A1 Refereed original research article in a scientific journal
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
Authors: Alarcon Sonia, Esteban Javier, Roos Robert, Heikkinen Päivi, Sanchez-Perez Ismael, Adamsson Annika, Toppari Jorma, Koskela Antti, Finnilä Mikko AJ, Tuukkanen Juha, Herlin Maria, Hamscher Gerd, Leslie Heather A, Korkalainen Merja, Halldin Krister, Schrenk Dieter, Håkansson Helen, Viluksela Matti
Publisher: PERGAMON-ELSEVIER SCIENCE LTD
Publication year: 2021
Journal: Reproductive Toxicology
Journal name in source: REPRODUCTIVE TOXICOLOGY
Journal acronym: REPROD TOXICOL
Volume: 102
First page : 109
Last page: 127
Number of pages: 19
ISSN: 0890-6238
eISSN: 1873-1708
DOI: https://doi.org/10.1016/j.reprotox.2021.04.004
Web address : https://www.sciencedirect.com/science/article/pii/S0890623821000642?via=ihub
Self-archived copy’s web address: https://research.utu.fi/converis/portal/Publication/59147944
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.
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