Schiffelers Marie-Jeanne W A, Blaauboer Bas J, Bakker Wieger E, Hendriksen Coenraad F M, Krul Cyrille
Utrecht University School of Governance, Bijlhouwerstraat 6, 3511 ZC Utrecht, The Netherlands.
Utrecht University, Institute for Risk Assessment Sciences (IRAS), P.O. Box 80.178, 3508 TD Utrecht, The Netherlands.
Regul Toxicol Pharmacol. 2015 Feb;71(1):114-24. doi: 10.1016/j.yrtph.2014.10.012. Epub 2014 Oct 28.
The two-generation study (OECD TG 416) is the standard requirement within REACH to test reproductive toxicity effects of chemicals with production volumes >100 tonnes. This test is criticized in terms of scientific relevance and animal welfare. The Extended One Generation Reproductive Toxicity Study (EOGRTS), incorporated into the OECD test guidelines in 2011 (OECD TG 443) has the potential to replace TG 416, while using only one generation of rats and being more informative. However, its regulatory acceptance proved challenging. This article reconstructs the process of regulatory acceptance and use of the EOGRTS and describes drivers and barriers influencing the process. The findings derive from literature research and expert interviews. A distinction is made between three sub-stages; The stage of Formal Incorporation of the EOGRTS into OECD test guidelines was stimulated by retrospective analyses on the value of the second generation (F2), strong EOGRTS advocates, animal welfare concern and changing US and EU chemicals legislation; the stage of Actual Regulatory Acceptance within REACH was challenged by legal factors and ongoing scientific disputes, while the stage of Use by Industry is influenced by uncertainty of registrants about regulatory acceptance, high costs, the risk of false positives and the manageability of the EOGRTS.
两代研究（经合组织测试指南416）是《化学品注册、评估、授权和限制法规》（REACH）中对产量超过100吨的化学品进行生殖毒性测试的标准要求。该测试在科学相关性和动物福利方面受到批评。2011年纳入经合组织测试指南的扩展一代生殖毒性研究（EOGRTS，经合组织测试指南443）有可能取代测试指南416，同时仅使用一代大鼠且提供更多信息。然而，其监管认可被证明具有挑战性。本文重构了EOGRTS监管认可和使用的过程，并描述了影响该过程的驱动因素和障碍。研究结果来自文献研究和专家访谈。区分了三个子阶段；EOGRTS正式纳入经合组织测试指南的阶段受到对第二代（F2）价值的回顾性分析、EOGRTS的坚定倡导者、动物福利关注以及美国和欧盟化学品法规变化的推动；REACH内实际监管认可阶段受到法律因素和持续科学争议的挑战，而行业使用阶段则受到注册者对监管认可的不确定性、高成本、假阳性风险以及EOGRTS可管理性的影响。
