Basic concepts of mixture toxicity and relevance for risk evaluation and regulation.

Humans Drug-Related Side Effects and Adverse Reactions Food Polychlorinated Dibenzodioxins Public Health Risk Assessment

Journal

Archives of toxicology

ISSN: 1432-0738

Titre abrégé: Arch Toxicol

Pays: Germany

ID NLM: 0417615

Informations de publication

Date de publication:
11 2023

Historique:

received: 19 07 2023

accepted: 26 07 2023

medline: 18 9 2023

pubmed: 24 8 2023

entrez: 24 8 2023

Statut: ppublish

Résumé

Exposure to multiple substances is a challenge for risk evaluation. Currently, there is an ongoing debate if generic "mixture assessment/allocation factors" (MAF) should be introduced to increase public health protection. Here, we explore concepts of mixture toxicity and the potential influence of mixture regulation concepts for human health protection. Based on this analysis, we provide recommendations for research and risk assessment. One of the concepts of mixture toxicity is additivity. Substances may act additively by affecting the same molecular mechanism within a common target cell, for example, dioxin-like substances. In a second concept, an "enhancer substance" may act by increasing the target site concentration and aggravating the adverse effect of a "driver substance". For both concepts, adequate risk management of individual substances can reliably prevent adverse effects to humans. Furthermore, we discuss the hypothesis that the large number of substances to which humans are exposed at very low and individually safe doses may interact to cause adverse effects. This commentary identifies knowledge gaps, such as the lack of a comprehensive overview of substances regulated under different silos, including food, environmentally and occupationally relevant substances, the absence of reliable human exposure data and the missing accessibility of ratios of current human exposure to threshold values, which are considered safe for individual substances. Moreover, a comprehensive overview of the molecular mechanisms and most susceptible target cells is required. We conclude that, currently, there is no scientific evidence supporting the need for a generic MAF. Rather, we recommend taking more specific measures, which focus on compounds with relatively small ratios between human exposure and doses, at which adverse effects can be expected.

Identifiants

DOI: 10.1007/s00204-023-03565-6 PMID: 37615677 PMC: PMC10504116

pubmed: 37615677

doi: 10.1007/s00204-023-03565-6

pii: 10.1007/s00204-023-03565-6

pmc: PMC10504116

doi:

Substances chimiques

Polychlorinated Dibenzodioxins 0

Types de publication

Review Editorial

Langues

eng

Sous-ensembles de citation

Pagination

3005-3017

Informations de copyright

Références

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