Syngenta Product Safety, Jealott's Hill International Research Centre, Bracknell, RG42 6EY, Berkshire, UK.
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
Arch Toxicol. 2023 Dec;97(12):3075-3083. doi: 10.1007/s00204-023-03601-5. Epub 2023 Sep 27.
In Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) the criterion for deciding the studies that must be performed is the annual tonnage of the chemical manufactured or imported into the EU. The annual tonnage may be considered as a surrogate for levels of human exposure but this does not take into account the physico-chemical properties and use patterns that determine exposure. Chemicals are classified using data from REACH under areas of health concern covering effects on the skin and eye; sensitisation; acute, repeated and prolonged systemic exposure; effects on genetic material; carcinogenicity; and reproduction and development. We analysed the mandated study lists under REACH for each annual tonnage band in terms of the information they provide on each of the areas of health concern. Using the European Chemicals Agency (ECHA) REACH Registration data base of over 20,000 registered substances, we found that only 19% of registered substances have datasets on all areas of health concern. Information limited to acute exposure, sensitisation and genotoxicity was found for 62%. The analysis highlighted the shortfall of information mandated for substances in the lower tonnage bands. Deploying New Approach Methodologies (NAMs) at this lower tonnage band to assess health concerns which are currently not covered by REACH, such as repeat and extended exposure and carcinogenicity, would provide additional information and would be a way for registrants and regulators to gain experience in the use of NAMs. There are currently projects in Europe aiming to develop NAM-based assessment frameworks and they could find their first use in assessing low tonnage chemicals once confidence has been gained by their evaluation with data rich chemicals.
在《化学品注册、评估、许可和限制制度》(REACH)中,决定必须进行的研究的标准是在欧盟制造或进口的化学物质的年吨位。年吨位可以被视为人类暴露水平的替代物,但这并没有考虑到决定暴露的物理化学性质和使用模式。化学品是根据涵盖对皮肤和眼睛影响、致敏作用、急性、重复和长期系统暴露、对遗传物质影响、致癌性以及生殖和发育等健康问题领域的 REACH 数据进行分类的。我们根据它们在每个健康问题领域提供的信息,分析了 REACH 下每个年吨位带的强制性研究清单。使用欧洲化学品管理局(ECHA)的超过 20,000 种已注册物质的 REACH 注册数据库,我们发现只有 19%的已注册物质在所有健康问题领域都有数据集。对于 62%的物质,只发现了仅限于急性暴露、致敏和遗传毒性的信息。该分析突出了低吨位物质所要求的信息不足的问题。在这个低吨位带采用新方法方法(NAMs)来评估目前未被 REACH 涵盖的健康问题,如重复和扩展暴露和致癌性,将提供额外的信息,并且是注册人和监管机构在使用 NAMs 方面获得经验的一种方式。目前欧洲有一些旨在开发基于 NAM 的评估框架的项目,一旦通过对富含数据的化学品进行评估获得信心,它们就可以首次用于评估低吨位化学品。