Propargyl alcohol (PA) is a high production volume chemical used in synthesis of many industrial chemicals and agricultural products. Despite the potential for prolonged or accidental exposure to PA in industrial settings, the toxicity potential of PA was not well characterized. To address the knowledge gaps relevant to the toxicity profile of PA, the National Toxicology Program (NTP) conducted 2-week, 14-week and 2-year studies in male and female F344/N rats and B6C3F1/N mice. For the 2-week inhalation study, the rats and mice were exposed to 0, 31.3, 62.5, 125, 250 or 500ppm. Significant mortality was observed in both rats and mice exposed to ≥125ppm of PA. The major target organ of toxicity in both mice and rats was the liver with exposure-related histopathological changes (250 and 500ppm). Based on the decreased survival in the 2-week study, the rats and mice were exposed to 0, 4, 8, 16, 32 or 64ppm of PA in the 14-week study. No treatment-related mortality was observed. Mean body weights of male (≥8ppm) and female mice (32 and 64ppm) were significantly decreased (7-16%). Histopathological changes were noted in the nasal cavity, and included suppurative inflammation, squamous metaplasia, hyaline droplet accumulation, olfactory epithelium atrophy, and necrosis. In the 2-year inhalation studies, the rats were exposed to 0, 16, 32 and 64ppm of PA and the mice were exposed to 0, 8, 16 and 32ppm of PA. Survival of male rats was significantly reduced (32 and 64ppm). Mean body weights of 64ppm male rats were significantly decreased relative to the controls. Both mice and rats showed a spectrum of non-neoplastic changes in the nose. Increased neoplastic incidences of nasal respiratory/transitional epithelial adenoma were observed in both rats and mice. The incidence of mononuclear cell leukemia was significantly increased in male rats and was considered to be treatment-related. In conclusion, the key findings from this study indicated that the nose was the primary target organ of toxicity for PA. Long term inhalation exposure to PA led to nonneoplastic changes in the nose, and increased incidences of respiratory/transitional epithelial adenomas in both mice and rats. Increased incidences of harderian gland adenoma may also have been related to exposure to PA in male mice.

中文翻译：

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F344/N 大鼠和 B6C3F1/N 小鼠全身吸入暴露后炔丙醇毒性和致癌性的评价。

炔丙醇 (PA) 是一种高产量化学品，用于合成许多工业化学品和农产品。尽管在工业环境中可能会长期或意外接触 PA，但 PA 的潜在毒性并未得到很好的表征。为了解决与 PA 毒性特征相关的知识空白，国家毒理学计划 (NTP) 对雄性和雌性 F344/N 大鼠和 B6C3F1/N 小鼠进行了为期 2 周、14 周和 2 年的研究。在为期 2 周的吸入研究中，大鼠和小鼠暴露于 0、31.3、62.5、125、250 或 500 ppm。在暴露于≥125ppm PA 的大鼠和小鼠中均观察到显着的死亡率。小鼠和大鼠的主要毒性靶器官是肝脏，具有与暴露相关的组织病理学变化（250 和 500 ppm）。基于 2 周研究中生存率的下降，在为期 14 周的研究中，大鼠和小鼠暴露于 0、4、8、16、32 或 64 ppm 的 PA。没有观察到治疗相关的死亡率。雄性 (≥8ppm) 和雌性小鼠 (32 和 64ppm) 的平均体重显着降低 (7-16%)。在鼻腔中观察到组织病理学变化，包括化脓性炎症、鳞状上皮化生、透明液滴积聚、嗅觉上皮萎缩和坏死。在为期 2 年的吸入研究中，大鼠暴露于 0、16、32 和 64 ppm 的 PA，小鼠暴露于 0、8、16 和 32 ppm 的 PA。雄性大鼠的存活率显着降低（32 和 64 ppm）。64ppm 雄性大鼠的平均体重相对于对照显着降低。小鼠和大鼠的鼻子均表现出一系列非肿瘤性变化。在大鼠和小鼠中均观察到鼻呼吸系统/移行性上皮腺瘤的肿瘤发生率增加。雄性大鼠单核细胞白血病的发生率显着增加，被认为与治疗有关。总之，这项研究的主要发现表明，鼻子是 PA 的主要毒性靶器官。长期吸入 PA 导致鼻子发生非肿瘤性变化，并增加小鼠和大鼠呼吸/移行上皮腺瘤的发生率。哈氏腺腺瘤发病率的增加也可能与雄性小鼠接触 PA 有关。这项研究的主要发现表明，鼻子是 PA 的主要毒性靶器官。长期吸入 PA 导致鼻子发生非肿瘤性变化，并增加小鼠和大鼠呼吸/移行上皮腺瘤的发生率。哈氏腺腺瘤发病率的增加也可能与雄性小鼠接触 PA 有关。这项研究的主要发现表明，鼻子是 PA 的主要毒性靶器官。长期吸入 PA 导致鼻子发生非肿瘤性变化，并增加小鼠和大鼠呼吸/移行上皮腺瘤的发生率。哈氏腺腺瘤发病率的增加也可能与雄性小鼠接触 PA 有关。