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    PESTICIDE RESIDUES IN FOOD - 1980


    Sponsored jointly by FAO and WHO






    EVALUATIONS 1980





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




    MECARBAM

    IDENTITY

    Chemical name (IUPAC)

    S-(N-ethoxycarbonyl-N-methylcarbamoylmethyl) O,O-diethyl
    phosphorodithioate

    Synonyms          Murfotox(R), P474, MC474, Pestan(R), Afos.(R),
                      Murphotox(R), Murotox(R)

    Structural formula

    CHEMICAL STRUCTURE 1

    Molecular formula C10H20O5NPS2

    Molecular weight  329.4

    Other information on identity and properties

    Mecarbam is a colourless oily liquid; the technical material may be
    pale yellow to brown.  Technical mecarbam contains >85%, typically
    92-95%, of mecarbam with small amounts of triethyldithiophosphate
    and S-(ethoxycarbonyl) diethyl dithiophosphate as impurities.  Its
    freezing point is 9°C, specific gravity is 1.222/20°C, refractive
    index nD20 is 1.5138, volatility is 6 × 10-6 g/litre of air at
    40°C.  It is slightly soluble in water, soluble in hexane (4%) and
    kerosene (2%) and miscible in all proportions with alcohols,
    ketones, aromatic hydrocarbons and chlorinated hydrocarbons.  It is
    stable at normal temperatures but hydrolyses at pH below 3 to yield
    (C2H5O)2PSSCH2COOH, CO2, C2H5OH and NH2CH3.

    The most widely used formulation is the 68% emulsifiable
    concentrate, but similar 50%, 90% and 100% formulations are
    available and dust and wettable powder preparations have also been
    marketed.

    DATA CONSIDERED FOR DERIVATION OF ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Absorption, distribution, and excretion

    Groups of rats were administered mecarbam (approximately 10 mg/kg
    body weight 14C-ethoxy-labelled in dimethyl sulphoxide).  Mecarbam
    was rapidly absorbed following oral dosing and was rapidly
    excreted, predominantly in the urine.  Within 48 hours, 92% of the
    radioactivity was excreted in urine, 2% in faeces and approximately
    5% was eliminated as CO2.  There was no accumulation of
    radioactivity in any of the tissues examined.  The highest
    concentrations of mecarbam in this study were found in the major
    metabolising and excretory tissues and organs (Aryton and Harnby,
    1977a).

    Further studies on the absorption and distribution of mecarbam,
    using dimethylformamide as a vehicle, suggested that mecarbam,
    while slowly absorbed from the GI tract following an acute oral
    dose, is rapidly distributed through the body and excreted
    primarily through the urine. Following an oral dose of 10 mg/kg
    body weight, it was observed that the 14C-radioactivity did not
    fully leave the stomach until 24-48 hours following administration
    (McCulloch, 1980).

    In a further experiment to demonstrate the rapid removal of
    mecarbam following absorption an intravenous dose of mecarbam was
    introduced into the tail vein of male rats.  Blood samples were
    taken in periods up to 6 hours following treatment.  Residues
    declined rapidly during the first 40 minutes and slower thereafter,
    demonstrating a biphasic excretion curve.  At the end of 6 hours,
    radioactivity in the blood had diminished to a point where it
    almost reached background levels (Ayrton and Harnby, 1977b).

    Biotransformation

    No data available.


    TOXICOLOGICAL STUDIES

    Special Studies on Potentiation

    Mecarbam was orally administered to male rats alone and in
    combination (1:1 w/w suspension in propylene glycol) with three
    other organophosphate insecticides (malathion, demeton-methyl,
    demeton-S-methyl sulphoxide and dimethoate).  The relationship of
    the observed LD50 with respect to that calculated from the acute
    toxicity curves indicated that there was no acute potentiation or
    additive effect of the presence of mecarbam with the other
    cholinergic insecticides tested.  Demeton-methyl and dimethoate,
    under the conditions of this test, appear to be somewhat protective

    with respect to the toxicity of mecarbam.  In no case was 
    potentiation observed (Middleton, 1960).

    Special studies on reproduction

    Groups of rats (25 male and 25 female rats/group) were fed mecarbam
    in their diet at dosage levels of 0, 2, or 50 mg/kg and subjected
    to a two-generation, two-litter per generation reproduction test. 
    Technical mecarbam was used with an active ingredient of 83.2% and
    the dietary levels were corrected to account for this
    concentration.  A modified teratology bioassay was incorporated
    into this reproduction study where 5 females per group were set
    aside and examined to determine day 0 of gestation.  The animals
    were fed mecarbam throughout gestation at the above dosage levels. 
    On day 19 or 20 of gestation some animals were sacrificed and the
    foetuses delivered by caesarean section.  This modified teratology
    programme was performed with the second litter of each generation. 
    The remaining animals of the second litter of the second generation
    were maintained for a three-month observation period to evaluate
    post-natal effects.  In the modified teratology examination soft
    tissue and skeletal examinations were performed on all foetuses. 
    All reproduction data were subjected to statistical analysis.

    The presence of mecarbam in the diet at 50 mg/kg resulted in a
    depression of growth of both males and females in both parental
    groups.  Food consumption was not affected.  In addition to growth
    reduction, the animals receiving the high dose showed clinical
    signs of toxicity with respect to an increased incidence of rough
    coat and hunched appearance, signs which have been noted in other
    dietary studies as being associated with mecarbam toxicity.  There
    was no compound-related mortality observed over the course of the
    study attributable to the presence of mecarbam in the diet.

    Examination of reproduction data failed to show any significant
    effects with respect to both litters of both generations
    administered 2 mg/kg in the diet.  In contrast, the 50 mg/kg
    dietary level affected a number of reproduction parameters
    including: a depression of numbers of pups born alive; an increased
    number of animals dying during lactation; a decreased number of
    animals ultimately weaned; and the weight of the weaned animals was
    significantly reduced.  These effects were present in both litters
    of both generations.  The surviving animals, in addition to being
    smaller, appeared unhealthy (were cold and somewhat cyanotic).

    Evaluation of those foetuses removed by caesarean section for
    potential teratogenic effects failed to show any compound-related
    differences from controls.  While there was a reduced number of
    implantation sites, ovarian corpora lutea, and an increased number
    of resorption sites at 50 mg/kg, there were no teratogenic
    occurrences in any of the foetuses examined with respect to either
    somatic or skeletal abnormalities.

    The presence of mecarbam in the diet at 50 mg/kg had a significant
    effect on both maternal and foetal development and well being but
    was not teratogenic (Rutter, 1974).

    Special studies on Neurotoxicity

    Preliminary studies to define the delayed neurotoxic potential of
    mecarbam were performed with adult hens.  The hens were
    administered mecarbam subcutaneously, one dose per week for three
    consecutive weeks at dosage levels corresponding to multiples of
    the acute LD50.  The animals were not treated with atropine and
    survival was low.  The surviving animals were observed over a
    period of time extending to nine months.  A small sample of the
    surviving hens were subjected to histological examinations of
    nervous tissue while a larger sample was examined macroscopically
    for gross alterations.

    In this preliminary trial, there was no evidence of delayed
    neurotoxicity induced by the multiple administration of mecarbam
    and the examination, either by gross or histological techniques,
    was negative (Anonymous, 1960).

    Two formulations of mecarbam (Pestcombi(R) and Testan(R)) were
    examined for their delayed neurotoxic potential with adult hens. 
    Pestcombi(R) contained mecarbam (22%) and EPN (30%) while Testan(R)
    contained mecarbam alone (28%).  Adult hens were administered these
    materials orally as a single maximum tolerated dose and were
    observed for clinical signs of delayed neurotoxicity for 21 days. 
    When no clinical signs of ataxia were observed, the animals were
    further treated in a similar manner and again observed for an
    additional 21 days.  At the conclusion of the 42-day experimental
    period, several of the survivors were sacrificed for microscopic
    examination of central and peripheral nerve tissue and skeletal
    muscle following H and E staining.

    There was no clinical sign of ataxia or histological evidence that
    mecarbam alone or in combination with EPN induced a clinical
    delayed neurotoxicity in hens (Shillam, 1968).

    Acute Toxicity

                                                                                                   
                                                   LD50
    Species        Sex       Route                (mg/kg)        Reference
                                                                                               

    Rat             M        Oral                 23-53          Tomich, 1958a, 1959, 1965;
                                                                 Davies and Collins, 1975
                    F        Oral                 31-33          Tomich, 1959, 1962; Davies and
                                                                 Collins, 1975
                    M        Dermal               >1222          Middleton, 1960;
                             Inhalation (1-5 µm   0.7 mg/l       Berczy and Binns, 1971
                             particle size)       (6 hr LC50)

    Mouse           M        IP                   120-130        Tomich, 1958a; Anony, 1962
                    M        SC                   600            Tomich, 1958
                    M        Oral                 106            Child, 1958
                    M        IV                   67             Tomich, 1968b

    Guinea Pig               Oral                 65             Tomich (no date)
                             Dermal               >1222          Middleton, 1960

    Rabbit                   Oral                 60             Tomich (no date)
                             Dermal               229            Middleton, 1960

    Cat                      Oral                 <50            Tomich (no date)

    Sheep                    Oral                 20-25          Nicolas Inst., 1966
                                                                                               
    
    Further acute studies in rats using formulated products, rather than
    technical mecarbam, demonstrated a sex difference with respect to
    acute toxicity (the females were more sensitive than the males).
    Additionally, these studies showed that concentrated formulated
    products appear to be more toxic than technical mecarbam probably due
    to an increased absorption of the active ingredient as a result of the
    presence of insecticidally-inert formulation products (Davies and
    Halliday, 1971; Kynoch et al, 1980a; 1980b).

    Signs of poisoning

    The signs of acute poisoning resulting from mecarbam administration
    are similar to those seen with other cholinergic organophosphate
    esters. These signs include: salivation, lacrimation (sometimes
    bloody), piloerection, hunched posture, abnormal gait, changes in the
    respiratory rate, and fine and coarse body tremors.  Death occurred in
    poisoned rats from one hour to three days following dosing.  Autopsy
    showed congestion and haemorrhage of the lungs and pale color in the
    liver, kidney, and spleen.  Following subacute administration recovery
    of survivors, as judged by external appearance and behaviour, was
    slow.  Recovery was complete within eight days of dosing.

    Special studies on antidotes

    As with other cholinergic organophosphates, 2-PAM was found to exert a
    protective effect on acute cholinergic signs of poisoning (Middleton,
    1960).  Atropine was not studied with respect to its antidotal effects
    on the acute toxicity of mecarbam.

    Short-term studies

    Rat inhalation

    Groups of rats (4 male and 4 female/group) were exposed to mecarbam by
    inhalation. Exposures were carried out for 6 hours/day for a total of
    14 exposure days over a 3-week experiment time.  The aerosol
    particulate was fully respirable and generated at concentrations of 0,
    2, 10 and 50 mg/l air.

    The animals were observed daily and growth was recorded at twice
    weekly intervals.  At the conclusion of the study urinalysis,
    haematology, and clinical blood chemistry parameters were evaluated.
    All rats were sacrificed, and gross and microscopic examination of
    tissues and organs was performed.

    Although respiratory irritation was observed in the two higher dose
    levels, the exposure to mecarbam did not appear to result in adverse
    behaviourial effects and growth was not affected.  At the high dose
    level, tremors were noted, and the animals became aggressive in the
    second week of exposure.  Urinalysis, haematology, and clinical
    chemistry parameters were unaffected by exposure to mecarbam.  At the
    highest dose level, erythrocyte (but not plasma) cholinesterase
    activity was depressed in male rats.  Females did not show a

    significant cholinesterase depression at any dose level although at 50
    mg/l, the activity was slightly depressed.

    Gross and microscopic examination of the lungs and major tissues and
    organs showed no changes in morphology that would be attributable to
    the presence of mecarbam.  Based upon the conditions of this
    experiment, the rat was shown to tolerate a concentration of 10 mg/l
    air for a daily 6-hour exposure over a three-week test interval
    (Berczy et al, 1972).

    Cow

    Groups of lactating dairy cows (4 cows/group) were administered
    mecarbam in their diet at dosage levels of 0, 2, and 10 mg/kg for 30
    days.  The study was designed to evaluate the presence of residues in
    milk and meat and to examine excretion and body burdens of mecarbam in
    this species.

    There was no mortality or signs of poisoning evident over the course
    of the study.  There were no changes in body weight or in milk
    production.  Although mecarbam was present in low levels in the milk
    of cows administered mecarbam at both dietary levels, there was no
    build up or evidence of bioaccumulation.  The levels of mecarbam in
    milk did not exceed 10 mg/kg.  At the conclusion of the study, animals
    were sacrificed at various intervals up to 1 week and 1 month
    following cessation of treatment.  There was no substantial evidence
    of mecarbam in tissues and organs in any of the animals receiving
    dietary administration.  From this study, it may be concluded that
    mecarbam, at levels of 10 mg/kg in the diet, does not elicit a toxic
    reaction in cows, is not bioaccumulated, nor is it found as a residue
    in meat, although low levels may be excreted in milk (Hepworth and
    Brown, 1978).

    Dog

    Groups of dogs (4 male and 4 female beagle dogs/group) were fed
    mecarbam in the diet at dosage levels of 0, 10, 20 or 50 mg/kg for 6
    months.  The respective dietary intake of mecarbam corresponding to
    the food intake data was 0, 0.35, 0.80 or 1.78 mg/kg body weight.

    The animals were observed daily for abnormal signs of behaviour and
    toxicity.  Data on food consumption and growth were recorded weekly.
    At periodic intervals during the course of the study, the control and
    high-dose group animals were examined with respect to haematological
    and blood biochemistry parameters.  Urinalyses were performed at the
    same time intervals (with the exception of the last time interval, at
    the conclusion of the study).  Cholinesterase determinations were
    performed by the electrometric measurement method examining red blood
    cell and plasma enzyme activity.  These analyses were performed
    periodically during the course of the study.  At the conclusion of the
    study, the animals were sacrificed and, in addition to RBC and plasma,
    brain cholinesterase activity was measured.

    At the completion of the study, all animals were sacrificed and a
    gross examination was made of selected tissues and organs. 
    Microscopic examinations were performed on tissues and organs of the
    control and 50 mg/kg dose group.

    There was no mortality over the 6-month trial.  Food consumption and
    growth were normal at all dose levels.  Urinalyses and blood chemistry
    values were within normal limits in all dose groups.  Although several
    haematological parameters did show some significant differences for
    control values periodically during the course of the study, there was
    no dose relationship nor time relationship noted with these findings.
    RBC and plasma cholinesterase activity depression was evident in both
    males and females in the high dose group.  Plasma cholinesterase
    appeared to be the more sensitive parameter and was reduced in both
    males and females at 20 mg/kg.  At this dose level, only females
    showed a reduced red blood cell cholinesterase activity (noted only at
    the conclusion of the study).  In general, females appear to show a
    slightly greater level of cholinesterase depression than males.  Brain
    cholinesterase, evaluated at the conclusion of the study, was
    depressed significantly at 50 mg/kg in both males and females and at
    20 mg/kg in males only.  There was no depression of cholinesterase
    activity in either sex at 10 mg/kg.

    Gross and microscopic examination of tissues and organs at the
    conclusion of the study did not show gross or microscopic
    abnormalities attributable to the presence of mecarbam.  It was
    concluded that there were no pathological conditions induced over the
    course of this study (Ward et al, 1979).

    Groups of dogs (4 male and 4 female beagle dogs/group) were
    administered mecarbam in the diet at dosage levels of 0, 1, 5 or 50
    mg/kg for 2 years.  Mecarbam was introduced into the dry diet, which
    was prepared weekly.

    All animals were examined daily for changes in behaviour and toxic
    signs of poisoning.  Growth and food consumption data were recorded
    thereafter.  At 0, 26, 68 and 104 weeks, haematology, clinical
    chemistry, and urinalysis examinations were performed on all animals.
    At 26 weeks, one male and one female of each group was sacrificed and
    subjected to gross and microscopic examination of tissues and organs.
    At the conclusion of the study, all animals were sacrificed and a
    similar evaluation was made.  Additionally, at the conclusion of the
    study, brain cholinesterase analyses were performed on all animals.

    There was no mortality over the course of the study.  Growth and food
    consumption data were comparable to control values at all time
    intervals examined.  Urinalysis, haematological and clinical
    biochemistry data, with the exception of cholinesterase values, showed
    no abnormalities attributable to the presence of mecarbam.  Inhibition
    of plasma and erythrocyte cholinesterase was noted at the highest dose
    level in all animals at all intervals examined.  Occasional slight
    reduction of cholinesterase activity at 5 mg/kg was observed

    periodically in the experiment.  At the conclusion of the study, brain
    cholinesterase depression was evident only at 50 mg/kg.

    Gross and microscopic examination of a wide variety of tissues and
    organs of animals sacrificed at the conclusion and during the course
    of the study failed to detect any compound related tissue damage in
    the series of tissues examined.  Occasional spontaneous lesions and
    incidental findings were not attributable to the presence of mecarbam
    in the diet.  A no-effect level, based upon cholinesterase depression
    (which appears to be the most sensitive parameter) is 5 mg/kg in the
    diet equivalent to a daily dietary intake of 0.15 mg/kg body weight
    (based upon actual food consumption in both males and females) (Rutter
    and Voelker, 1975).

    Rat

    Groups of rats (15 female rats per group) were administered mecarbam
    in the diet at dosage levels of 0, 1, 5, 10 or 50 g/kg for six months.

    Animals were examined daily and growth and food consumption data were
    recorded weekly.  Ophthalmological examination of animals in the
    control and 50 mg/kg groups were made at periodic intervals.
    Urinalyses, haematology, and blood chemistry parameters were recorded
    at periodic intervals during the course of the 26-week experiment.
    Plasma, red blood cell, and brain cholinesterase activity were
    measured using the electrometric procedure.

    At the conclusion of the 26-week feeding trial, all animals were
    sacrificed and gross examinations of tissues and organs was performed
    on all animals.  Microscopic tissue examinations were performed on all
    animals from the control and high dose group.

    There was no mortality observed over the course of the study. 
    Clinical signs of poisoning commonly seen as muscular tremors and a
    general unkempt appearance were observed at 50 mg/kg.  Data on growth
    and food consumption did not show a significant effect of mecarbam at
    any dose level over the course of the study.  Urinalysis, blood
    chemistry, and biochemistry parameters (with the exception of
    cholinesterase activity) were affected by mecarbam.  Cholinesterase
    depression was generally more pronounced in red blood cells than in
    plasma.  Enzyme depression was obvious at the two higher dose levels.
    At the conclusion of the study, brain cholinesterase was substantially
    depressed at two highest dose levels.

    There were no adverse effects noted on ophthalmological examination.
    Gross and microscopic examination of tissues and organs at the
    conclusion of the study failed to show any adverse effects that could
    be attributable to the presence of mecarbam in the diet (Rivett et
    al, 1972).

    Long-term study

    Rat

    Groups of rats (25 male and 25 female Sprague-Dawley rats/group) were
    fed mecarbam in the diet at dosage levels of O, 1, 5, or 50 mg/kg for
    104 weeks. (Based on an active ingredient of 83%, this corresponds to
    dietary levels of 0, 0.83, 4.15, and 41.5 mg/kg).  The animals were
    observed daily for mortality and changes in behaviour.  Growth and
    food consumption were reported weekly for 10 weeks, biweekly for 15
    weeks, and monthly thereafter to the termination of the study.  Groups
    of 5 rats per sex were sacrificed periodically for clinical chemistry,
    haematology, and urinalysis.  At 26 weeks and at the termination of
    the experiment, animals were sacrificed and gross and microscopic
    examination of tissues and organs were performed.  Microscopic
    examinations of the control and the high dose group animals were
    performed in detail at the conclusion of the study.  Animals of the
    low and mid-dose groups were also examined microscopically with
    respect to kidney and liver tissue.  In all cases, unusual lesions and
    tissue masses were examined microscopically, when observed.

    During the first 10 weeks of the study, there was no mortality and no
    unusual effects noted with respect to behaviour.  A hunched appearance
    was observed with increasing frequency at week 10, more frequently in
    the treated animals of the high-dose group than in the control or
    lower-dosed animals.  At the conclusion of the study, all surviving
    males and most of the surviving females had the hunched appearance.
    Over the course of the study, mortality was observed in the treated
    animals more frequently than in the control group although the
    differences were not significant statistically (the number of animals
    used in the study precludes an adequate evaluation of the increased
    mortality induced by mecarbam).  Growth was affected predominantly in
    the males at 50 mg/kg.  There were no effects noted with respect to
    food consumption, clinical chemistry studies (with the exception of
    cholinesterase), haematology, or urinalysis parameters.  A
    dose-related reduction of cholinesterase was observed.  This reduction
    was significant at 50 mg/kg in both males and females.  At 104 weeks,
    cholinesterase activity was substantially depressed in the high-dose
    group in both males and females.

    Gross and microscopic examination of tissues and organs at the 26-week
    and 104-week intervals did not show compound-related changes at any
    dietary dose level.  There was a high incidence of spontaneous lesions
    and neoplasms which were similar in both treated and control groups.
    There was no indication that mecarbam induced a carcinogenic change in
    any of the tissues examined.  Respiratory disease was present in most
    animals and was believed responsible for the reduction of surviving
    animals at the conclusion of the study.

    Based on cholinesterase depression, a no-effect level of 5 mg/kg was
    recognised as being equivalent to a dosage level of 0.21 mg/kg body
    weight (Rutter and Banas, 1975).

    Observations in Man

    None


    RESIDUES IN FOOD

    USE PATTERN

    Mecarbam is an insecticide effective against plant sucking insects
    such as aphids, leafhoppers, mealybugs, scale insects, lace bugs,
    thrips and stem and fruit mining pests.  It is also an effective
    acaricide in those few areas where resistance to organophosphorus
    compounds is absent, although resistant whitefly can be controlled by
    mecarbam.

    The principal use of mecarbam is for control of scale insects and
    mealybugs in citrus crops, with lesser usage against the same pests on
    vines, olives and deciduous fruits.  Applications on citrus fruits are
    usually made between petal fall and harvest during the period of
    movement of the larvae after release from the parent.  At this time
    its control of other pests, such as aphids and whitefly, can also be
    useful.  Applications can also be made in mixtures with summer or
    winter oils.

    It acts as a contact and stomach insecticide.  It is absorbed through
    the leaf surface, but is only slowly translocated in the plant sap
    from leaf application.  It is systemic by root absorption and treated
    plants remain toxic to insects for about 12 days.  The formulations
    are compatible with most commonly-used spray chemicals.  Transient
    phytotoxic effects have been observed on young, soft plants in
    greenhouses; more mature plants have not usually shown these symptoms
    but a wettable powder formulation has been tested for greenhouse use.

    Normal rates of use range from 0.03 to 0.075% ai for high volume
    spraying; low volume treatment requires appropriately higher
    concentrations.  Table 1 lists the crops treated and the pests
    controlled.

    TABLE 1. Crops treated and pests controlled.

                                                  

    Crop               Pest
                                                  
    Apples             aphids
                       codling moth
                       lace bug
                       scale insects
    Brassicas          cabbage root fly
    Carrots            carrot fly
    Cashew             whitefly
    Cherries           aphids
                       lace bugs
                       fruit fly
    Citrus             scale insects
                       mealybugs
                       mites
                       whitefly
    Olives             olive fly
                       scale insects
    Peaches            aphids
                       scale insects
                       mites
    Pears              aphids
                       leaf hoppers
                       lace bugs
                       pear sucker
                       mites
    Pistachio nuts     mites
                       scale insects
    Plums              aphids
                       leaf hoppers
                       mites
    Rice               leaf hoppers
                       plant hoppers
                       leaf miners
                       rice stem maggot
    Vines              vine moth
                       mites
                       mealybugs
    Glasshouse crops   whitefly
                                                  

    Open blossoms should not be sprayed and edible crops should not be
    harvested within 14 days from spray treatment.  Table 2 sets out
    information on recommended rates of use and pre-harvest intervals for
    various crops in seven countries.  Use on olives is discouraged other
    than very early in the season when the oil content is minimal.  Use on
    vegetable crops is very limited.



        TABLE 2.  Recommended rates of use and pre-harvest intervals

                                                                                                      
                                 % a.i.                                Maximum           Pre-harvest
    Country      Formulation    in spray         Crop                  No. of            Interval
                                                                      Treatments
                                                                                                      
    Egypt          68% e.c.      0.1             citrus                   -                   -
                   68% e.c.      0.1             fruit trees              -                   -

    Cyprus         68% e.c.      0.034-0.1       citrus                   -                   14
                   68% e.c.      0.34-0.085      apples, almonds,      repeat at              -
                                                 peaches, pears,      10-15 days
                                                 cherries

    Greece         68% e.c.      0.051-0.085     citrus                   -                   14
                   68% e.c.      0.051-0.085     fruit trees              14                  -
                   12% in        0.06            fruit trees              -                   -
                   oil.

    Iran           68% e.c.      0.051-0.085     citrus                   -                   14

    Japan          25% e.c.      0.025-0.043     citrus                   4                   30

    Morocco        50% e.c.      0.05-0.06       citrus                   -                   -
                   50% e.c.      0.0375-0.085    peaches, plums,          -                   -
                                                 apples, pears,
                                                 vines

    S. Africa      90% e.c.      0.0495          citrus                   2                   90
                   90% e.c.      0.054           apples, pears            4                   14
                                                 plums, peaches,
                                                 apricots.
                                                                                                      
    


    FATE OF RESIDUES

    In plants

    The degradation of mecarbam applied to dwarf bean plants has been
    examined (Murphy Chem. Ltd., 1977) following different methods of
    mecarbam application, root uptake and foliar absorption.  The results
    indicated that mecarbam is slowly translocated from the foliage to the
    roots but is rapidly metabolised in both places.  At least four
    metabolites were indicated (three identified) resulting from either
    oxidative or hydrolytic attack.  Levels of mecarbam and its
    metabolites declined from 10.4 to 0.05 mg/kg in 26 days after foliar
    application; all levels observed in the roots were low, the highest
    being 0.5 mg/kg at 5 days.  Root uptake studies showed rapid
    degradation of mecarbam and only low levels were found in the foliage.
    Figure 1 illustrates the metabolic formation of mecarboxon, diethoate
    and diethoxon from mecarbam.

    FIGURE 1

    In soils

    Mecarbam added to loam and to sandy soil was studied under sterile and
    nonsterile conditions (Murphy Chem. Ltd., 1977).  Analysis showed that
    the pesticide has a short life, levels dropping from the applied 7.5
    mg/kg to less than 0.4 mg/kg in 50 days in loam soil and to O.1 mg/kg
    in 34 days in sandy soil.  Degradation was shown to be mainly by
    chemical rather than by microbial action since similar degradation was
    obtained with soil that had been sterilised by autoclaving.


    In cooking

    The principal use of mecarbam is on citrus crops, and most residue
    resides in the peel or rind, not in the flesh of the fruit.  Since the
    peel is consumed in marmalade, the fate of residues on processing
    oranges into this preserve has been studied (Murphy Chem. Ltd., 1970).
    The yield of home-made marmalade is about 2-3 times the weight of
    fruit used.  Batches of marmalade were prepared using a normal
    domestic recipe, except that the peel was finely shredded at -30°C to
    minimise possible losses of mecarbam.  Oranges containing
    field-incurred residues and untreated oranges to which known amounts
    of mecarbam had been added were used in these tests.  The
    field-treated fruit had residues of 2.4 mg/kg (10.7 mg/kg in the peel)
    and the added mecarbam was at a level of 2.7 mg/kg immediately before
    cooking.  Levels of mecarbam in the marmalade ranged from 0.14 to 0.22
    mg/kg, giving an average loss on cooking of over 80%.  The maximum
    level of mecarbam to be expected in marmalade prepared from treated
    fruit is of the order of 0.05 to 0.1 mg/kg.


    RESIDUES RESULTING FROM SUPERVISED TRIALS

    Citrus fruit

    Data was available from supervised trials of mecarbam on various types
    of oranges grown in Japan, South Africa, Egypt, Israel and Morocco
    (Murphy Chem. Ltd., 1980).  In all of the studies only negligible
    amounts of mecarbam (less than 0.03 mg/kg) were found in the flesh of
    the fruit.  Residues on the peel, however, ranged up to about 10 mg/kg
    at the recommended 14 and 30 day pre-harvest intervals and up to 5
    mg/kg at about 90 days.  Residues of mecarbam in the peel of
    grapefruit were about 0.5 mg/kg at 34 days after treatment, with not
    more than 0.01 mg/kg in the flesh of the fruit.

    The principal metabolites were also determined on treated oranges
    resulting from three trials carried out in Egypt; the results are
    given in Table 3 (Murphy Chem. Ltd., 1980).  At 14 days after
    treatment, the parent mecarbam remains the predominant residue in the
    peel, the three metabolites together comprising only 5 to 10% of the
    total residue.

    TABLE 3.  Mecarbam and metabolite residues in oranges grown in Egypt,
    1975 (mg/kg)

                                                                          
    No. of days                        Peel                        Flesh
    after
    application    Mecarbam   Mecarboxon  Diethoate   Diethoxon   Mecarbam
                                                                          

        0            5.95        0.08       0.20        1.39        0.10
        7            7.0         0.17       0.22        0.31        0.05
       14            6.95        0.28       0.17        0.25        0.02
       28            5.45        0.22       0.13        0.11        0.01
    Untreated        <0.05         -          -           -         <0.002
        0            18.3        0.028      0.032       0.054       0.12
        7            14.0        0.68       0.036       0.050       0.05
       14            5.35        0.20       0.04        0.004       0.03
    Untreated        <0.05         -          -           -         <0.002
        0            14.4        0.103      0.024       0.30        0.06
                                                                          

    In all three trials mecarbam was applied at a final spray concentration
    of 0.1% ai.

    Other crops

    A limited amount of data was presented on mecarbam residues in olives,
    grapes, pears and various vegetable crops.  The analytical results
    were not easy to interpret but it appears that treated olives
    containing up to 1.5 mg/kg can yield olive oil containing up to 8.5
    mg/kg of mecarbam.  Residues in grapes and pears at 14 days or more
    after application were generally less than 0.3 mg/kg; no evidence of
    occurrence of metabolites was available (Murphy Chem. Ltd., 1980). 
    The data on residues on cabbage, cauliflowers, broccoli, Brussels
    sprouts, celery, carrots, onions, turnips, sugarbeet and lucerne had
    mostly been obtained during the 1960s when analytical procedures were
    less specific or accurate than current methods.  Results reported were
    very inconsistent and in many instances the control values were equal
    to or greater than the observed levels in treated crops, typically
    about 0.3 mg/kg on leafy vegetables.

    The data on these vegetable crops were not adequate to support
    recommendations for maximum residue levels.


    METHODS OF RESIDUE ANALYSIS

    Mecarbam is extracted from crops with hexane, cleaned up by solvent
    partition and/or column chromatography and determined by GLC with
    either electron capture or phosphorus specific detection (Lynch,
    1976).  The procedure should be suitable for regulatory purposes.


    NATIONAL MRLs REPORTED TO THE MEETING

    Available information on national MRLs is given in Table 4.

    TABLE 4. National MRLs for mecarbam reported to the meeting

                                                                  
    Country                  Commodity                MRL (mg/kg)
                                                                  

    Belgium        Fruit, vegetables (not potatoes)        1

    Netherlands    Fruit, vegetables (not potatoes)        1

    South Africa   Apples, apricots, peaches, pears,
                   plums                                   0.05
                   Citrus                                  0.05
                                                                  

    EVALUATION

    COMMENTS AND APPRAISAL

    Mecarbam is an organophosphorus insecticide effective against plant
    sucking pests such as aphids, scale insects, etc., and also acts as an
    acaricide.  Its principal use is for the control of scale insects and
    mealybugs on citrus fruits, with lesser uses against the same range of
    insects on vines, olives and deciduous fruits; it has also been used
    on vegetables.

    Mecarbam is rapidly absorbed following acute oral ingestion, with
    rapid distribution and elimination from the body.  Mecarbam does not
    bioaccumulate in the body on repeated administration.  The metabolism
    has not been elucidated.

    Mecarbam elicits parasympathomimetic signs of poisoning following high
    doses.  Antidotal studies with mecarbam are deficient, although it is
    presumed that atropine may be effective.

    Mecarbam appears not to induce a delayed neurotoxic response in hens
    although studies were not fully acceptable. Mecarbam does not affect
    reproduction in rats at levels below those at which dams might be
    affected.  Limited information derived from a teratology bioassay
    combined with the reproduction study did not suggest mecarbam to be
    teratogenic.  A more complete teratogenicity bioassay, specifically to
    evaluate this effect, is required.  There are no data available to
    assess the mutagenic potential of mecarbam.  There are no specific
    studies to assess the carcinogenic potential although long-term
    studies in rats alleviate concerns in this direction.  Adequate
    short-term dietary studies in dogs and long-term dietary studies in
    rats demonstrate that the principal effects attributable to mecarbam
    in the diet are reflective of cholinesterase depression.  In both
    species a no-effect level has been noted.

    On the basis of these levels a temporary acceptable daily intake was
    allocated and research suggested to complete the data base.

    Mecarbam is systemic by root absorption and absorbed through the leaf
    surface.  The three main metabolites are mecarboxon, diethoate and
    diethoxon, but these form only a small part of the total residue,
    which consists mainly of the parent mecarbam and remains in the peel
    of citrus fruits.  Preparation of marmalade from treated fruit results
    in residue losses of about 80%.  Available residue data were adequate
    for oranges but were scanty and difficult to interpret for other
    fruits, olives or vegetables.  A gas chromatographic method of
    analysis is available which can be adapted for regulatory purposes.


    Level causing no toxicological effect

    Rat: 5 mg/kg in the diet equivalent to 0.21 mg/kg bw/day
    Dog: 5 mg/kg in the diet equivalent to 0.15 mg/kg bw/day


    Estimate of temporary acceptable daily intake for man

    0-0.001 mg/kg bw/day

    RECOMMENDATIONS OF RESIDUES LIMITS

    From the data available the meeting was able to estimate a maximum
    residue level for oranges only.

    The meeting concluded that the level is suitable for establishing a
    temporary maximum residue limit.  The level applies to the parent
    compound, excluding any metabolites.

                                                                     
    Commodity     Estimated maximum       Treatment-harvest interval
                  residue level (mg/kg)   on which level is based
                                                                     

    oranges                2                          14
                                                                     

    FURTHER WORK OR INFORMATION

    Required (by 1983)

    1.  Complete metabolic studies in laboratory animals.
    2.  A complete teratogenicity bioassay.
    3.  Studies to define the mutagenic potential.
    4.  Studies in hens or other appropriate species to define the
    potential for delayed neurotoxicity.
    5.  Further data on residues of mecarbam in citrus fruits, olives,
    olive oil and other fruits to support additional recommendations for
    maximum residue levels.
    6.  Data on the use of mecarbam on vegetables and deciduous fruits
    together with residue data from supervised trials.
    7.  Data on residues occurring in meat or milk from feeding animals
    with citrus pulp prepared from treated fruit.
    8.  Further data on residues of mecarbam in citrus fruits, olives,
    olive oil and other fruits to support additional recommendations for
    maximum residue levels.
    9.  Data an use of mecarbam on vegetables and deciduous fruits,
    together with residue data from supervised trials.
    10. Data on residues occurring in meat or milk from feeding animals
    with citrus pulp prepared from treated fruit.

    Desirable

    1. Studies on antidotes.
    2. Epidemiological data on potential for adverse effects resulting
    from occupational exposure.


    REFERENCES

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    Aryton J. and Harnby G. Preliminary metabolic studies on Mecarbam
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    See Also:
       Toxicological Abbreviations
       Mecarbam (ICSC)
       Mecarbam (Pesticide residues in food: 1983 evaluations)
       Mecarbam (Pesticide residues in food: 1986 evaluations Part II Toxicology)