Air Pollution, the Automobile, and Public Health (1988) / Chapter Skim
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Health Effects of Aldehydes and Alcohols in Mobile Source Emissions
Health Effects of Aldehydes and Alcohols in Mobile Source Emissions
Pages 579-604
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(a) 1988 by the Health Effects Institute.
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From page 580... ...
Atmospheric Levels of Compounds Present in Mobile Source Emissions Compound Level % from Mobile Source Reference Carbon monoxide 5-13 ppm 70 Graedel, this volume Nitrogen oxides 20-30 ppb 50 Graedel, this volume Nonmethane hydrocarbons 1-2 ppmC 37 Graedel, this volume Sulfur dioxide 9 ppb <5 Graedel, this volume Formaldehyde 086 ppba 55-75 Grosjean (1982) Acetaldehyde 2-39 ppba 55-75 Hoshika (1977)
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These data suggest that mobile sources contribute sign111cantly to ambient concentrations. Estimates of the percentage contribution made by mobile emission sources to the levels of the various compounds are presented in table 1.
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Reports of the detection of phenols and catechols from mobile source emissions are extremely limited and usually do not provide quantitative information. As a result, knowledge of their levels in urban air and the contribution made by mobile sources is totally inadequate.
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a, ~ Recommendation 3. Chronic lowdose inhalation toxicology studies should be undertaken to determine if tissue damage occurs in response to exposure to levels of formaldehyde, acetaldehyde, and acrolein that are 10-100 times lower than their RDsos.
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~ Recommendation 4. A chronic inhalation toxicology study of acrolein should be undertaken in rats, with emphasis on .
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A chronic inhalation toxicology study of mixtures of formaldehyde and acrolein should be undertaken in rats and hamsters, with emphas~s on carc~nogen~c~ty. How one extrapolates the results of carcinogenicity studies in rodents to human exposure is uncertain.
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From page 586... ...
Experiments should be undertaken in cells cultured from various segments of the upper respiratory tract to determine the mechanisms by which aldehydes exert pathological changes such as toxicity, hyperplasia, ciliatoxicity, and so on. Such experiments should concentrate on identifying the critical targets for modification by each compound and the extent of modification that triggers the response.
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· Recommendation 7. A chronic inhalation toxicology study of methanol should be undertaken in rats and hamsters, with .
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Catechol has been identified as the major cocarcinogenic component of cigarette smoke (Van Duuren and Goldschmidt 1976; Hecht et al.
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The fact that a lag phase is observed before the onset of clinical symptoms of methanol toxicity, coupled with the findings that ethanol and alcohol dehydrogenase inhibitors antagonize methanol toxicity, suggests that a metabolite of methanol is responsible for its observed toxicologic effects. Alcohol dehydrogenase appears to be primarily responsible for the oxidation of methanol (McMartin et al.
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From page 590... ...
The half-life for conjugation of glutathione with 4-hydroxy-nonenal, a molecule structurally related to acrolein, is Aldehydes and Alcohols in Mobile Source Emissions approximately 4 sec in perfused rat heart (Ishikawa et al.
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On this basis, it is unlikely that one could ever detect increases in methanol inhalation resulting from exposure to mobile source emissions. Considering that formaldehyde is an intermediate in methanol and carbohydrate metabolism, one can extend this analysis to reach the conclusion that it is also impossible to detect inhalation exposure to formaldehyde by monitoring urinary levels of it or its initial metabolite formic acid.
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They may represent useful potential indicators of DNA damage in cells exposed to high concentrations of a,,~unsaturated aldehydes. It is interesting that cyclic adducts result from the reaction of cr,,l3 unsaturated aldehydes with DNA bases.
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The cellular targets for peroxyl radical reactions are unknown, but they epoxidize isolated double bonds and abstract hydrogen atoms from polyunsaturated fatty acid residues in phospholipids (Willson 1985)
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The stability and steric hindrance of phenoxyI radicals prevent them from abstracting hydrogen atoms from donors that will react with chaincarrying peroxyl radicals. Phenoxyl radicals couple to second molecules of peroxyl radical to form peroxycyclohexadienones.
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O b+o~ o to 11 rH \' (17) As discussed above, peroxyl radicals abstract hydrogen atoms from reactive molecules such as unsaturated fatty acids to initiate and propagate radical-chain oxidations.
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This does not seem a significant amount until one realizes that it is almost exclusively localized in the mucus and epithelial cells lining the upper respiratory tract. What is the starting point to be if one is to quantitate binding of aldehydes, alcohols, and phenols to critical intracellular targets for their toxic and carcinogenic effects?
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They exert toxicologic effects at concentrations approximately 10-100 times their ambient atmospheric levels. Variations in ambient levels have been reported with occasional toxicologically relevant concentrations reported in heavily polluted metropolitan areas.
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MEDIUM PRIORITY Recommendation 3 Chronic low-dose inhalation toxicology studies should be un dertaken to determine if tissue damage occurs in response to exposure to levels of formaldehyde, acetaldehyde, and acrolein that are 10-100 times lower than their RD50s. Recommendation 8 Attempts should be made to develop an initiation-promotion protocol for carcinogenesis testing of aldehydes and other compo nents of mobile source emissions.
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From page 599... ...
The techniques should then be applied to the detection of DNA adducts formed in target tissues after administration of carcino genic and subcarcingenic doses of the inhaled compounds. Detec tion of these adducts in cultured target cells would be a helpful intermediate step in adaption of the analytical methods to detection of in viva adducts.
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4:9~123. Aldehydes and Alcohols in Mobile Source Emissions Fassett, D
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1985. Cytotoxicity, thiol depletion, and inhibition of O6-methyl-guanine-DNA methyltransferase by various aldehydes in cultured human bronchial fibroblasts, Carcinogenesis 6:1755-1759.
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1985. Carcinogenicity of formalde Aldehydes and Alcohols in Mobile Source Emissions hyde and hydrogen chloride in rats, Toxicol.
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From page 603... ...
, pp. 41-72, Academic Press, New York.
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