title: Regulatory assessment of chemical mixtures: Requirements, current approaches and future perspectives.
abstract: This paper reviews regulatory requirements and recent case studies to illustrate how the risk assessment (RA) of chemical mixtures is conducted, considering both the effects on human health and on the environment. A broad range of chemicals, regulations and RA methodologies are covered, in order to identify mixtures of concern, gaps in the regulatory framework, data needs, and further work to be carried out. Also the current and potential future use of novel tools (Adverse Outcome Pathways, in silico tools, toxicokinetic modelling, etc.) in the RA of combined effects were reviewed. The assumptions made in the RA, predictive model specifications and the choice of toxic reference values can greatly influence the assessment outcome, and should therefore be specifically justified. Novel tools could support mixture RA mainly by providing a better understanding of the underlying mechanisms of combined effects. Nevertheless, their use is currently limited because of a lack of guidance, data, and expertise. More guidance is needed to facilitate their application. As far as the authors are aware, no prospective RA concerning chemicals related to various regulatory sectors has been performed to date, even though numerous chemicals are registered under several regulatory frameworks.
authors.affiliation: European Commission, Joint Research Centre, Institute for Health and Consumer Protection, Systems Toxicology Unit and EURL ECVAM, Via Enrico Fermi 2749, 21027, Ispra, VA, Italy.
authors.forename: Aude
authors.initials: A
authors.lastname: Kienzler
authors.affiliation: European Commission, Joint Research Centre, Institute for Health and Consumer Protection, Systems Toxicology Unit and EURL ECVAM, Via Enrico Fermi 2749, 21027, Ispra, VA, Italy. Electronic address: Stephanie.BOPP@ec.europa.eu.
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Bopp
authors.affiliation: European Commission, Joint Research Centre, Institute for Health and Consumer Protection, Systems Toxicology Unit and EURL ECVAM, Via Enrico Fermi 2749, 21027, Ispra, VA, Italy.
authors.forename: Sander
authors.initials: S
authors.lastname: van der Linden
authors.affiliation: European Commission, Joint Research Centre, Institute for Health and Consumer Protection, Systems Toxicology Unit and EURL ECVAM, Via Enrico Fermi 2749, 21027, Ispra, VA, Italy.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Berggren
authors.affiliation: European Commission, Joint Research Centre, Institute for Health and Consumer Protection, Systems Toxicology Unit and EURL ECVAM, Via Enrico Fermi 2749, 21027, Ispra, VA, Italy.
authors.forename: Andrew
authors.initials: A
authors.lastname: Worth
mesh_terms: D000818:Animals; D045424:Complex Mixtures / Q000009:adverse effects*; D003257:Consumer Product Safety / Q000331:legislation & jurisprudence; D003358:Cosmetics / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D058735:Environmental Policy / Q000331:legislation & jurisprudence / Q000639:trends; D033161:Government Regulation; D015386:Hazardous Substances / Q000009:adverse effects*; D006291:Health Policy / Q000331:legislation & jurisprudence / Q000639:trends; D006801:Humans; D011050:Policy Making; D011640:Public Policy / Q000331:legislation & jurisprudence* / Q000639:trends*; D018570:Risk Assessment; D018675:Toxicity Tests; D014874:Water Pollutants, Chemical / Q000009:adverse effects*
chemical_list: D045424:Complex Mixtures; D003358:Cosmetics; D015386:Hazardous Substances; D014874:Water Pollutants, Chemical
keywords: Combined effect; Mixture; Regulation; Risk assessment