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 DNOC Chemical name 2-methyl-4,6-dinitrophenol; 2,4-dinitro-6-methylphenol; 2,4-dinitro-o-cresol; 3,5-dinitro-o-cresol. Synonyms DNC Empirical formula C7H6N2O5 Structural formulaBIOLOGICAL DATA Biochemical aspects Like other dinitrophenols, DNOC increases the oxidative metabolism and heat production by direct cellular reaction. DNOC affects enzyme systems by inhibiting the formation of adenosine triphosphate and by blocking oxidative phosphorylation. In the blood, DNOC combines with the plasm proteins to form compounds that persist for variable times depending on the species (King & Harvey, 1953). In mammals and plants DNOC is reduced to a number of amino compounds (Wessels, 1960). Acute toxicity Animal Route LD50 mg/kg References body-weight Rat Oral 26-30 Lehman, 1951 Negherbon, 1959 Rat Intraperitoneal 28.5 Lawford et al., 1954 Mouse Intraperitoneal 24-26 Lawford et al., 1954 Guinea-pig Intraperitoneal 22.5 Lawford et al., 1954 Rabbit Intraperitoneal 23.5 Lawford et al., 1954 Goat Oral 100 Negherbon, 1959 Short-term studies Rat. Groups of 5-10 male rats were given diets containing 7.8, 15.6, 31.2, 62.5, 125, 250, 500 and 1000 ppm DNOC for 105 days. Dosages from 7.8 to 31.2 ppm did not affect growth or food consumption. Growth and food consumption were slightly increased in the 62.5 and 125 ppm groups. Dosages of 125 and 250 ppm killed 60% of the rats and growth was inhibited in the survivors on 250 ppm. The animals with 500 and 1000 ppm failed to grow and died in 2 or 3 days. No histopathological changes were noted in any organ (Ambrose, 1942). Groups of 20 male rats were given diets containing 20, 50, 100, 200, 500 and 1000 ppm DNOC for 6 months. Growth was normal in those on 20, 50 and 100 ppm; with 200 ppm, growth was decreased but not significantly; with 500 ppm there was poor weight gain and with 1000 ppm half the rats died by the tenth day. The reminder were killed for histopathological examination. Slight cloudy swelling of the liver at 1000 ppm was found (Spencer et al., 1948). Duckling. A group of nine ducklings given 0.25% DNOC showed bilateral cataracts within 24 hours. This dosage was lethal to all ducklings within 2 days (Spencer et al., 1948). Man. Two volunteers received 75 mg/day orally for 7 days. In one subject, lassitude, headache and malaise occurred on the seventh day. In the second no symptoms appeared (Negherbon, 1959). Five male volunteers were given daily doses of 75 mg of pure DNOC orally for 5 days. This dose ranged from 0.92 to 1.27 mg/kg body-weight per day. The volunteers on the highest dose developed symptoms of lassitude, headache and general malaise on the fifth day. Doses of the order of 1 mg/kg body-weight resulted in concentrations of 15-20 µg of DNOC per g of blood after 3-5 days. Symptoms occur when the concentration in the blood is of the order of 20 µg per g of blood (Harvey et al., 1951). Bilateral cataracts have occurred from the use of DNOC in the treatment of obesity (Bidstrup & Payne, 1951). Comments on the experimental studies reported Two relatively short studies in rats have indicated that a dosage of 100 ppm of DNOC in the diet is a "no-effect" level. However, human studies have shown that DNOC is more toxic to man than was indicated by these rat studies. Studies with ducks and reports of human use in obesity show that DNOC may produce cataracts. EVALUATION Estimate of acceptable daily intake for man In view of the fact that the maximum no-effect level in the rat was established on a six-month experiment only and because of the high toxicity of DNOC to man no maximum acceptable daily intake for man can be established. Further work required Chemical composition and toxicity of the plant residues. REFERENCES Ambrose, A. M. (1942) J. Pharmacol. exp. Ther., 76, 245 Bidstrup, P. L. & Payne, D. J. H. (1951) Brit. med. J., 2, 16 Harvey, D. G., Bidstrup, P. L. & Bonnell, J. A. L. (1951) Brit. med. J., 2, 13 King, E. & Harvey, D. G. (1953) Biochem. J., 53, 185 and 196 Lawford, D. J., King, E. & Harvey, D. S. (1954) J. Pharm. Pharmacol., 6, 619-624 Lehman, A. J. (1951) Quart. Bull. Assoc. Food and Drug Officials U.S., 15, 122 Negherbon, W. O. (1959) Handbook of Toxicology, Philadelphia & London, Saunders, vol. III Spencer, H. C., Rowe, V. K., Adams, E. M. & Irish, D. D. (1948) J. industr. Hyg., 30, 10 Wessels, J. S. C. (1960) Bioph. Biochem. Acta, 38, 195
See Also: Toxicological Abbreviations