Arsine toxicity

Based upon the available data, derivation of AEGL-1 values was considered inappropriate. The continuum of arsine-induced toxicity does not appear to include effects consistent with the AEGL-1 definition. The available human and animal data affirm that there is a very narrow margin between exposures that result in little or no signs or symptoms of toxicity and those that result in lethality. The mechanism of arsine toxicity (hemolysis that results in renal failure and death), and the fact that toxicity in humans and animals has been reported at concentrations at or below odor detection levels (-0.5 parts per million (ppm)) also support such a conclusion. The use of analytical detection limits (0.01 to 0.05 ppm) was considered as a basis for AEGL-1 values but was considered to be inconsistent with the AEGL-1 definition. 

Dubitski (1911) (as cited in Flury and Zernik 1931) noted that the dog was similar to the cat regarding arsine toxicity. Exposure to 10 ppm was without... 

Arsine toxicity data from acute and short-term inhalation exposures. Pp. 85-89 in Hazard Assessment and Control Technology in Semiconductor Manufacturing. American Conference of Governmental Industrial Hygienists. Chelsea, MI Lewis. 

Klimecki, W.T., and D.E.Carter. 1995. Arsine toxicity chemical and mechanistic implications. J. 

Reference The available human and animal data indicate that there is very little margin between seemingly inconsequential exposures and lethal exposures. The mechanism of arsine toxicity (hemolysis and subsequent renal failure) and the fact that toxicity has been demonstrated at or below the odor threshold justify the inappropriateness of AEGL-1 values for any exposure period. 

Uncertainty Factors/Rationale Total uncertainty factor 30 Interspecies 10—The 10-min LC50 value for the monkey was about 60% of the rat value and one-third the rabbit value. The mouse data were used to calculate the AEGL levels, because the data exhibited a good exposure-response relationship and the endpoint of decreased hematocrit levels can be considered a sensitive indicator of arsine toxicity. In addition, arsine has an extremely steep dose-response relationship, allowing little margin in exposure between no effects and lethality. 

Hatlelid, K.M., Brailsford, C., Carter, D.E. (1995). An in vitro model for arsine toxicity using isolated red blood cells. Fun-dam Appl. Toxicol. 25 302-6. 

The 10 min median lethal concentrations (LCsqs) reported in the literature for rats and rabbits are 120-210 and 200-300 ppm, respectively. The lethal effect of arsine is dependent on exposure concentration and duration. The rat LC50 at 0.5, 1 and 4-h exposures is 240, 178, and 45 ppm, respectively. Female rats have slightly greater mortality than males. The effects in animals include dyspnea, hematuria, dark material around the head or anogenital area, and pallor of ears and eyes. During necropsy the animals showed red, yellow, or orange fluid in the bladder, stomach, or intestine, and discoloration of the kidneys, lungs, and liver. Most of the available data come from experiments in rats however, some authors state that the rat is not a suitable model for arsine toxicity because of differences in arsenic methylation and excretion compared to humans. 

In vitro toxicity studies in the rat indicate that arsine toxicity is tissue-specific. Red blood cells are very susceptible to arsine toxicity, followed by the primary hepatocytes and renal cortical epithelial cells. In blood arsine is the only factor responsible for hemolysis whereas in other tissues it is only responsible for the early signs of toxicity. At later points the toxicity effect is a combination of many other factors, including formation of inorganic arsenicals and hemolysate (kidney toxicity). 

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