Arsine hemolysis caused

B. Stibine, like arsine, may cause hemolysis. It is also an irritant gas. ii. Toxic dose... 

Systemic Toxicity. Systemic toxicity refers to toxicity manifest in biologic tissues other than the tissues of contact with the offending agent. Absorption, at a minimum, must occur for systemic toxicity to exist distribution, metabolism, and/or excretion may also be involved. An example of systemic toxicity in which only absorption is involved is the red blood cell breakage (hemolysis) caused by the hydride gas arsine this hemolysis and subsequent anemia affect the central nervous system, the liver, and the kidneys. For most systemic toxins, a threshold level of agent must be reached before toxicity is manifest this threshold often represents the capacity of the body s defense mechanisms. With two general exceptions. 

The hemolytic potential of arsine is considerable. Arsine at 0.1-0.5 mM may cause significant hemolysis (Hatelid et al. 1995 Pernis and Magistretti 1960). Inhalation exposure of mice to arsine at 9 ppm for only 1 h resulted in a statistically significant decrease in hematocrit levels at 24 h to 11 d after exposure (Peterson and Bhattacharyya 1985). The practical significance of this finding is demonstrated by a simple calculation provided by Klimecki and Carter (1995) showing an arsine concentration of 0.26 mM resulting from a 4-h exposure to arsine at a concentration of 30 ppm. This calculation assumed a minute alveolar... 

Arsine is the most acutely toxic form of arsenic. It binds with oxidized hemoglobin, causing profound hemolysis of sudden onset. Inhalation of 250ppm may be fatal within 30 minutes, whereas 10-50 ppm may cause anemia and death with more prolonged exposure. Human experience has indicated that there is usually a delay of 2-24 hours after exposure before the onset of headache, malaise, weakness, dizziness, and dyspnea, with abdominal pain, nausea, and vomiting. Dark red urine is frequently noted 4—6 hours after exposure. This often progresses to brown urine, with jaundice appearing at 24-48 hours after exposure. 

Arsine, the most toxic form of arsenic, exhibits some characteristics that may make it useful as a chemical warfare (CW) agent. Arsine is a colorless, odorless, nonirritating gas and is 2.5 times denser than air (Henriksson et al, 1996 Pullen-James and Woods, 2006 Thomas and Young, 2001). At concentrations above 0.5 ppm, a garlic-like odor may be noted, but arsine is toxic at much lower concentrations. Acute arsine poisoning due to inhalation of arsine gas (AsHs) is rare but has no known antidote. It is the most acutely toxic form of arsenic causing rapid and severe hemolysis immediately on exposure. The mechanisms of hemolysis are not completely understood. Arsine has a short half-life (27-96 h) and is converted to various arsenic derivatives. Although it... 

Bone marrow depression, anemia, leukopenia, and basophilic stippling are associated with chronic arsenic exposure. Arsine (AsHj) poisoning can produce widespread hemolysis. Cirrhosis, ascites, and destruction of renal tissues have been reported. Arsine exposure may also cause renal failure (Forth et al. 1996). 

Arsine gas Arsine gas (AsH ) is formed during the refinement and processing of certain metals and is used in the semiconductor industry it is an occupational hazard. Arsine causes a unique form of toxicity characterized by massive hemolysis. Pigment overload from red cell breakdown may cause renal failure. Treatment is supportive. 

I. Mechanism of toxicity. Arsine is a potent hemolytic agent. Recent investigations suggest that hemolysis occurs en arsine interacts with heme to fomi a reactive intermediate that alters transmembrane ion flux and greatly increases intracellular calcium. Note Arsenite and other oxidized fomis 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. 

Arsine gas is a potent cause of massive hemolysis. It is of industrial importance in microelectronics manufacturing. 

FIGURE 15.1 Schematic diagram showing hemolytic activity of arsine. Figure shows that arsine reacts with the suifhydryi group of Na+K+-ATPase, leading to the impairment in the sodium-potassium pump which subsequently causes red cell swelling and hemolysis. 

Long-term exposure may cause symptoms similar to those observed in acutely poisoned individuals. The main differences from acute poisoning were in a delay in onset and development of peripheral neuritis, development of gastrointestinal track involvement, and development of hemolysis and renal impairment. Lowered hemoglobin levels were foxmd in zinc ore smelting workers exposed to arsine for long periods and who had urinary arsenic concentration less than 0.2mg/L (Watson and Griffin, 1992). 

Complications include hemolytic anemia, renal failure, hyperkalemia, and death. Overwhelming exposures cause rapid death from massive hemolysis. Most deaths occur from renal failure in patients who survive acute exposure. Patients surviving acute arsine exposiue may develop chronic arsenic toxicity, including anemia and peripheral neuropathy. 

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