PESTICIDE RESIDUES IN FOOD - 1981 Sponsored jointly by FAO and WHO EVALUATIONS 1981 Food and Agriculture Organization of the United Nations Rome FAO PLANT PRODUCTION AND PROTECTION PAPER 42 pesticide residues in food: 1981 evaluations the monographs data and recommendations of the joint meeting of the FAO panel of experts on pesticide residues in food and the environment and the WHO expert group on pesticide residues Geneva, 23 November-2 December 1981 FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS Rome 1982 METHIOCARB IDENTITY Chemical name (s) 4-methyl-3,5-xylyl methylcarbamate; 3,5-dimethyl-4-methylthiophenyl methylcarbamate Synonyms mercaptodimethur (methiocarb and mercaptodimethur are both standard ISO names) metmercapturonG, MXMC, DrazaTM, MesurolTM, B-37344 Structural formulaOther information on identity and properties See "Fate of residues - in water" No information was provided to the Meeting either on manufacturing processes or on the nature of possible contaminants. DATA FOR THE ESTIMATION OF ACCEPTABLE DAILY INTAKE BIOCHEMICAL ASPECTS Absorption, distribution, biotransformation and excretion Excretion, storage and metabolism of methiocarb has been investigated employing (ring-l-14C), (carbonyl-14C) and (methylthio-3H) labelled methiocarb (Bayer 1981). Rat Rats were orally dosed with both (carbonyl-14CP methiocarb and (methylthio-3H) methiocarb at a rate of 20 mg/kg (Gronberg and Everett 1964). The methiocarb was oxidized partially to methiocarb sulphoxide and methiocarb sulphone, and then the carbamates were hydrolysed to phenols, which were excreted in the urine as glycosidic conjugates. Some N-hydroxy-methyl sulphoxide was also detected. Over 60% of the carbonyl-14C label was expired as CO2. Rats treated with (carbonyl-14C)methiocarb, methiocarb sulphoxide and methiocarb sulphone at rates of 10 mg/kg appeared to exhibit the same metabolic pattern of methiocarb degradation (Gronberg and Everett 1964). In studies with male and female rats treated orally with a single dose of (ring-l-14C)methiocarb at a rate of 20 mg/kg or 0.25 mg/kg, nearly all of the radioactivity was excreted in the urine within 48 h. Only traces of the intact carbamates were detected in the urine. The principal metabolites appeared to be conjugated methiocarb sulphoxide phenol and conjugated methiocarb phenol. There were no appreciable differences in metabolic patterns between male and female rats (Stanley and Johnson 1976). Hen Hens, after receiving a single oral dose of (ring-l-14C) methiocarb at a rate of 4.4 mg/kg, excreted 84% of the dose in 24 h and an additional 1% in the next 72 h. Less than 1% of the dose was excreted as methiocarb. Conjugated and non-conjugated methiocarb phenol (21% and 13% of the dose respectively), methiocarb sulphoxide phenol (1% and 9%), and methiocarb sulphone phenol (1% and 7%) were detected in the excreta along with N-hydroxy-methyl methiocarb sulphoxide (2%). All eggs collected during the 96 h period collectively contained 0.1% of the administered dose, and no single egg contained more than 0.02 ppm methiocarb equivalents (Stanley et al 1979a). Hens were orally dosed with (ring-l-14C)methiocarb for 5 consecutive days at a rate of 4.4 mg/kg/day and then sacrificed after the fifth dose. Eggs collected during the dosing period and at sacrifice contained 0.1 ppm methiocarb equivalents each. Radioactive residues in the tissues ranged from 0.4 ppm in the breast muscle to 7.7 ppm in the gizzard (including lining). In the tissues, the principal metabolic pathway for methiocarb involved hydrolysis to methiocarb phenol, oxidation of methiocarb phenol to methiocarb sulphoxide phenol and methiocarb sulphone phenol, and subsequent conjugation of these phenols. Some oxidation of methiocarb to methiocarb sulphoxide, N-hydroxymethyl methiocarb, and N-hydroxy- methyl methiocarb sulphoxide also occurred (Stanley et al 1979a, b). Feed treated with methiocarb/methiocarb sulphoxide (9:1) at 20, 60, 120 and 360 ppm was distributed to chickens ad libitum for 28 days. Feed consumption decreased as the amount of methiocarb/ methiocarb sulphoxide in the feed increased and body weights reflected the reduced feed intake. Egg production was not affected by the treatments. Plasma cholinesterase activity decreased 40% to 50%, as compared to the control birds, at the 60, 120 and 350 ppm dosage levels. Residues were detected in the giblets from the 60, 120 and 360 ppm treatment groups, in the skin from the highest dosage, and in the eggs from the two highest levels. No residues were detectable in the muscle or fat (Strankowski and Minor 1976). Figure 1 illustrates the metabolic pathway of methiocarb in animals. The chemical names of the metabolites are given in Table 1. Dog Following oral administration of (ring-l-14C)Mesurol to dogs at a rate of 2 mg/kg, between 64% and 92% of the dose was recovered in the urine and faeces. At least 71% of the radioactivity found in the urine was present as conjugated methiocarb sulphoxide phenol and conjugated methiocarb sulphone phenol. Essentially all of the radioactivity found in the faeces was identified as methiocarb and tissue residues were 0.4 ppm (Bell 1974). Cow (ring-l-14C) methiocarb was administered to a dairy cow at a rate of 0.14 mg/kg. Within 144 h, 96% of the administered radioactivity was excreted in the urine, 1% in the faeces and 1% in the milk. Approximately 80% of the urine radioactivity was identified as conjugates of methiocarb phenol, methiocarb sulphoxide phenol and methiocarb sulphone phenol, which were present in nearly equal quantities (Minor and Murphy 1977a). A dairy cow was dosed once each day for 5 consecutive days with (ring-l-14C) methiocarb at a rate of 0.14 mg/kg/day and then sacrificed after the fifth dose. Radioactive residues in the milk reached a peak (0.062 ppm) after the third dose. Methiocarb sulphoxide (0.002 ppm) was the only carbamate detected in the milk. Kidney (0.108 ppm) and liver (0.073 ppm) were the only tissues with radioactive residues > 0.01 ppm. Methiocarb and its carbamate metabolites accounted for no more than 0.02 ppm residue in any tissue (Minor and Murphy 1977b). TABLE 1. Chemical names, structures and designations of methiocarb and metabolites identified in animals Designation Chemical name Methiocarb 3,5-dimethyl-4-(methyl thio)-phenol methylcarbamate
Methiocarb sulphoxide 3,5-dimethyl-'4-(methylsulphinyl)phenol methylcarbamate
Methiocarb sulphone 3,5-dimethyl-4-(methylsulphonyl) phenyl methylcarbamate
N-hydroxymethyl 3,5-dimethyl-4-(methylthio)-phenol N-Hydroxymethyl carbamate methiocarb
N-hydroxymethyl 3,5-dimethyl-4-(methylsulphinyl)phenol N-hydroxymethyl carbamate methiocarb suiphoxide
Methiocarb phenol 3,5-dimethyl-4-(methylthio)phenol
Methiocarb sulphoxide 3,5-dimethyl-4-(methylsulphinyl)phenol phenol
Methiocarb sulphone 3,5-dimethyl-4-(methylsulphonyl) phenol phenol CHEMICAL STRUCTURE 8;V081PR25.BMP Beef and dairy cattle were fed rations containing 10, 30 and 100 ppm methiocarb for 29 days (Mobay 1970). No toxic symptoms were observed during the test. One of the nine test animals did show a slight weight loss and decrease in milk production, but she was nearing the end of her lactation period and the decrease in production was expected. Residues were detected only in the liver (animals fed 30 and 100 ppm methiocarb) and kidney (animals fed 100 ppm methiocarb). All other tissues (brain, heart, muscle and fat) showed no detectable residues. Milk was collected on the 28th and 29th days of the study. Detectable residues (> 0.005 ppm) were found at all levels of treatment. The ranges of the residues were 0.005 to 0.007 at 10 ppm, 0.008 to 0.015 ppm at 30 ppm and 0.021 to 0.033 ppm at 100 ppm.
TOXICOLOGICAL STUDIES Acute toxicity The acute toxicity of methiocarb was tested in several animal species. Results are summarized in Table 2. Acute toxicity of methiocarb metabolites were tested in rats, and results are given in Table 3. Symptoms of poisoning after acute application The symptoms of poisoning were typical of cholinesterase activity depression, and were characterized by trembling, muscular fasciculations, ataxia, salivation, lachrymation and diarrhoea. Vomiting was also seen in dogs. The severity and duration of the symptoms were dose-related. Onset of symptoms was within minutes after oral and intraperitoneal administration, and they usually persisted for no more than a few hours. Deaths usually occurred within a few hours after administration (Bayer 1981). TABLE 2. Acute toxicity of methiocarb in animals Species Sex Route Solvent/vehicle LD50(mg/kg) Reference Rat M oral H2O + tragacanth ca. 100 Kimmerle 1960 oral polyethylene 67 " 1966a M oral glycol 400 13-15 Lamb and Matzkanin F oral " 31-32 1976 M oral " 28.0-35.1 Thyssen 1977a M oral " 33 Nelson 1979 F oral " 47 " F oral ethanol + polyethylene 100 DuBois and Raymund glycol 1962 M oral " 130 " F oral " 135 1961a M ip H2O + tragacanth ca. 100 Kimmerle 1960 F ip ethanol + polyethylene 25 DuBois and Raymund glycol 1962 M ip " 35 " ip " 30 1961b F dermal,24h ethanol >300 " 1962 M dermal,24h oil >1000 Kimmerle 1960 M&F dermal,24h polyethylene >5000 Thyssen 1977b glycol 400 M ip ethanol + polyethylene 6.0 DuBois and Raymund F ip glycol 5.5 1961b TABLE 2. (con't) Species Sex Route Solvent/vehicle LD50(mg/kg) Reference Guinea F oral H2O + emulsifier 50-100 Kimmerle 1969a pig M oral ethanol + polyethylene 40 DuBois and Raymund glycol 1961a F oral ethylene glycol 14.1 Crawford and Anderson 1972 M ip " 17 DuBois and Raymund 1961b Rabbit M&F dermal,24h saline >2000 Crawford and Anderson 1972 Dog M&F oral none (gelatin 25.4 Lamb and Matzkanin capsule) 1975 F oral H2O + emulsifier 10-25 Kimmerle 1969 Hen oral ethanol + polyethylene 175 DuBois 1962 glycol TABLE 3. Acute toxicity of several metabolites of methiocarb in the rat Chemical (M=methiocarb) Sex Route LD50(mg/kg) Reference M sulphoxide M oral 6-9 Lamb and Matzkanin F oral 7-8 1976a, b oral 42.9 Solmecke 1970a M sulphone oral >1000 " 1970b M phenol oral >10001 " 1970c M oral >10001 DuBois 1964 M dermal >10001 " M sulphoxide phenol M oral >10001 " oral >10001 Solmecke 1970d M dermal >10001 DuBois 1964 M sulphone phenol M oral >10001 " oral >10001 Solmecke 1970e M dermal >10001 DuBois 1964 N-hydroxymethyl M M oral >1121 Nelson 1979 F oral >1121 " N-hydroxymethyl M oral >1121 " M sulphone F oral >1121 " N-hydroxymethyl M oral >1601 " M sulphoxide F oral >1601 " 1 = no mortality. When ethanol solutions of methiocarb were applied to the skin of rats at dose levels of 100 and 200 mg/kg, cholinergic symptoms were observed at the higher dose hut no mortality occurred. Methiocarb was not well-absorbed from the skin, even when dissolved in a solvent that should increase dermal absorption. Following application of polythylene glycol 400 solutions of methiocarb to the skin of rats, mild cholinergic symptoms of brief duration were also observed at dose levels of 100 mg/kg bw and above, but no mortalities occurred at dose levels of up to and including 5 000 mg/kg bw (Bayer 1981). When one-half of the LD50 of methiocarb was given intraperitoneally to female rats in combination with the same fraction of the LD50 of trichlorfon, coumaphos, oxydemeton methyl, fenthion or propoxur, additive or less than additive acute toxicity was observed (DuBois and Raymund 1961b). Potentiation of acute toxicity was investigated in another study on female rats involving simultaneous intraperitoneal administration of equitoxic doses of methiocarb and 15 other anticholinesterase insecticides. The results of the tests demonstrated that potentiation of acute toxicity does not occur when methiocarb was given in combination with each of the 15 other anticholinesterase insecticides, including parathion, methyl parathion, malathion, azinophos methyl a.o. (DuBois and Raymund 1961b). Antidote studies Studies on the protective efficacy of atropine for the treatment of poisoning by methiocarb demonstrated that the intraperitoneal injection of 100 mg/kg of atropine sulphate 10 min before treatment with the carbamate raises the LD50 from 30 to 100 mg/kg. The intraperitoneal administration of 100 mg/kg of 2-PAM immediately before or at 15 min after methiocarb administration had no significant protective or antidotal activity (Dubois and Raymund 1961a). In another experiment, 50 mg/kg of atropine sulphate or of PAM or 20 mg/kg of Toxogonin, respectively, was injected intraperitoneally shortly before the appearance of acute symptoms following the oral application of methiocarb. Injection of atropine sulphate raised the LD50 from 67 to 467.5 mg/kg bw. PAM and Toxogonin had only a slight effect. These results demonstrate that atropine has an excellent antidotal effect in rats poisoned with methiocarb (Kimmerle 1966). Confirmation of the good antidotal effect of atropine sulphate was obtained in further experiments. Intraperitoneal injection of 50 mg atropine sulphate/kg bw at onset of cholinergic symptoms following acute oral administration of methiocarb to male rats raised the LD50 from 104.5 to 643 mg/kg bw (Kimmerle 1971). Atropine proved to be an effective antidote also in a dog accidentally poisoned with methiocarb (Udall 1973). Short-term studies Rat Male rats were dosed on 27 consecutive work-days with methiocarb suspended in water plus tragacanth and administered by oral intubation. The daily dose was 2 mg/kg on each of the first 3 days and 4 mg/kg bw thereafter. During and also after termination of treatment, groups of 3 rats were sacrificed twice weekly, and erythrocyte cholinesterase activity was measured. Cholinesterase activity decreased during the course of the treatment, amounted to about 80% after 14 days, and was 50% on termination of treatment. During the post-treatment observation period, activity increased again only at a very slow rate and did not return to normal until about 42 days after termination of treatment. Cholinergic symptoms were not seen during the treatment period (Kimmerle 1960). The subacute oral toxicity of methiocarb was investigated in male and female weanling Sprague-Dawley rats by feeding groups of animals diets containing 0, 5, 10 and 50 ppm of methiocarb for a period of 16 weeks. The rats tolerated methiocarb in the diet at levels as high as 50 ppm for 16 weeks without exhibiting any alteration of their growth rate or food consumption. Animals fed methiocarb at 10 ppm did not exhibit cholinergic or other toxic symptoms. Methiocarb could be fed to male and female rats at a dietary concentration of 10 ppm for 16 weeks without producing inhibition of the cholinesterase activity of the serum, erythrocytes, brain or submaxillary glands. When the dietary concentration was increased to 50 ppm, the activity of this enzyme was reduced in the semen by about 30% and that of the erythrocytes was decreased by about 15% (Doull et al 1962). Dog The subchronic oral toxicity of methiocarb was investigated in male and female beagle dogs to determine the level that can be added to the diet without producing detectable symptoms of poisoning or significant inhibitions of blood cholinesterase activity. Dietary levels of 0 (control), 50, 100 and 250 ppm were employed for these studies, in which 2 male and 2 female dogs were fed each of these dietary levels. Individual measurements of the serum and erythrocyte cholinesterase activity were made weekly for a period of 12 weeks. It was shown that dietary levels as high as 250 ppm can be fed to male and female beagle dogs for 12 weeks without causing any reduction of their normal growth rate or the appearance of other toxic symptoms. Levels as high as 250 ppm caused no significant inhibition of the cholinesterase activity of serum or erythrocytes and produced no cholinergic symptoms (Root et al 1963). Two male and two female beagle dogs were fed diets containing 0 (control), 50, 100 and 250 ppm of methiocarb for a period of 2 years. The animals were observed daily for symptoms of cholinergic stimulation. Measurements of the growth rate, food consumption and blood cholinesterase activity were carried out at intervals during the exposure period. At the end of the 2-year feeding period, the dogs were autopsied and the tissues removed and prepared for microscopic examination. Samples of the brain, liver and blood were also taken at autopsy for the terminal cholinesterase activity determinations. The inclusion of methiocarb in the diet at levels of 250 ppm or less did not significantly alter the growth rate-food consumption or general physical condition of either male or female dogs. None of the dietary levels of methiocarb used produced cholinergic symptoms or other indications of toxic effects that could be attributed to the presence of methiocarb in the diet. The dogs tolerated methiocarb in the diet at levels of 250 ppm or less for a period of 2 years without exhibiting a significant inhibition of either the serum or erythrocyte cholinesterase activity. Blood, brain and liver cholinesterase activity was also not seen to be depressed at termination of the study. Gross examination of the tissues and organs after the 2-year treatment failed to reveal any characteristic or significant indications of toxicity that could be attributed to the inclusion of methiocarb in the diet (Doull et al 1968). Groups of 4 male and 4 female beagle dogs were maintained for 104 weeks on a diet containing methiocarb at concentrations of 0 (control), 15 (week 1-2), 5 (week 3-104); 60 and 240 ppm. On termination of test diet administration, the dogs were sacrificed and necropsied and organs were weighed and histopathologically examined. Several dogs of the 240 ppm group were occasionally seen to have slightly weak hind limbs, to tremble and to be slightly less attentive during the first 14 treatment weeks. Increased vomiting was also seen in the dogs of this group. Food was consumed slowly by female dogs fed 60 and 240 ppm and by male dogs fed 240 ppm. Dietary levels of 15 ppm and above were observed in week 2 to depress plasma cholinesterase activity. Following reduction of the 15 ppm level to 5 ppm, plasma cholinesterase activity in this group rapidly returned to normal. The depression of plasma cholinesterase activity induced by 60 ppm and 240 ppm was observed to be of a slightly dose-related degree. It was more conspicuous at 2 h than at 24 h after feeding and remained somewhat constant throughout the 2-year test diet administration. Erythrocyte and brain cholinesterase activities were not depressed by dietary levels as high as 240 ppm. Thus, in the 104-week dietary administration of methiocarb to dogs, it was found that 60 ppm was the no-somatic-effect dose. The dietary level of 5 ppm had no effect on cholinesterase activity (Hoffman and Schilde 1980). Cow Feeding studies were carried out with cattle to determine the effects of several organophosphorus and carbamate compounds. Generally, 3 animals per treatment level were maintained for 1 month on a diet containing levels of residues expected from normal use (x), 3 x and 10x rates. Levels for methiocarb were 0.3, 0.9 and 3.0 mg/kg/day. Blood was collected throughout the test to monitor cholinesterase activity. Residues in tissues and milk were determined at the end of the test. Changes in weight and milk production were noted and gross observations were made. Residues from methiocarb were less than 0.05 ppm in tissues and ranged from 0.005 to 0.026 ppm in milk. Cholinesterase inhibition in blood was not seen. There were slight but insignificant effects on weight change and possible milk production (Waggoner and Olson 1971). Hen Four groups of laying hens were fed rations containing methiocarb/methiocarb sulphoxide (9:1) at levels of 20, 60, 120 and 360 ppm continuously for 28 days. A control group of 4 birds was also maintained. Feed consumption and body weights were both affected, but egg production was not affected by the treatment. A drop in cholinesterase activity was observed in chickens dosed at 60, 120 and 360 ppm. No residues were detected in muscle or fat. Only slight residues were seen in skin and egg at the highest level of testing, while residues were detected in giblets (heart, gizzard, liver) in all but the lowest dosage group (Strankowski and Minor 1976). Long-term studies Rat Twenty-four male and 24 female Sprague-Dawley rats per group were fed diets containing 0 (control), 25, 50 and 100 ppm for a period of about 20 months to investigate the chronic effect of methiocarb. Measurements of the effect of adding methiocarb to the diet on the growth rate, food consumption, life span and mortality were made at frequent intervals during the exposure period. Blood and tissue cholinesterase activity determinations were carried out at the end of the feeding period. The surviving animals were autopsied and the tissues removed, weighed and prepared for histological examination. Male and female rats were able to tolerate methiocarb in the diet at levels of 100 ppm or less for a period extending over most of their life span without exhibiting marked changes in food consumption, growth rate or survival time. The addition of methiocarb to the diet of male and female rats at dietary levels of 100 ppm or less did not produce cholinergic or other toxic symptoms and did not result in marked life-span shortening in either the male or female animals. There was no marked inhibition of the blood and brain cholinesterase activity in male and female rats at levels of 100 ppm or less for a period of about 20 months. Gross examination of the tissues failed to reveal any characteristic or significant pathology that could be attributed to the presence of methiocarb in the diet of these rats (Doull et al 1967). Methiocarb was evaluated for potential chronic toxicity and potential carcinogenicity in a 2-year study in which groups of 60 male and 60 female Wistar rats were maintained on a diet containing methiocarb at concentrations of 0 (control), 67, 200 and 600 ppm. Clinical laboratory tests (haematology, clinical chemistry, urinalysis, measurements of plasma and erythrocyte cholinesterase activities) were performed at several intervals during the study on 10 male and 10 female rats of each test group. On termination of the 24-month test diet administration, all survivors were sacrificed and grossly necropsied. The major organs were weighed, brain cholinesterase activity measured in 10 male and 10 female rats of each group and a comprehensive histological examination of tissues was performed. Dietary levels of 600 ppm and less did not have any untoward effects on the physical appearance, behavioural patterns, survival rate and food consumption of either male or female rats. No differences in weight gain were seen between control rats and the treated male and female rats fed dietary levels of 200 ppm and less. In the 600 ppm group, the body weights of both males and female were significantly lower than those of the control rats throughout the study. Haematology, clinical chemistry, urinalyses, gross pathology and organ weight measurements did not provide any indication of methiocarb-related alterations at dietary levels of 600 ppm or less. The methiocarb dietary level of 67 ppm did not depress plasma and erythrocyte cholinesterase activities. Rats fed 600 ppm had lower plasma and erythrocyte cholinesterase activities than the controls. In rats fed 200 ppm, cholinesterase activity decreased transiently below the control level only in erythrocytes. Brain cholinesterase activity was not depressed at any dietary level. Histopathology did not reveal any methiocarb-induced tissue alterations at dietary levels of 600 ppm or less. The study provided no indication of methiocarb having carcinogenic effects. In the 2-year feeding experiment on rats, it was thus found that the dietary level of 67 ppm had no untoward effect whatsoever on any of the investigated parameters, including cholinesterase activity (Krötlinger et al 1981). Special studies on reproduction Rat In a 3-generation study involving two matings per generation, groups of 10 male and 20 female Long Evans rat were fed a diet containing methiocarb at concentrations of 0 (control), 30, 100 and 300 ppm, respectively. The treatment was evaluated for effect on fertility, lactation performance and pup development. The rats receiving these dietary concentrations did not differ from the controls with respect to fertility, litter size, average pup weight at birth, potential survival and lactation performance of the dams. Because the number of pups per litter was larger than in the control group, the body weights in the 300 ppm dose group of the F2b generation and in the 100 and 300 ppm groups of the F3b generation were lower at the end of the lactation period. Groups with smaller litters consequently had higher body weights. Thus, these differences were not considered attributable to inclusion of methiocarb in the diet. The administered dietary concentrations did not cause any malformation in the progeny. Histopathological examinations of the 10 major tissues from the F3b generation pups did not reveal any methiocarb-related tissue alterations. In this reproduction study, haematological tests, clinical- chemical tests and urinalyses were performed at 10 and 24 weeks, i.e. at the end of the pre-treatment just before mating and on conclusion of lactation of the second litter of the F0 generation. These tests did not indicate any blood profile damage or interference with liver and kidney function at dietary levels of up to and including 300 ppm (highest concentration). Blood sugar and cholesterol levels generally were within the physiological range (Löser 1969, 1970). Special studies on embryotoxicity and teratogenicity Rat Nineteen to 20 fertilized rats (Long Evans strain) received methiocarb from gestation day 6 to 15 at dose levels of 0 (control), 1, 3 or 10 mg/kg bw. These dose levels were tested for general tolerance to the pregnant rats as well as for possible embryotoxic and teratogenic effects. The dose levels of 1 and 3 mg/kg bw were tolerated by the pregnant rats without inducing any signs of damage. Ten mg/kg bw did not affect general behaviour and appearance of the dams. However, the rats of this dose group showed less weight gain, although not significantly less, than the control animals during the treatment period. Methiocarb had no influence on reproduction parameters and had no teratogenic effect (Lorke 1971). Special studies on mutagenicity Microorganisms Methiocarb was tested for potential mutagenic effects on histidine-auxotrophic Salmonella typhimurium strains TA 1535, 100, 1537 and 98, with and without metabolic activation. No indication of methiocarb having mutagenic effects was found (Herbold 1978). Methiocarb was also found to be non-mutagenic when tested in three strains of Saccharomyces cerevisiae, using reversion from histidine and methionine auxotrophy as a measure of the induced mutation (Guerzoni and DelCupola 1976). Mammals in vivo A micronucleus test was conducted on male and female NMRI mice to evaluate methiocarb for potential mutagenic effects on the chromosomes of bone marrow erythroblasts. The mice received two applications at an interval of 24 h, and the femoral marrow was prepared 6 h after the second application. The methiocarb doses were 2 × 5, 2 × 10 and 2 × 20 mg/kg bw per os. The test provided no indication of methiocarb having a mutagenic effect at doses of up to and including 2 × 20 mg/kg bw per os; the highest tested dose level was in the lethal range. Erythrocyte production, measured against the ratio of polychromatic to normochromatic erythrocytes, was not adversely affected either. The co-tested positive control reference substance adriblastin had a strong mutagenic effect (Herbold 1979b). Dominant lethal In a dominant lethal test to evaluate methiocarb for potential mutagenicity, 50 male NMRI mice each received an acute oral dose of 6 mg methiocarb/kg bw. A vehicle control group consisted of the same number of male mice. The applied dose had no effect on mouse fertility or on the numbers of dead implants, viable implants, total implants or pre-implantation losses. The test revealed no indication of mutagenic effects of methiocarb (Herbold 1979a). Special studies on neurotoxicity Methiocarb administered twice orally at a 3-week interval, at a dose level of 380 mg/ kg bw (LD50), to atropinized adult female hens did not cause any delayed neurotoxicity. Neither clinical symptoms nor histopathological signs of delayed neurotoxicity were seen in the methiocarb-treated hens. Positive control hens treated orally with a single non-lethal dose of TOCP at a level of 375 mg/kg bw showed both clinical symptoms and histopathological manifestations of delayed neurotoxicity (Thyssen and Schilde 1978). Groups of 8 2-year old hens were fed methiocarb for 30 days at dietary levels of 0 (control), 200, 400 and 800 ppm, respectively. At the end of the 30-day feeding period, 4 hens of each group were sacrificed and histopathologically examined. The other hens were kept under observation, without treatment, for a further 30 days and then examined. The treated hens of all groups did not show any cholinergic symptoms or signs of paralysis. Histopathology did not reveal any nerve tissue alterations (Ives 1965). Special studies on cholinesterase inhibition Acute experiments Groups of Wistar rats, each consisting of 5 males and 5 females, received a single dose of methiocarb at levels of 1, 10, 25 and 50 mg/kg bw by stomach tube. Cholinesterase activity in plasma and erythrocytes was determined at intervals of 20 min, 2 h and 5 h after the application. Cholinesterase activity in the male rats receiving the highest dose was additionally determined after 90 min and 3 h. Typical symptoms of acute inhibition of cholinesterase activity were seen in the animals treated with doses of 10 mg/kg bw and above. These symptoms appeared within 5 to 10 min after application and cleared 2 h later. The male rats of the 50 mg/kg group died after 2 h. The maximum dose-related levels of cholinesterase activity depression were recorded 20 min after the application in the dose groups of 25 mg/kg and below, and 20 min to 2 h after application in the highest dose group. Two hours after the application, a marked increase in enzyme activity was seen again in all dose groups except the highest one. In another experiment, in which male rats received a single dose of methiocarb at levels of 10 and 20 mg/kg bw, cholinesterase activity was measured in the brain at intervals of 30 min, 1 h, 2 h, 3 h and 5 h after the application (3 animals/dose). Inhibition reached its maximum after 2 h; thereafter, activity increased again (Eben and Kimmerle 1973). Subacute experiment Groups of Wistar rats each consisting of 10 males and 10 females were treated daily for 4 weeks with methiocarb at dose levels of 1, 3 and 10 mg/kg bw by stomach tube. Only the animals receiving the highest dose level briefly exhibited cholinergic symptoms after the applications. Cholinesterase activity in plasma and erythrocytes was measured in 3 males and 3 females of each group 20 min after administration on days 4, 8, 14, 21 and 28, and additionally 5 h after the final application. Brain cholinesterase activity was measured in 5 male rats and 5 female rats of each group 2 h after the final application. Plasma and erythrocyte cholinesterase activity was depressed in the highest dose group (10 mg/kg bw). The degree of depression was almost constant throughout the experiment. Likewise, brain cholinesterase activity was depressed only in the 10 mg/kg group. With respect to cholinesterase activity depression, the no- effect level in this experiment was thus 3 mg methiocarb/kg bw/day (Eben and Kimmerle 1973). RESIDUES IN FOOD AND THEIR EVALUATION USE PATTERN Methiocarb is widely used world-wide as a bird repellent, molluscicide, and insecticide. It is registered for use in Europe (19 countries), Africa, America (USA and 13 countries of South America), Canada, New Zealand and Asia. It is formulated as a wettable powder, bait, and seed treatment and may be applied by spraying, broadcast, pelleting and as a seed dressing. The Meeting was provided with good agricultural practice information from Germany, Hungary, The Netherlands, New Zealand and the USA. National good agricultural practices are listed in Tables 4 and 5 according to type of treatment or country, and a summary of world-wide proposed or recommended uses is given in Table 6. Only minimal information was available on good agricultural practices for bait formulations. TABLE 4. National good agricultural practices for methiocarb Spray treatment (insecticidal or bird repellent) Country Crop Formulation Application Interval between rate last application and harvest (days) Fed. Rep. Germany Cereals(insecticidal) 50% 0.3 kg a.i./ha 28 Potato (insecticidal) 50% 0.3 kg a.i./ha 14 Pome fruit (insecticidal) 50% 0.05% 14 New Zealand Grape (bird repellent) - 75 g a.i./100 L 14 Cherry (bird repellent) - 75 g a.i./100 L 10 Seedling vegetables (bird repellent) - 750 g a.i./ha - Pea seed (bird repellent) - 300 g a.i./100 kg seed - Blueberry(bird repellent) - 75 g a.i./100 L 7 USA Blueberry (bird repellent) 75% WP 2.2 kg a.i./ha 0 Cherry (insecticidal) 75% WP 3.4-4.5 kg a.i./ha 7 (bird repellent) 75% WP 2.2-4.4 kg a.i./ha 7 Peach (insecticidal) 75% WP 3.4-4.5 kg a.i. 21 Fed.Rep. Germany Maize 50% 0.5 kg a.i./100 kg seed - Beet 50% 0.45 kg a.i./100 kg seed - USA Maize(field corn, sweet corn, popcorn) 50% dust1 0.25-0.5 kg a.i. - per 100 kg seed Hungary Maize (bird repellent) - 0.5 kg a.i./100 kg seed - TABLE 4. (con't) Country Crop Formulation Application Interval between rate last application and harvest (days) Bait Treatment Fed.Rep. Germany Vegetables,field crops, 4% 0.12 kg a.i./ha 14 strawberry, and ornamentals broadcast or (field and under glass) 40-120 mg/m/row USA Citrus and avocado 2%1 0.32 lb/100 sq.ft. - 2 applications/season (or half this rate with metaldehyde) 1 State registration. TABLE 5. National good agricultural practices for methiocarb, The Netherlands Crop Kind of pest Application Treatment In use situation1 controlled (kg a.i./ha) Formulation since2 Various l.s. snails 0.12-0.20 ) 4% granular bait 1968 vegetables s.s mole-cricket 0.12-0.20 ) 50% w.p. sprinkling between plants Strawberry m.s. strawberry seed beetle 0.20 50% w.p. sprinkling between plants Maize l.s. bird repellent 0.5 kg/100 kg 50 w.p. seed dressing 1972 seed Beet m.s. beet beetle + 0.5 kg/100 kg 50% w.p. seed dressing springtails Beet m.s. beet beetle + springtails 0.5 50% w.p. soil treatment (row) 1975 Rapeseed m.s. flea beetle 0.5 50% w.p. crop treatment between mid September and mid-October 1975 Ornamental plants l.s. bird repellent 50 g/100 L 50% w.p. plant treatment when necessary 1977 1 l.s. = large scale, ms = moderate scale, s.s. = small scale; 2 Other registered uses: on ornamental plants in combination with propoxur against insects. TABLE 6. Summary of world-wide proposed or recommended uses Recommended Dose Kind of No. of pre-harvest Crop Pest (a.i %) application Formulation applications interval (days) Pome, stone biting insects, 0.05 - 0.075 spraying WP 1 - 3 21 and berry- spider mites fruit mealybugs Potato biting insects 300 g/ha spraying WP 1 - 2 14 Sugarbeet pygmy mangold 450-900 g/ pelleting or Seed 1 beetle 100 kg seed as seed treatment dressing Maize to repel pheasants 500 g/100 kg seed coating Seed 1 - and frit fly control seed treatment Apple bird repellent 0.135 spraying WP 1 - 2 21 before harvest Peach bird repellent 0.12 spraying WP 1 - 2 21 before harvest Blueberry bird repellent 2.24 kg/ha spraying WP 3 0 before harvest Grape bird repellent 2.2 kg/ha spraying WP 3 1 before harvest Cherry bird repellent 4.48 kg/ha spraying WP 3 7 before harvest TABLE 6. (con't) Recommended Dose Kind of No. of pre-harvest Crop Pest (a.i %) application Formulation applications interval (days) Vegetables, slugs 120-200 g/ha broadcast Slug 1 - 2 Vegetables and strawberry, overall pellets strawberry 14; oilseed rape, oilseed rape cereals and cereals 90. RESIDUES RESULTING FROM SUPERVISED TRIALS Residue data are available in over 170 reports for 24 commodities and parts thereof from six countries. As noted earlier, there are no verified nationally-approved good agricultural practices for many of the commodities for which data were provided. Where nationally- approved uses have not been confirmed, uses are assumed to be proposed good agricultural practices or manufacturer recommended uses. Table 7 summarizes residue data provided to the Meeting and maximum residue estimates are discussed. Apple Whether the proposed or recommended uses are nationally-approved could not be determined. After multiple applications in six trials of two wettable powder formulations in three countries, according to proposed or recommended good agricultural practices, maximum residues ranged from 16 mg/kg at three days to about 8 mg/kg at the recommended safety interval of 21 days. Maximum apparent residue in controls were 0.14 mg/kg when analysed by methodologies with sensitivities as low as 0.04 mg/kg and capable of measuring parent sulphoxide and sulphone. Up to four months elapsed between last application and analysis. Artichoke Whether there are nationally-approved uses could not be determined. Multiple applications of a 2% bait and a flowable formulation of methiocarb in three trials in one state of the USA gave maximum residues of approximately 9 mg/kg at day of last application. However, no information was provided on established or proposed good agricultural practices for the wettable powder formulation that resulted in the high residues. Maximum residues for the bait formulation at proposed application rates were 0.05 mg/kg at seven days. Proposed good agricultural practices for the bait formulation on artichokes would permit harvest on day of application (maximum residue at one day is 0.03 mg/kg, no zero data are available). Up to five months elapsed between last application and analysis. Data are inadequate to permit an estimate of maximum residues. Barley Whether there are nationally-approved good agricultural practices could not be determined. At an interval approximating recommended or proposed pre-harvest intervals, no residues were detected using an analytical method capable of 0.05 mg/kg measurements when application rates were 0.6 × the maximum recommended. Up to six months elapsed between last application and analysis. Table 7. Methiocarb residues from supervised trials Residues (mg/kg) at intervals (days) after application Application (mean in parentheses where range is given)1 Crop Country Rate No. (Year) No (kg a.i./ha) Formulation 0 1 3 4-5 7-8 10 13-14 15 21 Untreated samples apple England 3 0.1% 50 WP 1.0 <0.15 <0.15 (1962) Germany 3 1.0 50 WP 0.6 0.15 0.13 0.14 (1975) Germany 3 1.0 50 WP 0.41 0.11 0.08 0.04 (1975) U.S.A. N.Y. 8 4.2 75 WP 6.6 5.3 5.0 7.3 7.9 0.05 (1974) (15 oz a.i./ 100 gal) WA (1974) 9 4.8 75 WP 4.9 4.6 4.8 3.6 3.3 0.14 (20 oz a.i./ 100 gal) WA 8 7.6 75 WP 11.2 16.2 4.1 5.9 4.5 0.14 (1974) (20 oz a.i./ 100 gal) apple fruit KS 8 20 oz a.i./ 75 WP 1.6 (1973) 100 gal wet pomace 3.3 dry pomace 0.7 juice 2.0 Table 7. (con't) Residues (mg/kg) at intervals (days) after application Application (mean in parentheses where range is given)1 Crop Country Rate No. (Year) No (kg a.i./ha) Formulation 0 1 3 4-5 7-8 10 13-14 15 21 Untreated samples artichokes U.S.A. CA 5 1.1 2% bait 0.03 0.03 0.05 <0.01 <0.01 (1975) (1977) 5 1.1 <0.01 <0.01 (1975) 5 1.1 75% WP 8.9 4.1 3.8 1.5 0.9 <0.2 barley Germany 3 0.12 4% 76-92 (1980) days grain N.D.3 3 straw N.D. 3 0 1 3-4 5 7-8 10 13-14 15 21 Untreated No. samples beans, snap U.S.A. 1.1 2% bait beans OR 5 0.03 <0.02 (1977) beans FL 6 <0.01 0.02 <0.01 <0.01 (1976) vines (1975) <0.01 <0.01 <0.01 <0.01 beans NY 5 0.5 0.02 0.02 <0.01 (1975) vines (1974 0.5 0.06 <0.01 beans IN 5 0.03 <0.01 0.04 0.02 (1975) vines (1974) 0.5 0.1 0.3 Table 7. (con't) Application Residues (mg/kg) at intervals (days) after application Crop Country Rate No. (Year) No (kg a.i./ha) Formulation 0 1 3-4 5 7-8 10 13-14 15 21 Untreated samples Canada 5 1.1 2% bait (1975) beans <0.01 <0.01 0.01 <0.01 vines <0.01 0.1 <0.01 beans, lima U.S.A. 1.1 2% bait (1975) pod CA 4 0.35 0.04 bean WI 5 <0.01 <0.01 0.02 0.08 pod 0.03 0.01 0.03 0.09 vine 0.03 0.6 0.04 <0.01 bean NJ 5 <0.01 <0.01 <0.01 <0.01 pod 0.02 0.01 0.02 <0.01 vine 0.2 0.02 U.S.A. beans, lima IN 5 1.1 2% bait (1975) bean <0.01 <0.01 <0.01 <0.01 pod <0.01 0.04 0.02 0.02 vine <0.01 - <0.01 Canada 5 1.1 2% bait (1975) bean 0.01 <0.01 <0.01 <0.01 pod 0.01 0.03 <0.01 <0.01 vine 0.02 0.11 Table 7. (con't) Application Residues (mg/kg) at intervals (days) after application Crop Country Rate No. (Year) No (kg a.i./ha) Formulation 0 1 3-4 5 7-8 10 13-14 15 21 Untreated samples blueberry U.S.A. 75 WP OR 3 1.7+1.7+2.2 3.3 5.2 5.4 <0.05 (1974) (1975) 2 2.2 (aerial) 5.4 3.4 3.6 0.27 MI 2 2+2.2 3.1 0.05 (1975) IN 2 2.2 25.6 0.17 (1975) broccoli U.S.A. 1.1 2% bait KS 5 boadcast head (1975) 0.06 0.66 0.2 leaves 0.44 0.28 1.8 head OR 5 <0.01 0.02 0.03 <0.01 (1975) leaves <0.01 0.06 0.01 <0.01 head TX 5 <0.02 <0.02 0.04 <0.02 (1976) leaves <0.05 0.04 0.05 <0.02 head CA 5 0.26 <0.01 (1978) Table 7. (con't) Application Residues (mg/kg) at intervals (days) after application Crop Country Rate No. (Year) No (kg a.i./ha) Formulation 0 1 3-4 5 7-8 10 13-14 15 21 Untreated samples brussel U.S.A. 1.1 2% bait sprouts (broadcast) IN 5 0.02 0.2 0.06 <0.01 (1975) 5 0.03 <0.01 <0.01 <0.01 KS 6 0.4 <0.01 0.3 <0.01 (1974) CA 5 <0.01 <0.01 <0.01 <0.01 (1975) 5 <0.01 <0.01 0.02 <0.01 Canada 6 1.1 2% bait 0.24 0.18 (1975) (broadcast) 0 4 7 14 21-28 No. sample cabbage Germany 2 0.12 4% 0 (white (1980) 0.06-0.9 ND-0.56 ND-0.09 ND 3 (0.03) (0.2) (0.05) 4 ND 7 14 21-28 Table 7. (con't) Application Residues (mg/kg) at intervals (days) after application Crop Country Rate No. (Year) No (kg a.i./ha) Formulation 0 1 3 4-5 7-8 10 13-14 15 21 28-35 Untreated samples currants, Germany 3 1 50 WP 12.8 5.7 4.6 2.9 red (1976) 21.7 7.4 6 2.8 6.5 3 1.6 4.3 1.5 0.28 citrus U.S.A. 5 1.1 2% bait Residues were <0.01 ppm in peel or pulp at 30-91 days after last (1975) broadcast treatment on 2 trials on oranges and one each on lemons and grapefruit. grapes U.S.A. (MI, NY, 3-4 2.2 75 WP 2-9 1.8-6.1 1.4-4.0 <0.01-0.09 66 CA) (4.2) (3.3) (2.7) grapes, NY Baco noir (1973) 3 2.2 75 WP grape 1.9 2.9 <0.02 juice 1.7 2.6 <0.02 wine 0.9 2.2 <0.04 Delaware NY 6 2.2 75 WP (1977) grape 2.6 2 <0.02 juice 1.7 1.6 <0.02 wine 1.1 1.0 1.3 Table 7. (con't) Application Residues in mg/kg Crop Country rate days after (Year) no kg a.i./ha formulation last Crop part No. application samples heads leaves whole2 cabbage Canada 5 1.1 2% bait 1 0.2 10 3.1 (1975) broadcast 3 0.4 1.1 0.6 7 0.04 0.8 0.3 untreated 0.06 0.06 0.06 U.S.A. 5-6 1.1 2% bait 1 <0.01-1.1 0.2-5.1 0.08-1.6 8 (1975) broadcast (0.2) (1.7) (0.6) (KS, TX, NY, OR, 3 <0.01-0.17 0.18-3.2 0.08-1.0 7 CA) (0.06) (1.1) (0.4) 7 <0.01-0.05 1.3-15 0.4-4.5 6 (0.02) (8.5) (2.3) untreated <0.01-<0.02 0.01-0.08 <0.01-0.02 6 (<0.01) (0.03) (0.02) Germany 1 0.12 4% 0 ND3-0.34 3 (1978) (0.13) (Savoy) 4 ND-1.7 3 (0.4) 7 ND-<0.05 3 (<0.05) Table 7. (con't) Application Residues in mg/kg Crop Country rate days after (Year) no kg a.i./ha formulation last Crop part No. application samples heads leaves whole2 14 ND-<0.05 3 (<0.05) 21 ND 3 cauliflower Canada 5 1.1 2% bait 1 0.03 0.12 0.05 1 (1975) broadcast 3 0.05 0.60 0.16 1 7 0.05 0.08 0.06 1 untreated 0.01 <0.01 <0.01 1 U.S.A. 5-6 1.1 2% bait (KS, MI, broadcast IN, OR, NY, CA, TX) 1 <0.01-3.0 0.06-6.8 .04-3.5 7 (1975- (0.75) (2.5) (1.5) 1976) 3 <0.01-2 0.04-12.4 0.08-4 6 (0.49) (3) 1.0 7 <0.01-1.1 <0.01-0.3 <0.01-1 6 (0.19) (0.09) (0.18) 8 0.29 11.4 2.4 1 untreated <0.01-0.01 <0.01 <0.01 7 Table 7. (con't) Application Residues in mg/kg Crop Country rate days after (Year) no kg a.i./ha formulation last Crop part No. application samples stem Germany 2 0.12 4% 0 0.3-2.3 0.07-0.8 0.61-5.9 4 (1980) (1.0) (0.41) (3.2) 4 0.1-0.27 0.07-0.36 0.2-1.6 4 (0.18) (0.2) (0.82) 7 0.05-0.14 <0.005-1.3 0.13-4.6 4 (0.09) (0.42) (2) 14 N.D.3 ND-<0.05 ND-0.2 4 28 N.D. ND-<0.05 ND-<0.05 4 cherries USA (OR, MI) 3 4.5 75 WP 0 0.29-2.9 3 1976 (1.4) 3 7 0.21-2.1 (0.9) 14-15 0.08-0.9 3 (0.4) untreated <0.02-0.4 3 (0.12) Table 7. (con't) Application Residues in mg/kg Crop Country rate days after (Year) no kg a.i./ha formulation last Crop part No. application samples heads leaves whole2 (sour) Germany 2 1.9-3.8 50 WP 0 5.4-11.9 4 1974-1976 (9.1) 1 5.9-11.9 2 (8.9) 3 0.8-7.9 4 (3.4) 7 2.3-8.2 4 (3.7) 10 1.8-3.5 2 (2.7) 21 1.2-4.1 2 (2.7) Table 7. (con't) Application Residues in mg/kg Crop Country rate days after (Year) no kg a.i./ha formulation last Crop part No. application samples green forage kernel cob husk corn, sweet U.S.A. (MN, FL, 4 1.1 2% bait 0 0.06-8.2 <0.01-<0.02 <0.01-0.1 <0.01-0.4 11 IN, PA, topical (1.2) (0.13) WI, OR, CA, ID). 1977 1 0.07-1.4 <0.01-<0.02 <0.01-0.02 <0.01-0.6 11 (0.4) (0.13) 3 0.08-2.1 <0.01-<0.02 <0.01-0.03 0.06-0.5 11 (0.6) (0.11) 7 0.07-3.4 <0.01-<0.02 <0.01-0.04 0.02-0.75 11 (0.8) (0.22) untreated <0.01-0.04 <0.01-0.02 <0.01-<0.02 <0.01-0.02 10 Table 7. (con't) Application Residues in mg/kg Crop Country rate days after (Year) no kg a.i./ha formulation last Crop part No. application samples shelled grain corn, field U.S.A. 4 1.1 2% bait 9 <0.03 1 1977 topical untreated <0.03 1 maize Germany 8 1979-1970 1 500/g 50 WP 144-219 ND5 100 kg seed lettuce Germany 1 0.12 4% 0 ND3-0.24 7 (1970) (0.1) 3-4 ND-0.1 7 (.05) 7 ND-0.1 6 (<0.05) 10 ND-0.5 7 (0.09) 14 ND 4 Table 7. (con't) Application Residues in mg/kg Crop Country rate days after (Year) no kg a.i./ha formulation last Crop part No. application samples outer or wrapper other head leaves leaves whole U.S.A. 5 1.1 2% bait 1 0.01 0.1 8.3 2.3 (1976) (band 3-4 0.03 11 1.3 2.6 side-dress 7 0.03 1.1 12.2 3.7 untreated 0.02 <0.01 <0.01 <0.01 FL 5 1.1 2% bait 3-4 1.8 (1976) band between rows outer or wrapper other head leaves leaves whole TX, AZ 5-6 1.1 2% bait 1 <0.02-7.1 0.1-12.7 0.18-5.5 0.02-6.5 67 FL, NJ, CA (broadcast) (1.4) (4.1) (2.4) (2.5) (1976- 1980) 3-4 <0.01-2.1 0.05-59 0.05-20 <0.02-30 6757 (0.5) (12.3) (5) (2.5) Table 7. (con't) Application Residues in mg/kg Crop Country rate days after (Year) no kg a.i./ha formulation last Crop part No. application samples outer or wrapper other head leaves leaves whole 7 <0.01-1.3 0.03-14 0.02-52 <0.02-11 57 (0.3) (5.7) (19) (3.7) untreated <0.01-0.11 <0.01-0.13 <0.01- <0.01- <0.02 0.12 57 peaches Canada 8 1.1 75 WP 7 6.6,20.5 (1973) foliar 14 3.8,13.5 21 2.3 4.7 untreated <0.05,0.08 U.S.A. (1973) 4-7 1.1 75 WP 0 14-18.9 (WVA, WA foliar (11.5) 2 NC, SC, CA) 3 18 1 7 5.4-23 (11) 6 14 1.8-11 6 (7) Table 7. (con't) Application Residues in mg/kg Crop Country rate days after (Year) no kg a.i./ha formulation last Crop part No. application samples 21 0.7-10 8 (5.3) untreated <0.03-0.22 8 (0.05) potatoes Germany (1972) 1 0.3 50 WP 14-28 ND5 6 prunes Germany 3 1 50 WP 0 0.6-1 3 (1976) (0.8) 14 0.5-0.7 3 (0.6) 21 0.4-0.8 3 (0.6) 28 0.3-0.5 3 (0.4) 35 0.3-0.6 3 (0.4) rape Germany 3 0.12 4% 0 ND3-5.0 (1980) (1.1) 4 14 ND-0.54 2 (0.3) Table 7. (con't) Application Residues in mg/kg Crop Country rate days after (Year) no kg a.i./ha formulation last Crop part No. application samples 20-21 ND-<0.05 3 (<0.05) 61-108 ND 5 grain straw rice, U.S.A. domestic (1977) 1 0.5 lb. 75 ST 105 0.03 0.14 (LA, MS, a.i. per i TX, AR) 100 lb. 119 0.24 0.84 seed 141 0.01 0.32 147 0.11 <0.01 untreated 0.02-0.4 0.05-0.9 processed hulls rice, wild U.S.A. (1977) 2 2.2 75 WP 7-10 0.06 1.2 MN post- emergence 14 0.08 0.11 broadcast untreated 0.14 0.04-0.09 Table 7. (con't) Application Residues in mg/kg Crop Country rate days after (Year) no kg a.i./ha formulation last Crop part No. application samples grain, green straw U.S.A. 2 2.2 75 WP 0 21-48 4.6-20 2 (1977) aerial 1 25-89 9.4-11 2 MN post- 3 12-18 5-6.2 2 emergence 7 6.6-18 3.9-10 2 10 6.8-23 0.6-8.4 2 untreated 0.1-1.6 0.04-0.05 spinach Germany 1 0.12 4% 0 ND5-1.8 4 (1978) (0.9) 4-21 ND 9 Strawberries Germany 1 0.12 4% 0 ND5 (under-glass (1974) 2 under 3-4 ND 6 plastic, 7-10 ND 6 and 14-21 ND 3 unspecified) Leaves roots sugar Germany 1 900g/100kg -- 135-136 ND5 ND5 2 beets (1971) seed 178-185 ND ND 3 Table 7. (con't) Application Residues in mg/kg Crop Country rate days after (Year) no kg a.i./ha formulation last Crop part No. application samples Tomatoes Canada 5 1.1 2% bait 0 <0.01 (1975) broadcast 7 0.05 U.S.A. 5-6 (FL, KS, 1.1 2% bait 0 <0.01-0.42 8 NY, TX, broadcast (0.06) IN, AZ, CA, WI) 1 <0.01-0.08 7 (0.03) 3-4 <0.01-0.07 8 (0.02) 7 <0.01-0.3 8 (0.08) untreated <0.01-0.1 9 (0.02) fruit dry pulp puree juice Tomato USA 6 1.1 2% bait 0 <0.02 <0.02 <0.02 <0.02 2 CA broadcast (1977) Table 7. (con't) 1 Residues given as <method sensitivity counted as 1/2 method sensitivity for mean; 2 estimated from a 2.5 head to leaf ratio; 3 ND = not detected with a method sensitivity of 0.05 ppm; 4 estimated from a 4.05 head to leaf ratio; 5 ND = not detected with a 0.02 ppm method sensitivity; 6 at each interval; 7 the number of samples given is for whole; for head, 5-6; for outer/wrapper leaves, 5-7; for other leaves, 3-4. * Table based on submissions to the 1981 JMPR by Bayer AG and Mobay. Beans Whether there are nationally-approved good agricultural practices could not be determined. Multiple applications of a 2% bait according to proposed good agricultural practices resulted in maximum residues of 0.46, 0.35 and 0.5 mg/kg, respectively, for beans (snap and lima), pods and vines at or after the zero to one day intervals from last application. Data were representative of seven states in the USA and one site in Canada. A one-day pre-harvest interval is proposed. Up to 15 months elapsed between last application and analysis. Blueberry When treated according to good agricultural practices, maximum residues were 25.6 mg/kg on last day of application. Samples were analysed up to one year after last application by methodology sensitive to 0.01 mg/kg. Maximum control values were 0.27 mg/kg. Summary residue data from trials in New Zealand at 1-2 times proposed good agricultural practices indicated residues can be up to 30 mg/kg at 7 days (New Zealand 1981). Broccoli Whether there are nationally-approved good agricultural practices could not be determined. Maximum residues after multiple applications according to proposed or recommended application rates were 0.26 mg/kg and 0.44 mg/kg respectively for the heads and leaves at one day after last application and 0.1 mg/kg and 2 mg/kg on heads and leaves at 3-4 and 7-8 days respectively when analysed with a method capable of 0.01 mg/kg sensitivity. Maximum control values were < 0.02 mg/kg. The proposed pre-harvest interval is zero days. Up to one year elapsed from last application to analysis. Brussels sprout Whether there are nationally-approved good agricultural practices could not be determined. When multiple applications of a bait formulation was applied according to proposed or recommended rates for brassica leafy vegetables in four sites in the USA and one in Canada, maximum residues were 0.38 mg/kg at a one-day pre-harvest interval. The proposed use on brassica leafy vegetables would allow use on day of harvest. Maximum apparent residue on controls was < 0.01 mg/kg (method sensitivity); up to 1.5 year elapsed from last application to analysis. Errors were made in one set of data which were listed as being from two different sites. Cabbage Whether there are nationally-approved uses for methiocarb on cabbage could not be determined. When multiple applications of a 2% bait formulation were applied to several varieties of cabbage at rates approximating proposed uses, maximum residues one day after last application (the nearest to the zero or one day pre-harvest intervals proposed) were 3 mg/kg on a whole head basis. Maximum apparent residues on control were 0.08 mg/kg. However, maximum residues at seven days were 4.5 mg/kg estimated on a whole head basis, with head to leaf weight ratios generally 2.45 to 3.9. There was an unexplained trend of increasing residues from one day after last day of application to seven days for the whole head basis and on the leaves for four out of the nine studies. These increases were by a factor range of 2 to 15 and suggest increasing plant uptake of soil residues with time. The analytical method employed was capable of detection at 0.01 mg/kg. Up to one year elapsed from last application to analysis. When a 4% formulation was applied at rates of 0.6x the proposed/recommended rates for vegetables, maximum residues at the proposed/recommended 14-day pre-harvest interval was < 0.05 mg/kg. Maximum residues at day of last application approach 1 mg/kg. The analytical method used in these studies had a sensitivity of 0.05 mg/kg. Cauliflower At one day or longer after the last day of up to six broadcast applications of a 2% bait to several varieties of cauliflower in Canada and seven states in the USA, at maximum proposed/recommended rates, maximum residues of methiocarb on whole plant, head and leaves were 4, 3 and 12.4 mg/kg respectively. The residue of the whole plant was calculated from a 4.05 head/leaf weight ratio. Proposed uses allow for harvest on day of last application. The maximum values for controls were at the 0.01 mg/kg analytical sensitivity. Up to 10 months elapsed between harvest and analysis. Maximum residues from recommended/proposed uses of an unspecified country at 0.6x the maximum proposed/recommended rates at the 14-day interval recommended were N.D. (method sensitivity 0.05 mg/kg), 0.2 and < 0.05 mg/kg for the head, stem and leaf respectively. Cherry Maximum residues on two varieties of cherries from maximum approved USA good agricultural practices application rates and 7-day pro-harvest interval were 2.1 mg/kg. Maximum control values were 0.35 mg/kg with an analytical sensitivity of 0.04 mg/kg. At rates approximating (1.6x) other proposed/recommended good agricultural practices for small fruits, the maximum average residue at 7 days from 1 application (up to three recommended) was 8.2 mg/kg (method sensitivity 0.05 mg/kg). Summary residue data reflecting 1-2 times New Zealand good agricultural practices gave up to 12 mg/kg at 7 days (New Zealand 1981). Maize When maize seed was treated in eight studies in one country according to good agricultural practices (approved and/or recommended) in three countries, residues were not detected at 114 to 219 days after one treatment before planting, by a method with an analytical sensitivity of 0.02 mg/kg. When sweet corn was topically treated four times at maximum proposed rates with a 2% bait in eight states of the USA, maximum residues were 8.2, <0.02, 0.1 and 0.75 mg/kg for the forage, kernel, cob and husk respectively at the milk stage and 0 to 7 days after last treatment. Proposed uses permit harvest on day of last application. The analytical capability was 0.01 mg/kg and maximum control values were 0.04, 0.02, < 0.02 and 0.02 mg/kg respectively for the forage, kernel, cob and husk. A similar treatment on field corn gave residues of less than 0.03 mg/kg on the shelled grain 9 days after last treatment. The interval from last application to analysis ranged up to one year. Currant, red The maximum residue on red currants at the 21-day pre-harvest interval proposed/recommended for small fruits was 6 mg/kg from three studies in one country after three treatments with 50 WP. It could not be determined whether the rate used was consistent with proposed/ recommended good agricultural practices, as application rates in the field and recommended good agricultural practice information were in different units. Citrus At 31 to 91 days after the last of five broadcast treatments of grapefruit, lemon and orange at fruit set and at proposed application rates, maximum residues were < 0.01 mg/kg in both the peel and the pulp of treated and control samples. The proposed pre-harvest interval is 31 days. Up to 15 months elapsed from last application to analysis. No residue data were available from approved uses. Grape When five varieties of grapes were treated in three states in the USA according to proposed good agricultural practices, maximum residues at the proposed 7-day pre-harvest interval were 4 mg/kg on grapes, and at 10 days, 2.6 mg/kg in juice and 2.2 mg/kg in wine. There were no residue data available on grape pomace. Up to 18 months elapsed from last application to analysis. Residues were up to 2 mg/kg from application rates of 1 to 2 times New Zealand good agricultural practices (New Zealand 1981). Lettuce No confirmed, approved good agricultural practice information was provided to the Joint Meeting, although the recommended use on vegetables in an unspecified location is listed as one to two broadcasts at 0.12-0.2 kg/ha a.i., formulation unspecified, and a 14-day pre-harvest interval. Data from the Federal Republic of Germany, representing one application of a 4% formulation at the lower rate, were provided. At the 14-day interval no residues (< 0.05 mg/kg according to method sensitivity) were detected in the four trials with 14-day interval, although one study had residues of 0.5 mg/kg at 10 days. The latter value was not consistent with data < 0.05 mg/kg) in the same study at early intervals, although this is not necessarily unexpected. Data from five studies in the USA, representing proposed uses of 5 broadcast or side band applications of a 2% bait at 1.1 kg a.i./ha, were available. Harvest on day of application is proposed. These data were for the head, wrapper leaves, "other leaves", whole, or outer leaves and were for intervals after application of 1 to 7 days. Residues for the whole plant were estimated from the parts (head to leaf weight ratios varies from 0.65 to 3), and the maximum residue at one day after last application was 6.5 mg/kg. However, as in the case of cabbage, in about one half the studies, residues were higher at intervals later than the one day after last application. The maximum residue (on the whole plant) was 29.5 mg/kg at three days. This suggests uptake by the plant with time. This high one-day value may be atypical. The next highest value is 11 mg/kg at three or seven days. Maximum residues on wrapper leaves were up to 58 mg/kg. The maximum value for untreated samples (whole basis) was 0.12 mg/kg although most were < 0.02 mg/kg. The analytical method was capable of sensitivities of 0.01 mg/kg and interval from last application to analysis was up to 13 months. The values for the "head" and leaves may be somewhat low because of the relative amount of wrapper or other leaves removed. Therefore, limits based on the head residue values would be somewhat misleading. Peach Two residues studies from Canada and six from the USA representing approved good agricultural practices were available. Maximum residues at the approved 21-day pre-harvest interval were 10 mg/kg. Maximum apparent residue in untreated samples was 0.22 mg/kg although they were generally < 0.08 mg/kg, even on the samples with the high value, when analysed by a different analytical procedure. Potato Approved national uses could not be confirmed. No residues could be detected at the 14-day pre-harvest interval recommended (apparently in the Federal Republic of Germany) when one of two permitted spray applications of a wettable powder formulation were made. The analytical sensitivity was 0.02 mg/kg. These minimal data are not sufficient to estimate maximum residues. Prune Whether there are nationally-approved good agricultural practices for use of methiocarb on prunes could not be determined. Residue trials conducted at application rates of 1 kg a.i./ha (0.05%) resulted in maximum residues of 0.8 mg/kg at the recommended 21-day pre-harvest interval. These application rates approximate recommended rates of 0.05 to 0.075% for stone fruit. These data are too minimal as a basis for estimating maximum residue limits. Rape Whether there are nationally-approved good agricultural practice for the use of methiocarb on rape could not be determined, except for one country from which no residue data were provided. When two applications of a 4% formulation was applied to rape at 0.12 kg a.i./ha (0.12-0.200 kg/ha recommended), no residues (<0.05 mg/kg) were detected at intervals approximating the recommended 90 days after last application. These application rates were thus only 0.6x the maximum recommended and would not be all adequate basis for estimating maximum residue. Rice Whether there are nationally-approved good agricultural practices for the use of methiocarb on rice could not be determined. Maximum residues at 105 to 147 days after the last application of a seed treatment at approximately 2x proposed/recommended rates were 0.24 mg/kg in grain and 0.84 mg/kg in the straw. Maximum apparent residues in untreated controls were 0.44 mg/kg in the grain and 0.84 mg/kg in the straw, although the untreated samples corresponding to the maximum residues in treated samples had substantially less apparent residue. When wild rice was treated according to proposed uses (with last application at late dough stage) maximum residues on day of last application were 48 mg/kg in the green grain. Maximum residues for the processed grain at 10 to 14 days after last application were 0.08 mg/kg (less than the 0.14 mg/kg in untreated samples). In the absence of more specific information on pre-harvest intervals, a zero-day interval must be assumed. Up to seven months elapsed from last application to analysis. These minimal data from one geographic location are inadequate for estimating maximum residues in wild rice. Spinach Whether there are nationally-approved good agricultural practices could not be determined. At 0.12 kg a.i./ha (proposed/recommended rate is two applications at 0.12 to 0.2 mg/kg for vegetables) no residues were detected using an analytical method with a limit of sensitivity of approximately 0.03 mg/kg at the recommended 14-day pre-harvest interval. These data are inadequate for estimation of maximum residues in terms of number of applications, quantity and as being representative of maximum recommended uses. Strawberry Whether there are nationally-approved good agricultural practices could not be determined. After a single application at rates 0.6 to 0.8x that recommended for a 4% formulation, no residues were detected from 0 to 21 days after last application. Recommended uses allow two applications. The analytical method was capable of measuring residues at approximately 0.02 mg/kg. No data were available for proposed uses of other formulations. Although only one application was made, the absence of residues at any level through the recommended 14-day interval suggests a limit at or about the method sensitivity of 0.02 mg/kg would be adequate for the recommended use. Sugarbeet Whether there are nationally-approved good agricultural practices could not be determined, except for one country from which no residue data were available. No residues (<0.02 mg/kg method sensitivity) were detected in the roots or leaves of sugarbeets at 135 to 185 days after seed treatment according to recommended usage. Tomato Whether there are approved national good agricultural practices for methiocarb uses on tomatoes could not be confirmed. No data were available for recommended/proposed uses on vegetables. Data were available for proposed use for 2% bait broadcast applications in North America where harvest on day of last application is proposed. Maximum residues were 0.42 mg/kg at day of application. Two processing studies were available in which the dry pulp, puree and juice of treated tomatoes were analysed, but these were not adequate for conclusions on the potential for residue concentration as the fruit that was processed did not have significant residues. FATE OF RESIDUES General Methiocarb is readily metabolized or degraded in the environment by plants, animals and microorganisms. While hydrolysis and oxidation are the principle paths for these chemical changes, the conditions of a particular situation determine the order and relative importance of these processes. Table 1 identifies metabolites and degradation products of methiocarb and provides abbreviated designations which are used in Figure 2, in which methiocarb metabolic routes are summarized. Similar analytical approaches have been used for determination of the fate of methiocarb. Typically, extractions of tissues, excretory products, milk etc. were made with organic solvents for extraction of non-conjugated moieties followed by enzymatic and/or acid hydrolysis of aqueous fractions to release conjugates. Analyses were by thin layer, radiometric, and scintillation techniques. In plants Methiocarb uptake, distribution and metabolism in lettuce and tomato plants were studied for up to 14 days and up to 56 days in tomato fruit. Direct soil or nutrient solution applications of (ring- l-14C)-methiocarb 75 WP were made at rates equivalent to 1 lb. a.i./acre (1 lb/acre = 1.121 kg/ha) (Strankowski and Murphy 1976). Radioactivity was rapidly taken up by tomato and lettuce plants, being translocated throughout within one day, levelling off at seven days in lettuce and continuing. Over 40 to 50% of applied radioactivity was contained in the plants within two weeks, with the organic soluble portion decreasing from 75 and 81% of total activity at one day respectively in lettuce and tomato plants, to 6 and 13% after two weeks. Radioactivity in the aqueous phase, on the other hand, increased from 25 and 19% at one day to 94 and 87% respectively on day 14. Organic phase residues in the plants at day one were 30 to 50% methiocarb sulphoxide, 15-20% methiocarb, and in tomato plants, also 6% methiocarb sulphoxide phenol. Predominant tissues in the aqueous phase after hydrolysis are methiocarb phenol and its sulphoxide phenol, with lesser amounts of methiocarb, its sulphoxide, sulphone and sulphone phenol. In the tomato fruit study, radioactivity was up to 12 mg/kg methiocarb equivalent in the leaves at day 28 (96% water soluble) and up to 0.1 mg/kg in fruit. No methiocarb or carbamate metabolites were detected in the organosoluble phase. The non-carbamate residues were not identified. Greenhouse-grown rice was treated in one study with one application of (ring-l-14C)-methiocarb 75 WP at a rate of 1 lb a.i./acre at planting to simulate seed treatment and in another with 1-2 foliar applications (Strankowski 1979) at 2 lb a.i./acre at soft dough stage. As in the case of soil-treated tomatoes and lettuce, radioactivity from the simulated seed treatment was steadily taken up through the 35-day test period (21% of applied in the rice stalks at day 35). From the foliar treatment, radioactivity decreased through the post-application period to about 12% of zero day radioactivity in the grain and to 20 to 60% in stalk at day 28. Surface rinses of the
grain indicated methiocarb penetration into the grain. Also as in the case of lettuce and tomato plants, organosoluble residues in plant or grain decreased with time after treatment. The predominant over-all residue distribution at day 28 in rice plants and grain from these studies show a decrease of methiocarb from > 90% at day zero to 2 to 20% at day 28; an increase in methiocarb sulphoxide from 2 to 6% at day zero to approximately 35% and an increase of methiocarb phenol conjugate and methiocarb sulphoxide phenol from none to approximately 10%, all in the same period. There were lesser amounts < 3%) of other metabolites at day 28. The hydroxymethyl methiocarb sulphoxide occurred up to about 3%. A metabolism study and a cumulative residue study were conducted on apples (Morgan and Parton 1974). In the metabolism study a single 50% ethanol solution syringe application of (ring-l-14C)-methiocarb and methiocarb (1:1 ratio) was made to each of 37 apples at a combined rate of 2 mg/apple with no run-off. Samples of three apples or more were analysed at intervals from 0 to 43 days post-application. As a percent of that applied, radioactivity declined from 94% at day zero to about 30% at day 17, where it levelled off for the duration of the 43 days. The bulk of observed residue was surface residues removable by a benzene wash (from 99% on day zero to around 60 to 65% after day 29) and was said to consist of 96 to 100% methiocarb and the rest its sulphoxide. As a percent of applied radioactivity, the decline was more rapid, down to about 20% after day 29. Following the pattern on other plants, the water soluble residues increased with time in peel and pulp relative to organsolubles. Total analysis of the 43-day residue was methiocarb 65.3%, methiocarb sulphoxide 9.4%, methiocarb sulphone 0.4%, methiocarb phenol 18%, methiocarb sulphone 0.8% and water soluble unknown 1.5%. In the residue study, eight syringe applications of a 75 WP methiocarb formulation (1:9 ratio (ring-l-14C)-methiocarb:methiocarb) were made to each of 24 apples to run-off at a rate equivalent to 1.5 lb. a.i./100 gal. (1 lb/US gal = 120 g/l). Apples were sampled throughout and up to day 14 after the last application. Residues peaked at about 3 to 8 mg/kg after the fourth treatment. With approximately 95% of the residue identified, the over-all distribution 14 days post-application (77 days from initial application) in terms of percent and mg/kg (methiocarb equivalents) was methiocarb 61 (2.7), methiocarb sulphoxide 7 (0.3), methiocarb sulphone 0.1 (0.0), methiocarb phenol 4.6 (0.2), methiocarb sulphoxide phenol 22.1 (1.0), methiocarb sulphone phenol 1.1 (0.05) and unknowns < 5 (0.2). Therefore, methiocarb is the predominant residue shortly after application and up to 14 days post-application, and while methiocarb phenol was the second largest residue in the metabolism study, the sulphoxide phenol is second in the residue study (14 days post- treatment or 77 days from initial application). The primary metabolic route in plants, therefore, appears to be methiocarb -> its sulphoxide -> sulphoxide phenol -> glycosidic conjugation with a minor route of methiocarb -> its phenol -> phenol conjugate. The relative abundance of any one moiety varies with time and crop. In animals The metabolism of methiocarb in rats (Gronberg and Everett 1964 and Stanley and Johnson 1926) and in dogs (Bell 1974) is discussed under "Biochemical Aspects". The animal studies discussed in this section indicate that the primary difference between liver and kidney metabolism in the cow and hen is less methiocarb phenol in chicken liver and kidney but higher overall methiocarb equivalent residues in chicken tissues than in that of cows. It is also noteworthy that N-hydroxymethyl methiocarb sulphoxide is an analytically significant residue in chicken tissues, especially in muscle. Apparently no attempt was made to identify the hydroxy metabolites during the cow studies. Hydrolysis and conjugation were the major metabolic routes in liver and kidney of chickens whereas oxidation was also important in fat skin, and muscle. Cow In two studies a dairy cow was dosed with (ring-l-14C)methiocarb (Minor and Murphy 1977a,b). Details are reported under "Biochemical Aspects". In the first study maximum radioactivity in milk peaked at 0.02 mg/kg (methiocarb equivalent) at 24 to 32 hours post-treatment. One week later, the same cow was dosed in the same manner. Maximum radioactive residues in milk were 0.06 mg/kg methiocarb equivalent. Nineteen percent of the radioactivity in milk was organosoluble although most of this residue was unidentified. Only methiocarb sulphoxide was positively identified in this fraction. Another 9% was precipitated in a coagulation step. About 56% of the milk radioactivity in the form of conjugates was released by enzyme and acid hydrolysis. Most of this 56% was equally divided between methiocarb sulphoxide phenol and methiocarb sulphone phenol with a < 1% each of methiocarb, its sulphoxide, its phenol, and an unknown. In tissues, radioactive residues were 0.11 mg/kg in kidney, 0.07 mg/kg in liver, approximately 0.01 mg/kg in udder, heart and renal fat and < 0.01 mg/kg in round, shoulder, loin, brain and omental fat. Therefore, only kidney and liver contained sufficient residues for further characterization. The distribution of residues in kidney and liver and the relative portions which are organosoluble or requiring hydrolysis for release of conjugated moieties are given in Table 8. it can also be seen in Table 8 that methiocarb phenol is the principal metabolite in liver and kidney (25 and 55% respectively). While methiocarb sulphoxide phenol and methiocarb sulphone phenol are also present in analytically significant amounts in liver and kidney, methiocarb, its sulphoxide and to a lesser extent its sulphone, occur in analytically significant amounts in the liver but not in kidney. Methiocarb, together with its carbamate metabolites, accounted for no more than 0.02 mg/kg in any tissue. TABLE 8. Percent distribution of radioactivity among methiocarb and its metabolites extracted from kidney and liver tissue of a dairy cow dosed five times with (ring-1-14C)-methiocarb Percent distribution Kidney Liver Compound Acid Acid Organosoluble reflux Organosoluble reflex Methiocarb <1 0 12 2 Methiocarb sulphoxide 0 0 4 3 Methiocarb sulphone <1 0 <1 1 Methiocarb phenol 11 44 14 11 Methiocarb sulphoxide phenol 7 0 7 2 Methiocarb sulphone phenol 16 1 3 3 Origin unknown 2 1 3 9 Total extractable 38 46 44 30 Beef and dairy cattle were fed rations containing 10 (0.3 mg/kg bw/day), 30 and 100 mg/kg methiocarb for 29 days, three cows at each feeding level (Mobay 1970). Milk was collected on the days 28 and 29 of feeding and cattle sacrificed on day 29 for tissue analyses. A copy of the method used was not provided, although it is known that the procedure measures methiocarb, its sulphoxide and sulphone as one gas chromatographic response after oxidizing the sulphone and silylating. It is apparently basically the same procedure as that of Thornton and Drager (1973). As such, it would not be expected to determine conjugated residues as there is no hydrolysis step. For this reason, up to 50% of the total residue may not have been determined in some tissues. Phenolic metabolites, the major part of the residue in some tissues, may not have been determined if extracted. It cannot be concluded whether the hydroxy metabolites would have been determined. Except for one 0.05 mg/kg residue in heart at the 100 mg/kg feeding level, residues in steak (loin, round, flank) heart, brain and fat (omental, renal, back) were < 0.05 mg/kg at the 10 to 100 mg/kg feeding levels. Residues (mg/kg) in milk, liver and kidney are given in Table 9. TABLE 9. Residues recovered from cattle tissues and milk after methiocarb feeding No. samples Dose level Milk Liver Kidney Each Milk tissue 10 <0.05-0.007 <0.05 <0.05 3 6 (mean <0.005) 30 0.008-0.02 <0.05,<0.05, <0.05 3 6 (mean 0.014) 0.08 (mean <0.05) 100 0.021-0.033 <0.05,0.09,0.1 <0.05,0.06,0.08 3 6 (mean 0.026) (mean 0.07) (mean 0.06) control <0.05 <0.05 <0.05 1 9 Hen Eight White Leghorn hens were given a single dose of (ring-l- 14C)-methiocarb by intubation at 4.4 mg/kg bw and the excreta and eggs monitored at regular intervals up to 96 h post-treatment (Stanley et al 1979). About 84% of the dose was excreted within 24 h and only 1% more in the next 72 h. Thirty-four percent of the dose was found in the excreta as non-conjugated methiocarb, methiocarb phenol, methiocarb sulphoxide phenol, methiocarb sulphone phenol, and hydroxymethylmethiocarb sulphoxide with a distribution of < 1, 13, 9, 7 and 2% of the dose respectively. Of the 49% of the administered dose in the aqueous excreta fraction, 41% was released by acid hydrolysis. Methiocarb phenol, methiocarb sulphoxide phenol and methiocarb sulphone phenol released by the acid hydrolysis constituted 21, 1 and 10% respectively of the applied dose. The remaining 17% of the dose in the aqueous fraction was not identified. In the combined eggs, maximum radioactivity peaked at 6 to 24 h after administration of the dose and was 0.02 mg/kg methiocarb equivalents. The residues in eggs were not further characterized. Three weeks later, these same hens were dosed by tube at the same level with (ring-l-14C)-methiocarb for each of five consecutive days and sacrificed for tissue studies (Stanley et al 1979a). Radioactive methiocarb equivalent were: kidney 3.3 mg/kg, liver 2.0 mg/kg; gizzard (including lining), 7.7 mg/kg; fat, 0.7 mg/kg; skin, 1.3 mg/kg; breast muscle, 0.4 mg/kg; leg muscle, 0.5 mg/kg; heart, 0.8 mg/kg and egg, 0.02 - 0.08 mg/kg. Because residues in eggs were < 0.1 mg/kg, they were not further characterized. Non-conjugated residues as a percent of residue in the specific tissue ranged from 28% in kidney to 84% in the gizzard and residues released used by acid hydrolysis ranged from 3% in the gizzard to 47% in the kidney. Unidentified residues remaining in solids or unreleased by acid hydrolysis accounted for 25, 19, and 13% of radioactivity in kidney, liver and fat respectively with 7% or less in other tissues. Although all compounds listed in Table 1 except methiocarb sulphone were identified in varying concentrations in one or more tissues, the major residues as a percent of radioactivity in each tissue (abbreviations as in Table 1) according to non-conjugated and acid released conjugates respectively were as given in Table 10. TABLE 10. Residues recovered from hen tissues after dosing with (ring-l-14C)-methiocarb Tissue Non-conjugated conjugates Kidney MSOP 11% MSOP 18%, MP 13%, HMSO 3% Liver MSOP 17% MP 10%, MSOP 7%, HMSO 6% Gizzard(with lining) M 75% < 1% MP, MSOP, MSO2P Fat M 41%, MP 14% MP 12% Skin M 16% MP 30% Breast muscle MSOP 24%, HMSO 17% MP 8% Leg muscle MSOP 15%, HMSO 18% MSOP 9%, MP 6% Heart HMSO 16% MP 32% Hens were fed, ad libitum, with methiocarb/methiocarb sulphoxide (9:1) at 20, 60, 120 and 360 ppm in the diet for 28 days, four hens per feeding level and for controls (Strankowski and Minor 1976). Giblets (heart, gizzard, liver), muscle (composite), skin, fat tissues (composite) and eggs (collected on the even and last three days) were analysed. While the method used was not provided, it is known that it measures methiocarb and its sulphoxide by oxidation both to the sulphone, hydrolysis to the sulphone phenol and silylation for gas chromatographic detection and with a reported sensitivity of 0.02 mg/kg. Except for 0.02 mg/kg in skin at the 360 mg/kg feeding level, average residues were < 0.02 mg/kg in muscle, skin and fat at all feeding levels and in all tissue controls. Average residues in giblets were 0.13, 0.13, 0.06 and < 0.02 mg/kg at the 360, 120, 60 and 20 mg/kg feeding levels respectively. Residues on individual tissues were not available. Residues in eggs were < 0.02, < 0.02, <0.02, < 0.02 to 0.03, and 0.03 to 0.06 mg/kg in controls, feeding levels 20, 60, 120 and 360 mg/kg respectively. In soil Adsorption and desorption Absorption and desorption of (ring-l-14C)-methiocarb of an aqueous solution by loam soil was studied over a concentration range of 0.25 to 4.8 mg/ml (Atwell and Murphy 1978). Ten gram air-dried soil samples with 3% moisture were treated with 50 ml pH 6 buffered test solution and shaken at 25°C for 16h before analysis. Residue absorbed was determined by the residue in the decant vs. the initial concentration. Desorption was conducted similarly, using a pH 6 buffered solution, the most stable pH for methiocarb. Equilibrium was established at 7 to 9 and 9 to 11 h for adsorption and desorption respectively. Under the test conditions 70 to 82% were adsorbed over the concentration range, decreasing from the highest to the lowest as the concentration increased. Desorption was proportional to the amount adsorbed and ranged from 17 to 22% from over the 10 to 170 mg/kg range of soil-adsorbed methiocarb. Freundlich constants were k=12.6 and l/n=0.8. Leaching (Ring-l-14C)-methiocarb was applied to thin layers of six soils (ranging from sand to loam to clay), one from each of six states in the USA and compared with 23 other pesticides for leaching behaviour on the basis of Rf values (Thornton et al 1976). On a scale of 1.0, the Rf of methiocarb ranged from 0.22 to 0.42 (mean 0.33) in the six soils and was considered to be of low relative mobility. Other pesticides ranged from an Rf of 0.01 to 0.02 for DDT to 0.91 to 0.99 for trichlorfon. The mobilities were directly related to water solubility. (Ring-l-14C)-methiocarb was applied to 30 cm × 7.6 cm segmented columns containing six soil types with organic matter ranging from 0.6 to 77% and eluted with 50 cm of water at the rate of 2.5 cm per hour (Houseworth and Tweedy 1974). Radioactivity was leached, but in three of the soils > 70% remained in the top two inches of soil. Leaching was generally inversely related to organic matter. Radioactivity was found in the leachate of only the sandy loam, and this could have been due to the pH of 8 and possible degradation of methiocarb. The other soils had a pH of < 6.2. The same authors (Tweedy and Houseworth 1974) also eluted 30 cm high columns of aged sandy loam topped with (ring-l-14C)-methiocarb with distilled water at a rate of 0.5 acre. inch/day (1 acre. in = 1 ha.cm) for 45 days. The top one third of the column contained 91.2% of the radioactivity while 5% was in the leachate. Persistence Methiocarb 50 WP was sprayed at a rate of 20 lb a.i./acre onto two soil plots and incorporated to a depth of 9 to 15 cm to achieve a theoretical concentration of 10 mg/kg (Mobay 1973). Samples were taken from the 0 to 9 cm depth and analysed for methiocarb, methiocarb sulphoxide and methiocarb sulphone, in total, at various intervals in a period from 0 to 370 days. The methiocarb residue half-life was approximately 15 days in silt loam and approximately 45 days in clay. Residues ranged from 5 mg/kg at zero day to < 0.25 mg/kg at 370 days. A second set of three soil plots was sprayed twice with methiocarb 75 WP at a rate of 20 lb a.i./acre with a one-year interval between the applications (Mobay 1974). The applications were incorporated, and the soil was sampled and analysed as described previously. The methiocarb half-life in these plots (two sandy loams and one silt loam) ranged from 15 to 50 days and residues ranged from 28 mg/kg at day zero to 0.13 mg/kg at 343 days. Two additional studies were concluded with methiocarb 2% bait or methiocarb 75 WP applied in broadcast fashion to the soil at a rate of 5 lb a.i./acre (Mobay 1979-81). Subsequent soil samples taken from both the 0 to 15 cm and 15 to 30 cm depths were analysed for methiocarb, methiocarb sulphoxide and methiocarb sulphone individually. In these studies methiocarb residues declined rapidly (from a maximum residue of 4.7 mg/kg at the 0 - 15 cm depth), while the residues of methiocarb sulphoxide and sulphone rose to maximum peak levels of 0.6 mg/kg and 0.3 mg/kg respectively at 30 to 82 days and then also declined to less than 0.1 mg/kg each by 365 days and < 0.02 mg/kg each in all cases by 553 days. The half-life of methiocarb for each of the soils varied between 6 and 64 days. Although some residues do occur in the 15 to 30 cm depth (up to a combined residue of 0.4 mg/kg), at the zero-time samplings the combined residue was generally well below 0.1 mg/kg. This suggests that methiocarb and its carbamates do not have a strong propensity for leaching. Rotational crops A radioactive rotational crop study was performed in greenhouse planters to test for possible residues from (14C)-methiocarb in crops planted 30, 120 and 365 days (601 days for wheat) after a (ring-l- 14C)-methiocarb 75 WP soil treatment at a rate equivalent to 5 lb a.i./acre (Strankowski and Parker 1981). Radioactive residues in the soil declined from 0.934 to 0.623 mg/kg methiocarb equivalents during the two-year study, while the actual carbamate residue decreased from 0.828 to 0.121 mg/kg methiocarb equivalents during the same period. The rotational crops contained radioactive residues at harvest, but only a portion of this residue could be attributed to intact carbamates. Maximum total radioactivity as methiocarb equivalents decreased in mature crops over the course of the study (30 to 365 day plantings) 5.7 to 0.3 mg/kg in wheat heads, 7.8 to 0.6 mg/kg in wheat stalks, 64 to 3 mg/kg in wheat forage, 1.4 to 0.2 mg/kg in beet tops, 0.3 to 0.1 mg/kg in beet roots, and 2 to 0.2 mg/kg in kale. Total carbamate residues made up 19 to < 1% (1.9 to < 0.006 mg/kg) of total residues. Methiocarb sulphoxide was the principal carbamate found, along with small amounts of its sulphone, N-hydroxymethyl sulphoxide, and N-hydroxymethyl sulphone. As radioactive residues were detected in these greenhouse-grown rotational crops at levels higher than expected, a field study, using formulated products, was undertaken to determine if residues would occur in subsequent crops under actual use conditions (Murphy and Morris 1979; Mobay 1977-81). Methiocarb 75 WP was applied at rates of 1.25, 2.5, 5 and 10 lb. a.i./acre to bare soil. The single application at the exaggerated rates was an attempt to simulate a full season's application of methiocarb. At 30 and 365 days after the methiocarb treatment, grains (sorghum and corn), pod vegetables (snap beans and black-eyed peas) and root crops (radishes and turnips) were planted in the plots as representative of rotational crops that may be planted after use of methiocarb on a target crop. The total residue of methiocarb, methiocarb sulphoxide and methiocarb sulphone in each crop was determined. Maximum residues determined as total methiocarb, its sulphoxide and sulphone, found in mature crops were sorghum (some wheat) < 0.02 mg/kg (green forage), < 0.02 mg/kg (grain), 0.07 mg/kg (straw); corn, 0.14 mg/kg (green forage 10 lb. a.i./acre, 30 day plant), < 0.02 mg/kg (kernel); snap beans or peas, 0.03 mg/kg (green vines), 0.11 mg/kg (snap beans, planted at 355 days and at 1.25 lb a.i./acre or 0.03 mg/kg at 1.25 lb a.i./acre 30-day plant), < 0.02 mg/kg (pod); blackeyes, 0.15 mg/kg (green vines 5 lb a.i./acre 30-day plant), 0.07 mg/kg (peas, 1 lb a.i./acre 90-day plant), < 0.02 mg/kg (pod); radish, 0.03 (root), 0.05 mg/kg (top), both at 1.25 lb a.i./acre, 120-day plant; turnip, < 0.02 mg/kg (root), 0.29 mg/kg (top, 10 lb a.i./acre 30-day plant); soil, 7 mg/kg (30 day plant, 10 lb a.i./ acre). These studies indicate that methiocarb carbamate residues in mature crops can generally be expected to be quite low or non- detectable in rotational crops planted at 30 or more days after maximum treatments of less than 5 lb a.i./acre. The data do indicate, however, that on occasion residues of < 0.03 mg/kg can occur in legumes or root crops grown under these conditions, and that even higher residues can occur in the tops of root crops or vines/forage parts. Metabolism In a preliminary study, the fate of (carbonyl-14C, methylthio- 3H) methiocarb was monitored in sandy loam and two silt loam soils for 17 days (Church and Flint 1971). The pH of the soils varied from 5.4 to 6.4. Metabolism of methiocarb in these soils was quite similar, and the average distribution of radioactivity at 17 days was methiocarb, 81%, methiocarb sulphoxide, 15%; ethereal sulphate of methiocarb sulphoxide phenol, 1% and unknown, 3%. Based on sampling dates of 2, 7 and 17 days, the estimated half-life for methiocarb was < 20 days for each of the soils tested. A second study of longer duration (6 weeks) was conducted with (carbonyl-14C)-methiocarb in three soils having alkaline pH (loamy sand, loam and sandy clay loam) and three soils having acidic pH (all loams) (Starr and Cunningham 1973). The half-life of methiocarb was <14 days in the alkaline soils and <50 days in the acidic soils. Hydrolysis of the parent carbamate appeared to be the primary route of degradation in the alkaline soils, while oxidation of methiocarb to methiocarb sulphoxide followed by hydrolysis of the sulphoxide to the corresponding phenol seemed to be the metabolic route in the acidic soils. A third study was conducted with (ring-l-14C)-methiocarb in sandy loam (Stanley and Flint 1974). Although the soil was very slightly alkaline, the half-life of methiocarb was approximately 28 days. Over a 16-week period, methiocarb was oxidized to its sulphoxide phenol. Soil-bound methiocarb-related residues increased over time, but they did not exceed 10% in the 16-week investigation. No unknown accounted for >10% in the applied radioactivity. Behaviour in soil micro-organisms Selected soil bacteria and fungi were individually incubated for 14 days at 30°C in a nutrient broth containing (ring-l-14C)- methiocarb (Strankowski 1978). These studies indicate that soil micro- organisms are capable of metabolizing methiocarb by hydrolysis, oxidation, hydroxylation and conjugation. The major degradation products detected were methiocarb sulphoxide, methiocarb sulphoxide phenol and N-hydroxyl methyl methiocarb. In water Solubility The solubility of methiocarb in distilled water at 20°C was reported by the manufacturer to be 10 ppm, although the documentation (Stanley and Parker 1981) was not provided. Octanol/water partition The octanol/water partition co-efficient for methiocarb was determined at 20°C with an octanol to water volume ratio of 1:44 (Stanley and Parker 1981). The partition coefficient (K) was 915. Again, the documentation was not provided. Hydrolysis The stability of methiocarb in buffered solutions from pH's of 5 to 9 have been studied (Church 1970; Saakvitne et al 1981). Half-lives varied from 40 to 321 days at pH 5, 6h to 24 days at pH 7 and 0.2 days to instantaneous hydrolysis at pH 9. There was a direct relationship between temperature and hydrolysis at a given pH. Stability in pond or river water was also investigated (Eichelberger and Lichtenberg 1971; Minor and Atwell 1979; Flint and Shaw 1974). The half-life varied from less than 3 to 14 days, depending on conditions. The principal route was hydrolysis to the phenol which then decreased while methiocarb sulphoxide phenol increased (63% of radioactivity at 14 days in one study). Aquatic metabolism (Ring-l-14C)-methiocarb was applied at 2 ppm to a pond water/sediment system. The half-life of methiocarb was less than three days (Minor and Atwell 1979). In this anaerobic aquatic environment, methiocarb decreased to <1% of the total radioactivity in the pond water and to 5% in the sediment extracts within 21 days. Methiocarb degradation in a water/sediment system involves hydrolysis of the carbamate to yield methiocarb phenol and subsequent formation of sediment-bound components. Fish accumulation Bluegill were continuously exposed to (ring-l-14C)-methiocarb at a concentration of 10 ppb for 34 days (Lamb 1974). The fish reached an equilibrium with their surroundings at approximately 0.7 ppm at about 7 days after exposure. These residues were reduced to 0.07 ppm within 7 days on transfer of the blue-gill to uncontaminated water. Over 60% of the radioactivity was unextractable and therefore unidentified. Of the extracted residues, identified compounds were methiocarb 3%, its sulphoxide 6%, its sulphone 8%, methiocarb phenol sulphoxide 17%, methiocarb phenol sulphone 35% and unknown 31%. Methiocarb, methiocarb sulphoxide and methiocarb sulphone accounted for only 6% of the whole- body radioactive residues and did not accumulate in the fish. In storage and processing The effects of 0 to 109 F storage of over 20 food or feed items (most fortified separately with 1.0 mg/kg methiocarb, its sulphoxide and sulphone) were studied (Mobay 1981). This is of particular importance, as the interval from harvest to analysis for much of the residue data submitted to the Meeting was 6 to 18 months. The storage interval in the investigation ranged from 57 to 805 days and over-all decomposition averaged approximately 17%. Average decomposition can be substantial in some individual commodities - strawberry 47% (643 days), grape 32% (807 days), rice grain 32% (95 to 365 days), lettuce 28% (804 days), fish (edible part) 24% (93 to 204 days), brassica leafy vegetables 22% (804 to 805 days). Processing of apples with field-incurred methiocarb residues of 1.6 ppm resulted in residues of 3.3, 0.7 and 2 ppm respectively in wet pomace, dry pomace and juice respectively (Table 7). As a percent of original fruit residue, the values were 77, 68 and 2 in the juice, wet pomace and dry pomace respectively. Therefore, there is an approximate 2X concentration from the fruit to wet pomace. Grape juice had approximately the same residue and wine 0.4 to 0.7X that of the grape with field-incurred residues from which they were processed (Table 7). Photodecomposition The degradation of (ring-l-14C)-methiocarb on glass, silica gel and soil surfaces and in aqueous solution under artificial ultraviolet light was investigated (Houseworth and Tweedy 1974). The half-life of methiocarb was <2 h on glass and in water, <4 h on silica gel, and <16 h in soil. There was no evidence for volatile degradation products. Major degradation products were sulphoxide, sulphones and more polar materials. METHODS OF RESIDUE ANALYSIS Numerous analytical methods have been developed for the determination of residues of methiocarb and its metabolites in a variety of crops and animal products. Although each is unique, the approaches have certain similarities. Typically, chopped or ground samples are blended (or seeped) with a variety of solvents, filtered, purified by partitions and/or chromatographic columns, derivatized (or hydrolysed to the sulphone then derivatized) and determined on methyl silcone gas chromatographic columns. Determination is usually by a flame photometric detector. Chopped and buffered apples and pears were extracted with acetone and the sulphide sulphoxides and sulphones of methiocarb separated on silica, further separated into the carbamate and phenols on an alumina column, the carbamates hydrolysed to their phenols and all underivatized phenols analysed on a flame photometric detector (FPD) (Bowman and Beroza 1969). Recoveries compared favourably with Soxhlet extraction and were 68 to 108% at 0.1 to 5 mg/kg fortification levels for the five compounds, and a sensitivity of 0.01 mg/kg was claimed. Thornton (1969) also used acetone for the extraction of methiocarb and its sulphoxide and sulphone from apples and pears, followed by a NH4Cl:H3PO4 precipitation step, oxidation to the sulphone with KMnO4, overnight silylation and determination by FPD. Recoveries of 58 to 117% were attained at 0.05 to 0.5 mg/kg fortification levels and a sensitivity of 0.04 mg/kg claimed. This method was validated by the US Environmental Protection Agency down to 0.03 mg/kg for methiocarb and its sulphoxide respectively in maize grain with recoveries of 108 and 106%. The same basic procedure was used to analyse a variety of plant and animal tissues (Thornton and Drager 1973). Modifications were made for animal products and high-fat products, including a florosil column clean-up step. Recoveries were similar, with a sensitivity (accurately measurable) of 0.03 mg/kg achieved, and a 0.01 mg/kg limit of detection. The limits were approximately 10X better for milk. This method was validated in US Environmental Protection Agency laboratories down to 0.01 mg/kg for milk, except that a hydrolysis step was added. Recoveries were > 80% when a 1% mineral oil in benzene keeper solution (8 drops) was added before concentration of the chloroform solutions after hydrolysis and oxidation. A similar approach, using CH3CN extraction, the precipitating step, and for the first time a specific hydrolysis step to hydrolyse the sulphone to the phenol, was used on a variety of commodities (Strankowski and Stanley 1975). This is again followed by silylation, which does not require overnight silylation, with the hydrolysis step included and analysis by FPD. As in the earlier versions, the individual carbamates could be determined separately, if the oxidation step is omitted. It is included for analytical convenience. Recoveries for all three compounds were 70 to 112% at 0.05 to 0.1 mg/kg fortification levels and an analytical sensitivity of 0.01 mg/kg was claimed. This method is of particular importance as it is used for the analysis of well over half of the commodities for which analytical residue data were provided to the Meeting. A similar method was used for the determination of methiocarb residues in poultry and eggs (Strankowski 1976a). Modifications improved the latter method and made it suitable for the determination of the N-hydroxy sulphoxide and sulphone metabolites, as well as methiocarb and its sulphoxide and sulphone (Delphia and Stanley 1980). Acetone or CH3CN extraction of peaches and cherries was followed by a precipation step, hydrolysis to the phenols and silylation (without the oxidation step) to determine methiocarb and its sulphoxide and sulphone separately by FPD (Stanley 1976). Recoveries were 56 to 110% at 0.05 to 0.1 mg/kg fortification levels and sensitivity of 0.03 mg/kg. Blueberries were extracted with buffered acetone, partitioned with CHCl3, cleaned up on a silica gel column and derivatized with trifluoroacetic anhydride for the separate determination of the respective trifluoroacetyl derivatives of methiocarb and its sulphoxide and sulphone (Greenhalgh et al 1977). Recoveries were > 94% at 0.1 and 0.3 mg/kg fortifications with methiocarb, its sulphoxide and sulphone respectively. The sensitivity was given as 1.3, 2.3 and 5.8×10-11 g/sec of methiocarb, its sulphoxide and sulphone respectively. Maitlen (1981) modified Thornton's procedure by steeping of chopped commodities (five) with 1:3 acetone:CH2Cl2, to minimize emulsions, and oxidized methiocarb and its sulphoxide with peroxide and acetic acid before hydrolysing the sulphone to its phenol and derivatizing with methanesulphonyl chloride followed by a florosil column clean-up. The modification of the oxidation step minimizes problems with impurities in acetone experienced by earlier investigators. Although only the mesylated sulphone phenol is determined, recoveries of methiocarb, its sulphoxide and sulphone were 67 to 129% from 0.05 to 3 mg/kg fortifications. Little difficulty was required to attain a 0.05 lower limit of detection (the chromatograms suggest this could be a limit of determination, although it was not so validated). An extraction procedure using 1:1 CHCl3:methanol (Morris 1976) and an analytical procedure using the familiar precipation, oxidation, silylation techniques and FPD detection was developed (Norris and Olson 1973). Recoveries were > 80% at 0.5 mg/kg fortifications in four soils with a 0.13 mg/kg sensitivity. Methiocarb may also be determined by HPLC multi-residue methods (Krause 1980) or by electron capture gas chromatography after hydrolysis and derivatization with pentafluorobenzyl bromide (Coburn et al 1975). Because other pesticides registered on the same commodities can interfere with the analysis of methiocarb, confirmatory methods using QF-1 (Thornton 1970a) and OV-17 (Thornton 1970b) instead of the less polar methyl silcone gas chromatographic liquid phases have been developed. Interference studies of various pesticides in several crops have been conducted (Olson 1970; Olson 1971; Thornton 1969b; Strankowski 1976; Morris and Strankowski 1978). Potential interfering pesticides can be malathion, methyl parathion, dioxathion, ronnel, thiono systox, phorate, thimet and prometryne. All but the first two may be separated from methiocarb sulphone derivatives by QF-1 phases. The first two may be separated using OV-17 (Thornton 1969a). NATIONAL MAXIMUM RESIDUE LIMITS National maximum residue limits (MRLs) were reported to the Meeting by several countries and are summarized in Table 11. TABLE 11. National maximum residue limits reported to the Meeting Pre-harvest Country Crop/Commodity interval MRL (days) (mg/kg) Argentina Pome fruit 21 Stone fruit 21 Australia Orchards 7 Berry crops 7 Vegetable crops 7 Field crops 7 Pastures 7 Gardens 7 Cherry 7 15 Grape 7 25 Orange 1 5 Belgium Ornamentals only 7 Bulgaria General 21 Czechoslovakia Hops 35 Ornamentals 7 Denmark Food crops 7 Pastures 7 Federal Republic Head cabbage 14 0.1 * of Germany Red cabbage 14 0.1 * Cauliflower 14 0.1 * Spinach 14 0.1 * Lettuce (also under glass) 14 1.0 * Small fruit (berries) 28 0.1 * Pome fruit 14 0.2 * Stone fruit 28 0.1 * TABLE 11. (con't) Pre-harvest Country Crop/Commodity interval MRL (days) (mg/kg) Strawberry 14 0.1 * Cereals 28 0.1 * Potato 14 0.1 * Sugarbeet 28 0.1 * Fodder beet 28 0.1 * Clover 28 Lucerne 28 Lupines 28 Hops 21 France Potato 15 German Fruit 14 Democratic Leafy vegetables 14 Republic Stem vegetables 14 Brassices 14 Root vegetables 14 Fruiting vegetables 4 Hungary Maize 0.1 Israel Vegetables 30 Beet 30 Citrus fruit 30 Fruit 30 Grape 30 Artichoke 30 Italy Fruit 21 0.05 Vegetables 21 0.05 Sugarbeet 21 0.05 Cereals 21 0.05 Mexico Peach 21 New Zealand Pastures 21 Norway General 7 TABLE 11. (con't) Pre-harvest Country Crop/Commodity interval MRL (days) (mg/kg) Poland Fruit 42 Vegetables 42 Pulse crops 42 Root crops 42 Other crops 42 Portugal General 21 New Zealand Cereals 10 Grape 3 Stone fruit 7 Blueberry 25 (under consideration) South Africa Apple 14 0.2 Pear 14 0.2 Apricot 14 0.2 Plum 0.2 Table grape 14 0.2 Wine grape 28 - 42 0.2 (according to variety) Spain Pastures 15 Cotton 21 Hops 21 Hazelnut 21 United Kingdom Cereals 7 Potato 7 Brassicas 7 Sugarbeet 7 Pea 7 USA Citrus fruit 0.02 Maize, fodder and forage 0.03 Maize, fresh, includes 0.03 sweet corn (kernels plus cobs) Maize, grain, field and 0.03 TABLE 11. (con't) Pre-harvest Country Crop/Commodity interval MRL (days) (mg/kg) popcorn Peach 21 15 Blueberry 0 25 Cherry 7 25 Venezuela Rice 21 1 * Proposed. EVALUATION COMMENTS AND APPRAISAL Methiocarb has a relatively high acute oral toxicity in the rat (LD50 13 to 47 mg/kg bw) and dog (LD50 10 to 25 mg/kg bw) and exhibits a rapid, reversible toxic action characteristic of a carbamate. There are no marked differences in the sensitivity of the tested animal species or the sexes. Metabolites formed in the experimental animal species tested are of slight toxicity, with the exception of methiocarb sulphoxide, which has a higher acute toxicity than the parent compound. Potentiation tests by the I.P. routes with a number of other anticholinesterase compounds did not result in more than additive effects. Atropine sulphate proved to be a very effective antidote in cases of methiocarb poisoning. Neurotoxicity, embryotoxicity, teratogenicity, multigeneration reproduction and mutagenicity tests did not indicate any observable adverse effects due to methiocarb. Short-term rat, hen, rabbit, dog and cattle studies and long-term rat studies were performed with methiocarb. Methiocarb did not have a carcinogenic effect, and in two-year feeding experiments on dogs and rats no-effect levels were determined. Methiocarb is widely used around the world, either as a seed treatment, spray or bait for the control of a variety of pests. The most important uses are as a bait treatment for control of slugs and snails and as a bird repellent, either as a spray or seed treatment. Residue data were available for a wide range of food crops, representing good agricultural practices. They were not adequate for the estimation of maximum residue levels for artichokes, barley, potatoes, rape, wild rice and spinach, but were adequate for the estimation of maximum residue levels on several commodities when residues resulted from seed or spray treatments. In the case of bait treatments, most of the available residue data were the result of broadcast treatments. The Meeting was aware that methiocarb is widely used in this manner. However, the Meeting concluded that information on good agricultural practices using broadcast bait applications were inadequate to permit estimation of full maximum residue levels, but the Meeting was able to estimate temporary maximum residue levels. In estimating these temporary residue levels, the Meeting was aware, and the data indicate, that on occasion residue levels on the various commodities so treated may exceed the estimated residue levels. The Meeting was of the opinion that these occasional high residues result from the presence of actual bait pellets or fragments thereof, or contamination, which will be dislodged by normal handling procedures before consumption. Methiocarb is relatively stable for lengthy periods under acidic conditions and hydrolyses rapidly under alkaline conditions. The degradation rate is increased with temperature. Methiocarb is readily metabolized or degraded in the environment by plants, animals and microorganisms. Hydrolysis of the carbamate to the phenol, oxidation of the sulphide to the sulphoxide and subsequently to the sulphone, often followed by conjugation, are the basic chemical changes that occur. The relative order and extent of each varies with the conditions of each particular situation. In animals, (ring-l-14C)-methiocarb radioactivity is rapidly eliminated in the urine (96% of administered within 144 h in the cow) with low levels in the faeces and milk. Conjugated phenols accounted for 85% of urine radioactivity. Most of the organosoluble radioactive residue in milk was unidentified, only methiocarb sulphoxide being positively identified. The greater part of the milk radioactivity was in the form of conjugated methiocarb sulphoxide and sulphone phenols. In cow liver and kidney, methiocarb phenol was the principal residue, with lesser amounts of the sulphoxide and sulphone phenols and even less of other moieties. Methiocarb was found at appreciable levels only in the liver. In cow feeding studies mean residues in kidney and liver were greater than the 0.05 mg/kg method sensitivity only at the 100 ppm feeding level. In milk, measurable residues (mean) were found at both the 30 and 100 mg/kg feeding levels at 0.014 and 0.03 mg/kg respectively. Excretion and metabolism in poultry was in many respects similar to that of the cow, although measurable and identifiable residues were found in most tissues of poultry, whereas residues were sufficient for characterization only in liver and kidney of the cow. A primary difference between the cow and poultry is less methiocarb phenol in liver and kidney of poultry and higher over-all radioactive equivalents in poultry tissues. Analytically significant levels of N-hydroxymethyl methiocarb were also found in chicken tissues (organosoluble and/or conjugated) but apparently not tested in cow tissues. In poultry feeding studies, except for skin at the highest feeding level, residues were found only in the giblets and were 0.02, 0.06, 0.13 and 0.13 mg/kg from lowest to highest feeding levels. Residue data on individual tissues were not provided. Neither is it clear whether the N-hydroxymethyl methiocarb residues would have been measured. In eggs, residues were greater than the 0.02 mg/kg method sensitivity only at the highest feeding level. Residues in crops at levels estimated from recommended or approved practices examined by the Meeting would not be expected to result in analytically significant residue in animal meat tissues, eggs or milk. When methiocarb is applied to soil, it is rapidly taken up by plants and translocated throughout. Different studies show that residues can penetrate plants from surface treatments. Studies show that shortly after treatment, residues in plants are largely organosoluble and predominantly methiocarb sulphoxide, methiocarb and methiocarb sulphoxide phenol. As time from treatment increases organosoluble residues decrease while conjugated aqueous soluble residues (primarily conjugated methiocarb sulphoxide phenol and methiocarb phenol) increase. The degree varies with the plant. There may be low levels of N-hydroxymethyl methiocarb sulphoxide and other moieties. In some commodities, (e.g. cabbage and lettuce) there is evidence that residues increase for a period after last application. In soils, methiocarb desorption is proportional to the amount adsorbed and has relatively low mobility compared to other pesticides. Studies show leaching to be inversely related to organic content of the soil, although methiocarb does not appear to have a strong propensity for leaching. Persistence in soil varies with soil type and pH, with a half-life of 6 to 64 days, depending on conditions. Studies indicate some potential for low level residues in mature rotational crops grown in soils previously treated, especially for legumes and root crops, and substantially higher residues in vines and forage (leaf parts). Residues will accumulate in fish from water containing 10 ppb levels of methiocarb, but rapidly decrease when they are returned to uncontaminated water. On topically treated apples, residues are primarily surface ones, which were found to be mostly methiocarb with some sulphoxide. As in other plants, water soluble residues increased with time in the peel and pulp, while there was some decrease in surface organosoluble residues. Only a limited amount of information is available on the effects of processing on residues of methiocarb foods and none on residues in commerce or at consumption. Decomposition of methiocarb residues on commodities under prolonged storage conditions does occur, averaging approximately 17% over all commodities and over 30% on some commodities. Because many of the samples analysed for field-incurred residues were stored for periods up to 18 months before analysis, the resulting actual residues at sampling can reasonably be expected to have been somewhat higher than recorded. This was taken into account when limits were estimated. Numerous methods have been developed for the determination of methiocarb residues in a variety of crops and foods. Typically, residues are extracted with an organic solvent, cleaned up by partitioning and/or column chromatography, methiocarb residues oxidized to the sulphone, hydrolysed to the phenol, derivatized and analysed on gas chromatography using a flame photometric detector. Total residues are typically measured as the sulphone phenol derivative for analytical convenience, although methiocarb, its sulphoxide and sulphone phenol derivatives can be determined separately if the oxidation step is omitted. Several of the methods are probably suitable for enforcement, as they are all remarkably similar. The methods of Thornton (1969 a,b) and Thornton and Drager (1973) are preferred methods as they are published, have been tested on several commodities and have been validated. The method of Strankowski and Stanley (1925), although presumably unpublished, should also receive special consideration as it was the basis of much of the residue data provided. The method of Bowman and Beroza (1969) is probably too long for routine enforcement but does offer an approach for a more detailed characterization of individual residues, The method of Maitlen (1981) shows promise, although it is relatively new and perhaps has not been used to the same extent as other ones. Confirmatory gas chromatographic methods are available to eliminate pesticides interfering with methiocarb analysis. Level causing no toxicological effect Rat: 25 ppm in the diet equivalent to 1.3 mg/kg bw/day Dog: 5 ppm in the diet equivalent to 0.125 mg/kg bw/day Estimation of acceptable daily intake for man 0 - 0.001 mg/kg bw RECOMMENDATIONS OF RESIDUE LIMITS The Meeting examined residue data from residue trials reflecting the basic uses for the control of slugs and snails or bird repellency. For those crops treated by spray applications or as seed treatments, the Meeting was able to estimate maximum residue levels likely to occur when methiocarb is used in accordance with approved agricultural practice and at the specified intervals between last application and harvest. For those crops treated by bait applications the Meeting was able to estimate temporary maximum residue levels, pending additional information on good agricultural practices. The levels refer to the sum of methiocarb, its sulphoxide and sulphone. Commodity Estimated Pre-harvest interval and/or Maximum Residue uses on which recommendations levels (mg/kg) are based (days) Seed treatments Maize 0.05 -1 Rice 0.5 - Sugarbeets 0.02 - Spray Apple 10 21 Blueberry 25 0 Cherry 10 7 Currant, red 5 21 Grape 5 7 Peach 15 21 Plum 1 21 Strawberry 0.02 14 Commodity Estimated Pre-harvest interval and/or Maximum Residue uses on which recommendations level3 (mg/kg) are based (days) Bait Beans, snap 0.2 7 (broadcast) Beans, lima 0.2 7 (broadcast) Broccoli 0.2 7 (broadcast) Brussels sprout 0.2 7 (broadcast) Cabbage 0.2 7 (broadcast)2 Cauliflower 0.2 7 (broadcast)2 Maize, sweet corn 0.05 0 (broadcast) Citrus 0.02 30 (broadcast) Lettuce 0.2 7 (broadcast)2 Tomato 0.2 7 (broadcast) 1 Data were also available from topical treatments; 2 Data were also available from spray treatments; 3 Pending additional information on good agricultural practices (see further work required). FURTHER WORK OR INFORMATION Required (by 1983) Information on good agricultural practice for commodities on which bait applications are recommended/used. Desirable 1. If future uses on animal feed items could result in potential residues in meat, milk, poultry and eggs, additional metabolism and residue data will be necessary. This would include (a) additional residue data on the pertinent animal feed items, (b) identification of radioactive residues observed in the organosoluble milk fractions, (c) from feeding studies, analysis of ruminant liver and kidney tissues for N-hydroxymethyl methiocarb, (d) from poultry feeding studies, residue data from individual giblets and analysis of giblets and muscle tissues for N-hydroxymethyl methiocarb. 2. Information on levels of methiocarb residues in foods at commerce or at consumption. (this is an example of a selective survey, para 2.10, 1979 JMPR Report). 3. Observations in man. REFERENCES Atwell, S.H. and Murphy, J.J. 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Report no. 9424, University of Chicago, Department of Pharmacology, submitted by Bayer AG. (Unpublished) Eben, A. and Kimmerle, G. Mercaptodimethur - effect of acute and 1973 subacute oral doses on acetylcholinesterase activity in plasma, erythrocytes and brain of rats, 9 November. Report no 4284, Bayer AG, Institut fur Toxikologie, submitted by Bayer AG. (Unpublished) Eichelberger, J.W. and Lichtenberg, J.J. Persistence of pesticides in 1971 river water. Environmental Science and Technology, 5:541-544. Ernst, G.F., Saskia, J.R., Gwan, H.T. and Jansen, J.T.A. Thin layer 1975 chromatographic detection and indirect gas chromatographic determination of three carbamate pesticides. Journal of the Association of Official Analytical Chemists, 58:1015-1019. Flint, D.R. and Shaw, H.R. II. The mobility of Mesurol residues in 1974 soil runoff water and the degradation of Mesurol-14C in pond water. Mobay Ag Chem Report no.39258, 30 January. (Unpublished) Greenhalgh, R., Wood, C. and Pearce, P.A. A rapid GC method of 1977 monitoring Mesurol (4-(methylthio)-3.5-xylyl-N-methyl carbamate) and its sulphoxide and sulphone metabolites and their persistence in low bush blueberries. Journal of Environmental Science and Health, B 12(4):229-244. Gronberg, R.R. and Everett, L.J. The metabolic fate of 4-(methylthio 1964 3,5-xylyl methylcarbamate (BAY 37344 sulphoxide) and 4-(methylsulphonyl)-3,5-xylyl methylcarbamate (BAY 37344 sulphone) in white rats, Mobay Ag Chem Report no. 26819, submitted by Mobay Chemical Corp.(Unpublished) Guerzoni, M.E. and DelCupola, L. Attivitá mutagenica degli 1976 antiparassitari, S-TANU,6(3):161-165. Herbold, B. H321 (active ingredient of Mesurol) Salmonella/microsome 1978 test for determination of point mutations, 6 December. Report no. 7978, Bayer AG, Institut für Toxikologie, submitted by Bayer AG. (Unpublished) 1979a H321 - dominant lethal study on male mouse to test for mutagenic effects, 23 May. Report no. 8395, Bayer AG, Institut für Toxikologie, submitted by Bayer AG. (Unpublished) 1979b H321 (active ingredient of Mesurol) micronucleus test for mutagenic effect on mice, 8 June. Report no. 8426, Bayer AG,Institut für Toxikologie, submitted by Bayer AG. (Unpublished) Hoffman, K. and Schilde, B. H321 (mesurol-Workstoff, Mercaptodimethur) 1980 Chronischer Toxizitätsversuch an Hunden bei Verabreichung im Futter (2 Jahre - Fütterungs-versuch), 12 Dez. Bericht Nr. 9626, Bayer AG, Institut für Toxikologie, submitted by Bayer AG. (Unpublished) Houseworth, L.D. and Tweedy, B.G. Parent leaching studies for 1974 MesurolR. Mobay Ag. Chem Report no. 40568, 21 March 1974. (Unpublished) Ives, M. Demyelination study in chickens/Bayer 37344, 16 April. Report 1965 no.16063, Wedge's Creek Research Farm, Inc., Subsidiary of Industrial Bio-Test Lab., Inc., Biological Evaluations, USA, submitted by Bayer AG. (Unpublished) Kraus, R.T. Multi-residue method for N-methyl carbamate pesticides in 1980 crops using HPLC. Journal of the Association of Official Analytical Chemists, 63:1114-1124. Kimmerle, G. Product Dr. Wedemeyer II 321 (E 37 344) Production no. 1960 2410, 25 March, Bayer AG, Toxicological and Industrial Hygiene Laboratory, report submitted by Bayer AG. (Unpublished) 1966a Mesurol active ingredient (Wedemeyer H321; Ht. no. 3657) antidotal effect - translation - 8 August. Report no. 34267, Bayer AG, Institut für Toxikologie, submitted by Bayer AG. (Unpublished) 1966b Wirkstoff Wedemeyer H 321 (Ht.-Nr. 3657) Inhalationsversuche, Dez.7. Bayer AG, Institut für Toxikologie, report submitted by Bayer AG. (Unpublished) 1969a Bay 37344 (subacute dermal toxicity study on rabbits, 1 April. Report no.1291, Bayer AG, Institut für Toxikologie, submitted by Bayer AG. (Unpublished) 1969b Bay 37344(=H 321) Lo-Nr.691, 20 May. Bayer AG, Institut für Toxikologie, report submitted by Bayer AG. (Unpublished) 1971 Comparison of the antidotal actions of tetraethylammonium chloride and atropine in acute poisoning of carbamate insecticides in rats, 9 January. Archives of Toxicology, 27:311-314. Krötlinger, F., Löser, E. and Voge, O. H 321 (Mercaptodimethur) 1981 Akarizide, toxikologische Untersuchungen an Ratten. Br. 10039 v. 2.7.81, report submitted by Bayer AG to WHO. (Unpublished) Lamb, D.W. Accumulation and persistence of residues in bluegill fish 1974 exposed to Mesurol-14C. Mobay Ag Chem Report no. 40096, 8 March 1974. (Unpublished) Lamb, D.W. and Matzkanin, C.S. The acute oral toxicities of Mesurol 1975 technical to dogs, 25 August. Report no. 45074, Mobay Chemical Corp., Agr. Division, submitted by Bayer AG. (Unpublished) 1976a The acute oral toxicities of mesurol technical and Mesurol sulphoxide, 12 July. Report no. 49541, Mobay Chemical Corp., Agr. Division, submitted by Bayer AG. (Unpublished) 1976b The acute oral toxicities of Mesurol technical and Mesurol sulphoxide, 19 August. Report no. 50541, Mobay Chemical Corp., Agr. Division, Submitted by Bayer AG. (Unpublished) Löser, E. Bay 37344/Blut-, hart- und Klinisch-Chemische Untersuchungen 1969 nach oraler applikationan Ratten, 3 March, Bericht Nr. 1358, Bayer AG, Institut für Toxikologie, report submitted by Bayer AG. (Unpublished) Löser, E. Bay 37344/Generation studies on rats, 10 July. Report no. 1970 2208, Bayer AG, Institut für Toxikologie, submitted by Bayer AG, Addenda: Histopathology - Huntingdon Research Centre, Huntingdon, England. (Unpublished) Lorke, D. Mesurol active ingredient (Bay 37344) studies on rats for 1971 embryotoxic and teratogenic effects, 30 November. Report no. 3133, Bayer AG, Institut für Toxikologie, submitted by Bayer AG. (Unpublished) Maitlen, J.C. Gas-liquid chromatographic determination of residues of 1981 methiocarb and its toxic metabolites with the flame photometric detector after derivatization with methanesulphonyl chloride. Journal of Agricultural and Food Chemistry, 29:260-264. Minor, R.G. and Atwell, S.H. Metabolic fate of Mesurol(R) in aerobic 1979 and anaerobic aquatic environments. Mobay Ag Chem Report no. 66775, 30 January 1979. (Unpublished) Minor, R.G. and Murphy, J.J. Metabolism and excretion of Mesurol by a 1977a dairy cow, Mobay AG Chem Report no. 51144 (1977), submitted by Mobay Chemical Corp. (Unpublished) 1977b Radioactive residues of (ring-l-14C)-Mesurol in a lactating dairy cow. Mobay Ag Chem Report no. 51145 (1977) submitted by Mobay Chemical Corp. (Unpublished) Mobay Residues of Mesurol in bovine tissues and milk. Mobay Ag 1970 Chem Report 26848, 26 February, 1970 and Mobay Ag Chem Report no. 26879, 3 March, 1970. (Unpublished) Mobay Residues of Mesurol in soils. Mobay Ag Chem Report Nos. 1973 2680, and 26883, 3 March (Unpublished) Mobay Residues of Mesurol in soils. Mobay Ag Chem Report nos. 1974 38948, 38949 and 38950, 30 November 1973. (Unpublished) Mobay Residues of Mesurol in rotational crops. Mobay Ag. Chem 1977-81 Reports: 48847, April 5, 1978; 50430, August 3, 1978; 48865, April 5, 1978; 50431, August 3 1978; 50382, April 17 1978; 53816, October 4, 1977; 50422 April 17 1978; 53855 October 4 1977; 53815 October 17 1977; 54055 October 4 1977; 53854 October 4 1977; 66805 April 4 1978; 66809 April 5 1978; 66806 April 5 1978; 66810 April 5 1978; 66807 April 5 1978; 66813 April 22 1978; 66808 April 5 1978; 66814 April 22 1978; 66821 April 5 1978; 66817 April 4 1978; 66822 July 13 1978. 66818 April 4 1978; 66823 July 13 1978; 66825 July 13 1978; 66824 July 13 1978; 66828 April 22 1978; 66831 April 27 1978; 66835 April 22 1978; 66832 April 27 1978; 66836 April 22 1978; 66833 April 27 1978; 49835 April 17 1978; 66834 April 27 1978; 45379 August 3 1978; 66839 August 3 1978; 45850 August 3 1978; 66840 August 3 1978; 46257 August 3 1978; 66841 August 3 1978; 46436 August 3 1978; 66842 August 3 1978; 49231 April 6 1978; 66843 January 5 1979; 49431 April 6 1978; 66843 January 5 1979 49456 August 3 1978; 66844 January 5 1979; 49591 August 3 1978; 66845 January 5 1979; 49693 April 17 1978; 66846 January 5 1979; 49835 1978; 69256 January 28 1981; 50335 April 17 1978; 69257 January 29 1981; 50423 August 3 1978; 69259 January 29 1981; 50429 August 3 1978; 69260 January 29 1981; 69261 January 29 1981; 69262 January 29 1981. (Unpublished) Mobay Residues of Mesurol in soils. Mobay Ag Chem Reports: 66929, 26 1979-81 February 1979; 67052 26 February 1979; 69230 20 January 1981; 69231 20 January 1981; 69233 16 February 1981; 69234 19 January 1981; 69236 20 January 1981; 69239 21 January 1981. (Unpublished) Mobay The effect of frozen storage at 0 to 10°F on Mesurol residues 1981 in crops, Mobay Ag Chem Reports: 49948 1976; 27072 March 19 1970; 51168 January 12 1977; 27081 March 30 1979; 66101 May 3 1978; 49580 January 21 1977; 67923 March 2 1979; 49729 September 20 1976; 68013 July 19 1979; 49947 November 1 1976; 68205 October 5 1979. (Unpublished) Morgan, J.G. and Parton, K. Metabolism of Mesurol in apples. Mobay Ag 1974 Chem Report no. 40208, 1 April 1974. (Unpublished) Morris, R.A. and Olson, T.J. Determination of Mesurol and metabolites 1973 in soil by flame photometric gas chromatography. Mobay report no. 38319, 10 September 1973. (Unpublished) Morris, R.A. and Strankowski, K.J. An interference study for the 1978 residue method for Mesurol on rice. Mobay report no. 66095, 12 June 1978. (Unpublished) Murphy, J.J. and Morris, R.A. Residues of Mesurol in rotational crops. 1979 Mobay Chem Ag Report no. 66926, 1 February 1979. (Unpublished) Nelson, D.L. Acute oral toxicity of Mesurol technical and metabolites 1979 to rats, 27 June. Report no. 67815, Mobay Chemical Corp., submitted by Bayer AG. (Unpublished) New Zealand, Information provided by the New Zealand Government, which 1981 also included undated documents: methiocarb as a bird repellent in blueberries, P.T. Holland, D.W. McFarlane and R.M. Bates, Proc. 33rd N.Z. Weed Pest Control Conference, and, Further experiments with methiocarb on blueberries, P.T. Holland, D.W. McFarlane and G. Lawn, Proc. 34th N.Z. Weed and Pest Control Conference. Olson, T.J. An interference study for Mesurol residue determinations 1970 on apple, pear, meat and milk. Mobay report no. 27080, 30 March 1970. (Unpublished) Olson, T.J. Interference study for the residue method for Mesurol and 1971 its metabolites on corn. Mobay report no. 29412, 18 February 1971. (Unpublished) Root, M., Doull, J. and Cowan, J. Determination of the safe dietary 1963 level of Bayer 37344 for dogs, 23 March. Report no. 11159, University of Chicago, Department of Pharmacology, submitted by Bayer AG. (Unpublished) Saakvitne, J.A., Gustafson, D.E. and Wilkes, L.C. Mesurol hydrolysis 1981 in sterile buffers Mobay Ag Chem, 22 January 1981. (Unpublished) Solmecke, B. Akute oral Toxizität KLN 1584/1, April 6. Bayer AG, 1970a Institut für Toxikologie, report submitted by Bayer AG. (Unpublished) 1970b Akute oral Toxizität KLN 1584/2, April 6. Bayer AG, Institut für Toxikologie, report submitted by Bayer AG. (Unpublished) 1970c Akute oral Toxizität KLN 1584/3, April 6. Bayer AG, Institut für Toxikologie, report submitted by Bayer AG. (Unpublished) 1970d Akute oral Toxizität KLN 1584/4, April 6. Bayer AG, Institut für Toxikologie, report submitted by Bayer AG. (Unpublished) 1970e Akute oral Toxizität Mesurol-Phenol, 14 May. Bayer AG, Institut für Toxikologie, report submitted by Bayer AG. (Unpublished) Stanley, C.W. Determination of residues of Mesurol and its toxic 1976 metabolites separately in peaches and cherries. Mobay report no. 49727, 1 September 1976. (Unpublished) Stanley, C.W. and Flint, D.R. The metabolic fate of Mesurol in sandy 1974 loam soil. Mobay Ag Chem Report 39429, 29 January 1974. (Unpublished) Stanley, C.W. and Johnson, G.A. II. Metabolites of Mesurol in rat 1976 urine. Mobay Ag Chem Report no. 50732, submitted by Mobay Chemical Corp. (Unpublished) Stanley, C.W., Kottman, R.F. and Bingman, K.J. Metabolism and 1979a excretion of Mesurol by poultry. Mobay Ag Chem Report no. 66777, submitted by Mobay Chemical Corp. (Unpublished) 1979b Radioactive residues of (14C)-Mesurol in poultry. Mobay Ag chem Report no.66778, submitted by Mobay Chemical Corp. (Unpublished) Stanley, and Parker - cited by Manufacturer, but the document was not 1981 provided or identified. Starr, R.I. and Cunningham, D.J. Metabolism of 14C-labelled methiocarb 1973 (4-methylthio)-3.4-xylyl methyl carbamate) in soil and water. Mobay Ag Chem Report no. 38747. (Unpublished) Strankowski, K.J. An interference study for the residue method for 1976a Mesurol in various crops. Mobay Report no. 49467, 1 July 1976. (Unpublished) 1976b Method for the determination of Mesurol and its toxic metabolites in poultry and eggs. Mobay Report no. 49078, 29 January 1976. (Unpublished) Strankowski, K.J. Microbial degradation of Mesurol. Mobay Ag Chem 1978 Report no. 66625, 19 October 1978. (Unpublished) Strankowski, K.J. Metabolism of Mesurol in rice. Mobay Ag Chem Report 1979 no. 66776, 30 January 1979. (Unpublished) Strankowski, K.J., Delphia, L.M. and Murphy, J.J. Cattle acceptance 1978 (palatability) of alfalfa pellets treated with Mesurol, 15 June. Report no. 66391, Mobay Chemical Corp., submitted by Mobay Chemical Corp. (Unpublished) Strankowski, K.J. and Minor, R.G. Effects of feeding Mesurol/Mesurol 1976 sulphoxide (9:1) to chickens for 28 days, 7 January. Report no. 49639, Mobay Chemical Corp., Agr. Division, submitted by Mobay Chemical Corp. (Unpublished) Strankowski, K.J. and Murphy, J.J. Mesurol uptake and metabolism by 1981 lettuce and tomato plants. Mobay Ag Chem Report 50863, 12 November 1976. (Unpublished) Strankowski, K.J. and Parker, G.D. (14C)-Mesurol rotational crop 1981 study. Mobay Ag Chem Report no. 69270, 10 February 1981. (Unpublished) Strankowski, K.J. and Stanley, C.W. Determination of residues of 1975 Mesurol and its toxic metabolites in crops. Mobay report no. 45089, 15 August 1975. (Unpublished) Thornton, J.S. Determination of residues of BAY 37344 and metabolites 1969a in apples and pears by flame photometric gas chromatography. Mobay Report no. 25168, 12 June 1969. Published as Method I of the U.S. Food and Drug Administration Pesticide Analytical Manual, Vol. II. 1969b An interference study for the residue methods for BAY 37344 and metabolites. Mobay report no. 26438, 18 December 1969. (Unpublished) Thornton, J.S. A confirmation procedure for the BAY 37344 residues 1970a methods. Mobay report no. 26964, 13 March 1979. (Unpublished) 1970b A secondary confirmatory procedure for the Mesurol (BAY 37344) residue methods. Mobay report no. 27147, 9 April 1970. (Unpublished) Thornton, J.S. and Drager, G. Determination of residues of Mesurol and 1973 its toxic metabolites in plant and animal tissues. International Journal of Environmental Analytical Chemistry, 2:229-239. Thornton, J.S., Hurley, J.B. and Obrist, J.J. Soil thin-layer mobility 1976 of twenty-four pesticide chemicals. Mobay Ag Chem Report no. 51016, 15 December 1976. (Unpublished) Thyssen, J. Bestimmung der akuten Toxizität (LD50), 15 November. Bayer 1977a AG, Institut für Toxikologie, report submitted by Bayer AG. (Unpublished) 1977b Bestimmung der akuten Toxizität (LD50), 30 November. Bayer AG, Institut für Toxikologie, report submitted by Bayer AG. (Unpublished) Thyssen, J. and Schilde, B. H 321 (Mesurol active ingredient) 1978 neurotoxicity studies on hens, 20 June. Report no. 7637, Bayer AG, Institut für Toxikologie, submitted by Bayer AG. (Unpublished) Tweedy, B.G. and Houseworth, L.D. Leaching of aged residues of Mesurol 1974 (ring-l-14C) in sandy loam soil. Mobay Ag. Chem Report no. 40568, 15 May 1974. (Unpublished) Udall, N.D. The toxicity of the molluscicides metaldehyde and 1973 methiocarb to dogs. The Veterinary Record, 13 October 1973. Waggoner, T.B. and Olson, T.J. Effect of feeding organophosphorus and 1971 carbamate pesticides to cattle. Chemagro Corp., 12-17 September, Paper no. 45, Division of Pesticide Chemistry, 162nd National ACS Meeting, Washington, submitted by Bayer AG. (Unpublished) Wheeler, L. and Strother, A. Placental transfer, excretion and 1974 disposition of (14C)-Mesurol in maternal and foetal rat tissues. Toxicology and Applied Pharmacology, 30:163-174.
See Also: Toxicological Abbreviations Methiocarb (ICSC) Methiocarb (Pesticide residues in food: 1983 evaluations) Methiocarb (JMPR Evaluations 1998 Part II Toxicological)