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对Fischer 344大鼠进行的三氟碘甲烷蒸汽急性和亚慢性吸入研究。

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

作者信息

Dodd D E, Kinkead E R, Wolfe R E, Leahy H F, English J H, Vinegar A

机构信息

ManTech Environmental Technology, Inc., Wright-Patterson Air Force Base, Dayton, Ohio 45437-0009, USA.

出版信息

Fundam Appl Toxicol. 1997 Jan;35(1):64-77. doi: 10.1006/faat.1996.2260.

Abstract

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).

摘要

三氟碘甲烷(CF3I)正被考虑用作哈龙灭火剂的替代化合物。它的结构与哈龙1301(CF3Br)相似,但与CF3Br相比,其臭氧消耗潜能值非常低。作为制定环境和健康影响标准过程的一部分,在Fischer 344大鼠中进行了急性、为期2周和13周的仅经鼻吸入毒性研究。在急性研究中,将三组每组30只雄性大鼠分别暴露于0(对照)、0.5%或1.0%(v/v)的CF3I中4小时,并在暴露后立即、暴露后3天或暴露后14天实施安乐死。在整个研究过程中没有死亡,也没有毒性的临床体征。对选定组织的组织病理学检查未发现具有病理意义的病变。在为期2周的研究中,将四组每组5只雄性大鼠每天暴露2小时、每周5天,分别暴露于0、3%、6%或12%的CF3I中。未观察到死亡,尽管在每次每日暴露结束时,6%和12%组的大鼠出现嗜睡和轻微不协调。6%和12%组大鼠的平均体重增加受到抑制。在所有暴露水平下,血清甲状腺球蛋白和反三碘甲状腺原氨酸(rT3)值均升高。尸检时,未发现大体病变,绝对或相对器官重量也无差异。对甲状腺和甲状旁腺的组织病理学检查表明,暴露于CF3I的大鼠没有形态学异常。在为期13周的研究中,将四组每组15只雄性和15只雌性大鼠每天暴露2小时、每周5天,分别暴露于0、2%、4%或8%的CF3I中13周。暴露于4%或8% CF3I的大鼠平均体重低于对照组。在2%和8%组中观察到的死亡归因于所采用的约束系统导致的意外事故。血液学改变极小,被认为无显著意义。在所有三个CF3I组的大鼠中均观察到微核化骨髓多染红细胞频率增加。在所有CF3I暴露组的大鼠中观察到的血清化学改变包括三碘甲状腺原氨酸(T3)降低以及甲状腺球蛋白、rT3、甲状腺素(T4)和促甲状腺激素(TSH)升高。相对器官重量增加(8% CF3I组)出现在脑、肝和甲状腺;在胸腺和睾丸中观察到重量减轻。在2%和4%组的大鼠中也观察到相对胸腺重量降低和相对甲状腺重量增加。组织病理学结果包括暴露于4%或8% CF3I的大鼠鼻甲出现轻度炎症,睾丸轻度萎缩和退化(4%和8% CF3I组),以及所有CF3I暴露组大鼠甲状腺滤泡胶体含量轻度增加。尽管在选定的靶器官(如鼻甲、睾丸)中观察到了未观察到有害作用水平(NOAEL),但在所有检查的靶器官(如甲状腺、骨髓)中并非都明显存在NOAEL。

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