Methodology for health risk assessment of combined exposures to multiple chemicals

Beronius, Anna; Zilliacus, Johanna; Hanberg, Annika; Luijten, Mirjam; Voet, Hilko van der; Klaveren, Jacob van

doi:10.1016/j.fct.2020.111520

Cited by 42 publications

(28 citation statements)

References 12 publications

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“…Due to the complexity and multiplicity of mixtures, as well as the various possible routes of exposure, the associated risk is difficult to characterize. Over the past decade, considerable efforts have been made to propose concepts, methods, guidance, and applications for the risk assessment of mixtures ( Beronius et al. 2020 ; Boobis et al.…”

Section: Introductionmentioning

confidence: 99%

Integrating Selection and Risk Assessment of Chemical Mixtures: A Novel Approach Applied to a Breast Milk Survey

Crépet

Vasseur

Jean

et al. 2022

Environ Health Perspect

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Background: One of the main challenges of modern risk assessment is to account for combined exposure to the multitude of various substances present in food and the environment. Objective: The present work proposes a methodological approach to perform chemical risk assessment of contaminant mixtures across regulatory silos regarding an extensive range of substances and to do so when comprehensive relevant data concerning the specific effects and modes of action of the mixture components are not available. Methods: We developed a complete step-by-step approach using statistical methods to prioritize substances involved in combined exposure, and we used a component-based approach to cumulate the risk using dose additivity. The most relevant toxicological end point and the associated reference point were selected from the literature to construct a toxicological threshold for each substance. Discussion: By applying the proposed method to contaminants in breast milk, we observed that among the 19 substances comprising the selected mixture, , , and arsenic were main joint contributors to the risk of neurodevelopmental and thyroid effects for infants. In addition, contributed to the thyroid effect and to the neurodevelopmental effect. Our case study on contaminants in breast milk demonstrated the importance of crossing regulatory silos when studying mixtures and the importance of identifying risk drivers to regulate the risk related to environmental contamination. Applying this method to another set of data, such as human biomonitoring or in ecotoxicology, will reinforce its relevance for risk assessment. https://doi.org/10.1289/EHP8262

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Section: Introductionmentioning

confidence: 99%

Integrating Selection and Risk Assessment of Chemical Mixtures: A Novel Approach Applied to a Breast Milk Survey

Crépet

Vasseur

Jean

et al. 2022

Environ Health Perspect

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“…The project strongly relied on adverse outcome pathways (AOP) and thus in turn substance interactions such as for example the ability of a test compound to interact with certain molecular targets and exert toxicological effects. As a consequence mixture selection in “EuroMix” was essentially based on the toxicodynamic properties of the individual test chemicals (Alarcan et al 2021 ; Beronius et al 2020 ). This is also further substantiated in the recent European Food Safety Authority (EFSA) Mixtox Guidance (EFSA 2021 ).…”

Section: Introductionmentioning

confidence: 99%

An approach for mixture testing and prioritization based on common kinetic groups

et al. 2022

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In light of an ever-increasing exposure to chemicals, the topic of potential mixture toxicity has gained increased attention, particularly as the toxicological toolbox to address such questions has vastly improved. Routinely toxicological risk assessments will rely on the analysis of individual compounds with mixture effects being considered only in those specific cases where co-exposure is foreseeable, for example for pesticides or food contact materials. In the field of pesticides, active substances are summarized in so-called cumulative assessment groups (CAG) which are primarily based on their toxicodynamic properties, that is, respective target organs and mode of action (MoA). In this context, compounds causing toxicity by a similar MoA are assumed to follow a model of dose/concentration addition (DACA). However, the respective approach inherently falls short of addressing cases where there are dissimilar or independent MoAs resulting in wider toxicokinetic effects. Yet, the latter are often the underlying cause when effects deviate from the DACA model. In the present manuscript, we therefore suggest additionally to consider toxicokinetic effects (especially related to xenobiotic metabolism and transporter interaction) for the grouping of substances to predict mixture toxicity. In line with the concept of MoA-based CAGs, we propose common kinetics groups (CKGs) as an additional tool for grouping of chemicals and mixture prioritization. Fundamentals of the CKG concept are discussed, along with challenges for its implementation, and methodological approaches and examples are explored.

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“…form the basis of the CAGs, are frequently used as a basis for the selection of chemicals for mixture testing. One example is the EU-funded project EuroMix: within that project, methodologies and tools for mixture risk assessment have been developed anchored in the adverse outcome pathway (AOP) concept and mixture selection mainly based on the toxicodynamic profiles of the test chemicals (Alarcan et al 2021 ; Beronius et al 2020 ).…”

mentioning

confidence: 99%

Mixture prioritization and testing: the importance of toxicokinetics

Braeuning

Marx‐Stoelting

2021

Arch Toxicol

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Methodology for health risk assessment of combined exposures to multiple chemicals

Cited by 42 publications

References 12 publications

Integrating Selection and Risk Assessment of Chemical Mixtures: A Novel Approach Applied to a Breast Milk Survey

Integrating Selection and Risk Assessment of Chemical Mixtures: A Novel Approach Applied to a Breast Milk Survey

An approach for mixture testing and prioritization based on common kinetic groups

Mixture prioritization and testing: the importance of toxicokinetics

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