Acute and subchronic inhalation studies on trifluoroiodomethane vapor in Fischer 344 rats

Trifluoroiodomethane (CF3I) is being considered as a replacement compound for halon fire suppressants. Its structure is similar to that of Halon 1301 (CF3Br), but it has very low ozone depletion potential compared to CF3Br. As part of the process of developing environmental and health effects criteria, acute, 2-week, and 13-week nose-only inhalation toxicity studies were conducted in Fischer 344 rats. In the acute study, three groups of 30 male rats each were exposed to 0 (control), 0.5, or 1.0% (v/v) CF3I for 4 hr and euthanized immediately following exposure, 3 days postexposure, or 14 days postexposure. There were no deaths and no clinical signs of toxicity throughout the study. Histopathologic examination of select tissues showed no lesions of pathologic significance. In the 2-week study, four groups of 5 male rats each were exposed for 2 hr/day, 5 days/week to 0, 3, 6, or 12% CF3I. No deaths were observed, though lethargy and slight incoordination were noted in rats of the 6 and 12% groups at the conclusion of each daily exposure. Mean body weight gains were depressed in rats of the 6 and 12% groups. Serum thyroglobulin and reverse T3 (rT3) values were increased at all exposure levels. At necropsy, no gross lesions or differences in absolute or relative organ weights were noted. Histopathologic examination of the thyroid and parathyroid glands indicated no morphological abnormalities in the CF3I-exposed rats. In the 13-week study, four groups of 15 male and 15 female rats were exposed to 0, 2, 4, or 8% CF3I 2 hr/day, 5 days/week for 13 weeks. Rats exposed to 4 or 8% CF3I had lower mean body weights than the controls. Deaths observed in the 2 and 8% groups were attributed to accidents resulting from the restraint system employed. Hematologic alterations were minimal and considered insignificant. Increases in the frequency of micronucleated bone marrow polychromatic erythrocytes were observed in rats of all three CF3I groups. Serum chemistry alterations observed in rats of all CF3I exposure groups included decreases in T3 and increases in thyroglobulin, rT3, T4, and TSH. Relative organ weight increases (8% CF3I group) occurred in the brain, liver, and thyroid glands; decreases were observed in the thymus and testes. A decrease in relative thymus weights and an increase in relative thyroid weights were observed also in rats of the 2 and 4% groups. Histopathological findings included a mild inflammation in the nasal turbinates of rats exposed to 4 or 8% CF3I, mild atrophy and degeneration of the testes (4 and 8% CF3I groups), and a mild increase in thyroid follicular colloid content in rats of all CF3I exposure groups. Though NOAELs were observed for select target organs (e.g., nasal turbinates, testes), NOAELs were not apparent in all target organs examined (e.g., thyroid glands, bone marrow).