Long Term Pulmonary Toxicity of Indium Arsenide and Indium Phosphide Instilled Intratracheally in Hamsters

Long Term Pulmonary Toxicity of Indium Arsenide and Indium Phosphide Insti l led Intratracheally in Hamsters: Koji YAMAZAKI, et al. Department of Hygiene, Graduate School of Medical Sciences, Kyushu University—We examined the long-term toxicological effects of III-V semiconductor particles on laboratory animals. Eight-week-old male Syrian golden hamsters were given 4 mg/kg indium arsenide (InAs) or 3 mg/kg indium phosphide (InP) particles, both containing 2.4 mg/kg as indium, intratracheally twice a week for 8 weeks. Control hamsters were given only a vehicle, phosphate buffer solution. Over a 2-yr period, these animals were euthanized serially and the biological effects were determined. Weight gain was significantly suppressed in both InAs and InP groups, compared to the control group, with greater suppression in the InAs group. The serum indium concentration in the InAs group was about twice as high as that in the InP group, in each period. Histopathologically, severe pulmonary inflammation and localized lesions with bronchioloalveolar cell hyperplasia were present in both InAs and InP groups from just after the last administration. The localized lesions gradually transformed to proteinosislike lesions with periodic acid Schiff reagent positive exudation after 16 wk. By means of immunostaining of proliferating cell nuclear antigen and argyrophilic proteins associated with nucleolar organizer regions staining, proliferative activities were evidenced in the localized lesions at each time and were noticeable in their early stage. K-ras, a known oncogene, was not mutated in association with these lesions. In conclusion, InAs and InP particles caused severe systemic toxicity and pulmonary localized hyperplastic lesions with proliferative activity were derived via the respiratory route. Neoplastic change was nil even in a Received Jan 18, 2000; Accepted March 14, 2000 Correspondence to: K. Yamazaki, Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3–1–1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan 2-yr observation period. (J Occup Health 2000; 42: 169–178)