Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 367461
Title Food-associated estrogenic compounds induce estrogen receptor-mediated luciferase gene expression in transgenic male mice
Author(s) Veld, M.G.R. ter; Zawadzka, E.; Berg, J.H.J. van den; Saag, P.T. van der; Rietjens, I.M.C.M.; Murk, A.J.
Source Chemico-Biological Interactions 174 (2008)2. - ISSN 0009-2797 - p. 126 - 133.
Department(s) Sub-department of Toxicology
Publication type Refereed Article in a scientific journal
Publication year 2008
Keyword(s) sprague-dawley rats - reporter male-mice - in-vivo - bisphenol-a - phthalate-esters - p-nonylphenol - er-alpha - beta - vitro - assays
Abstract The present paper aims at clarifying to what extent seven food-associated compounds, shown before to be estrogenic in vitro, can induce estrogenic effects in male mice with an estrogen receptor (ER)-mediated luciferase (luc) reporter gene system. The luc induction was determined in different tissues 8 h after dosing the ER-luc male mice intraperitoneally (IP) or 14 h after oral dosing. Estradiol-propionate (EP) was used as a positive control at 0.3 and 1 mg/kg bodyweight (bw), DMSO as solvent control. The food-associated estrogenic compounds tested at non-toxic doses were bisphenol A (BPA) and nonylphenol (NP) (both at 10 and 50 mg/kg bw), dichlorodiphenyldichloroethylene (p,p¿-DDE; at 5 and 25 mg/kg bw), quercetin (at 1.66 and 16.6 mg/kg bw), di-isoheptyl phthalate (DIHP), di-(2-ethylhexyl) phthalate (DEHP) and di-(2-ethylhexyl) adipate (DEHA) all at 30 and 100 mg/kg bw. In general IP dosing resulted in higher luc inductions than oral dosing. EP induced luc activity in the liver in a statistically significant dose-related way with the highest induction of all compounds tested which was 20,000 times higher than the induction by the DMSO-control. NP, DDE, DEHA and DIHP did not induce luc activity in any of the tissues tested. BPA induced luc in the liver up to 420 times via both exposure routes. BPA, DEHP and quercetin induced luc activity in the liver after oral exposure. BPA (50 mg/kg bw IP) also induced luc activity in the testis, kidneys and tibia. The current study reveals that biomarker-responses in ER-luc male mice occur after a single oral exposure to food-associated estrogenic model compounds at exposure levels 10 to 104 times higher than the established TDI's for some of these compounds. Given the facts that (i) the present study did not include chronic exposure and that (ii) simultaneous exposure to multiple estrogenic compounds may be a realistic exposure scenario, it remains to be seen whether this margin is sufficiently high
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