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In this study, laboratory-reared amphibians were exposed to multiple pesticides, analogous to field exposures, resulting in an impact to both pesticide body concentrations and the amphibians\u2019 hepatic metabolome. These data can be used in the environmental and ecological risk assessment of multiple pesticides in non-target species.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Pesticide mixtures are frequently co-applied throughout an agricultural growing season to maximise crop yield. Therefore, non-target ecological species (e.g. amphibians) may be exposed to several pesticides at any given time on these agricultural landscapes. The objectives of this study were to quantify body burdens in terrestrial phase amphibians and translate perturbed metabolites to their corresponding biochemical pathways affected by exposure to pesticides as both singlets and in combination. Southern leopard frogs (Lithobates sphenocephala) were exposed either at the maximum or 1\/10th maximum application rate to single, double or triple pesticide mixtures of bifenthrin (insecticide), metolachlor (herbicide) and triadimefon (fungicide). Tissue concentrations demonstrated both facilitated and competitive uptake of pesticides when in mixtures. Metabolomic profiling of amphibian livers identified metabolites of interest for both application rates; however, the magnitude of changes varied for the two exposure rates. Exposure to lower concentrations demonstrated downregulation in amino acids, potentially owing to their usage for glutathione metabolism and\/or increased energy demands. Amphibians exposed to the maximum application rate resulted in upregulation of amino acids and other key metabolites likely owing to depleted energy resources. Coupling endogenous and exogenous biomarkers of pesticide exposure can be used to form vital links in an ecological risk assessment by relating internal dose to pathophysiological outcomes in non-target species.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1071\/en18163","type":"journal-article","created":{"date-parts":[[2018,11,27]],"date-time":"2018-11-27T17:05:31Z","timestamp":1543338331000},"page":"55-67","source":"Crossref","is-referenced-by-count":24,"title":["Endogenous and exogenous biomarker analysis in terrestrial phase amphibians (Lithobates sphenocephala) following dermal exposure to pesticide mixtures"],"prefix":"10.1071","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7934-5666","authenticated-orcid":true,"given":"Donna A.","family":"Glinski","sequence":"first","affiliation":[{"name":"AGrantee to U.S. Environmental Protection Agency via Oak Ridge Institute of Science and Education, Athens, GA 30605, USA."},{"name":"BDepartment of Environmental Health Science, Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602, USA."},{"name":"CPresent address: School of Chemical Sciences, Dublin City University, Dublin D09 W6Y4, Ireland."},{"name":"FCorresponding author. Email: donna.glinski@dcu.ie"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Thomas","family":"Purucker","sequence":"additional","affiliation":[{"name":"DU.S. Environmental Protection Agency, Office of Research and Development, National Exposure Research Laboratory, Athens, GA 30605, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin J.","family":"Van Meter","sequence":"additional","affiliation":[{"name":"EDepartments of Biology and Environmental Science\/Studies, Washington College, Chestertown, MD 21620, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marsha C.","family":"Black","sequence":"additional","affiliation":[{"name":"BDepartment of Environmental Health Science, Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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