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A Novel Approach to Chemical Mixture Risk Assessment—Linking Data from Population-Based Epidemiology and Experimental Animal Tests
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Number of Authors: 92019 (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
2019. Vol. 39, no 10, p. 2259-2271
Keywords [en]
Chemical exposure, mixtures, risk assessment, sexual development
National Category
Earth and Related Environmental Sciences Public Health, Global Health and Social Medicine
Identifiers
URN: urn:nbn:se:su:diva-175856DOI: 10.1111/risa.13323ISI: 000489373200010PubMedID: 31173660OAI: oai:DiVA.org:su-175856DiVA, id: diva2:1369328
Available from: 2019-11-11 Created: 2019-11-11 Last updated: 2025-02-20Bibliographically approved

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Stamatakis, AntoniosRudén, ChristinaShu, HuanLindh, ChristianGennings, Chris

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Stamatakis, AntoniosRudén, ChristinaShu, HuanLindh, ChristianGennings, Chris
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