Tyl R W, Gerhart J M, Myers C B, Marr M C, Brine D R, Seely J C, Henrich R T
Research Triangle Institute, Research Triangle Park, North Carolina 27709-2194, USA.
Fundam Appl Toxicol. 1997 Nov;40(1):90-100. doi: 10.1006/faat.1997.2373.
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.
对大鼠进行了磷酸三丁酯（TBP）的生殖毒性测试。将30只断奶幼鼠/性别（F0）随意暴露于含0、200、700或3000 ppm TBP的饲料中，持续10周，然后在组内随机交配3周，同时继续暴露。对F0代亲代和10只F1代断奶幼鼠/性别/剂量组进行尸检，并对成年生殖器官、膀胱（两性）、肾脏（雄性）和肝脏（雌性）进行组织学评估。30只F1代断奶幼鼠/性别/剂量组继续暴露11周，并按上述方法进行繁殖。然后对F1代亲代和F2代断奶幼鼠，10只/性别/剂量组，按上述方法进行尸检。在700和3000 ppm剂量下，两代两性均观察到成年毒性；观察结果包括体重减轻、体重增加和采食量减少、膀胱上皮增生（两性）、仅在3000 ppm时出现肾盂上皮增生（雄性肾脏）和小叶中心肥大（雌性肝脏）。在200 ppm时，F0代和F1代雌性出现短暂体重减轻，F0代雄性和雌性以及F1代雄性出现膀胱上皮增生。在任何测试剂量下，均未发现生殖毒性、生殖器官病理学证据或对妊娠或哺乳的影响。产后毒性表现为在3000 ppm时F1代和F2代幼崽体重持续减轻，在700 ppm时F2代幼崽偶尔体重减轻，并且与在这些剂量和时间观察到的母体毒性有关。在本研究条件下，未确定成年毒性的无观察到有害作用水平（NOAEL）；生殖毒性的NOAEL至少为3000 ppm，产后毒性的NOAEL约为200 ppm。
