MONOCROTOPHOS JMPR 1972 IDENTITY Chemical name Dimethyl-1-methyl-2-methyl carbamoyl-vinyl phosphate (E)- Synonyms "Azodrin", "Azodrin(R) Insecticide", "Nuvacron", SD9129 Structural formulaPhysical and chemical properties of technical monocrotophos Physical state: reddish-brown mixture of solid and liquid (at 25-30°C) Odour: that of a mild ester Melting point: 25-30°C (technical) 54-55°C (pure) Vapour pressure: 7 x 10-5 mm Hg (at 20°C) Solubility: soluble in water, acetone and alcohol; very slightly soluble in mineral oils. Stability: stable when stored in glass and polyethylene containers. Technical grade has a half-life of 2 500 days at 38°C. Rate of hydrolysis in solution is slow. Half-life in solution (2 ppm) at pH 7.0 and 38°C is 23 days; at pH 4.6 and 100°C, half-life is 80 minutes. Purity: Analysis of a typical sample of technical monocrotophos gave the following results: % w Monocrotophos 77 Dimethyl-1-methyl-2-methylcarbamoyl-vinyl phosphate (Z)- 9 N-methylacetoacetamide 2 Dimethyl phosphate 5 Others (less than 1% w each) 7 100 EVALUATION FOR ACCEPTABLE DAILY INTAKE BIOCHEMICAL ASPECTS Absorption, distribution and excretion Following an oral dose of 1 mg/kg to male and female rats, monocrotophos was rapidly eliminated in the urine primarily as hydrolysis products (70% of the urinary excretion within six hours), unchanged monocrotophos (25%) and traces of the N-hydroxymethyl and desmethyl metabolites. In 24 hours the rate of excretion had diminished substantially, indicating rapid absorption and elimination (Menzer and Casida, 1965). Monocrotophos administered orally to a goat was found in the milk within one hour after treatment. Other metabolites were found in lesser quantity than the parent monocrotophos. Within 24 hours, the major quantity had cleared, and only minute residues were found (Menzer and Casida, 1965). Monocrotophos is a minor metabolite of dicrotophos (Bidrin(R)), its N,N-dimethyl crotonamide analogue, and treatment of rats with dicrotophos yielded small quantities of monocrotophos in the urine within two hours (Bull and Lindquist, 1964). Monocrotophos was fed to lactating dairy cows at a level of 45 ppm in the diet. Monocrotophos and two metabolites were found in milk. In urine further metabolites were observed (Potter, 1965). Biotransformation Monocrotophos injected into bean plants was metabolized to the N-hydroxy-methylamide (SD 12657) and the amide (SD 11319). Monocrotophos was more persistent in this plant study than dicrotophos-Bidrin(R), its N,N dimethyl analogue (Menzer and Casida, 1965). In cotton, monocrotophos has been shown to be metabolized to the hydroxymethyl derivative (SD 12657) but not to the amide (SD 11319). The oxidative route of metabolism yielding substituted crotonamides was found to be slower than the metabolic route yielding substituted phosphoric acid esters (Lindquist and Bull, 1967). A major water-soluble metabolite observed in plants by these authors was identified as a glycoside of the N-hydroxymethyl (SD 12657) derivative (Shell Chemical Co., 1972). The metabolic fate of monocrotophos in mammals has been well documented (Menzer and Casida, 1965; Bull and Lindquist, 1964; 1967). These data are summarized in Figure 1. Effect on enzymes and other biochemical parameters As with other organo-phosphorus esters, monocrotophos acts on the organism as a direct cholinesterase inhibitor. The selectivity of inhibition of cholinesterase from various sources in the body suggests that blood cholinesterase activity is the most sensitive parameter for exposure; brain cholinesterase activity is depressed only at higher levels of exposure. Penetration into the brain may be the cause, rather than a difference in sensitivity, although in vitro studies have shown that monocrotophos has a somewhat greater affinity (k2) and activity (I50) against rat RBC cholinesterase (Reiffy 1969). Monocrotophos is metabolized to compounds which are less potent inhibitors of human plasma cholinesterase, as evidenced by in vitro pI50 values, i.e., monocrotophos (SD 9129) - 6.5; N-Methyl hydroxy monocrotophos - 5.9; N-desmethyl monocrotophos - 5.6 (Menzer and Casida, 1965).
TOXICOLOGICAL STUDIES Special studies on metabolites The acute toxicity of metabolites of monocrotophos in mouse and rat is summarized in Table 1. The acute toxicity of components of technical monocrotophos in rat is summarized in Table 2. TABLE 1 Acute toxicity of monocrotophos metabolites Metabolite Reference N-methyl hydroxy monocrotophos (SD = 12657) Mouse ip LD50 = 12 mg/kg (Menzer and Casida, 1965) Rat oral LD50 = 27 mg/kg (Shellenberger, 1966a) N-desmethyl monocrotophos (SD 11319) Mouse ip LD50 = 3 mg/kg (Menzer and Casida, 1965) Mouse oral LD50 = 5.5 (Shellenberger, 1966a) Glycoside of N-desmethyl monocrotophos (SD 13311) Rat (M) oral LD50 = 168 mg/kg (Shell Chemical Co., 1966) N-methyl acetoacetamide Rat oral LD50 = >2 000 mg/kg (Shellenberger, 1966a) TABLE 2 Acute toxicity of components of technical monocrotophos Component Species Route LD50 (mg/kg) Dimethyl phosphate of 3-hydroxy-N-methyl-trans-crotonamide Rat Oral 420 Dimethyl phosphate of 2-chloro-3 hydroxy-N-methyl-cis-crotonamide Rat Oral 14 Dimethyl phosphate of 2-chloro-3 hydroxy-N-methyl-trans-crotonamide Rat Oral 140 Short-term studies on the glycoside metabolite (SD 13311) Groups of rats (42 males and 42 females per group, except for the highest level which had 22 of each sex) were fed the glycoside metabolite of monocrotophos (a glycoside of the dimethyl phosphate of 3-hydroxy-N-(hydroxymethyl)-cis-crotonamide) for 9 days at levels of 0, 1, 3, 9, 18 and 90 ppm (the 1 ppm was fed for seven weeks and the dosage increased to 18 ppm for the final five weeks). Rats were fed a normal diet for four weeks after the feeding study ended. Slight growth effects were noted at 90 ppm from 7-12 weeks in both sexes. Blood cholinesterase was depressed at 9 ppm in both sexes. At 18 ppm, brain cholinesterase was depressed. Cholinesterase activity was not affected at 3 ppm. No effects were observed on blood parameters or gross and microscopic histology (Shell Chemical Co., 1966). Special studies on neurotoxicity Groups of adult White Leghorn hens (ten hens per group) were fed monocrotophos in the diet at levels of 0, 1, 10 and 100 ppm for four weeks. A single group of ten hens was fed TOCP in the diet at 1 000 ppm for four weeks. At the end of the feeding interval, five birds from each group were sacrificed, and histological examinations of brain, spinal cord and sciatic nerve were performed. Physiological response, body-weight, food consumption and egg production data were collected. Monocrotophos at all dose levels produced a weight loss in hens. Egg production was not affected at 1 ppm but was inhibited at 10 and 100 ppm. Mortality occurred at 100 ppm, and although several birds showed tremors 10-12 days after feeding started, all were able to stand and walk normally. TOCP fed birds developed typical signs of ataxia after 16-17 days. All survivors were unable to stand at the end of the treatment period. Histological examination of TOCP-treated hens showed severe demyelination in the posterior horns of the spinal cord. Examination of nervous tissue from monocrotophos fed and control hens showed slight evidence of demyelinated tracts, primarily in the anterior horns. No differences were noted in controls and hens undergoing monocrotophos treatments. Monocrotophos does not produce delayed neurological signs of poisoning when compared to the response induced by TOCP (Shellenberger, 1965b). Special studies on potentiation Male rats were given oral doses of a combination of monocrotophos and the following anticholinesterase compounds, with no signs of potentiation: dioxathion, dimethoate, carbaryl, disulfoton, EPN, Folex, malathion, parathion, schradan, demeton, azinphos-methyl, dicrotophos, crotoxyphos, coumaphos, dichlorvos, diazinon, naled, trichlorphon, ethion, mevinphos, carbophenothion and phosphamidon. Potentiation of the acute oral toxicity was observed with monocrotophos in combination with fenchlorphos (Shellenberger, 1965a). Special studies on reproduction Groups of rats (10 males and 20 females per group) were fed monocrotophos in the diet at 0, 2, 5, 12 and 30 ppm, and subsequently mated. The progeny of this mating were maintained on this dietary regime and mated. This was followed for three generations (Eisenlord and Loquram, 1965). In a separate study groups of rats (10 males and 20 females per group) were fed monocrotophos at the same levels and subjected to a three-generation, two-litter per generation study (Eisenlord and Loquram, 1966). Effects due to monocrotophos were noted in both studies at levels of 5 ppm and above. Appearance and behaviour was affected at 12 and 30 ppm, as manifested in stunted growth and emaciation. Thinned or missing hair on the flanks or head was seen in all monocrotophos groups among adult females and pups, but not in adult males or controls. The level of 30 ppm was lethal to pups and reduced pregnancies. Pup mortality was evidenced at 5 ppm in both studies and absent at 2 ppm. Weight of parents was adversely affected at 30 ppm. At 12 ppm, several parents were affected (F2 and F3 males in one study and F2 females and F3 males in the second). No effects were noted on any parameter at 2 ppm. Gross and histopathological examinations showed no differences from the control values. Special studies on teratogenicity Groups of pregnant rabbits received oral daily doses of 0.7 and 2 mg/kg monocrotophos from day 6 to 18 of gestation. On day 28 of pregnancy, the foetuses were removed and examined. No compound-related teratogenic effects were observed (Thorpe and Dix, 1972). Acute toxicity The results of acute toxicity studies in animals are summarized in Table 3. TABLE 3 Acute toxicity of monocrotophos in animals Species Sex Route LD50 Reference (mg/kg) Rat M IP 5 Bull & Lindquist, 1967 M Oral 14-23 Shellenberger & Newell, 1963 Shellenberger, 1965b; 1966a F SC 7 Reiff, 1969 M Oral 18 Gaines, 1969 F Oral 20 Ibid. Mouse M&F IP 8 Menzer & Casida, 1965 Oral 15 Shellenberger & Newell, 1963 Guinea Pig M&F SC app.60 Hunter, 1964 Signs of poisoning following monocrotophos are typical of other anticholinesterase organo-phosphates. Toxic signs occur rapidly and in animals include tremors, lacrimation, diarrhea, salivation, tonic and clonic convulsions and other signs of cholinergic stimulation. Deaths occur rapidly, usually within four hours, and animals surviving 24 hours generally recover and appear normal. Atropine alone, but preferably in combination with reactivators (P2S or Toxogonin), was shown to be an effective antidote to monocrotophos poisoning in rodents (Hunter, 1964: Reiff, 1969). Short-term studies Japanese quail Groups of Japanese quail (12 males and 12 females per group) were fed monocrotophos at 0, 0.5, 5 and 50 ppm in the diet for three weeks. Mortality and weight loss occurred at 50 ppm. Food consumption was reduced at 5 ppm, while egg production was normal. Blood cholinesterase activity was depressed at all feeding levels, while brain cholinesterase activity was depressed at 5 ppm and above. At 5 ppm in the diet of adult females, monocrotophos had no effect on the embryo heart beat or development of the chicks (Shellenberger, 1966b). Rat Groups of rats were fed monocrotophos in the diet at dosage levels of 0 (42 males and 42 females), 0.5, 1.5 (30 males and 30 females/group), 15 (42 males and 42 females), 45 and 135 ppm (12 males and 12 females/group) for twelve weeks. Growth was depressed at 45 ppm. Cholinesterase depression was observed on haematology or gross and microscopic pathology (Shellenberger and Newell, 1964). Dog Groups of Beagle dogs were fed monocrotophos in the dry diet at levels of 0, 0.5, 1.5, 15 (four dogs of each sex/group), 45 and 135 ppm (two dogs of each sex/group) for 13 weeks. After 8 weeks, the dogs fed 135 ppm were changed to 270 ppm for weeks 9-10, then to 540 ppm for weeks 11-12, and to 1 080 ppm for the final week. Body-weights were reduced at dietary levels of 270 ppm. Organ weights were also affected in this high feeding level group. Cholinesterase depression was observed at 1.5 ppm in blood and brain. There were no compound-related effects on haematological values, blood biochemistry, organ weights or gross and microscopic pathology (Shellenberger and Newell, 1964). Groups of dogs were fed monocrotophos in the diet for two years at levels of 0 (four males and four females) 0.16, 1.6, 16 ppm (three males and three females/group) and for one year at 100 ppm (two males and two females). Moderate cholinergic stimulation was observed at 100 ppm as tremors and salivation. Blood cholinesterase depression was noted at 16 and 100 ppm in both males and females. Marginal brain cholinesterase depression was also noted at a dose level of 1.6 ppm after 93 and 104 weeks. No effects were noted on growth, mortality, haematological parameters, urinalyses or physiological measurements. Gross and histopathological examination showed no compound-related effects (Johnston et al., 1967a). Long-term studies Rat Groups of rats were fed monocrotophos in the diet for two years at levels of 0 (40 males and 40 females), 1, 10 and 100 ppm (25 males and 25 females/group). Growth of males and females at 100 ppm was depressed. Food consumption was also lower than controls at this level. RBC and plasma cholinesterase depression was observed at 10 and 100 ppm in both males and females. Brain cholinesterase depression in males and females was significantly inhibited at all levels. At 100 ppm, the weights of liver, gonad, thyroid and pituitary were reduced in females. Thyroid and pituitary/body-weight ratios were depressed at 100 ppm. No effects were noted on survival, haematology or histopathological examination of organs and tissues (Johnston et al., 1967b). COMMENT Monocrotophos is rapidly absorbed, metabolized and eliminated by mammals. Plant and animal metabolites are similar. Potentiation was observed with fenchlorphos but not with other cholinesterase-inhibiting compounds. No delayed neurotoxic effects were observed. Short-term studies in rats and dogs indicate no-effect levels at 0.5 ppm for cholinesterase depression. In long-term studies a no-effect level has not been demonstrated in the rat, the lowest dose tested (1 ppm) causing significant brain cholinesterase depression. In dog, two-year studies indicated a no-effect level of 0.16 ppm with regard to brain cholinesterase depression. An effect was observed at 1.6 ppm. In estimating an ADI for this compound, it was noted that in rat a firm no-effect level was 0.5 ppm, with minimal effect level at 1 ppm. In dog a no-effect level of 0.5 ppm was also demonstrated but the minimal effect level was 1.5 ppm. Since the no-effect level is more closely defined in rat, the latter species was used as a basis for determining the ADI. TOXICOLOGICAL EVALUATION Level causing no toxicological effect Rat: 0.5 ppm in the diet, equivalent to 0.025 mg/kg/day Dog: 0.5 ppm in the diet, equivalent to 0.0125 mg/kg/day ESTIMATE OF ACCEPTABLE DAILY INTAKE FOR MAN 0 - 0.0003 mg/kg body-weight RESIDUES IN FOOD AND THEIR EVALUATION USE PATTERN Monocrotophos is an organo-phosphorus insecticide, which finds its main use for foliar application to cotton (over 80% of monocrotophos applied). It is also recommended for application against foliage pests of maize, sugar cane, sugarbeet, vegetables, potatoes and certain fruits. It is particularly effective against Lepidoptera, Homoptera and certain Coleoptera, acting by both systemic and residual contact properties. Monocrotophos is known to be officially registered and/or approved for use in the following countries: Angola Yugoslavia Argentina Mexico Australia Mozambique Austria Nicaragua Brazil Pakistan Bulgaria Peru Chile Philippines South Africa Colombia Spain Costa Rice Sudan Ecuador Switzerland El Salvador Thailand Egypt Trinidad France Turkey Greece Uruguay Guatemala U.S.A. India Venezuela Israel Viet-Nam Italy Zambia USE RECOMMENDATIONS Typical maximum recommended application rates are: 1.0 kg a.i./ha for cotton, potatoes and fruit; 1.5 kg a.i./ha for maize; 0.8 kg a.i./ha for sugar cane; and 0.5 - 0.6 kg a.i./ha for vegetables and sugar beet. The recommended minimum period between treatment and harvest varies from country to country, but is generally about 7 - 15 days for vegetables and potatoes, 14 days for cotton, 21 days for tomatoes, maize and citrus and 28 - 30 days for other crops. Multiple applications of monocrotophos are often made, depending on pest incidence, and use recommendations allow for these treatments. The detailed use recommendations are given in Table 4. TABLE 4 APPLICATIONS OF MONOCROTOPHOS TO CROP FOLIAGE Crop Recommended Recommended period application rates between treatment (kg. a.i./ha) and harvest (days)1 Cotton 0.25 -1.0 Australia - 21 Mexico - 14 S. Africa - 30 Spain - 30 U.S.A. - 21 Maize 0.25 -1.5 Colombia - 30 Uruguay - 28 Sugarcane 0.25 -0.75 Uruguay - 28 Venezuela - 30 U.S.A. - 30 Carrots, turnips, onions 0.25 -0.5 Potatoes 0.25 -1.0 Colombia - 30 Italy - 21 S. Africa - 14 Venezuela - 14 U.S.A. - 7 Sugar beet 0.25 - 0.80 Italy - 21 TABLE 4 (Cont'd.) Brussels sprouts, 0.2 -0.6 Yugoslavia - 28 cauliflower and cabbage Colombia - 30 Peru - 15 Venezuela - 21 Vietnam - 21 Tomatoes 0.25 -1.0 Hops 0.25 -0.5 Soybeans 0.25 -0.5 Colombia - 30 Vietnam - 21 Peas and beans 0.5 Colombia - 30 Pom - 15 Apples, pears2 0.01 - 0.04% a.i. Australia - 28 Italy - 30 Citrus 0.5 - 1.0 Venezuela - 21 Coffee 0.25 - 0.8 1 Monocrotophos is not recommended for post-harvest use on agricultural commodities. 2 Monocrotophos is recommended for use on apples and pears in Australia, and Italy only. RESIDUES RESULTING FROM SUPERVISED TRIALS Residue data are available from supervised trials carried out in 24 countries on food crops grown under various conditions, using various rates of application and pre-harvest intervals. In most trials, dosage rates, number of applications and pre-harvest intervals were observed, in accordance with label recommendations, and the data from these trials are summarized in Table 5. Residues of monocrotophos in grain crops and root vegetables are usually below, or close to, the limit of determination of the analytical method, while leafy vegetables and fruit often contain detectable residues. TABLE 5 Residues of monocrotophos in crops following recommended foliage treatments Maximum Minimum recommended preharvest Trials Results Range of Crop rate interval residues (ppm) (kg a.i./ha) (days) (no.) (no.) Cotton (seed) 1.0 14 11 14 <0.02-0.08 Cotton (oil) 1.0 14 5 6 <0.02-0.04 Sugarcane 0.75 30 4 5 <0.05 Potatoes 1.0 7 14 27 <0.08-0.20 Maize grain 1.5 14 14 25 <0.01-0.05 Tomatoes 1.0 21 10 17 <0.01-0.51 Brussels sprouts 0.6 15 4 8 <0.05-0.21 Cauliflower 0.6 15 6 8 <0.01-0.14 Cabbage 0.6 21 9 23 <0.02-0.19 Carrots 0.5 14 2 5 <0.01-0.04 Turnips 0.5 10 1 3 <0.05 Onions 0.5 10 3 6 <0.02-0.09 Sugar beet 0.8 14 8 25 <0.01-<0.05 Peas 0.5 15 2 2 <0.07-0.60 Beans 0.5 21 3 6 <0.01-0.22 Soybeans 0.5 14 7 12 <0.01-0.03 Coffee 0.8 42 2 2 <0.01-0.08 Hops 0.5 28 1 2 0.3 - 0.41 Citrus fruit 1.0 21 11 26 <0.01-0.45 Apples 1.0 28 7 20 <0.05-1.0 Pears 1.0 28 5 10 <0.01-0.76 Cotton Since the major outlet for monocrotophos is as a foliage insecticide on cotton, numerous studies have been undertaken to examine the extent of residues of monocrotophos in cottonseed and oil, if any, likely to arise from recommended treatments. Cottonseed Monocrotophos is recommended for application to cotton foliage at a maximum dosage rate of 1 kg a.i./ha, applications being made at 5-7 day intervals, where pest incidence dictates, with a final treatment to harvest interval of 14 days. Trials in which these recommendations were followed showed that residues of monocrotophos in cottonseed were below the limit of determination of the analytical method employed (<0.02 - <0.07 ppm) with the exception of one sample which contained an apparent residue of monocrotophos of 0.08 ppm. This sample had an unusually long pre-harvest interval of 94 days, and the untreated corresponding sample contained 0.05 ppm monocrotophos. Cottonseed oil Following recommended treatments of cotton with monocrotophos, residues (max. 0.04 ppm) have only been detected occasionally in the oil. A tendency was observed for residues to be lower in the crude oil when they were detected in the corresponding seed. Cotton foliage On foliage, residue levels of monocrotophos were proportional to the dosage rates at short pre-harvest intervals. The half-life on foliage was between less than three days to six days. In U.S.A., where monocrotophos is widely used on cotton, no grazing of livestock or feeding of treated trash is permitted since the residue levels range from 8 to >100 ppm. Potatoes The data developed relative to the use of monocrotophos on potatoes showed that, when treated at the recommended rate of 0.25 - 1.0 kg a.i./ha, with a minimum pre-harvest interval of seven days, residues of monocrotophos were consistently less than the limit of determination of the analytical method employed (<0.01 - <0.08 ppm). Sugarcane Analyses of sugarcane which had been repeatedly treated at 0.5 - 1.0 kg a.i./ha, and products from the sugarcane, showed that the residue levels of monocrotophos were consistently less than the limit of determination of the analytical method (<0.05 ppm) when a pre-harvest interval of 30 days was observed. Maize The results of a considerable number of studies, carried out to determine the residues of monocrotophos in maize are given below: Grain No residues of monocrotophos (<0.01 - <0.05 ppm) have been found in maize grain treated according to label recommendations (max. dosage of 1.5 kg a.i./ha, pre-harvest interval of 14 days). Residues in maize grain have been detected only in trials where very short pre-harvest intervals have been used. Husks and cobs Extensive data show no significant residues of monocrotophos in samples of husks and cobs from maize plants which had received applications of monocrotophos. Residues of monocrotophos which occur at short pre-harvest intervals (1-3 days) decrease rapidly. At intervals of 14 days or longer they had decreased to an average level of 0.04 ppm (range 0.005 - 0.40 ppm) from treatments up to the maximum recommended dose rate of 1.5 kg a.i./ha. Silage Following recommended treatments of monocrotophos to maize, residues of monocrotophos in maize silage ranged from less than 0.01 ppm to 1.4 ppm (mean of 0.15 ppm). Stover Residues of monocrotophos in maize stover, following recommended treatments, ranged from less than 0.01 ppm to 0.06 ppm (mean of 0.02 ppm). Levels of 13 - 17 ppm present in stover one day after application rapidly decreased to 0.20 - 0.06 ppm 23 days later. Tomatoes Following recommended applications of monocrotophos (maximum rate of 1.0 kg a.i./ha, pre-harvest interval of 21 days) to tomatoes, residues of monocrotophos ranged from less than 0.01 ppm to 0.51 ppm (mean of 0.11 ppm). Brussels sprouts Following recommended applications (dosage rate up to 0.6 kg a.i./ha, pre-harvest interval of 15 days) of monocrotophos to Brussels sprouts, residues of monocrotophos ranged from less than 0.05 ppm to 0.21 ppm, with an arithmetic mean of 0.10 ppm. Cauliflower Residues of monocrotophos in samples of cauliflower, which had received recommended applications of monocrotophos (up to 0.6 kg a.i./ha, pre-harvest interval of 15 days) ranged from less than 0.01 ppm to 0.14 ppm (arithmetic mean of 0.03 ppm). Cabbage The results of studies carried out to determine the residues of monocrotophos in cabbage, following recommended treatments (dosage rate up to 0.6 kg a.i./ha, four applications and pre-harvest interval of 21 days), were evaluated. Residues of monocrotophos in cabbage from these trials ranged from less than 0.02 ppm to 0.19 ppm. Carrots Following recommended applications (maximum dosage rate of 0.5 kg a.i./ha, pre-harvest interval of 14 days), maximum residues of monocrotophos found in carrots were 0.04 ppm; generally no residues (less than 0.01 ppm) were detected. Corresponding levels in the carrot tops were 0.65 - 1.6 ppm (mean of 1.1. ppm). Turnips No residues of monocrotophos (less than 0.05 ppm) have been detected in turnips, even when the turnips were harvested immediately after application. Onions Onions, treated with monocrotophos at recommended applications (maximum dosage rate of 0.5 kg a.i./ha, pre-harvest interval of ten days) did not contain residues exceeding 0.09 ppm monocrotophos (mean value of 0.03 ppm). Sugar beet Residues of monocrotophos in sugar beet roots did not exceed the limit of determination of the analytical method employed (0.01 - 0.05 ppm), following treatment at a maximum dosage rate of 0.8 kg a.i./ha. The data cover applications made within 14 days of lifting, although in practice applications as late as this are unusual. Corresponding residues of monocrotophos in sugar beet leaves ranged from less than 0.01 ppm to 0.55 ppm. Peas Following application of monocrotophos to peas, at dosage rates up to 0.5 kg a.i./ha with pre-harvest intervals of 15 days or longer, the only positive residue detected was 0.06 ppm, all the other samples being below the limit of determination of the analytical methods (<0.01 - <0.07 ppm). Beans Residues of monocrotophos in beans, following recommended treatments (up to 0.5 kg a.i./ha, pre-harvest interval of 21 days), ranged from less than 0.01 ppm to 0.22 ppm. Soybeans Residues of monocrotophos in soybeans did not exceed 0.03 ppm, following treatment of monocrotophos according to label recommendations (maximum dosage rate of 0.5 kg a.i./ha, pre-harvest interval of 14 days). Maximum residue of monocrotophos in soybean foliage was 0.87 ppm (mean of 0.22 ppm). Coffee Residues of 0.08 ppm in raw coffee beans, following a recommended treatment of monocrotophos, were reduced to below the limit of determination of the analytical method (less than 0.01 ppm) on processing. Hops In a field trial carried out in Germany, with monocrotophos at 0.5 kg a.i./ha and a minimum of 28 days pre-harvest interval, residues of monocrotophos in dried hops ranged from 0.3 to 0.41 ppm. Citrus fruit Residues of monocrotophos in citrus fruit treated with monocrotophos at label recommendations (up to 1.0 kg a.i./ha, pre-harvest interval of 21 days) ranged from less than 0.01 ppm to 0.45 ppm (mean of 0.08 ppm). Apples Monocrotophos is recommended for use on apple trees in Australia and Italy only, at dosage rates equivalent to 0.04% a.i. in the spray, with a final treatment to harvest interval of four weeks. Data from trials carried out in these countries were examined. Residues of monocrotophos in apples treated according to this recommendation range from <0.01 ppm to 1.5 ppm. These upper figures, however, derive from experiments in which the spray was applied by hand, which usually requires a somewhat higher volume; it is considered that in practical conditions of use, 1.0 ppm would be the highest level reported. Pears Monocrotophos is only recommended for application to pears in Australia and Italy. Maximum recommended dosage rate is 0.04% a.i. in the spray with a final treatment to harvest interval of 28 days in Australia and 30 days in Italy. Residues of monocrotophos treated according to these recommendations ranged from 0.08 ppm to 0.76 ppm (mean - 0.41 ppm) in pears from these two countries. FATE OF RESIDUES General comments Residues of breakdown products do not occur in food commodities to a significant extent. Extensive studies with monocrotophos have shown that degradation can occur by hydrolytic and/or oxidative mechanisms. From the experimental work it appears that the primary metabolic pathway is hydrolysis, yielding metabolic products which are non-cholinesterase inhibiting and of low toxicity. Evidence of secondary metabolic pathways involving oxidation reactions have been found in that small quantities of the N-methylol analogue of monocrotophos, its glycoside and the unsubstituted amide analogue were detected in the radiotracer studies. Residues of cholinesterase inhibiting breakdown products have been detected in crops only rarely, following recommended treatments, and then at levels close to the limit of determination of the analytical method employed. Likewise in meat and milk from animals fed monocrotophos in their diet, at levels far exceeding those likely to be encountered in practice, only extremely low levels of breakdown products have been detected, if at all. In animals Studies have been conducted with monocrotophos fed to cattle and goats to determine whether residues in feed give rise to residues in meat and milk. 32P monocrotophos was fed continuously to two lactating cows at a level equivalent to 45 ppm in their total diet (Shell Development Co., undated). This level is approximately 20 times that which would occur in practice, assuming a maximum of 50% of monocrotophos-treated feedstuff in the total diet. Levels of monocrotophos found in the milk from the two cows were 0.01 ppm and 0.008 ppm. Average levels of dimethyl phosphate and of N-hydroxy methyl monocrotophos were 0.002 ppm and 0.001 ppm, respectively (Ibid.). No residues of glycosides of the N-hydroxy methyl compound were detected. After 14 days of this feeding regime, the two cows were slaughtered and residues determined on the red meat and liver. These results are given in Table 6. TABLE 6 Residues of monocrotophos and its breakdown products present in meat from cows fed monocrotophos Residues present (ppm) Sample dimethyl N-hydroxy methyl analysed monocrotophos phosphate monocrotophos Red meat 0.02, 0.04 0.005, 0.008 0.003, 0.0084 Liver 0.11, 0.13 0.05, 0.06 0.02, 0.04 32P monocrotophos was administered orally to goats (Menzer and Casida, 1965) at a single dose of 1 mg/kg body-weight. Within 72 hours of the application, only 1.4% of the applied radioactivity was present in the goats' milk. The authors suggested that, in animals, monocrotophos degradation took place by oxidative N-demethylation to N-hydroxy methyl monocrotophos and unsubstituted amide. Residues of these compounds and monocrotophos in samples of the milk from the treated goats up to 24 hours after treatment are given in Table 7. TABLE 7 Residues of monocrotophos and its breakdown products found in milk from goats administered monocrotophos Residues present in goats' milk (ppm) Hours after N-hydroxy methyl unsubstituted total organo- administration monocrotophos monocrotophos amide extractable 1 0.045 0.0001 <0.0001 0.067 2 0.032 0.0086 0.0007 0.061 4 0.034 0.0086 0.0015 0.074 6 0.023 0.011 0.0013 0.057 8 0.012 0.0099 0.0007 0.042 12 0.007 0.0044 0.0006 0.025 16 0.006 0.0020 0.0001 0.012 20 0.012 0.0009 0.0003 0.022 24 0.001 0.0007 <0.0001 0.007 As indicated in Table 7, residues of monocrotophos fell from a maximum value of 0.0451 ppm one hour after administration to 0.0014 ppm 23 hours later. Maximum levels of N-hydroxy methyl monocrotophos, and the unsubstituted amide, detected were 0.0105 ppm (after six hours) and 0.0015 ppm (after four hours), respectively. These levels had decreased by a fifteen-fold factor 24 hours after application. To determine whether residues in animal feeds could give residues of the conjugate of N-hydroxy methyl monocrotophos in meat and milk, two Guernsey cows were fed for ten days with the conjugate at a level of 20 ppm in the total diet (this level is more than 2 000 times that which may be encountered in practice). The results showed that the combined residues of the conjugate and its hydrolysis products, N-hydroxy methyl monocrotophos and the unsubstituted amide, in milk, were all below 0.01 ppm. At the end of the ten day study the cows were slaughtered and their tissues analysed. The results are given in Table 8. TABLE 8 Residues of monocrotophos breakdown products found in tissues of cows fed monocrotophos conjugate Tissues Residues present (ppm) analysed conjugate of N-hydroxy N-hydroxy methyl monocrotophos methyl monocrotophos plus unsubstituted amide fat <0.01 0.02, 0.04 kidney 0.02, 0.01 <0.01, 0.01 meat <0.01, <0.01 0.01, 0.01 liver <0.01, 0.01 <0.01, 0.01 In plants In order to elucidate the mode of breakdown in leaves, 32P monocrotophos was applied to cotton plants, both in the glasshouse and in the field, either as a foliar spray, a stem banding treatment, a seed dressing or by petiole injection (Lindquist and Bull, 1967). For the foliar treatment, monocrotophos was applied at a rate of 40 mg/cotton leaf. In the field studies, 85% of the applied radioactivity was lost during the first two days, presumably through volatilization. Breakdown was shown to take place on both the surface and the inside of the treated leaves. Principal breakdown products found were O-desmethyl monocrotophos, dimethyl phosphate and N-hydroxy methyl monocrotophos. When monocrotophos was applied as a stem bending treatment, the recovered radioactivity after 21 days was unchanged monocrotophos, probably because the lanolin in the formulation had a stabilizing effect. Following the application of monocrotophos as a seed treatment (not a recommended application) at a rate of 0.5 mg monocrotophos/cotton seed, 50% of the radioactivity recovered after one week was unchanged monocrotophos. O-desmethyl monocrotophos was present in all samples, indicating the cleavage of a methyl-phosphate bond. Dimethyl phosphate (formed by hydrolysis of the vinyl phosphate bond) was recovered in increasing amounts with time. The N-hydroxy methyl monocrotophos was only detected at 21 days after treatment, while an unknown compound, later identified as a glycoside of N-hydroxy methyl monocrotophos (Shell Development Co., undated), was the major metabolite at 14 and 21 days. Petiole injection of monocrotophos at 70 mg monocrotophos/cotton leaf indicated half-lives of monocrotophos in cotton leaves of eight days in the glasshouse and seven days in the field. Small amounts of the N-hydroxy methyl monocrotophos and its conjugate were detected. No residues of the unsubstituted amide (N-desmethyl monocrotophos) were detected in cotton plants. The authors proposed the pathways shown in Figure 2 for the degradation of monocrotophos. Menzer and Casida (1965) injected 32P-monocrotophos into bean plants at a level of 43.5 ppm and found trace amounts of the N-hydroxy methyl monocrotophos (0.14% of monocrotophos applied) and the unsubstituted amide (0.10% of monocrotophos applied) eight days after injection. However, 20 and 32 days after application monocrotophos was the only compound detected. In studies with 14C-labelled monocrotophos (Shell Research Ltd., undated) on the foliage of maize, cabbage and apples, and on apple fruit, the breakdown products present were the unsubstituted amide, N-hydroxy methyl monocrotophos, (both in the free and conjugated forms), O-desmethyl-monocrotophos acid and traces of N-methylacetoacetamide and 3-hydroxy-N-methyl butyramide. Since, of the breakdown products detected in plants following application of monocrotophos, only the unsubstituted amide (N-desmethyl monocrotophos) and the free and bound N-hydroxy methyl monocrotophos can cause cholinesterase inhibition, analytical methods (Ibid.) were developed for the determination of these compounds. Samples from field trials were analysed using these methods. Results from trials with sugar beet, potatoes, Brussels sprouts, cauliflower, maize, pears, peas, onions and soybeans (Ibid.) showed that residues of the unsubstituted amide and the N-hydroxyl methyl monocrotophos (free and conjugated) could not be detected, nor could monocrotophos.
Further data, obtained in cases where monocrotophos residues were above detectable levels, are shown in Table 9. It will thus be seen that, in practice, where crops have been treated with monocrotophos in the field, residues of cholinesterase inhibiting degradation product in the edible parts did not reach detectable levels. The only exception was a single sample of carrots in which a residue of conjugated methylol at a level near to the level of determination of the analytical method was reported. In soils Although monocrotophos is not used as a soil-applied pesticide, a series of tests were conducted to determine the half-life of monocrotophos in soil (Shell Chemical Co., undated). In Ripperdam sandy loam and Sacramento clay loam, the half-lives of monocrotophos were 18 and 6 days, respectively. In an early experiment (Shell Research Ltd., undated), where monocrotophos was applied to soil at rates of 0.25 or 0.5 kg a.i./ha, initial residues, immediately after application, of 5.6 - 6.6 ppm monocrotophos had fallen to below the limit of determination of the analytical method employed (less than 0.04 ppm) five months later. In storage and processing Studies to determine the effects of storage on residues of monocrotophos in apples (Shell Research Ltd., undated) have shown that these residues are not significantly reduced on storage at 15 - 20°C for 24 days, or at 5 - 10°C for two to three months. Long-term deep-freeze storage trials have shown that monocrotophos residues are stable in broccoli and soybean foliage for 11-19 months, although exceptionally 90% of monocrotophos residues were lost from cabbage after 14 months deep-freeze storage (Shell Development Co., undated). Numerous studies on the effect of domestic and commercial processing on residues of monocrotophos in food crops have been carried out. Domestic processes, such as washing, peeling and cooking, reduce the levels of residues of monocrotophos in fruit and vegetables by between 35% and 95%. Commercial processes often have greater effects on residues of monocrotophos. This canning can reduce typical levels by over 90%, while the preparation of processed coffee beans, refined cottonseed and soybean oil, and dried citrus pulp reduced typical residues to below the limits of the analytical methods employed. TABLE 9 Residues of monocrotophos breakdown products found in crops1 Preharvest Residues present (ppm) Crop Country Interval Crop monocrotophos amide plus conjugated part methylol methylol 21 roots <0.01 <0.01 <0.05 Sugar beet Italy 21 leaves 0.14 <0.01 - 31 roots <0.01 <0.03 <0.05 Sugar beet France 31 leaves 0.10 <0.03 - 31 roots <0.01 <0.03 - 31 leaves 0.04 0.06 - Maize Italy 14 husk + 0.10 0.20 - straw 0.10 0.30 - 13 grain <0.01 <0.01 <0.05 Maize S. Africa 13 husk 0.90 0.10 <0.10 13 straw 1.0 0.50 <0.20 3 whole 0.39 <0.05 - Cabbage S. Africa 13 whole 0.22 <0.05 <0.10 3 whole 0.50 <0.05 - 13 whole 0.38 <0.05 <0.10 28 whole <0.02 <0.04 - Onions U.K. 14 whole 0.14 <0.04 - 7 whole 0.17 <0.04 - 6 whole 0.06 <0.012 - Tomatoes S. Africa 20 whole 0.08 <0.012 - 6 whole 0.34 <0.012 - 49 whole <0.01 <0.02 <0.05 Tomatoes S. Africa 28 whole 0.03 <0.02 - 49 whole 0.01 <0.02 <0.05 28 whole 0.10 <0.02 <0.05 TABLE 9 (Cont'd.) Preharvest Residues present (ppm) Crop Country Interval Crop monocrotophos amide plus conjugated part methylol methylol 67 whole 0.18 <0.05 <0.05 Apples Australia 37 whole 0.51 <0.05 <0.05 8 whole 1.8 <0.05 0.06 Apples Italy 30 whole 1.0 <0.04 <0.03 Pears Italy 39 whole 0.15 <0.04 <0.05 14 roots 0.06 <0.02 0.10 Carrots S. Africa 21 roots 0.04 <0.02 <0.05 28 roots <0.01 <0.02 <0.05 1 Data from Shell Research Ltd. 2 Analysed only for unsubstituted amide. Analyses of fruit with monocrotophos residues have demonstrated that residues are mainly in the peel. Thus peeling removed 66% of residues present in oranges, 35 - 70% in apples (Shell Research Ltd.; Shell Chemical Co., undated) and 80 - 95% in grapefruit (Ibid.). In another study to determine the levels of monocrotophos present in different parts of apples, it was shown that 57 - 64% of the residues were present in the pulp, 5% in the waxy surface layer, the remainder being in the peel. The removal of the outer leaves of cabbages reduced the monocrotophos levels by 95%, of cauliflower by 90% and of Brussels sprouts by over 75% (Shell Research Ltd., undated). Cold water washing can also reduce residues. Thus washing tomatoes reduced residues of monocrotophos by up to 35% (Shell Development Co.; Shell Chemical Co., undated). Domestic cooking reduced levels by 60 - 70% in green beans and 80 - 85% in Brussels sprouts (Shell Research Ltd., undated). The effect of the various steps in the commercial canning of beans (Fahey et al., 1969) and tomatoes (Fahey et al., 1971) has been studied. Cold water washing of beans effected a 27% reduction and blanching a 40% reduction. Residues in the canned beans were only 2% of the residues in the fresh beans. The processes of cold washing and lye peeling reduced residues in tomatoes by 63% and 87%, respectively. An 85% reduction in residues of monocrotophos was achieved in tomato juice and a 91% reduction in whole tomatoes by canning. The process of juicing oranges reduced the levels of monocrotophos from 0.8 ppm in the pulp to 0.10 ppm and below (Shell Research Ltd., undated). Commercial processing of raw coffee beans by removing the berry flesh mechanically, followed by fermentation, and sun-drying to a moisture level of 10%, reduced residues of 0.08 ppm monocrotophos in the raw beans to below the limit of determination of the analytical method (less than 0.01 ppm) in the processed beans (Ibid.). The preparation of refined soybean oil reduced residues of 0.13 ppm monocrotophos in beans to less than 0.01 ppm in the finished oil (Shell Chemical Co., undated). Similarly, residues of 0.03 ppm in kernels were reduced to less than 0.01 ppm in processed corn meal and oil (Ibid.). With cottonseed oil (Shell Research Ltd., unpublished) it has been shown that 1 ppm monocrotophos added to the crude oil was reduced to below the limit of determination of the analytical method (<0.01 ppm) by the alkali refining step. Experiments to determine the residues of monocrotophos likely to occur in beer prepared from monocrotophos-treated hops have demonstrated that residues of 1.8 ppm monocrotophos in hops were reduced to levels at or below the limit of determination of the analytical method (0.02 ppm) in filtered and unfiltered beer (Ciba-Geigy Ltd., undated). During the commercial preparation of citrus pulp cattle feed (Westlake et al., 1970) from monocrotophos-treated oranges, residues were reduced to below the limit of determination (less than 0.03 ppm), with over 50% being lost during grinding and liming and the remainder during drying. The following sections summarize these effects in terms of individual crops, in order to give an estimate of upper levels to be expected in foods when they are ready to eat. Cottonseed and soybean oils Since the process of alkali refining destroys residues in crude cottonseed oil at levels well above those in practice, refined cottonseed oil products will not contain detectable residues of monocrotophos. The same conclusion may be drawn for soybean oil. Brassicas In the case of Brussels sprouts, removal of outer leaves followed by cooking reduced typical levels by 95%. Thus sprouts with initial residues of 0.2 ppm (proposed tolerance levels) would not be expected to contain more than 0.01 ppm when cooked and ready to be eaten. In the case of cauliflower, removal of outer leaves alone reduced residue levels some 10-fold so that even without cooking, levels in trimmed cauliflower at an initial level of 0.5 ppm (proposed tolerance) would be reduced to 0.05 ppm. In the case of cabbage, where removal of outer leaves reduced residues 20-fold, cabbage with residues at the proposed tolerance level of 0.05 ppm would not be expected to contain more than 0.03 ppm when trimmed ready for cooking. Fresh tomatoes Fresh tomatoes with 0.5 ppm monocrotophos residues (proposed tolerance) would lose, according to available data, an average 25% of their residues, leading to a little less than 0.4 ppm at the point of consumption. Commercially processed tomatoes The combined effects of washing and lye peeling reduced residues to approximately 5% of their initial value so that residues in tomatoes ready for canning would not exceed 0.01 ppm, a level which would be further reduced by canning itself. Similar considerations apply to canned tomato juice, and neither of these finished products would contain detectable residues of monocrotophos. Beans Domestic cooking of beans with monocrotophos residues at the tolerance level of 0.2 ppm would reduce these to approximately 0.1 ppm. Commercial canning would reduce these levels to below 0.01 ppm, whereas freezing, which involves washing and blanching, would reduce levels to 0.1 ppm. Coffee Coffee beans with initial residue at the tolerance level of 0.1 ppm would be unlikely to contain detectable residues (< 0.01 ppm) after fermentation and drying. For this reason, subsequent processes such as roasting and brewing were not studied. Hops Hops with residues at the tolerance level do not give rise to detectable residues in beer. Citrus fruit Residues in citrus fruit were reduced to an average of 30% of their initial value on peeling, so that the raw fruit after peeling would not contain residues above 0.15 ppm, where initial residues were at the tolerance level of 0.5 ppm. Juicing reduced levels of around 0.8 ppm in the pulp of oranges to 0.10 ppm in the juice. Potatoes, maize grain and root vegetables With the exception of carrots, where two samples out of five were reported to contain low residues, these crops, treated as recommended, have not contained measurable residues so that work to demonstrate the effects of processing on reducing residues could not meaningfully be undertaken. Sugarcane and sugar beet In the case of sugarcane the absence of detectable residues has been demonstrated not only in the raw commodity but also in the manufactured products. In neither crop were residues detected following recommended treatments. METHODS OF RESIDUE ANALYSIS Residues of monocrotophos can be determined by specific methods utilizing either gas-liquid chromatographic procedures or a cholinesterase inhibition method. Gas chromatographic methods Gas chromatographic methods of analysis for monocrotophos are the methods of choice, based on accuracy, specificity, sensitivity and speed. Monocrotophos can be determined by the general procedure using the flame photometric detector (Beroza and Bowman, 1968; Brody and Chaney, 1966). Specific methods for monocrotophos using this detector have been developed (Shell Research Ltd., undated; Bowman and Beroza, 1967) and allow analyses of crops down to a limit of determination of 0.01 ppm. The following procedure (Shell Research, Ltd., undated) has proved satisfactory in analysing crops: samples are extracted by maceration with chloroform, low water content crops are first dampened with water. Co-extracted natural products are removed using a column adsorption chromatographic clean-up technique. The monocrotophos-containing extract is analysed using the flame photometric detector (FPD). Using this procedure, mean recoveries are 75 - 120% from crops at the 0.05 - 0.20 ppm level. The thermionic detector has also been employed in the analyses of crops for residues of monocrotophos (Shell Chemical Co., undated). In this method, the sample is extracted with dichloromethane followed by clean-up using a series of solvent exchanges and washings, prior to injection of an aliquot of the extract onto the GLC instrument. Mean recoveries with this method are 80 - 120% for crops, with a limit of determination of 0.03 - 0.05 ppm. Enzymatic inhibition Specific enzymatic methods for the detection and determination of monocrotophos in crops and milk have been developed (Shell Development Co., undated). The samples for analysis are extracted with chloroform, followed by a solvent exchange to hexane and concentration of the extract. Column chromatography using a gradient column elution technique with hexane/dichloromethane removes co-extractives. The separated monocrotophos is transferred to water and determined by enzyme inhibition spectrophotometric methods. Using this procedure, the limit of determination of monocrotophos is about 0.10 ppm in crops and 0.01 ppm in milk. Recoveries are in the range of 70 - 125%. Methods for analyses of monocrotophos breakdown products The analytical data for the N-methylol and for the unsubstituted amide reported in this summary were developed using the method described for monocrotophos (Shell Research Ltd., undated). The conjugate of the N-methylol was determined using the method, which depends on converting the conjugate to the sec-butyl thio-ether of the methylol and subsequent determination by T.L.C. and enzyme inhibition (Ibid.). A further method, using the thermionic detector (Griang and Beckman, 1968) has been developed for analysing crops for residues of O-desmethyl monocrotophos, N-hydroxy methyl monocrotophos and its conjugate. NATIONAL TOLERANCES Officially approved tolerances for monocrotophos have been established in some countries and examples of these are given in Table 10. TABLE 10 Examples of national tolerances as reported to the meeting Country Crop(s) Tolerance (ppm) Australia Cottonseed, potatoes 0.1 Apples, pears 1.0 Italy Apples, pears 0.5 South Africa All treated crops 0.1 U.S.A. Cottonseed, potatoes, sugarcane 0.1 Venezuela Cottonseed, rice, maize, potatoes, sugarcane, vegetables, citrus fruit 0.1 Yugoslavia All treated crops 0.1 APPRAISAL Monocrotophos is an organophosphorus insecticide which finds its main use for foliar application to cotton. It is also recommended for application against foliage pests of maize, sugarcane, sugar beet, vegetables, potatoes and certain fruits. It possesses both systemic and residual contact properties. Approved uses involve the application of from 0.25 - 1.0 kg a.i./ha. The recommended pre-harvest interval varies according to crop and country, ranging from seven days on potatoes to 30 days on fruit and vegetables. Extensive studies have shown that degradation of monocrotophos residues on and in plants can occur by hydrolytic and/or oxidative mechanisms. The products of hydrolysis are non-cholinesterase inhibiting and of low toxicity. Only insignificant amounts of secondary metabolites have been found during radiotracer studies. Volatilization appears to be the major factor in the rapid loss of residues following application. Monocrotophos itself is the principal residue found on most plants even 7 - 28 days after application. Metabolism studies suggest that ruminants receiving monocrotophos-treated feedstuff metabolize the residue to metabolites similar to those found on plants. There appears to be no tendency for residues to accumulate in animals receiving contaminated rations. Only low levels of monocrotophos and trace amounts of breakdown products were detected in red meat, liver and milk of cattle receiving feedstuffs containing monocrotophos at levels many times the maximum likely to occur in practice. Residue data, obtained from supervised trials in 24 different countries clearly demonstrated the level of residues to be expected under widely differing conditions on a wide range of crops. Except for samples of leafy materials collected within one or two days of application of heavy dosages of monocrotophos, residues in excess of 1.0 ppm were seldom encountered. No substantial residue occurs in any fraction of the cotton plant used for food, even when unprocessed. As cotton foliage retains significant residues for more than three weeks following application of approved rates of monocrotophos, feeding of treated cotton foliage to cattle should be avoided. Domestic processes, such as washing, peeling and cooking reduce the levels of monocrotophos residues in fruit and vegetables by between 35% and 95%. Commercial processes often have greater effects on reducing residues of monocrotophos. The peeling of citrus fruits removes 60 - 73% of the total residue. Beer produced from treated hops was shown to contain no detectable residues. The absence of residue has been demonstrated in sugarcane and in sugar products manufactured therefrom. For determining monocrotophos residues, either gas-liquid chromatography or cholinesterase inhibition methods are used, with the former being the methods of choice from the aspect of accuracy, specificity, sensitivity and speed. The limit of determination is 0.01 ppm. Using GLC methods recoveries of 75 - 120% were obtained from crop material containing 0.05 - 0.2 ppm. Several of the available methods appear suitable for regulatory purposes, but the method of Bowman and Beroza (1967) is recommended. RECOMMENDATIONS The following recommended tolerances for animal products reflect a value at or just above the limit of determination. The time interval between application and harvest which has been used in determining the maximum residue limits is appropriate to the agricultural practices in numerous countries. TOLERANCES Interval between Foodstuff Tolerance treatment and (ppm) harvest (days) Cottonseed 0.1 14 Cottonseed oil (raw) 0.05* 14 Potatoes 0.05* 7 Maize (grain) 0.05* 14 Tomatoes 0.5 21 Brussels sprouts 0.2 15 Cabbage, cauliflower 0.2 21 Carrots, turnips 0.05* 14 Onions 0.1 10 Sugar beet 0.05* 14 Peas 0.1 15 Beans 0.2 21 Soybeans 0.05* 14 Coffee (raw beans) 0.1 42 Hops (dried) 1 30 Citrus fruit 0.2 28 Apples and pears 1 (temporary 28 1975) Meat and edible offal of cattle, sheep, goats, pigs and poultry 0.02* from feeding Milk 0.002* treated plant Milk products 0.02* products Eggs (shell free) 0.02* " * at or about the limit of determination FURTHER WORK OR INFORMATION DESIRABLE 1. Studies on human exposure. 2. Information on the incidence of residues in apples and pears. REFERENCES Beroza, M. and Bowman, M.C. (1968) Chromatography of pesticide residues containing phosphorus or sulphur with the flame photometric detector. Environ. Sci., Technol., 2: 450. Bowman, M.C. and Beroza, M. (1967) Chromatographic analysis of azodrin and Bidrin. J. Agr. Fd. Chem., 15: 465 Brody, S.S. and Chaney, J.E. (1966) Flame photometric detector. J. Gas. Chromat., 4: 42. Bull, D.L. and Lindquist, D.A. (1964) Metabolism of 3-hydroxy-N, N-dimethyl-crotonamide dimethylphosphate by cotton plants, insects and rats. J. Agr. Fd. Chem., 12: 310-317. Bull, D.L. and Lindquist, D.A. (1967) Metabolism of 3-hydroxy-N-methyl-cis-crotonamide dimethyl phosphate (azodrin) by insects and rats. J. Agr. Fd. Chem., 14: 105-109. Gaines, T.B. (1969) Acute toxicity of pesticides. Tox. Appl. Pharmacol., 14: 515-534. Ciba-Geigy Ltd. (undated) Reports on monocrotophos nos. 86 - 88, 90 - 93, 97, 111, 116 - 131. (unpublished) Einsenlord, G. and Loquram, G.S. (1965) Results of short route reproduction study of rats fed diets containing SD 9129 insecticide over three generations. Data from the Hine Laboratory submitted by the Shell Chemical Company. (unpublished) Einsenlord, G. and Loquram, G.S. (1966) Results of long route reproduction study of rats fed diets containing SD 9129 insecticide over three generations. Data from the Hine laboratory submitted by the Shell Chemical Co. (unpublished) Fahey, J.E., Gould, G.E. and Nelson, P.E. (1969) Removal of gardona and azodrin from vegetable crops by commercial preparative methods. J. Agr. Fd. Chem., 17: 1204. Fahey, J.E., Gould, G.E. and Nelson, P.E. (1971) Removal of azodrin residues from tomatoes by commercial preparative methods. J. Agr. Fd. Chem., 19: 81. Griang, B.Y. and Beckman, H.F. (1968) Determination of bidrin, azodrin and their metabolites with the thermionic detector. J. Agr. Fd. Chem., 16: 899. Hunter, C.G. (1964) The efficacy of atropine and oxime therapy as an antidote to poisoning by SD 9129 in guinea pigs. Report Tunstall Laboratory submitted by the Shell Chemical Co. (unpublished) Johnston, C.D., Thompson, W.M. and Donoso, J. (1967a) Azodrin safety evaluation by a chronic feeding study in the dog for two years. Data from Woodard Research Corporation submitted by Shell Chemical Co. (unpublished) Johnston, C.D., Thompson, W.M. and Donoso, J. (1967b) Azodrin safety evaluation by a chronic feeding study in the rat for two years. Data from Woodard Research Corporation submitted by Shell Chemical Co. (unpublished) Lindquist, D.A. and Bull, D.L. (1967) Fate of 3-hydroxy-N- methyl-cis-crotonamide dimethyl phosphate in cotton plants. J. Agr. Fd. Chem., 15: 267-272. Menzer, R.L. and Casida, J.E. (1965) Nature of toxic metabolites formed in mammals, insects and plants from 3-(dimethoxy phosphinyloxy)-N,N-dimethyl-cis-crotonamide and its N-methyl analogue. J. Agr. Fd. Chem., 13: 102-112. Potter, J.C. (1965) Cattle feeding studies with 32P-labelled azodrin. Data submitted by Shell Chemical Co. (unpublished) Reiff, B. (1969) Pharmacological studies into the toxic actions of cholinesterase inhibitors: (a) The effect of antidotes on the subcutaneous toxicity of azodrin in the rat. Report of Tunstall Laboratory submitted by Shell Chemical Co. (unpublished) Shellenberger, T.E. (1965a) Potentiation studies - rats. Data from Stanford Research Institute submitted by Shell Chemical Co. (unpublished) Shellenberger, T.E. (1965b) Demyelination study - hens. Data from Stanford Research Institute submitted by Shell Chemical Co. (unpublished) Shellenberger, T.E. (1966a) Acute toxicity of azodrin and metabolites. Data from Stanford Research Institute submitted by Shell Chemical Co. (unpublished) Shellenberger, T.E. (1966b) Cholinesterase inhibition and toxicological evaluations of two organophosphate pesticides in Japanese quail. Tox. Appl. Pharm. 8: 22. Shellenberger, T.E. and Newell, G.W. (1963) Acute oral toxicity. Data from Stanford Research Institute submitted by Shell Chemical Co. (unpublished) Shellenberger, T.E. and Newell, G.W. (1964) Subacute toxicity and cholinesterase study of Shell compound SD 9129 - rat and dog. Data from Stanford Research Institute submitted by Shell Chemical Co. (unpublished) Shell Chemical Co. (1966) Subacute toxicity and cholinesterase study of Shell compound SD 13311 in rats. Data from Stanford Research Institute submitted by Shell Chemical Co. (unpublished) Shell Chemical Co. (1972) Identification of unknown 4. Report Shell Chemical Co. (unpublished) Shell Chemical Co. (undated) Reports on monocrotophos nos 50 - 67, 69 - 74, 76, 77, 79 - 81, 89, 101, 115, 132 - 136, 139 - 151, 153, 172, 176, 182 - 184. (unpublished) Shell Development Co. (undated) Reports on monocrotophos nos. 68, 75, 78, 82 - 85, 100, 110, 112, 114, 137, 138, 152, 155, 171, 173 - 175, 177 - 181. (unpublished) Shell Research Ltd. (undated) Reports on monocrotophos nos. 1 - 49, 94, 95, 98, 99, 154, 156 -170. (unpublished) Thorpe, E. and Dix, M. (1972) Toxicity studies on azodrin: Teratological studies in rabbits. Summary submitted by Shell Chemical Co. (unpublished) Westlake, W.E., Gunther, F.A. and Jeppson, L.R. (1970) Persistence of azodrin residues on and in Valencia oranges and in laboratory-processed citrus pulp cattle feed. J. Agr. Fd. Chem., 18: 864. Young, J.R. and Bowman, M.C. (1967) Azodrin for corn earworm and fall armyworm control and its persistence in sweet corn. J. Econ. Ent., 60: 1282.
See Also: Toxicological Abbreviations Monocrotophos (HSG 80, 1993) Monocrotophos (ICSC) Monocrotophos (WHO Pesticide Residues Series 5) Monocrotophos (Pesticide residues in food: 1991 evaluations Part II Toxicology) Monocrotophos (Pesticide residues in food: 1993 evaluations Part II Toxicology) Monocrotophos (Pesticide residues in food: 1995 evaluations Part II Toxicological & Environmental)