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 PIRIMICARB Explanation Pirimicarb was evaluated by the 1976, 1977 and 1979 Meetings.* A temporary ADI for man was established and temporary maximum residue limits (MRLs) were recommended on a wide range of crops. At an evaluation of pirimicarb by the 1977 Meeting, it was recommended that information on carcinogenicity in an appropriate mammalian species using a currently acceptable protocol be available by 1980. Information dealing with cytogenicity and foetal and maternal brain acetylcholinesterase isoenzyme changes induced by pirimicarb and additional data on residues are summarized in this monograph addendum. DATA FOR THE ESTIMATION OF ACCEPTABLE DAILY INTAKE TOXICOLOGICAL STUDIES Short-term studies Rat In order to determine a no-effect level as regards the growth depression found in previous long-term studies, particularly in female rats, groups of 20 female rats were maintained on diets containing 0, 100, 175, 250 and 750 ppm pirimicarb for a period of 8 weeks. The feeding did not adversely affect the general health. At 750 ppm, reduction of the body weight gain was observed, accompanied by lower food consumption compared to the control animals, especially in the first half of the study (Paul et al 1978). In a paired feeding study, female rats fed with dietary levels of 0, 250 and 750 ppm were paired with rats receiving restricted diets at concentrations of 250 and 750 ppm respectively. A treatment-related growth depression was observed that was slight at the 250 ppm dietary level and marked at 750 ppm after ad libitum or restricted feeding. The results indicate that the growth depression seems not to be due to reduced palatability of the supplemented food (Richards et al 1978). Dog To define the susceptibility to haemolytic anaemia in the beagle strain (Jackson et al 1977) another study was undertaken employing the foxhound as an experimental animal. Groups of dogs received pirimicarb at dietary levels of 0 (2 animals) and 2 mg/kg bw * See Annex II for FAO and WHO documentation. (2 animals) over a period of 16 weeks. A third group (6 animals) was maintained on a diet containing the test compound at a level of 25/50 mg/kg. The dose level of 50 mg/kg was subsequently reduced back to 25 mg/kg as soon as marked haematological changes appeared. The treatment was followed by a recovery period from week 17 to 23. One dog of the 25/50 mg/kg group which showed behavioural changes and clinical deterioration as weight loss, inappetence and ataxia, was killed after a 2-week treatment with 50 mg/kg pirimicarb. Loose faeces were seen in dogs from all treatment groups. At 25 mg/kg vomiting was observed sporadically. Over the first 4 weeks the male animals showed reduced body weight gains. At 50 mg/kg, usually a few hours after feeding, excessive salivation occurred; some dogs showed toxic effects as laboured respiration, vomiting, bloody faeces and flaccid muscles. The weight loss in some animals was accompanied by a slight reduction in food intake. The treatment at 50 mg/kg was associated with marked anaemia characterized by reduction in haemoglobin, packed cell volume and erythrocyte count and an increase in reticulocytes. The direct Coombes test failed to produce positive results (Jackson and Royle 1978a). The examination of the bone marrow revealed a tendency to an increased number of normoblasts and toward suppressed activity (hypoplasia). Anaemia, reticulocytosis and bone marrow changes were reversible and normal values were measured after the recovery period. Maximum inhibition of plasma cholinesterase activity of about 50 to 79% and 80 to 90% was measured at the 25 mg/kg and the 50 mg/kg dose level respectively. No dose-related alterations as regards the biochemical parameters GOT, GPT, SAP, glucose and BUN and the common parameters of urinalyses were found at any dose level. No abnormal macroscopic findings were detected. Owing to the small number of control animals the significance of various alterations in relative organ weights, particularly of the kidney and the spleen, could not be determined (Fox 1978). Monkey Groups of 4 rhesus monkeys (2 of each sex) were orally treated with 2 and 25 mg/kg pirimicarb over a period of 91 days; additionally, 2 monkeys were used as controls. The treatment had no effect on mortality, appearance, behaviour and body weight gain. The parameters of the haematological examinations and the results of urinalyses were within normal limits. There was no evidence of haemolytic anaemia and all direct Coombs tests were negative throughout the dosing period. The results of clinical chemistry with respect to the parameters of bilirubin, LAP, SGOT, SGPT, SAP, total serum protein, plasma glucose, and plasma urea showed no abnormal alterations. A dose-related inhibition of the cholinesterase activity in the erythrocytes of 16% and 38% and in plasma of 8% and 74% was found at the dose levels of 2 mg/kg and 25 mg/kg 2 h after dosing. The examination of the bone marrow revealed no pathological findings. The few incidental macroscopic findings are not attributable to treatment and the organ weights were considered to be within normal limits (Heywood et al 1977). In a similar study, groups of 4 rhesus monkeys of each sex were orally dosed with 0, 2, 7 and 25 mg/kg pirimicarb for up to 17 weeks, followed by a recovery period of 8 weeks. The survival, appearance and behaviour were not adversely affected by treatment and the only clinical effect was loose faeces in animals of all treatment groups. At 25 mg/kg a slight reduction in body weight gain was observed in the female animals. The results of haematological investigations gave no indication of a treatment-related anaemia. The parameters of clinical chemistry and urinalyses varied within normal limits. The inhibition of the cholinesterase activity in erythrocytes was 19, 18 and 31% and in plasma it was 23, 35 and 63% at the dose levels of 2, 7 and 25 mg/kg respectively. The cholinesterase activity measured after 2 weeks after cessation of treatment was normal. The findings of the bone marrow examinations were normal as well as any macroscopic post mortem findings. No group differences in organ weights were discovered. In the direct Coombs test, sporadically positive reactions were found (Heywood et al 1978a). Additional serological studies on monkeys confirmed the weak positive reactions in the Coombs test in some animals treated with 0, 2, 7 and 25 mg/kg pirimicarb (Jackson and Royle: 1978b). As could be demonstrated in a test performed on 30 untreated monkeys isolated positive reactions can occur spontaneously (Heywood et al 1978b; Jackson and Royle 1978c). Special studies on plant metabolites Rat Groups of 40 rats (20 of each sex) were orally treated with daily doses of 1.5 and 50 mg/kg of the plant metabolite carbamate (R 34885) for a period of 14 or 28 days. The control group consisted of 10 animals of each sex. The treatment had no effect on the clinical condition, behaviour and mean body weight gain. The results gave no evidence of hypochromic anaemia as suggested in a previous study. The histopathological examination revealed no abnormal findings. In a similar experiment, designed to study the inhibition of the cholinesterase activity of the metabolite, groups of 10 rats (5 males and 5 females) were treated with daily oral doses of 0, 3 and 12.5 mg/kg for 28 consecutive days. No significant inhibition of the enzyme was found in erythrocytes and brain, whereas the plasma cholinesterase activity showed a depression of 32% compared to control in females after treatment with 28 doses of 12.5 mg/ kg (Parkinson 1978a). Groups of 40 rats (20 males and 20 females) were orally treated with 25 and 100 mg/kg of the plant metabolite 5,6-dimethyl-2- methylamino-pyrimidin-4-yl dimethylcarbamate (R34836) for 14 or 28 days. Additionally, a control group consisting of 10 animals of each sex was included in the study. The test compound had no adverse effect when administered at a dose level of 20 mg/kg; at 100 mg/kg, however, 5 male and 6 female animals died during the study between 2 and 7 doses with clinical signs of cholinesterase inhibition. Some animals lost weight at 100 mg/kg. The examination of blood and bone marrow revealed no abnormal findings and gave no indication for hypochromic anaemia. The results of urinalyses fell into normal limits, with the only exception of slightly higher urinary protein values in male animals treated with 14 and 28 doses of 100 mg/kg respectively. No adverse histopathological effects were found at 100 mg/kg. To determine the degree of cholinesterase inhibition, groups of 10 rats (5 male and 5 female animals) were orally dosed with 0, 1.5, 5, 25 and 100 mg/kg of the test compound for 28 days. The cholinesterase activity was not affected in erythrocytes and brain. The plasma cholinesterase activity, however, showed inhibition at 25 mg/kg after 28 days of about 30% in male and about 55% in female animals; after 14 days of treatment with 100 mg/kg the depression was 40%, after 28 days of treatment depression was 63% in female animals only (Parkinson 1978b). Special studies on mutagenicity The mutagenic activity of a number of pesticides, e.g., pirimicarb, Polimartin and Cuprosan, was studied in human peripheral blood lymphocyte cultures from two donors with different levels of spontaneous chromosomal aberrations. Incubation of lymphocyte culture with pirimicarb increased the yield of chromosomal aberrations regardless of the level of spontaneous aberrations (Polimartin and Cuprosan failed to induce chromosomal aberrations). The potential mutagenicity of pirimicarb was also confirmed on the basis of its cytogenic activity in mice bone marrow cells (Pilinskaya 1981). Special studies on induction of foetal and maternal acetylcholinesterase isoenzymes Pregnant rats (18th day) were orally given 20 mg/kg pirimicarb. (Other insecticidal carbamates with anticholinesterase properties which were analogously tested were: 50 mg/kg carbaryl, 0.1 mg/kg aldicarb and 2.5 mg/kg carbaryl.) The acetylcholinesterase (ACLE) isoenzymes from the brain of mothers and their foetuses were separated by electrophoresis on polyacrylamide gel. The four carbamate derivates caused a significant lowering of the percentage of the least mobile isoenzyme (isoenzyme 1) in the mothers. Pirimicarb, aldicarb and carbaryl also caused a significant decrease in the percentage of the first foetal brain isoenzyme (Cambon et al 1980). RESIDUES IN FOOD Data reviewed by the 1976 and 1978 Meetings showed that pirimicarb is rapidly lost from plants after spraying. Half of the initial residue is lost, primarily by volatilization, in 1 to 3 days; the higher the ambient temperature, the greater the percentage of pirimicarb lost by volatilization. Pirimicarb also undergoes photochemical and metabolic degradation. The major carbamate- containing degradation products are compounds II and III (Figure 1). Other degradation products include the hydroxypyrimidines V, VI and VII which can be present either free or as conjugates. The hydroxypyrimides are major metabolites of pirimicarb in the rat, dog and cow. Guanidine and its 1-methyl and 1:1 - dimethyl derivatives are also formed following the application of pirimicarb to plants. A gas-chromatographic method using a nitrogen-selective detector to determine residues of pirimicarb plus its two major carbamate- containing plant metabolites Figure 1 (II and III) was reviewed as the preferred crop residue method by the 1976 and 1978 Meetings. This method was used during the residue determinations reviewed below, and all values quotes are corrected for percentage recovery, unless stated otherwise. RESIDUES RESULTING FROM SUPERVISED TRIALS Cereal grains At 0.125-0.25 kg a.i./ha pirimicarb controls the grain aphid, Macrosiphum avenae, on cereals. Spraying is conducted at an immature growth stage, normally several weeks before harvest. As a result of the data available to it, the 1976 Meeting proposed a temporary MRL in wheat grain of 0.05 mg/kg, at or about the limit of determination. Data available in 1978 re-affirmed the appropriateness of this proposal and facilitated similar recommendations on barley and oats. The 1978 appraisal noted that no data were available on residues in other grains such as maize or rice. Further data now available on wheat and oats sprayed in Canada with a 50% formulation re-affirm the appropriateness of the earlier proposals (Table 1). The half-life for pirimicarb on both crops was between 1 and 5 days (Bullock and Kennedy 1981).TABLE 1. Residues of pirimicarb in barley and wheat, Canada 1978 Application rate Crop part Total carbamate residues (mg/kg) after Crop (kg a.i./ha) analysed (days) 1 5 7 14 Barley 0.07 Grain 0.47 0.15 0.11 0.04 0.14 Grain 0.82 0.30 0.14 0.07 0.07 Ears - - 0.04 <0.02 0.14 Ears - - 0.05 0.02 Wheat 0.07 Ears 0.10 0.02 <0.02 <0.02 0.14 Ears 0.93 0.41 0.05 <0.02 A trial was conducted in Japan in 1979, in which sweet corn was sprayed at the unusually high rate of 2 kg a.i./ha, using a 48% WP formulation and 2 000 to 4 000 l of water/ha. Residue samples taken 23 days later contained no detectable pyrimidine-carbamate residues (limit of determination 0.02 mg/kg) (Bullock and Kennedy 1981). This was an anticipated finding, as sweet corn on the cob is protected from spray by the surrounding foliage. Pirimicarb is not registered for use on rice at this time and no data on residues are available. Citrus fruit The 1976 Meeting proposed a temporary MRL in citrus fruits of 0.05 mg/kg, at or about the limit of determination of the analytical method. Interpretation of much of the data available in 1976 was rendered difficult by the fact that often the peel and flesh were analysed separately. Whole fruits had been analysed on only a limited number of occasions, although the available data justified the proposed MRL. Supportive evidence was provided by the separate analysis of peel and flesh of oranges treated in Australia and in Spain. Residues were less than 0.02 mg/kg in edible flesh and did not exceed 1 mg/kg in the peel. At the time, results for samples obtained from Japan were deemed unrepresentative, particularly since there was a concern over possible contamination of the edible flesh with residues during peeling. Aphids usually occur on citrus early in the season. This is several months before the first fruits are mature. However, the harvesting period often extends from the autumn through to the following spring. As a result, fruit can remain on the tree at the time of the first sprays against aphids during the following year, and then a short pre-harvest withholding interval is appropriate. Ferreira and Tainha (1981) in Portugal have now provided new evidence of residues on whole oranges. In Portugal, pirimicarb is approved as a 50% WP formulation for use in citrus at a spray concentration of 37.5 g a.i./hl, applied to "run off". The pre-harvest withholding interval is two weeks. Two spray applications were made, fourteen days apart, to three separate replicate trees. Samples of 15 fruits were collected from each tree 1, 4, 7, 11, 21 28 and 35 days after the second spray. Analyses by a slight modification of the standard residue method yielded results as shown in Table 2. TABLE 2. Residues of pirimicarb in organge, Portugal, 1980 Application Days between Total carbamate residues (mg/kg) Rate last treatment and harvest Tree No.11 Tree No.21 Tree No. 31 Mean 1 0.69 0.64 0.99 0.77 37.5 g a.i./h 4 0.27 0.27 0.52 0.35 applied to 7 0.27 0.30 0.35 0.31 "run off" , 11 0.37 0.16 0.30 0.28 twice, fourteen 14 0.21 0.14 0.22 0.19 days 21 0.14 0.20 0.29 0.21 apart. 28 0.20 0.22 0.28 0.23 35 0.18 0.20 0.24 0.21 1 mean of three analyses (uncorrected for recovery). Residues in oranges are present mainly in the oil glands of the peel, in which they tend to remain stable. Levels in the edible flesh have been consistently below 1 mg/kg (Table 3) (Manley 1972; Edwards and Dick 1976; Bullock and Kennedy 1981). Apple and pear The 1976 Meeting proposed a temporary MRL for apples at 1 mg/kg. Additional residues data now available from trials in Canada in 1980 and Federal Republic of Germany in 1977 confirm the appropriateness of this value (Table 4) (Bullock and Kennedy 1981). TABLE 3. Residues of pirimicarb in orange, Australia and Japan, 1970-78. Days Country Rate Volume Crop between Total Reference and Fomulation of of spray part last carbamate Year application (l/ha) analysed application residues and (mg/kg) harvest Australia 50% WP 0.025 kg "High Whole 0 <0.01 Edwards and Dick 1973-4 a.i./hl volume" fruit 1 <0.01 1976 7 <0.01 14 <0.01 Skin 0 0.95 1 0.60 7 0.32 14 0.36 Flesh 0 <0.02 1 <0.02 7 <0.02 14 <0.02 Japan 50% WP 0.05 kg 5000 Skin 11 13.0 Manley 1970 a.i./hi 21 4.9 1972 (four 31 7.2 applications 42-43 2.1-3.0 over 9-10 49 0.72-2.4 weeks) 59-63 0.67-3.6 TABLE 3. (con't) Days Country Rate Volume Crop between Total Reference and Fomulation of of spray part last carbamate Year application (l/ha) analysed application residues and (mg/kg) harvest 0.05 kg 5000 Skin 11 16.5 a.i./hl 31 5.1-11.6 (five 42-43 5.2 applications 49 2.4 over 9-10 59-63 1.6-4.7 weeks) 0.05 kg 5000 Flesh 11-63 <0.01-0.88 a.i./hi (mean 0.19; (4-6 16 samples) applications over 9-11 weeks) Japan 48% 0.05 kg 3300- Skin >123 days 0.03-0.34 Bullock and Kennedy 1977 Dispersible a.i./hl 5000 (four 1981 Grain (3 or 2 results) applications Flesh <0.02 approx. (four 11 weeks results) apart) Juice <0.02 (two results) TABLE 4. Residues of pirimicarb in apple, Canada 1980 and Federal Republic of Germany 1977 Country Rate of Days between Total Carbamate residues (mg/kg) and application last application Year Formulation (kg a.i./ha) and harvest Minimum Maximum Mean Canada 50% WP 0.56 0 - - 0.58 (1)1 1980 3 - - 0.42 (1) 8 - - 0.19 (1) 14 - - 0.05 (1) Germany 50% 0.5 0 0.42 0.69 0.49 (4) 1977 Dispersible 3 0.22 0.51 0.31 (4) grain 7-8 0.17 0.51 0.27 (4) 10-11 0.16 0.45 0.21 (4) 14 0.17 0.49 0.24 (3) 20-21 0.09 0.49 0.13 (3) 1 Figures in parentheses are the numbers of results on which the means are based. A trial was also carried out in the UK on pears, using a single application of a 50% dispersible grain formulation at a rate of 0.21 kg a.i./ha. Samples for residue analysis were taken at 0, 2, 7 and 107 days. The initial total carbamate residue of 0.39 mg/kg decayed slowly over the following seven days, to 0.27 mg/kg. No residue was detected in the 107-day sample (limit of determination, 0.02 mg/kg) (Bullock and Kennedy 1981). Two trials were also carried out on pears in Japan in 1973. Two or three applications of a 50% dispersible powder formulation were made at 0.05 kg a.i./hl, at 2500 l of spray per ha. Samples for residue analysis were taken 54 and 64 days after the last applications. As expected with such long intervals, no residues were detected in any of the four samples analysed (limit of determination, 0.02 mg/kg) (Edwards and Dick 1976). Data reviewed at the 1976 Meeting indicated that pirimicarb residue levels on apples tend to decline more slowly than on many other crops, such as leafy vegetables. The data now available on pears are consistent with the findings on apples, in terms both of the levels of residues present and in the pattern of residue decline. Pecan At 0.0125-0.025 kg a.i./hl applied 'high volume', pirimicarb controls the black margined aphid, Monellia costalis, yellow aphid, Monellia sp. and black pecan aphid, Tinocallis caryaefoliae, on pecans. Aphids usually occur on pecans early in the season, although a second infestation can appear a few weeks before harvest. At that time, the nut is still protected by the hull and as a result it is unlikely that residues would be detected in the nut. That expectation was confirmed in four trials conducted in the USA in 1975. Pirimicarb was sprayed at 0.125 to 0.375 kg a.i./ha up to three times, using a 50% WP formulation. Nuts were harvested 17 to 77 days after the last application. No pyrimidine-carbamate residues were detected in any of the ten samples analysed (limit of determination, 0.05 mg/kg) (Ussary 1976). Cotton At 0.03 to 0.06 kg a.i./ha, pirimicarb controls the cotton aphid, Aphis gossypii. Aphid attack on cotton occurs early in the growing season and it is unlikely that a residue would be detected in the seeds at harvest. This expectation was confirmed in six trials conducted in the USA in 1976-78. Two to four applications of pirimicarb were made using a 50% WP at 0.06 or 0.12 kg a.i./ha. The cotton was harvested 40 to 122 days after the last application. No pyrimidine-carbamate residues were detected in any of the ten samples analysed (limit of determination, 0.05 mg/kg ) (Ussary 1979). Leeks, spinach and watercress Pirimicarb is particularly useful when a pre-harvest clean-up of aphid infestations is required. Aphids controlled by the compound include the peach-potato aphid, Myzus persicae, on leeks and watercress, shallot aphid, Myzus ascalonicus, on leeks, and the black bean aphid, Aphid fabae, on spinach. Three trials were conducted on outdoor leeks in Germany in 1977. A 50% dispersible grain formulation was applied on three occasions at 0.15 kg a.i./ha. Initial total carbamate residues on the leeks of 1.5 to 4.0 mg/kg declined rapidly with a half-life of less than one day (Table 5) (Bullock and Kennedy 1981). Work on three varieties of spinach was undertaken in Germany in 1974, using a single application of a 50% dispersible grain formulation at 0.5 kg a.i./ha. In three further trials in Germany in 1977, a 50% dispersible grain formulation was applied on three occasions at 0.15 kg a.i./ha. Initial total carbamate residues of approximately 3 to 8 mg/kg declined rapidly with a half-life of less than one day (Table 5) (Bullock and Kennedy 1981; Edwards and Dick 1976). Three trials were conducted on watercress in the UK in 1972, in which a 50% WP formulation was applied at 0.25 kg a.i./ha (recommended rate) or 0.50 kg a.i./ha. Total carbamate residue levels on the watercress again declined very quickly in the period immediately after application (Table 5)(Bullock 1972). The pattern of residues on these three crops are similar to those reviewed on various leafy vegetables at the 1976 Meeting. Glasshouse crops Some additional data on residues of pirimicarb on glasshouse crops have been received (Greve and van de Kamp 1974) and are recorded in Table 6. They are in line with data previously received on these crops. Other crops Trials involving the application of pirimicarb to broccoli, Brussels sprouts, peas, potatoes, soybeans, sugarbeet and turnips in various countries, gave rise to no residues above the limits of determination (generally <0.02 mg/kg). Further trials data on pirimicarb residues in some other fruits and vegetables are listed in Table 7 (Bullock and Kennedy 1981). TABLE 5. Residues of pirimicarb in leek, spinach and watercress1 Country Rate of Days Between Total Carbamate Residues Crop and Formulation application last application (mg/kg) Year (kg a.i./ha) and harvest Minimum Maximum Mean Leeks Germany 50% 0.15 0 1.5 4.0 2.6 (3)2 1977 dispersible × 3 1 0.3 0.65 0.48 (2) grain 2 - - 0.15 (1) 4 0.06 0.12 0.09 (3) 7 0.02 0.05 0.04 (3) 10 <0.02 0.02 0.02 (3) 14 <0.02 0.03 0.02 (3) Spinach Germany 50% 0.15 0 4.6 7.3 5.6 (3) 1977 dispersible × 3 1 0.72 2.0 1.3 (3) grain 4 0.16 0.50 0.29 (3) 7 0.05 0.06 0.06 (3) 10 <0.02 0.02 0.02 (3) Germany 50% 0.5 0 2.7 6.0 4.1 (3) 1974 dispersible (× 1) 1 1.5 2.1 1.7 (3) grain 3 0.14 0.65 0.39 (3) 5 0.01 0.12 0.07 (3) 7 <0.01 0.03 0.02 (3) 10 <0.01 0.02 0.02 (3) 12 - - <0.01 (1) TABLE 5. (con't) Country Rate of Days Between Total Carbamate Residues Crop and Formulation application last application (mg/kg) Year (kg a.i./ha) and harvest Minimum Maximum Mean Watercress UK 50% WP 0.25 0 5.9 22 11 (3) 1972 (× 1) 1 - - 1.1 (1) 2 0.43 0.51 0.44 (3) 4 0.37 0.39 0.38 (3) 7 0.16 0.20 0.18 (2) 0.5 0 - - 13 (1) (× 1) 2 - - 0.86 (1) 4 - - 0.95 (1) 7 - - 0.50 (1) 1 Bullock and Kennedy, 1981; Edwards and Dick, 1976; 2 Figures in parentheses are the numbers of results upon which the means are based. TABLE 6. Residues of pirimicarb in glasshouse crops1 Crop Residues (mg/kg) at intervals (days) after treatment 0 3 Range Mean Range Mean Eggplants 0.16-0.24 0.19 0.05 0.05 " 0.13-0.19 0.16 0.10-0.24 0.17 Gherkins 0.38-0.64 0.47 0.09-0.13 0.11 " <0.05 <0.05 <0.05 <0.05 Cucumber (whole) <0.05 <0.05 <0.05 <0.05 " (peel) 0.06-0.24 0.11 0.05-0.14 0.08 Tomato 0.12-0.21 0.14 " 0.09-0.13 0.12 <0.05 <0.05 Pepper (bell) 0.18-0.30 0.25 0.05-0.07 0.06 " " <0.05-0.11 <0.06 <0.05-0.14 <0.08 1 In each case, one treatment with 50% WP at 0.375 kg a.i./ha. FATE OF RESIDUES In processing Two studies were conducted in the USA in 1977 to determine residues of pirimicarb and its carbamate metabolites in processed cotton fractions. Cotton plants were sprayed with a 50% WP formulation of pirimicarb at 0.07 to 0.13 kg a.i./ha. Two to four applications were made with an interval of 49 to 122 days between the last application and harvest. The cotton was harvested, fractioned and submitted to the laboratory for residue analysis. The results are shown in Table 8. Although no pyrimidine-carbamate residues were observed in cottonseed, slight residues of up to 0.05 mg/kg were observed in crude oil. A trace was noted in cottonseed meal at the 0.13 kg a.i./ha rate (twice the maximum recommended). However, as no residue was detected in the cottonseed, it is unlikely that residues should be present in both the meal and oil. The trace residues in meal are most likely due to lack of sample homogeneity or possibly to minor contamination (Ussary 1979). TABLE 7. Pirimicarb residues in some fruits and vegetables Pre-harvest Pirimicarb residues (mg/kg) Crop Country Year Interval (days) Range Mean Cherry Fed.Rep.Germany 1977 0 1.5 - 1.9 1.4 4 0.03- 0.89 0.41 7 0.02- 0.52 0.26 14 <0.02- 0.33 0.15 UK 1976 62 <0.02 <0.02 Peach Japan 1976 27-61 0.13- 0.40 0.28 Canada 1980 60-107 <0.02 <0.02 Plum Canada 1976 21-30 0.14- 0.17 0.15 Pepper Denmark 1976 0 - 0.13 3 - 0.10 7 - 0.04 14 - 0.02 Tomato Canada 1976 1 - 0.10 3 - 0.03 7 - <0.02 Denmark 1977 0 - 0.46 3 - 0.16 7 - 0.09 14 - 0.02 Cucumber Denmark 1977 0 0.13, 0.47 - 3 0.08, 0.30 - 7 0.07, 0.38 - 14 0.02, 0.05 - 21 0.02, 0.07 - TABLE 7. (con't) Pre-harvest Pirimicarb residues (mg/kg) Crop Country Year Interval (days) Range Mean Parsley Netherlands 1976 0 - 23 1 - 15 3 - 8.6 7 - 6.3 14 - 4.6 TABLE 8. Pirimicarb residues on cottonseed fractions, USA 1977 Residue (mg/kg)1 Type of No of Days after last Sample applications application Control 0.07 kg ai/A 0.13 kg ai/A4 to harvest P2 DMP3 Total P DMP Total P DMP Total Cottonseed 4 49 ND ND ND ND ND ND ND ND ND Hulls ND ND ND ND ND ND Meal ND TR 0.01 ND 0.01 Crude oil ND ND ND 0.02 0.01 0.03 Cottonseed 2 122 ND ND ND Hulls ND ND ND Meal ND ND ND Crude oil 0.04 0.01 0.05 1 ND=none detected (<0.01 ppm of the individual compounds); 2 P = pirimicarb; 3 DMP = desmethyl pirimicarb; 4 Twice maximum use rate. METHODS OF ANALYSIS The preferred method for determining residues of pirimicarb and its carbamate-containing metabolites in crops and in products of animal origin is by gas-liquid chromatography with selective nitrogen detection. The method was reviewed at the 1976 and 1978 Meetings. NATIONAL MAXIMUM RESIDUE LIMITS The national MRLs listed in Table 9 have been established for residues of pirimicarb plus its two carbamate-containing metabolites, II and III (Figure 1). TABLE 9. National maximum residue limits reported to the Meeting Country Crop MRL (mg/kg) Australia Vegetables, fruit and hops 0.5 Belgium Potato 0.5 Other crops 0.3 Brazil Cabbage, cauliflower 0.5 Aubergine, cucumber, pepper, tomato 0.2 Potato 0.05 Fed. Rep. of Lettuce, cherry 1.0 ) from Germany Other leaf, sprout and fruit vegetables 0.5 ) 1.1.82 Cereals, potato, sugarbeet 0.1 ) France Cereals 0.05 (proposed) Hungary Fruit 0.5 Vegetables 1 Other crops 0.5 Japan Fruits and vegetables 0.3 Netherlands Fruits, vegetables, herbs and spices 1.0 Grain, potato 0.05 New Zealand Beans, lettuce, pea, brassicae, tomato 1 Potato, fodder crops 0.5 TABLE 9. (con't) Country Crop MRL (mg/kg) South Africa Cruciferae, oats, sorghum, wheat, peach 0.3 Peanut, pecan, potato 0.05 Switzerland Fruits and vegetables 1 USA Potato 0.1 Venezuela All Crops 0.5 EVALUATION COMMENTS AND APPRAISAL The Meeting was informed that the data requested by the 1978 Meeting would not be available until 1982. The Meeting therefore agreed to extend the existing temporary ADI until 1982. Additional data on residues of pirimicarb in a range of crops have been received and reviewed. The pattern of residue data is generally similar to that reviewed at previous meetings, although the new data on oranges show the need for an upward revision of the present limit to cover residues arising from use close to harvest in some countries. On outdoor vegetables and field crops the residues decline very quickly after spraying; on fruits, however, decline is slower. Data on pears, together with old and new data on apples, allowed a recommendation for limits on pome fruits. Additional and altered limits are proposed. RECOMMENDATIONS OF RESIDUE LIMITS The following new or altered temporary limits refer to the sum of pirimicarb, its N-formyl (methylamino) analogue (desmethylformamido pirimicarb) and desmethyl pirimicarb. Pre-harvest interval on Temporary MRL which the recommendations Commodity (mg/kg) are based (days) Pome fruits 1 7 Spinach 1 3-4 Watercress 1 2-4 Leeks 0.5 1-2 Oranges 0.5 7-14 Citrus fruits (other than oranges) 0.051 - Cottonseed 0.051 - Pecan 0.051 - Sweet corn 0.051 - 1 At or about the limit of determination. FURTHER WORK OR INFORMATION Desirable 1. Data on residues on oranges due to applications made close to harvest in countries other than Portugal. 2. Data on residues on other citrus fruits from countries where applications close to harvest are recommended or permitted. REFERENCES Bullock, D.J.W. Pirimicarb residues data on watercress: UK 1972. ICI 1972 Plant Protection Division. (Unpublished) Bullock, D.J.W. and Kennedy, S.H. Pirimicarb : residues in crops from 1981 field trials during 1976-80. ICI Plant Protection Division Report no. TMJ 1883A. (Unpublished) Cambon, C., Declume, C. and Derace, R. Foetal and maternal rat brain 1980 acetylcholinesterase: isoenzymes changes following insecticidal carbamate derivates poisoning. Archives of Toxicology 45: 257-262. Edwards, M.J. and Dick, J.P. Pirimicarb residue summary: Residues in 1976 crops from field trials during 1973-1975. ICI Plant Protection Division Report No. TMJ 1360B. (Unpublished) Ferreira, J.R. and Tainha, A. Residues of pirimicarb in field-treated 1981 oranges. Ministry of Agriculture and Fisheries, Toxicology and Analytical services Directorate, Portugal. Report PPA (TR)-12/81. (Unpublished) Fox, T. Pirimicarb dietary toxicity study in foxhounds. Report from 1978 Hazelton Labs. Europe Ltd., no. 1371-72/2, submitted by ICI Ltd. to WHO. (Unpublished) Greve, P.A. and van de Kamp, C.G. Residuen van bestrijdingsmiddeln in 1974 de groenteteelt onder glas. Report 96/74 Tox - ROB. Report from the Netherlands. (Unpublished) Heywood, R., Sortwell, R.J., Pulsford, A.H., Brown, G. and Street, 1977 A.E. Pirimicarb preliminary oral toxicity study in rhesus monkeys (repeated dosages for 13 weeks). Report from Huntingdon Research Centre, no. 164/77825, submitted by ICI Ltd. to WHO (Unpublished) Heywood, R., Sortwell, R.J., Pulsford, A.H,, Brown, G. and Street, 1978a A.E. Pirimicarb oral toxicity study in rhesus monkeys (repeated dosages for 17 weeks, followed by a recovery period of 8 weeks). Report (final report) from Huntingdon Research Centre no. 198/78444, submitted by ICI Ltd. to WHO. (Unpublished) 1978b Pirimicarb comparative data from native rhesus monkeys (white blood cell counts and direct Coombs Tests). Report from Huntingdon Research Centre, No. 219/78445, submitted by ICI Ltd. to WHO. (Unpublished) Jackson, J.A., Chart, I.S., Sanderson, J.H. and Garner, R. Pirimicarb 1977 induced immune hemolytic anaemia in dogs, Scandinavian Journal of Haematology, 19: 360-366. Jackson, J.A. and Royle, G. Pirimicarb: dietary toxicity study in 1978a foxhounds. Addendum: results of additional serological investigations. Report from ICI Central Toxicology Laboratory, no. CTL/P/420, submitted by ICI Ltd. (Unpublished) Jackson, J.A.; and Royle, G. Pirimicarb: oral toxicity study in rhesus 1978b monkeys. Addendum: results of additional serological investigations. Report from ICI Central Toxicology Laboratory, no. CTL/P/421, submitted by ICI Ltd. (Unpublished) 1978c Pirimicarb: comparative data from native rhesus monkeys (white blood cell counts and direct Coombs tests). Addendum: results of additional serological investigations. Report from ICI Central Toxicology Laboratory, no. CTL/P/419 submitted by ICI Ltd. (Unpublished) Manley, C.A. residue summary: Pirimicarb in crops. ICI Plant 1972 Protection Division Report no. TMJ 585/2. (Unpublished) Parkinson, G.R. Pirimicarb metabolite R 34885: subacute oral toxicity 1978a to rats. Report from ICI Central Toxicology Laboratory, No. CTL/P/402, submitted by ICI to WHO. (Unpublished) 1978b Pirimicarb metabolite R34836: subacute oral toxicity to rats. Report from ICI Central Toxicology Laboratory, no. CTL/P/401, submitted by ICI to WHO. (Unpublished) Paul, J.D., Richards, D., Banham, P.B. and Weight, T.M. Pirimicarb: 1978 growth study to determine a no-effect level in the female rat. Report from ICI Central Toxicology Laboratory no. CTL/P/408, submitted by ICI to WHO. (Unpublished) Pilinskaya, M.A. Cytogenic effect of a number of pesticides in a 1981 culture of human peripheral blood lymphocytes with different levels of spontaneous aberrations. Tsitologiya i Genetika, 15(2) : 82-84 Richards, D., Banhan, P.B. and Weight, T M. Pirimicarb paired feeding study in a female rat. Report from ICI Central Toxicology Laboratory, no. CTL/P/407. Submitted by ICI to WHO. (Unpublished) Ussary, J.P. Pirimicarb residues in pecan, 1975. ICI Americas Inc. 1976 Reports. (Unpublished) 1979 Pirimicarb residues on cottonseed. ICI Americas Inc, Report no. TMU 0442/B. (Unpublished)
See Also: Toxicological Abbreviations Pirimicarb (Pesticide residues in food: 1976 evaluations) Pirimicarb (Pesticide residues in food: 1978 evaluations) Pirimicarb (Pesticide residues in food: 1979 evaluations) Pirimicarb (Pesticide residues in food: 1982 evaluations)