Comparative Potency Method for Cancer Risk Assessment: Application to Diesel Particulate Emissions¹

Abstract

An estimation of the human lung cancer “unit risk” from diesel engine particulate emissions has been made using a comparative potency approach. This approach involves evaluating the tumorigenic and mutagenic potencies of the particulates from four diesel and one gasoline engine in relation to other combustion and pyrolysis products (coke oven, roofing tar, and cigarette smoke) that cause lung cancer in humans. The unit cancer risk is predicated on the linear nonthreshold extrapolation model and is the individual lifetime excess lung cancer risk from continuous exposure to 1 μg carcinogen per m3 inhaled air. The human lung cancer unit risks obtained from the epidemiologic data for coke oven workers, roofing tar applicators, and cigarette smokers were, respectively, 9.3 × 10−4, 3.6 × 10−4, and 2.2 × 10−6 per μg particulate organics per m3 air. The comparative potencies of these three materials and the diesel and gasoline engine exhaust particulates (as organic extracts) were evaluated by in vivo tumorigenicity bioassays involving skin initiation and skin carcinogenicity in SENCAR mice and by the in vitro bioassays that proved suitable for this analysis: Ames Salmonella microsome bioassay, L5178Y mouse lymphoma cell mutagenesis bioassay, and sister chromatid exchange bioassay in Chinese hamster ovary cells. The relative potencies of the coke oven, roofing tar, and cigarette smoke emissions, as determined by the mouse skin initiation assay, were within a factor of 2 of those determined using the epidemiologic data. The relative potencies, from the in vitro bioassays as compared to the human data, were similar for coke oven and roofing tar, but for the cigarette smoke condensate the in vitro tests predicted a higher relative potency. The mouse skin initiation bioassay was used to determine the unit lung cancer risk for the most potent of the diesel emissions. Based on comparisons with coke oven, roofing tar, and cigarette smoke, the unit cancer risk averaged 4.4 × 10−4. The unit lung cancer risks for the other, less potent motor‐vehicle emissions were determined from their comparative potencies relative to the most potent diesel using three in vitro bioassays. There was a high correlation between the in vitro and in vivo bioassays in their responses to the engine exhaust particulate extracts. The unit lung cancer risk per μg particulates per m3 for the automotive diesel and gasoline exhaust particulates ranged from 0.20 × 10−4 to 0.60 × 10−4; that for the heavy‐duty diesel engine was 0.02 × 10−4. These unit risks provide the basis for a future assessment of human lung cancer risks when combined with human population exposure to automotive emissions.

Tracing the Sources of Indoor Aerosols Using Evolved Gas Analysis

“…Indoor combustion sources can substantially increase the indoor concentrations of particulate organic matter and its mutagenic activity (Lofroth et al, 1983, Traynor et al, 1983, Lewtas et al, 1987, Daisey et al, 1989. Both the chemical composition and the biological activity of particles vary, depending upon their sources (Albert et al, 1983), and their health impacts are also expected to differ. Thus, it *To whom correspondence should be addressed.…”

On cancer risk estimation of urban air pollution

“…Lewtas et al (22,23) applied the principle for risk estimation of particulate organic matter (POM) from automotive engine exhausts and from other combustion processes, using the epidemiologically established coefficients for lung cancer risk in coke oven topside work as reference standard. The bioassay systems they used comprised a data base ofseveral tests including tumor initiation by painting mouse skin with the methylene chloride (CH2C12) extracts to be compared.…”

Detection and comparison of DNA adducts after in vitro and in vivo diesel emission exposures.

“…The metabolites were eluted from the column using 10 Diesel Modified-CalfThymus DNA. Preparation of the diesel particle extracts used in the study have been previously described (5). To obtain oxidative metabolites, CT DNA (1 mg of a 2-mg/mL DNA solution) was modified with diesel combustion particle extract (100 ug/mL), and rat liver S9 (0.5 mg/mL) under aerobic conditions for 1.5 hr at 37 'C.…”