Review of Inhalants - ARCHIVES - National Institute on Drug Abuse

humans and experimental animals (Browning, 1965; Snyder and
Kocsis, 1975). Modest, variable effects on body weight gain,
organ weight, and histology <strong>of</strong> the liver, kidney, spleen, and
testes were occasionally seen in rats, guinea pigs, and rabbits
subjected for 7 hours daily to benzene vapors for as long as 11
months (Wolf et al., 1956). Determinations <strong>of</strong> levels <strong>of</strong> various
serum enzymes have failed to reveal significant organ damage
upon chronic exposure <strong>of</strong> rats, guinea pigs, monkeys, and dogs
(Jenkins et al., 1970), and upon acute exposure <strong>of</strong> rats
(Wirtschafter and Cronyn, 1964) and guinea pigs (DiVincenzo and
Krasavage, 1974) to benzene.
Myelotoxicity. The most significant toxic action <strong>of</strong> benzene is
upon the blood-forming elements <strong>of</strong> the body. This toxic effect is
thought to be unique, in that simple alkyl substitution <strong>of</strong> the
benzene ring apparently negates myelotoxicity. Although susceptibility
and hematologic findings vary markedly among individuals
, classic benzene-induced abnormalities include anemia, leukopenia,
and thrombocytopenia. These alterations in the circulating
blood may also be elicited in a variety <strong>of</strong> animals, although leukopenia
appears here to be the most sensitive and consistent manifestation
<strong>of</strong> benzene exposure. Benzene is believed to produce
chromosomal abnormalities in humans and animals, as well as
induce leukemias in humans (Vigliani and Forni, 1976). It is
beyond the scope <strong>of</strong> the present. discussion to relate in detail the
majority <strong>of</strong> topics pertaining to benzene myelotoxicity . This
subject matter is reviewed in detail in a Criteria Document (1974)
and Snyder and Kocsis (1975).
A variety <strong>of</strong> factors have been considered as potentially important
in benzene myelotoxicity Shils and Goldwater (1949) found that
inadequate dietary protein intake by dogs and rats predisposed to
benzene-induced blood dyscrasias, raising the possibility <strong>of</strong>
altered formation, intracellular binding, and conjugation <strong>of</strong> toxic
metabolites. Although a history <strong>of</strong> infection preceding symptoms
<strong>of</strong> benzene poisoning has been recorded on occasion, it appears
more likely that. increased susceptibility to infection will result
from benzene-induced leukopenia. It has been widely held that
women are more prone to chronic benzene poisoning than are men,
and that. the young are more susceptible than adults. Animal
studies have been conducted which support this concept
(Hirokawa and Nomiyama, 1962; Ikeda, 1964; Nomiyama et al.,
1965). These age and sex differences in experimental animals
have generally been linked to differences in benzene metabolism.
The relationship <strong>of</strong> animal studies to man is quite tenuous, however,
since marked sex differences in chemical metabolism seen in
animals (e.g., rats) likely (10 not occur in humans. Although
certain epidemiologic studies and individual case reports have
supported the belief that sex and/or age are predisposing factors
in benzene myelotoxicity, sufficient numbers <strong>of</strong> findings to the
contrary have largely discounted this concept at present (Criteria
Document, 1974; Snyder and Kocsis, 1975). Nevertheless, marked
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