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Scientific methodologies for the assessment of combined effects of chemicals - a survey and literature review

Abstract

Exposure of humans and wildlife to chemicals via food, consumer products, the environment etc. can imply exposure to an infinite number of different combinations of chemicals in mixtures. It is practically impossible to test all these possible mixtures experimentally and it is therefore needed to find smart strategies to assess the potential hazards using new tools that rely less on in vivo testing and incorporate instead alternative experimental and computational tools. In this report the current state of the art for the application of these alternative tools for assessing the hazard of chemical mixtures is briefly reviewed. The focus is hereby on the adverse outcome pathway (AOP) concept, in vitro methods, omics techniques, in silico approaches such as quantitative structure activity relationships (QSARs) and read-across, toxicokinetic and dynamic energy budget (DEB) modelling, and on integrated approaches to testing and assessment (IATA). Furthermore, an expert survey was performed to collect up to date information and experience on the current use of different approaches for assessing human and environmental health risks from exposure to chemical mixtures, with a view to informing the development of a consistent assessment approach. An online survey was performed among experts in the field of combined exposure assessment in the period of January to March 2014, addressing both, human health and environmental risk assessment. Fifty-eight experts from 21 countries, different stakeholder groups and sectors of legislation participated in the survey. The main sectors where most experience is already gained in assessing mixtures are in the area of plant protection products and chemicals. These were also rated highest regarding the priority for performing mixture assessments. Experts have experience with the whole mixture as well as the component-based approaches applying them to both, intentional and unintentional mixtures. Mostly concentration addition (CA) based methods are used for predicting mixture effects. Regarding the use of novel and alternative tools in the risk assessment of mixtures, expert opinions are split between those applying them (often more in a research context) and those that generally think these tools are valuable but their use is currently limited because of lack of guidance, lack of data, or lack of expertise. A general need for clear guidance for combined exposure assessments was identified. Overall, a high potential in applying novel tools and scientific methodologies for the assessment of chemical mixtures can be identified. They allow deriving meaningful information on individual mixture components or whole mixtures, enabling a better understanding of the underlying mechanisms of mixture effects. Their main strengths lie in their integrated use and smart combination to put different aspects regarding the hazard from combined exposure to multiple chemicals into context. In order to benefit from these tools in the hazard assessment of mixtures, more guidance on their use is needed to facilitate a more widespread application.JRC.I.5-Systems Toxicolog

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