INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY WORLD HEALTH ORGANIZATION TOXICOLOGICAL EVALUATION OF SOME FOOD COLOURS, EMULSIFIERS, STABILIZERS, ANTI-CAKING AGENTS AND CERTAIN OTHER SUBSTANCES FAO Nutrition Meetings Report Series No. 46A WHO/FOOD ADD/70.36 The content of this document is the result of the deliberations of the Joint FAO/WHO Expert Committee on Food Additives which met in Rome, 27 May - 4 June 19691 Food and Agriculture Organization of the United Nations World Health Organization 1 Thirteenth report of the Joint FAO/WHO Expert Committee on Food Additives, FAO Nutrition Meetings Report Series, in press; Wld Hlth Org. techn. Rep. Ser., in press. PROPYLENE CHLOROHYDRIN Biological Data Biochemical aspects Wesley et al. (1965) identified propylene chlorohydrin as the residue formed in foods fumigated with propylene oxide. The chlorohydrin is formed by the reaction of the epoxide with the chloride of food. Previously, it had been believed that propylene glycol, formed by reaction with water in the food, was the residue. Propylene chlorohydrin is also formed in starches modified by hydroxypropylation. Both propylene chlorohydrin isomers have been identified in fumigated foods (Ragelis et al. 1966). When volatilization was precluded, a combination of high temperature and prolonged time in cooking did not appreciably alter the propylene chlorohydrin content of food, but when volatilization was possible, the chlorohydrin content was reduced 50 per cent. by cooking (Wesley et al. 1965). When propylene chlorohydrin was added to a standard ground laboratory rat diet, 20 minutes of mixing in an open mixer at room temperature resulted in a 65 per cent. decrease in the propylene chlorohydrin content (USFDA, 1966). Acute toxicity Animal Route LD50 Reference (mg/kg body weight) Rat oral 218 USFDA, 1969 Dog oral 150 mg/kg - no deaths USFDA, 1969 200 mg/kg - 1/7 deaths 250, 300 mg/kg - 6/6 deaths Short-term toxicity Rat. Groups of 10 male and 10 female five-week-old rats were fed, for 25 weeks, diets to which propylene chlorohydrin had been added. The planned dietary levels were 0, 1000, 2500, 5000, and 10 000 ppm, but analysis of the 10 000 ppm diet after mixing in the test compound (open mixer, 20 minute mixing time, room temperature) showed an actual concentration of 3568 ppm or 35 per cent. of the planned level. The 2-chloro isomer constituted 27 per cent. of the total found. The actual level in this diet, after seven days exposure to laboratory conditions, was reduced to 838 ppm, with 32 per cent. of the 2-chloro isomer, or less than 10 per cent. of the planned concentration. Weight gain in both sexes on the 5000 and 10 000 ppm levels was depressed. The depression was slight in the males on the 5000 ppm level and both groups of females and moderate in the males on the 10 000 ppm level. Food consumption was slightly decreased in these groups but food efficiency was normal. The average liver, and kidney weights of the males and the liver weight of the females on the 10 000 ppm level were decreased but the organ weight/body weight ratios were normal. The decreased spleen weights and spleen/body weight ratios in the males and other minor organ weight variations appeared to be unrelated to the treatment. No effects on haematological values, mortality, or gross or microscopic lesions in the tissues were observed (USFDA, 1969). Propylene chlorohydrin was administered to groups of 10 male and 10 female eight-week old rats by stomach tube in doses of 0, 25, 50, 75, and 100 mg/kg/day for 22 weeks. The dose for the high level was increased from 100 mg/kg to 150 mg/kg in the eleventh week, to 200 mg/kg in the fourteenth week, and to 250 mg/kg in the sixteenth week. Doses of 200 mg/kg and less did not increase mortality. All the rate on the high level were dead by the nineteenth week with all but one of the deaths occurring between the sixteenth and nineteenth weeks after the dose had been increased to 250 mg/kg. On the high level, weight gain was moderately depressed in the males and slightly depressed in the females while the dose was 100 or 150 mg/kg. Both sexes lost weight when the dose was increased to 200 mg/kg. Weight gain was slightly, but not significantly, decreased in both sexes on the 75 mg/kg level. Food consumption was slightly decreased in the males of the high level while the dose was 100 mg/kg and decreased to a greater extent when the dose was raised. The females on the high level also showed a slight decrease in food consumption when the dose was increased. With the rats losing weight when the dose was increased to 200 mg/kg, the food efficiency values have no meaning. The liver weight/body weight ratios of both males and females on the 75 mg/kg dose and the liver weight and liver weight/body weight ratio of the males on the 25 mg/kg dose were increased, but this increase was not accompanied by gross or microscopic alterations in the liver. Other organ weight and organ weight/body weight ratio changes did not appear to be related to the treatment. No haematological effects or gross or microscopic effects on the tissues of the treated rats, at a dose of 75 mg/kg or less, were seen. The tissues of the high level rats were not examined microscopically (USFDA, 1969). Comments Although in vitro enzymatic digestion tests revealed no abnormalities there was some evidence that a high degree of substitution rendered the product less digestible at the 25 per cent. dietary level. The 90-day tests are adequate and point to 10 per cent. in the diet as the no-effect level. Information is desirable on the metabolic behaviour preferably in man - of the moiety containing the propylene glycol ether. EVALUATION Level causing no toxicological effect in the rat Ten per cent, (= 100 000 ppm) in the diet equivalent to 5000 mg/kg body weight/day. Estimate of acceptable daily intake for man Temporary acceptance mg/kg body weight 0 - 25 Further work required by June 1972 Ninety-day tests in a non-rodent mammalian species using material modified to the highest degree employed as food additive. REFERENCES Feron, V. J., Til, H. P. & de Groot, A. P. (1967) Unpublished report by Centraal Instituut voom Voedings anderzoek TNO, No. R2456 Kay, J. H. & Calandra, J. C. (1961) Unpublished report by Industrial Bio-Test Laboratories, Inc. 17th November 1961 Kay, J. H. & Calandra, J. C. (1962) Unpublished report by Industrial Bio-Test Laboratories, Inc. 22nd January 1962 Majors, P. A. & Rubenkoenig, H. L. (1959) Unpublished report by Hill Top Research Institute, Inc. 18th May 1959 Pallotta, A. J. (1959) Unpublished report by Hazleton Laboratories, Inc. 22nd May 1959 Ragelis, E. P., Fisher, B. S. & Klimeck, B. A. (1966) J.O.A.C., 49, 963 Rubenkoenig, H. L. (1959) Unpublished report by Hill Top Research Institute, Inc. 13th May 1959 United States Food and Drug Administration (1969) Unpublished data Wesley, F., Rourke, B. & Darbishire, O. (1965) J. Fd. Sci., 30, 1037
See Also: Toxicological Abbreviations