Dc. Thake et al., P-CHLOROPHENYL METHYL SULFIDE, P-CHLOROPHENYL METHYL SULFOXIDE, AND P-CHLOROPHENYL METHYL SULFONE .2. SUBCHRONIC EFFECTS IN RODENTS AND RHESUS-MONKEYS, Journal of the American College of Toxicology, 12(4), 1993, pp. 377-395
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 inc
luded 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 megalocyt
ic 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 additi
onal 15 days allotted for a recovery phase in one-half the test animal
s. Compound-related findings included lethality, CNS depression, and e
mesis. There were no significant compound-induced alterations in elect
rocardiographic or ophthalmic parameters. Serum blood urea nitrogen an
d serum glutamic pyruvic transaminase values were elevated in the high
est dosage groups for the three test materials concomitant with increa
ses in liver and kidney weights. Microscopic lesions included prolifer
ative changes in lymph nodes, spleen, and bone marrow; hepatocellular
vacuolization, degeneration, and necrosis; thyroid follicular cell hyp
erplasia; and degenerative lesions in gastric and intestinal epitheliu
m. No-observable-effect levels (NOELs) were not established for any of
the three test chemicals in the species tested.