Thyroid homeostasis in B6C3F1 mice upon sub-chronic exposure to trifluoroiodomethane (CF₃I)

Trifluoroiodomethane (CF₃I) is a fire suppressant gas with potential for use in low global-warming refrigerant blends. Data from studies in rats suggest that the most sensitive health effect of CF₃I is thyroid hormone perturbation, but the rat is a particularly sensitive species for disruption of thyroid homeostasis. Mice appear to be less sensitive than rats but still a conservative model with respect to humans. The purpose of this study was to test tolerance and thyroid response to CF₃I in B6C3F1 male mice. Male mice were exposed to CF₃I for 6 h per day, for 28 days, via whole body exposure at concentrations of 2500, 5000 and 10,000 ppm. A 16-day recovery period was included to evaluate reversibility. No adverse clinical signs were observed throughout the study, and body weights were unaffected by exposure. CF₃I exposure had no effect on thyroid histology. An increase in relative thyroid weight was observed at 10,000 ppm on day 28 but not in a separate group of animals evaluated on day 29, and thyroid weight was not different from controls at 44 days. Slight and sporadic changes in serum triiodothyronine, thyroxine, and thyroid-stimulating hormone were observed but did not follow a consistent pattern with respect to timing, dose, or direction. Overall, exposure at up to 10,000 ppm (1.0%) of CF₃I gas for 28 days produced no overt general toxicity and only transient, recoverable effects on thyroid weight and hormones at certain concentrations. On the basis of the effect of CF₃I exposure on the thyroid, including evaluation of thyroid histopathology, the no observed adverse effect level for this study is 10,000 ppm. Considering the apparently greater toxicity reported in prior studies in male rats, our data suggest a species difference between rats and mice in terms of susceptibility to CF₃I-induced thyroid hormone perturbation.