A. studies have been initiated to evaluate the prechronic toxicity of arsine gas via inhalation. Fischer 344 rats, B6C3F1 and C57BL/6 mice, and golden hamsters will be exposed to arsine gas at concentrations of between 10-5000 ppb for 14 or 90 days. The animals are being evaluated by a number of ultrastructural/biochemical/teratological/teratological criteria for evidence of toxicity following prolonged exposure to tolerated doses of this gas alone or in combination with GaAs particles administered via intratracheal instillation. These studies are in progress. B. Intratracheal administration of GaAs to CD-1 rats has been found to produce marked inhibition of Delta-aminolevulinic acid dehydratase (ALAD) in blood and to a lesser extent in liver and kidney with resultant increases in the urinary excretion of aminolevulinic acid (ALA). In vitro studies showed that ALAD is highly sensitive to gallium and appears to be primarily responsible for the in vivo inhibition of this enzyme since inorganic arsenicals were without effect except at high concentrations. The mechanism of gallium inhibition of this enzyme appears to involve zinc displacement from the enzyme. The data suggest that measurement of urinary ALA in combination with assays of blood ALAD activity may provide one approach to the development of early biological indicators for workers exposed to this binary chemical compound.
