FAO Meeting Report No. PL/1965/10/1 WHO/Food Add./27.65 EVALUATION OF THE TOXICITY OF PESTICIDE RESIDUES IN FOOD The content of this document is the result of the deliberations of the Joint Meeting of the FAO Committee on Pesticides in Agriculture and the WHO Expert Committee on Pesticide Residues, which met in Rome, 15-22 March 19651 Food and Agriculture Organization of the United Nations World Health Organization 1965 1 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 CHLORFENSON Chemical name p-chlorophenyl-p-chlorobenzene sulfonate; 4-chlorophenyl-4-chlorobenzene-sulfonate. Synonyms Ovotram; Ovex; Mitran; Orthotran; Ovotex; Difenson; CPCBS. Empirical formula C12H8O3Cl2S Structural formulaBIOLOGICAL DATA Biochemical aspects Absorption from the alimentary tract of dogs and rats after single oral doses varying from 15 to 500 mg/kg body-weight was variable. Intravenous doses of 15 mg/kg body-weight in dogs disappeared from the plasma within 22 hours and less than 1% of the total dose was recovered in the urine. There is evidence that accumulation occurs in depot fat of dogs after the administration of 50 mg/kg body-weight daily for 6 months. Only traces could be found in the fat depots and tissues or organs in dogs given doses of 15 and 5 mg/kg body-weight per day for the same period (Dow, 1962). Female rats tended to accumulate chlorfenson in depot fat more than males after dose levels of 300 and 3000 ppm in the diet for 370 days. Small quantities were also found in the liver and muscles. At the level of 100 ppm no traces could be found in tissues or organs of rats (Dow, 1962). Acute toxicity Animal Route LD50 mg/kg References body-weight Rat Oral 2 000 Dow, 1951 Dow, 1962 Short-term studies Rat. Female rats (5 per group) were fed 300, 1000, 3000 and 10 000 ppm in the diet for 130 days. Those at 300 ppm showed no evidence of adverse effects as judged by general appearance and behaviour, mortality rate, growth, organ weights, and microscopic examination of the tissues. The animals receiving 1000 and 3000 ppm showed an increase in liver and kidney weights, and slight histological degenerative changes in these organs. Those on the highest dose level, 10 000 ppm, showed more pronounced effects (Dow, 1962). Dog. Sixteen male and female dogs were divided into 4 groups and were given 5, 15 and 50 mg/kg body-weight per day for 6 months. At the lowest dose level, 5 mg, no effect was reported. At doses of 15 and 50 mg/kg body-weight per day only a questionable increase in the average weights of the liver were found. No histological changes were noted in this organ (Dow, 1962). Long-term studies Rat. Groups of 80 rats (40 female and 40 male were maintained for one year on diets containing 100, 300 and 3000 ppm of chlorfenson. Growth retardation, increases in average liver and kidney weight and histological changes in these organs were found in the rats receiving 300 and 3000 ppm. At 100 ppm only a slight increase in liver weight and histological changes in liver and kidneys were found (Dow, 1951). The slight changes in the liver were characterized by the presence of congestion and cloudy swelling, mainly in the portal areas which had the appearance of beginning portal cirrhosis without fibrosis. The kidneys showed some evidence of glomerular fibrosis with degeneration, vacuole formation, cloudy swelling of the tubular epithelium, and the presence of casts, oedema and congestion. Half the rats from this experiment were placed on the normal diet for 30 days. Gross examination at autopsy showed no abnormalities in the animals that had previously received 100 and 300 ppm of chlorfenson in the diet. Microscopic examination of the tissues of the rats that had received 100 ppm showed slight pathological changes in the liver and kidney. The liver showed beginning portal cirrhosis and a few large fat vacuoles and areas of necrosis. The kidney showed glomerular and tubular fibrosis (Dow, 1962). Groups of 20 rats (10 females and 10 males) were given a diet containing 0.63, 1.25, 2.5, 5, 15 and 50 mg/kg body-weight per day for two years. Increases in the average weights of liver and kidney and histopathological changes in these organs were noted at doses of 2.5 mg/kg and above. Microscopically there were fatty changes in the liver and chronic glomerulonephritis in the kidneys. In the groups of rats that had ingested doses of 1.25 and 0.63 mg/kg per day, no significant effects were found as judged by general appearance and behaviour, growth, mortality rate, food consumption, average organ weights, and gross and microscopic examination of the tissues (Dow, 1962; Weil & McCollister, 1963). Comments on the experimental studies reports Adequate experimental data on the short-term and long-term toxicity in the rat and short-term toxicity in the dog have been presented. Almost all the information obtainable on long-term toxicity has been derived from one reliably conducted study with adequate numbers of animals. Biochemical data on the accumulation and excretion of chlorfenson have also been presented, but no information is available on its metabolism. EVALUATION Level causing no significant toxicological effect in the rat The maximum no-effect level in rats is 25 ppm equivalent to 1.25 mg/kg body-weight per day. Estimate of acceptable daily intake for man 0-0.01 mg/kg body-weight. Further work desirable Metabolic studies in animals. Short-and long-term studies in other species than the rat. REFERENCES Dow Chemical Company (1951) Midland Michigan, Technical Bulletin Dow Chemical Company (1962) Midland Michigan, Unpublished data Weil, C. S. & McCollister, D. D. (1963) Agric. Food Chem., 11, 486
See Also: Toxicological Abbreviations