significant growth (body weight) depression at the highest dose level.
    There were no effects noted with respect to gross liver or kidney
    weight at the conclusion of the study.  Erythrocyte and plasma
    cholinesterase activity was depressed by aldicarb at the highest dose
    level; with aldicarb sulfoxide, erythrocyte-cholinesterase activity
    was also depressed at the highest dose level; with aldicarb sulfone,
    plasma and erythrocyte cholinesterase activity was also depressed at
    the two highest dose levels, while brain cholinesterase was inhibited,
    in both males and females only at the highest dose level (20 mg/kg).
    The erythrocyte cholinesterase appeared to be the most sensitive
    parameter with all three materials tested.  A no-effect level based on
    erythrocyte-cholinesterase depression or decreased body weight over
    the 7-day interval was suggested to be: aldicarb - 0.8 mg/kg; aldicarb
    sulfoxide - 0.4 mg/kg; and aldicarb sulfone - 2.5 mg/kg (Nycum and
    Carpenter, 1968b).

    Aldicarb/Aldicarb Metabolites

    Groups of rats (5 male and 5 female rats per group, 7 weeks of age)
    were fed dietary levels of aldicarb (0.3 mg/kg body weight), aldicarb
    sulfoxide (0.4, 0.8 and 1.6 mg/kg body weight), aldicarb sulfone (0.6,
    5.0 and 20 mg/kg body weight), a 1:1 mixture of aldicarb sulfoxide and
    aldicarb sulfone (1.2 mg/kg body weight) or a control diet.  Animals
    were weighed three times during the course of the study and were
    examined daily for clinical signs of toxic reaction.  At the end of
    the seven days of feeding, animals were placed on control diets for
    one day after which they were sacrificed for cholinesterase
    determination and for examination for liver and kidney toxicity.

    A second one-week feeding trial was performed to compare the data with
    other strains of rats.  Aldicarb sulfoxide was fed to groups of 5 male
    rats at dosage levels of 0, 0.4, 0.8 or 1.6 mg/kg body weight.
    Aldicarb sulfone was also fed to male rats at dosage levels of 0, 5.0
    or 20 mg/kg body weight.

    In the initial study, aldicarb did not affect growth in males but did
    reduce female growth substantially (during the course of the one week
    study.  Aldicarb sulfoxide substantially reduced growth at 0.8 mg/kg
    and above in males and females.  Aldicarb sulfone reduced growth at 5
    mg/kg and above in males and at 0.6 mg/kg and above (all dose levels
    in females).  The combination of the sulfoxide and sulfone reduced
    growth only in females and only at the least measurement interval.

    In males, aldicarb did not appear to affect liver or kidney weight
    while in females there was a slight but significant decrease in liver
    weight at the conclusion of the study.  Aldicarb sulfoxide reduced
    both liver and kidney weight in males and females at the highest dose
    level.  Aldicarb sulfone in both males and females reduced kidney and
    liver weight over the course of the study at the highest dose level
    tested.  The 1:1 combination of the sulfoxide and sulfone in males and
    females had no adverse affect on liver and kidney.

    As might be expected with the protocol followed in the study,
    cholinesterase depression was not observed in either plasma,
    erythrocyte or brain at the conclusion of the study.

    The second trial using both the same and a different strain of rats
    was performed in an effort to explain a slight but non-significant
    inhibition of erythrocyte cholinesterase activity measured in the
    initial study.  Over the course of this study, there were no effects
    noted on erythrocyte cholinesterase activity.  With aldicarb
    sulfoxide, growth was slightly reduced at the two highest dose levels
    (0.8 and 1.6 mg/kg) in both strains and at 5 mg/kg body weight and
    above with aldicarb sulfone.  Liver and kidney weight were unaffected
    by aldicarb sulfoxide but were slightly reduced with aldicarb sulfone
    at the highest dose level (Weil and Carpenter, 1970d).

    Aldicarb Sulfoxide

    Groups of rats (15 male and 15 female rats/group) were fed aldicarb
    sulfoxide in the diet at dose levels of 0, 0.125, 0.25, 0.5 and 1.0
    mg/kg body weight for 6 months.  Animals were sacrificed at 3 months
    and at the conclusion of the study for cholinesterase determinations
    and for gross and microscopic examination of liver and kidney.  There
    was no mortality noted during the course of the study, although
    growth, especially in males, at 0.25 mg/kg and above was reduced.  In
    females growth was depressed only at the highest dose level.
    Cholinesterase activity was substantially reduced at the three highest
    dose levels, especially in plasma and erythrocytes of males.  In
    females, erythrocyte and plasma cholinesterase depression was noted at
    the two highest dose levels.  Gross examination of liver and kidney
    revealed no abnormalities attributable to aldicarb.

    In an attempt to resolve the question of cholinesterase depression and
    rapid recovery, groups of rats (5 male and 5 female rats per group)
    were administered aldicarb sulfoxide for one week or one week plus one
    day of control diets at a dietary level of 1 mg/kg body weight.  When
    the study was concluded (within one week), animals were sacrificed at
    0 and 24 hours after the dietary feeding interval (the 24 hour animals
    were fed control diets).  Cholinesterase depression was noted at the 0
    hour sacrifice in erythrocyte and plasma preparations.  Administration
    of a control diet for one day (24 hour sacrifice) completely reversed
    the cholinesterase depression noted when animals were sacrificed
    without any recovery interval.

    Groups of 5 male and 5 female rats were also fed aldicarb sulfoxide in
    the diet at dosage levels of 0, 0.0625, 0.125, 0.25, 0.50 and 1.0
    mg/kg body weight for 3 and 6 months after which some of the animals
    were sacrificed immediately and others were placed on a control diet
    for 24 hours prior to sacrifice and cholinesterase analyses. 
    Cholinesterase activity in the brain was unaffected by aldicarb
    sulfoxide.  Plasma and erythrocyte cholinesterase was substantially
    reduced at the 0 hour sacrifice in both males and females.  Males were
    slightly more sensitive with depression being noted at 0.25 mg/kg and
    above, while with females depression was noted at 0.5 mg/kg and above.
    There was no cholinesterase depression noted in any of the animals
    treated for either 3 months or 6 months when the animals were allowed
    to recover from cholinesterase depression for a one-day recovery
    interval.  Depression of cholinesterase activity, of as much as 89% of
    control values, was completely reversed within one day on a control
    diet.  A no-effect level of 0.125 mg/kg body weight was observed (Weil
    and Carpenter, 1968b).

    Aldicarb Sulfone

    In a series of studies similar to those reported with aldicarb
    sulfoxide, groups of rats (15 male and 15 female rats per group) were
    administered aldicarb sulfone in the diet at dosage levels of 0, 0.2,
    0.6, 1.8, 5.4 and 15.2 mg/kg body weight for 6 months.  Animals were
    sacrificed at 3 and 6 months for examination of liver and kidney

    abnormalities and for evaluation of cholinesterase activity.
    Cholinesterase determinations were made at the end of 3 and 6 month
    intervals with rats fed continuously until sacrifice for analysis.

    Additional rat studies using 5 male and 5 female rats per group were
    performed for one week or for 3 months on diets containing aldicarb
    sulfone at dose levels comparable to the levels reported above.  In
    these studies, animals were either sacrificed at the end of the
    feeding regimen or were allowed to consume a control diet for 24 hours
    prior to sacrifice and determination of cholinesterase activity.

    There was no mortality over the course of the study.  A transient but
    significant growth depression was noted at the highest level in the
    6-month feeding study.  There were no effects noted with respect to
    diet consumption or on gross and microscopic examinations of liver and
    kidney.  Plasma, erythrocyte and brain cholinesterase were
    significantly depressed at 5.4 mg/kg dose level and above. 
    Erythrocyte cholinesterase depression was also noted at 1.8 mg/kg.
    There was no cholinesterase depression noted at 0.6 mg/kg in any of
    the tissues examined.  In the study to evaluate recovery of
    cholinesterase activity, aldicarb sulfone was fed for 7 days at a
    dosage of 5.4 mg/kg body weight.  At the conclusion of dosing,
    significant depression of cholinesterase (plasma, erythrocyte and
    brain) was noted.  When animals were allowed to equilibrate for 1 day
    on control diets, all depressed cholinesterase values returned to
    normal.  A similar study was run for 3 months and 3 months and 1 day
    at dietary levels of 0, 0.2, 0.6, 1.2, 1.8, 5.4 and 16.2 mg/kg.  The
    data showed that extensive cholinesterase depression, noted at the
    conclusion of the feeding trial was completely recovered within one
    day of feeding control diets.  In this 3-month trial there was a
    substantial depression of plasma cholinesterase activity at 1.8 mg/kg
    erythrocyte activity at 5.4 mg/kg and brain activity at 16.2 mg/kg. 
    At 1.2 mg/kg cholinesterase was not substantially depressed (Weil and
    Carpenter, 1968c).

    Aldicarb Oxime

    Groups of rats (the number of males and females per group was not
    stated) were administered aldicarb oxime in the diet at dose levels of
    0, 31.25, 62.5, 125, 250, 500 and 1000 mg/kg body weight for 7 days.
    There was no mortality over the course of the study.  Growth was
    slightly reduced at the initiation of the study at dose levels of 125
    mg/kg and above, but at the end of one week only the two highest dose
    levels appeared to show a retardation in growth.  Gross changes were
    noted in both liver and kidney at the two highest dose levels in both
    males and females.  A dietary dosage level without substantial effect
    appeared to range between 62.5 and 250 mg/kg body weight over the
    course of this short term trial (Weil and Carpenter, 1974b).

    2-Methyl-2-(methylsulfinyl)propanol-1

    Groups of rats (5 male and 5 female rats per group, 6 weeks of age)
    were fed the hydrolytic metabolite of aldicarb

    (2-methyl-2-(methylsulfinyl)propanol-1) in the diet for 7 days at
    dosage levels of 0, 500 and 1000 mg/kg body weight.

    Growth was depressed at both dosage levels fed to males but only at
    the highest dosage level in females.  In females, while growth was
    depressed within one day of treatment, the animals appeared to recover
    during the rest of the week.  There was no apparent effect on major
    organs, although, in females at the high dosage level, kidney weight
    was slightly depressed.  Cholinesterase was not measured (Weil and
    Carpenter, 1969c).

    Mice

    Aldicarb/Aldicarb Metabolites

    Groups of mice (5 males and 5 females per group) were fed aldicarb in
    the diet at dosage levels of 0, 0.1, 0.3, 0.6 and 1.2 mg/kg body
    weight for 7 days.  Mortality was noted in both males and females at
    the high dose level.  Growth was not affected over the course of the
    study.  Liver and kidney weight were also unaffected.  In this one
    week study, an actual dosage level of aldicarb, based on food
    consumption data varying from 0.65 mg/kg body weight for females to
    0.75 mg/kg body weight for males was without substantial acute effects
    (Weil and Carpenter, 1970f).

    Groups of mice (3 male and 5 female mice per group) were fed a mixture
    of aldicarb and aldicarb sulfone (1:1) in the diet at dosage levels of
    0, 2, 6, 18, and 36 mg/kg body weight for 7 days.  Growth was measured
    three times during the course of the study, and animals were observed
    daily for any signs of abnormality.

    No mortality was noted at any dosage level.  Severe cholinergic signs
    of poisoning were observed at the high dose level in males. 
    Depression of growth, observed at the two highest dose levels, was
    statistically significant in both males and females.  Reduced body
    weights were, however, observed in all animals on the study at all
    dosage levels.  Kidney weight was depressed at the highest dose level
    within one week in both males and females.  No effects on the kidney
    were noted at dose levels of 18 mg/kg and below.  Liver weight was
    reduced substantially at dosage levels of 6 mg/kg and above in both
    males and females.  Significant liver reduction was observed at the
    two highest dose levels in males and at the highest dose level in
    females (Weil and Carpenter, 1970e).

    Dog-Aldicarb

    Groups of beagle dogs (2 male and 2 female dogs per group) were fed
    dietary levels of aldicarb at dosage levels of 0, 0.2, 0.3 and 0.7
    mg/kg body weight for 7 days.  Dogs were weighed three times during
    the week and observed daily for clinical signs of poisoning.  At the
    end of 7 days of feeding, 24 hours after being placed on control
    diets, the dogs were sacrificed for cholinesterase examinations and
    for gross examinations of kidney and liver.

    There was no mortality over the course of the one-week study.  Plasma,
    erythrocyte and brain cholinesterase activity, measured one day after
    conclusion of the dietary treatment, was normal.  Gross liver and
    kidney weight and organ-to-body weight ratios were unaffected by
    aldicarb in the diet (Weil and Carpenter, 1973).

    Groups of beagle dogs (4 male and 4 female dogs per group) were fed
    aldicarb in the diet for five days per week at dosage levels of 0,
    0.2, 0.3 and 0.7 mg/kg body weight for 99-100 days.  Clinical
    chemistry (including plasma and erythrocyte cholinesterase) and
    haematology parameters were examined prior to the initiation of
    feeding and at two intervals during the course of the study.  At the
    conclusion of the study, a final clinical chemistry and haematology
    evaluation and gross and microscopic examinations of tissues and
    organs were performed.  At the conclusion of the study, brain
    cholinesterase activity was also measured.

    There was no mortality over the course of the study.  Growth was
    comparable within all dosage groups.  At the conclusion of the study,
    organ weight and organ-to-body weight ratios were slightly affected
    only at the highest level of aldicarb.  A slightly decreased testes
    weight was observed in all treated groups with a significant effect
    noted only at the highest level.  A slight increase in adrenal weight
    was also noted at this level.  There were no effects in females on any
    of the tissues and organs examined.  Microscopic analysis did not
    suggest any abnormalities including tissues where gross changes had
    been seen to occur.  Cholinesterase values, as well as other clinical
    chemistry and haematology parameters were unaffected by the presence
    of aldicarb in the diet.  As the animals had been removed from
    aldicarb exposure for 24 to 48 hours prior to cholinesterase analyses,
    and considering the reversibility of inhibition, this parameter was
    not useful in this study in defining an effect of aldicarb.  A
    no-effect level in the study is 0.3 mg/kg body weight (Weil and
    Carpenter, 1974c).

    Aldicarb Metabolites

    Groups of dogs (3 male and 3 female dogs/group) were fed aldicarb
    sulfoxide in the diet at dosage levels of 0, 0.0625, 0.125, 0.25 and
    0.5 mg/kg body weight five days per week for three months.  There was
    no mortality over the course of the study.  Slight body weight changes
    were noted in many of the dogs at the highest dose level within the
    first week of treatment and thereafter the body weight changes were
    similar to, but lower than, control values.  No effects on
    haematologic and blood chemistry were observed.  Cholinesterase
    depression measured 24-48 hours after the final exposure was not
    observed in plasma, erythrocytes or brain of any of the animals at the
    conclusion of the study.  Gross and microscopic examination of tissues
    and organs did not show any adverse effect attributable to the
    presence of aldicarb.  A no-effect level based on somatic effects is
    0.25 mg/kg body weight (Weil and Carpenter 1968b).

    Groups of dogs (3 male and 3 female dogs per group) were fed aldicarb
    sulfone in the diet at dosage levels of 0, 0.2, 0.6, 1.8 and 5.4 mg/kg
    five days per week for 90 days.  Prior to the study and at 1, 2 and
    3-month intervals, plasma and erythrocyte cholinesterase were
    examined.  In addition, at the beginning and end of the study, blood
    chemistry and haematologic values were examined.  At the conclusion of
    the study, gross and microscopic examination of a variety of tissues
    and organs was performed.

    There was no mortality over the course of the study.  Slight body
    weight depression was noted at the highest dose level, although the
    body weight was not statistically lower than control levels.  There
    were no effects noted with respect to biochemical and haematologic
    parameters and gross and microscopic examination of tissues and organs
    revealed no effects attributable to the presence of aldicarb sulfone
    in the diet.  Cholinesterase depression was not noted over the course
    of the study.  Based upon available information, a no-effect level of
    5.4 mg/kg for dogs was observed (Weil and Carpenter, 1968).  In all of
    the three previous dog studies, cholinesterase activity is not a
    significant parameter to be considered in a toxicological evaluation
    because the animals were not administered aldicarb continuously, but
    were removed from dietary treatment for 1-2 days before the enzyme
    activity was measured.

    Long-Term Studies

    Rat

    Groups of rats (20 male and 20 female rats per group) were fed
    aldicarb in the diet for 2 years at dosage levels of 0, 0.005, 0.025,
    0.05 and 0.1 mg/kg body weight.  Additional groups of 16 of each sex
    were maintained for serial sacrifices at 6 and 12 months.

    There was no mortality over the course of the study attributable to
    the presence of aldicarb in the diet.  Growth was normal at all dosage
    levels, as was consumption of food, and behavioural characteristics.
    Results of gross examination of liver and kidney weight at 6 months
    and at one year did not differ from control values.  Haematologic
    values, including cholinesterase analyses, were normal.  (Haematologic
    data included red blood cell or haematocrit determinations in the
    highest dosage level and control groups.)  Blood and brain
    cholinesterase activity, measured at 6 and 12 months, were normal.
    Microscopic examination of tissues and organs for histopathologic
    occurrences and neoplasms showed the incidence of lesions to be
    similar in aldicarb-treated and in control groups.  An apparent
    no-effect level in the study is 0.1 mg/kg body weight (2 ppm) in the
    diet (Weil and Carpenter, 1965).

    Groups of rats (20 male and 20 female rats per group) were fed
    aldicarb in the diet at dosage levels of 0 and 0.3 mg/kg body weight.
    In addition, groups of rats were fed aldicarb sulfoxide (0.3 and 0.6
    mg/kg body weight).

    There was no significant mortality observed over the course of the
    study with any of the individual chemicals or the mixture of sulfoxide
    and sulfone.  In the initial phases of the study, there was a slightly
    higher mortality noted in the high dosage level of aldicarb sulfoxide
    and in the group receiving the combined aldicarb sulfoxide and
    aldicarb sulfone.  A slight increase in mortality was also noted at
    the latter part of the study with aldicarb sulfoxide.  Growth was
    slightly depressed at the high dose level of the sulfoxide:sulfone
    mixture, primarily in males.  There were no apparent effects on growth
    with respect to the aldicarb, aldicarb sulfoxide or aldicarb sulfone
    administered alone.  Hemocrit values observed at various intervals
    over the course of the study did not differ from controls. 
    Cholinesterase determinations were made periodically over the course
    of the study (6, 12 and 24 months).  Plasma, erythrocyte and brain
    cholinesterase were examined only at a 24-hour interval after animals
    were removed from test diets.  There was a slight depression of plasma
    cholinesterase noted in males administered the high dose level of the
    combination aldicarb sulfoxide and sulfone at the 24-month interval. 
    A repeat of the data within the final week of the study showed slight
    depression in all chemical groups with respect to plasma
    cholinesterase.  There were no effects noted at any interval with
    respect to red blood cell or brain cholinesterase.  The plasma
    cholinesterase depression noted at the 24-month interval was limited
    to male rats.

    An evaluation of the incidence of tumors suggested that there was no
    statistical difference between treated and control groups.  Gross and
    microscopic examination of tissues and organs at various periods over
    the two-year test interval showed that these sporadically distributed
    lesions were not considered to be indicative of damage induced by
    aldicarb, its major metabolites, or the combination of the sulfoxides
    and sulfone (Weil and Carpenter, 1972a).

    Groups of rats (50 male and 50 female F344 rats per group, 25 of each
    sex were used as controls) were administered aldicarb in the diet at
    dosage levels of 0, 2 and 6 ppm for 103 weeks.  A preliminary dietary
    study used 10 male and 10 female rats fed dietary levels of aldicarb
    (0, 5, 10, 20, 40, 80, 160 and 320 ppm) for 13 weeks.  Microscopic
    examinations performed on male and female rats of the 0 and 80 ppm
    dosage levels at the conclusion of the preliminary trial showed no
    significant somatic effects.

    In the long-term carcinogenicity study, there was no mortality noted
    attributable to aldicarb in the diet.  A variety of benign and 
    malignant tumors occurring at different sites in both control and
    aldicarb treated rats were not unusual for this strain of rat and were
    evaluated to be independent of the administration of aldicarb.  Gross
    and microscopic examination of tissues, organs and all gross lesions
    was performed and it was concluded that aldicarb was not carcinogenic
    for the F344 strain of rat of either sex (NIH, 1979).

    Dog

    Groups of beagle dogs (3 male and 3 female dogs per group) were fed
    aldicarb in the diet at dose levels of 0, 0.025, 0.05 and 0.1 mg/kg
    body weight for 2 years.  Aldicarb was administered in a moistened
    diet and the concentration was adjusted monthly to correspond to the
    mean body weight and diet consumed.  The dogs, 8 to 20 months of age
    at the initiation of the study, were administered aldicarb in the diet
    5 days per week for the two-year test interval.

    There was no mortality over the course of the study and growth and
    food consumption data were comparable to control values.  Haematology
    parameters and clinical chemistry values evaluated at five intervals
    over the course of the study were normal.  Plasma and erythrocyte
    cholinesterase, evaluated over the course of the study, did not differ
    from control values.  At the conclusion of the study brain
    cholinesterase,  while somewhat lower at the high dosage level, was
    not statistically different from controls.  Gross and microscopic
    examination of tissues and organs showed no lesions which could be
    attributable to the presence of aldicarb in the diet at dosage levels
    up to and including 0.1 mg/kg/day (Weil and Carpenter, 1966c).

    Mouse

    Groups of male mice (50 male and 50 female B6C3F1 mice per group, 25
    of each sex were used as controls) were administered aldicarb in the
    diet at dosage levels of 0, 2 and 6 ppm for 103 weeks in a
    carcinogenicity bioassay.  A preliminary dietary study used 10 male
    and 10 female mice fed dietary levels of aldicarb (0, 0.5, 1.0, 2.5,
    5.0, 10, 20 and 40 ppm) for 13 weeks.  Microscopic examinations,
    performed on male and female mice of the 0, 20 and 40 ppm dose levels
    at the conclusion of the preliminary trial showed no significant
    somatic effects.

    In the long-term carcinogenicity study there was no mortality noted
    attributable to aldicarb in the diet.  A variety of benign and
    malignant tumors occurring at different sites in both control and
    aldicarb-treated mice were not unusual for this strain of mice and
    were evaluated to be independent of the administration of aldicarb.
    Gross and microscopic examination of tissues, organs and all gross
    lesions was performed and it was concluded that aldicarb was not
    carcinogenic for the B63F1 strain of mice of either sex (NIH, 1979).

    Groups of mice (44 male and 44 female CD-1 mice per group) were fed
    aldicarb in the diet at dosage levels of 0, 0.1, 0.2, 0.4 and 0.7
    mg/kg body weight for 18 mouths (539 days or 77 weeks or 17.8 months
    of actual dosing).  Gross and microscopic examinations were performed
    on all surviving animals and on those mice that died during the course
    of the study.

    Mortality was evident in males at the two highest dosage levels and in
    females at the three highest dosage levels during the first two and
    one-half months of the study.  Following this period, aldicarb was

    mixed with the diet in a different manner which appeared to eliminate
    its acutely toxic effects. (In the early parts of the study, aldicarb
    was mixed in a dry fashion using a finely ground aldicarb preparation.
    At the 2.5 month interval, aldicarb was dissolved in acetone and the
    acetone-aldicarb solution was dispersed in the diet at a more uniform
    rate.  It was assumed that consumption of small crystalline particles
    of aldicarb may have led to the high mortality during the initial
    phases of the study.)  At the high dosage level in males there was a
    statistically significant increase in hepatomas found predominantly in
    the survivors at the termination of the study and an increase in
    lymphoid neoplasias which occurred in the mice that died.  None of the
    male mice surviving at the end of the study were found to have
    lymphoid neoplasias.  There were no significant increases in any other
    types of tumors at dosage levels of 0.4 mg/kg and below (Weil and
    Carpenter, 1972c).

    Groups of 50 male CD-1 mice were fed aldicarb in the diet at dosage
    levels of 0, 0.1, 0.3 and 0.7 mg/kg body weight in an effort to verify
    the results of the previous mouse carcinogenicity bioassay.  A group
    of 150 mice were used as concurrent controls with a mouse being
    sacrificed for each treated animal that died during the course of the
    study.  Diets were prepared by dissolving aldicarb in acetone and
    mixing the solution with the diet.  The aldicarb was the same sample
    as used in the previous study and the duration of the study was
    approximately the same as in the previous trial.

    There was no mortality observed in the study an a result of aldicarb
    in the diet.  At the end of 18 months cumulative mortality at all
    dosage levels was the same as noted in controls.  There was no effect
    of aldicarb on growth in any of the groups.

    An examination of the animals that died during the course of the study
    and those that were sacrificed at the end of 18 months was made and
    the data compared with control values.  There was no significant
    association between aldicarb in the diet and the formation of tumors,
    particularly with respect to the incidence of hepatomas, lung
    adenomas, and lymphoid neoplasias.  The data were evaluated with
    respect to the mice that died, those that survived the test and the
    total of all animals.   It was concluded that the administration of
    aldicarb at levels up to and including 0.7 mg/kg body weight for
    approximately 18 months did not result in a higher than normal
    incidence of tumors and the inclusion of aldicarb in the diet of CD-1
    mice did not result in an increased incidence of carcinogenic response
    (Weil and Carpenter, 1974d).

    Observations in Humans

    Groups of 4 adult male volunteers were administered aldicarb orally in
    aqueous solution at dosage levels of 0.025, 0.05 and 0.1 mg/kg body
    weight.  Clinical signs of poisoning were recorded and whole blood
    cholinesterase activity was measured up to six hours after
    administration of the sample.  Total urine voided was collected and
    aldicarb-excretion patterns for the initial eight hours after dosing

    were evaluated.  In addition, spot samples were taken at 12 and 24
    hours.

    Acute signs of poisoning, typical of anticholinesterase agents, were
    observed at the high dose level within one hour after administration
    of aldicarb.  There were no signs of poisoning observed at the 0.05
    mg/kg body weight dose level.  Cholinesterase depression was observed
    in all volunteers predominantly within 1-2 hours after treatment.
    Within the first six hours of treatment almost all cholinesterase
    depression and clinical signs of poisoning were diminished.
    Examination of urinary excretion patterns showed that approximately
    10% of the administered dose was excreted as carbamates (toxic
    residues) within the first eight-hour interval.  Cholinesterase
    analyses confirmed the same rapid inhibition and recovery pattern with
    man as had been observed in experimental animals (Haines, 1971).

    In another study, two additional subjects were administered aldicarb
    in water solution at dosage levels of 0.05 and 0.26 mg/kg body weight.
    Acute signs of poisoning were recorded at the higher dose level and
    atropine was administered to aid recovery.  No signs of poisoning were
    recorded with the lower dose level.  Urinary excretion of carbamate
    residues within 24 hours accounted for approximately 10% of the
    administered dose (Cope and Romine, 1973).

    A series of human exposure episodes was reported occurring as a result
    of a variety of field and glasshouse conditions in an effort to assess
    the potential for human harm from exposure under actual occupational
    conditions.  In several instances, slight blood cholinesterase
    depression attested to the actual exposure situation.  Exposure data,
    as indicated by cholinesterase depression or urinary excretion,
    suggested that there was no change in the general health of workers
    exposed under any of the working conditions.  Although there were
    acute clinical signs of poisoning there was no indication that the
    workers exposed were harmed once removed from exposure situation
    (Williams, 1966; Burrows, et al., 1970; Wakefield, et al., 1973;
    Shrivastava, 1975; Pandey, 1977).

    From 1966 to 1979, 133 cases of apparent overexposure to aldicarb
    formulations were reported (Abdalla, 1977; 1979).  Of these cases, 40
    were confirmed aldicarb poisoning episodes where clinical diagnosis
    and/or urinalysis for aldicarb and its metabolites were performed.
    There have been no confirmed deaths resulting from (predominantly
    occupational) overexposure, and, as has been the case with other
    carbamate insecticides, the acute signs of toxicity are rapidly
    dissipated, although atropine therapy and hospitalization have been
    useful therapeutic regimens.

    California, which has one of the best pesticide reporting systems for
    accidental overexposure, reported that in 1974, 75 & 76 a total of 10,
    14 and 13 cases of human illnesses were reported respectively for the
    three years (Peoples, et al., 1977).  In these incidents, people
    were directly exposed to aldicarb and illness was brought on by
    dermal, inhalation and in one instance, ocular exposure.  While most

    illnesses resulted from aldicarb exposure in loading or applying the
    formulated pesticide, some illness has been reported from the handling
    of plants and soils treated with aldicarb (Abdalla, 1977; 1979).

    COMMENTS

    Aldicarb is an N-methyl carbamate ester of an aliphatic oxime
    currently used as an insecticide in agriculture.  Aldicarb has been,
    and is currently formulated as, a granular preparation for use as a
    soil treatment having systematic activity in plants against a variety
    of insect, mite and nematode pests.  Aldicarb in extremely toxic with
    an extremely low LD50 value in a wide variety of mammalian species.
    The onset of acute signs of poisoning appears to be due to reversible
    cholinesterase inhibition resulting in parasympathomimetic signs of
    poisoning.  The acute signs of poisoning are alleviated rapidly
    usually without treatment, and frequently within hours, but always
    within 1-2 days of exposure.

    Aldicarb is rapidly absorbed, widely distributed in the body and
    rapidly excreted.  Bioaccumulation does not appear to be a factor with
    aldicarb.  Aldicarb metabolism has been widely studied in a variety of
    organisms and appears to be similar in all species examined.  Aldicarb
    is rapidly metabolized through oxidation of the sulfur atom to produce
    a toxic, relatively stable metabolite, aldicarb sulfoxide.  Aldicarb
    sulfoxide in slowly converted by hydrolytic and/or oxidative
    mechanisms to aldicarb sulfone and related oxime and other degradation
    products.

    A wide variety of special studies have been performed to evaluate the
    toxicological hazard associated with the use of aldicarb.  Aldicarb
    does not affect reproduction, is not teratogenic or carcinogenic in
    mammals and there is no evidence of a delayed neurotoxic potential.

    Cholinesterase depression is the most significant parameter of
    exposure that can be evaluated with respect to the toxicology of
    aldicarb.  Considerable attention was paid to the analytical
    methodology used to develop cholinesterase depression data.

    Short-term and long-term dietary studies were conducted with aldicarb
    and aldicarb metabolites both alone and in combination, and no-effect
    levels were noted.  In some of these studies, there was a
    discontinuation of feeding of aldicarb or its metabolites for short
    periods prior to the evaluation of cholinesterase activity.  This
    practice served to point to the rapid reversibility of cholinesterase
    depression, although in the toxicological evaluation, continuous
    exposure prior to analysis of cholinesterase activity was thought to
    be very important.

    Erythrocyte and plasma cholinesterase were the most sensitive
    parameters of exposure.  In a short-term study in rats with aldicarb
    sulfoxide, cholinesterase depression served as the basis for
    evaluating a dietary no-effect level.  Cholinesterase depression in

    plasma and erythrocytes, measured through the use of an acceptable
    analytical procedure, was not observed at 0.125 mg/kg body weight.

    Studies on dogs have been performed with aldicarb, aldicarb sulfoxide
    and sulfone for various time intervals up to and including two years.
    Cholinesterase depression was not noted in the dog studies because of
    interrupted treatment.  An appropriate short-term cholinesterase study
    in dogs would be desirable to allow further evaluations to be made.
    Currently, standardized tests for mutagenicity have not been reported,
    although a dominant lethal assay in mice suggested no potential for
    mutagenic events.  Microbial mutagenicity tests were considered to be
    desirable.

    Human volunteer studies show that man reacts in a similar manner to
    experimental animals.  Data on the rapid onset and diminution of signs
    of poisoning and depression and recovery of cholinesterase activity
    parallel those observed in animal bioassays.

    As the slope of the acute toxicity curve is so steep, an additional
    margin of safety reflected the high acute toxicity of aldicarb.  The
    rapid reversibility of cholinesterase depression, the lack of
    long-term pathological events and the lack of effects in a wide
    variety of toxicological parameters were all reassuring in estimating
    an acceptable daily intake for man.

    TOXICOLOGICAL EVALUATION

    Level Causing No Toxicological Effects

    Rat: 2.5 ppm in the diet, equivalent to 0.125 mg/kg body weight
    Dog: 0.25 mg/kg body weight

    Estimate of Acceptable Daily Intake for Man

    0-0.001 mg/kg body weight

    RESIDUES IN FOOD AND THEIR EVALUATION

    USE PATTERN

    Pre-harvest treatments

    Aldicarb is employed as a systemic pesticide to control insect, mite
    and nematode pests in plants.  Technical aldicarb is so extremely
    toxic to man that it has never been commercially available in
    conventional wettable powder, emulsifiable or solution form.  The
    inventor and sole manufacturer, Union Carbide Corporation, markets
    aldicarb only as granular products containing 5 to 15 percent active
    ingredient.  This formulation allows the product to be handled and
    applied with minimal hazard to man.

    The granular products employ ground corn cobs, gypsum, or ground
    charcoal as substrates.  Granular particle size range is 16 to 60

    mesh, or about 0.25 to 1.5 mm diameter.  Technical aldicarb is
    produced in acetone or methylene chloride solution, impregnated into
    granules and the solvent in removed by evaporation.  One percent of
    water-soluble resin is added as a bonding agent to hold the aldicarb
    on the granule.  Various antistatic or colouring agents may be added
    in small amounts.  The finished granular products are clean,
    free-flowing, and stable in storage for at least two years.  Aldicarb
    is marketed worldwide in waterproof dispensers, bags or cartons
    containing 1.5 or 10 kg of granular product.

    The pesticide is most commonly applied by mechanical tractor-mounted
    applicators which deliver the granules 2.5 to 5 cm beneath the soil
    surface.  For field crops like cotton, sugar beets, and potatoes,
    granules are applied in the seed furrow, adjacent to the seed, or
    alongside the row after crop emergence.  In some cases, surface
    application followed by immediate rototilling to incorporate the
    granules into the soil is recommended.  In glasshouse usage for
    treating commercially grown ornamental plants, smaller hand-held
    applicators spread the granules over beds, benches, or pots and the
    aldicarb is watered into the soil.

    Rate of use range from one to three kg/ha for row crops.  As much as 5
    kg ai/ha may be used in potatoes against the golden nematode.  Citrus
    and some ornamentals require higher rates, up to 11 kg ai/ha. 
    Usually, only one application is made per crop either at planting or
    within six weeks after emergence.  In bananas, 2.5 to 3 g ai/mat/6 mos
    is applied.  Aldicarb is also used as a seedling treatment for coconut
    and cacao.  For most food crops, a 90-120 day pre-harvest interval is
    required for residues to be reduced below acceptable levels.  There
    are no post-harvest uses.

    Aldicarb is used on numerous crops in many countries.  Registered
    usages include potatoes, coffee, sugar beets, cotton, soybeans, dry
    beans, bananas, oranges, sugarcane, peanuts, sweet potatoes, pecans
    and ornamentals.  In 1979, Temik 15G was tke major product used in the
    USA for aphids, golden nematode, and Colorado potato beetle on
    potatoes; for early season insects and nematodes on cotton; and for
    aphids, maggots, and nematodes on sugar beets.  The USA consumes 70%
    of world production; Pan America, 15%; Europe, 10%; and other areas,
    5%.

    RESIDUES RESULTING FROM SUPERVISED TRIALS

    Extensive data provided by the manufacturer on residues of aldicarb
    and its toxic metabolites are the basis for the following discussions.

    Cotton

    During 1966 through 1968 with aldicarb applied at planting time, as
    sidedress treatment, and a combination of the two treatments, 75% of
    244 samples showed no residues above the sensitivity of the method;
    90% less than 0.07 mg/kg and 1% more than 0.1 mg/kg.  Aldicarb itself

    was not detected in any sample, but the sulfone formed the main
    portion of the residue.

    Potatoes

    Residue data was collected in the United States for nine consecutive
    crop years (1964 through 1972).  There was a total of 342 samples from
    21 states in the USA, representing all the potato growing areas.
    Samples were also collected from Quebec and Ontario.

    Growth dilution is the important factor as regards residues in tubers.
    In the period from 70 to 90 days after planting, the tuber is growing
    rapidly with much increase in bulk.  The uptake of new pesticide
    apparently cannot match the dilution by new tissue, and there is a
    rapid decrease in residue concentration.  From 90-110 days, residues
    are still increasing at a slowing rate, an average decrease of about
    40 percent, and after 110 days, the tuber residue changes very little.

    Aldicarb itself has not been found as a residue in potato tubers.  The
    toxic tuber residue consists entirely of aldicarb sulfoxide and
    aldicarb sulfone.  At harvest, a ratio of 78 percent aldicarb
    sulfoxide and 22 percent aldicarb sulfone has been found.

    There was considerable variation in tuber residue even for those
    seemingly grown under identical cultural practices and climatic
    conditions, pointing to the need to rely on the determined values
    rather than general assumptions.  Samples collected from Maine, USA
    for potatoes treated at the rate of 0.5 to 1.5 kg in-furrow ranged
    from 0.01 to 0.5 mg/kg after 107 days.  Of the 248 samples from
    recommended at-planting treatments, only two show residues which might
    exceed one mg/kg at harvest assuming a pre-harvest interval of 90
    days.  Sidedressing after an application at planting time did not add
    significantly to tuber residues.

    In South Africa measurements of residues in potatoes, at periods
    ranging from 90 to 180 days after treatment in eight sites and at the
    registered application rate of 7.5 kg ai/ha, show that the recommended
    120 days PHI could accommodate the national limit of 1 mg/kg.  (As the
    PHI is normally extended up to 150-170 days, the evidence indicates
    that this figure would not generally be exceeded.)  In New Zealand
    single pre-planting applications at 10 kg ai/ha gave ca. 0.1 mg/kg
    aldicarb at harvest 118 days later (New Zealand, 1979).

    In the Netherlands, trials in several localities with aldicarb applied
    90-160 days before harvest at the 5 kg ai/ha application rate gave
    levels mainly in the 0.06 - 0.5 mg/kg range.  Only one sample out of
    52 had residues in the 0.6 - 1 mg/kg range.  At the normally
    recommended application rate of 3 kg ai/ha, the maximum residues
    occurred in the 0.06 - 0.1 mg/kg range.

    Peanuts

    Aldicarb is generally applied at 1 to 2 lbs ai/A in-furrow at
    planting.  In the samples of harvest peanuts from at-planting
    treatments of up to 4 lbs. ai/A, the range of residues were as
    follows:

    Residue Range in Whole Nuts (mg/kg)     No.    Samples in Range %

                >0.2                         0             -
                0.1 - 0.2                    1             2
                0.05 - 0.1                   5            11
                0.01 - 0.05                 20            43.5
                <0.01                       20            43.5

    Whole nut residues were concentrated primarily in the hull and peanut
    kernels generally contained less than 0.02 mg/kg aldicarb.

    Citrus

    Analysis of over 200 samples of oranges treated at rates of 2.3 to 22
    kg ai/ha showed that the maximum residues in ripe oranges was 0.2
    mg/kg.  Residues are higher in immature green fruit than in ripe fruit
    and residues in peel are higher than in edible pulp, averaging about
    4:1 peel-pulp in both green and ripe fruits.  The maximum residue
    found in ripe orange pulp was 0.1 mg/kg in a Valencia, 30 days after a
    treatment of 11 kg ai/ha.  The peel residue was 0.5 mg/kg, resulting
    in a calculated whole fruit residue of 0.2 mg/kg.  Fruits becoming
    ripe six to seven months after the ripe fruit cited above continued to
    show whole fruit residues of 0.1 - 0.2 mg/kg.

    When aldicarb was applied to the soil around orange trees at rates of
    0.09, 0.45, and 2.26 g ai/929 cm2, analysis of the orange peel and
    pulp at approximately 100 days after treatment did not detect the
    presence of aldicarb.  The aldicarb sulfoxide residues in the peel
    from the three treatments were 0.06, 1.4, and 12.8 mg/kg, while the
    residues in the pulp were 0.03, 0.4, and 2.6 mg/kg.  The aldicarb
    sulfoxide residues in the peel from the three treatments were 0.06,
    1.4, and 12.8 mg/kg, while the residues in the pulp were 0.01, 0.1 and
    0.6 mg/kg.

    Iwata et al. (1977) detected 0.03 - 0.05 mg/kg residues in orange
    pulp 28 days after treatment with 22 kg ai/ha, but not at 11 kg ai/ha.

    Bananas

    Samples were obtained from Ecuador, Peru, Philippines and Costa Rica.
    The maximum residue found in whole bananas treated either at or near
    the recommended rate of three g ai/mat (i.e. ca. m2) is 0.2 mg/kg.
    The data are summarized in Table 3.  Measurements in Ecuador, Peru,
    the Philippines and S. Africa of residues in fruit at known periods
    after application show that peak levels are reached in 40 to 100 days.

    This is illustrated in Table 4 (S. Africa).  The variation in time
    after treatment when peak residues occur is probably a combined effect
    of differences in moisture, plant size, soils, temperature and growth
    dilution.  Apparently, residues in harvest fruit are not additive nor
    accumulative from multiple treatments at six months intervals.

    Analysis of the pulp and peel showed that there is no significant
    difference in residues and that the whole fruit data could represent
    the edible pulp residues as well.  There is also no discernible
    difference in the residue content of the top, middle and bottom hands
    on the stem.  The first application resulted in residues in some
    samples slightly higher than the proposed MRL; but the Meeting viewed
    the more extensive residues data from Ecuador, Peru, Philippines and
    Costa Rica, the traditional banana suppliers of the world, as being
    more indicative of the residues situation.

    Dry Beans

    About 75 dry beans seed samples have been analyzed.  Aldicarb was
    applied at a maximum treatment rate of 22 kg ai/ha in-furrow at
    planting time.  The maximum residue found at normal harvest was 0.07
    mg/kg after application of the highest rate tested, 3.3 kg ai/ha at
    planting.  At normal rates, the maximum residues was 0.02 mg/kg.  The
    type of application at planting did not influence residues at harvest. 
    Each sample was a composite of green ripe fruit from bottom, middle
    and top of bunch.

    Bean (Dry) forage

    The highest residue found in dry bean forage was 2.8 mg/kg in a sample
    of straw after an at-planting application of 3.3 kg ai/ha.  Harvest
    residues in other samples from this application, timing and use rate
    ranged from 0.2 to 1.2 mg/kg.

    Residues in green forage may approach 30 mg/kg at recommended use
    rates, but decline as the plants mature, lose some of their leaves and
    become dry toward harvest.  Dry bean straw, green forage, and hay are
    restricted from use by directions to the label.

    Aldicarb was applied at 0.8 to 3.3 kg ai/ha at planting.  Forty-eight
    soybean seed samples and 44 forage samples were collected.  No
    detectable residues (0.02 mg/kg) were found in any soybean seed at
    harvest, regardless of the application rate or type of application.
    Low level aldicarb residues were found in some immature seeds but
    these residues quickly diminished as the seed matured to become
    non-detectable at harvest.  The highest residue found in any soybean
    seed was 0.15 mg/kg in very immature seed 58 days before threshing.
    Three weeks later (still 36 days before normal harvest) the residues
    diminished to non-detectable (0.02 mg/kg) and remained so at harvest).

    Table 3.  Maximum Residues of Aldicarb (mg/kg) in Bananas Collected
    from Different Countries

                                                                     
                                             Rate
                                      (ai/mat/treatment)
                                                                      

    Location             21         3           4           6        7-8

    Ecuador             0.04       0.09                    0.1
    Peru                 -         0.2         0.2          -        0.6
    Philippines
      1973               -         0.1          -           -         -
      1975              0.05       0.09         -           -        0.8
    Costa Rica           -          -          0.3          -         -
                                                                      

    1  Application to the nearest gram.
       (mat similar or equal to sq.m)



    Table 4.  Aldicarb Residues in Bananas at Different Periods after
    Application (South Africa)

                                                                      
                               Residues of Aldicarb (mg/kg)
    Days After           First Treatment       Treatment 6 Months Later
    Application     A-3g ai/m2   A-6g ai/m2    B-3g ai/m2   B-6g
    ai/m2

                                                                      

         15            0.04         0.05          0.04         0.2
         30            0.2          0.4           0.03         0.04
         45            0.3          0.7           0.06         0.1
         60            0.4          0.7           0.1          0.2
         90            0.4          0.6           0.2          0.2
        120            0.4          0.5           0.3          0.05
        180            0.1          0.4           0.2          0.4
                                                                      


    Soybean forage and straw

    At-harvest residues in soybean straw are generally quite low and do
    not exceed 0.1 mg/kg.  Aldicarb residues in green soybean forage may
    exceed 5 mg/kg at the proposed treatment rates two months before
    harvest and younger plants would contain even higher residues.  Use of
    soybean forage or hay as animal feed is not recommended.

    Soybean oil and meal

    Soybean seeds do not contain detectable residues (<0.01 mg/kg) when
    treated up to two to three times the recommended rates; higher rates
    are generally phytotoxic to soybeans.  Just the same, soybeans from
    fields treated at 1 and 2 the recommendations were composited and
    fractionated by procedures closely paralleling the commercial solvent
    extraction process to yield oil and meal.  No residues were found in
    either the oil or meal components.  The procedure applied would have
    detected residues at 0.005 mg/kg in soybean oil and 0.01 mg/kg in the
    meal.

    Coffee

    Only 6 of the 47 samples of green coffee analyzed show analytically
    significant residues at a method sensitivity of 0.02 mg/kg.  These
    samples include exaggerated treatment rates (up to 2) as well as
    multiple treatments (1-3) and preharvest intervals from 15 days to 274
    days.  Aldicarb residues seem to preferentially concentrate in the
    hulls of the dry coffee berry as shown below:

                   Hulls                    0.01 mg/kg
                   Parchment                0.05 mg/kg
                   Green coffee             0.04 mg/kg

    The higher residue level in hulls is logical since more water is lost
    from the pulpy hull on drying than from either the parchment or seeds.

    Strawberry

    From the results of supervised trials undertaken in Finland, it was
    noted that quite high residues could be found after application of
    aldicarb to strawberries (Finland, 1979).  It was also noted that use
    on this crop has not been recommended.

    Sugarcane

    Applications of 5.5 kg ai/ha at planting time into the furrows and to
    ratoon canes resulted in residues shown in Table 5 (South Africa,
    1979).  Aldicarb appears to be concentrated in the leaves.

    Table 5.  Residues of Aldicarb in Sugarcane following application of
    5.5 kg ai/ha at Planting Time (An extract from results received from
    South Africa)

                                                                     
    Treatment                  Application intervals (days)
                    18      25     32      46        60       75
                                    (Residues in mg/kg)
                                                                     
    I.  Plant cane

    Site A. T1      18.3    5.7    5.1     4.3(L)    0.9      0 6(L)
                    21      5.5    5.1     4.0(L)    1.0      0:6(L)
                                                     1.0(S)   0.3(S)
                                                     0.9(S)   0.3(S)

    Site A. T3      12.8    4.0    4.7     3.9(L)    1.1      0.8(L)
                    11.1    3.4    3.9     3.6(L)    1.2      0.8(L)
                                           0.8(S)             0.3(S)
                                           0.9(S)             0.3(S)


    II.  Ratoon cane

    Site A.         15      29     54      91
                                               
                    5.1     12.3   4.7     0.01
                    5.4     11.6   4.5     0.01

    Site B.         7       13     20      28
                                               
                    7.3     2.1    0.4     0.2
                    7.5     2.0    0.5     0.2
                                                                     

    L = leaves
    S = stalk

    Sugarbeet fodder

    It is seen below that aldicarb is concentrated on the sugarbeet tops
    (Denmark, 1979).  Low level residues occurred 135 and 180 days after
    application at dosage rates of 0.7 and 1.4 kg ai/ha.  The numbers
    refer to mg/kg aldicarb sulfone.

                             135 days                 180 days
                      root             top      root            top

    0.7 kg ai/ha      0.007            1.0      n.d.            0.05
                      0.007            1.0      n.d.            0.08

    1.5 kg ai/ha      0.009            1.4      n.d.            0.2
                      0.02             2.9      n.d.            0.3

    Onions

    Residue trials in the Netherlands showed residues less than the 0.05
    mg/kg limit of detection after application of 1.5 kg ai/ha as row
    treatment, 150-168 days after application (Netherlands, 1979).

    FATE OF RESIDUES

    General

    The common metabolic pathway for aldicarb in plants, animals, insects
    and soils is shown in Figure 2.  The consistency of aldicarb
    metabolism in plants has been illustrated with cotton, potatoes,
    spearmint, lettuce, sugarbeets, peanuts and tobacco.  Following soil
    treatment, aldicarb is readily absorbed by the plant with subsequent
    translocation.  Within the plant, the initial step is thioether
    oxidation to aldicarb sulfoxide.  This biochemical conversion occurs
    rapidly since no parent aldicarb is found in the plant after a few
    weeks.  Aldicarb sulfoxide is subsequently metabolized primarily by
    hydrolysis to yield the sulfoxide oxime.  It also produces aldicarb
    sulfone through slow thioether oxidation.  Both the sulfoxide and the
    sulfone suffer extensive degradation through hydrolysis elimination,
    oxidation, reduction and conjugation reactions.  Such products include
    the oximes and the resulting alcohols and their glycoside conjugates,
    the amides, the nitriles and the carbonic acids.  Essentially, these
    are of no toxicological significance.  There has been no evidence of
    conjugated carbamate metabolites in plants resulting from aldicarb
    treatment.  Consequently, the only significant terminal carbamate
    containing residues in plants following aldicarb treatment are the
    aldicarb sulfoxide and aldicarb sulfone, and depending on the
    harvesting time, a minor residue of parent aldicarb.

    There is essentially no retention of aldicarb and its carbamate
    metabolites in tissues, milk and eggs.  Residues can be detected in
    milk only when cows were fed with exaggerated dosages.  At residue
    levels normally resulting from aldicarb usage, no residues can be
    detected in milk.  Excretion is mainly through the urine.  In laying

    hens, excretion of aldicarb sulfoxide and sulfone is rapid for both
    single oral and continuous feeding for up to 10 days.  About 75
    percent of the doses are in the faeces by 24 hours and a large portion
    of the metabolites are water-soluble materials.  Only minute
    quantities of the toxic carbamate compounds were observed.

    A positive correlation exists between temperature and moisture and the
    rate of loss of aldicarb in soils.  Aldicarb is very susceptible to
    alkaline hydrolysis and is presumably unstable at higher soil pH.
    Upward movement is observed with most soils with aldicarb apparently
    leaving the soil surface entrained with water vapour.  Only in pure
    sand is downward movement readily achieved through water action so
    that aldicarb does not pose a hazard through ground water
    contamination.

    Aldicarb is degraded by micro-organisms and the catalytic action of
    clays and other inorganic soil constituents.  No hazard from carryover
    residues is expected.  Bacteria or fungi do not appear to be
    susceptible to the toxic action of aldicarb and the compound could
    even serve as a carbon source for some micro-organisms.

    In animals

    (see Biochemical Aspects).

    In plants

    Metcalf et al. (1966) demonstrated that aldicarb was completely
    oxidized to aldicarb sulfoxide in cotton foliage within four to nine
    days.  Further hydrolysis yielded the sulfoxide oxime, and oxidation
    of the aldicarb sulfoxide to aldicarb sulfone occurred.  Coppedge et
    al. (1967) confirmed these findings, and identified the sulfoxide
    nitrile as a definite metabolite in cotton.  Once formed, aldicarb
    sulfone is not reduced to provide a secondary source of aldicarb
    sulfoxide, nor could evidence of oxidative N-demethylation be found.
    The total radioactivity in the cotton plant in reduced with time
    through volatilization and dilution by plant growth.

    Field-grown cotton was treated with radioactive aldicarb by in-furrow
    at planting and by side-dressed applications (Andrawes and Bagley,
    1968c).  The residues were identified, quantitated, and the rates of
    decline determined.  The metabolic pattern of aldicarb in vivo was
    in agreement with that described by earlier investigators.  A second
    field study employed petiole injection and obtained similar results
    (Bull, 1968).  A complete distribution of radioactivity in the cotton
    plant was described and the residue in the maturing fruit was
    characterized.  After four weeks no toxic residues were present in the
    bolls.

    Bartley, et al. (1970) showed that sulfoxide oxime in further
    transformed to a mixture of water-soluble products.  These consist
    primarily of sugar conjugates of sulfoxide alcohol, as well as smaller
    quantities of sulfoxide and sulfone acids and sulfone amide.  There is

    no evidence for the presence of N-methylol or N-demethyl derivatives
    as sugar conjugates.

    After gaining entrance into the potato plant, aldicarb residues move
    primarily by xylem transport with highest concentrations appearing in
    the foliage.  Stem injection studies have shown that only limited
    quantities of aldicarb and its metabolites move downward into the
    tuber.  The toxic carbamate residues appearing in the tuber do not
    persist, but are actively degraded to non toxic water-soluble products
    similar to those formed in the foliage (Andrawes and Bagley, 1968b;
    Andrawes et al., 1971b).

    Systemic movement and concomitant metabolism of aldicarb resulted in a
    preferential accumulation of the residues in peanut foliage
    (Andrawes,l972).  A small fraction of the observed radioactivity was
    found in the fruits.  Translocation of residues to the forming fruit
    is facilitated by the polar nature of the metabolic products present
    in the maturing plants.  These water-soluble metabolites were the
    predominant component of the terminal residues in the foliage and
    constituted 90 to 95 percent of the recovered radioactivity in the
    kernels.

    Aldicarb sulfoxide, aldicarb sulfone, and the non-toxic water soluble
    metabolites constituted the major portion of the residual C14
    materials in sugar beets (Andrawes et al., 1970).  Most of the
    absorbed radioactivity was found in the foliar portion of the plant
    throughout the growing season.  At maturity (140 days after treatment)
    total C14 residues were 27.2 mg/kg in the foliage and 2.5 mg/kg in
    the roots.  The corresponding values for total toxic residues was 11.0
    mg/kg in the foliage and 0.6 mg/kg in the roots.

    In soil

    The chemical changes that occur in soil are essentially the same as
    for plants, animals and insects.  Series of parallel experiments have
    been performed under the same environmental conditions with single
    factors varied to assess the roles in controlling the persistence of
    aldicarb in the soil.  These factors include soil types, moisture, pH,
    and temperature (Coppedge, et al., 1967; Bull, 1968; Romine et
    al., 1968; Bull et al., 1970; Quraishi, 1972; Supak, 1972; Gawaad
    et al., 1971).

    A positive correlation exists between temperature moisture and rate
    loss from soil.  Changes in pH in the 6 to 8 range do not appear to
    adversely affect aldicarb although the compound in is very susceptible
    to alkaline hydrolysis so that it is anticipated that it would be
    unstable in high soil pH.

    Under greenhouse and field conditions, aldicarb and its breakdown
    products leave the soil with unexpected rapidity; a half-life of seven
    days was observed (Bull et al., 1968).  This emission is definitely
    linked to the degree of soil moisture and consists primarily of an

    upward movement.  This phenomenon has been studied in an elaborate
    series of percolation experiments with different soil types in
    assorted sizes of columns (Bull et al., 1968; Romine et al., 1968)
    and under field conditions (Bull, 1968; Bull et al., 1968).  Only in
    pure sand is downward movement readily achieved through water action.
    Aldicarb and related compounds probably leave the soil entrained with
    water vapour as little movement has been noted in dry soils.

    The dissipation of aldicarb in the soil is sufficiently rapid and
    complete that recommended rates will offer no hazard of contamination
    of subsequent crops in a treated area (Andrawes and Bagley, 1968;
    Andrawes et al., 1971a; Quraishi, 1972).  Predictably, discing or
    other soil manipulations will serve to disperse and dilute aldicarb
    that has been placed in-furrow.  Tomatoes transplanted into fields 90
    days after a 3.3 kg/ha application of radioactive aldicarb showed no
    detectable radioactivity when analyzed seven days later.  Bioassays of
    volunteer potato plants taken from fields treated the previous year
    with 6.6 kg/ha active ingredient were completely non-toxic to the
    highly sensitive Colorado potato beetle (Clarkson, 1968).

    Extensive laboratory screening tests in which high concentrations of
    aldicarb and its metabolites were incorporated into various nutrient
    media and then inoculated with bacteria or fungi suggest that the
    pesticide has no toxic effect on microorganisms (Spurr and Chancey,
    1968; Spurr and Sousa, 1974; Anderson, 1971).  Gawaad et al., (1972)
    also found no effect on the nodulation rate of Rhizobium phaseoli
    and R. trifolii in broad beans and Egyptian clover.  Soil
    enrichment experiments even demonstrated that aldicarb could serve as
    a carbon source for certain microbes (Spurr and Chancey, 1968).
    Aldicarb was however very toxic to oribatid mites while it was less
    toxic than several other materials to earthworms, enchytraeids,
    predatory mites and collembola (Heungens, 1970).

    Since aldicarb does not readily move downward through different soil
    types by leaching action except in sandy soil, resultant contamination
    of ground water from surface-treated fields is unlikely.  Clarkson et
    al. (1968a) treated a graded 0.2 ha with 4.5 kg of aldicarb.  They
    did not find any significant movement of the pesticide during the
    30-day test period and over 20 cm of rainfall.  On the other hand,
    Gawaad et al. (1971) showed that aldicarb had leaching rates of
    47.12, 42.3 and 56.14 percent from sand, loam and sandy clay loam
    soils respectively.  Lateral movement of aldicarb is low (Woodham et
    al., 1973).

    Kearby et al. (1970) in a study of the distribution and persistence
    of residues in a Pennsylvania tree farm soil, wherein aldicarb was
    applied at 0.23 and 0.45 kg trees, found no apparent chemical residues
    in soil samples taken at depths of 15 and 30 cm, 36 and 63 days after
    treatment.  The half-lives of aldicarb and its major metabolites were
    estimated to be 15 days.

    In Water

    The disappearance of aldicarb was determined over a 30-day period in
    distilled water at pH 6, 7 and 8, and in pond water and lake water,
    the latter two in the presence and absence of their respective bottom
    material (Moorefield, 1974).  The initial concentration of aldicarb in
    all samples was 0.5 mg/kg.  There was little or no degradation of
    aldicarb carbamates in the distilled water, or in the pond and lake
    water in the absence of bottom material.  In the pond water with about
    5% mud (percent by weight, dry basis) present, the aldicarb carbamate
    residue degraded to a concentration of 0.02 mg/kg in 20 days, the
    half-life being about 5 days.  After 20 days, the bottom mud contained
    less than 0.01 mg/kg aldicarb carbamates.  In lake water in the
    presence of bottom silt, aldicarb carbamates degraded to a
    concentration of 0.03 mg/kg in 25 days; half-life is about 6 days.

    Moorefield (1974) further reported on a field study in which a farm
    pond was treated with aldicarb at an initial concentration of 3 mg/kg.
    Samples of water and bottom and were taken periodically.  Aldicarb
    carbamate residues in the pond water declined to 1.1 mg/kg after 2
    weeks; 0.26 mg/kg after 4 weeks; 0.06 mg/kg (the limit of sensitivity
    of the method) after 6 weeks.  The half-life was about 7 to 10 days.
    The maximum concentration of aldicarb carbamate residues in the bottom
    mud was 0.09 mg/kg at 4 weeks.  The dissipation of aldicarb carbamate
    residues on this farm pond was rapid and complete, without residue
    buildup in pond sediment.

    Quraishi (1972) studied the persistence of aldicarb in water collected
    from fields.  Treatment at 100 mg/kg of aldicarb resulted in residues
    of aldicarb and metabolites at 0.4 mg/kg after 11 months.

    In storage and processing

    Cotton

    Processed cotton meal from seed treated at 0.1 mg/kg contained only a
    fraction of the residue present in the whole seed and no detectable
    residues (<0.003 mg/kg) were found in refined cottonseed oil.

    Potatoes

    The processing of potatoes into potato chips, potato flakes and the
    process of baking, boiling, making into french fries, hash browning
    and canning of potatoes was investigated for their effect on residues
    in raw tubers.  In the case of potato chips, 95 percent of the residue
    in raw tubers is lost during the manufacturing.  However, since up to
    5 lbs. of tubers are required to produce kg  kg of chips, the
    concentrative effect results in chips having an apparent loss of only
    69 percent.  The maximum residues found in potato chips was 0.2 mg/kg
    and resulted from tubers having 0.45 mg/kg residues.  The rest shows
    residue of 0.1 mg/kg or less.  In potato flakes, the maximum residues
    found from harvest tubers treated at recommended rates was 0.12 mg/kg.
    Aldicarb residues destroyed in the other processes were: baking, 65

    percent; boiling, 60 percent; french frying, 36 percent; hash
    browning, 72 percent; canning, 65 percent.  This in an average
    destruction of about 60 percent of the raw tuber residue for these
    commonly used cooking procedures.

    Smelt et al. (1975) found in five samples of peeled potatoes and
    peelings that the contents in the peelings were on the average 11%
    higher than in the peeled potatoes.  Hence, peeling does not lead to a
    significant decrease of the residue.  On boiling with 2% NaCl solution
    for 20-24 minutes 42-52% lower residues were observed than before
    cooking.  Only about 2.5 -8.1% of the initial residue was found in the
    water drained off potatoes.  Storage of potatoes at 20C for two
    months also resulted in 42-55% lower residues.

    Peanuts

    Fractionation of peanuts containing 0.01 to 0.04 mg/kg residues on the
    whole dry nuts (equivalent to 0.002 to 0.02 mg/kg residues in the
    kernel) resulted in peanut oil with no detectable residues (<0.003
    mg/kg), whether the oil was recovered by the screwpress or solvent
    extraction procedure.  The peanut meal contains about the same level
    of residues as the kernels.

    Sugar beet

    In a simulated commercial processing operation for using roots of
    treated sugar beet, the residue was <0.005 mg/kg in all fractions
    except the diffusion juice which had a maximum of 0.02 mg/kg.  When
    diffusion juice was fortified with lime water under conditions
    simulating plant processing, <0.005 mg/kg residue remained at the
    exaggerated fortification level of 13.0 mg/kg.  No detectable residues
    were found in fortified beet pulp after simulating plant drying
    conditions.  Therefore, there in no reasonable expectation of
    detectable residues in sugar, molasses or beet pulp.

    Oranges

    Aldicarb-treated oranges were processed as in a commercial operation
    and the different fractions were analyzed for residues.  It is seen in
    Table 6 that the residues in the whole fresh fruit can be concentrated
    in the dried citrus pulp by a factor of 1.75%.  The portion of the wet
    peel residues which do not survive the dried citrus pulp process are
    believed to be destroyed by the liming process prior to screw pressing
    and during the application of heat in the pulp drier.  Orange juice
    residues are equal to fresh pulp residues. Concentrated orange juice
    (concentrated about 3) shows residues greater then fresh juice and
    reconstitution prior to consumption would generate the original juice
    residue.  The other by-products of commercial processing which were
    investigated, molasses oil, press liquor and oil water layer contain
    only low level residues, not exceeding 0.04 mg/kg.

    Table 6. Effect of Commercial Processing on Aldicarb Residues in
    Oranges

                                                                      
                                    Aldicarb Residues, mg/kg
                        First Fractionation      Second Fractionation
    Orange Fraction       UCC1        UCR          UCC         UCR
                                                                      

    Whole fruit           0.22        -            0.07        0.1
    Wet pulp              0.1         0.1          -           -
    Wet peel              0.6         0.4          0.08        0.09
    Dried citrus pulp     0.4         0.4          0.04        0.07
    Dilute juice          0.1         0.2          0.06        0.09
    Conc. juice           -           -            0.2         0.3
    Press liquor          -           -            0.02        0.02
    Molasses              0.04        0.04         0.04        0.02
    Oil                   0.02        0.02         0.03        0.02
                                                                      

    1  Analyzed by UCC = Union Carbide Corp., UCR = University of
    California (Riverside)

    2  The orange pulp is 75% by weight of the whole fruit and the wet
    peel 25%.  The calculated whole fruit residue from the pulp and wet
    peal analysis in 0.24 mg/kg [(0.1  0.8) + (0.6  0.2) = 0.2].  Whole
    fruit containing 0.2 mg/kg aldicarb residues resulted in 0.4 mg/kg in
    the dried citrus pulp or a 1.75-fold concentration.


    Dry beans (cooking)

    Cooking as usually done in homes reduces dry beans residues by 85%
    after 1 hour and over 90 percent after 3 hours.  Apparently, the
    residues are diluted by water absorption and resultant weight gain of
    the seed or diffuse from the dry seed into the water during the
    soaking process.  This is reflected in 0.5 mg/kg residues in the dry
    seed becoming 0.2 mg/kg in the soaked seeds.  Most of the residues are
    then destroyed during cooking at 100c.

    EVIDENCE OF RESIDUES IN FOOD IN COMMERCE OR AT
    CONSUMPTION

    Aldicarb in generally not yet included in pesticide monitoring
    programmes.  Therefore no data were available to the Meeting.

    METHODS OF RESIDUE ANALYSIS

    The most widely-used procedure is that wherein aldicarb and aldicarb
    sulfoxide are converted to the sulfone by hydrogen peroxide-acetic
    acid oxidation and quantitated by GLC (Maitlen et al., 1968, 1969,
    1970).  The method is simple and rapid.

    Generally, aldicarb residues are extracted from the crop by blending
    the sample in a mixed solvent consisting of 75 percent acetone and 25
    percent water.  The aldicarb residues are oxidized to aldicarb sulfone
    by addition of peracetic acid to the extracting solvent.  After
    clean-up on a Florisil column, the residues are determined with a
    flame photometric detector and reported as aldicarb.  Alternatively,
    the metabolites may be separated by Florisil column chromatography
    prior to oxidation.  Detection limits of 0.007 to 0.01 mg/kg have been
    obtained in apples alfalfa, bananas, beans, coffee, cucumbers,
    oranges, potatoes, soybeans and sugar beets.

    NATIONAL MRLs REPORTED TO THE MEETING

    The following were reported:

    Country                       Crop                     Limit
                                                           mg/kg
                                                                  

    USA            cattle (meat, fat, meat by-products)    0.01
                   citrus                                  0.3
                   citrus pulp, dried                      0.6
                   cottonseed                              0.1
                   cottonseed hulls                        0.3
                   goats, hogs, horses, sheep (meat,fat,
                   meat by-products)                       0.01
                   milk                                    0.002
                   oranges                                 0.3
                   potatoes                                1.0
                   peanut hulls                            0.5
                   peanuts                                 0.05
                   sugar beets                             0.05
                   sugar beet tops                         1.0
                   sweet potatoes, sugar cane              0.02

    Argentina      cottonseed                              0.1
                   peanuts                                 0.05
                   potatoes                                1.0
                   sweet potatoes                          0.02

    Brazil         cottonseed                              0.1
                   peanuts                                 0.05
                   potatoes                                1.0
                   sugarcane                               0.02

    Panama         potatoes                                1.0

    Mexico         cottonseed                              0.1
                   peanuts                                 0.05
                   potatoes                                1.0
                   sugarcane                               0.02
                                                                  

    National MRLs, Continued...

    Country                       Crop                     Limit
                                                           mg/kg
                                                                  

    Netherlands    onions, bulb                            0.1
                   potatoes                                0.3
                   sugar beets                             0.02
                   other products of plant origin          0.01*

    Federal Rep.
    of Germany     strawberries                            0.05
                   sugar beets                             0.05

    East Germany
    (DDR)          onions, bulb                            0.1

    Switzerland    corn                                    0.02

                   sugar beets                             0.05

    Hungary        sugar beets                             0.05
                   sugar                                   0.01

    South Africa   potatoes                                0.1
                   sugarcane                               0.1
                   bananas                                 0.5
                                                                  

    APPRAISAL

    Aldicarb is a very toxic systemic pesticide for the control of
    insects, mites and nematodes.  It is sold only an the granular
    material containing 5 to 15 percent active ingredient.  Among the
    crops for which aldicarb in registered are bananas, citrus, cotton,
    coffee, potatoes, peanuts, sugar beets, sugarcane, sweet potatoes, dry
    beans and soybeans.  Application rate is generally from 1 to 3 kg/ha.
    For most food crops the use pattern involves a 90 day pre-harvest
    interval.  There is a common metabolic pathway in plants, animals,
    insects and soils.  The initial step in the rapid thioether oxidation
    to the sulfoxide followed by a slower conversion to sulfone.  Both the
    sulfoxide and sulfone undergo extensive degradation; the primary
    metabolic step is hydrolysis to the corresponding oximes.  Aldicarb,
    aldicarb sulfone and aldicarb sulfoxide are the toxicologically
    important residues, but aldicarb itself is seldom detected at harvest.

    Feeding studies with dairy cows at 0.12, 0.6 and 1.2 ppm for 14 days
    showed no apparent harmful effects.  There were also no changes in
    blood cholinesterase levels, milk production, quantity of excretory

                   
    * At or about the limit of detection.

    products, or food consumption.  About 90 percent of the applied dose
    was excreted in the urine.  At feeding levels above that normally
    encountered as a result of field treatment, no toxic carbamate
    residues could be detected in milk.

    Considerable residue data for potatoes, cottonseed, sugar beets,
    peanuts, coffee and bananas were reviewed.  Residue levels were
    normally low following the long pre-harvest intervals prescribed.
    Processing further reduced the residue levels either due to dilution
    or to thermal degradation.

    The most widely-used analytical procedure requires the conversion of
    aldicarb and the sulfoxide to the sulfone and then quantitation by gas
    chromatography with a flame photometric detector in the sulfur mode.
    Residues are expressed as aldicarb.  Alternatively, the three
    carbonate materials can be separated by column chromatography prior to
    oxidation.  For a variety of crops limits of determination ranged from
    0.007 to 0.01 mg/kg.

    RECOMMENDATIONS

    The following levels are recommended as MRLs which need not be
    exceeded when aldicarb is used according to good agricultural
    practice.  They refer to aldicarb, aldicarb sulfoxide, and aldicarb
    sulfone determined as aldicarb sulfone and expressed as aldicarb.

                                           Pre-harvest intervals
                             Limit         on which recommendations
    Commodity                mg/kg         are based
                                                                     

    bananas                  0.5                     1
    beans, dry               0.1                     2
    citrus fruits            0.2                     90
    cottonseed               0.1                     90
    meat                     0.01*                   -
    milk                     0.002*                  -
    peanuts                  0.05*                   90
    potatoes                                         120
    soybeans                 0.02*                   3
    sugar beets              0.05*                   90
    sugar beet tops                                  120
    coffee beans (green)     0.1                     2
    onions                   0.05*
                                                                     

    1  No PHI because of continuous harvesting
    2  At planting time only.
    *  at or about the limit of determination

    FURTHER WORK

    Desirable:

    1.  Studies on cholinesterase activity in dogs associated with
    short-term continuous dietary exposure.

    2.  Examination of the mutagenic potential of aldicarb using
    short-term microbial bioassays.


    3.  Data on use patterns and resultant residues in important crops in
    countries other than USA.

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      Alleged Human Overexposure Cases Reported from Use of Temik
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    Anderson, J.P.E.  Factors influencing insecticide degradation by a
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      Degradation of 2-methyl-2-(methylthio)
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    UCC Project Report 10495, Nov. 11 (1968b), Unpublished.

      Metabolism of C14 Temik in cotton plants under field conditions. 
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      Degradation and carry-over properties of 2-methyl-2-(methylthio)
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      Metabolism of 2-methyl-2-(methylthio) propionaldehyde
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    Andrawes, N.R. The metabolism of (UC 21865) Sulfocarb Pesticide in the
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      Miscellaneous Toxicity Studies. (1969) Unpublished report from
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    Carpenter, C.P. and Smyth, H.F. A 4-hour Test for Evaluation of
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      Temik 10G (10.5% Granular Formulation of Compound 21149). 15-Day
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    Clarkson, V.A. Rowe, B.K.and Romine, R.R.  Field evaluation of the
    persistence and movement of Temik and its carbonate metabolites in
    soil.  UCC Project Report 10485. October 28 (1968a), Unpublished.

    Cope, R.W. and Romine, R.R.  Temik 10G Aldicarb Pesticide. Results of
    Aldicarb Ingestion and Exposure Studies with Humans and Results of
    Monitoring Human Exposure In Working Environments. (1973) Unpublished
    Report from UCC submitted by UCC.

    Coppedge, J.R., Lindquist, D.A., Bull, D.L. and Dorough, H.W. Fate of
    2-methyl-2 (methylthio) propionaldehyde O-(methylcarbamoyl) oxime
    (Temik) in cotton plants and soil. J. Agr. Food Chem. 15. 902.

    Denmark.  Data submitted to the 1979 JMPR.

    Dorough, H.W., Davis, R.B. and Ivie, G.W.  Fate of Temik-Carbon-14 in
    lactating cows during a 14-day feeding period. J. Agr. Food Chem. 18,
    135-142.

    Dorough, H.W. and Ivie, G.W.  Temik-S35 Metabolism in a Lactating
    Cow.  J. Agr. Food Chem., 16(3): 460-464.

    Finland.  Data submitted to the 1979 JMPR.

    Gawaad, A.A.A., Ali, E.S.N.M. and Shazli, A.Y.  Leaching of some
    soilinsecticides in three Egyptian soils. Bull. Entomol. Soc., Egypt
    Econ. Ser. (5), 23-26.

    Haines, R.G.  Ingestion of Aldicarb by Human Volunteers: A controlled
    Study of the Effect of Aldicarb on Man.  (1971) Unpublished report
    from UCC submitted by UCC.

    Heungers, A.  The Influence of some pesticides in the soil fauna in
    Azalea culture.  Ueded, Fac. Landbonwivet. Ryksuniv, Gent, 35(2),
    717-729.

    Hicks B.W., Dorough, H.W. and Mehendale, H.M.  Metabolism of Aldicarb
    Pesticide in Laying Hens. J. Agr. Food Chem. 20(l): 151-156.

    Iwata Y., Westlake, W.E., Barkley, J.H., Carman, G.E. and Gunther,
    F.A.  Aldicarb residues in oranges, citrus by-products, orange leaves,
    and soil after an aldicarb soil-application in an orange grove. J.
    Agr. Food Chem. 25, 933.

    Johnson, H.E.  and Carpenter, C.P. Temik (Technical Grade Compound
    21149).  Demyelination Potential in Chickens. (1966a) Unpublished
    report from Mellon Institute submitted by Union Carbide Corporation.

      Temik (Technical Grade Compound 21149). Comparative Behavioural
    effect in Rats. (1966b) Unpublished report from Mellon Institute
    submitted by UCC.

    Johnson, H.E., and Sullivan, L.J. Studies on an Effective Therapy for
    Overdoses of Temik, Temik Sulfoxide, and Temik Sulfone in the Rat.
    (1968a) Unpublished report from Mellon Institute submitted by UCC.

    Temik (UC 21149) Antidotal Therapy in Rats Following Administration of
    Multiple Lethal Doses. (1968b) Unpublished report from Mellon
    Institute submitted by UCC.

    Knaak. J.B., Tallant, M.J. and Sullivan, L.J.  The Metabolism of
    2-Methyl-2-(methylthio) propionaldehyde O-(methylcarbamoyl) oxime in
    the Rat. J. Agr. Food Chem. 14(6):573-578.

    Maitlen, J.C. McDonough, L.M. and Berosa, M.  Determination of
    residues of 2-Methyl-2(methylthio) propionaldehyde O-(methylcarbamoyl)
    oxime (UC 21149), Temik) and its sulfoxide and sulfone by gas
    chromatography. J. Agr. Food Chem. 16, 549.

      Rapid method for the extraction, cleanup and GC determination of
    toxic residues of Temik. J. Assoc. Official Anal. Chem. 52, 786.

    Maitlen, J.C., McDonough, L.M., Dean, F., Butt, B.A., and Landis B.J.
    Aldicarb residues in apples, pears, sugar beets, and cottonseed;
    performance in apples and pears, U.S.D.A. ARS-33-135. March, 1970.

    Metcalf, R.L., Fukuto, T.R., Collins, C., Borck, K., Burk, J.,
    Reynolds, H.T. and Osman, M.F.  Metabolism of
    2-methyl-2-(methylthio)-propionaldehyde O-(methylcarbamoyl) oxime in
    Plant and Insect. J. Agr. Food Chem. 14(6) : 579-584.

    Moorefield, H.H. Data on Temik aldicarb pesticide environmental
    impact.  In submission of Union Carbide to 1979 JMPR.

    Natoff, I.L., and Reiff, B.  Effect of Oximes on the Acute Toxicity of
    Anticholinesterase Carbamates. Toxicol. Appl. Pharmacol.p 25: 569-575.

    NIH  Bioassay of Aldicarb for Possible Carcinogenicity. U.S. DHEW Pub.
    No. (NIH) 79-1391, 103 pages.

    Nycum, J.S. and Carpenter, C.P.  Toxicity Studies on the Probably
    "Non-Carbamate" Plant Metabolites of Temik.  (1968a) Unpublished
    report from Mellon Institute submitted by Union Carbide Corporation.

    Toxicity Studies on Temik and Related Carbamates. (1968b) Unpublished
    report from Mellon Institute submitted by UCC.

    Pandey, S.Y.  Human Exposure Study on Temik 10G. (1977) Unpublished
    report from Union Carbide India Ltd. submitted by UCC.

    Peoples, S.A., Maddy, K.T. and Smith, C.R.  Human Health Problems
    Associated with Temik (Aldicarb) in California. (1977) Unpublished
    report from California Department of Food and Agriculture submitted by
    UCC.

    Pozzani, U.C.  and Carpenter, C.P. Sensitizing Potential in Guinea
    Pigs as Determined by a Modified Landsteiner Test. (1968a) Unpublished
    report from Mellon Institute submitted by UCC.

    Temik 10G and Temik 10G-V. Response of Rats to Saturated Vapors
    Generated under Simulated Greenhouse Conditions. (1968b) Unpublished
    report from Mellon Institute submitted by UCC.

    Quraishi, M.S.  Edaphic and water relationships of aldicarb and its
    metabolites.  Canadian Entomol. 104(3), 1191-1196.

    Romine, R.R.  Aldicarb Pesticide. Aldicarb Residues in Milk and Meat
    of Cows Fed Aldicarb Sulfoxide and Aldicarb Sulfone in the Daily Diet.
    (1973) Unpublished report submitted by UCC.

    Romine, R.R., Halstead, G.B. and Gibson, C.E. Leaching characteristics
    of Temik 1OG in soils. UCC Project Report 10902. Nov. 11 (1968),
    Unpublished.

    Shrivastara, K.N.  Determination of Human Exposure Levels in
    Commercial Application of Temik 10G on Potatoes by Gloved Hand and
    Hand-Operated Applicators. (1975) Unpublished report from Union
    Carbide India Ltd.

    South Africa.  Data submitted to the 1979 JMPR

    Spurr, H.W., Jr. and Chancey, E.L.  Interactions between Temik and
    micro-organisms and their importance to ecological relationships in
    soil.  UCC Project Report 9208. April 22 (1968), Unpublished.

    Spurr, H.W., Jr. and Sonsa, A.A.  Potential interactions of aldicarb
    and its metabolites on non-target organisms in the environment. J.
    Environ. Quality 3(2), 130-133.

    Striegal, J.A. and Carpenter, C.P.  Range Finding Tests on Compound
    21149.  (1962) Unpublished report from Mellon Institute of Industrial
    Research submitted by UCC.

    Sullivan, L.J.  The Urinary Excretion of C14 Equivalents of Temik in
    the Dog and their Metabolic Profile as Revealed by Silica Gel
    Chromatography. (1968a) Unpublished report from Mellon Institute
    submitted by UCC.

      Urinary Metabolic Profiles as Determined by Silica Gel
    Chromatography of Urines from Rats and Dogs Dosed with Temik Sulfone.
    (1968b) Unpublished report from Mellon Institute submitted by UCC.

      The Excretion of C14 Equivalents of Temik Sulfone by the Rat after
    a Single Peroral Dose.  (1968c) Unpublished report from Mellon
    Institute submitted by UCC.

    Sullivan, L.J. and Carpenter, C.P.  Preliminary Metabolism of
    14C-S-Methyl Aldicarb Nitrile in the Rat. (1974) Unpublished report
    from Carnegic-Mellon Institute of Research submitted by UCC.

    Supak, J.R.  The volatilization degradation, absorption, and
    desorption characteristics of aldicarb in soils and clays. Diss.
    Abstr. Int. 33(3), 982B.

    Wakefield, M., Orme, J.P.R., Ruston, E.A., and Andrews, L.  The
    Determination of Levels of Aldicarb in Urine and Face Masks. (1973)
    Unpublished report from Huntingdon Research Centre submitted by UCC.

    Weil, C.S. and Carpenter, C.P.  Unpublished reports from Mellon
    Institute submitted by UCC.

      Results of a Three Generation Reproduction Study on Rats Fed
    Compound 21149 in their Diet.  (1964)

      Two Year Feeding of Compound 21149 in the Diet of Rats.  (1965)

      Insecticide Temik. Teratogenic Potential in Rats.  (1966a)

      Results of Long-Term Tests for Mouse Skin Carcinogenicity of Three
    Process Residues, One Epoxide and Three Compounds.  (1966b)

      Two Year Feeding of Compound 21149 in the Diet of Dogs.  (1966c)

      Temik 10G-V (10.3% Granular Formulation of Compound 21149). Acute
    and 14-Day Dermal Applications to Rabbits.  (1968a)

      Temik Sulfoxide. Results of Feeding in the Diet of Rats for Six
    Months and Dogs for Three Months.  (1968b)

      Temik Sulfone. Results of Feeding in the Diet of Rats for Six Months
    and Dogs for Three Months.  (1968c)

      Temik Sulfoxide and Temik Sulfone Single Rabbit Skin Penetration
    Studies.  (1969a)

      Purified and Technical Temik. Results of Feeding in the Diets of
    Rats for One Week.  (1969b)

      2-Methyl-2-(Methysulfinyl) Propanol-1. Results of Feeding in the
    Dicta of Rats for One Week.  (1969c)

      Temik and Other Materials. Miscellaneous Single Dose Peroral and
    Peroral and Parenteral LD50 Assays and Some Joint Action Studies.
    (1970a)

      Comparative Skin Penetration Toxicity of Temik 10G-V and 15 Other
    Pesticide Formulations as Marketed.  (1970b)

      Temik. Results of Feeding in the Diets of Rats for 7 Days.  (1970c)

      Temik (T) Temik Sulfoxide (TSO), Temik Sulfone (TS02), 1:1
    TSO-TS02. Results of Feeding in the Diet of Rats for 7 Days.  (1970d)

      1:1 Temik: Temik Sulfone. Results of Feeding in the Diet of Mice for
    7 Days.  (1970e)

      Temik. Results of Feeding in the Diet of Mice for 7 Days.  (1970f)

      Aldicarb (A), Aldicarb Sulfoxide (ASO), Aldicarb Sulfone (ASO2) and
    a 1:1 Mixture of ASO:ASO2.  Two Year Feeding in the Diet of Rats. 
    (1972a)

      Miscellaneous Toxicity Studies.  (1972b)

      Aldicarb. 18 Month Feeding in Diet of Mice.  (1972c)

      Aldicarb.  Seven-Day Inclusion in Diet of Dogs.  (1973)

      Aldicarb. Inclusion in the Diet of Rats for Three Generations and a
    Dominant Lethal Mutagenesis Test.  (1974a)

      Aldicarb Oxime (All). Results of Feeding in the Diet of Rats for 7
    Days.  (1974b)

      Aldicarb. Inclusion in the Diets of Dogs for Three Months.  (1974c)

      Aldicarb. 18-Month Feeding in the Diet of Mice, Study II.  (1974d)

    Weil, C.S. and Cox, E.F.  Aldicarb Sulfoxide and Aldicarb Sulfone
    Cholinesterase Inhibition Results after Periods of One to Fifty-Six
    Days of Inclusion in the Diets of Rats. (1975) Unpublished report from
    Carnegie Mellon Institute of Research submitted by UCC.

    West, J.S. and Carpenter, C.P.  Unpublished reports from Mellon
    Institute submitted by UCC.

      The Single Dose Peroral Toxicity of Compounds 20299, 21149, 19786
    and 20047A for White Leghorn Cockerels.  (1965)

      Temik (Compound 21149, Technical). Joint Action with Selected
    Organic Phosphate and Carbamate Pesticides.  (1966a)

      Miscellaneous Acute Toxicity Data. (1966b)

    WHO  Insecticide Evaluation and Testing Programme, Stage I, Mammalian
    Toxicity Report (WHO). (1966) Unpublished report from Toxicology
    Research Univ., Carshalton, U.K. submitted by UCC.

    Williams, F.  Human Exposure Study in the Field Application of Temik
    10G on Cotton. Unpublished report from UCC.
    


    See Also:
       Toxicological Abbreviations
       Aldicarb (EHC 121, 1991)
       Aldicarb (HSG 64, 1991)
       Aldicarb (ICSC)
       Aldicarb (Pesticide residues in food: 1982 evaluations)
       Aldicarb (Pesticide residues in food: 1992 evaluations Part II Toxicology)
       Aldicarb (IARC Summary & Evaluation, Volume 53, 1991)