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Can sustained exposure to PFAS trigger a genotoxic response? A comprehensive genotoxicity assessment in mice after subacute oral administration of PFOA and PFBA

TitoloCan sustained exposure to PFAS trigger a genotoxic response? A comprehensive genotoxicity assessment in mice after subacute oral administration of PFOA and PFBA
Tipo di pubblicazioneArticolo su Rivista peer-reviewed
Anno di Pubblicazione2019
AutoriCrebelli, R., Caiola S., Conti L., Cordelli Eugenia, De Luca G., Dellatte E., Eleuteri Patrizia, Iacovella N., Leopardi P., Marcon F., Sanchez M., Sestili P., Siniscalchi E., and Villani P.
RivistaRegulatory Toxicology and Pharmacology
Volume106
Paginazione169-177
Parole chiaveanimal cell, animal experiment, animal tissue, antioxidant assay, article, bioaccumulation, butyric acid derivative, controlled study, Cytotoxicity, DNA strand breakage, drinking water, genotoxicity, germ cell, Liver, liver hypertrophy, lymphocyte, male, micronucleus, mouse, nonhuman, Oxidative stress, perfluorobutyric acid, perfluorooctanoic acid, priority journal, reticulocyte, Spleen, unclassified drug
Abstract

PFAS (perfluoroalkyl substances)are considered non-genotoxic. However, PFAS exposure has been associated with the induction of oxidative stress in vitro and in vivo, and the possible induction of indirect genotoxic effects under sustained PFAS exposure has not been investigated. In order to shed light on this aspect, in this study a comprehensive assessment of genotoxicity was carried out in mice administered with perfluorooctanoic acid (PFOA, 0.1, 1 and 5 mg/kg body weight)and its C4 analogue perfluorobutyric acid (PFBA, 5 mg/kg body weight)for five weeks through drinking water. Markers of cell toxicity, oxidative stress and DNA strand breaks were measured in liver, the main target of toxicity of PFOA in rodents; systemic genotoxicity was also assessed by the analysis of micronuclei in reticulocytes and spleen lymphocytes, and germ cell effects by the Comet assay on testis cells. PFOA administration at the highest dose (5 mg/kg body weight)induced marked liver hypertrophy with signs of cell injury (elevated ALT and AST), with no concurrent evidence of lipid peroxidation and oxidative stress (decreased antioxidant capacity). Only mild liver hypertrophy, with no other signs of toxicity, was determined by PFBA administration. No evidence of treatment related genotoxicity was observed in any experimental group. Overall, data indicate that under the experimental conditions of this study, severe liver toxicity induced by PFOA administration is not associated with oxidative stress. Accordingly, no genotoxic effect is observed in liver and in the other tissues examined. Milder evidence of liver toxicity, with no genotoxicity, and a lower tendency to bioaccumulation were observed in PFBA treated mice. © 2019 Elsevier Inc.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85065442299&doi=10.1016%2fj.yrtph.2019.05.005&partnerID=40&md5=36eca84dae348b1df542b1d393b1840b
DOI10.1016/j.yrtph.2019.05.005
Citation KeyCrebelli2019169