ToxSci Advance Access originally published online on March 22, 2007
Toxicological Sciences 2007 97(2):308-317; doi:10.1093/toxsci/kfm063
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Low-Dose Effects of Ammonium Perchlorate on the Hypothalamic-Pituitary-Thyroid Axis of Adult Male Rats Pretreated with PCB126
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* Interdisciplinary Toxicology Program, University of Georgia, Athens, Georgia 30602
Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602
Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Air Force Research Laboratory, Human Effectiveness Directorate, Biosciences and Protection Division, Applied Biotechnology Branch, Wright-Patterson Air Force Base, Ohio 45433
¶ Section of Endocrinology, Diabetes, and Nutrition Center, Boston Medical Center, Boston, Massachusetts 02118
|| Statistics and Modeling Supporting Informed Decisions, Athens, Georgia 30606
||| Division of Toxicology, Agency for Toxic Substances and Disease Registry, Atlanta, Georgia 30333
1 To whom correspondence should be addressed at 206 Environmental Health Sciences Department, University of Georgia, Athens, GA 30602-2102, USA. Fax: 706-542-7472. E-mail: evad{at}uga.edu.
Received January 18, 2007; accepted March 16, 2007
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Abstract |
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The objective of this research was to characterize the disturbances in the hypothalamic-pituitary-thyroid (HPT) axis resulting from exposure to a binary mixture, 3,3',4,4',5-pentachlorobiphenyl (PCB126) and perchlorate (ClO
), known to cause hypothyroidism by different modes of action. Two studies were conducted to determine the HPT axis effects of ClO on adult male Sprague-Dawley rats pretreated with PCB126. In dosing study I, rats were administered a single oral dose of PCB126 (0, 7.5, or 75 µg/kg) on day 0 and 9 days later ClO (0, 0.01, 0.1, or 1 mg/kg day) was added to the drinking water until euthanasia on day 22. Significant dose-dependent trends were found for all thyroid function indices measured following ClO in drinking water for 14 days. Seventy-five micrograms PCB126/kg resulted in a significant increase in hepatic T4-glucuronide formation, causing a decline in serum thyroxine and fT4, and resulting in increased serum thyroid-stimulating hormone (TSH). Serum TSH was also increased in animals that received 7.5 µg PCB126/kg; no other HPT axis alterations were found in these animals. When pretreated with PCB126, the ClO dose trends disappeared, suggesting a less than additive effect on the HPT axis. In dosing study II, animals were given lower doses of PCB126 (0, 0.075, 0.75, or 7.5 µg/kg) on day 0, and followed with ClO (0 or 0.01 mg/kg day) in drinking water beginning on day 1 and continuing for several days to explore transient HPT axis effects. No statistical effects were seen for PCB126 or ClO alone, and no perturbations were found when administered sequentially in dosing study II. In conclusion, these studies demonstrate that HPT axis disturbances following exposure to ClO are less than additive when pretreated with relatively high doses of PCB126. At relatively low doses, at or near the no-observed-effect-level for PCB126 and ClO, no interactions between the chemicals occur.
Key Words: PCB126; perchlorate; rat; T4; thyroid; TSH; UDPGT.
2 Barry Harmon has passed away since submission of this article.
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