Work Environment Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Philosophy and History, Royal Institute of Technology, Stockholm, Sweden.
Crit Rev Toxicol. 2018 Aug;48(7):513-521. doi: 10.1080/10408444.2018.1483891. Epub 2018 Jul 10.
Decision on the safety margin, for instance by using uncertainty factors (UFs), is a key aspect in setting Occupational Exposure Limits (OELs). We analyzed the UFs in 128 OEL recommendations from the European Commission's Scientific Committee on Occupational Exposure Limits (SCOEL). We investigated factors expected to potentially influence the UFs, as well as a selection of factors that might influence how expert groups perceive quality or reliability of key studies. We extracted UFs explicitly stated in the recommendations (EUFs) and, when EUFs were missing, calculated an implicit safety margin (ISM) by dividing the point of departure (PoD) by the OEL. EUFs and ISMs were lower for recommendations based on human data than those based on animal data. EUFs and ISMs were also lower for No-Observed Adverse Effect Concentrations (NOAECs) than Lowest Observed Adverse Effect Concentrations (LOAECs). We saw no differences based on local vs systemic critical effects. Acute data resulted in lower EUFs and ISMs than subchronic. We saw no influence from status of key study (publication status, performer or funder), but high tonnage substances (1,000,000+ tonnes) have lower EUFs and ISMs than substances currently not registered under REACH. Although SCOEL methodology stated that UF should be documented, only 65 out of 128 OEL recommendations included an EUF. Indeed, the ratio of EUFs to ISMs even decreased from 1991-2003 to 2004-2017. Additionally, EUFs were, on average, 1.8 times higher than ISMs. We conclude that a more articulate framework for using UFs could enhance consistency and transparency of the SCOEL recommendations.
例如，通过使用不确定性因素（UFs）来确定安全裕度是制定职业接触限值（OELs）的关键方面。我们分析了欧盟委员会职业接触限值科学委员会（SCOEL）的 128 项 OEL 建议中的 UFs。我们调查了预计可能影响 UFs 的因素，以及可能影响专家组如何感知关键研究质量或可靠性的因素。我们提取了建议中明确规定的 UFs（EUFs），当 EUFs 缺失时，通过将起始点（PoD）除以 OEL 来计算隐含安全裕度（ISM）。基于人体数据的建议的 EUFs 和 ISMs 低于基于动物数据的建议。NOAEC 比 LOAEC 的 EUFs 和 ISMs 更低。我们没有看到基于局部与系统关键效应的差异。急性数据导致的 EUFs 和 ISMs 低于亚慢性数据。我们没有看到关键研究（发布状态、执行者或资助者）的状态有影响，但高吨位物质（100 万+吨）的 EUFs 和 ISMs 低于目前未在 REACH 下注册的物质。尽管 SCOEL 方法规定 UF 应记录在案，但在 128 项 OEL 建议中，只有 65 项包含 EUF。事实上，EUFs 与 ISMs 的比率甚至从 1991-2003 年下降到 2004-2017 年。此外，EUFs 的平均值比 ISMs 高 1.8 倍。我们得出结论，更清晰的 UF 使用框架可以提高 SCOEL 建议的一致性和透明度。
