title: Changes in the Metabolome in Response to Low-Dose Exposure to Environmental Chemicals Used in Personal Care Products during Different Windows of Susceptibility.
abstract: The consequences of ubiquitous exposure to environmental chemicals remain poorly defined. Non-targeted metabolomic profiling is an emerging method to identify biomarkers of the physiological response to such exposures. We investigated the effect of three commonly used ingredients in personal care products, diethyl phthalate (DEP), methylparaben (MPB) and triclosan (TCS), on the blood metabolome of female Sprague-Dawley rats. Animals were treated with low levels of these chemicals comparable to human exposures during prepubertal and pubertal windows as well as chronically from birth to adulthood. Non-targeted metabolomic profiling revealed that most of the variation in the metabolites was associated with developmental stage. The low-dose exposure to DEP, MPB and TCS had a relatively small, but detectable impact on the metabolome. Multiple metabolites that were affected by chemical exposure belonged to the same biochemical pathways including phenol sulfonation and metabolism of pyruvate, lyso-plasmalogens, unsaturated fatty acids and serotonin. Changes in phenol sulfonation and pyruvate metabolism were most pronounced in rats exposed to DEP during the prepubertal period. Our metabolomics analysis demonstrates that human level exposure to personal care product ingredients has detectable effects on the rat metabolome. We highlight specific pathways such as sulfonation that warrant further study.
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.|Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
authors.forename: Sander M
authors.identifier: http://orcid.org/0000-0002-6167-9147
authors.initials: SM
authors.lastname: Houten
authors.affiliation: Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.|Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.|Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.|Department of Medicine, Hematology, and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Cesare Maltoni Cancer Research Centre, Ramazzini Institute, Bentivoglio (Bologna), Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Belpoggi
authors.affiliation: Cesare Maltoni Cancer Research Centre, Ramazzini Institute, Bentivoglio (Bologna), Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Manservisi
authors.affiliation: Steroid Research and Mass Spectrometry Unit, Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, 35392, Giessen, Germany.
authors.forename: Alberto
authors.initials: A
authors.lastname: Sánchez-Guijo
authors.affiliation: Steroid Research and Mass Spectrometry Unit, Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, 35392, Giessen, Germany.
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Wudy
authors.affiliation: Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Teitelbaum
mesh_terms: D000818:Animals; D003358:Cosmetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D055442:Metabolome; D010226:Parabens / Q000008:administration & dosage*; D019800:Phenol / Q000378:metabolism; D010795:Phthalic Acids / Q000008:administration & dosage*; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014260:Triclosan / Q000008:administration & dosage*
chemical_list: D003358:Cosmetics; D010226:Parabens; D010795:Phthalic Acids; D019800:Phenol; D014260:Triclosan; D019289:Pyruvic Acid; C015358:methylparaben; C007379:diethyl phthalate