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A Novel Approach to Chemical Mixture Risk Assessment—Linking Data from Population-Based Epidemiology and Experimental Animal Tests
Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences (from 2013). Icahn School of Medicine at Mount Sinai, United States.ORCID iD: 0000-0003-0417-1686
National and Kapodistrian University of Athens, Greece.
National and Kapodistrian University of Athens, Greece.
National and Kapodistrian University of Athens, Greece.
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2019 (English)In: Risk Analysis, ISSN 0272-4332, E-ISSN 1539-6924, Vol. 39, no 10, p. 2259-2271Article in journal (Refereed) Published
Abstract [en]

Humans are continuously exposed to chemicals with suspected or proven endocrine disrupting chemicals (EDCs). Risk management of EDCs presents a major unmet challenge because the available data for adverse health effects are generated by examining one compound at a time, whereas real-life exposures are to mixtures of chemicals. In this work, we integrate epidemiological and experimental evidence toward a whole mixture strategy for risk assessment. To illustrate, we conduct the following four steps in a case study: (1) identification of single EDCs (“bad actors”)—measured in prenatal blood/urine in the SELMA study—that are associated with a shorter anogenital distance (AGD) in baby boys; (2) definition and construction of a “typical” mixture consisting of the “bad actors” identified in Step 1; (3) experimentally testing this mixture in an in vivo animal model to estimate a dose–response relationship and determine a point of departure (i.e., reference dose [RfD]) associated with an adverse health outcome; and (4) use a statistical measure of “sufficient similarity” to compare the experimental RfD (from Step 3) to the exposure measured in the human population and generate a “similar mixture risk indicator” (SMRI). The objective of this exercise is to generate a proof of concept for the systematic integration of epidemiological and experimental evidence with mixture risk assessment strategies. Using a whole mixture approach, we could find a higher rate of pregnant women under risk (13%) when comparing with the data from more traditional models of additivity (3%), or a compound-by-compound strategy (1.6%).

Place, publisher, year, edition, pages
John Wiley & Sons, 2019. Vol. 39, no 10, p. 2259-2271
Keywords [en]
Chemical exposure, mixtures, risk assessment, sexual development, Animals, Chemicals, Endocrine disrupters, Health risks, Population statistics, Risk management, Risk perception, Adverse health effects, Assessment strategies, Endocrine disrupting chemicals, Experimental evidence, Statistical measures, Systematic integration
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Public Health Science
Identifiers
URN: urn:nbn:se:kau:diva-73364DOI: 10.1111/risa.13323ISI: 000489373200010PubMedID: 31173660Scopus ID: 2-s2.0-85067401773OAI: oai:DiVA.org:kau-73364DiVA, id: diva2:1334213
Available from: 2019-07-02 Created: 2019-07-02 Last updated: 2020-04-27Bibliographically approved

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