ToxSci Advance Access originally published online on July 25, 2003
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Toxicological Sciences 75, 468-480 (2003)
Copyright © 2003 by the Society of Toxicology
SYSTEMS TOXICOLOGY |
Effects of Postnatal Exposure to Mixtures of Non-ortho-PCBs, PCDDs, and PCDFs in Prepubertal Female Rats
* Health Canada, Environmental and Occupational Toxicology Division, Tunney’s Pasture, A.L:0803D, Ottawa, Ontario, Canada K1A 0L2;
Reproductive Biology Unit and Division of Reproductive Medicine, Departments of Obstetrics and Gynaecology and Cellular and Molecular Medicine, University of Ottawa; Hormones, Growth and Development Program, Ottawa Health Research Institute, 725 Parkdale Avenue, Ottawa, Ontario, Canada K1Y 4E9; and
INRS-Institut Armand Frappier, Université du Québec, 245, Boulevard Hymus, Pointe-Claire, Québec, Canada H9R 1G6
There are concerns that postnatal exposure to organochlorines present in breast milk could lead to adverse health effects. We reconstituted four mixtures of aryl-hydrocarbon receptor (AhR) agonists (3 non-ortho polychlorinated biphenyls [PCBs], 6 polychlorinated dibenzodioxins [PCDDs], 7 polychlorinated dibenzofurans [PCDFs], or all 16 chemicals together [referred to as AhRM]) based on their concentrations in breast milk, and examined their effects following exposure by gavage from day 1 until day 20 of age. Female neonates received dosages of AhRM equivalent to 1, 10, 100, or 1000 times the amount consumed by an infant over the first 24 days of life. Other groups received the PCBs, the PCDDs, or the PCDFs at the 1000x level. All rats were sacrificed at 21 days of age. Changes in ethoxyresorufin-o-deethylase hepatic activity, thymus and body weights, and serum thyroxin were linked to the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalents (TEQ) of the four mixtures (1000x-AhRM > PCDDs > PCBs > PCDFs). To test for AhRM antiestrogenicity, two additional groups received 1.5 µg/kg of 17
-ethynyl estradiol (EE) with or without the 1000x-AhRM. The AhRM had no effect on uterine weight or EE-stimulated uterine growth. The actions of the combined EE and AhRM treatments suggest additive effects in decreasing pentoxyresorufin-o-deethylase activity and spleen weight, but nonadditive/antagonistic effects on adrenal weight and serum thyroxin. In conclusion, (1) 10x-AhRM had no detectable effects, (2) TEQ values relate to observed toxicities, even when testing complex mixtures of AhR agonists, and (3) indications of tissue-specific additive and nonadditive/antagonistic effects, but no synergism, were observed when doses of AhRM were increased, or combined with EE.
Key Words: uterotrophic bioassay; prepubertal; rat; mixture; CYP 2B; toxic equivalent; polychlorinated biphenyls; polychlorinated dibenzodioxins; polychlorinated dibenzofurans; breast milk.
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