title: Arsine toxicity is induced by inhalation but not by percutaneous exposure in hairless mice.
abstract: Arsine (AsH₃) is used in many industries, but there is insufficient knowledge about the potential for percutaneous absorption. In order to examine possible percutaneous absorption of arsine, we conducted inhalation studies. Arsine was generated by reducing arsenic trioxide with NaBH₄. Male 5-week-old Hos:HR-1 hairless mice were subjected to a single percutaneous exposure or whole-body inhalation exposure of ca. 300 ppm arsine for 5 min. The examination was performed 0-6 hr after the exposure. Total arsenic in whole blood and hematocrit (Ht) values were measured. Generation of an arsenic-hemoglobin (As-Hb) adduct in the blood was detected using high-performance liquid chromatography with an inductively coupled plasma mass spectrometer (HPLC-ICP-MS). Ht values in the inhalation group significantly decreased after 3 hr, but those in the percutaneous exposure group did not. Total arsenic in the inhalation group was 9.0-14.2 mg/l, which was significantly higher than that in the percutaneous group. The As-Hb adduct was detected only in mice in the inhalation group. Histopathological changes were noted only in the inhalation group, with marked deposition of eosinophilic globules in the proximal convoluted tubules of the kidneys, the Kupffer cells of the liver, and the red pulp in the spleen, but not in the lungs. Immunohistochemically, these eosinophilic globules were stained positively by hemoglobin (Hb) antibody. In the present study, arsine-induced hemolysis and deposition of Hb occurred in the kidney via the inhalation route but not via percutaneous exposure. The presence of As-Hb adduct may be a useful indicator for confirming arsine poisoning.
authors.affiliation: Laboratory of Environmental Toxicology and Carcinogenesis, School of Pharmacy, Nihon University.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
authors.forename: Kenzo
authors.initials: K
authors.lastname: Yamanaka
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Shimoda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yamano
authors.forename: Kasuke
authors.initials: K
authors.lastname: Nagano
authors.forename: Akihisa
authors.initials: A
authors.lastname: Hata
authors.forename: Yoko
authors.initials: Y
authors.lastname: Endo
authors.forename: Mariko
authors.initials: M
authors.lastname: Tachikawa
authors.forename: Ginji
authors.initials: G
authors.lastname: Endo
mesh_terms: D000280:Administration, Inhalation; D000287:Administration, Topical; D000818:Animals; D001151:Arsenic / Q000378:metabolism; D020261:Arsenic Poisoning / Q000175:diagnosis; D001152:Arsenicals / Q000008:administration & dosage* / Q000009:adverse effects* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003594:Cytoplasmic Granules / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology / Q000378:metabolism; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism*; D006461:Hemolysis / Q000187:drug effects; D007684:Kidney Tubules / Q000378:metabolism*; D007728:Kupffer Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D012869:Skin Absorption; D013154:Spleen / Q000378:metabolism
chemical_list: D001152:Arsenicals; D015415:Biomarkers; D006454:Hemoglobins; D001151:Arsenic; C006633:arsine