Other systemic effects have also been seen. Those effects, such as hemodynamic effects, increased the risk of heart attack and stroke and effects on hematopoiesis are thought to be secondary to the lung injury seen (EPA 2003a).

One component of PM that might provide some biologic plausibility for its toxic effects is PAHs. As discussed earlier, reactive epoxide intermediates can form in the metabolism of PAHs; the intermediates are genotoxic and could lead to carcinogenicity. Schulte et al. (1994) saw an increase in all lung tumors and a dose-dependent increase in malignant tumors in mice exposed to PAH-enriched exhaust containing benzo[a]pyrene at 0.05 or 0.09 mg/m3. Tumors of the nasal cavity, pharynx, larynx, and trachea were seen in a dose-dependent manner in hamsters exposed to benzo[a]pyrene at 9.5 or 46.5 mg/m3 for 109 weeks, but no lung tumors were seen in those animals (Thyssen et al. 1981). No effects were seen in the lungs, nose, and kidneys of Fischer rats exposed by nose to an aerosol of benzo[a]pyrene at 7.7 mg/m3 for 2 hr/day 5 days/week for 4 weeks (Wolff et al. 1989).

Skin disorders have been seen in animals after dermal exposure to PAHs. In an early study, suppression of sebaceous glands was seen in Swiss mice treated with benzo[a]pyrene, benz[a]anthracene, and dibenz[a,h]anthracene, but no controls were used (Bock and Mund 1958). Increased cell proliferation and inflammation were seen after exposure to a single treatment of 16, 32, or 64 µg once a week for 29 weeks (Albert et al. 1991). There is also evidence that PAHs are photosensitizers in mice, but that effect appears to be reversible (Forbes et al. 1976) and there is evidence of skin carcinogenicity in animals treated dermally with PAHs; a number of studies showed that intermediate exposure to PAHs produces skin tumors (ATSDR 1995d).


Because of variations in genetic makeup, a genetically susceptible person will exhibit responses to a hydrocarbon fuel or to combustion products different from those of most persons exposed to an identical dose.

Little has been documented about specific differences in genetic susceptibility to hydrocarbon fuels and their components, but exploration of the human genome promises advances in the near future. Some information suggests that people with an erythrocyte glucose-6-phosphate dehydrogenase deficiency may have increased susceptibility to the hemolytic effects of naphthalene (ATSDR 1999b). People with aryl hydrocarbon hydroxylase that is particularly susceptible to induction and people with genetic diseases associated with DNA-repair deficiencies (such as Down syndrome and familial retinoblastoma) may be particularly susceptible to the carcinogenic effects of PAHs (ATSDR 1999b).

Little is known also about specific differences in genetic susceptibility with respect to combustion products. Some components of combustion products are metabolized to active metabolites, which are later detoxified. Differences in the activity of the enzymes involved in those toxification and detoxification pathways can alter a person’s susceptibility to combustion-product components. For example, increased formation of the epoxide intermediates by increased activity of p450 enzymes that activate PAHs would increase a person’s susceptibility to PAHs, whereas increased activity of epoxide hydrolase, which detoxifies epoxide metabolites, would protect against the toxicity of PAHs (Klaassen 2001). In addition to altered susceptibility resulting from enzyme activity, whether genetic or by induction of enzymes by coexposure to other compounds, people could have altered susceptibility to combustion products because of

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