Comparative pulmonary toxicity of gallium arsenide, gallium(III) oxide, or arsenic(III) oxide intratracheally instilled into rats.
The relative toxicity of gallium arsenide (GaAs) and its metal oxides was assessed by intratracheally instilling particulate suspensions of GaAs (100 mg/kg), equimolar gallium as Ga2O3 (65 mg/kg), or a maximally tolerated nonlethal dose of arsenic as As2O3 (17 mg/kg). Two weeks after dosing, five rats from each group were randomly selected for the biochemical determination of lung lipid, protein, DNA, and collagen (4-hydroxyproline; 4-HP) content. The pulmonary retention of gallium and/or arsenic and the concentration of these metals in blood were also determined. Lungs from the remaining rats (n = 3) were examined histopathologically. Pulmonary exposure to Ga2O3 particulates significantly (p less than 0.05) increased the total lipid content of lungs relative to that observed in the vehicle-treated control animals. This response appeared to be associated with the pulmonary retention of gallium particulates (means = 36% of the gallium dose). In contrast, As2O3 particulates were not retained in the lung. Blood arsenic concentrations were 36 ppm which represented 20% of the total arsenic administered. Treatment with As2O3 significantly elevated lung dry weight as well as protein, DNA, and 4-HP content. These data suggest that As2O3 induced an acute fibrogenic response. The intratracheal instillation of GaAs particulates produced effects similar to those observed with the individual oxides. The total lung content of lipids, protein, and DNA was significantly elevated. These biochemical changes were accompanied by significant increases in lung dry weight and lung wet weight. Lungs from rats receiving GaAs particulates retained 44% of the dose as gallium and 28% of the dose as arsenic at the end of the 14-day study. Blood arsenic concentrations were 44 ppm (7% of the arsenic dose) while gallium was not detected in blood at this time. The primary histopathological observations 14 days after the intratracheal instillation of all metal particulates were an inflammatory response and pneumonocyte hyperplasia. The biological severity of these lesions, in descending order, was GaAs greater than As2O3 much greater than Ga2O3. It must be noted, however, that As2O3 was dosed at 0.25 X moles of GaAs.
D000704:Analysis of Variance; D000818:Animals; D001151:Arsenic / Q000032:analysis / Q000097:blood / Q000633:toxicity*; D000077237:Arsenic Trioxide; D001152:Arsenicals; D005708:Gallium / Q000032:analysis / Q000097:blood / Q000633:toxicity*; D007442:Intubation, Intratracheal; D008168:Lung / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010087:Oxides; D051381:Rats; D011916:Rats, Inbred F344
D001152:Arsenicals; D010087:Oxides; C043055:gallium arsenide; C038863:gallium oxide; D005708:Gallium; D001151:Arsenic; D000077237:Arsenic Trioxide