a Department of Pesticides Safety , German Federal Institute for Risk Assessment - BfR , Berlin , Germany.
b Institute of Environmental Medicine, Karolinska Institutet , Stockholm , Sweden.
Crit Rev Toxicol. 2018 Oct;48(9):796-814. doi: 10.1080/10408444.2018.1541964. Epub 2019 Jan 10.
This article reviews the current legislative requirements for risk assessment of combined exposure to multiple chemicals via multiple exposure routes, focusing on human health and particularly on food-related chemicals. The aim is to identify regulatory needs and current approaches for this type of risk assessment as well as challenges of the implementation of appropriate and harmonized guidance at international level. It provides an overview of the current legal requirements in the European Union (EU), the United States and Canada. Substantial differences were identified in the legal requirements for risk assessment of combined exposure to multiple chemicals and its implementation between EU and non-EU countries and across several regulatory sectors. Frameworks currently proposed and in use for assessing risks from combined exposure to multiple chemicals via multiple routes and different durations of exposure are summarized. In order to avoid significant discrepancies between regulatory sectors or countries, the approach for assessing risks of combined exposure should be based on similar principles for all types of chemicals. OECD and EFSA identified the development of harmonized methodologies for combined exposure to multiple chemicals as a key priority area. The Horizon 2020 project "EuroMix" aims to contribute to the further development of internationally harmonized approaches for such risk assessments by the development of an integrated test strategy using in vitro and in silico tests verified for chemical mixtures based on more appropriate data on potential combined effects. These approaches and testing strategies should be integrated in a scientifically based weight of evidence approach to account for complexity and uncertainty, to improve risk assessment.
本文综述了目前通过多种暴露途径对多种化学物质的联合暴露进行风险评估的立法要求，重点关注人类健康，特别是与食品相关的化学物质。目的是确定这种类型的风险评估的监管需求和当前方法，以及在国际层面实施适当和协调的指导方针的挑战。本文概述了欧盟（EU）、美国和加拿大的现行法律要求。在对多种化学物质的联合暴露及其在欧盟和非欧盟国家以及多个监管部门的实施进行风险评估方面，发现了法律要求方面的实质性差异。总结了目前用于评估通过多种途径和不同暴露时间对多种化学物质联合暴露风险的框架。为避免监管部门或国家之间存在重大差异，评估联合暴露风险的方法应基于所有类型化学物质的类似原则。经合组织和欧洲食品安全局确定，制定针对多种化学物质联合暴露的协调方法是一个关键优先领域。“EuroMix”地平线 2020 项目旨在通过开发基于基于潜在联合效应的更适当数据的基于体外和基于计算机的混合物验证测试的综合测试策略，为此类风险评估的进一步制定国际协调方法做出贡献。这些方法和测试策略应整合到基于证据的权重方法中，以考虑到复杂性和不确定性，从而改善风险评估。
