title: Bioassay-directed fractionation and salmonella mutagenicity of automobile and forklift diesel exhaust particles.
abstract: Many pulmonary toxicity studies of diesel exhaust particles (DEPs) have used an automobile-generated sample (A-DEPs) whose mutagenicity has not been reported. In contrast, many mutagenicity studies of DEPs have used a forklift-generated sample (SRM 2975) that has been evaluated in only a few pulmonary toxicity studies. Therefore, we evaluated the mutagenicity of both DEPs in Salmonella coupled to a bioassay-directed fractionation. The percentage of extractable organic material (EOM) was 26.3% for A-DEPs and 2% for SRM 2975. Most of the A-EOM (~55%) eluted in the hexane fraction, reflecting the presence of alkanes and alkenes, typical of uncombusted fuel. In contrast, most of the SRM 2975 EOM (~58%) eluted in the polar methanol fraction, indicative of oxygenated and/or nitrated organics derived from combustion. Most of the direct-acting, base-substitution activity of the A-EOM eluted in the hexane/dichloromethane (DCM) fraction, but this activity eluted in the polar methanol fraction for the SRM 2975 EOM. The direct-acting frameshift mutagenicity eluted across fractions of A-EOM, whereas > 80% eluted only in the DCM fraction of SRM 2975 EOM. The A-DEPs were more mutagenic than SRM 2975 per mass of particle, having 227 times more polycyclic aromatic hydrocarbon-type and 8-45 more nitroarene-type mutagenic activity. These differences were associated with the different conditions under which the two DEP samples were generated and collected. A comprehensive understanding of the mechanisms responsible for the health effects of DEPs requires the evaluation of DEP standards for a variety of end points, and our results highlight the need for multidisciplinary studies on a variety of representative samples of DEPs.
authors.affiliation: National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. demarini.david@epa.gov
authors.forename: David M
authors.initials: DM
authors.lastname: DeMarini
authors.forename: Lance R
authors.initials: LR
authors.lastname: Brooks
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Warren
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kobayashi
authors.forename: M Ian
authors.initials: MI
authors.lastname: Gilmour
authors.forename: Pramila
authors.initials: P
authors.lastname: Singh
mesh_terms: D001681:Biological Assay / Q000379:methods; D002274:Carcinogens, Environmental / Q000633:toxicity*; D023381:Endpoint Determination; D004781:Environmental Exposure; D016368:Frameshift Mutation; D005742:Gasoline / Q000633:toxicity*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D018986:Motor Vehicles; D009152:Mutagenicity Tests / Q000379:methods; D010316:Particle Size; D012475:Salmonella / Q000235:genetics*; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D002274:Carcinogens, Environmental; D005742:Gasoline; D001335:Vehicle Emissions