A TWO-GENERATION REPRODUCTIVE TOXICITY STUDY OF BUTYL BENZYL PHTHALATE IN RATS

A two-generation reproductive toxicity study with extra parameters was performed for Butyl benzyl phthalate (BBP). The compound was administered orally by gavage with the doses of 0, 100, 200, or 400 mg/kg/day to groups of 24 Crj:CD®(SD)IGS rats of both sexes to confirm the utility of the protocol for identification of non-steroid chemicals with endocrine activity by ssessing effects on parental animals and offspring. Softening of the testes, diffuse atrophy of testicular seminiferous tubules, decreased spermatozoa and/or residual germ cells in the epididymal lumina were observed in the F1generation after doses more than 100 mg/kg, lowering of the F1 epididymal weights at doses more than 200 mg/kg, along with low F0 epididymal weights, Leydig cell hyperplasia, residual germ cells in the epidimymal lumina, and low seminal vesicle weights, small testes and epididymes, partial aplasia or aplasia of the epididymes, and Leydig cell hyperplasia in the F1 generation with 400 mg/kg. With regard to effects on the reproductive capacity, F1 parents at the dose of 400mg/kg showed a reduced fertility index and delayed preputial separation of the penis. In the offspring, lowered body weights in the F1 case, and change in anogenital distance in the F1 females and F2 males were observed at doses more than 100 mg/kg, with low splenic weights at 400 mg/kg in both generations. Thus, the utility of this protocol was confirmed. In the parental animals, the no observed effect level (NOEL) and the no observed adverse effect level (NOAEL) were less than 100 mg/kg/day, and no serious effects on the reproductive capacity were induced at doses less than 200 mg/kg/day. The NOEL and NOAEL for the growth and development of offspring were concluded to be less than 100 mg/kg/day.