Critical review and analysis of literature on low dose exposure to chemical mixtures in mammalian in vivo systems

Elcombe, C. S., Evans, N. P. and Bellingham, M. (2022) Critical review and analysis of literature on low dose exposure to chemical mixtures in mammalian in vivo systems. Critical Reviews in Toxicology, 52(3), pp. 221-238. (doi: 10.1080/10408444.2022.2091423) (PMID:35894754)

Abstract

Anthropogenic chemicals are ubiquitous throughout the environment. Consequentially, humans are exposed to hundreds of anthropogenic chemicals daily. Current chemical risk assessments are primarily based on testing individual chemicals in rodents at doses that are orders of magnitude higher than that of human exposure. The potential risk from exposure to mixtures of chemicals is calculated using mathematical models of mixture toxicity based on these analyses. These calculations, however, do not account for synergistic or antagonistic interactions between co-exposed chemicals. While proven examples of chemical synergy in mixtures at low doses are rare, there is increasing evidence that, through non-conformance to current mixture toxicity models, suggests synergy. This review examined the published studies that have investigated exposure to mixtures of chemicals at low doses in mammalian in vivo systems. Only seven identified studies were sufficient in design to directly examine the appropriateness of current mixture toxicity models, of which three showed responses significantly greater than additivity model predictions. While the remaining identified studies were unable to provide evidence of synergistic toxicity, it became apparent that many results of such studies were not always explicable by current mixture toxicity models. Additionally, two data gaps were identified. Firstly, there is a lack of studies where individual chemical components of a complex mixture (>10 components) are tested in parallel to the chemical mixture. Secondly, there is a lack of dose-response data for mixtures of chemicals at low doses. Such data is essential to address the appropriateness and validity of future chemical mixture toxicity models.

• Item Type: Articles
• Additional Information: This research received funding from the National Institute of Environmental Health Sciences (grant number R01 ES030374).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bellingham, Dr Michelle and Elcombe, Mr Chris and Evans, Professor Neil

Creator Roles

Elcombe, C.: Conceptualization, Data curation, Investigation, Methodology, Writing – original draft, Writing – review and editing
Evans, N.: Conceptualization, Writing – review and editing
Bellingham, M.: Conceptualization, Writing – review and editing

• Authors: Elcombe, C. S., Evans, N. P., and Bellingham, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Critical Reviews in Toxicology
• Publisher: Taylor and Francis
• ISSN: 1040-8444
• ISSN (Online): 1547-6898
• Published Online: 27 July 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Critical Reviews in Toxicology 52(3): 221-238
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
302571		Transgenerational consequences of pre-conceptional and in utero exposure to real-life chemical mixtures on fertility and metabolic health	Neil Evans	National Institutes of Health (NIH)	1 R01 ES030374-01A1	Institute of Biodiversity, Animal Health and Comparative Medicine