Health Effects of Exposure to Diesel Engine Emissions: A Summary of Animal Studies Conducted by the U.S. Environmental Protection Agency's Health Effects Research Laboratories at Cincinnati, Ohio

Pepelko, William E.; Peirano, W.B.

doi:10.3109/10915818309141011

Cited by 35 publications

(13 citation statements)

References 49 publications

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“…An alternative lung tumor model based on A/J strain mice with a constitutively high spontaneous lung tumor rate did not confirm our results: DEE and an ETS surrogate at doses similar to the present study had no tumorigenic effect (Pepelko & Peirano, 1983;Witschi et al, 1995). However, at 20 times higher doses, an ETS surrogate (whole smoke as well as gas phase) and MS exposure led to increased lung tumor multiplicity (Curtin et al, 2004;Stinn et al, 2005;Witschi et al, 2004).…”

Section: Discussioncontrasting

confidence: 76%

“…In addition, there is a considerable volume of published work on DEE inhalation encompassing varying experimental designs, experimental animals, exposure durations, and endpoints, including lung cancer (Brightwell et al, 1989;Heinrich et al, 1986Heinrich et al, , 1995Ishihara & Kagawa, 2002, 2003Mauderly et al, 1987Mauderly et al, , 1996Pepelko & Peirano, 1983;U.S. Department of Health and Human Services, 2002).…”

mentioning

confidence: 98%

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Chronic Nose-only Inhalation Study in Rats, comparing Room-aged Sidestream Cigarette Smoke and Diesel Engine Exhaust

Stinn

Teredesai

Anskeit

et al. 2005

Inhalation Toxicology

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Nose-only exposure of male and female Wistar rats to a surrogate for environmental tobacco smoke, termed room-aged sidestream smoke (RASS), to diesel engine exhaust (DEE), or to filtered, fresh air (sham) was performed 6 hours/day, 7 days/week for 2 years, followed by a 6-month post-exposure period. The particulate concentrations were 3 and 10 mg/m3. Markers of inflammation in bronchoalveolar lavage showed that DEE (but not RASS) produced a dose-related and persistent inflammatory response. Lung weights were increased markedly in the DEE (but not RASS) groups and did not decrease during the 6-month post-exposure period. Bulky lung DNA adducts increased in the RASS groups, but not in the DEE groups. Cell proliferation in the lungs was unaffected by either experimental treatment. Histopathological responses in the RASS groups were minimal and almost completely reversible; lung tumors were similar in number to those seen in the sham-exposed groups. Rats exposed to DEE showed a panoply of dose-related histopathological responses: largely irreversible and in some cases progressive. Malignant and multiple tumors were seen only in the DEE groups; after 30 months, the tumor incidence (predominantly bronchiolo-alveolar adenomas) was 2% in the sham-exposed groups, 5%in the high RASS groups, and 46% in the high DEE groups (sexes combined). Our results suggest that in rats exposed to DEE, but not to RASS, the following series of events occurs: particle deposition in lungs --> lung "overload" --> pulmonary inflammation --> tumorigenesis, without a significant modifying role of cell proliferation or DNA adduct formation.

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Section: Discussioncontrasting

confidence: 76%

mentioning

confidence: 98%

Chronic Nose-only Inhalation Study in Rats, comparing Room-aged Sidestream Cigarette Smoke and Diesel Engine Exhaust

Stinn

Teredesai

Anskeit

et al. 2005

Inhalation Toxicology

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“…The phenomenon of inhibited tumorigenesis of known A/J mouse carcinogens by concomitant inhalation has also been observed in other A/J inhalation carcinogenicity studies using irritant test materials, such as oxygen and ozone (Witschi, 1991), and by diesel engine exhaust as another example of a combustion aerosol (Pepelko & Peirano, 1983). Also, lung tumorigenesis by 3-methylcholanthrene was inhibited by ETSS (Witschi et al, 1997a).…”

Section: Discussionmentioning

confidence: 84%

Mechanisms Involved in A/J Mouse Lung Tumorigenesis Induced by Inhalation of an Environmental Tobacco Smoke Surrogate

Stinn

Teredesai

Kühl

et al. 2005

Inhalation Toxicology

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Lung tumors have been reproducibly induced in A/J mice exposed to a surrogate for experimental environmental tobacco smoke (ETSS) in a 5-mo inhalation period followed by 4 mo without further exposure. In order to increase our mechanistic understanding of this model, male mice were whole-body exposed for 6 h/d, 5 d/wk to ETSS with a particulate matter concentration of 100 mg/m(3). Food restriction regimens were included to model or exceed the ETSS-related impairment of body weight development. Half of the mice were pretreated with a single ip injection of urethane to study the effect of the above treatments on lung tumor development induced by this substance. At 5 mo, the tumor response was statistically the same for all groups of non-pretreated mice; however, the expected urethane-induced lung tumorigenesis was significantly inhibited by approximately 25% by ETSS and food restriction. This inhibition was accompanied by a threefold increase in blood corticosterone as a common stress marker for both ETSS and food restriction. At 9 mo, in mice not pretreated, the lung tumor incidence and multiplicity were significantly increased by twofold in the ETSS group; in the urethane-treated groups, the same high tumor multiplicity was reached regardless of previous treatment. The predominant tumor type in all groups was bronchiolo-alveolar adenoma. There was no induction of a specific K-ras mutation pattern by ETSS exposure. These data suggest a stress-induced inhibition of lung tumorigenesis in this model, explaining the need for the posttreatment period.

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“…This approach made substantial use of observations of the mutagenicity and shortterm predictors of carcinogenicity for extracts from diesel exhaust particles from both light-and heavy-duty engines, gasoline engine exhaust particles, and extracts of related known human carcinogens (cigarette smoke, roofing tar, and coke oven emissions) to estimate the carcinogenicity of diesel engine exhaust (Cuddihy et al, 1982;Albert, 1983). The animal studies conducted by the U.S. EPA have been reviewed elsewhere (Pepelko and Peirano, 1983).…”

Section: Historical Development Of Research On Carcinogenicity Of Engmentioning

confidence: 99%

Carcinogenicity Studies of Diesel Engine Exhausts in Laboratory Animals: A Review of Past Studies and a Discussion of Future Research Needs

Hesterberg¹,

Bunn²,

McClellan

et al. 2005

Critical Reviews in Toxicology

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Diesel engines play a vital role in world economy, especially in transportation. Exhaust from traditional diesel engines using high-sulfur fuel contains high concentrations of respirable carbonaceous particles with absorbed organic compounds. Recognition that some of these compounds are mutagenic has raised concern for the cancer-causing potential of diesel exhaust exposure. Extensive research addressing this issue has been conducted during the last three decades. This critical review is offered to facilitate an updated assessment of the carcinogenicity of diesel exhaust and to provide a rationale for future animal research of new diesel technology. Life-span bioassays in rats, mice, and Syrian hamsters demonstrated that chronic inhalation of high concentrations of diesel exhaust caused lung tumors in rats but not in mice or Syrian hamsters. In 1989, the International Agency for Research on Cancer (IARC) characterized the rat findings as "sufficient evidence of animal carcinogenicity," and, with "limited" evidence from epidemiological studies, classified diesel exhaust Category 2A, a "probable human carcinogen." Subsequent research has shown that similar chronic high concentration exposure to particulate matter generally considered innocuous (such as carbon black and titanium dioxide) also caused lung tumors in rats. Thus, in 2002, the U.S. Environmental Protection Agency (EPA) concluded that the findings in the rats should not be used to characterize the cancer hazard or quantify the cancer risk of diesel exhaust. Concurrent with the conduct of the health effects studies, progressively more stringent standards have been promulgated for diesel exhaust particles and NOx. Engine manufacturers have responded with new technology diesel (improved engines, fuel injection, fuels, lubricants, and exhaust treatments) to meet the standards. This review concludes with an outline of research to evaluate the health effects of the new technology, research that is consistent with recommendations included in the U.S. EPA 2002 health assessment document. When this research has been completed, it will be appropriate for IARC to evaluate the potential cancer hazard of the new technology diesel.

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Health Effects of Exposure to Diesel Engine Emissions: A Summary of Animal Studies Conducted by the U.S. Environmental Protection Agency's Health Effects Research Laboratories at Cincinnati, Ohio

Cited by 35 publications

References 49 publications

Chronic Nose-only Inhalation Study in Rats, comparing Room-aged Sidestream Cigarette Smoke and Diesel Engine Exhaust

Chronic Nose-only Inhalation Study in Rats, comparing Room-aged Sidestream Cigarette Smoke and Diesel Engine Exhaust

Mechanisms Involved in A/J Mouse Lung Tumorigenesis Induced by Inhalation of an Environmental Tobacco Smoke Surrogate

Carcinogenicity Studies of Diesel Engine Exhausts in Laboratory Animals: A Review of Past Studies and a Discussion of Future Research Needs

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