Acute and Subchronic Inhalation Studies on Trifluoroiodomethane Vapor in Fischer 344 Rats

Trifluoroiodomethane (CF₃I) is being considered as a replacementcompound for halon fire suppressants. Its structure is similarto that of Halon 1301 (CF₃Br), but it has very low ozone depletionpotential compared to CF₃Br. As part of the process of developingenvironmental and health effects criteria, acute, 2-week, and13- week nose-only inhalation toxicity studies were conductedin Fischer 344 rats. In the acute study, three groups of 30male 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 nodeaths and no clinical signs of toxicity throughout the study.Histopathologic examination of select tissues showed no lesionsof pathologic significance. In the 2-week study, four groupsof 5 male rats each were exposed for 2 hr/day, 5 days/week to0, 3, 6, or 12% CF₃I No deaths were observed, though lethargyand slight incoordination were noted in rats of the 6 and 12%groups at the conclusion of each daily exposure. Mean body weightgains were depressed in rats of the 6 and 12% groups. Serumthyroglobulin and reverse T₃ (rT₃) values were increased atall exposure levels. At necropsy, no gross lesions or differencesin absolute or relative organ weights were noted. Histopathologicexamination of the thyroid and parathyroid glands indicatedno morphological abnormalities in the CF₃I-exposed rats. Inthe 13-week study, four groups of 15 male and 15 female ratswere exposed to 0, 2, 4, or 8% CF₃I 2 hr/day, 5 days/week for13 weeks. Rats exposed to 4 or 8% CF₃I had lower mean body weightsthan the controls. Deaths observed in the 2 and 8% groups wereattributed to accidents resulting from the restraint systememployed. Hematologic alterations were minimal and consideredinsignificant. Increases in the frequency of micronucleatedbone marrow polychromatic erythrocytes were observed in ratsof all three CF₃I groups. Serum chemistry alterations observedin rats of all CF₃I exposure groups included decreases in T₃and increases in thyroglobulin, rT₃, T₄, and TSH. Relative organweight increases (8% CF₃I group) occurred in the brain, liver,and thyroid glands; decreases were observed in the thymus andtestes. A decrease in relative thymus weights and an increasein relative thyroid weights were observed also in rats of the2 and 4% groups. Histopathological findings included a mildinflammation in the nasal turbinates of rats exposed to 4 or8% CF₃I, mild atrophy and degeneration of the testes (4 and8% CF₃I groups), and a mild increase in thyroid follicular colloidcontent in rats of all CF₃I exposure groups. Though NOAELs wereobserved for select target organs (e.g., nasal turbinates, testes),NOAELs were not apparent in all target organs examined (e.g.,thyroid glands, bone marrow).