Newton P E, Bolte H F, Daly I W, Pillsbury B D, Terrill J B, Drew R T, Ben-Dyke R, Sheldon A W, Rubin L F
Pharmaco LSR Inc., East Millstone, New Jersey 08875-2360.
Fundam Appl Toxicol. 1994 May;22(4):561-76. doi: 10.1006/faat.1994.1063.
Fischer 344 rats were exposed by inhalation to Sb2O3 (antimony trioxide) dust at exposure levels of 0, 0.25, 1.08, 4.92, and 23.46 mg/m3 for 6 hr/day, 5 days/week for 13 weeks followed by a 27-week observation period. Subsequently, an inhalation oncogenicity study was conducted at exposure levels of 0, 0.06, 0.51, and 4.50 mg/m3 for 12 months followed by a 12-month observation period. The Sb2O3 in the subchronic study had a mass median aerodynamic diameter (MMAD) of 3.05 +/- 0.21 microns (mean +/- SD) with a geometric standard deviation (GSD) of 1.57 +/- 0.06. In the chronic study, the MMAD was 3.76 +/- 0.84 and the GSD was 1.79 +/- 0.32. Except for the eyes, no adverse clinical observations were attributed to Sb2O3 in either study. In the subchronic study, corneal irregularities were seen after about 2 weeks of exposure and did not abate during the observation period. In the chronic study, ophthalmoscopic evaluation at 24 months revealed a dose-related increase in cataracts of 11, 24, 28, and 32% (both sexes combined) for each group, respectively. Body weights were significantly lower (6%) than the control group's weights in the 23.46 mg/m3 males in the subchronic study. These rats did not recover this weight during the 27-week observation period. Body weights of the females in both studies and males in the chronic study were unaffected. There were no Sb2O3 effects on clinical chemistry or hematology in either study. Mean absolute and relative lung weights were significantly increased in the 4.92 and 23.46 mg/m3 groups in the subchronic study. The 23.46 mg/m3 group's lung weights did not recover to control levels during the 27-week observation period. Lung weights for rats in the chronic study were unaffected. Microscopic changes in the lungs in the subchronic and chronic study were limited to subacute-chronic interstitial inflammation, increased numbers of alveolar-intraalveolar macrophages, foreign material in the alveolar-intraalveolar macrophages in the peribronchial and perivascular (chronic study only) lymphoid aggregates and in the peribronchial lymph nodes, granulomatous inflammation/granulomas, and fibrosis. In the chronic study, any observed neoplasms occurred with comparable incidence among all groups and were within the historical range for controls. Clearance of Sb2O3 from the lung was burden dependent and was reduced by 80% in the 4.50 mg/m3 group in the chronic study. The previously reported studies, which found Sb2O3 to be a carcinogen, were run at higher lung burdens. Under the exposure conditions of the current study, Sb2O3 was not a carcinogen.
将Fischer 344大鼠每天吸入暴露于浓度分别为0、0.25、1.08、4.92和23.46毫克/立方米的三氧化二锑（Sb2O3）粉尘中，每周暴露5天，每天暴露6小时，持续13周，随后进行27周的观察期。随后，进行吸入致癌性研究，大鼠每天吸入暴露于浓度分别为0、0.06、0.51和4.50毫克/立方米的Sb2O3中，持续12个月，随后进行12个月的观察期。亚慢性研究中使用的Sb2O3的质量中位空气动力学直径（MMAD）为3.05±0.21微米（平均值±标准差），几何标准差（GSD）为1.57±0.06。在慢性研究中，MMAD为3.76±0.84，GSD为1.79±0.32。在两项研究中，除眼睛外，未观察到与Sb2O3相关的不良临床症状。在亚慢性研究中，暴露约2周后出现角膜不规则，且在观察期内未减轻。在慢性研究中，24个月时的眼底镜检查显示，每组白内障发生率与剂量相关，分别为11%、24%、28%和32%（两性合计）。在亚慢性研究中，23.46毫克/立方米组的雄性大鼠体重显著低于对照组（低6%）。在27周的观察期内，这些大鼠的体重未恢复。两项研究中的雌性大鼠以及慢性研究中的雄性大鼠体重均未受影响。两项研究中，Sb2O3对临床化学或血液学均无影响。在亚慢性研究中，4.92和23.46毫克/立方米组的平均绝对肺重和相对肺重显著增加。23.46毫克/立方米组的肺重在27周观察期内未恢复到对照水平。慢性研究中大鼠的肺重未受影响。亚慢性和慢性研究中肺部的微观变化仅限于亚急性-慢性间质性炎症、肺泡-肺泡内巨噬细胞数量增加、支气管周围和血管周围（仅慢性研究）淋巴聚集以及支气管周围淋巴结内的肺泡-肺泡内巨噬细胞中有异物、肉芽肿性炎症/肉芽肿和纤维化。在慢性研究中，所有组中观察到的任何肿瘤发生率相当，且在对照组的历史范围内。在慢性研究中，肺中Sb2O3的清除取决于负荷，4.50毫克/立方米组的清除率降低了80%。先前报道的发现Sb2O3为致癌物的研究是在更高的肺部负荷下进行的。在本研究的暴露条件下，Sb2O3不是致癌物。
