Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants Volume 3 (1996) / Chapter Skim
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B7: Ethanol
B7: Ethanol
Pages 171-207
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From page 171... ...
Synonym: Ethyl alcohol Formula: CH3CH2OH CAS number: 64-17-5 Molecular weight: 46.07 Boiling point: 78.5°C Melting point: Specific gravity: Vapor pressure: Solubility: Conversion factors: -~14.1°C 0.789 at 20°C 43 tort at 20°C Miscible with water and most organic solvents Ippm=l.~Smg/m3=0.0018Smg/L ~ mg/m3 = 0.531 ppm = 0.001 mg/L OCCURRENCE AND USE Ethanol is used as a fuel additive and in the manufacture of chemicals and medicines. It is used as a solvent in the manufacture of expio 171
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From page 172... ...
Orally ingested ethanol is absorbed rapidly from the gastrointestinal tract by simple diffusion; peak blood concentrations are reached in 0.5 to I.5 h after ingestion has ended. Food in the stomach delays gastric emptying and consequently delays the delivery of ethanol to the small intestine, where absorption is more rapid than it is in the stomach (Rail, 1990~.
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From page 173... ...
These inhalation models were developed to solve problems associated with variable blood alcohol concentrations after repeated oral or intravenous administrations. After the initial rise in blood ethanol concentration, continued inhalation of ethanol at a fixed concentration will result in gradually decreasing blood concentrations unless alcohol dehydrogenase (ADH)
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From page 174... ...
When exposures were conducted without an ADH inhibitor, the blood alcohol could be kept reasonably constant by doubling the exposure concentration progressively during the first 10 ~ of exposure. In rats exposed for 24 h at 28 mg/L, the blood concentration reached 340 mg/~L (0.34%~.
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From page 175... ...
Several investigators showed that the overall metabolic rate of an organism was not altered by ingestion of ethanol (Jacobsen, 1952~. Understanding of Ethanol Metabolism by 1950 investigations during the next half century resulted in much more detailed understanding of ethanol metabolism in experimental animals and humans.
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From page 176... ...
Starved animals have a lower rate of alcohol metabolism than well-fed animals. Long before 1950, investigators conducted studies using hepatectomized dogs, liver slices, and perfused livers to show that the liver was the predominant organ to metabolize ethanol.
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From page 177... ...
In addition, some of the early con cepts about ethanol metabolism, especially the degree of variability among individuals, have been corrected by new data. Genetic variations in the enzymes involved in ethanol metabolism control the immediate response to ingested ethanol; however, no studies could be found in which differences in susceptibility to inhaled ethanol were evaluated.
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From page 178... ...
is thought to be most important in oxidizing acetaldehyde, and because approximately 50% of the Japanese and Chinese lack an active form of this enzyme, they experience much higher blood acetaldehyde concentrations after ethanol ingestion (Bosron and Li, 1986~. It was suggested that Asian individuals who exhibit the "flush" reaction to ethanol have the highly active ADH2 and the deficient ALDH2 enzymes (Yoshida et al., 1983~.
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From page 179... ...
showed that the output of acetate from the splanchnic area was 50% to 100% of the ethanol disappearance rate (Lun~quist et al., 1962~; that result was confirmed in another human study (Tygstrup et al., 19651. TOXICITY SUMMARY The number of toxicity studies involving ethanol is enormous; however, the goal of this document is to provide a rationale for setting inhalation exposure limits.
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From page 180... ...
depression, and possibly a flush response in certain individuals. The first two effects have been demonstrated by inhalation exposure; however, the flush reaction has only been demonstrated by oral ingestion.
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From page 181... ...
The table shows that in mice, guinea pigs, and rats exposed for 7 to 10 h, the concentration x time needed to induce death is about 400 h mg/L. Quantifying the effect of inhaled ethanol on the human nervous system depends on correlating inhalation exposures with blood alcohol levels (BALs)
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From page 182... ...
In test subjects exposed to ethanol vapor, they reported an increased feeling of heat in the forehead and ears, warmth in the head and trunk, and fatigue. It is unlikely that any of the three subjects had flush responses, because only about 10% of Caucasians have them; however, because acetaldehyde mediates the response, it is plausible that during the high-concentration exposures, a
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From page 183... ...
Finally, it should be noted that liver injury is found in many of the inhalation models used to produce withdrawal effects in rodents. Such models use doses of pyrazole to maintain constant high blood concentrations of ethanol; however, the confounding effects of pyrazole preclude the conclusion that inhaled ethanol alone could induce hepatotoxicity (Goldstein, 1980~.
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From page 184... ...
More recent evidence suggests that ethanol acts as a cocarcinogen primarily by inducing cytochrome-P-450-dependent mixed-function oxidase systems that activate such carcinogens as benzofa~pyrene, nitrosamines, and aflatoxins. It is important to note that the induction of microsomal enzymes by orally ingested ethanol occurs in the lung as well as the intestine and liver (Lieber et al.,
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From page 185... ...
Despite the extensive studies of ethanol carcinogenesis, the findings do not tell us whether inhaled ethanol can act as a carcinogen or a cocarcinogen in the lung. Aside from the lung, it is very unlikely that inhaled ethanol would pose a significant cancer risk unless other symptoms of toxicity were present.
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From page 186... ...
Reproductive Toxicity Many experiments have demonstrated some degree of reproductive toxicity by ethanol (Gavaler and Van Thiel, 1987~; however, the doses used are typically 5% or more of the calories consumed or the liquid volume ingested. Such experiments may be pertinent to the human population consuming large quantities of alcoholic beverages, but the findings have little bearing on inhaled ethanol vapor.
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From page 187... ...
have stimulated research to define the concentrations of alcohol consumption that might cause the syndrome and to better characterize the many adverse effects that are associated with maternal alcohol consumption. Nearly all developmental toxicity studies of ethanol involve oral ingestion; however, a few inhalation studies of rodents have been reported in an effort to address concerns about occupational exposure to ethanol vapor.
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From page 188... ...
The response of the animal mode} depends on strain, dose of ethanol, and gestational age at which ethanol is administered. From rodent models, it appears that reduced body weights in offspring are one of the most sensitive indicators.
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From page 189... ...
Rats exposed to toluene at 2000 ppm (S hid for 2 w) and given 6% ethanol in drinking water showed reduced weight gain and abnormal clinical chemistry changes compared with toluene-exposed controls (Pryor et al., 19851.
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From page 192... ...
192 I Em V, ~ ,~ _ ~ o ~ _ Vat o ~ m m U
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From page 193... ...
Dept. of Labor, 1995 NIOSH's REL 1000 ACGIH, 1991 TLV, Threshold Limit Value; TWA, time-weighted average; PEL, permissible exposure limit; REL, recommended exposure limit TABLE 7-3 Spacecraft Maximum Allowable Concentrations , Exposure Concentration, Concentration, Duration ppm mg/m3 a Target Toxicity 1 h 2000 4000 CNS, flush response, irritation 24 h 2000 4000 CNS, flush response, irritation 7 db 1000 2000 Irritation, hepatotoxicity, CNS effects, flush response 30 d 1000 2000 Irritation, hepatotoxicity, CNS effects, flush response 180 d 1000 2000 Irritation, hepatotoxicity, CNS effects, flush response at mg/L = 1000 mg/m3.
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From page 194... ...
Neurotoxicity Estimating the inhaled concentration of ethanol that will not induce neurobehavioral or performance decrements involves the results of two studies. First, the observations of Loewy and von der Heide (1918)
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From page 195... ...
Eye pain was not reported by Loewy and von der Heide (1918) in subjects exposed at concentrations below Il.5 mg/L (average)
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From page 196... ...
ACs were not set for liver damage. Flush Response No studies have directly measured the dose-response or NOAEL in a population of people known to exhibit the flush response.
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From page 197... ...
~197 below the typical lowest dose of 0.3 mL/~ used to elicit s Ousb response. Hence, the 1-b ~ 24-b ACs were set ~ ~ -/L.
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198 Cat .o ad Cal ¢ .~ C: o C: _ O~ ¢ _ o ~ ce ·E~ Cd ~ C-.)
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From page 199... ...
1983. Odor as an aid to chemical safety: Odor thresholds compared with threshold limit values and volatilities for 214 industrial chemicals in air and water dilution.
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1986. Genetic polymorphism of human liver alcohol and acetaldehyde dehydrogenases and their relationship to alcohol metabolism and alcoholism.
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1980. Inhalation of ethanol vapor.
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1962. The effect of acute ethanol intoxication on chloroform-induced liver damage.
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von der Heide.
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1992. Guidelines for Developing Spacecraft Maximum Allowable Concentrations for Space Station Contaminants.
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1979. Long-term ethanol administration methods for rats: Advantages of inhalation over intubation or liquid diets.
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1966. Reproductive variables and alcohol consumption of the C57BL/Crg!
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From page 207... ...
ETHANOL 207 types of human aldehyde dehydrogenase ALDH2 locus.
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