Arsenic - Toxicology of Metals - page 387

10 ARSINE

by blockage of the renal tubules by hemoglobin casts
seems to be the cause of death (Fowler and Weissberg,
1974). Residual functional impairment of the kidneys
has been reported in one person after an acute episode
of arsine poisoning (Muehrcke and Pirani, 1968).
The use of BAL for arsine poisoning has not had
desirable results. Symptomatic therapy, which is gen-
erally used, is considered more reliable, particularly
in the treatment of anuria. Blood transfusions may be
necessary for severe anemia. Arsine toxicity and treat-
ment have been reviewed extensively by Fowler and
Weissberg (1974).
The mechanisms of arsine gas toxicity and more
recent studies in experimental animal/ in vitro model
systems have also been studied over the last 20 years
primarily because of possible health effects related to
its use in the semiconductor industry.
Arsine is used in doping the silicon-based chips
and in producing III-semiconductors, such as GaAs
and InAs. Before the recent uses of arsine gas in the
semiconductor industry, the main concerns regarding
human health were related to its use as a war gas and
from industrial accidents (Fowler and Weisberg, 1974).
In the past, the chief clinical effects observed in persons
with acute occupational arsine exposure were mas-
sive hemolysis followed by death from renal failure.
Patients typically presented with decreased hematocrit
values and red “port wine”-colored urine because of
the presence of hemoglobin. Histopathological evalua-
tions of postmortem kidney samples demonstrated the
presence of renal tubular obstruction from hemoglobin
casts that resulted in renal failure. With the develop-
ment of renal dialysis, mortality from acute exposure
has been greatly reduced in recent decades (Fowler
and Weisberg, 1974).

Arsine (hydrogen arsenide, AsH 3 ) is a color-
less, infl ammable gas with a slight garlic odor. It is
generated whenever nascent hydrogen is liberated in
material containing arsenic. Because arsenic is present
as an impurity in many metal ores, arsine may be gen-
erated in metal industries, nonferrous metal refi neries,
and in the manufacture of silicon steel, if the ores being
processed accidentally come into contact with acid.
Arsine may also be released when the hydrogen ion is
formed by hydrolysis and in the reaction of moisture
with arsenic-containing dross.
The toxicity and toxicological mechanisms of ars-
ine are quite different from those of other inorganic or
organic arsenic compounds. Arsine acts as a powerful
hemolytic poison in cases of both acute and chronic
exposure.
Henderson and Haggard (1943) observed that the
lethal dose of arsine for humans was 250 mg/m 3 for
30 minutes, and that symptoms of poisoning occur
after a few hours of exposure to 3-10 mg/m 3 . Elkins
(1959) reported a serious, nonfatal, acute case of arsine
poisoning in a person who had worked in an atmos-
phere contaminated with an average of 0.5 mg arsine/
m 3 . Five workers, examined by Kipling and Fothergill
(1964), developed typical arsine poisoning when work-
ing a plant where an acetylene-like odor was detected.
This odor occurred during the slag-dissolving process
that took place in a rotating drum. The concentration
of arsine in this factory was 5 mg/m 3 .
Morse and Setterlind (1950) studied two fatal cases
of arsine poisoning in which aluminum had been used
to extract arsenic. The concentration of arsine in this
instance was 70-300 mg/m 3 .
Arsine poisoning is characterized by nausea,
abdominal colic, vomiting, backache, and shortness
of breath, followed by dark blood urine and jaundice
(Kipling and Fothergill, 1964). According to Bulmer et
al . (1940), the following symptoms appeared after vari-
ous lengths of exposure to arsine: shortness of breath
on exertion, general malaise, nausea, poor appetite,
palpitation on exertion, and headache. In some groups
of workers, a tingling sensation in the feet, chills, gar-
lic breath, changes in complexion, weakness, vomit-
ing, and drowsiness were observed. Jaundice was also
noted in a number of people. Some of the workers with
the longest exposure had anemia. Arsenic in urine was
almost always elevated and ranged from 0.04-4.3 mg/
L. Even after the workers had left the arsine-contami-
nated area, arsenic in urine ranged from 0.04-0.1 mg/L.
Peripheral neuritis was seen in arsine-exposed workers
(Dudley, 1919). Liver disturbances may accompany ars-
ine poisoning. In most fatal cases, renal failure caused

10.1 Experimental Model Studies
Prolonged inhalation exposures of rodents to arsine
at sublethal lower doses (Blair et al ., 1990ab; Fowler
et al ., 1989; Hong et al ., 1989; Morrissey et al ., 1990;
Rosenthal et al ., 1989) have been shown to produce a
regenerative anemia with immature erythrocytes and
the presence of Howell-Jolley bodies in the peripheral
blood. Splenomegaly and the characteristic arseni-
cal-induced porphyrinuria (Woods and Fowler, 1978)
dominated by increased excretion of uroporphyrins
with lesser quantities of coproporphyrin (Fowler et
al ., 1989) are also major manifestations of arsine toxic-
ity to the hematopoietic system. Other effects include
alterations in immune system function that have been
noted in animals exposed to arsine for prolonged peri-
ods of time (Rosenthal et al ., 1989), indicating concomi-
tant perturbation of this important biological defense