Mutagenic and carcinogenic potency of extracts of diesel and related environmental emissions: Study design, sample generation, collection, and preparation

Lewtas, Joellen; Bradow, Ronald L.; Jungers, Robert H.; Harris, B.D.; Zweidinger, Roy B.; Cushing, K.M.; Gill, Brad; Albert, Roy E.

doi:10.1016/0160-4120(81)90087-8

Cited by 36 publications

(16 citation statements)

References 4 publications

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“…A solvent exchange method, which has been used extensively in petroleum diesel exhaust research [16,[19][20][21] was used to prepare aqueous solutions of the biodiesel and diesel PM extracts. Each DCM particle extract had a reported concentration (μg PM eq/ml DCM), which was needed to calculate the stock concentration and the serial dilutions for the exposure doses.…”

Section: Aqueous Preparation Of Organic Biodiesel and Diesel Pm Extractsmentioning

confidence: 99%

Release of the Pro-Inflammatory Markers by BEAS-2B Cells Following In Vitro Exposure to Biodiesel Extracts

Swanson¹,

Kado²,

Funk³

et al. 2009

TOTOXIJ

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Biodiesel, an alkyl ester of plant oils that can be used in an unmodified diesel engine, is the first renewable diesel fuel alternative to become a commercially accepted part of our nation's energy infrastructure. For traditional diesel fuel exhaust, it has been demonstrated that the particulate matter (PM) organic components play a role in acute inflammatory reactions. However, there have been only a few cytotoxicity and mutagenicity studies on biodiesel emissions. In this study, BEAS-2B cells, a transformed human airway epithelial cell line, were exposed in vitro to the PM organic extracts from Standard Reference Material (SRM) 1975, soy ethyl ester (SEE), soy methyl ester (SME), and petroleum diesel for 24 hours. This study demonstrated that the organic extracts of biodiesel PM in an aqueous solution can increase the release of pro-inflammatory cytokines IL-8 and IL-6 by respiratory epithelial cells. On a microgram PM equivalent per ml (μg PM eq/ml) basis, exposure to biodiesel extracts was associated with a greater release of IL-8 and IL-6 relative to organic extracts of two diesel PM samples. The dose range tested was not cytotoxic. It was also noted that the solvent exchange method, which was used to prepare the aqueous exposure doses, may not be appropriate for the investigation of biodiesel extracts, though it has been used extensively in petroleum diesel research. A valuable new finding from these experiments is that the soluble organic fraction (SOF) of biodiesel PM begins to elicit a cytokine response in BEAS-2B cells at an exposure lower than petroleum diesel PM extract (approximately 40 μg PM eq/ml). However, more research is required to better characterize the potency of the organic fraction of biodiesel compared to petroleum diesel.

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Section: Aqueous Preparation Of Organic Biodiesel and Diesel Pm Extractsmentioning

confidence: 99%

Release of the Pro-Inflammatory Markers by BEAS-2B Cells Following In Vitro Exposure to Biodiesel Extracts

Swanson¹,

Kado²,

Funk³

et al. 2009

TOTOXIJ

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“…Thus, the carcinogenic effect of diesel soot extracts on mouse skin by Kotin et al (1955) as identified many years ago (also found for household chimney soot and urban air condensates) and the bioassays of diesel soot extracts in bacteria and mammalian cells (Lewtas et al, 1981) showing mutagenic effects of the extracted organics are the only scientifically robust results that could make diesel exhaust an apparently very weak borderline carcinogen by chemical carcinogenesis. So far, however, this has not manifested itself in any other way but in those particular bioassays relying on extracts of diesel soot.…”

Section: Summary Of the Key Studies On Truck Driversmentioning

confidence: 91%

Revisiting Epidemiological Key Studies on Occupational Diesel Exhaust Exposure and Lung Cancer in Truck Drivers

Stöber

1998

Inhalation Toxicology

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Over the last 25 years, railroad workers and truck drivers occupationally probably exposed to diesel exhaust were investigated in numerous epidemiological studies for prevalence of lung cancer. A recent assessment of 21 of these studies, including 11 truck driver studies by the Health Effects Institute ( HEI, 1995), claimed that the studies showed consistently a lung cancer risk increase of 20 to 40% for the study subjects. The supposedly most reliable study of railroad workers in the United States is presently under serious dispute. With regard to the assessed truck driver studies, uncontemplated, incomplete, or incorrect reporting on more than half of the 11 truck driver investigations warranted a reanalysis of the original study results. The quality and power of the truck driver studies varied widely. Two older studies-one of them showing significant risk increases-were already rejected in 1981 by the National Research Council in the United States as being inadequate. Of 7 studies reporting nonsignificant results, 6 indicated increases and 1 showed a decrease of lung cancer risk. In 4 studies, no adjustment was made for the smoking habits of the study groups and their controls. The reported risk increases-two of them supposedly significant-could be due to the lack of smoking adjustment. Most of the studies compared the truck drivers to the general population, although the unusual working conditions of long-haul truck drivers effected an unhealthy way of life along the road that could easily be a stronger confounder in comparison to the general public than cigarette smoking. A study supposedly showing a significant relative risk of 2.3 was particularly poor with regard to correction of smoking habits and lack of information on potential exposure. In another study, the original investigators aggravated their results by using one-sided p-tests and 90% confidence intervals. At least two of the HEI analyses were flawed. One of the two better qualified hospital-based case-control studies shows a maximum likelihood odds ratio below 1.0. The HEI report, however, indicated an erroneous value in excess of 1.0, which incorrectly supports the HEI conclusion that the observed lung cancer increases of 20 to 40% are consistent. The other qualified study was an earlier, equivalent investigation where adjustment for cigarette smoking was incomplete and 1045

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“…The comparative potency method has been the focus of a major research effort initiated in 1979 to develop a new approach to assess cancer risk from complex mixtures of POM from diesel and gasoline vehicle exhaust (32). This approach has been used in research to improve the estimation ofhuman cancer risk when there are no human cancer data for the specific POM mixture being assessed but there are human cancer data for a similar POM mixture (33,34).…”

Section: Dose-response Assessment Using the Comparative Potency Approachmentioning

confidence: 99%

Complex Mixtures of Air Pollutants: Characterizing the Cancer Risk of Polycyclic Organic Matter

Lewtas¹

1993

Environmental Health Perspectives

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Complex mixtures of polMyclic organic matter (POM) are used to illustrate the scientific problems and issues associated with characterizing the comparative risk ofrelated complex nmxtures. Thecomplexity of mixtures in whichthe active components are not well characterized present special challenges, which include identifying the critical components of mixtures, their sources, and the appropriate biomarker(s) ofexposure and dose; developing the appropriate experimental models for dose-response assessment; species extrapolation; and developing a scientific basis for pedkicting from one mixture to another. Strategies for addressing these issues include bioassay-direced chemical characterization of bioactive components of complex mixtures, apportionment methods to determine the source of biological activity and risk, DNA adduct methods to determine tissue exposure and target dose of mixtures, and comparative approaches to determining the relative similarity, potency, and risk of complex mixtures. Epidemiological data are available for humans exposed to POM from coke ovens, coal roofing tar, coal smoke, aluminum smelters, and cigarette smoke. These emissions are characterized and compared to POM from automotive emissions (diesel and gasoline), woodstove emnissions, residential oil furnace emissions, and ambient air particles. The tumor potency and estimated cancer risks for these POM mixtures ranges over nearly three orders of magnitude.

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Mutagenic and carcinogenic potency of extracts of diesel and related environmental emissions: Study design, sample generation, collection, and preparation

Cited by 36 publications

References 4 publications

Release of the Pro-Inflammatory Markers by BEAS-2B Cells Following In Vitro Exposure to Biodiesel Extracts

Release of the Pro-Inflammatory Markers by BEAS-2B Cells Following In Vitro Exposure to Biodiesel Extracts

Revisiting Epidemiological Key Studies on Occupational Diesel Exhaust Exposure and Lung Cancer in Truck Drivers

Complex Mixtures of Air Pollutants: Characterizing the Cancer Risk of Polycyclic Organic Matter

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