Blair P C, Thompson M B, Morrissey R E, Moorman M P, Sloane R A, Fowler B A
Chemical Pathology Branch, NIEHS, Research Triangle Park, North Carolina 27709.
Fundam Appl Toxicol. 1990 May;14(4):776-87. doi: 10.1016/0272-0590(90)90302-z.
In order to examine possible species differences in response to arsine exposure, multiple inhalation studies consisting of acute (1-day), subacute (14- and 28-day), and subchronic (90-day) exposures to this agent were conducted using three different species of rodents. Evaluations of hematopoietic organs and alterations in the heme biosynthetic pathway were the focus of these studies. Species used were B6C3F1 mice (exposed 1, 14, or 90 days), Fischer 344 rats (exposed 14, 28, or 90 days), and Syrian Golden hamsters (exposed 28 days). All arsine exposures were at concentrations of 0.5, 2.5, or 5.0 ppm except for 90-day studies, in which concentrations were lowered to 0.025, 0.5, or 2.5 ppm. No changes in body weight gain were observed in either sex of mice or hamsters. The only decrease in body weight gain occurred in male rats exposed to 5.0 ppm arsine for 28 days. Significant exposure-related increases in relative spleen weights occurred in both sexes of mice and rats in the 0.5 (except 14-day female rats), 2.5, and 5.0 ppm exposure groups from all studies and in hamsters in the 2.5 and 5.0 ppm exposure groups. Generally, increases in relative liver weight occurred in fewer exposure groups and were of a lesser magnitude than increases in spleen weight. Other parameters affected included decreased packed cell volumes (mice, rats, and hamsters), hematology profiles (rats), and an increase in delta-aminolevulinic acid dehydratase activity in all species. Arsenic content was measured in livers of rats after 90 days of exposure. Concentrations increased in relation to atmospheric concentrations of arsine. Histopathologic changes included increased hemosiderosis and extramedullary hematopoiesis in spleen and intracanalicular bile stasis (mice only) in liver. Additionally, bone marrow hyperplasia was observed in rats. Effects on other organs were not observed, suggesting that the hematopoietic system is the primary target for arsine. In conclusion, we have determined that the effects of arsine exposure upon mice, rats, and hamsters are similar. Most importantly, even though no effects on the hematopoietic system were observed following a single exposure to 0.5 ppm arsine which is 10 times the Threshold Limit Value (TLV) set by the American Conference of Governmental Industrial Hygienists, repeated exposure to 0.025 ppm (one-half the TLV) caused a significant anemia in rats.
为了研究不同物种对胂暴露的可能差异，使用三种不同的啮齿动物进行了多项吸入研究，包括对该试剂的急性（1天）、亚急性（14天和28天）和亚慢性（90天）暴露。这些研究的重点是造血器官的评估和血红素生物合成途径的改变。使用的物种有B6C3F1小鼠（暴露1天、14天或90天）、Fischer 344大鼠（暴露14天、28天或90天）和叙利亚金黄地鼠（暴露28天）。除90天研究外，所有胂暴露的浓度均为0.5、2.5或5.0 ppm，在90天研究中，浓度降至0.025、0.5或2.5 ppm。在小鼠和地鼠的雌雄两性中均未观察到体重增加的变化。唯一体重增加减少的情况发生在暴露于5.0 ppm胂28天的雄性大鼠中。在所有研究中，0.5 ppm（14天雌性大鼠除外）、2.5 ppm和5.0 ppm暴露组的小鼠和大鼠雌雄两性以及2.5 ppm和5.0 ppm暴露组的地鼠中，脾脏相对重量均出现与暴露相关的显著增加。一般来说，相对肝脏重量增加的暴露组较少，且增加幅度小于脾脏重量增加的幅度。其他受影响的参数包括红细胞压积降低（小鼠、大鼠和地鼠）、血液学指标（大鼠）以及所有物种的δ-氨基乙酰丙酸脱水酶活性增加。在暴露90天后测量大鼠肝脏中的砷含量。浓度与大气中胂的浓度相关增加。组织病理学变化包括脾脏中铁沉积增加和髓外造血以及肝脏中的肝内胆管淤积（仅小鼠）。此外，在大鼠中观察到骨髓增生。未观察到对其他器官的影响，表明造血系统是胂作用的主要靶器官。总之，我们已经确定胂暴露对小鼠、大鼠和地鼠产生的影响相似。最重要的是，尽管单次暴露于0.5 ppm胂（是美国政府工业卫生学家会议设定的阈限值的10倍）后未观察到对造血系统的影响，但重复暴露于0.025 ppm（阈限值的一半）会导致大鼠出现明显贫血。
