The MCRA toolbox of models and data to support chemical mixture risk assessment

Hilko van Der Voet (1) , Johannes W. Kruisselbrink (1) , Waldo J. de Boer (1) , Marco S. van Lenthe (1) , J.J.B. van den Heuvel (1) , Amélie Crepet (2) , Marc C. Kennedy (3) , Johanna Zilliacus (4) , Anna Beronius (4) , Cléo Tebby (5) , Céline Brochot (5) , Claudia Luckert (6) , Alfonso Lampen (6) , Emiel Rorije (7) , Corinne Sprong (7) , Jakob D. van Klaveren (7)

1 WUR - Wageningen University and Research [Wageningen]
2 DER - Direction de l'Evaluation des Risques
3 Food and Environment Research Agency
4 Karolinska Institute
5 INERIS - Institut National de l'Environnement Industriel et des Risques
6 BfR - Bundesinstitut für Risikobewertung - Federal Institute for Risk Assessment
7 RIVM - National Institute for Public Health and the Environment [Bilthoven]

A model and data toolbox is presented to assess risks from combined exposure to multiple chemicals using probabilistic methods. The Monte Carlo Risk Assessment (MCRA) toolbox, also known as the EuroMix toolbox, has more than 40 modules addressing all areas of risk assessment, and includes a data repository with data collected in the EuroMix project. This paper gives an introduction to the toolbox and illustrates its use with examples from the EuroMix project. The toolbox can be used for hazard identification, hazard characterisation, exposure assessment and risk characterisation. Examples for hazard identification are selection of substances relevant for a specific adverse outcome based on adverse outcome pathways and QSAR models. Examples for hazard characterisation are calculation of benchmark doses and relative potency factors with uncertainty from dose response data, and use of kinetic models to perform in vitro to in vivo extrapolation. Examples for exposure assessment are assessing cumulative exposure at external or internal level, where the latter option is needed when dietary and non-dietary routes have to be aggregated. Finally, risk characterisation is illustrated by calculation and display of the margin of exposure for single substances and for the cumulation, including uncertainties derived from exposure and hazard characterisation estimates.

Keywords: Risk assessment; Exposure; Hazard; Mixtures; Probabilistic model; Software

Domains: Toxicology

Hilko van Der Voet, Johannes W. Kruisselbrink, Waldo J. de Boer, Marco S. van Lenthe, J.J.B. van den Heuvel, et al.. The MCRA toolbox of models and data to support chemical mixture risk assessment. Food and Chemical Toxicology, 2020, 138, pp.111185. ⟨10.1016/j.fct.2020.111185⟩. ⟨ineris-03318304⟩