Two-generation reproductive toxicity study of dietary tributyl phosphate in CD rats

Tributyl phosphate (TBP) was tested for reproductive toxicity in rats. Thirty weanlings/sex (F0) were exposed to TBP in the diet ad libitum at 0, 200, 700, or 3000 ppm for 10 weeks and then randomly mated within groups for 3 weeks with continued exposure. F0 parents and 10 F1 weanlings/sex/dose were necropsied, and adult reproductive organs, urinary bladders (both sexes), kidneys (males), and livers (females) were evaluated histologically. Thirty F1 weanlings/sex/dose continued exposure for 11 weeks and were bred as described above. F1 parents and F2 weanlings, 10/sex/dose, were then necropsied as described above. Adult toxicity was observed in both sexes and generations at 700 and 3000 ppm; observations included reduced body weights, weight gain and feed consumption, urinary bladder epithelial hyperplasia (both sexes), renal pelvis epithelial hyperplasia only at 3000 ppm (male kidneys), and centrilobular hypertrophy (female livers). At 200 ppm, transient reductions in body weight were observed in F0 and F1 females, with urinary bladder epithelial hyperplasia in F0 males and females and in F1 males. There was no evidence of reproductive toxicity, of reproductive organ pathology, or of effects on gestation or lactation at any dose tested. Postnatal toxicity was evidenced by consistent reductions in F1 and F2 pup body weights at 3000 ppm and by occasional weight reductions in F2 litters at 700 ppm, and was associated with maternal toxicity observed at these doses and times. Under the conditions of this study, a NOAEL was not determined for adult toxicity; the NOAEL for reproductive toxicity was at least 3000 ppm and the NOAEL for postnatal toxicity was approximately 200 ppm.