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A Novel Approach to Chemical Mixture Risk Assessment—Linking Data from Population‐Based Epidemiology and Experimental Animal Tests
Author(s) -
Bornehag CarlGustaf,
Kitraki Efthymia,
Stamatakis Antonios,
Panagiotidou Emily,
Rudén Christina,
Shu Huan,
Lindh Christian,
Ruegg Joelle,
Gennings Chris
Publication year - 2019
Publication title -
risk analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.972
H-Index - 130
eISSN - 1539-6924
pISSN - 0272-4332
DOI - 10.1111/risa.13323
Subject(s) - epidemiology , risk assessment , population , exposure assessment , identification (biology) , adverse effect , medicine , environmental health , statistics , computer science , risk analysis (engineering) , econometrics , biology , mathematics , pharmacology , botany , computer security
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%).