Gelbke H P, Kayser M, Poole A
Department of Product Safety, GUP-Z 470, 67056 Ludwigshafen, Germany.
Toxicology. 2004 Dec 1;205(1-2):17-25. doi: 10.1016/j.tox.2004.06.034.
The question whether (man-made or natural) chemical substances may have an adverse effect on the endocrine system has gained high visibility in the public as well as in the scientific community. This relates to possible effects on the environment as well as on human health for chemicals with (anti)estrogenic, (anti)androgenic or (anti)thyroid activity. Taking into account the broad universe of chemicals to which humans or the environment may be exposed, a sound testing strategy and robust test methods are urgently needed. Both subjects have been addressed by a specific OECD working group (EDTA-Endocrine Disruptor Testing and Assessment Task Force) involving regulatory agencies, the scientific community, chemical industry and NGOs. Like other organizations the OECD has adopted a tiered-testing strategy with the first tier using screening assays as quick and inexpensive tools, providing a way of generating alerts to potential endocrine activity that can be used to prioritize substances for definitive tests that then can determine the toxicological consequences of endocrine toxicity. The efforts of the OECD have therefore concentrated on the validation of specific screening and testing guidelines, like the uterotrophic, the Hershberger, and the "enhanced TG 407" test. The experimental testing necessary for this validation procedure is completed for the uterotrophic and the "enhanced TG 407" tests and near completion for the Hershberger assay. The data obtained so far have been published (for the uterotrophic assay) or will be submitted to the EDTA working group for final evaluation. Overall, the validation program has been very successful and should be sufficient for setting up OECD test guidelines for these experimental procedures. This will add substantially to the "tool-box" of OECD test methods that is available internationally to regulatory agencies and chemical industry for the identification and assessment of possible endocrine disruptors. Despite this success it is well recognized that the methodological "tool-box" should be supplemented by further screening and testing procedures related to effects on human health and the environment.
(人造或天然)化学物质是否会对内分泌系统产生不良影响这一问题,在公众和科学界都备受关注。这涉及到具有(抗)雌激素、(抗)雄激素或(抗)甲状腺活性的化学物质对环境以及人类健康可能产生的影响。鉴于人类或环境可能接触到的化学物质种类繁多,迫切需要一个完善的测试策略和可靠的测试方法。经济合作与发展组织(OECD)的一个特定工作组(EDTA - 内分泌干扰物测试与评估特别工作组),其中包括监管机构、科学界、化学工业界和非政府组织,已着手处理这两个问题。与其他组织一样,OECD采用了分层测试策略,第一层使用筛选分析作为快速且廉价的工具,提供一种对潜在内分泌活性发出警报的方法,可用于确定需进行确定性测试的物质优先级,进而确定内分泌毒性的毒理学后果。因此,OECD的工作重点集中在特定筛选和测试指南的验证上,如子宫增重试验、赫什伯格试验和“增强版TG 407”试验。子宫增重试验和“增强版TG 407”试验已完成该验证程序所需的实验测试,赫什伯格试验也接近完成。目前已获得的数据(关于子宫增重试验)已发表,或将提交给EDTA工作组进行最终评估。总体而言,验证计划非常成功,应该足以制定OECD关于这些实验程序的测试指南。这将极大地丰富OECD测试方法的“工具箱”,供国际监管机构和化学工业界用于识别和评估可能的内分泌干扰物。尽管取得了这一成功,但人们也清楚地认识到,该方法“工具箱”应通过与人类健康和环境影响相关的进一步筛选和测试程序加以补充。