Laboratory for Health Protection Research, Center for Substances and Integrated Risk Assessment, National Institute for Public Health and the Environment, RIVM, Bilthoven, The Netherlands.
Crit Rev Toxicol. 2011 Jul;41(6):545-54. doi: 10.3109/10408444.2011.554794. Epub 2011 May 24.
This paper surveys the scientific basis for the current threshold approach for reproductive hazard and risk assessment. In some regulatory areas it was recently suggested to consider reproductive toxicants under the stringent linear extrapolation risk assessment paradigm that was developed for genotoxic carcinogens. First, the current risk assessment paradigm for genotoxic carcinogens is addressed, followed by an overview of reproductive toxicology and its threshold dose approach for hazard and risk assessment, the testing procedures for assessing the reproductive toxicity of chemicals, and the derivation of conclusions on their risk assessment and Classification, Labelling and Packaging (CLP). Relevant details of testing methodologies are discussed, such as exposure time windows, parameters determined, and the coverage of the entire reproductive cycle. In addition, the dose-response relationship is considered, illustrated with several examples. It is concluded that the current risk assessment methodology for genotoxic carcinogens is a debatable worst-case scenario and that for risk assessment of reproductive toxicants the threshold dose approach remains valid.
本文调查了当前生殖危害和风险评估阈值方法的科学基础。在一些监管领域，最近有人建议在为遗传毒性致癌物制定的严格线性外推风险评估范式下考虑生殖毒性物质。首先，本文介绍了当前遗传毒性致癌物的风险评估范式，接着概述了生殖毒理学及其用于危害和风险评估的阈值剂量方法、评估化学品生殖毒性的测试程序，以及对其风险评估和分类、标签和包装 (CLP) 的结论。讨论了测试方法学的相关细节，例如暴露时间窗口、确定的参数以及整个生殖周期的覆盖范围。此外，还考虑了剂量-反应关系，并举例说明了这一关系。结论认为，当前遗传毒性致癌物的风险评估方法是一个有争议的最坏情况，而对于生殖毒性物质的风险评估，阈值剂量方法仍然有效。
