Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants Volume 2 (1996) / Chapter Skim
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B11 2-Proponol
B11 2-Proponol
Pages 351-372
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From page 351... ...
Kaplan, Ph.D. Johnson Space Center Toxicology Group Biomedical Operations and Research Branch Houston, Texas PHYSICAL AND CHEMICAL PROPERTIES Isopropyl alcohol is a colorless, volatile liquid at room temperature (Rowe and McCollister, 19821.
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From page 352... ...
(Wax et al., 1949~. In four workers exposed at a mean concentration of 410 ppm, the alveolar air contained an average of only 100 ppm, whereas nine workers exposed at an average of 140 ppm had an alveolar air concentration of only 56 ppm (FolIand et al., 1976~.
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From page 353... ...
was found in the expired air of four workers exposed to {PA at an average of 410 ppm, and an acetone concentration of 7.5 ppm was found in nine workers exposed at an average of 140 ppm (Foliand et al., 19761. In another study involving 12 printing-plant workers exposed to TPA at 3-260 ppm for 7 h the elimination of acetone from the lungs reached a steady state in 6-7 h, suggesting that blood concentrations of TPA and acetone had also reached steady-state concentrations (Brugnone et al., 1983~.
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From page 354... ...
In contrast, pre-exposure of rats to 3amino-l,2,4-triazole, an inhibitor of catalase, did not result in blood alcohol or acetone concentrations that were different from concentrations in control animals (Nordmann et al., 1973~. TOXICITY SUMMARY Acute Toxicity Isopropyl alcohol vapor is irritating to the eyes and upper respiratory tract, and is a CNS depressant at higher concentrations.
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-C7 7 ~ ~_, An, ~ ~ Surviving animals recovered rapidly from the depressant effects completely returned to normal behavior. in another study, the oral LDso in young adult rats was 4.7 g/kg, and the first observable toxic signs were at a dose of 2.4 g/kg (Kimura et al., 1971~.
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From page 356... ...
There were also no significant changes in clinical chemistry measurements of blood or urine, BSP excretion, optical properties of the eyes, or the general welI-being of the subjects. Chronic Toxicity Rats exposed to IPA vapor at 8.4 ppm, 24 in/d, for 3 mo showed alterations in reflexes, enzyme activities, BSP retention, leukocyte count, total nucleic acids, urine coproporphyrin, and morphology of the Jung, liver, spleen, and CNS (Baykov et al., 19741.
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From page 357... ...
At 8000 ppm, there was an increase in liver enzymes, and liver and spleen weights were reduced. Using 8-h daily exposures, 5 d/w for 20 w, the authors found delayed transmission velocity in the tail peripheral nerve in rats exposed at 8000 ppm but not in rats exposed at 1000 ppm (Nakaseko et al., l991b)
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From page 358... ...
Pre-exposure of rats with TPA before intraperitoneally injected carbon tetrachIoride resulted in increased serum SGPT activity, hepatic triglyceride content, and total serum bilirubin and in decreased hepatic glucose-6-phosphatase activity (Traiger and Plaa, 19711. Suggested mechanisms for the potentiation include lysosomal alterations, changes in the endoplasmic reticulum, stimulation of drug-metabolizing enzymes, and increased sensitivity of hepatocytes to carbon tetrachIoride (Cote et al., 1974~.
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From page 359... ...
2-PROPANOL 3 5 9 In mice, pre-exposure with TPA or acetone by gavage potentiated the hepatotoxic response to chloroform, 1,1,2-trichIoroethane, and trichIoroethylene, as measured by serum SGPT activity, but not to I,l,1-trichIoroethane (Traiger and Plaa, 19741. In an industrial exposure of workers, toxic effects, including renal failure and hepatitis, were attributed to the potentiation of carbon tetrachIoride toxicity by {PA, following the inhalation of vapors of the two chemicals (Folland et al., 19761.
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360 Cal ._ Cal ._ x o m V)
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361 _ ~ ~ ~ ~ ~_ ~_ ~ _ :' ~ 0 ~5 ~ E E AO fib E ~_ ~ E , ~ s D 3 ~ ~ ~ ' .
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RATIONALE FOR ACCEPTABLE STANDARDS CNS depression should be of primary concern in setting SMAC values for IPA vapor; however, hepatotoxicity must also be considered because of early reports of fatty liver in mice (Weese, 1928) and liver enzyme elevation after prolonged exposures at high concentrations (Nakaseko et al., l991b)
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From page 363... ...
Guidelines from the National Research Council's Committee on Toxicology have been used to structure the rationale for astronaut exposure limits (NRC, 1984~. CNS Depression A combination of animal inhalation studies, structure-activity arguments, and human-worker studies were used to derive ACs to protect against CNS effects.
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From page 364... ...
These data indicate that any CNS effects would correlate with blood acetone concentrations rather than {PA concentrations. In 22 subjects exposed to acetone at 250 ppm, the blood concentrations after 4 h averaged 15 mg/L, and there were slight psychomotor performance decrements; however, at exposures to acetone at 125 ppm (plus methyl ethyl ketone at 100 ppm)
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From page 365... ...
= 100 ppm. Peripheral Nerve Damage Prolonged exposure of a total of 800 h induced decreases in peripheral nerve conduction velocity in rats exposed to TPA at 8000 ppm but not in those exposed at 1000 ppm (Nakaseko et al., 199lb)
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From page 366... ...
In addition, methods of measuring CNS effects in animals, and performance decrements in humans have improved considerably over the past 40 years. Hence, standardized inhalation studies in rodents, including a long-term, continuous-exposure study with multiple end-point assessments (to determine the accuracy of Baykov et al., 1974)
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367 .g 52: o 3 ~L a~ C~ ¢ C~ ~0 Ct ._ Ct cn S~ o ._ ~_ C~ o Cd C)
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From page 368... ...
1986. Mortality of workers on an isopropyl alcohol plant and two MEK dewaxing plants.
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1967. Potentiation of carbon tetrachloride toxicity by aliphatic alcohols.
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1945. Isopropyl alcohol: Acquired tolerance in dogs, rate of disappearance from the bloodstream in various species, and effects on successive generation of rats.
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From page 371... ...
1969. Effects on man of daily ingestion of small doses of isopropyl alcohol.
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