Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/15047
Title: Programming of metabolic effects in C57BL/6JxFVB mice by in utero and lactational exposure to perfluorooctanoic acid
Authors: Sales, LB
Dolle, MET
Hakansson, H
Herlin, M
Legler, J
van der Ven, LTM
Keywords: Science & Technology;Life Sciences & Biomedicine;Toxicology;Endocrine disrupting compounds;Developmental exposure;Metabolic effects;Perfluorooctanoic acid;Programming;MAMMARY-GLAND DEVELOPMENT;RESTRICTED GESTATIONAL EXPOSURES;CD-1 MICE;PRENATAL EXPOSURE;POLYFLUOROALKYL COMPOUNDS;PERFLUORINATED COMPOUNDS;SERUM CONCENTRATIONS;PROSPECTIVE COHORT;SULFONATE PFOS;FETAL-GROWTH
Issue Date: 2015
Publisher: SPRINGER HEIDELBERG
Citation: ARCHIVES OF TOXICOLOGY, 2016, 90 (3), pp. 701 - 715 (15)
Abstract: Perfluorooctanoic acid (PFOA) is known to cause developmental toxicity and is a suggested endocrine disrupting compound (EDC). Early life exposure to EDCs has been implicated in programming of the developing organism for chronic diseases later in life. Here we study perinatal metabolic programming by PFOA using an experimental design relevant for human exposure. C57BL/6JxFVB hybrid mice were exposed during gestation and lactation via maternal feed to seven low doses of PFOA at and below the NOAEL used for current risk assessment (3–3000 μg/kg body weight/day). After weaning, offspring were followed for 23–25 weeks without further exposure. Offspring showed a dose-dependent decrease in body weight from postnatal day 4 to adulthood. Growth under high fat diet in the last 4–6 weeks of follow-up was increased in male and decreased in female offspring. Both sexes showed increased liver weights, hepatic foci of cellular alterations and nuclear dysmorphology. In females, reductions in perigonadal and perirenal fat pad weights, serum triglycerides and cholesterol were also observed. Endocrine parameters, such as glucose tolerance, serum insulin and leptin, were not affected. In conclusion, our study with perinatal exposure to PFOA in mice produced metabolic effects in adult offspring. This is most likely due to disrupted programming of metabolic homeostasis, but the assayed endpoints did not provide a mechanistic explanation. The BMDL of the programming effects in our study is below the current point of departure used for calculation of the tolerable daily intake.
URI: http://bura.brunel.ac.uk/handle/2438/15047
DOI: http://dx.doi.org/10.1007/s00204-015-1488-7
ISSN: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000370343000016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=f12c8c83318cf2733e615e54d9ed7ad5
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000370343000016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=f12c8c83318cf2733e615e54d9ed7ad5
0340-5761
1432-0738
Appears in Collections:Dept of Clinical Sciences Research Papers

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