VAMIDOTHION EXPLANATION Vamidothion was evaluated by the Joint Meetings in 1973 and 1982 (Annex 1, FAO/WHO, 1974a and 1983a). A temporary ADI was allocated in 1982. A toxicological monograph was prepared by the Joint Meeting in 1973 (Annex 1, FAO/WHO, 1974b) and a monograph addendum was prepared in 1982 (Annex 1, FAO/WHO, 1983b). Several studies, including a teratogenicity study, a multi- generation reproduction study, a delayed neurotoxicity study, and a dog study of adequate duration, were required by 1985. Some of the required studies and some mutagenicity studies have been submitted and are summarized in the following monograph addendum. EVALUATION FOR ACCEPTABLE DAILY INTAKE Toxicological studies Special studies on embryotoxicity/teratogenicity Rat Groups of 20-23 pregnant Sprague-Dawley rats were administered by stomach tube vamidothion (technical material; 94.3% purity) dissolved in distilled water at dose levels of 0, 5, 10, or 20 mg/kg b.w./day from day 6 through day 15, inclusive, of pregnancy. On day 20 of pregnancy, the dams were sacrificed and foetuses removed by caesarean section for external, visceral and skeletal abnormalities. No noteworthy clinical signs were observed. In the highest-dose group, one female died on day 16 of preganancy, average body weights of dams were significantly lower than those of controls on days 15 and 20, and decreased food consumption during the treatment and post- treatment period was observed. Corpora lutea and implantations were comparable in all groups. There were no dose-related differences between the control and treated groups with respect to resorptions, post-implantation losses, live foetuses, male-to-female ratios, or mean body weights of foetuses. No dead foetuses were observed. The examination of foetuses for external, visceral, and skeletal abnormalities gave no indication of treatment- related effects. The no-effect level for embryotoxic/teratogenic effects in this study was 20 mg/kg b.w./day (Savary & Read, 1985a). Rabbit Groups of 12 to 15 pregnant New Zealand albino rabbits were administered by stomach tube vamidothion (technical material; 94.3% purity) dissolved in distilled water at dose levels of 0, 5, 10, or 20 mg/kg b.w./day from day 6 through day 18, inclusive, of pregnancy. On day 28 the dams were sacrificed and the foetuses were removed by Caesarean section for examination for external, visceral, and skeletal abnormalities. Diarrhoea was the main clinical sign observed in the dams during the treatment. The frequency of this symptom was dose-related. Mortality and abortions were not treatment-related. On day 18 and day 21 of pregnancy, but not on day 24 and day 28, the average body weights of the dams in the highest-dose group were significantly lower than those of the controls. Food consumption was lower than in the controls for the dams in the highest-dose group only. The numbers of corpora lutea and implantations were on the same order for all groups. There were no dose-related differences between the control and treated groups with respect to resorptions, post-implantation losses, live foetuses, male-to-female ratios, or mean body weights of foetuses. No dead foetuses were observed. The examination of foetuses for external, visceral, and skeletal abnormalities gave no indication of a treatment-related effect. The no-effect level for embryotoxic/teratogenic effects in this study was 20 mg/kg b.w./day (Savary & Read, 1985b). Special studies on mutagenicity Table 1: Special studies on mutagenicity with vamidothion Test Organism Test substance Range tested Result Reference S. typhimurium vamidothion 125-1000 negative Benazet & TA1535, TA1537 (purity not µg/plate * Cartier,1977a TA98 & TA100 stated) S. typhimurium vamidothion 1-40 positive at 5 Benazet & TA1535 (pure mg/plate mg/plate & Cartier,1977b standard) above * S. typhimurium vamidothion 0.1 ml of a) positive Shirasu a) TA1535 (pure 25% solution b) negative et al., 1976 b) TA1536 standard) in methyl- TA1537 ethylketone TA1538 S. typhimurium vamidothion 50-40,O00 a) sig. dose- Shirasu a) TA1535 (95% purity) µg/plate related increase et al., 1978 TA100 of revertants at b) TA1537 >5000 µg/plate* TA1538 b) negative TA98 S. typhimurium vamidothion up to 5000 a) positive Moriya et a) TA1535 µg/plate al., 1983 TA100 b) TA1537 b) negative * TA1538 E. coli (WP2 vamidothion 0.1 ml of 25% positive Shirasu et try hcr+/hcr-) (pure solution in al., 1976 standard) methylethylketone Table 1: (Con't) Test Organism Test substance Range tested Result Reference E. coli vamidothion 50-4000 sig. dose-related Shirasu et WP2 hcr (95% purity) µg/plate increase of revertants al., 1978 at > 5000 µg/plate* E. coli vamidothion up to 5000 positive* Moriya et WP2 hcr µg/plate al., 1983 Chinese hamster vamidothion 1-5 × 10-3M dose-related Tezuka et cells in vitro (standard increase in SCE, al., 1980 sample) chromosomal aberrations, polyploids Micronucleus vamidothion 0, 5, 10, or no sig. differences Pasquet & test on CD1 (400 g/litre 20 mg/kg b.w. compared Fournier,1980 mice (2 mice) in methylethyl (oral) to control in % sex/dose) ketone (LD50 of polychromatic =55 mg/kg b.w.)) erythrocytes with micronuclei B. subtilis vamidothion 0.02 ml of positive Shirasu et H17 rec+/ 25% methylethyl al., 1976 M45 rec- ketone B. subtilis vamidothion 1000-20,000 dose-related Shirasu et H17 rec+/ (95% purity) µg/disk differences in al., 1978 M45 rec- length of inhibitory zone * With and without S-9 mix Special studies on acute toxicity of vamidothion metabolites Table 2: Acute toxicity of vamidothion sulphone LD50 Species Sex Route (mg/kg b.w.) Reference Mouse M&F oral 75 Desmoras et al., 1967 Rat F oral 140 Desmoras et al., 1967 Special studies on the effect of vamidothion on cholinesterase In 2 different studies, groups of Wistar female rats (30 rats/group) were fed diets containing vamidothion at levels of 0 or 1 ppm for 1 month. Serum, RBC, and brain ChE activities, as determined after the 1-month administration, were not significantly different between the treated and the control group. The no-effect level with respect to serum, RBC, and brain ChE activities was 1 ppm for female rats (Sato et al., 1978; Toyoshima et al., 1978). Special study on delayed neurotoxicity Hen Groups of SPF White Leghorn hens (10-11 months old; 10-13/group) were administered single oral doses (gelatin capsule) of vamidothion (99.8% purity) at dose levels of 0, 50, 75, or 100 mg/kg b.w. A positive control group received by gavage tri-O-cresyl phosphate at a dose level of 500 mg/kg b.w. In a preliminary study all the animals of the 75 mg/kg b.w. group and higher, without atropine, died. The animals of the 75 mg/kg b.w. group were treated with atropine and 2-PAM, while the animals of the 100 mg/kg b.w. group received atropine alone. The animals were observed for 3 weeks after treatment for their clinical symptoms. The animals that died during the experiment and all the animals surviving after the 3-week observation period were sacrificed for autopsy and histopathological examination. Animals of the vamidothion-treatment groups showed symptoms of acute intoxication consisting of depression, diarrhoea, and vomiting immediately after treatment. In accordance with manifestation of these symptoms, body weights, food consumption, and food efficiency were markedly reduced compared to the negative controls. Seven animals died in the 100 mg/kg b.w. group. The surviving animals recovered and the symptoms were alleviated; no animal was found significantly abnormal at the termination of the experiment. Histopathological examination did not reveal alterations in nervous tissues similar to those observed in the positive control animals. Animals of the positive control group showed marked motor incoordination or paralysis at 3 weeks. Histopathological examination of the animals showing such symptoms revealed that they had degeneration of the axon and the myelin sheath in the cerebellum, medulla oblongata, spinal cord, and sciatic nerve. The authors concluded that vamidothion, administered at dose levels up to 100 mg/kg b.w., had no delayed neurotoxicity (Yoshida et al., 1980). Acute toxicity Table 3: Acute toxicity of vamidothion LD50 Species Sex Route (mg/kg b.w.) Reference Mouse M&F oral 45 Desmoras et al., 1967 Rat F oral 110 Desmoras et al., 1967 Rat M&F inhalation LC50: Coggins et al., (4 hr. exp.) 1.73 mg/l 1985 Short-term studies Rabbit - dermal Groups of rabbits (2 males and 2 females/dose level) were treated dermally with vamidothion (as aqueous solution) at dose levels of 0, 100, 300, or 900 mg/kg b.w. for 2 weeks (5 days/week). The animals were observed for mortality for 2 days after the end of treatment. The subacute LD50 value was calculated to be 380 mg/kg b.w. Most deaths occurred after 3 or 4 applications. The in vivo ID50 was determined to be about 240 mg/kg b.w., less than 100 mg/kg b.w., and about 40 mg/kg b.w. for plasma, erythrocyte, and brain cholinesterase activity, respectively (Fournel et al., 1969). Observations in man Fifteen workers engaged in the industrial synthesis of vamidothion or of its precursors for periods of 1-6 months did not show health impairment or significant variations of plasma or erythrocyte cholinesterase activity (Bioche, 1984). Eighteen people using vamidothion on crops were examined. The concentration of the product in air was 0.024 mg/m3 50 metres away from the point of application. Symptoms recorded were a very slight drop in pulse rate and arterial blood pressure in 8 subjects. For 10 minutes, a reduction of 4-11% in blood cholinesterase was observed (Lelievre, 1981). A study was carried out investigating the effects of low concentrations of vamidothion on the reflex activity of man. The product was administered by inhalation, even though vamidothion is not very volatile. The results were recorded as encephalograms. The 4 people subjected to these tests were tested with 2 concentrations of vamidothion, 0.009 mg/m3 or 0.016 mg/m3. At the higher concentration the product caused significant desynchronization of alpha rhythms in all subjects; vamidothion at the lower concentration had no effect. On the basis of this study, the authors concluded that the maximum acceptable limit of vamidothion in atmospheric air of inhabited zones is 0.01 mg/m3 (Lelievre, 1981). COMMENTS Several studies, including a teratogenicity study, a multi- generation reproduction study, a delayed neurotoxicity study, and a dog study of adequate duration were required by 1985. Teratogenicity studies in rats and rabbits gave no indication that vamidothion has embryotoxic/teratogenic potential at dose levels up to 20 mg/kg b.w./day. Vamidothion was not mutagenic in some bacterial systems, while in some others it was positive only at very high concentration levels. Vamidothion induced low SCE and chromosomal aberrations in vitro, but in an in vivo micronucleus test no conclusions could be reached because of the small number of animals used. Delayed neuropathy was not induced in hens. Pending the receipt of a 1-year dog study and a multi-generation reproduction study, the Meeting decided to maintain the temporary ADI at the level set in 1982. TOXICOLOGICAL EVALUATION CAUSING NO TOXICOLOGICAL EFFECT Mouse: 1 ppm in the diet, equal to 0.137 mg/kg b.w. Rat: 1 ppm in the diet, equal to 0.054 mg/kg Dog: 5 ppm in the diet, equivalent to 0.125 mg/kg b.w. ESTIMATE OF TEMPORARY ACCEPTABLE DAILY INTAKE FOR MAN 0 - 0.0003 mg/kg b.w. FURTHER WORK OR INFORMATION REQUIRED (by 1988) 1. Multi-generation reproduction study. 2. One-year dog study. DESIRED Observations in man. REFERENCES Benazet, F. & Cartier, J.R.: Vamidothion (10465 RP). Study of (1977a) mutagenic activity in Salmonella typhimurium. Unpublished report RP/RD/CNG 19228-E from Centre Nicolas Grillet, Rhône- Poulenc, submitted to WHO by Rhône-Poulenc Agrochimie, France. Benazet, F. & Cartier, J.R.: Vamidothion (10465 RP). Etude de (1977b) l'activité mutagène vis-à-vis de Salmonella typhimurium. Unpublished report RP/RD/CNG No. 19301-E from Centre Nicolas Grillet, Rhône-Poulenc, submitted to WHO by Rhône-Poulenc Agrochimie, France. Bioche, F: Relèves des examens biologiques concernant 15 personnes (1984) ayant été affectées a diverses phases del la synthes du vamidothion. Unpublished report EB/HL from Usine d'Elbeuf of Rhône-Poulenc, submitted to WHO by Rhône-Poulenc Agrochimie, France. Coggins, C.R.E., Haroz, R.K., Nikiforov, A.I., Fleissner, H., & (1985) Bouvier, C.: Final report on vamidothion LC50. Unpublished report from Battelle-Geneva, submitted to WHO by Rhône- Poulenc Agrochimie, France. Desmoras, J., Fournel, J., Julon, L., Koenig, F., & Pasquet, J.: (1967) Comparaison des activités insecticides et des toxicites aigües du vamidothion (10465 RP et du 12284 RP). Unpublished report, submitted to WHO by Rhône-Poulenc Agrochimie, France. Fournel, M., Julon, L., Koenig, F., & Mazuret, A.: Vamidothion (10465 (1969) RP). Toxicité subaigüe (2 semaines) chez le lapin par voie percutanée. Unpublished report No. 13947, submitted to WHO by Rhône-Poulenc Agrochimie, France. Lelievre, D.: Vamidothion in the environment. Assessment of potential (1981) danger to man. Unpublished report CRV/CNG No. 21190, submitted to WHO by Rhône-Poulenc Agrochimie, France. Moriya, M., Ohta, T., Watanabe, K., Miyazawa, T., Kato, K., & Shirasu, (1983) Y.: Further mutagenicity studies on pesticides in bacterial reversion assay system. Mut. Res. 128, 185-216. Pasquet, J. & Fournier, E.: Vamidothion (10465 RP) (solution of (1980) 400 g/litre in methylethyl ketone). Micronucleus test in the mouse. Unpublished report RP/RD/CNG No. 20553-E from Centre Nicolas Grillet, Rhône-Poulenc, submitted to WHO by Rhône- Poulenc Agrochimie, France. Sato, R., Sato, S., & Motoyama, M.: Consideration on the effect of (1978) vamidothion on cholinesterase. Unpublished report from Nihon Experimental Medical Institution, submitted to WHO by Rhône- Poulenc Agrochimie, Franceœ Savary, M.H. & Read, M.H.: Vamidothion: Assessment of possible (1985a) embryotoxic or teratogenic effects in the rat. Unpublished report No. 794 RSR from Centre International de Toxicologie, submitted to WHO by Rhône-Poulenc Agrochimie, France. Savary, M.H. & Read, M.H.: Vamidothion; Assessment of possible (1985b) embryotoxic or teratogenic effects in the rabbit. Unpublished report No. 795 RSL, from Centre International de Toxicologie, submitted to WHO by Rhône-Poulenc Agrochimie, France. Shirasu, Y., Moriya, M., Kato, K., Furuhashi, A., & Kada, T.: (1976) Mutagenicity screening of pesticides in the microbial system. Mut. Res. 40, 19-30. Shirasu, Y., Moriya, M., & Otha, T.: Microbial mutagenicity testing on (1978) vamidothion. Unpublished report from Institute of Environmental Toxicology, Tokyo, submitted to WHO by Rhône- Poulenc Agrochimie, France. Tezuka, H., Ando, R., Suzuki, R., Terahota, M., Moriya, M., & Shirasu, (1980) Y.: Sister-chromatid exchanges and chromosomal aberrations in cultured Chinese hamster cells treated with pesticides positive in microbial reversion assays. Mut. Res. 18, 177-191. Toyoshima, H., Seto, T., & Fujita, H.: Influence of vamidothion on (1978) cholinesterase. Unpublished report from Department of Chemotherapy, Pharmacochemistry Institute, Faculty of Medicine, Keio University, submitted to WHO by Rhône-Poulenc Agrochimie, France. Yoshida, A., Saito, T., Maita, K., & Shirasu, Y.: Vamidothion. 3-week (1980) acute delayed neurotoxicity study in hens. Unpublished report from Institute of Environmental Toxicology, Tokyo, submitted to WHO by Rhône-Poulenc Agrochimie, France. ANNEX 1 REPORTS AND OTHER DOCUMENTS RESULTING FROM PREVIOUS JOINT MEETINGS OF THE FAO PANEL OF EXPERTS ON PESTICIDE RESIDUES IN FOOD AND THE ENVIRONMENT AND WHO EXPERT GROUPS ON PESTICIDE RESIDUES FAO/WHO. Principles governing consumer safety in relation to (1962) pesticide residues. Report of a meeting of a WHO Expert Committee on Pesticide Residues held jointly with the FAO Panel of Experts on the Use of Pesticides in Agriculture. FAO Plant Production and Protection Division Report, No. PL/1961/11; WHO Technical Report Series, No. 240. FAO/WHO. Evaluation of the toxicity of pesticide residues in food; (1964) report of a Joint Meeting of the FAO Committee on Pesticides in Agriculture and the WHO Expert Committee on Pesticide Residues. FAO Meeting Report, No. PL/1963/13; WHO/Food Add./23. FAO/WHO. Evaluation of the toxicity of pesticide residues in food. (1965a) Report of the Second Joint Meeting of the FAO Committee on Pesticides in Agriculture and the WHO Expert Committee on Pesticide Residues. FAO Meeting Report, No. PL/1965/10; WHO/Food Add./26.65. FAO/WHO. Evaluation of the toxicity of pesticide residues in (1965b) food. FAO Meeting Report, No. PL/1965/10/1; WHO/Food Add./27.65. FAO/WHO. Evaluation of the hazards to consumers resulting from the (1965c) use of fumigants in the protection of food. FAO Meeting Report, No. PL/1965/10/2; WHO/Food Add./28.65. FAO/WHO. Pesticide residues in food. Joint report of the FAO Working (1967a) Party on Pesticide Residues and the WHO Expert Committee on Pesticide Residues. FAO Agricultural Studies, No. 73; WHO Technical Report Series, No. 370. FAO/WHO. Evaluation of some pesticide residues in food. (1967b) FAO/PL:CP/15; WHO/Food Add./67.32. FAO/WHO. Pesticide residues. Report of the 1967 Joint Meeting of (1968a) the FAO Working Party and the WHO Expert Committee. FAO Meeting Report, No. PL:1967/M/11; WHO Technical Report Series, No. 391. FAO/WHO. 1967 Evaluation of some pesticide residues in food. FAO/ (1968b) PL:1967/M/11/1; WHO/Food Add./68.30, FAO/WHO. Pesticide residues in food. Report of the 1968 Joint (1969a) Meeting of the FAO Working Party of Experts on Pesticide Residues and the WHO Expert Committee on Pesticide Residues. FAO Agricultural Studies, No. 78; WHO Technical Report Series, No. 417. FAO/WHO. 1968 Evaluation of some pesticide residues in food. FAO/ (1969b) PL:1968/M/9/1; WHO/Food Add./69.35. FAO/WHO. Pesticide residues in food. Report of the 1969 Joint (1970a) Meeting of the FAO Working Party of Experts on Pesticide Residues and the WHO Expert Group on Pesticide Residues. FAO Agricultural Studies, No. 84; WHO Technical Report Series, No. 458. FAO/WHO. 1969 evaluations of some pesticide residues in food. FAO/ (1970b) PL:1969/M/17/1; WHO/Food Add./70.38. FAO/WHO. Pesticide residues in food. Report of the 1970 Joint (1971a) Meeting of the FAO Working Party of Experts on Pesticide Residues and the WHO Expert Committee on Pesticide Residues. FAO Agricultural Studies, No. 87; WHO Technical Report Series, No. 474. FAO/WHO. 1970 Evaluations of some pesticide residues in food. AGP: (1971b) 1970/M/12/1; WHO/Food Add./71.42. FAO/WHO. Pesticide residues in food. Report of the 1971 Joint (1972a) Meeting of the FAO Working Party of Experts on Pesticide Residues and the WHO Expert Committee on Pesticide Residues. FAO Agricultural Studies, No. 88; WHO Technical Report Series, No. 502. FAO/WHO. 1971 Evaluations of some pesticide residues in food. AGP (1972b) 1971/M/9/l; WHO Pesticide Residues Series, No. 1. FAO/WHO. Pesticide residues in food. Report of the 1972 Joint (1973a) Meeting of the FAO Working Party of Experts on Pesticide Residues and the WHO Expert Committee on Pesticide Residues. FAO Agricultural Studies, No. 90; WHO Technical Report Series, No. 525. FAO/WHO. 1972 Evaluations of some pesticide residues in food. (1973b) AGP:1972/M/9/l; WHO Pesticide Residues Series, No. 2. FAO/WHO. Pesticide residues in food. Report of the 1973 Joint (1974a) Meeting of the FAO Working Party of Experts on Pesticide Residues and the WHO Expert Committee on Pesticide Residues. FAO Agricultural Studies, No. 92; WHO Technical Report Series, No. 545. FAO/WHO. 1973 Evaluations of some pesticide residues in food. (1974b) FAO/AGP/1973/M/9/1; WHO Pesticide Residues Series, No. 3. FAO/WHO. Pesticide residues in food. Report of the 1974 Joint (1975a) Meeting of the FAO Working Party of Experts on Pesticide Residues and the WHO Expert Committee on Pesticide Residues. FAO Agricultural Studies, No. 97; WHO Technical Report Series, No. 574. FAO/WHO: 1974 Evaluations of some pesticide residues in food. (1975b) FAO/AGP/1974/M/11; WHO Pesticide Residues Series, No. 4. FAO/WHO. Pesticide residues in food. Report of the 1975 Joint (1976a) Meeting of the FAO Working Party of Experts on Pesticide Residues and the WHO Expert Committee on Pesticide Residues. FAO Plant Production and Protection Series, No. 1; WHO Technical Report Series, No. 592. FAO/WHO. 1975 Evaluations of some pesticide residues in food. (1976b) AGP:1975/M/13; WHO Pesticide Residues Series, No. 5. FAO/WHO. Pesticide residues in food. Report of the 1976 Joint (1977a) Meeting of the FAO Panel of Experts on Pesticide Residues and the Environment and the WHO Expert Group on Pesticide Residues. FAO Food and Nutrition Series, No. 9; FAO Plant Production and Protection Series, No. 8; WHO Technical Report Series, No. 612. FAO/WHO. 1976 Evaluations of some pesticide residues in food. (1977b) AGP:1976/M/14. FAO/WHO. Pesticide residues in food - 1977. Report of the Joint (1978a) Meeting of the FAO Panel of Experts on Pesticide Residues and Environment and the WHO Expert Group on Pesticide Residues. FAO Plant Production and Protection Paper 10 Rev. FAO/WHO. Pesticide residues in food: 1977 evaluations. FAO Plant (1978b) Production and Protection Paper 10 Sup. FAO/WHO. Pesticide residues in food - 1978. Report of the Joint (1979a) Meeting of the FAO Panel of Experts on Pesticide Residues and Environment and the WHO Expert Group on Pesticide Residues. FAO Plant Production and Protection Paper 15. FAO/WHO. Pesticide residues in food: 1978 evaluations. FAO Plant (1979b) Production and Protection Paper 15 Sup. FAO/WHO. Pesticide residues in food - 1979. Report of the Joint (1980a) Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Group on Pesticide Residues. FAO Plant Production and Protection Paper 20. FAO/WHO. Pesticide residues in food: 1979 evaluations. FAO Plant (1980b) Production and Protection Paper 20 Sup. FAO/WHO. Pesticide residues in food - 1980. Report of the Joint (1981a) Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Group on Pesticide Residues. FAO Plant Production and Protection Paper 26. FAO/WHO. Pesticide residues in food: 1980 evaluations. FAO Plant (1981b) Production and Protection Paper 26 Sup. FAO/WHO. Pesticide residues in food - 1981. Report of the Joint (1982a) Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Group on Pesticide Residues. FAO Plant Production and Protection Paper 37. FAO/WHO. Pesticide residues in food: 1981 evaluations. FAO Plant (1982b) Production and Protection Paper 42. FAO/WHO. Pesticide residues in food - 1982. Report of the Joint (1983a) Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Group on Pesticide Residues. FAO Plant Production and Protection Paper 46. FAO/WHO. Pesticide residues in food: 1982 evaluations. FAO Plant (1983b) Production and Protection Paper 49. FAO/WHO. Pesticide residues in food - 1983. Report of the Joint (1984) Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Group on Pesticide Residues. FAO Plant Production and Protection Paper 56. FAO/WHO. Pesticide residues in food: 1983 evaluations. FAO Plant (1985a) Production and Protection Paper 61. FAO/WHO. Pesticide residues in food - 1984. Report of the Joint (1985b) Meeting on Pesticide Residues. FAO Plant Production and Protection Paper 62. FAO/WHO. Pesticide residues in food - 1984 evaluations. FAO Plant (1985c) Product[on and Protection Paper 67. FAO/WHO. Pesticide residues in food - 1985. Report of the Joint (1986a) Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and a WHO Expert Group on Pesticide Residues. FAO Plant Production and Protection Paper 68. FAO/WHO Pesticide residues in food - 1985 evaluations. Part I - (1986b) Residues. FAO Plant Production and Protection Paper 72/1. ANNEX 2 ACCEPTABLE DAILY INTAKES, RESIDUE LIMITS AND GUIDELINE LEVELS PROPOSED AT THE 1985 MEETING These figures are additional to, or amend, those recorded in Annexes of the reports of earlier meetings. Limits recommended at meetings from 1965-1977 inclusive are summarized in document FAO/WHO 1978c. This table includes maximum acceptable daily intake (ADIs), maximum residue limits (MRLs) and guideline levels (GLs). These terms are defined in Annex 3 of the report of the 1975 meeting. Part 1 lists ADIs and MRLs. Some ADIs and MRLs are temporary: in these cases the year in which further data are required is specified in parenthesis below the ADI and/or following the MRL(s). Part 2 lists GLs. New, as distinct from amended, recommendations are identified by the symbol * before the commodity or before the ADI. Residue levels at or about the limit of determination are followed by the symbol **. Amended recommendations are followed by the previous recommendation in parenthesis. The table includes the Codex Classification Numbers (CCNs) of both the compounds and the commodities listed, to facilitate reference to the Guide to Codex Maximum Limits for Pesticide Residues. CCNs for commodities are those of the revised Classification (see section 2.7 of the 1985 Report). ANNEX 2 PART 1 - ACCEPTABLE DAILY INTAKES (ADIs) AND MAXIMUM RESIDUE LIMITS (MRLs) Pesticides, CCN and Recommended Recommended years of previous maximum ADI Commodity MRL or ERL evaluations (mg/kg bw) CCN Name (mg/kg) Aldicarb 0.005 AS 0645 Maize forage 5 CCN 117 (fresh weight 1979, 1982 basis) (prev. 20 dry weight basis) Remarks: MRLs are for the sum of aldicarb, its sulphoxide and its sulphone, expressed as aldicarb. Azocyclotin: See cyhexatin/azocyclotin. Captafol Temporary All MRLs CCN 006 ADI WITHDRAWN 1969, 1973, 1974, WITHDRAWN 1976, 1977, 1982 Remarks: Temporary MRLs NOT replaced by GLs. Chlordimeform 0.0001 CCN 013 (1987) 1971, 1975, 1977, 1978, 1979, 1980 Remarks: Temporary ADI extended at the same level. PART 1 (Con't) Pesticides, CCN and Recommended Recommended years of previous maximum ADI Commodity MRL or ERL evaluations (mg/kg bw) CCN Name (mg/kg) Chlorothalonil 0.0005 FB 0269 Grapes 10 CCN 081 (prev. 5) 1974, 1977, 1978, 1979, 1981, 1983 Remarks: Temporary ADI extended at lower level. The limit for grapes remains temporary only because the ADI is temporary. TMRLs are for clorothalonil. Metabolites are not included. Cyhexatin 0.008 FP 0226 Apples 2 a/,b/ CCN 067 VP 0526 Beans 0.2 a/, 1970, 1973, (as VO 0445 Bell peppers 0.5 a/ tricyclohexyltin FC 0001 Citrus fruits 2 a/ hydroxide), 1974, VC 0424 Cucumbers 0.5 a/ 1975, 1977, 1978, VO 0440 Egg plants 0.1** b/ 1980, 1981, 1982, VC 0425 Gherkins 1 a/ 1983 FI 0328 Kiwi fruit 5 a/ FB 0269 Grapes 2 b/ MM 0095 Meat 0.2 a/ VC 0046 Melons 0.5 a/ ML 0812 Milk of cattle 0.05** a/ Milk products 0.05** a/ FS 0246 Peaches 5 a/ FP 0230 Pears 2 a/ FS 0014 Plums 2 a/ FB 0275 Strawberries 2 a/, b/ DT 1114 Tea 2 a/ and VO 0448 Tomatoes 2 a/ PART 1 (Con't) Pesticides, CCN and Recommended Recommended years of previous maximum ADI Commodity MRL or ERL evaluations (mg/kg bw) CCN Name (mg/kg) Azocyclotin 0.003 CN 129 1979, 1981, 1982, 1983 Remarks: MRLs replace separate lists for the two compounds. They are numerically unchanged. MRLs are for the sum of azocyclotin (when azocyclotin has been applied), cyhexatin and dicyclohexyltin oxide expressed as cyhexatin. Cypermethrin 0.05 SO 0089 Oilseeds 0.2 CCN 118 (except peanuts) 1979, 1981, 1982 SO 0697 Peanuts 0.05** 1983, 1984 VD 0541 Soybeans 0.05** Remarks: MRLs are for cypermethrin (sum of isomers). Metabolites are not included. The MRL of 0.2 mg/kg previously applied to oilseeds, which did not include peanuts in the original Codex Classification. The MRLs for peanuts and soybeans replace the MRL for legume oil-seeds at the same level. Deltamethrin 0.01 SB 0721 Coffee beans 0.02 CCN 135 (prev. 2) 1980, 1981, 1982, 1984 Remarks: The change is to correct an error in the 1980 report and evaluations. MRLs are for deltamethrin. Metabolites are not included. PART 1 (Con't) Pesticides, CCN and Recommended Recommended years of previous maximum ADI Commodity MRL or ERL evaluations (mg/kg bw) CCN Name (mg/kg) Dichlofuanid 0.3 DH 1100 Hops, dry MRL WITHDRAWN CCN 082 (prev. 1) 1969, 1974, 1977, CG 0640 Barley 0.1] (previous 1979, 1981, 1982, CG 0647 Oats 0.1] 0.1 for 1983 CG 0650 Rye 0.1] cereal CG 0654 Wheat 0.1] grains) Remarks: MRLs are for dichlofluanid. Metabolites are not included. Diflubenzuron 0.02 CCN 130 1981, 1983, 1984 Remarks: Temporary ADI replaced by ADI at higher level. TMRLs replaced by MRLs. MRLs are for diflubenzuron. Metabolites are not included. Dimethipin *0.003 SO 0691 *Cottonseed 0.5 ] CCN 151 (1987) *Flaxseed 0.2 ] SO 0495 *Rapeseed 0.1 ] (1987) SO 0702 *Sunflower seed 0.2 ] VR 0589 *Potatoes 0.1**] Remarks: TMRLs are for dimethipin. Metabolites are not included. All limits are temporary pending receipt of the required information, irrespective of the status of the ADI. PART 1 (Con't) Pesticides, CCN and Recommended Recommended years of previous maximum ADI Commodity MRL or ERL evaluations (mg/kg bw) CCN Name (mg/kg) Dithiocarbamate fungicides VL 0482 Lettuce, head- 5 CCN 105 (previously 1965, 1967, 1970, 1 mg/kg for 1974, 1977, 1980, lettuce) 1983 (propineb and thiram) 1984 (propineb and thiram) Remarks: The recommendation was incorrectly shown as a new proposal in the Report 1985. Limits are for residues determined and expressed as CS2. Limits no longer apply to propineb or thiram because their temporary ADIs were withdrawn by this meeting. TMRLs for propineb are withdrawn; those for thiram are replaced by GLs. Endosulfan 0.008 CCM 032 (1989) 1965, 1967, 1968, 1971, 1974, 975, 1982 Remarks: Temporary ADI extended at same level. Ethion 0.0005 CCN 034 (1986) 1968, 1969, 1970, 1972, 1975, 1982, 1983 Remarks: Temporary ADI extended at lower level. PART 1 (Con't) Pesticides, CCN and Recommended Recommended years of previous maximum ADI Commodity MRL or ERL evaluations (mg/kg bw) CCN Name (mg/kg) Fenamiphos 0.0003 CCN 085 (1987) 1974, 1977, 1978, 1980 Remarks: ADI replaced by temporary ADI at lower level. MRLs replaced by TMRLs. Fenvalerate 0.02 SO 0697 Peanuts 0.1 CCN 119 (1986) VD 0541 Soybeans 0.1 1979, 1981, 1982, ML 0812 Milk of cattle 0.1 1984 (prev. 0.01) Remarks: TMRLs are for fenvalerate. Metabolites are not included. The recommendation for milk was omitted in 1984. The TMRLs for peanuts and soybeans replace the TMRL for legume oilseeds at the same level. Flucythrinate *0.02 FP 0009 *Pome fruits 0.5 CCN 152 FB 0269 *Grapes 1 FS 0246 *Peaches 0.5 VS 0620 *Artichokes 0.5 VD 0071 *Beans (dry) 0.5 VB 0400] *Brassicas, flower- VB 0404] head (broccoli, cauliflower) 0.2 VB 0041 *Cabbages, head (Brussels sprouts; green,red,white, savoy cabbages) 0.2 PART 1 (Con't) Pesticides, CCN and Recommended Recommended years of previous maximum ADI Commodity MRL or ERL evaluations (mg/kg bw) CCN Name (mg/kg) VD 0561 *Peas, field (dry) 0.05** VR 0589 *Potatoes 0.05** VR 0591 *Radish, Japanese 0.05** VR 0596 *Sugar beet 0.05** AV 0596 *Sugar beet leaves 2 VO 0448 *Tomatoes 0.2 CG 0640 *Barley 0.2 CG 0647 *Oats 0.2 CG 0654 *Wheat 0.2 AS 0640 *Barley straw and fodder, dry 5 AS 0647 *Oat straw and fodder, dry 5 AS 0654 *Wheat straw and fodder, dry 5 AG 0645 *Maize forage (green) 0.2 SO 0691 *Cotton seed 0.1 SO 0495 *Rapeseed 0.05** SB 0721 *Coffee beans 0.05** DT 1114 *Tea,dry mftd 20 DH 1100 *Hops, dry 10 MM 0812 *Cattle meat 0.5 (in the fat) MM 0814 *Goat meat 0.5 (in the fat) ML 0812 *Milk of cattle 0.1 PE 0112 *Eggs of poultry 0.05** Remarks: Limits are for flucythrinate. Metabolites are not included. Limits for cattle meat, goat meat, milk of cattle and eggs of poultry are temporary until required information is provided. PART 1 (Con't) Pesticides, CCN and Recommended Recommended years of previous maximum ADI Commodity MRL or ERL evaluations (mg/kg bw) CCN Name (mg/kg) Imazalil 0.01 FS 0012 *Stone fruits 5 CCN 110 (1986) 1977, 1980, 1984 Remarks: Temporary ADI extended at same level. TMRLs are for imazalil. Metabolites are not included. Mecarbam 0.0005 CCN 124 (1986) Remarks: Temporary ADI extended at lower level. Metalaxyl 0.03 FP 0226 *Apples 0.05** ] CCN 138 FI 0311 Avocados 0.05** ] 1982, 1984 (prev.0.1**) ] VB 0402 *Brus.sprouts 0.2 ] FB 0269 Grapes 2 ] (prev.5) ] (1986) SO 0691 *Cottonseed 0.05** ] FI 0341 *Pineapples ] (flesh) 0.05** ] VD 0541 *Soybeans 0.1 ] FB 0275 *Strawberries 0.2 ] Remarks: MRLs are for metalaxyl. Metabolites are not included. All MRLs are temporary pending evaluation of data based on improved analytical method. PART 1 (Con't) Pesticides, CCN and Recommended Recommended years of previous maximum ADI Commodity MRL or ERL evaluations (mg/kg bw) CCN Name (mg/kg) Methamidophos 0.0006 CCN 100 1976, 1979, 1981, 1982, 1984 Remarks: Temporary ADI replaced by ADI at slightly higher level. TMRLs replaced by MRLs. Methiocarb 0.001 CCN 132 1981, 1983 Remarks: The withdrawal by the 1983 meeting of the MRLs for apples, blueberries, cherries, currants (red), grapes and peaches is now confirmed. Omethoate 0.0003 CCN 055 1971, 1975, 1978, 1979, 1981, 1984 Remarks: Temporary ADI replaced by ADI at slightly lower level. TMRLs replaced by MRLs. PART 1 (Con't) Pesticides, CCN and Recommended Recommended years of previous maximum ADI Commodity MRL or ERL evaluations (mg/kg bw) CCN Name (mg/kg) Oxamyl 0.03 FC 001 Citrus fruits 5 CCN 126 (prev. 3) 1980, 1983, 1984 VP 0526 Beans, kidney 5 (prev. 3) VP 0534 Beans, Lima 5 (prev. 3) VD 0526 Beans, kidney (dry) 0.05** (1986) VS 0624 Celery 5 (prev. 3) VC 0424 Cucumbers 2 (prev. 0.5) VO 0445 Pepper, bell 2 (prev. 3 for peppers) VR 0075 *Root and tuber vegetables 0.1 Remarks: MRLs are for the sum of oxamyl and its oxime, expressed as oxamyl. The level of the limit for kidney beans (dry) is confirmed, but the limit remains temporary pending confirmation of nationally approved uses. Limit for root and tuber vegetables replaces individual limits at same level for sugar beets, beets, carrots, potatoes and sweet potatoes. PART 1 (Con't) Pesticides, CCN and Recommended Recommended years of previous maximum ADI Commodity MRL or ERL evaluations (mg/kg bw) CCN Name (mg/kg) Paraquat 0.001 CCN 057 (1986) 1970, 1972, 1976, 1978, 1981, 1982 Remarks: Temporary ADI extended at same level. It refers to paraquat dichloride. 2-Phenylphenol 0.02 CCN 056 (1989) 1969, 1975, 1983 Remarks: Temporary ADI extended at same level. Phorate 0.0002 CCN 112 1977, 1982, 1983, 1984 Remarks: Temporary ADI replaced by ADI at same level. TMRLs replaced by MRLs. Phosphamidon 0.0005 CCN 061 (1986) 1965, 1966, 1968, 1969, 1972, 1974, 1982 Remarks: Temporary ADI extended at lower level. PART 1 (Con't) Pesticides, CCN and Recommended Recommended years of previous maximum ADI Commodity MRL or ERL evaluations (mg/kg bw) CCN Name (mg/kg) Pirimiphos-methyl 0.01 FC 0001 Citrus fruits 2 CCN 086 (prev. 0.5) 1974, 1976, 1977, MD 0180 *Dried fish 10 1979, 1983 SO 0697 Peanuts (whole) 25 (prev. 50) SO 0697 Peanuts(kernels) 2 (prev. 5) OR Peanut oil 15 (prey. 10) Remarks: MRLs are for pirimiphos-methyl. Metabolites are not included. Prochloraz 0.01 CG 0640 Barley 0.5 CCN 142 (prev. 0.05**a/) 1983 CG 0647 Oats 0.5 (prev. 0.05**a/) CG 0650 Rye 0.5 (prev. 0.05**a/) CG 0654 Wheat 0.5 (prev. 0.05**a/) AS 0640 Barley straw and 15 fodder, dry (prev. 0.2a/) AS 0647 Oat straw and 15 fodder, dry (prev. 0.2a/) AS 0650 Rye straw and 15 fodder, dry (prev. 0.2a/) AS 0654 Wheat straw and 15 fodder, dry (prev. 0.2a/) Mushrooms 2 PART 1 (Con't) Pesticides, CCN and Recommended Recommended years of previous maximum ADI Commodity MRL or ERL evaluations (mg/kg bw) CCN Name (mg/kg) FC 0001 Citrus fruits 5 (TMRL) (prev. 5a/) MM 0812 *Cattle meat 0.1** (TMRL) MM 0812 *Cattle meat 0.1** (TMRL) (in the fat) MO 0812 *Edible offal of cattle 2 (TMRL) ML 0812 *Milk of cattle 0.1** (TMRL) a/ Previous limits were for prochlorate only. Remarks: MRLs for all commodities are now for the sum of prochloraz and its metabolites containing the 2,4,6-trichlorophenol moiety, expressed as prochloraz. TMRLs for citrus fruits and animal products are temporary until required information is provided. Previously proposed TMRLs for avocado, banana, mango and rapeseed are no longer temporary. Those for stone fruits and papaya remain temporary. MRLs for avocado and mango cover cumulative residues from pre- and post-harvest treatments. Propineb Temporary All TMRLS CN 105 ADI WITHDRAWN (dithiocarbamates) WITHDRAWN 1977, 1980, 1983, 1984 Remarks: TMRLs for propineb are NOT replaced by GLs. GLs for prophylene-thiourea (PTU) are withdrawn. PART 1 (Con't) Pesticides, CCN and Recommended Recommended years of previous maximum ADI Commodity MRL or ERL evaluations (mg/kg bw) CCN Name (mg/kg) Pyrazophos no ADI CCN 153 See Part 2 Thiodicarb *0.01 SO 0691 *Cottonseed 0.5 CCN 154 (1987) OR 0691 *Cottonseed oil (refined) 0.02** VD 0541 *Soybeans 0.2 OR 0541 *Soybean oil (refined) 0.02** CG 0654 *Maize 0.05** AS 0645 *Maize fodder 50 AS 0645 *Maize forage 50 VO 0447 *Sweet corn 2 VO 0448 *Tomatoes 1 MM 0812 *Cattle meat 0.02** ML 0812 *Milk of cattle 0.02** Remarks: TMRLS are for the sum of thiodicarb, methomyl and methyl hydroxy- thioacetimidate ("methomyloxime"), expressed as thiodicarb. Thiram Temporary CCN 105 ADI (dithiocarbamates) WITHDRAWN 1965, 1967, 1970, 1974, 1977, 1983, 1984 Remarks: TMRLs converted to GLs. See Part 2. PART 1 (Con't) Pesticides, CCN and Recommended Recommended years of previous maximum ADI Commodity MRL or ERL evaluations (mg/kg bw) CCN Name (mg/kg) Triadimefon 0.03 CCN 133 1979, 1981, 1983, 1984 Remarks: Temporary ADI replaced by ADI at higher level. TMRLs replaced by MRLs. Vamidothion 0.0003 VB 0402 Brussels WITHDRAWN CCN 078 (1988) sprouts (prev. 1) 1973, 1982 FP 0009 *Pome fruits 1 FS 0246 *Peaches 0.5 CG 0080 *Cereal grains, including rice (hulled) 0.2 Remarks: Temporary ADI extended at same level. TMRLs are for the sum of vamidothion, its sulphoxide and its sulphone, expressed as vamidothion. The limit for pome fruits replaces separate limits of 2 mg/kg for apples and pears. PART 2 - GUIDELINE LEVELS (NO ACCEPTABLE DAILY INTAKES) Pesticides, CCN and Guideline years of previous Commodity level evaluations CCN Name (mg/kg) Binapacryl FC 0004 *Oranges 0.1 CCN 003 DH 1100 *Hops 0.5 1969, 1974, 1982 Remarks: GLs are for binapacryl. Metabolites are not included. Dialifos CCN 098 1976, 1982 Remarks: The definition of the residue in commodities of plant origin is changed and is now identical to that in commodities of animal origin: dialifos. Pyrazophos FP 0226 *Apples 0.5 CCN 153 FB 0275 *Strawberries 0.2 VB 0402 *Brussels sprouts 0.1 VC 0424 *Cucumbers 0.1 VC 0046 *Melons 0.1 VR 0577 *Carrots 0.2 CG 0640 *Barley 0.05 CG 0654 *Wheat 0.05 DH 1100 *Hops, dry 10. Remarks: GLs are for pyrazophos. Metabolites are not included. Thiram CCN 105 (dithiocarbamates) 1965, 1967, 1970, 1974, 1977, 1983, 1984 Remarks: As the temporary ADI has been withdrawn, previously recommended TMRLs are converted to GLs. The GLs are determined and expressed as CS2.
See Also: Toxicological Abbreviations Vamidothion (ICSC) Vamidothion (WHO Pesticide Residues Series 3) Vamidothion (Pesticide residues in food: 1982 evaluations) Vamidothion (Pesticide residues in food: 1988 evaluations Part II Toxicology)