PESTICIDE RESIDUES IN FOOD - 1981 Sponsored jointly by FAO and WHO EVALUATIONS 1981 Food and Agriculture Organization of the United Nations Rome FAO PLANT PRODUCTION AND PROTECTION PAPER 42 pesticide residues in food: 1981 evaluations the monographs data and recommendations of the joint meeting of the FAO panel of experts on pesticide residues in food and the environment and the WHO expert group on pesticide residues Geneva, 23 November-2 December 1981 FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS Rome 1982 sec-BUTYLAMINE Explanation In 1975, the Joint Meeting evaluated sec-butylamine. A temporary ADI (0-0.1 mg base/kg bw) wag allocated.* Further work or information required by 1981 (FAO/WHO 1979) included the following: required by 1981: (1) further studies to resolve the question of carcinogenic risk; desirable: (1) quantitative metabolic studies to determine whether metabolites in test animals are the same as those in food, plants and animals; (2) information on the formation and, if found, toxicity of potential nitrosated derivatives; (3) mutagenicity studies with techniques currently available and (4) clinical and metabolic observations in humans. Of the remaining required and desirable information, only information on mutagenesis for sec-butylamine has been received for evaluation in 1981. DATA FOR THE ESTIMATION OF ACCEPTABLE DAILY INTAKE TOXICOLOGICAL STUDIES Special studies on mutagenicity A recent study examined sec-butylamine and sec-butylamine + H3PO4 for mutagenic activity. Tests included Escherichia coli WP2 and the standard Salmonella/microsome assay with Salmonella typhimurium strains TA 1535, 1537, 1538, 98 and 100, as well as the induction of mitotic recombination in the yeast S. cerevisiae D3. Each assay was performed with or without a rat liver S9 mix for metabolic activation. Neither sec-butylamine nor sec-butylamine + H3PO4 exhibited a mutagenic or recombinogenic response in these systems (Mortelmans and Riccio 1980). The compound was tested in S. typhimurium and E. coli WP2 over a range of 0.1 to 50.0 µl/plate (about 0.07 to 36.5 mg/plate, density approx. or = 0.73) and retested at doses ranging from 0.1 to 25.0 µl/plate (approx. 0.07 to 18.3 mg/plate). No reproducible, dose- related increases in the number of revertants was observed. Toxicity was seen with all strains at 25.0 µl/plate except for WP2, which showed toxicity at 50.0 µl/plate. No recombinogenic activity was * See Annex II for FAO and WHO documentation. observed with this compound when it was tested in S. cerevisiae D3 over concentrations ranging from 0.05 to 0.5% and retested from 0.05 to 0.18%. Toxicity was observed at 0.2% without metabolic activation and at 0.3% with metabolic activation. In another Salmonella and E. coli WP2 assays, the compound was first tested over a concentration range of 1 to 100 µl/plate. A second experiment was conducted over the same range for all strains except TA 98 and TA 100, which were tested up to 500 µl/plate. This was due to the shortage of samples remaining and the desirability of testing this toxicity with strains of TA 98 and TA 100. A toxic response was obtained at the concentration of 500 µl/plate with these two strains, both with and without metabolic activation. In another S. cerevisiae D3 assay, the compound was first tested at concentrations ranging from 0.1 to 5.0% and then retested at higher concentrations ranging from 1.0 to 7.5%. No reproducible, dose- related increase in the number of mitotic recombinants was observed (Mortelmans and Riccio 1980). EVALUATION COMMENTS Although data were received pertaining to mutagenic potential of sec-butylamine, they were deemed to be insufficient to permit assessment of carcinogenic risk. Thus, although data was received that alleviated doubts regarding genotoxic potential, the overall concern regarding the carcinogenic potential of sec-butylamine remains unresolved. As sec-butylamine is a primary amine, the possibility of nitrosamine formation was considered to be remote. Concern regarding this compound, although reduced, has not been eliminated. The temporary ADI of 0.01 mg free amine/kg bw/day was extended for a further three years. Level causing no toxicological effect Rat: 686 ppm free amine (1250 ppm acetate salt in the diet), equivalent to 35 mg free amine/kg bw/day (63 mg acetate salt/kg bw/day). Dog: 69 mg free amine/kg bw/day (125 mg acetate salt/kg bw/day). Estimate of temporary acceptable daily intake for mail 0 - 0.1 mg free amine/kg bw. FURTHER WORK OR INFORMATION Required (by 1984) 1. Further studies to resolve the question of carcinogenic potential. Desirable 1. Adequate toxicological studies on a non-rodent species. 2. Clinical and metabolic observations in humans. REFERENCES Mortelmans, K. and Riccio, E.S. In vitro microbiological genotoxicity 1980 assay of acetonitrile, sec-butylamine (2-AB) and sec- Butylamine (2-AB) + H3PO4. SRI International Project LSU-7558-24. Contract No. 68-02-2947, Final Report, March 1980. (Unpublished)
See Also: Toxicological Abbreviations Butylamine, sec- (WHO Pesticide Residues Series 5) Butylamine, sec- (Pesticide residues in food: 1977 evaluations) Butylamine, sec- (Pesticide residues in food: 1978 evaluations) Butylamine, sec- (Pesticide residues in food: 1979 evaluations) Butylamine, sec- (Pesticide residues in food: 1980 evaluations)