Abstract
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%).
Highlights
Humans are exposed to suspected or proven endocrine disrupting chemicals (EDCs) that com-prise a variety of chemical classes, with detectable concentrations from biomonitoring data in humans
The current study aims to set the stage for a novel approach to risk assessment of chemical mixtures related to endocrine disruption, using as a paradigm their effects on male sexual development in both young boys and male mice
We have integrated four important parts of environmental health research: (1) epidemiological data from a pregnancy cohort with recorded exposures and health effects in children for identification of “bad actors,” (2) biomonitoring data for construction of a “typical” mixture consisting of these “bad actors,” (3) animal data on describing adverse effects from controlled in vivo experiments for identification of dose–response relationships and PODs, and (4) biostatistical analyses to assess the similarity of mixtures and, for those determined to be sufficiently similar to the reference mixture, to construct an index related to the POD and human exposure
Summary
Humans are exposed to suspected or proven endocrine disrupting chemicals (EDCs) that com-prise a variety of chemical classes (e.g., phthalates, alkyl phenols, perfluorinated alkylated substances [PFASs]), with detectable concentrations from biomonitoring data in humans. Epidemiology studies (generally observational studies evaluating single chemicals one at a time) demonstrate association of EDC concentrations with multiple adverse health outcomes. Experimental studies, typically in vivo animal studies, are used to establish a causative link between exposures to environmental chemicals and adverse effects. Humans may be more or less sensitive to chemical exposures compared to animals, and experimental studies cannot reasonably represent all possible exposure patterns for humans. It is the integration of observational human and experimental animal studies that may improve the scientific understanding of the implicated health effects as well as risk assessment of environmental chemicals
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
