P-Chlorophenyl Methyl Sulfide, p-Chlorophenyl Methyl Sulfoxide, and p-Chlorophenyl Methyl Sulfone. II. Subchronic Effects in Rodents and Rhesus Monkeys

Abstract

Rats, mice, and rhesus monkeys were subjected in subchronic exposures to the chemicals p-chlorophenyl methyl sulfide, p-chlorophenyl methyl sulfoxide, and p-chlorophenyl sulfone. Ninety-one-day toxicity studies were conducted by administering test chemicals to rodents at dietary concentrations of 750, 1500, and 3000 ppm. Clinical signs observed included transient central nervous system (CNS) depression, anorexia, and depressed weight gains. Minor alterations of hematologic and clinical chemistry parameters were also present. Gross and microscopic tissue findings in mice and rats included enlargement, necrotic and megalocytic changes of the liver. Damage to bronchiolar epithelium was observed in mice only at the highest exposure level. A 14-day gavage study in monkeys used daily dosages ranging from 2.5 to 80 mg/kg with an additional 15 days allotted for a recovery phase in one-half the test animals. Compound-related findings included lethality, CNS depression, and emesis. There were no significant compound-induced alterations in electrocardiographic or ophthalmic parameters. Serum blood urea nitrogen and serum glutamic pyruvic transaminase values were elevated in the highest dosage groups for the three test materials concomitant with increases in liver and kidney weights. Microscopic lesions included proliferative changes in lymph nodes, spleen, and bone marrow; hepatocellular vacuolization, degeneration, and necrosis; thyroid follicular cell hyperplasia; and degenerative lesions in gastric and intestinal epithelium. No-observable-effect levels (NOELs) were not established for any of the three test chemicals in the species tested.