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',5-5-entachlorobiphenyI (PCB126) and perchlorate (004), 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 1, rats were administered a single oral dose of PCB126 (0, 7.5, or 75 mu g/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 T-4-glucuronide formation, causing a decline in serum thyroxine and fF(4), and resulting in increased serum thyroid-stimulating hormone (TSH). Serum TSH was also increased in animals that received 7.5 mu g 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 11, animals were given lower doses of PCB126 (0, 0.075, 0.75, or 7.5 mu g/kg) on day 0, and followed with 004 (0 or 0.01 mg/kg day) in drinking water beginning on day I 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.