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A Novel Approach to Chemical Mixture Risk Assessment-Linking Data from Population-Based Epidemiology and Experimental Animal Tests.

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%).

SUBMITTER: Bornehag CG

PROVIDER: S-EPMC6973107 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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A Novel Approach to Chemical Mixture Risk Assessment-Linking Data from Population-Based Epidemiology and Experimental Animal Tests.

Bornehag Carl-Gustaf CG Kitraki Efthymia E Stamatakis Antonios A Panagiotidou Emily E Rudén Christina C Shu Huan H Lindh Christian C Ruegg Joelle J Gennings Chris C

Risk analysis : an official publication of the Society for Risk Analysis 20190607 10

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 step ...[more]

PMID: 31173660

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Project description:Toxicology is traditionally divided between human and eco-toxicology. In the shared pursuit of environmental health, this separation does not account for discoveries made in the comparative studies of animal genomes. Here, we provide evidence on the feasibility of understanding the health impact of chemicals on all animals, including ecological keystone species and humans, based on a significant number of conserved genes and their functional associations to health-related outcomes across much of animal diversity. We test four conditions to understand the value of comparative genomics data to inform mechanism-based human and environmental hazard assessment: (1) genes that are most fundamental for health evolved early during animal evolution; (2) the molecular functions of pathways are better conserved among distantly related species than the individual genes that are members of these pathways; (3) the most conserved pathways among animals are those that cause adverse health outcomes when disrupted; (4) gene sets that serve as molecular signatures of biological processes or disease-states are largely enriched by evolutionarily conserved genes across the animal phylogeny. The concept of homology is applied in a comparative analysis of gene families and pathways among invertebrate and vertebrate species compared with humans. Results show that over 70% of gene families associated with disease are shared among the greatest variety of animal species through evolution. Pathway conservation between invertebrates and humans is based on the degree of conservation within vertebrates and the number of interacting genes within the human network. Human gene sets that already serve as biomarkers are enriched by evolutionarily conserved genes across the animal phylogeny. By implementing a comparative method for chemical hazard assessment, human and eco-toxicology converge towards a more holistic and mechanistic understanding of toxicity disrupting biological processes that are important for health and shared among animals (including humans).

Dataset Information

A Novel Approach to Chemical Mixture Risk Assessment-Linking Data from Population-Based Epidemiology and Experimental Animal Tests.

Publications

A Novel Approach to Chemical Mixture Risk Assessment-Linking Data from Population-Based Epidemiology and Experimental Animal Tests.

Similar Datasets

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