Tinwell H, Joiner R, Pate I, Soames A, Foster J, Ashby J
Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, SK10 4TJ, United Kingdom.
Regul Toxicol Pharmacol. 2000 Aug;32(1):118-26. doi: 10.1006/rtph.2000.1412.
Bisphenol A (BPA) has been evaluated in eight independent immature mouse uterotrophic assays using the subcutaneous route of administration, and in a single study employing oral gavage. The dose range covered was from 0.02 microg to 300 mg/kg BPA and some experiments were supplemented by assessments of uterine hypertrophy and hyperplasia. Pooling of the test data indicates no uterotrophic activity for the chemical. However, in a subset of the subcutaneous injection studies, where control uterine weights were relatively low, significant, but weak, uterotrophic activity was observed over a range of dose levels, but in the complete absence of a dose relationship. In the oral gavage study, no increases in uterine weight were seen, but there were increases in uterine labeling with bromodeoxyuridine at 200-300 mg/kg BPA. The present study illustrated that when a large number of observations are made, a certain level of chance observations may be made, and that surrogates for an increase in uterine weight do not necessarily enhance assay sensitivity, albeit such data may complement uterine weight data. The data indicate that reducing control uterine weights may enhance assay sensitivity, but that animal body weight is an imperfect indicator of control uterine weight. The data also show that it is possible for individual investigators to be unable to confirm their own observations. It is concluded that BPA may be weakly uterotrophic to the mouse under specific conditions of test, and in the complete absence of a dose-response relationship to this activity. However, overall, we have failed to define BPA as reproducibly active in the immature mouse uterotrophic assay, and in that sense, our data are broadly consistent with those reported earlier by Coldham et al. (Environ. Health Perspect. 105, 734-742, 1997) in 1997 using a similar assay.
双酚A（BPA）已在八项使用皮下给药途径的独立未成熟小鼠子宫增重试验以及一项采用灌胃法的研究中进行了评估。所涵盖的剂量范围为0.02微克至300毫克/千克BPA，并且一些实验通过评估子宫肥大和增生进行了补充。汇总测试数据表明该化学物质没有子宫增重活性。然而，在皮下注射研究的一个子集中，对照子宫重量相对较低，在一定剂量范围内观察到了显著但微弱的子宫增重活性，但完全不存在剂量关系。在灌胃研究中，未观察到子宫重量增加，但在200 - 300毫克/千克BPA剂量下，子宫用溴脱氧尿苷标记增加。本研究表明，当进行大量观察时，可能会出现一定水平的偶然观察结果，并且子宫重量增加的替代指标不一定会提高检测灵敏度，尽管此类数据可能补充子宫重量数据。数据表明，降低对照子宫重量可能会提高检测灵敏度，但动物体重是对照子宫重量的一个不完美指标。数据还表明，个别研究人员有可能无法证实他们自己的观察结果。得出的结论是，在特定测试条件下，BPA可能对小鼠有微弱的子宫增重作用，并且完全不存在与该活性的剂量 - 反应关系。然而，总体而言，我们未能将BPA定义为在未成熟小鼠子宫增重试验中具有可重复的活性，从这个意义上说，我们的数据与Coldham等人在1997年（《环境健康展望》105，734 - 742，1997）使用类似试验报告的数据大致一致。
