ARSINE 791 



Indeed, it is well known that arsine can be fixed in blood in a nonvolatile 

 form and the formation of arsenite was shown over 100 years ago. When 

 rabbit blood is treated with arsine, 47-60% of the arsenic is found to be 

 nondialyzable, and when crystalline horse hemoglobin solutions are so 

 treated, 33-41% is nondialyzable (Graham et al., 1946). It was suggested 

 that the nondialyzable material consists of two fractions, one arsenite and 

 the other unknown. Arsine is quite unstable to light and heat, breaking 

 down into hydrogen and arsenic. The redox potential of the AsHgiAs couple 

 is Eq (pH = 7) = — 1.16 V and hence arsine is readily oxidized, a fact 

 which should be considered in biological work. The alkyl arsines are liquids 

 which are also readily oxidized to the corresponding arsine oxides. The 

 structure of arsine is similar to that of ammonia, and infrared data have 

 shown the bond angles to be 91 ^35' and the length of the As — H bonds 

 to be 1.52 A (Nielsen, 1952). 



The relationship between the effects of arsine and of the arsenicals pre- 

 viously discussed is complex. Arsine is one of the most toxic substances 

 and a few bubbles of the gas may be fatal. Concentrations of 0.04-0.05% 

 (about 2 X 10"^ mole/liter of air) in the inhaled air are toxic to animals 

 in several hours. In cats 8 X 10"® mole/liter inhaled leads to toxic symp- 

 toms and death in 12-20 hr; the total lethal dose may be around 7-10 mg. 

 The symptoms of poisoning depend on the rate at which it is introduced 

 into the body, and in chronic poisoning a large part of the effects may be 

 due to the arsenite formed from it. The acute effects are nausea, dizziness, 

 weakness, dyspnea, and loss of consciousness; later there may be oliguria, 

 cyanosis, icterus, reduced blood pressure, and variable central disturbances. 

 The chief effects seems to relate to the blood and the central nervous system. 

 Arsine alters the color of the blood and produces certain changes in the 

 hemoglobin, and extensive hemolysis may occur. Many of the symptoms 

 arise from the hypoxemia resulting from the rapid drop in erythrocytes, 

 which may occur within a few hours, as well as the changes in hemoglobin. 

 Furthermore, the renal damage results mainly from the reduction in avail- 

 able oxygen and the debris from hemolyzed erythrocytes. 



The mechanism of the hemolysis has been partially elucidated. Hemolysis 

 occurs in vitro but requires the presence of oxygen (Naunyn, 1868). Fixation 

 in a nonvolatile form in the blood is rapid and occurs only aerobically 

 (Meissner, 1913; Hughes and Levvy, 1947), preceding the hemolysis by 

 a brief period (Thauer, 1934). Hemoglobin is the only blood component 

 reacting readily with arsine (Meissner, 1913). There is no doubt that arsine 

 reacts with hemoglobin in the presence of oxygen catalytically to form a 

 product which is hemolytic, either directly or indirectly. The end product 

 seems to be arsenite (Eulenberg, 1865) and numerous workers have detected 

 its presence following exposure to arsine; in fact, the dialyzable fraction 

 after reaction in the blood is arsenite (Graham et al., 1946). Arsenite, how- 



