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Research article2018Peer reviewedOpen access

Dose-Related Severity Sequence, and Risk-Based Integration, of Chemically Induced Health Effects

Sand, Salomon; Lindqvist, Roland; von Rosen, Dietrich; Ilback, Nils-Gunnar

Abstract

Risk assessment of chemical hazards is typically based on single critical health effects. This work aims to expand the current approach by characterizing the dose-related sequence of the development of multiple (lower- to higher-order) toxicological health effects caused by a chemical. To this end a "reference point profile" is defined as the relation between benchmark doses for considered health effects, and a standardized severity score determined for these effects. For a given dose of a chemical or mixture the probability for exceeding the reference point profile, thereby provoking lower- to higher-order effects, can be assessed. The overall impact at the same dose can also be derived by integrating contributions across all health effects following severity-weighting. In its generalized form the new impact metric relates to the probability of response for the most severe health effects. Reference points (points of departure) corresponding to defined levels of response can also be estimated. The proposed concept, which is evaluated for dioxin-like chemicals, provides an alternative for characterizing the low-dose region below the reference point for a severe effect like cancer. The shape and variability of the reference point profile add new dimensions to risk assessment, which for example extends the characterization of chemical potency, and the concept of acceptable effect sizes for individual health effects. Based on the present data the method shows high stability at low doses/responses, and is also robust to differences in severity categorization of effects. In conclusion, the novel method proposed enables risk-based integration of multiple dose-related health effects. It provides a first step towards a more comprehensive characterization of chemical toxicity, and suggests a potential for improved low-dose risk assessment.

Keywords

risk assessment; BMD; severity; risk-based; integrated; multiple effects

Published in

Toxicological Sciences
2018, Volume: 165, number: 1, pages: 74-89 Publisher: OXFORD UNIV PRESS

      Sustainable Development Goals

      SDG3 Good health and well-being

      UKÄ Subject classification

      Pharmacology and Toxicology

      Publication identifier

      DOI: https://doi.org/10.1093/toxsci/kfy124

      Permanent link to this page (URI)

      https://res.slu.se/id/publ/96839