Irreversible thyroid disruption induced after subchronic exposure to hexachlorobenzene in male rats

Thyroid hormones play a complex role in the toxicity of hexachlorobenzene (HCB) and related compounds. Time-course and dose-response experiments for free- and total thyroxine (T-4) and triiodothyronine (T-3) plasma levels for thyroid-stimulating hormone (TSH) and thyroid gland histomorphology were determined in male Wistar rats. Also, we examined the possible reversibility of changes noted after removal of HCB. Rats treated with this organochlorine compound resulted in a hypertrophy of the thyroid gland and altered thyroid function by decreasing significantly the levels of total- and free T-4 in a dose-dependent manner (total T-4: 28 and 51%; free T-4: 21 and 37%), and this decrease was seen as early as 21 days and thereafter. Free T-3 was also decreased by 21% with the highest dose starting from day 21. No significant changes were observed in the circulating levels of total T-3. In response to the decrease of thyroid hormones, a dose-dependent increase of TSH levels (27 and 31%, respectively, for 4 mg and 16 mg/kg of HCB body weight) was observed after 21 days of HCB treatment. We have observed a hypertrophy and hyperplasia of follicular cells and a decrease in colloid volume in histological picture. When HCB was removed and changed by vehicle, the thyroid relative weight and plasma TSH continued to rise and serum thyroid hormones remained suppressed. These findings suggest that subchronic exposure of rats to HCB induced an irreversible hypothyroidism state.