Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants Volume 3 (1996) / Chapter Skim
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B2: 1-Butanol
B2: 1-Butanol
Pages 53-77
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From page 53... ...
B2 I-Butanol John T James, Ph.D.
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After a 30min exposure at 100 or 200 ppm, the arterial blood concentrations were only 0.3 and 0.5 mg/kg (3 and 5 mg/dL) , respectively.
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These investigators reported that n-butylaldehyde was found in the serum as a metabolite. Likewise, male rats given 0.45 g/kg showed a maximum plasma concentration of 70 ,ug/mL (7 Meg/ after ~ h and undetectable concentrations after 4 h (DiVincenzo and Hamilton, 19791.
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Because the enzymes involved in metabolism of i-butanoi are similar to those involved in metabolism of ethanol, the kinetics of the oxidations can reasonably be expected to be qualitatively similar. In fact, isolated perfused rat livers have shown that both alcohols are oxidized according to zero-order kinetics above a certain concentration and ac
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From page 57... ...
(1943) reported that 3- to 5-min exposures of 10 test subjects resulted in mild irritation of nose and throat in the majority of test subjects exposed at 25 ppm and eye irritation in the majority of subjects exposed at 50 ppm, which was considered an "objectionable" concentration.
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exposed at concentrations ranging from 100 to 200 ppm concluded that eye irritation resulting in corneal inflammation, lacrimation, and photophobia were occasionally encountered in workers exposed at 200 ppm (Sterner et al., 1949~. Complaints of irritation in association with exposures at 100 ppm were "rare." Because both studies in workers seemed to use adequate analytical techniques, but were limited by subjective assessments of irritation end points, it is difficult to select one result over the other.
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mg/L and 15.3 mg/L, respectively. In a study of alcohol-induced hypothermia and decreased Rotorod performance in mice given a single oral dose, no effects were observed when blood concentrations were at or below 16 mug/.
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These reports are in contrast to a subchronic oral-exposure study conducted by Toxicology Research Laboratories in the late 1980s in which no adverse effects except ataxia were found in rats (TRL, 19861. Because the reported effects in the inhalation studies are so diverse and the primary issue is the quality of each study rather than the f~ndings, the studies will be discussed individually.
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study cited in the WHO report is a short-term human inhalation study involving iS subjects exposed at concentrations of 0.5 to 1.2 mg/m3 (see acute exposures section)
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Oral Exposures Although the continuous inhalation studies reported by the Russians are not directly comparable to the 13-w oral Savage study, there are striking contrasts in the details reported and the adverse effects found. The oral study involved 92-93 ~ of daily administration of I-butano!
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In the 92-d rat oral-exposure study, assuming an average body weight of I/3 kg, the dose delivered was 15,000 mg over the entire study. In the 120-d inhalation study, assuming a daily inhalation volume of 0.15 mild and an uptake of 50%, the cumulative amount delivered to rats exposed to the highest concentration was 360 ma.
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Only a few minor behavioral or neurochemical effects were reported in the offspring of female rats exposed at 3000 or 6000 ppm (7 hid) throughout gestation or to offspring of unexposed females mated to males that had been exposed at the same concentra
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. The same group reported that offspring of female Sprague-Dawley rats exposed at 8000, 6000, or 3500 ppm for 7 hid during gestational days ~ to 19 showed teratogenicity (rudimentary cervical ribs)
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66 A ._ ._ Cal a: C)
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Labor, 1995 TLV, Threshold Limit Value; PEL, permissible exposure limit. TABLE 2-3 Spacecraft Maximum Allowable Concentrations Exposure Concentration, Concentration, Duration ppm mg/m3 Target Toxicity 1 h 50 150 Eye irritation 24 h 25 80 Eye irritation 7 d 25 80 Eye irritation, systemic injury 30 d 25 80 Eye irritation, systemic injury 180 d 12 40 Systemic injury RATIONALE FOR ACCEPTABLE CONCENTRATIONS Acceptable concentrations (ACs)
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Unfortunately, no attempt was made in either study to take objective measurements of performance in the exposed workers. It is clear, however, from animal studies that narcosis or decrements in rotorod performance can be induced by inhalation or other routes of administration, but the findings were not appropriate to use for setting human exposure limits because of the severity of the end points.
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Long-Tenn Systemic Injury The 92-d oral-exposure rat data, even though it is not directly pertinent to continuous inhalation exposures, can be extrapolated to a human estimate (TRL, 1986~. For reasons discussed in the toxicity section, the Russian data were not used to set ACs.
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] -BUTANOL 7 1 Spaceflight Effects The toxic effects induced by I-butano!
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A short-term human inhalation study is needed to measure the irritation thresholds and uptake of the compound over several hours (at least) and to quantify performance decrements at higher concentrations of exposure.
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1983. Concentration-dependent behavioral changes in mice following short-term inhalation exposure to various industrial solvents.
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1989a. Lack of selective developmental toxicity of three butano!
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1992. Guidelines for Developing Spacecraft Maximum Allowable Concentrations for Space Station Contaminants.
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1960. Relative intoxicating effects on rats of ethyl, propy} and butyl alcohols.
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