FAO/PL:1968/M/9/1 WHO/FOOD ADD./69.35 1968 EVALUATIONS OF SOME PESTICIDE RESIDUES IN FOOD THE MONOGRAPHS Issued jointly by FAO and WHO The content of this document is the result of the deliberations of the Joint Meeting of the FAO Working Party of Experts and the WHO Expert Committee on Pesticide Residues, which met in Geneva, 9-16 December, 1968. FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS WORLD HEALTH ORGANIZATION Geneva, 1969 ENDOSULFAN Since the previous evaluation (FAO/WHO, 1968), additional data has become available and is summarized and discussed in the following monograph addendum. EVALUATION FOR ACCEPTABLE DAILY INTAKE Biochemical aspects A full account of the metabolism of endosulfan in rats and mice has been reported by Schuphan et al. (1968) which extends the previous report of Ballschmitter et al. (1967). After oral or intraperitoneal doses of endosulfan-A or endosulfan-B (4 or 8 mg/kg) were given to rats, the unchanged compounds, along with endosulfate, alpha-hydroxy endoether, and endolactone were excreted in the faeces in a ratio of 10 : 0.3 : 0.3 : 1 respectively. Endodiol and endoether were not metabolites. In the urine after oral administration of endosulfan-A, the ratio of endosulfan-A to endosulfate, endolactone, and an unidentified metabolite, M1, was 3 : 1 : 1 : 2; after endosulfan-B was administered the ratio of unchanged endosulfan-B to endosulfate, endolactone, and M1 was 2 : 1 : 6 : 20. In the bile following endosulfan-A administration by means of a duodenal fistula there were large amounts of endoketone and traces of M1 present, while after endosulfan-B administration there were large amounts of M1 and traces of endolactone. Using C14-labelled endosulfan in mice, it was found that the identified lipophilic metabolites comprised 20 per cent of the total endosulfan metabolites (Schuphan et al. 1968). Undiluted endosulfan is slowly and incompletely absorbed in the digestive tract of warm-blooded animals. Absorption is more rapid in the presence of alcohols, oils and emulsifiers. These substances also accelerate the absorption of endosulfan through the skin (Maier-Bode, 1968). The danger of accumulation of endosulfan appears to be slight (Hoescht, 1965). Acute toxicity No further information available. Reproduction study Groups of eight male and 16 female rats were fed diets containing endosulfan at levels of 2 and 50 ppm through three generations. No adverse effects wore noted among either the parental animals or their progeny in all the generations. The growth, mortality, behavioural reactions, organ weights, gross- and histo-pathology, reproduction performances and survival indices of the progeny were comparable in both the test and control groups of animals (Industrial Bio-Test Laboratories, 1965). Comments From the available data, a no-effect level in two species of animals can now be set. TOXICOLOGICAL EVALUATION Level causing no significant toxicological effect Rat: 50 ppm in the diet, equivalent to 2.5 mg/kg per day Dog: 0.75 mg/kg per day Estimate of acceptable daily intake for man (endosulfan A, endosulfan B and endosulfan sulfate) 0-0.0075 mg/kg body-weight RESIDUES IN FOOD AND THEIR EVALUATION Residues resulting from supervised trials McCaskey and Liska (1967) have studied losses in subsequent processing of endosulfan sulfate added, both by oral administration and by direct dissolution, to milk. Endosulfan sulfate, but not endosulfan, residues were found in the whole milk after feeding high doses (2 g per cow for 11 days). The level of both endosulfan and endosulfan sulfate decreased on processing, as shown below: Endosulfan residues (ppm on fat basis) in milk and milk products From dosed cows By direct addition Milk Fat (per cent.) Residue Fat (per cent.) Residue (ppm)* (ppm) Raw 3.95 15.2 3.15 15.9 Forewarmed 3.94 12.7 3.14 12.7 Condensed 7.92 12.6 7.04 11.4 (continued) Endosulfan residues (ppm on fat basis) in milk and milk products From dosed cows By direct addition Milk Fat (per cent.) Residue Fat (per cent.) Residue (ppm)* (ppm) Spray-dried 29.7 8.8 24.8 10.1 Evaporated 7.92 8.8 7.04 9.9 Drum-dried 28.8 4.5 18.85 8.0 * Endosulfan sulfate. There is some indication for residues on apples and corn that, for an initial ratio of alpha to beta isomers of about 3 : 2 the final ratio is of the order of 1 : 2 (apples, 21 days) or 2 : 3 (corn, 35 days) (Hoechst, 1968). Evidence of residues in food in commerce or at consumption Residue data summarized previously (FAO/WHO, 1968) has been consolidated and presented in greater detail by Maier-Bode (1968). Some total residue levels for endosulfan A, endosulfan B and endosulfan sulfate are included but these residues are not separately reported. There is some evidence to show that, as the residues disappear, endosulfan sulfate becomes an important feature, and that endosulfan B is somewhat more stable than endosulfan A. The total residue at harvest can contain a significant proportion (about 30 per cent) of endosulfan sulfate. In general, however, the amount of endosulfan sulfate residue cannot be assessed from the extensive residue data evaluated in 1967. There is still a need, therefore, for further information on the total residues of endosulfans A and B and endosulfan sulfate in treated produce. Duggan (1968) has summarized the results from the United States dietary residue monitoring programme for the period mid-1963 to mid-1967. Endosulfan (thiodan) residues were found in 1.2 per cent of raw agricultural produce (only 0.4 per cent of imported produce) the average level not exceeding 0.005 ppm; and in only 1.4 per cent of the ready-to-eat composite samples, the average level not exceeding 0.001 ppm. Results (in ppm) for individual market basket samples were as follows: Domestic (a) Imported (a) Composite (b) Large fruit T T TT Small fruit T T - Leaf, stem vegetables 0.01 T - Vine, ear vegetables T T - (a) Raw; (b) ready-to-eat; T = less than 0.005 ppm; TT = less than 0.001 ppm. No information is given for grains and cereals, root vegetables, beans, eggs, nuts, milk or milk products. No endosulfan isomers or endosulfan sulfate were detected in total diet studies in 1966-67 in England and Wales (Abbott et al. 1969) using methods of analysis sensitive to 0.001 ppm. Some information is also available for total diet samples collected in the Federal Republic of Germany. No alpha- or beta-endosulfan or endosulfan sulfate was detected in any sample, the limits of detectability in the different food groups being 0.001 ppm for cereals, vegetables, meat and fish, fruits, sugar, preserves, beverages, and 0.005 ppm for milk products, fats and eggs. All samples contained DDT; in addition, lindane was also found in cereals, meat and fish. RECOMMENDATIONS FOR TOLERANCES AND PRACTICAL RESIDUE LIMITS Appraisal Endosulfan is a broad spectrum insecticide, but nevertheless relatively harmless to bees. Data from supervised trials in which endosulfan is used in accordance with good agricultural practice suggest that for fruit and vegetables there is a requirement for residue levels of combined endosulfan A and B (and including also in some cases endosulfan sulfate) of up to 2.0 ppm. Some evidence is available on the pattern of terminal residues arising in treated produce which tends to show that, as they disappear, endosulfan sulfate becomes the predominant residue whilst endosulfan B is somewhat more stable than endosulfan A. However, the total residue at harvest can contain a significant proportion (about 30 per cent) of endosulfan sulfate. In general, the amount of endosulfan sulfate residue cannot be assessed from the extensive residue data evaluated in 1967, although there is some additional data which give a total figure for the combined residues of endosulfans A and B and endosulfan sulfate. There is still a need, therefore, for further information on the total residues of endosulfans A and B and endosulfan sulfate in treated produce, either separately or together. Recommendations Temporary tolerances Since an adi has now been established, and in the light of the residue data discussed above, the following temporary tolerances to be in effect until 1971 are recommended: Fruit and vegetables 2.0 ppm The individual residues of endosulfan A, endosulfan B and endosulfan sulfate are to be determined individually but expressed as their sum. The above temporary tolerances are to apply to raw agricultural products moving in commerce unless otherwise indicated. In the case of fruit and vegetables the tolerances should be applied as soon as practicable after harvest and in any event prior to actual retail to the public. In the case of commodities entering international trade, the tolerances should be applied by the importing country at the point of entry or as soon as practicable thereafter. Further work or information Required before 30 June 1971 1. Further information on the relative amounts of endosulfan A, endosulfan B, and endosulfan sulfate on fruit and vegetables - in particular on lettuce, celery and brassicas - arising from the use of technical endosulfan in accordance with good agricultural practice. 2. Data on the disappearance of the residues during storage and processing. 3. Comparative evaluation of multidetection systems of analysis (including sample extraction techniques for agricultural produce) to select a method suitable for consideration as a referee method for residues of endosulfan A, endosulfan B, and endosulfan sulfate, determined separately. 4. Data on residue levels of endosulfan A, endosulfan B, and endosulfan sulfate in total diet studies. Desirable 1. Clarification of the extent of use, if any, other than on fruit and vegetables. 2. Metabolic studies in man, with particular reference to storage of the original compound and metabolites. REFERENCES Abbott, D. C., Holmes, D. C. and Tatton, J. O'G. (1969) Organochlorine pesticide residues in total diet in England and Wales (In press) Ballschmitter, K., Schuphan, I. and Tölg, G. (1967) The metabolization of endosulfan in insects and mammals. Paper presented to the VI International Plant Protection Congress, Vienna Duggan, R. E. (1968) Residue in food and feed. Pesticides Monitoring J., 2 (1): 2-12 FAO/WHO. (1968) 1967 Evaluations of some pesticide residues in food (FAO, PL: 1967/M/11/1; WHO/Food Add./68.30) Hoechst. (1965) Farbwerke Hoechst, A. G. Data sheet for endosulfan/Thiodan. Unpublished report Hoechst. (196) Farbwerke Hoechst, A. G. Hoechst. (1968) Farbwerke Hoechst, A. G. (Private communication to FAO). Industrial Bio-Test Laboratories, Inc. (1965) Three generation reproduction study on Thiodan - Albino rats. Unpublished report. Maier-Bode, H. (1968) Properties, effects, residues and analytics of insecticide endosulfan. Residue Reviews, 22: 1.44 McCaskey, T. A. and Liska, B. J. (1967) Effect of milk processing methods on endosulfan, endosulfan sulfate and chlordane residues in milk. J. Dairy Sci., 50: 1991-1993 Schuphan, I., Ballschmitter, K. and Tölg, G. (1968) Zum Metabolismus des Endosulfans in Ratten und Mäusen. Z. Naturforsch., 23: 701-706
See Also: Toxicological Abbreviations Endosulfan (EHC 40, 1984) Endosulfan (HSG 17, 1988) Endosulfan (PIM 576) Endosulfan (FAO Meeting Report PL/1965/10/1) Endosulfan (FAO/PL:1967/M/11/1) Endosulfan (WHO Pesticide Residues Series 1) Endosulfan (WHO Pesticide Residues Series 4) Endosulfan (WHO Pesticide Residues Series 5) Endosulfan (Pesticide residues in food: 1982 evaluations) Endosulfan (Pesticide residues in food: 1989 evaluations Part II Toxicology) Endosulfan (JMPR Evaluations 1998 Part II Toxicological)