Interpreting the toxicologic significance of alterations in anogenital distance: potential for confounding effects of progeny body weights
Interpreting the toxicologic significance of alterations in anogenital distance: potential for confounding effects of progeny body weights
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DOI：
10.1016/s0890-6238(99)00036-2
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发表时间：
1999-09-01
影响因子：
3.3
通讯作者：
Reynolds, VL
中科院分区：
文献类型：
--
作者：
Gallavan, RH;Holson, JF;Reynolds, VL
肛门生殖器距离（AGD）是美国环境保护署（EPA）最近在生殖毒性研究测试指南中增加的一个终点。这个终点对测试化学物质的激素效应很敏感。在用影响幼犬整体体型的药物治疗后，AGD的明显改变可能会发生。在这种情况下，激素活动可能与测试治疗错误地联系在一起。本报告的分析评估了对照窝幼犬体重与AGD之间的统计相关性。在两项独立的两代生殖毒性研究中，对113只未经治疗的雌性Sprague-Dawley大鼠的1501只幼鼠在出生后第1天测量了AGDs。AGD与体重、AGD与体重立方根呈显著相关。雄鱼体重每增加1 g， AGD增加0.26 mm。雌性体重每增加1 g， AGD增加0.13 mm。尽管使用体重作为协变量预测雄性或雌性AGD的回归模型与基于体重立方根的回归模型之间基本上没有差异，但在体重范围比本分析中遇到的更大的动物中可能不会出现这种相似性。通过体重除以AGD的正常化明显过度补偿了体型的差异。用体重的立方根进行归一化，在本研究中观察到的体重范围内，AGD/体重的立方根比值是恒定的。综上所述，协方差分析是解释体型对AGD影响的首选方法。如果直接进行归一化，则AGD与体重的立方根之比是更合适的度量。(C) 1999 Elsevier Science Inc.；版权所有。
Anogenital distance (AGD) is an endpoint that was recently added to the U.S. EPA testing guidelines for reproductive toxicity studies. This endpoint is sensitive to hormonal effects of test chemicals. It is possible that apparent alterations in AGD might occur after treatment with agents that affect overall pup body size. In such cases, hormonal activity might be associated incorrectly with the test treatment. The analyses in this report evaluated statistical correlations between pup body weight and AGD in control litters. AGDs were measured on postnatal day 1 in 1501 pups derived from 113 untreated female Sprague-Dawley rats in two independent two-generation reproductive toxicity studies. Significant correlations were detected between AGD and body weight and between AGD and the cube root of body weight. In males, AGD increased 0.26 mm for each 1 g increase in body weight. In females, AGD increased 0.13 mm per I g increase in body weight. Although there were essentially no differences between the regression models developed to predict AGD in either males or females using body weight as a covariate and those based on the cube root of body weight, such similarities in predictivity might not occur in larger animals with broader weight ranges than those encountered in this analysis. Normalization of AGD by dividing by body weight significantly overcompensated for differences in body size. Normalizing with the cube root of body weight resulted in an AGD/cube root of body weight ratio that was constant across the range of body weights observed in this study. In conclusion, as a preferred method to account for body size effects on AGD, analysis of covariance is recommended. If a normalization is done directly, the ratio of AGD to the cube root of body weight is the more appropriate metric. (C) 1999 Elsevier Science Inc. All rights reserved.