Selevan S G, Kimmel C A, Mendola P
National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA.
Environ Health Perspect. 2000 Jun;108 Suppl 3(Suppl 3):451-5. doi: 10.1289/ehp.00108s3451.
Several authors have considered the importance of exposure timing and how this affects the outcomes observed, but no one has systematically compiled preconceptional, prenatal, and postnatal developmental exposures and subsequent outcomes. Efforts were undertaken to examine the information available and to evaluate implications for risk assessment for several areas: a) respiratory and immune systems, b) reproductive system, c) nervous system, d) cardiovascular system, endocrine system, and general growth, and e) cancer. Major conclusions from a workshop on "Critical Windows of Exposure for Children's Health" included a) broad windows of sensitivity can be identified for many systems but detailed information is limited; b) cross-species comparisons of dose to target tissue and better data on the exposure-dose-outcome continuum are needed; c) increased interaction among scientific disciplines can further understanding by using laboratory animal results in designing epidemiological studies and human data to suggest specific laboratory studies on mechanisms and agent-target interactions; and d) thus far, only limited attention has been given to peripubertal/adolescent exposures, adult consequences of developmental exposures, and genome-environment interactions. More specific information on developmental windows will improve risk assessment by identifying the most sensitive window(s) for evaluation of dose-response relationships and exposure, evaluation of biological plausibility of research findings in humans, and comparison of data across species. In public health and risk management, information on critical windows may help identify especially susceptible subgroups for specific interventions.
几位作者已经考虑了暴露时间的重要性以及它如何影响所观察到的结果,但没有人系统地汇总孕前、孕期和产后发育过程中的暴露情况以及随后的结果。已开展工作来审查现有信息,并评估以下几个领域的风险评估影响:a) 呼吸系统和免疫系统,b) 生殖系统,c) 神经系统,d) 心血管系统、内分泌系统和一般生长发育,以及 e) 癌症。关于“儿童健康关键暴露窗口期”研讨会的主要结论包括:a) 可以确定许多系统存在广泛的敏感窗口期,但详细信息有限;b) 需要对靶组织剂量进行跨物种比较,并获取关于暴露-剂量-结果连续体的更好数据;c) 各科学学科之间加强互动,通过在设计流行病学研究时运用实验动物结果以及利用人类数据来提示关于机制和毒物-靶标相互作用的具体实验研究,能够增进理解;d) 到目前为止,对青春期前/青春期暴露、发育暴露对成人的影响以及基因组-环境相互作用的关注有限。关于发育窗口期的更具体信息将通过以下方式改进风险评估:确定用于评估剂量-反应关系和暴露的最敏感窗口期、评估人类研究结果的生物学合理性以及跨物种数据比较。在公共卫生和风险管理中,关于关键窗口期的信息可能有助于识别特别易受影响的亚组以便进行特定干预。