Low-Dose Effects of Ammonium Perchlorate on the Hypothalamic-Pituitary-Thyroid Axis of Adult Male Rats Pretreated with PCB126

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 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 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.