Ashby J, Tinwell H, Lefevre P A, Odum J, Paton D, Millward S W, Tittensor S, Brooks A N
Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, United Kingdom.
Regul Toxicol Pharmacol. 1997 Aug;26(1 Pt 1):102-18. doi: 10.1006/rtph.1997.1159.
Butyl benzyl phthalate (BBP) has been administered in drinking water (1000 micrograms/liter) to pregnant AP rats during gestation and lactation. The sexual development of the pups was then monitored until their termination at postnatal day 90 (pnd 90). Pups derived from animals exposed to diethylstilbestrol (DES) in drinking water (50 micrograms/liter) acted as a positive control group. Glass drinking bottles were employed following demonstration of absorption of BBP into plastic drinking bottles. Drinking water intake was monitored and the estimated average exposures of the dams was 182.6 micrograms/kg/day BBP and 8.6 micrograms/kg/ day DES. A total of 240 control pups, 204 BBP pups, and 64 DES pups were obtained for study. The sexual development of both genders of pups was monitored. The body weights of the DES pups were significantly reduced at birth, an effect that persisted until pnd 90. The body weights of the BBP pups were marginally increased at birth, but this difference resolved by pnd 90. DES affected the sexual development of the pups for all endopoints monitored-anogenital (AG) distance on pnd 2; average day of vaginal opening and prepuce separation; uterus, testes, and accessory sex gland weight; and cauda epididymis sperm count and homogenization resistant testicular sperm count at pnd 90. BBP failed to affect any of these parameters, with the exception of a 1.1-day advance in the average day of vaginal opening and a small increase in male AG distance on pnd 2. These last two effects are related to the increased weight of the BBP pups. The incidence of FSH-containing cells in the pituitary gland of animals from each group was unaffected at pnd 90. The effects observed for the DES pups are consistent with the results of earlier studies by Sharpe et al. (Environ. Health Perspect. 103, 1136-1143, 1995). However, the absence of an effect of BBP administration on pup testis weight and testicular sperm count at pnd 90 is in contrast to reductions in these measurements reported earlier by Sharpe et al. (Environ. Health Perspect. 103, 1136-1143, 1995) for similarly derived BBP pups.
在孕期和哺乳期，将邻苯二甲酸丁苄酯（BBP）以1000微克/升的剂量添加到饮用水中，喂食怀孕的AP大鼠。随后监测幼崽的性发育情况，直至它们在出生后第90天（pnd 90）处死。将饮用水中添加己烯雌酚（DES）（50微克/升）的动物所产幼崽作为阳性对照组。在证明BBP可被塑料饮水瓶吸收后，改用玻璃饮水瓶。监测饮水量，估计母鼠的平均暴露剂量为每天182.6微克/千克BBP和每天8.6微克/千克DES。共获得240只对照幼崽、204只BBP幼崽和64只DES幼崽用于研究。监测了幼崽雌雄两性的性发育情况。DES幼崽出生时体重显著降低，这种影响一直持续到pnd 90。BBP幼崽出生时体重略有增加，但这种差异在pnd 90时消失。DES对所监测的所有终点指标的幼崽性发育均有影响，包括pnd 2时的肛殖（AG）距离；阴道开口和包皮分离的平均天数；子宫、睾丸和附属性腺重量；以及pnd 90时附睾尾精子计数和抗均质化睾丸精子计数。BBP未影响这些参数中的任何一项，但阴道开口平均天数提前了1.1天，且pnd 2时雄性AG距离略有增加。最后这两个影响与BBP幼崽体重增加有关。在pnd 90时，每组动物垂体中含促卵泡激素细胞的发生率未受影响。DES幼崽所观察到的影响与Sharpe等人早期研究（《环境健康展望》103，1136 - 1143，1995年）的结果一致。然而，在pnd 90时，给予BBP对幼崽睾丸重量和睾丸精子计数无影响这一情况，与Sharpe等人（《环境健康展望》103，1136 - 1143，1995年）早期报道的类似来源BBP幼崽的这些测量值降低形成对比。
