Faustman E M, Wellington D G, Smith W P, Kimmel C A
Department of Environmental Health, University of Washington, Seattle 98195.
Environ Health Perspect. 1989 Feb;79:229-41. doi: 10.1289/ehp.8979229.
The Rai and Van Ryzin dose-response model proposed for teratology experiments has been characterized for its appropriateness and applicability in modeling the dichotomous response data from developmental toxicity studies. Modifications were made in the initial probability statements to reflect more accurately biological events underlying developmental toxicity. Data sets used for the evaluation were obtained from the National Toxicology Program and U.S. EPA laboratories. The studies included developmental evaluations of ethylene glycol, diethylhexyl phthalate, di- and triethylene glycol dimethyl ethers, and nitrofen in rats, mice, or rabbits. Graphic examination and statistical evaluation demonstrate that this model is sensitive to the data when compared to directly measured experimental outcomes. The model was used to interpolate to low-risk dose levels, and comparisons were made between the values obtained and the no-observed-adverse-effect levels (NOAELs) divided by an uncertainty factor. Our investigation suggests that the Rai and Van Ryzin model is sensitive to the developmental toxicity end points, prenatal deaths, and malformations, and appears to model closely their relationship to dose.
为致畸实验提出的Rai和Van Ryzin剂量反应模型，已被证明在对发育毒性研究中的二分反应数据进行建模时具有适用性。对初始概率陈述进行了修改，以更准确地反映发育毒性背后的生物学事件。用于评估的数据集来自美国国家毒理学计划和美国环境保护局实验室。这些研究包括对大鼠、小鼠或兔子进行的乙二醇、邻苯二甲酸二异辛酯、二乙二醇二甲醚和三乙二醇二甲醚以及除草醚的发育评估。图形检查和统计评估表明，与直接测量的实验结果相比，该模型对数据敏感。该模型用于内插到低风险剂量水平，并将所得值与未观察到有害作用水平（NOAELs）除以不确定性因子后的值进行比较。我们的研究表明，Rai和Van Ryzin模型对发育毒性终点、产前死亡和畸形敏感，并且似乎紧密模拟了它们与剂量的关系。
