Sonia Alarcón, Javier Esteban, Robert Roos, Päivi Heikkinen, Ismael Sánchez-Pérez, Annika Adamsson, Jorma Toppari, Antti Koskela, Mikko A.J. Finnilä, Juha Tuukkanen, Maria Herlin, Gerd Hamscher, Heather A. Leslie, Merja Korkalainen, Krister Halldin, Dieter Schrenk, Helen Håkansson, Matti Viluksela, Endocrine, metabolic and apical effects of in utero and lactational exposure to non-dioxin-like 2,2′,3,4,4 ,5,5′-heptachlorobiphenyl (PCB 180): A postnatal follow-up study in rats, Reproductive Toxicology, Volume 102, 2021, Pages 109-127, ISSN 0890-6238, https://doi.org/10.1016/j.reprotox.2021.04.004
Endocrine, metabolic and apical effects of in utero and lactational exposure to non-dioxin-like 2,2′,3,4,4′,5,5′-heptachlorobiphenyl (PCB 180) : a postnatal follow-up study in rats
|Author:||Alarcón, Sonia1,2; Esteban, Javier1; Roos, Robert2;|
1Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Elche (Alicante), Spain
2Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
3Environmental Health Unit, Finnish Institute for Health and Welfare (THL), P.O. Box 95, Kuopio, FI-70701, Finland
4Research Center for Integrative Physiology and Pharmacology and Centre for Population Health Research, Institute of Biomedicine, University of Turku, Department of Paediatrics, Turku University Hospital, Turku, FI-20520, Finland
5Department of Anatomy and Cell Biology, Institute of Cancer Research and Translational Medicine, University of Oulu, Oulu, Finland
6Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland
7Institute of Food Chemistry and Food Biotechnology, Justus Liebig University, Giessen, D-35392, Germany
8Department of Environment and Health, Vrije Universiteit Amsterdam, De Boelelaan 1108, Amsterdam, NL-1081 HZ, The Netherlands
9Food Chemistry and Toxicology, University of Kaiserslautern, Kaiserslautern, D-67663, Germany
10School of Pharmacy (Toxicology), Department of Environmental and Biological Sciences, University of Eastern Finland, Kuopio, Finland
|Online Access:||PDF Full Text (PDF, 3.2 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2021063040627
|Publish Date:|| 2021-06-30
PCB 180 is a persistent and abundant non-dioxin-like PCB (NDL-PCB). We determined the developmental toxicity profile of ultrapure PCB 180 in developing offspring following in utero and lactational exposure with the focus on endocrine, metabolic and retinoid system alterations. Pregnant rats were given total doses of 0, 10, 30, 100, 300 or 1000 mg PCB 180/kg bw on gestational days 7−10 by oral gavage, and the offspring were sampled on postnatal days (PND) 7, 35 and 84. Decreased serum testosterone and triiodothyronine concentrations on PND 84, altered liver retinoid levels, increased liver weights and induced 7-pentoxyresorufin O-dealkylase (PROD) activity were the sensitive effects used for margin of exposure (MoE) calculations. Liver weights were increased together with induction of the metabolizing enzymes cytochrome P450 (CYP) 2B1, CYP3A1, and CYP1A1. Less sensitive effects included decreased serum estradiol and increased luteinizing hormone levels in females, decreased prostate and seminal vesicle weight and increased pituitary weight in males, increased cortical bone area and thickness of tibial diaphysis in females and decreased cortical bone mineral density in males. Developmental toxicity profiles were partly different in male and female offspring, males being more sensitive to increased liver weight, PROD induction and decreased thyroxine concentrations. MoE assessment indicated that the 95th percentile of current maternal PCB 180 concentrations do not exceed the estimated tolerable human lipid-based PCB 180 concentration. Although PCB 180 is much less potent than dioxin-like compounds, it shares several toxicological targets suggesting a potential for interactions.
|Pages:||109 - 127|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
This study was funded by the European Commission (ATHON, FOOD-CT-2005-022923). The authors are solely responsible for the contents of this paper, which does not necessarily represent the opinion of the European Community. Additionally, the work was supported by the FARO global (Ministry of Education, Spain), the National Fund Research, Luxembourg (FNR) and co-funded under the Marie Curie Actions of the European Commission (FP7-COFUND).
© 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0).