title: Assessment of serum biomarkers in rats after exposure to pesticides of different chemical classes.
abstract: There is increasing emphasis on the use of biomarkers of adverse outcomes in safety assessment and translational research. We evaluated serum biomarkers and targeted metabolite profiles after exposure to pesticides (permethrin, deltamethrin, imidacloprid, carbaryl, triadimefon, fipronil) with different neurotoxic actions. Adult male Long-Evans rats were evaluated after single exposure to vehicle or one of two doses of each pesticide at the time of peak effect. The doses were selected to produce similar magnitude of behavioral effects across chemicals. Serum or plasma was analyzed using commercial cytokine/protein panels and targeted metabolomics. Additional studies of fipronil used lower doses (lacking behavioral effects), singly or for 14 days, and included additional markers of exposure and biological activity. Biomarker profiles varied in the number of altered analytes and patterns of change across pesticide classes, and discriminant analysis could separate treatment groups from control. Low doses of fipronil produced greater effects when given for 14 days compared to a single dose. Changes in thyroid hormones and relative amounts of fipronil and its sulfone metabolite also differed between the dosing regimens. Most cytokine changes reflected alterations in inflammatory responses, hormone levels, and products of phospholipid, fatty acid, and amino acid metabolism. These findings demonstrate distinct blood-based analyte profiles across pesticide classes, dose levels, and exposure duration. These results show promise for detailed analyses of these biomarkers and their linkages to biological pathways.
authors.affiliation: Neurotoxicology Branch/Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA. Electronic address: Moser.ginger@epa.gov.
authors.forename: Virginia C
authors.initials: VC
authors.lastname: Moser
authors.affiliation: Neurotoxicology Branch/Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Stewart
authors.affiliation: Neurotoxicology Branch/Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Freeborn
authors.affiliation: Analytical Chemistry Research Core/Research Cores Unit, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
authors.forename: James
authors.initials: J
authors.lastname: Crooks
authors.affiliation: Analytical Chemistry Research Core/Research Cores Unit, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
authors.forename: Denise K
authors.initials: DK
authors.lastname: MacMillan
authors.affiliation: Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
authors.forename: Joan M
authors.initials: JM
authors.lastname: Hedge
authors.affiliation: Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Wood
authors.affiliation: ORISE fellow, Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: McMahen
authors.affiliation: Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Strynar
authors.affiliation: Neurotoxicology Branch/Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Herr
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D018925:Chemokines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006728:Hormones / Q000097:blood; D007306:Insecticides / Q000633:toxicity; D008297:Male; D055432:Metabolomics; D010575:Pesticides / Q000737:chemistry* / Q000633:toxicity*; D011720:Pyrazoles / Q000633:toxicity; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D015415:Biomarkers; D018925:Chemokines; D006728:Hormones; D007306:Insecticides; D010575:Pesticides; D011720:Pyrazoles; C082360:fipronil
keywords: Biomarkers; Cytokines; Hormones; Metabolomics; Pesticides