Mammalian Toxicological Evaluation of p-Chlorophenyl Methyl Sulfide, p-Chlorophenyl Methyl Sulfoxide, and p-Chlorophenyl Methyl Sulfone.

Abstract : The purpose of this project was to determine the toxic potential of p-chlorophenyl methyl sulfide, sulfoxide and sulfone. Studies included in this report are: (1) acute oral LD50 in mice and rats, (2) acute dermal toxicity in rats, (3) skin irritation in rabbits, (4) eye irritation in rabbits, (5) skin sensitization in guinea pigs, (6) 28-day feeding studies in rats and mice, (7) 28-day gavage studies in rats, (8) 91-day feeding studies in rats and mice with interim sacrifices and 14-day reversibility studies, (9) 14-day gavage studies in rhesus monkeys with 14-day reversibility studies, (10) metabolism and pharmacokinetic studies, (11) Ames bacterial mutagenesis studies, (12) hexobarbital sleep time studies for microsomal enzyme induction. Death was achieved in the dermal toxicity studies only at the highest dosage level (5630 mg/kg). Results of the skin irritation studies in rabbits showed no irritation for sulfide, mild irritation for sulfone and sulfoxide. Sulfone induced no eye irritation in rabbits, while sulfide induced mild corneal responses which were reversible. Sulfoxide produced positive responses in cornea, iris, and conjunctiva, with the corneal opacity persisting throughout the 21-day observation period. None of the 3 compounds demonstrated unequivocal skin sensitization in guinea pigs. None of the 3 compounds were mutagenic in the Ames assay. Pathologic changes which were observed in this study included hepatic megalocytosis with syncitial cell formation and hepatic necrosis all of which occurred in both mice and rats given each of the 3 compounds.