Review of Inhalants - ARCHIVES - National Institute on Drug Abuse

1961). The threshold limit value for industrial exposures in the
United States was set at 100 ppm (Criteria Document, 1975). It
was felt that this standard would protect against minimal irritation
or depressant effects which might impair attention, judgment, or
perception.
Results <strong>of</strong> inhalation studies <strong>of</strong> the relative acute toxicity <strong>of</strong> the
isomers <strong>of</strong> xylene and related solvents, such as toluene and
benzene) are conflicting. Consideration <strong>of</strong> the reports leads one
to conclude, however, that each is <strong>of</strong> the same order <strong>of</strong> acute
toxicity. Individual isomers (Cameron et al., 1938) are seemingly
equivalent in narcotic potency/acute toxicity with mixed xylene
vapors (Carpenter et al., 1975). Carpenter and coworkers report
the 4-hour LC 50 for rats to be 6,700 ppm, and the LT 50 at 11,000
ppm to he 92 minutes. Prostration <strong>of</strong> the animals was Seen within
20 minutes at the 11,000 ppm level.
Metabolism
Upon systemic absorption, xylene is metabolized primarily to toluic
acid. Bray et al. (1949) demonstrated in rabbits that from 60 to
88 percent <strong>of</strong> the three isomers were oxidized to their corresponding
toluic acids, with formation <strong>of</strong> xylenols a relatively minor
pathway. These findings are confirmed in later studies in
rabbits, rats, and guinea pigs (Fabre et al., 1960; Bakke and
Scheline, 1970) and in humans (Ogata et al., 1970). Ogata and
coworkers state that m- and p-xylene are metabolized in man
principally to m- and p-hippuric. acid, which can be readily
quantitated in the urine. The rapidity <strong>of</strong> formation and excretion
<strong>of</strong> these relatively nontoxic metabolites, coupled with the small
amounts <strong>of</strong> phenolics produced, is believed responsible for the low
degree <strong>of</strong> systemic toxicity usually seen upon xylene exposure.
Organ Toxicity
Systemic toxicity has been attributed on occasion to xylene inhalation
Although early investigators believed that xylene shared
myelotoxic properties with benzene, more recent studies (Speck
and Moeschlin, 1968; Jenkins et al., 1970; Carpenter et al., 1975)
indicate that xylene uncontaminated with benzene does not exert
myelotoxicity Toxicity to the cardiovascular (Hirsch, 1932;
Sikora and Gala, 1957), female reproductive (Michon, 1965), and
skeletal (Kucera, 1968) systems has been reported in humans, but
not substantiated. Liver and/or kidney damage was diagnosed in
workers exposed to xylene (Ghislandi and Fabiani, 1957; Joyner
and Pegues, 1961; Morley et al., 1970). Fabre et al. (1960) saw
histopathologic evidence <strong>of</strong> renal injury in rats and rabbits subjected
to mixed xylene vapors for up to 130 days, though Jenkins
et al. (1970) and Carpenter et al. (1975) could not detect
hepatorenal damage in several species <strong>of</strong> animals tested comparably.
The absence <strong>of</strong> toxicity in these latter two studies may be
attributahle to an insufficient xylene exposure level. DiVincenzo
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