Arsine is a colorless hydride gas (AsH3) formed when arsenic comes in contact with hydrogen or with reducing agents in aqueous solution. Typically, exposure to arsine gas occurs in smelting operations or other industrial settings when arsenic-containing ores, alloys, or metallic objects come in contact with acidic (or occasionally alkaline) solutions and newly formed arsine is liberated. Arsine is also used as a dopant in the microelectronics industry.
Mechanism of toxicity. Arsine is a potent hemolytic agent. Recent investigations suggest that hemolysis occurs when arsine interacts with oxyheme in hemoglobin to form a reactive intermediate that alters transmembrane ion flux and greatly increases intracellular calcium. Note: Arsenite and other oxidized forms of arsenic do not cause hemolysis. Deposition of massive amounts of hemoglobin in the renal tubule can cause acute renal injury. Massive hemolysis also decreases systemic oxygen delivery and creates hypoxic stress, and arsine and/or its reaction products exert direct cytotoxic effects on multiple organs.
Toxic dose. Arsine is the most toxic form of arsenic. Acute exposure guideline levels (AEGLs) recently developed by the US Environmental Protection Agency and the National Research Council indicate that disabling effects (AEGL-2) may occur after 30 minutes of exposure to ≥0.21 ppm, 1 hour of exposure to ≥0.17 ppm, or 8 hours of exposure to ≥0.02 ppm. Lethal or life-threatening effects (AEGL-3) may occur from 30 minutes of exposure to ≥0.63 ppm, 4 hours of exposure to ≥0.13 ppm, or 8 hours of exposure to ≥0.06 ppm. The level considered by the National Institute for Occupational Safety and Health (NIOSH; 1994) as “immediately dangerous to life or health” (IDLH) is 3 ppm. The odor threshold of 0.5–1.0 ppm provides insufficient warning properties.
Acute effects. Because arsine gas is not acutely irritating, inhalation causes no immediate symptoms. Those exposed to high concentrations may sometimes detect a garlic-like odor, but more typically they are unaware of the presence of a significant exposure. In most industrial accidents involving arsine, the hazardous exposure occurred over the course of 30 minutes to a few hours.
After a latent period of 2–24 hours (depending on the intensity of exposure), massive hemolysis occurs, along with early symptoms that may include malaise, headache, fever or chills, and numbness or coldness in the extremities. There may be concomitant GI complaints of nausea, vomiting, and cramping pain in the abdomen, flank, or low back. In severe exposures, abrupt cardiovascular collapse and death may occur within 1 or 2 hours.
Hemoglobinuria imparts a dark, reddish color to the urine, and the skin may develop a copper, bronze, or “jaundiced” discoloration that may be attributable to elevated plasma hemoglobin.
Oliguria and acute renal failure often occur 1–3 days after exposure and are a major aspect of arsine-related morbidity.
A minority of patients may develop agitation and delirium within 1–2 days of presentation.
Chronic arsine poisoning, a rarely reported condition, has been associated with headache, weakness, shortness of breath, nausea, vomiting, and anemia.
Diagnosis. Arsine poisoning ...