A two-generation reproductive toxicity study of benzophenone in rats.

The reproductive toxicity of benzophenone (BZP) was evaluated in a two generation test in which male and female Sprague-Dawley (SD) rats, parental (F0) and first generation (F1), were exposed to BZP by feeding diet containing BZP at concentrations of 0 (control), 100, 450 or 2000 ppm. With regard to the effects of BZP on the F0 and F1 parental animals, inhibition of body weight gain and food consumption, significantly elevated renal weights, dilatation of the renal proximal tubules, and regeneration of the proximal tubular epithelium were recognized at doses of 450 ppm and 2000 ppm, along with an increase in hepatic weight and centrilobular hepatocytic hypertrophy, considered as vital adaptive changes, at the doses of 100 ppm or more. Obvious effects on the endocrine system and reproductive toxicological effects were not found even at the dose of 2000 ppm in the F0 or F1 parent. There were no test substance related changes in the estrous cycle, reproductive capability, delivery and lactation, sperm parameters, serum hormone levels, or necropsy findings. As for effects on the offspring, inhibition of body weight gain was observed in both the F1 and F2 males and females of the 2000 ppm group. No effects of BZP treatment were recognized in the number of male and female F1 or F2 pups delivered, viability, anogenital distance (AGD), physical development, the results of reflex and response tests, or on the observation results of external abnormalities. From the present study of BZP administered to rats over two successive generations, the no observed effect level (NOEL) on the parental animals is concluded to be less than 100 ppm. Concerning the effects on the endocrine system and the reproductive toxicity in the parental animals, the NOEL is 2000 ppm. In terms of the effects on the offspring, the NOEL is considered to be 450 ppm.