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      Understanding the Chemical Exposome During Fetal Development and Early Childhood: A Review

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          Abstract

          Early human life is considered a critical window of susceptibility to external exposures. Infants are exposed to a multitude of environmental factors, collectively referred to as the exposome. The chemical exposome can be summarized as the sum of all xenobiotics that humans are exposed to throughout a lifetime. We review different exposure classes and routes that impact fetal and infant metabolism and the potential toxicological role of mixture effects. We also discuss the progress in human biomonitoring and present possiblemodels for studying maternal–fetal transfer. Data gaps on prenatal and infant exposure to xenobiotic mixtures are identified and include natural biotoxins, in addition to commonly reported synthetic toxicants, to obtain a more holistic assessment of the chemical exposome. We highlight the lack of large-scale studies covering a broad range of xenobiotics. Several recommendations to advance our understanding of the early-life chemical exposome and the subsequent impact on health outcomes are proposed.

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          Most cited references151

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          Complementing the genome with an "exposome": the outstanding challenge of environmental exposure measurement in molecular epidemiology.

          C Wild (2005)
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            Evolution of the immune system in humans from infancy to old age

            This article reviews the development of the immune response through neonatal, infant and adult life, including pregnancy, ending with the decline in old age. A picture emerges of a child born with an immature, innate and adaptive immune system, which matures and acquires memory as he or she grows. It then goes into decline in old age. These changes are considered alongside the risks of different types of infection, autoimmune disease and malignancy.
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              Per‐ and Polyfluoroalkyl Substance Toxicity and Human Health Review: Current State of Knowledge and Strategies for Informing Future Research

              Reports of environmental and human health impacts of per- and polyfluoroalkyl substances (PFAS) have greatly increased in the peer-reviewed literature. The goals of the present review are to assess the state of the science regarding toxicological effects of PFAS and to develop strategies for advancing knowledge on the health effects of this large family of chemicals. Currently, much of the toxicity data available for PFAS are for a handful of chemicals, primarily legacy PFAS such as perfluorooctanoic acid and perfluorooctane sulfonate. Epidemiological studies have revealed associations between exposure to specific PFAS and a variety of health effects, including altered immune and thyroid function, liver disease, lipid and insulin dysregulation, kidney disease, adverse reproductive and developmental outcomes, and cancer. Concordance with experimental animal data exists for many of these effects. However, information on modes of action and adverse outcome pathways must be expanded, and profound differences in PFAS toxicokinetic properties must be considered in understanding differences in responses between the sexes and among species and life stages. With many health effects noted for a relatively few example compounds and hundreds of other PFAS in commerce lacking toxicity data, more contemporary and high-throughput approaches such as read-across, molecular dynamics, and protein modeling are proposed to accelerate the development of toxicity information on emerging and legacy PFAS, individually and as mixtures. In addition, an appropriate degree of precaution, given what is already known from the PFAS examples noted, may be needed to protect human health.
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                Author and article information

                Journal
                Annual Review of Pharmacology and Toxicology
                Annu. Rev. Pharmacol. Toxicol.
                Annual Reviews
                0362-1642
                1545-4304
                January 20 2023
                January 20 2023
                : 63
                : 1
                : 517-540
                Affiliations
                [1 ]Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Vienna, Austria;, ,
                [2 ]Swiss Federal Laboratories for Materials Science and Technology, Laboratory for Particles Biology Interactions, St. Gallen, Switzerland;
                [3 ]Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria;
                [4 ]Exposome Austria, Research Infrastructure and National EIRENE Hub, Austria
                [5 ]Center for Public Health, Department of Epidemiology, Medical University of Vienna, Vienna, Austria;
                [6 ]Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA
                [7 ]Division of Neonatology, Pediatric Intensive Care and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria;
                Article
                10.1146/annurev-pharmtox-051922-113350
                36202091
                5777c43d-e0a4-48ac-8f69-ffc9c55ea7e2
                © 2023

                http://creativecommons.org/licenses/by/4.0/

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