Τίτλος:
A Novel Approach to Chemical Mixture Risk Assessment—Linking Data from Population-Based Epidemiology and Experimental Animal Tests
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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%). © 2019 Society for Risk Analysis
Συγγραφείς:
Bornehag, C.-G.
Kitraki, E.
Stamatakis, A.
Panagiotidou, E.
Rudén, C.
Shu, H.
Lindh, C.
Ruegg, J.
Gennings, C.
Περιοδικό:
Microbial Risk Analysis
Εκδότης:
Blackwell Publishing Inc.
Λέξεις-κλειδιά:
Animals; Chemicals; Endocrine disrupters; Health risks; Mixtures; Population statistics; Risk management; Risk perception, Adverse health effects; Assessment strategies; Chemical exposure; Endocrine disrupting chemicals; Experimental evidence; Sexual development; Statistical measures; Systematic integration, Risk assessment, chemical pollutant; dose-response relationship; endocrine disruptor; epidemiology; health risk; pollution exposure; risk assessment; testing method; womens health, Animalia, endocrine disruptor, animal; drug mixture; environmental exposure; female; human; infant; pollutant; pregnancy; risk assessment; toxicity, Animals; Complex Mixtures; Endocrine Disruptors; Environmental Exposure; Environmental Pollutants; Female; Humans; Infant; Pregnancy; Risk Assessment
