Low-dose effects of ammonium perchlorate on the hypothalamic-pituitary-thyroid axis of adult male rats pretreated with PCB126

Eva D. McLanahan, Jerry L. Campbell, Duncan C. Ferguson, Barry Harmon, Joan M. Hedge, Kevin M. Crofton, David R. Mattie, Lewis Braverman, Deborah A. Keys, Moiz Mumtaz, Jeffrey W. Fisher

Research output: Contribution to journalArticlepeer-review

Abstract

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 (ClO4-), known to cause hypothyroidism by different modes of action. Two studies were conducted to determine the HPT axis effects of ClO4- 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 ClO4- (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 ClO4 - 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 thyroidstimulating hormone (TSH). Serum TSH was also increased in animals that received 7.5 mg PCB126/kg; no other HPT axis alterations were found in these animals. When pretreated with PCB126, the ClO4- 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 ClO4 - (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 ClO4 - 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 ClO4- 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 ClO4-, no interactions between the chemicals occur.

Original languageEnglish (US)
Pages (from-to)308-317
Number of pages10
JournalToxicological Sciences
Volume97
Issue number2
DOIs
StatePublished - Jun 2007
Externally publishedYes

Keywords

  • PCB126
  • Perchlorate
  • Rat
  • T
  • TSH
  • Thyroid
  • UDPGT

ASJC Scopus subject areas

  • Toxicology

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