13-WEEK SUBCHRONIC TOXICITY STUDY OF THIAMPHENICOL IN F344 RATS

A 13-week subchronic toxicity study of thiamphenicol (TAP) was perform ed in F344 rats. The minimum lethal dose was estimated to be greater t han 10 g/kg body weight, when a single dose of 4-10 g/kg of TAP was gi ven orally. In the subchronic toxicity study, groups of 12 F344 rats o f each sex were given solutions containing 0 (control), 125, 250 and 5 00 ppm of TAP as their drinking water ad libitum for 13 weeks. Body we ight gain was significantly suppressed in both sexes of the 250 and 50 0 ppm groups. Slight suppression of erythropoiesis was observed in the highest-dose group along with slightly reduced spermatogenesis in the testes of the males. In addition, spermatogranulomas were found in th e epididymis of both middle- and highest-dose groups. The no observed adverse effect level (NOAEL) was concluded to be 125 ppm (daily doses of 9.0 mg/kg in males and 11.6 mg/kg in females). From the above descr ibed results, doses of 250 and 125 ppm were selected as appropriate fo r a 2-year carcinogenicity study. (C) 1997 Elsevier Science Ireland Lt d.