Mutation as a Toxicological Endpoint for Regulatory Decision-Making
- DOI
- Language of the publication
- English
- Date
- 2019-10-10
- Type
- Article
- Author(s)
- Heflich, Robert H.
- Johnson, George E.
- Zeller, Andreas
- Marchetti, Francesco
- Douglas, George R.
- Witt, Kristine L.
- Gollapudi, B. B.
- White, Paul A.
- Publisher
- Wiley
Abstract
Mutations induced in somatic cells and germ cells are responsible for a variety of human diseases, and mutation per se has been considered an adverse health concern since the early part of the 20th Century. Although in vitro and in vivo somatic cell mutation data are most commonly used by regulatory agencies for hazard identification, that is, determining whether or not a substance is a potential mutagen and carcinogen, quantitative mutagenicity dose–response data are being used increasingly for risk assessments. Efforts are currently underway to both improve the measurement of mutations and to refine the computational methods used for evaluating mutation data. We recommend continuing the development of these approaches with the objective of establishing consensus regarding the value of including the quantitative analysis of mutation per se as a required endpoint for comprehensive assessments of toxicological risk.
Plain language summary
Health Canada is responsible for evaluating the hazards posed by new and existing chemicals, including assessment of a chemical’s ability to damage genetic material. Of particular importance is the ability of chemicals to induce mutations (ie, changes in the DNA sequence), which are associated with diseases such as cancer. Consequently, the ability to induce mutations has traditionally been used by regulatory agencies to identify substances that have the potential to cause cancer. However, a more recent approach recognizes mutation in and of itself as an adverse effect. Health Canada has been leading an international effort to endorse the contention that mutation itself is an adverse outcome that can be used to regulate new and existing substances. In this commentary, scientists from several international agencies, universities and private-sector organizations argue that is it time to consider mutation per se as a required endpoint for a comprehensive toxicological assessment and apply appropriate computational approaches to identify dose levels below which the risk to human health is negligible.
Subject
- Health,
- Health and safety