PIRIMIPHOS-METHYL JMPR 1976 Explanation Pirimiphos-methyl was first evaluated at the 1974 Joint FAO/WHO Meeting on Pesticide Residues (FAO/WHO, 1975). A temporary acceptable daily intake for man was established. Additional toxicological and residue studies on this compound have become available and are summarized in this addendum. EVALUATION FOR ACCEPTABLE DAILY INTAKE BIOCHEMICAL ASPECTS Absorption, distribution and excretion Additional data are presented on the concentration of pirimiphos-methyl and metabolites in rat tissues and on the blood profile following a single oral dose. When rats were given a single oral dose of 2-14C-labelled pirimiphos-methyl at 7.5 mg/kg the uptake of radioactivity into blood and its subsequent disappearance from the blood stream were both very rapid. More than 50% of the radioactivity present in the blood 30 minutes after dosing had disappeared at 1 hour after dosing. Total radioactive residues in the blood 24 hours after dosing (generally 0.2-0.3 mg/l pirimiphos-methyl equivalents) did not increase following daily dosing of 2-14C-labelled pirimiphos-methyl for a further 3 days. Unchanged pirimiphos-methyl normally represented less than 10% of the total residue in the blood 24 hours after dosing. When 2-14C-labelled pirimiphos-methyl was administered orally to rats at 7.5 mg/kg/day for four days, total radioactive residues in the liver, kidney and fat did not normally exceed 2 mg/kg pirimiphos-methyl equivalents. Levels of unchanged pirimiphos-methyl where detected were very small and did not exceed 0.15 mg/kg in fat or 0.1 mg/kg in liver and kidneys. There is no evidence to show that either pirimiphos-methyl or its metabolites accumulated in the liver, kidney or adipose tissue of rats following daily dosing with the insecticide over 4 days (Mills, 1976). TOXICOLOGICAL STUDIES Special studies on mutagenicity Pirimiphos-methyl was tested for dominant lethal mutagenic activity in mice. Male animals were given orally 15, 80 or 150 mg/kg body weight for 5 days before mating. Groups receiving ethylmethanesulphonate (EMS) and cyclophosphamide were used as positive controls. Mating was carried out during 8 consecutive weeks, each week with new virgin females (2 females per male). These were killed 15 or 16 days after caging and examined for live implantations and early and late foetal deaths. The ovaries were examined for the number of corpora lutea. Pregnancy frequency was statistically significantly lower in the 150 mg/kg group. No other effects were noted in the pirimiphos-methyl groups which give an indication of any mutagenic activity. Such effects were amply demonstrated in the positive control groups (McGregor, 1975). Pirimiphos-methyl has shown evidence of mutagenic activity in Salmonella typhimurium but not in Escherichia coli. No metabolic activation was used in this study (Hanna and Dyer, 1975). Special studies on neurotoxicity Pirimiphos-methyl was tested for neurotoxicity in the hen. Two groups of five hens were given single oral doses of 50 and 60 mg/kg (dose rates for LD50) respectively. They were observed for 21 days. Four birds survived in the first group and 2 birds in the second group. On day 21 of the study one additional bird was added to the group dosed with 50 mg/kg and three to the group dosed with 60 mg/kg. The birds were protected with intramuscular injections of atropine and pralidoxime and then re-dosed at 50 or 60 mg/kg. No neurotoxic symptoms were observed on clinical assessment or during histological examination after a further 21 days. Tri-o-tolyl phosphate (500 mg/kg) was used as a positive control compound and all birds showed signs of ataxia and significant neuropathological changes. It is concluded that pirimiphosmethyl is not neurotoxic (Ross et al., 1975) Special studies on potentiation A test for potentiation of the acute toxicity of a combination of pirimiphos-methyl and bioresmethrin was conducted by administration of a suspension of the two compounds mixed in the ratio of their LD50 values. The degree of potentiation was assessed by finding the ratio between the expected toxicity and the observed toxicity of the mixture. The results obtained suggested that potentiation between pirimiphos-methyl and bioresmethrin does occur (ratio of expected to observed) but the extent does not appear sufficient to be of practical significance (Parkinson, 1975). Special studies on reproduction In an assessment of the effect of pirimiphos-methyl on reproductive functions of the rat, dietary concentration of 5, 10 and 100 ppm were fed continuously to three generations of rats. There were no consistent dose-related effects on parent animals in respect of signs of reaction, mortalities, food consumption, bodyweight change, mating performance, pregnancy rate or duration of gestation. There were no consistent dosage related effects on values for litter size, pup mortality rates, litter weight, mean pup weight or the incidence of anomalies. Terminal observations of the F3 generation showed no conclusive differences in organ weight. The only differences to attain statistical significance related to the higher absolute liver weight of males at 10 ppm and the lower absolute thyroid weight of males at 100 ppm. However, the significance of these differences was not maintained following adjustment for differences in body weight. For both sexes depression of both plasma and erythrocyte cholinesterase activity in excess of 20%, considered biologically significant, was recorded at 100 ppm in each generation, but not at 5 and 10 ppm levels. Pirimiphos-methyl at 100 ppm has no significant effect on growth and reproductive functions of the rat (Palmer and Hill, 1976). Special studies on egg production and hatchability The study was designed to assess the effect of dietary inclusion of pirimiphos-methyl on body weight and food consumption of laying hens and on their egg production and hatchability. Groups of 35 hens and 4 cockerels were fed doses of 0, 4, 12 and 40 ppm pirimiphos-methyl for 28 days and then allowed a 14 day recovery experimental period. The effect of pirimiphos-methyl on number of eggs laid, egg quality, fertility and hatchability, chick body weight and mortality was examined, together with body weight and food consumption of parent birds. At all levels tested pirimiphos-methyl had no significant effect on egg quality, production, hatchability, or any other effect that could be observed on any of the parameters measured. This study was undertaken in view of the large number of chicks dead in the shell found in a previous experiment, the validity of which was doubted when a fault was discovered in the incubator. In addition, samples of egg, liver and mixed flesh were analysed for pirimiphos-methyl and two of its metabolites. Values were below the level of detection in egg yolk following the 7 day withdrawal period. Except in the mixed flesh from samples taken on day 21 of the study all samples were below detection (Ross et al., 1975a,b). Acute toxicity 2-ethylamino-4-hydroxy-6-methylpyrimidine (I) and 2-amino-4-hydroxy-6-methylpyrimidine (II) have both been identified as degradation products of pirimiphos-methyl in animals, in plants and in stored products. Their acute oral mammalian toxicity has been assessed and found of low order. The acute oral LD50 of compound (I) in the female rat is 2093 mg/kg. 95% confidence limits: 1841-2380 mg/kg. Toxic symptoms set in rapidly and were of short duration. They included urinary incontinence and salivation. Deaths occurred within 24 hours and surviving animals were fully recovered within four days. No deaths and no toxic symptoms were observed after the administration of compound (II) to the tested female rat at 4000 mg/kg (Parkinson, 1974).Short-term studies Rat Pirimiphos-methyl was administered to young rats at doses of 0, 5, 8, 10 and 50 ppm in the diet for a period of 28 days in order to determine the no-effect level on plasma cholinesterase activity and body weight gain. Plasma cholinesterase activity was inhibited at the 50 ppm level throughout the dosing period by 30% and 50% in male and female animals respectively. No effect on erythrocyte cholinesterase activity was detected. There was a tendency towards poorer food utilization in the group but there was no effect on body weight gain. There were sporadic instances of statistically significant depressions of plasma cholinesterase activity at the 8 and 10 ppm levels but less than 25% and not dose related. The "no effect" level for pirimiphos-methyl in the young rat was 10 ppm in the diet administered for a period of 28 days. This is also the no-effect level established for pirimiphos-methyl in the rat over two years (FAO/WHO, 1975; Berry and Gore, 1975). Dog In order to examine the potential hepatic effect of pirimiphos-methyl in the dog, ten more dogs were given 25 mg/kg/day with six dogs acting as controls. Three of the dogs were killed after four weeks dosing for histopathological examination. The remaining animals were maintained at the same dose level for a total period of 13 weeks except for two dogs whose dose was raised progressively to 50 mg/kg/day from week eight onwards. Slight bile duct proliferation was present in two dogs given 25 mg/kg pirimiphos-methyl for 13 weeks. None of the other dosed animals showed this effect even when the dose was increased to 50 mg pirimiphos-methyl/kg/day in two other dogs. The effects in the dog liver characterised by bile duct proliferation in a certain number of dogs given 25 mg/kg/day was confirmed. However the changes appear to be small and dependent upon individual animal sensitivity and reversible; the mode of action could not be ascertained. Focal inflammation was present in the livers of control and dosed animals. Liver changes were shown in the rat at levels of 300-600 ppm in the diet and in dogs dosed at 10 mg/kg/day for two years (Garuti et al., 1976). Long-term studies Mouse Four groups of 52 male and 52 female mice of the CFLP strain were fed 0, 5, 250 and 500 ppm pirimiphos-methyl in the diet for 80 weeks. Three extra groups of 12 male and 12 female mice were fed 0, 5 and 500 ppm and were used for the investigation of cholinesterase levels. There were no significant differences in mortality between control and treated groups. Macroscopic examination of descendants gave no indication of treatment-related change. Efficiency of food utilization and overall body weight gain were not affected. Food consumption was reduced slightly among females receiving 500 ppm only. No changes ascribable to the administration of pirimiphos- methyl were seen during gross and histological examination at autopsy. Changes in the kidneys, namely foci of lymphocytic infiltration in the interstitium, or minimal perivascular or peribronchiolar lymphoid aggregations in the lung and abscesses and small haemorrhages in ovaries and other morphological changes in various tissues were seen in a proportion of animals of all groups including controls and were considered to be of no toxicological significance. Similarly the liver tumour incidence was comparable to that of the controls. There was no evidence to suggest that treatment with pirimiphos-methyl altered the tumour profile of the CFLP mouse at levels up to 500 ppm. However, animals of both sexes showed marked inhibition of plasma and erythrocyte cholinesterase activities at the 500 ppm dietary inclusion level. When corrected for differences prevailing between groups at the start of the study, differences in erythrocyte cholinesterase activity between the control and 5 ppm pirimiphos-methyl groups were normally less than 20% and consistently less than 25%. Plasma cholinesterase activities in both untreated and 5 ppm dietary inclusion level groups followed similar, slightly fluctuating patterns during the study, although levels in both sexes in the treated group appeared inhibited by comparison with controls. However there was no evidence of progressive inhibition during treatment and differences between the control and 5 ppm groups were considered to be of borderline biological significance (Hunter et al., 1976). A "no-effect" level at 5 ppm in the diet, equivalent to approximately 0.5 mg/kg/day was established over an 80 week period. OBSERVATIONS IN MAN A group of seven healthy volunteers, consisting of three males and four females, was given orally a dose of 0.25 mg pirimiphos-methyl/kg bw, in capsule form for a period of 56 days. No effect due to the administration of pirimiphos-methyl was seen on liver function tests, blood count or erythrocyte or plasma cholinesterase activity (Howard and Gore, 1976). COMMENTS Results of studies on the effect of pirimiphos-methyl on rat reproduction in a three generation test, on avian-egg production and hatchability and of special tests on mutagenicity were negative. Hydronephrosis incidence noted in a previous test has been shown to be well within the limits of control values pertaining to the same species. Two studies were performed to investigate the potential hepatotoxicity of pirimiphos-methyl. In an 80 week mouse study the tumour incidence (including that in liver) was comparable in test and control groups. In a three month dog study slight bile duct proliferation was observed in animals dosed at 25 mg/kg/day, however the effect was absent at 50 mg/kg/day. Focal inflammation occurred equally in the livers of control and dosed animals. In a 56 day human study, 0.25 mg/kg/day did not induce any changes in liver function tests, blood count or erythrocyte or plasma cholinesterase activity. Additional biochemical data presented established that the substance is very rapidly absorbed, metabolised and excreted. The Meeting agreed that the previously indicated further studies have been carried out satisfactorily, and there is no objection to estimating a permanent acceptable daily intake. TOXICOLOGICAL EVALUATION Levels causing no toxicological effects Mouse 5 ppm in the diet equivalent to 0.5 mg/kg bw/day Rat 10 ppm in the diet equivalent to 0.5 mg/kg bw/day Man 0.25 mg/kg bw/day ESTIMATE OF ACCEPTABLE DAILY INTAKE FOR MAN 0 - 0.01 mg/kg bw/day RESIDUES IN FOOD AND THEIR EVALUATION The 1974 evaluation of pirimiphos-methyl (FAO/WHO, 1975) was principally in relation to its use as a treatment of stored grains. However the insecticide is also used on growing crops, in public health and in industrial outlets. Therefore, arising out of the list of requirements in the report of the 1974 Joint Meeting, the following additional data are now presented. 1. Information on pre-harvest use patterns and residues in fruit and vegetables. 2. Information on residues in peanuts and other stored products. 3. Further information on the level and fate of residues at the point of consumption following the use of pirimiphos-methyl for the control of various stored product pests. USE PATTERN Pre-harvest Pirimiphos-methyl is a fast-acting broad-spectrum organophosphorus insecticide with both contact and fumigant actions. It is effective against a wide range of flying and crawling insects, including aphids, scales, mealy bugs, whiteflies, bugs, thrips, beetles, caterpillars, moths and ants. It also has acaricidal activity. It controls both adult and immature stages of insects such as whiteflies, and is effective against strains of insects which have developed resistance to malathion. Because it has only limited biological persistence on leaf surfaces, pirimiphos-methyl is particularly attractive for uses in which a broad spectrum of insecticidal activity is required for a short period. e.g. pre-harvest clean-up of vegetables. Rates of 0.5-1.0 kg a.i./ha "low volume" or 0.05-0.1% a.i. "high volume" are normally recommended. 0.5-0.75 kg a.i./ha (or 20-30 mg a.i. per m3) is normally effective in controlling greenhouse whiteflies by fogging. A fogging rate of 40 mg per m3 is used to control mushroom flies. The principal formulation is a 50% emulsifiable concentrate. A 50% oil-based formulation is available for ultra-low volume application to outdoor crops and a 10% oil-based formulation is used for whitefly control under glass. An 8% emulsifiable concentrate is sold to the amateur gardener. Dust and aerosol formulations are under development for crop uses. A pre-harvest withholding interval of four days is normally recommended after spraying. No pre-harvest withholding interval is normally recommended after the use of a fog to control 1. whiteflies on greenhouse tomatoes, cucumbers and peppers. 2. mushroom flies. Pirimiphos-methyl is not generally recommended for use on celery. RESIDUES RESULTING FROM SUPERVISED TRIALS Pre-harvest uses Data reviewed by the 1974 Joint Meeting showed that pirimiphos-methyl is rapidly lost from leaf surfaces during the first 2-3 days after spraying, mainly by volatilisation. Levels of the parent insecticide and the major degradation product, compound II (Figure 1), represent less than 10% of the applied material after two to three days. After foliar treatment the hydroxy- pyrimidine IV, formed by hydrolysis of the insecticide, is unlikely to be a significant residue - the compound is usually present only in trace amounts and is degraded photochemically and bound to plant material. Photochemical degradation of pirimiphos-methyl on leaf surfaces leads to the formation of compound II which is not accumulated. When applied to water in which rice seedlings were growing, pirimiphos-methyl was not translocated significantly into the foliage; in these conditions the hydrolysis product IV is likely to represent the predominant pyrimidine residue. Compounds V and VI occur only in trace amounts. The new data show that pirimiphos-methyl residues on growing crops decline rapidly during the first few days after spraying. Bullock (1972) has studied extensively residues of pirimiphos-methyl in crops grown world-wide. Samples were analysed for residues of pirimiphos-methyl and of the phosphorus-containing metabolites II and III. However significant amounts of the metabolites did not appear and so were not reported. The highest initial residues are found in leafy vegetables. However, pirimiphos-methyl residues decline very quickly on these crops so that after four days levels on vegetables generally are below 2 mg/kg except on celery and occasionally on lettuce, spinach or Brussels sprouts where they may be higher (Table 1). Residues on tree fruits are normally less than 2 mg/kg after four days, while on soft fruits (currants and berries) they are generally below 1 mg/kg (Table 2). There was good agreement between the results obtained by Bullock and those obtained by a second laboratory on a set of apple samples from Japan. The residues which Bullock found in rice in husk (up to 0.21 mg/kg), in dehusked rice and in maize (<0.01 mg/kg in both cases) following pre-harvest spray uses are all within the temporary tolerance levels recommended by the 1974 Joint Meeting for post-harvest uses on these commodities. The use of fogs to control whiteflies under glass results in initial residues of 0.3 mg/kg or less in cucumbers, tomatoes and peppers (Table 3). Although treatments for whitefly control may need to be made every 3-5 days, the available data (ICI Plant Protection Division, 1973) indicate that no accumulation of pirimiphos-methyl residues occur in these fruits on repeated application. There is also no accumulation of residues in mushrooms following multiple applications of a fog (Table 3). Initial residues of up to 2.5 mg/kg were found to decline rapidly to below 0.5 mg/kg after two days (Bullock and Stephens, 1974). The new aerosol and dust formulations yield residues (Table 4) similar to those observed previously with sprays of the emulsifiable concentrate formulations on lettuce and blackcurrants (Boxwell and Bullock, 1976). Residues on tomatoes were marginally higher than after fogging but were still below 1 mg/kg immediately after application at normal rates.
Stored product uses In contrast to its short persistence on growing crops, pirimiphos-methyl possesses exceptional stability on stored products such as grains. Although high temperatures and high moisture levels in grain reduce the life of the deposit, the effect of these influences is much less than with other grain protectants approved or evaluated to date (FAO/WHO, 1975). During degradation, residues of pirimiphos-methyl on wheat grains are degraded by hydrolysis of the phosphorus-ester side chain, to give principally the parent hydroxy-pyrimidine IV (Figure 1) and also the related compounds V and VI. Levels of compound II are always extremely low (approximately 0.05 mg/kg over a period of 32 weeks in wheat grain treated at 4 mg/kg). No residues of the chemically unstable oxygen analogue III have been detected. The limit of detection for compound III is 0.01 mg/kg. Residues of the hydroxypyrimidine IV in stored grains are normally below 0.5 mg/kg. Peanuts Pirimiphos-methyl residues in undecorticated peanuts treated at the intended rate of 20 mg/kg did not exceed 5.0 mg/kg. Two trials were conducted in the U.S.A. in 1971-2 in which pirimiphos-methyl was applied at 20 and 50 mg/kg to undecorticated peanuts. Analytical results indicated that the target rates of treatment were achieved. Very little change occurred in the level of residues during the first month following application. Even at the end of three months substantially all of the deposit remained. The data suggest that the half-life is of the order of 5 months from the time of application. Twelve months after application the residue in the whole undecorticated nuts was approximately 20-25% of the original amount applied. These data have recently been published (Redlinger, 1976). A larger scale trial was conducted in the U.S.A. during 1972-73 (Ussary, 1975). Pirimiphos-methyl was applied at 10, 20 and 30 mg/kg as an admixture treatment to undecorticated peanuts. Analytical results again indicated that the target rate of treatment was achieved. 20-50% of the initial residue was present on the undecorticated peanuts after twelve months storage, compared with 10% in the case of malathion. During four commercial scale trials in the U.S.A. in 1973-74, in which pirimiphos-methyl was applied at the proposed commercial application rate of 20 mg/kg, 30-60% of the initial residue was present at bin emptying, that is after 4 ´-6 months storage (Ussary, 1975). TABLE 1. Residues of pirimiphos-methyl resulting from supervised spray trials on leafy vegetables and root crops (EC formulations) No. of Residues (mg/kg) at intervals (days) Rate a.i. applications after last application Crop Country Formulation % or kg/ha 0 4 7 Beans West Germany 50% EC 0.15 kg/ha 1 0.15-0.25 <0.01-0.07 <0.01-0.01 (Bush) 0.3 kg/ha 1 0.05-0.47 <0.01-0.08 <0.01-0.04 (French) U.K. 50% EC or 0.05% 1 0.06-0.07 0.01-0.03 <0.01-0.01 8% EC 0.1% 1 0.08-0.14 0.10-0.14 <0.01-0.06 0.2% 1 - 0.26 0.14 Peas U.K. 50% EC 0.1 % 1 - - <0.01 0.2 % 1-2 - <0.01 <0.01 Lettuce U.K. 50% EC or 0.025% 3 0.19-0.73 0.07-0.13 0.30-0.12 25% EC 0.05% 1-3 11-18 0.60-1.8 0.37-0.88 0.1% 1-3 19-39 1.8-2.9 0.63-2.1 West Germany 50% EC 0.025% 1 2.6-2.7 0.23 0.07-0.13 0.05% 1 3.4-7.3 0.52 0.14-0.71 0.1% 4.7 - 0.52 West Germany 25% EC (0.15 kg/ha 1 4.6-8.1 0.02-0.24 0.02-0.19 0.3 kg/ha 1 6-13 0.05-0.50 0.01-0.11 Spinach West Germany 25% EC 0.025% 1 3.2-6.7 0.35-1.0 0.22 0.05% 1 12-14 1.5-1.6 0.19-0.43 0.1% 1 21 3.4 0.75 Cabbage U.K. 25% EC 1.0 kg/ha 1 - 0.30-0.50** <0.02-0.28 2.0 kg/ha 1 - 0.31-1.8 0.09-0.40 West Germany 25% EC 0.15 kg/ha 1 0.13-1.4 0.05-0.18 <0.01-0.09 0.3 kg/ha 1 0.57-4.6 <0.01-0.69 <0.01-0.40 0.6 kg/ha 1 4.1 1.5 0.18 TABLE 1. (Cont'd.) No. of Residues (mg/kg) at intervals (days) Rate a.i. applications after last application Crop Country Formulation % or kg/ha 0 4 7 Cabbage Malaysia 25% EC 1.0 kg/ha 18 - - 0.01*** 2.0 kg/ha 18 - - 0.01-0.02*** Cauliflower U.K. 50% EC or 0.1% 1 0.20-2.0 0.01-0.11 <0.01 8% EC (Hearts) 0.2% 1 0.15-1.4 0.04-0.24 <0.01-0.04 (leaves) 50% EC or 0.1% 1 0.66-12 0.50-1.3 0.02-0.35 8% EC 0.2% 1 1.5-13 0.65-1.1 0.04-2.2 Brussels U.K. 50% EC 1.4 kg/ha 3 1.7-3.3 0.30-1.7 0.28-0.66 sprouts (0.1%) (buttons) 2.28 kg/ha 3 2.9-6.8 0.96-4.5 0.67-2.3 (0.2%) Brussels Netherlands 50% EC 0.5 kg/ha 1 0.26* 0.14** 0.07 sprouts (0.05 %) (buttons) 0.75 kg/ha 1 0.49* 0.39** 0.21 (0.075%) Spring U.K. 50% EC or 0.05% 1 0.28-1.6 <0.01-0.07 <0.01-0.08 onions 8% EC 0.1% 1 2.3-4.2 0.04-0.49 <0.01-0.46 Celery U.K. 8% EC 0.05% 1 18-34 3.1-8.8 1.2-2.7 0.1% 1 26-69 5.1-14 3.70-8.0 Carrots U.K. 50% EC 1.14 kg/ha 1 0.32-0.95 0.09-0.16 0.10-0.22 (0.1%) 2.28 kg/ha 1 0.57-2.2 0.17-0.48 0.12-0.50 (0.2%) TABLE 1. (Cont'd.) No. of Residues (mg/kg) at intervals (days) Rate a.i. applications after last application Crop Country Formulation % or kg/ha 0 4 7 Potatoes U.K. 50% EC 0.1% 2 <0.01 <0.01 0.2% 2 <0.01 <0.01 <0.01-0.02 Sugar West Germany 25% EC 0.05% 1 18 - 1.7 beets (0.3 kg/ha) 0.1% 1 38 - 3.1 (0.6 kg/ha) * Samples taken after 1 day ** Samples taken after 3 days *** Samples taken after 9-15 days TABLE 2 Residues of pirimiphos-methyl resulting from supervised spray trials on tree and sort fruits (EC and ULV formulations No. of Residues (mg/kg) at intervals after last application Formulation Rate a.i., Application Crop Country % or kg/ha 0 days 4 days 7 days Other Apples U.K. 50% EC or 0.1 % 3 0.51-1.3 0.25-0.67 0.10-0.80 8 % 0.05% 1 0.2 % 3 0.76-2.8 0.58-1.9 0.16-1.5 0.1% 1 France 50% EC 0.075% 6 - - - 2 weeks: 0.32 Japan 50% EC 0.1 % 1-3 - - - 10 days: 0.15-1.4 Pears Spain 50% EC 0.1 % 1 - - - 12 weeks: <0.01 Plums U.K. 50% EC 0.1 % 2 0.47-0.96 0.24-0.55 0.02-0.25 0.2 % 2 1.6-2.2 1.3-1.5 0.06-0.55 Lemons Italy 25% EC 0.05 % 1 - - - 9 weeks: 0.25 in peel 0.03 in flesh 0.075% 1 - - - 0.75 in peel 0.03 in flesh 0.01 % - - 0.27-0.35 - - in peel 0.02-0.03 in flesh Oranges Australia 25% EC 0.075% 2 - - - 4´ months: 0.69 in peel <0.01 in flesh 0.1 2 - - - 0.92 in peel <0.01 in flesh TABLE 2 (Cont'd.) No. of Residues (mg/kg) at intervals after last application Formulation Rate a.i., Application Crop Country % or kg/ha 0 days 4 days 7 days Other Oranges South 25% EC 0.075% 1 - - - 2-8 months: <0.01-0.01 in peel Africa <0.01 in flesh 0.01-0.125% 1 - - - <0.01-0.1 in peel <0.01-0.1 in flesh Olives Spain 50%ULV 0.25 kg/ha 2 - - 0.46 9-20 days: 0.07-0.36 0.5 kg/ha 2 - - - 0.16-0.45 1.0 kg/ha 2 - - - 0.18-1.4 Blackcurrants U.K. 8% EC 0.05 % 2 0.25-0.75 0.06-0.20 0.01-0.18 0.1 % 2 0.86-2.3 0.25-0.62 0.08-0.34 Raspberries U.K. 50% EC or 0.05% 1-2 0.81 0.23 0.13 2-5 weeks: <0.01-0.03 8% EC 0.01% 1-2 2.5 0.53 0.31 <0.01-0.09 Strawberries U.K. 50% EC or 0.05% 1 0.14-0.79 0.17-0.39 0.04-0.16 4´-7 weeks: <0.01-0.05 8% 0.1% 1 0.40-2.9 0.31-0.71 0.13-0.25 <0.01-0.05 TABLE 3. Levels of pirimiphos-methyl resulting from supervised residue trials on greenhouse crops and mushrooms using a 10% fogging formulation Number of Residues (mg/kg) at intervals after last application crop Country Rate (a.i.) Applications 0 days 1 day 2 days 3 days 4 days Cucumbers U.K. 0.75 kg/ha 1-4 0.06-0.30 0.03-0.11 0.02-0.11 0.01-0.04 <0.01 (=20 mg/m3) Netherlands 20 mg/m3 1-5 0.08-0.19 0.03-0.08 0.02 <0.01-0.02 0.02 20 mg/m3 5 +30mg/m3 1-5 - 0.04-0.20 - 0.01-0.08 0.02-0.03 Tomatoes U.K. 0.5 kg/ha 2 - 0.15 - - - (= 15 mg/m3) 1 kg/ha or 1-4 - 0.16-0.62 0.16 0.12 - 30 mg/m3 Netherlands 0.75 kg/ha 1-3 - <0.01-0.12 <0.01-0.18 0.08 - (= 20 mg/m3) 30 mg/m3 1-5 - 0.06-0.17 - 0.08-0.14 0.08-0.11 (= 1 kg/ha) Peppers U.K. 1 kg/ha 1 - 0.26 - - - Mushrooms U.K. 40 mg/m3 1 and 6 0.99 0.19 0.12 - 0.14-0.16 (two trials) -2.5 -1.4 -0.44 - (4-5 days) TABLE 4. Residues of pirimiphos-methyl resulting from supervised trials in the U.K. using dust and aerosol formulations (single application date per trial) Residues (mg/kg) at intervals after Crop Formulation Rate 0 days 2 days 4 days 7-8 days Lettuce Dust Normal 2.1-10 0.53-7.9 0.33-2.1 0.06-1.9 Overdosed 8.3-47 2.2-19 1.1-5.6 0.32-5.2 Aerosol Normal 1.6-21 0.53-11 0.34-2.8 0.16-1.8 Overdosed 13-40 6.2-25 2.0-7.6 0.75-3.8 Tomatoes Dust Normal 0.01-0.93 <0.01-0.15 0.07-0.09 0.04-0.07 Overdosed 0.18-1.4 0.08-0.89 0.05-0.13 0.02-0.03 Aerosol Normal 0.09-0.67 0.04-0.43 0.02-0.38 0.03-0.05 Overdosed 0.03-4.1 0.01-1.3 0.02-0.46 0.01-0.03 Blackcurrants Dust Normal 0.10-0.59 0.03-0.05 - - Overdosed 0.44-1.4 0.08-0.22 - - Aerosol Normal <0.01-0.27 <0.01-0.04 - - Overdosed 0.04-0.59 <0.01-0.29 - - During these studies there were wide variations between different samples analysed from the same bin. These were probably caused by non-representative sampling. Dust, estimated to constitute up to 10% of the contents of the bins, settles into layers in the bins. It contains several hundred mg/kg pirimiphos-methyl and in large bins it was impossible to sample the dust in a representative manner. However, residues in individual samples of undecorticated peanuts in the U.S.A. trials were generally below 5.0 mg/kg during the period after treatment at the proposed recommended rate of 20 mg/kg. The walls of the four warehouses used in the commercial scale trials were sprayed with a 0.5% aqueous suspension of pirimiphos-methyl and probe samples were taken adjacent to the walls during the storage period. Residues in the undecorticated peanuts were similar to those from the bulk of the warehouse and it was concluded that there was no major transfer of pirimiphos-methyl from the walls to the peanuts (Ussary, 1975). Rice The 1974 Joint Meeting recommended temporary tolerances of 10 mg/kg in rice (in husk), 20 mg/kg in rice bran, 2 mg/kg in dehusked rice and 1 mg/kg in polished rice. Cogburn (1976) in the U.S.A. found that an admixture treatment of pirimiphos-methyl at 10 mg/kg protected rice from all insect infestation for twelve months. At this rate residues in the rice in husk, bran, dehusked rice and polished rice were all within the temporary tolerance levels proposed by the 1974 Joint Meeting. Dates In supervised trials in Iraq, MacCallum, Deighton and Pascoe (1976) found that 500 mg pirimiphos-methyl per square metre sprayed onto packaging materials (cardboard or wooden boxes) was effective in protecting export dates from insect attack. A deposit of 125 mg per square metre was effective for the treatment of waxed paper liners. At these rates pirimiphos-methyl residues in the dates during the following six months were invariably small - i.e. less than 0.5 mg/kg. Cheese There is very little movement of pirimiphos-methyl into cheese stored on surfaces treated with the insecticide for mite control. Thomas and Rowlands (1975) treated a wooden plank at 440 mg per square metre with 2-14C-labelled pirimiphos-methyl and then stored a 22 kg Cheshire cheese, wrapped in a cloth, on it for fourteen weeks. The cheese was turned to stand on alternate ends weekly, as in normal storage practice. The radioactive residue was confined to the outer 4 mm of the cheese in which there was no detectable breakdown of pirimiphos-methyl. Levels of pirimiphos-methyl were approximately 40 mg/kg in the outer 1 mm and 5-10 mg/kg in the outer 6 mm of the cheese. On a "whole cheese" basis, this represents a residue of approximately 0.4 mg/kg. FATE OF RESIDUES In animals Extensive data were evaluated by the 1974 Joint Meeting on the fate of pirimiphos-methyl in goats, cows, hens, their edible tissues and in foods of animal origin. When fed to these animals, pirimiphos-methyl is rapidly metabolised and the metabolites are excreted, principally in the urine. Only very small quantities are excreted into milk or eggs. Cattle receiving pirimiphos-methyl in their ration do not accumulate significant quantities in edible tissues, including fat. Such organophosphorus residues as are detectable are of the parent compound. No residues of the phosphorus-containing metabolites II and III could be detected in meat, milk, butter or eggs (limit of detection: 0.01 mg/kg or below). Since the 1974 Joint Meeting, data on the fate in pigs and additional data on the fate in hens have become available. Pigs Davis et al. (1976) maintained groups of pigs for 21 and 29 days on diets containing 3, 10 and 34 mg/kg pirimiphos-methyl. No residues of pirimiphos-methyl or of its phosphorus containing metabolites II or III were detected in the kidney, liver, lung, heart or muscle (limit of detection: 0.005 mg/kg in each case). Small residues of pirimiphos-methyl and compound II were found in the fat of pigs fed pirimiphos-methyl at 10 and 34 ppm in the diet (Table 15). No residues were detected in the fat of pigs returned for eight days to untreated diet prior to slaughter. No residues of the P=0 analogue (III) were detected in any fat tissues (limit of detection 0.005 mg/kg). No residues of the hydroxypyrimidines IV and V were found in any of the above-mentioned tissues (limits of detection 0.01 mg/kg for compound IV and 0.04 mg/kg for compound V). Hens Ross et al. (1975b) confirmed the low residue levels in eggs and meat previously reported by other authors (FAO/WHO, 1975). Groups of laying hens were maintained for 28 days on diets containing 0, 4, 12 and 40 ppm pirimiphos-methyl. At all but the highest dose level, pirimiphos-methyl levels in the eggs were below 0.01 mg/kg. At the 40 ppm dietary inclusion level, pirimiphos-methyl levels in the egg yolk reached a plateau of 0.03-0.04 mg/kg after seven days. After the hens had been returned to untreated diet for seven days, pirimiphos-methyl residues in the yolks were below the limit of detection (i.e. less than 0.008 mg/kg). Residues in the albumen were negligible (less than 0.01 mg/kg). Residues of pirimiphos-methyl in meat tissues were below 0.01 mg/kg at all dose levels. No residues of the phosphorus-containing metabolites II and III were detected in any samples of eggs or meat (limit of detection: 0.006-0.02 mg/kg). In processing Initial data on the fate of pirimiphos-methyl residues or processing of stored products were reviewed by the 1974 Joint Meeting (FAO/WHO, 1975). Subsequent studies are described below. TABLE 5. Residues of pirimiphos-methyl and its desethyl metabolite in the fat of pigs fed pirimiphos-methyl in the diet Desethyl Days Level in diet Pirimiphos-methyl Metabolite on diet (ppm) (mg/kg) (mg/kg) 21 control ND ND 3 ND ND 10 0.008 0.016 34 0.034 0.034 29 3 ND ND 10 0.006 0.009 34 0.05 0.036 29 control ND ND + 8 days 3 ND ND recovery 3 ND ND 10 ND ND 10 ND ND 34 ND ND 34 ND ND ND: Not detected, less than 0.005 mg/kg Wheat Residues of pirimiphos-methyl in flour are relatively stable to the conditions found during baking to bread and biscuits. However, because of the dilution which the flour undergoes during these processes flour initially containing 1 mg/kg pirimiphos-methyl is likely to yield bread/biscuits containing residues of the order of 0.5 mg/kg. Bullock and co-workers (1976) have studied extensively the fate of pirimiphos-methyl during processing to bread and biscuits. In studies with the radiolabelled compound, flour was dosed with 2-14C-labelled pirimiphos-methyl and baked to produce white bread, wholemeal bread and biscuits. Although pirimiphos-methyl is known to be a relatively volatile compound, there was no significant loss of radioactivity by volatilisation. Distribution of radioactivity throughout the bread was fairly uniform. Unchanged pirimiphos-methyl accounted for 75-90% of the radioactivity in the baked product. The major degradation products formed during baking were the hydroxypyrimidines IV and VI, which accounted for 3-10% of the radioactivity in the final product. Similar results were obtained by residue analysis in a second set of studies. After correction for the weight increase when flour is baked to bread, residues of pirimiphos-methyl fell by 11-18%. Likewise, residue analysis of biscuits showed average losses of 8%. However, owing to the dilution of the flour which occurs during baking, the residue level of pirimiphos-methyl in bread will be lower than that in the corresponding flour. During extensive residue studies Bullock et al.(1976) found that levels of pirimiphos-methyl in bread and biscuits are likely to be about 50% of those in the flour from which they were derived. These findings agree well with the earlier work of Bullock (1973, 1974) which was reviewed by the 1974 Joint Meeting. No residues of the phosphorus-containing compounds II and III were detected in bread baked from flour treated with pirimiphos-methyl at 1 mg/kg or in biscuits baked from flour treated at up to 5 mg/kg (limit of detection: 0.03 mg/kg)(Bullock et al., 1976). The hydroxypyrimidine IV also undergoes little degradation during the baking process. This compound has previously been shown to constitute a minor part (generally less than 0.5 mg/kg) of the residue in stored grains (FAO/WHO 1975). When bread was baked from flour containing 2-14C-labelled compound IV, the unchanged hydroxypyrimidine constituted more than 90% of the radioactive residue in the bread (Bullock et al., 1976). By analogy with pirimiphos-methyl residues, it can be concluded that residues of compound IV in baked products will not exceed 0.2 mg/kg and will normally be considerably lower. The pattern and levels of residues found in semolina and cooked pasta prepared from pirimiphos-methyl treated wheat are similar to those found in flour and bread/biscuits respectively. Unchanged pirimiphos-methyl constitutes the major proportion of the residue. Bullock and May (1976) studied the fate of residues in wheat on processing to semolina and pasta. White semolina prepared from Durum wheat treated at 10 mg/kg contained only 1.6 mg/kg pirimiphos-methyl. Pirimiphos-methyl levels in both white and wholemeal pasta were approximately 85-90% of those in the corresponding semolina. 70% of the pirimiphos-methyl residue in semolina was transferred unchanged to cooked pasta. However the weight of pasta increases by 100% on cooking so that the concentration of pirimiphos-methyl in cooked pasta is likely to be approximately 35% of that in the corresponding semolina. Peanuts Pirimiphos-methyl residues in peanuts are found mainly on the hulls. There is little transfer of residue to the kernels. Pirimiphos-methyl residues in processed fractions obtained from the kernel are normally very much smaller than in the whole raw agricultural commodity. Ussary (1975) has reviewed the available unpublished data for pirimiphos-methyl residues in peanut fractions. He concluded that residues in the kernels depend upon the degree of contamination by the hulls which occurs in the differing shelling processes. Nevertheless in the commercial scale trials in the U.S.A. during 1973-74, where peanuts were treated at 20 mg/kg by admixture, pirimiphos-methyl levels in the sound mature kernels were normally less than 5 mg/kg. Undecorticated peanuts containing a mean residue of 10 mg/kg pirimiphos-methyl yielded oil containing 9-14 mg/kg pirimiphos-methyl. In the 1972-3 trials in the U.S.A. undecorticated peanuts treated at 20 mg/kg yielded peanut butter containing mean residues of 3 mg/kg (Ussary, 1975). In the series of admixture trials in the U.S.A, pirimiphos-methyl residues in the peanut hulls were normally below 50 mg/kg (Ussary, 1975). Residues in food in commerce Pirimiphos-methyl has not yet been widely used and therefore no information is available on residues in food moving in commerce. METHODS OF RESIDUE ANALYSIS The preferred method of residue analysis, by gas chromatography with a phosphorus detector, was reviewed by the 1974 Joint Meeting. The method was recently published (Zweig, 1976). It is suitable for the determination of residues of pirimiphos-methyl and the phosphorus- containing metabolites II and III in crops. The limit of determination is normally 0.01 mg/kg in each case. NATIONAL TOLERANCES The following national tolerances have been reported to the Meeting. Country Commodity Tolerance, mg/kg France Cereals 4 Fruit and vegetables 2 Netherlands Cucumbers, courgettes, peppers and tomatoes 0.2 West Germany Cereals 4* Grain parts 2* In the UK, where tolerances are not normally specified, pirimiphos-methyl is registered for uniform admixture with small grain cereals at 4 mg/kg. APPRAISAL Pirimiphos-methyl was evaluated by the 1974 Joint Meeting when, in addition to the required toxicological information, further data were considered desirable on its use on stored products other than grain, on residues on fruit and vegetables following approved uses, and on terminal levels in various foods. These data have been provided. In use on outdoor and indoor crops, since pirimiphos-methyl has only a limited biological persistence on leaf surfaces it can be used where a broad spectrum of insecticidal activity is required for a short period, e.g., pre-harvest clean-up of vegetables. Rates of 0.5-1.0 kg. a.i./ha "low volume" or 0.05 to 0.1% a.i. "high volume" are normally recommended. A fogging rate of 20-30 mg a.i./m3 is normally effective in controlling greenhouse whiteflies, and a fogging rate of 40 mg/m3 is used to control mushroom flies. *Temporary tolerance. A pre-harvest withholding interval of four days is normally recommended after spraying. but 0 to 3 days after the use of a fog to control whiteflies on greenhouse tomatoes, cucumbers and peppers or mushroom flies. Pirimiphos-methyl residues on growing crops decline rapidly during the first few days after spraying. On the leaf surfaces and other aerial parts of the plant the compound is lost principally by volatilization; photochemical or other degradation also occurs. However, there are no significant amounts of the degradation compounds containing the intact phosphorus ester grouping and the phosphorus-containing residue can be expressed as the parent compound. Following treatment at recommended rates, levels on vegetables are normally less than 2 mg/kg after four days but higher applications can occasionally lead to residues on some green leafy vegetables (lettuce, spinach, Brussels sprouts) not exceeding 5 mg/kg. On celery, on which it is not generally recommended, residues my be higher than this. Residues on tree fruit are below 2 mg/kg after 4 days whilst on soft fruits they are below 1 mg/kg. When used for fogging under glass, initial levels are 0.3 mg/kg or less on cucumbers, tomatoes and peppers. Residues of pirimiphos-methyl are relatively stable in the conditions found during baking to bread and biscuits. Flour containing 1 mg/kg of pirimiphos-methyl is likely to yield bread or biscuits containing about 0.5 mg/kg of the unchanged compound; the main degradation products do not contain phosphorus. Approximately similar changes occur when durum wheat is milled to white or whole meal semolina and this is subsequently made into pasta and cooked. Preparation of white semolina reduces the residue by about 80% (most of the pericarp is removed) but what is left is largely retained in pasta, even on cooking, although the proportion is halved in cooked pasta by uptake of water. These results, and the additional results obtained in stored rice, do not suggest a need for any alteration in the maximum residue levels proposed temporarily for wheat and wheat products and rice at the 1974 Joint Meeting and these are confirmed as maximum residue limits. Data evaluated by the 1974 Joint Meeting on the fate of pirimiphos-methyl in goats, cows, hens, their edible tissues and foods from them has now been supplemented by work with pigs which has shown no accumulation in the fat or meat of pigs maintained on diets containing pirimiphos-methyl at levels up to 34 mg/kg. Any residues of the parent compound or its phosphorus-containing metabolites were below the limit of detection (0.005 mg/kg) in muscle, kidney, liver, lung and heart, and very small in fat. When hens were fed for 28 days on diets containing up to 40 mg/kg of pirimiphos-methyl small residues (0.03 - 0.04 mg/kg) were found in eggs at the highest level of treatment. Residues of pirimiphos-methyl in meat tissues were below 0.01 mg/kg at all doses, and neither the desethyl compound nor the oxon was detectable in any samples of eggs or meat. RECOMMENDATIONS As an ADI has now been established, the temporary tolerances recommended by the 1974 Meeting are converted to maximum residue limits. The following additional limits are recommended. They refer to the sum of pirimiphos-methyl, its oxygen analogue and N-desethyl- pirimiphos-methyl expressed as pirimiphos-methyl. Commodity Limit, mg/kg Peanut hulls, peanuts (whole) 50 Peanut oil 10 Lettuce, mushroom, olives, peanuts (kernels), spinach 5 Apples, Brussels sprouts, cabbage, cauliflower, cherries, pears, plums 2 Blackcurrants, carrots, cucumber, gooseberries, peppers, raspberries, spring onions, strawberries, tomato 1 Beans with pod, cheese, citrus, dates 0.5 Peas, potatoes 0.05* * At or about the limit of determination FURTHER WORK OR INFORMATION DESIRABLE 1. Results of studies now in progress on the residues in peanuts and peanut products. 2. Results from commercial trials on other commodities. REFERENCES Berry, D., and Gore, C.W. Pirimiphos-methyl (PP511): Determination 1975 of no effect level during a 28 day rat feeding study. Unpublished report received from ICI Central Toxicology Laboratory. Submitted to the World Health Organization by ICI. Boxwell, J.W., and Bullock, D.J.W. Pirimiphos-methyl: Residues on 1976 crops following application of aerosol and dust formulations (UK). ICI Plant Protection Division Report No. TMJ1305A. (Unpublished) Bullock, D.J.W. Residue summary: Pirimiphos-methyl in crops. ICI 1972 Plant Protection Ltd. Report No. TMJ595/1. (Unpublished) Bullock, D.J.W., Harrison, P.J., and Day, S.R. Pirimiphos-methyl: 1976 Degradation of residues in flour during baking. ICI Plant Protection Division Report No. AR2666A. (Unpublished) Bullock, D.J.W., and May, M.S. Pirimiphos-methyl: Residue transfer 1976 from durum wheat to semolina and pasta. ICI Plant Protection Division Report No. TMJ1345A. (Unpublished). Bullock, D.J.W., and Stephens, P.P. Pirimiphos-methyl: Residues in 1974 mushrooms following application of pirimiphos-methyl by `Fumovap' gun and Swingfog machine. ICI Plant Protection Ltd. Report No. AR2543A. (Unpublished). Cogburn, R.G. Pirimiphos-methyl and a protectant for stored rough 1976 rice: Small bin tests. J. Econ. Ent., 69(3): 369. Davis, J.A., Day, S.R., Hemingway, R.J., Jegatheeswaren, T., 1976 and Bullock, D.J.W. Pirimiphos-methyl: residue transfer study with pigs. ICI Plant Protection Division Report No. AR2665A. (Unpublished) FAO/WHO 1974 Evaluations of some pesticide residues in food. AGP: 1975 1974/M/11; WHO Pesticide Residues Series No. 4. Garuti, A., Gore, C.W., Ishmael, J., and Kalinowski, A.E. 1976 Pirimiphos-methyl (PP511): A study of hepatic changes in the dog. Unpublished report from ICI. Hanna, P.J., and Dyer, K.F. Mutagenicity of organophosphorus 1975 compounds. Mutat. Res., 28: 405. Hodge, M.C.E., and Moore, S. Pirimiphos-methyl (PP511) teratological 1972 studies in the rat. Unpublished report from ICI Industrial Hygiene Research Laboratories. Howard, S.K., and Gore, C.W. The human response to long-term 1976 oral administration of low doses of pirimiphos-methyl. Unpublished report from ICI. Hunter, B., Graham, C., Street, Ae., Offer, J.M., and Printice, 1976 D.E. Long-term feeding of pirimiphos-methyl (PP511) in mice. (Final report 0-80 weeks). Unpublished report from Huntingdon Research Centre No. ICI/34/7650, submitted by ICI. ICI Plant Protection Ltd. Pirimiphos-methyl: Residues data for fogging 1973 use on cucumbers, tomatoes and peppers. (Unpublished). MacCullum Deighton, J., and Pascoe, R. Pirimiphos-methyl: Protection 1976 of stored dates: Trials in Iraq 1974/5. ICI Plan-Protection Ltd. Report No. AR2642A. (Unpublished) McGregor, D.B. Dominant lethal study in mice of pirimiphos methyl. 1975 Unpublished report from Inveresk Research International (No. 289). Mills, I.H. Pirimiphos-methyl: Blood concentrations and tissue 1976 retention in the rat. ICI Central Toxicology Report No. CTL/P/247. Palmer, A.K., and Hill, P.A. Effect of pirimiphos-methyl (PP511) 1976 on reproductive functions of multiple generations in the rat. Huntingdon Research Centre Report, submitted by ICI. Parkinson, G.R. Pirimiphos-methyl metabolites (R4039 and R35510): 1974 Acute oral toxicity. Unpublished report from ICI Central Toxicology Laboratory No. CTL/P/137, submitted by ICI. Parkinson, G.R. Pirimiphos-methyl potentiation studies with 1975 bioresmethrin. Unpublished report from ICI Central Toxicology Laboratory (No. CTL/P/166B). Submitted by ICI. Redlinger, L.M. Pirimiphos-methyl as a protectant for farmers 1976 stock peanuts. J.Econ. Ent., 69(3): 377. Ross, D.B., Burroughs, S.J., and Roberts, N.L. Examination of 1975a pirimiphos-methyl for neurotoxicity in the domestic hen. Unpublished report from Huntingdon Research Centre (No. ICI/49/75220) submitted by ICI. Ross, D.B., Christopher, D.H., Cameron, D.M., Dollery, R., 1976 Almond, R.H., and Roberts, N.L. Egg production and hatchability following inclusion of pirimiphos-methyl at various levels in the diet of the laying hen. Huntingdon Research Centre Report No. ICI/31A/75924. Thomas, K.P., and Rowlands, D.G. The uptake and degradation of 1975 pirimiphos-methyl by cheshire cheese. J. Stored Prod. Res., 11: 53. Ussary, J.P. ActellicR residues in peanuts. ICI United States 1975 Inc. Interim Report. (Unpublished) Zweig, G. Analytical methods for pesticides and plant growth 1976 regulators. Academic Press, 8: 125.
See Also: Toxicological Abbreviations Pirimiphos-methyl (WHO Pesticide Residues Series 4) Pirimiphos-methyl (Pesticide residues in food: 1977 evaluations) Pirimiphos-methyl (Pesticide residues in food: 1979 evaluations) Pirimiphos-methyl (Pesticide residues in food: 1983 evaluations) Pirimiphos-methyl (Pesticide residues in food: 1992 evaluations Part II Toxicology)