Arsine Toxic effect

Arsine is extremely toxic and a potent hemolytic agent, ultimately causing death via renal failure. Numerous human case reports are available, but these reports lack definitive quantitative exposure data. The reports, however, affirm the extreme toxicity and latency period for the toxic effects of arsine in humans. 

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. 

A case report of acute arsine poisoning in which a 27-y-old man was exposed to arsine during chemical manufacturing was reported by Pinto (1976). The subject was exposed to arsine as a result of arsine production via a reaction between a galvanized bucket and an arsenic-containing sulfuric acid solution. The exposure (duration not specified) produced toxic effects characterized by abdominal cramping, thoracic discomfort, and hematuria. Over the next week, the patient s hematocrit declined from 42.5 to 27.1 and hemoglobin dropped from 14.1 to 9.5 g/dL even with medical intervention (blood transfusions and mannitol diuresis). Nine hours after exposure, blood arsenic was 159 g/dL and urinary arsenic was 1862 ug/L. 

The occupational exposure of five workers to arsine was reported by Phoon et al. (1984). All cases involved hematuria and, except for one patient, abdominal pain and jaundice. One worker was exposed for approximately 1 3/4 h, while the others were exposed for approximately 2 1/4 h. The latency in appearance of toxic effects was unusually short U-3 h). The following day, the arsine level in the workers breathing zone was 0.055 mg/m3 (0.017 ppm), although no processing of arsenic-containing material was taking place at the time of measurement. It was hypothesized by the report authors that the arsine... 

RTECS (Registry of Toxic Effects of Chemical Substances). 1987. Arsine. DHHS (NIOSH) Publ. No. 87-114. National Institute for Occupational Safety and Health, Cincinnati, OH. P. 159. 

NOTE The following analysis served as an initial estimate for the AEGL-1. However, it is believed that it is not appropriate to derive AEGL-1 values for arsine because of the steep dose-response and the inability of available data to justify an exposure that would result in little or no toxic effect. 

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. 

Caution Arsine is a flammable and highly toxic gas that does not provide adequate warning of hazardous levels. Inhalation is the major route of arsine exposure, although there is little information about absorption through the skin or toxic effects on the skin or eyes. Contact with liquid arsine may result in frostbite. 

Field First Aid Evacuate the Hot Zone at once when there is any release of arsine consider any victims who may have inhaled arsine to have suffered a potentially toxic dose. Although small amounts of arsine can be trapped in the victim s clothing or hair, these quantities are not likely to cause a danger for first response personnel outside the Hot Zone. Toxic effects could be delayed for up to two to twenty-four hours after exposure arsine exposure victims should all be evaluated at a medical facility. There is no specific antidote for arsine treatment is symptomatic and consists of actions to support respiratory, vascular, and renal functions. 

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. 

The main chronic toxic effect in animals exposed to arsine for 28-90 days is in the hematopoietic system, including a decrease in packed erythrocyte volume and a peripheral erythrocyte regenerative response. The reproductive and developmental toxicity has not been completely studied. Rats exposed to 2.5 ppm arsine 6 h day on gestation days 6-15 exhibited an increase in fetal body weight. 

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). 

Blood agents Also known as cyanogens, they include arsine (SA), cyanogen chloride (CK), and hydrogen chloride (AC), and are transported in the bloodstream through the body. Blood agents do not typically affect the blood but may interrupt the production of blood components and cause toxic effect at the cellular level. 

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