A framework for chemical safety assessment incorporating new approach methodologies within REACH

Arch Toxicol. 2022 Mar;96(3):743-766. doi: 10.1007/s00204-021-03215-9. Epub 2022 Feb 1.

Abstract

The long-term investment in new approach methodologies (NAMs) within the EU and other parts of the world is beginning to result in an emerging consensus of how to use information from in silico, in vitro and targeted in vivo sources to assess the safety of chemicals. However, this methodology is being adopted very slowly for regulatory purposes. Here, we have developed a framework incorporating in silico, in vitro and in vivo methods designed to meet the requirements of REACH in which both hazard and exposure can be assessed using a tiered approach. The outputs from each tier are classification categories, safe doses, and risk assessments, and progress through the tiers depends on the output from previous tiers. We have exemplified the use of the framework with three examples. The outputs were the same or more conservative than parallel assessments based on conventional studies. The framework allows a transparent and phased introduction of NAMs in chemical safety assessment and enables science-based safety decisions which provide the same level of public health protection using fewer animals, taking less time, and using less financial and expert resource. Furthermore, it would also allow new methods to be incorporated as they develop through continuous selective evolution rather than periodic revolution.

Keywords: Chemical risk assessment; New approach methodology; Regulatory framework; Tiered assessment; Toxicity.

MeSH terms

  • Animal Testing Alternatives
  • Animals
  • Chemical Safety / legislation & jurisprudence
  • Chemical Safety / methods*
  • Computer Simulation
  • Environmental Exposure / prevention & control
  • Humans
  • Risk Assessment / legislation & jurisprudence
  • Risk Assessment / methods*
  • Toxicity Tests / methods*