In vivo study of arsine exposure in hairless mice: percutaneous absorption vs. whole-body inhalation

摘要

Background: Arsine (AsH3) is widely used in the semiconductor industry. Primary cause of death in exposure to workers is kidney damage due to hemolysis, but the mechanism and potential for percutaneous absorption are unclear. Aim: Mice were exposed to arsine to detect percutaneous absorption and determine the toxicity mechanism. Methods: Arsine gas was generated by reduction of arsenic trioxide with NaBH4. Male 5-week-old Hos:HR-l hairless mice (n=4 each) were subjected to single percutaneous or whole-body inhalation exposure of arsine gas (ca. 300 ppm) for 5 minutes. Total arsenic in blood (T-As) was determined using an ICP-MS, and hematocrit values (Ht) were measured. Histopathological examination was performed 6 h after exposure, and liver, spleen, kidneys, and lungs were subjected to immunohistochemical hemoglobin (Hb) and HE staining. Results: Mice subjected to whole-body inhalation at 320 ppm had reddening around the eyes, purple skin, and listless behavior. No changes were observed in the percutaneous exposure group at 310 ppm. Ht values in the inhalation group decreased significantly (p＜0.02), down to 16% after 3 h, and all blood samples were hemolyzed. T-As in the inhalation group was 9.0-14.2 mg/L, significantly higher than in the control group (＜2.0 mg/L, p＜0.02). In contrast, Ht and T-As in the percutaneous group were comparable to control group values. Histopathological changes were only noted in the inhalation group, with marked deposition of eosinophilic globules in the proximal convoluted tubules of the kidney, Kupffer cells of the liver, and red pulp in the spleen. No changes were noted in the lungs. Immunohistochemically, these eosinophilic globules reacted positively to hemoglobin antibody. Conclusion: in the present study, arsine was not absorbed through the skin. Findings for exposure to arsine further suggest that hemolysis occurs first, followed by release of Hb and accumulation in the proximal tubules of the kidney, ultimately leading to renal dysfunction.