Sample characterization of automobile and forklift diesel exhaust particles and comparative pulmonary toxicity in mice.

Abstract

Two samples of diesel exhaust particles (DEPs) predominate in health effects research: an automobile-derived DEP (A-DEP) sample and the National Institute of Standards Technology standard reference material (SRM 2975) generated from a forklift engine. A-DEPs have been tested extensively for their effects on pulmonary inflammation and exacerbation of allergic asthmalike responses. In contrast, SRM 2975 has been tested thoroughly for its genotoxicity. In the present study, we combined physical and chemical analyses of both DEP samples with pulmonary toxicity testing in CD-1 mice to compare the two materials and to make associations between their physicochemical properties and their biologic effects. A-DEPs had more than 10 times the amount of extractable organic material and less than one-sixth the amount of elemental carbon compared with SRM 2975. Aspiration of 100 micro g of either DEP sample in saline produced mild acute lung injury; however, A-DEPs induced macrophage influx and activation, whereas SRM 2975 enhanced polymorphonuclear cell inflammation. A-DEPs stimulated an increase in interleukin-6 (IL-6), tumor necrosis factor alpha, macrophage inhibitory protein-2, and the TH2 cytokine IL-5, whereas SRM 2975 only induced significant levels of IL-6. Fractionated organic extracts of the same quantity of DEPs (100 micro g) did not have a discernable effect on lung responses and will require further study. The disparate results obtained highlight the need for chemical, physical, and source characterization of particle samples under investigation. Multidisciplinary toxicity testing of diesel emissions derived from a variety of generation and collection conditions is required to meaningfully assess the health hazards associated with exposures to DEPs. Key words: automobile, diesel exhaust particles, forklift, mice, pulmonary toxicity, SRM 2975.

Bioassay-directed fractionation and salmonella mutagenicity of automobile and forklift diesel exhaust particles.

“…This indicated that, across chemical classes, A-EOM contained more S9-dependent mutagenicity than did the SRM 2975 EOM. Consistent with this is the evidence presented here and by Singh et al (2004) for greater amounts of PAH-type mutagenicity and PAHs in the A-DEPs compared with SRM 2975. There is ample evidence that the genotoxic activity associated with the EOM of DEPs inhaled into the lung may be bioavailable by virtue of the solubilization and dispersion properties of pulmonary surfactant components (Belisario et al 1984;Keane et al 1991;King et al 1981).…”

“…The lack of mutagenic activity in the hexane fraction (Tables 7 and 8) was consistent with the presence of unsubstituted alkanes and alkenes, which are not mutagenic. These results are also supported by the photomicrographs and other chemical and combustion data demonstrating that much of the A-EOM is uncombusted fuel, possibly neutral alkanes and alkenes (Singh et al 2004), which would have eluted in the hexane fraction.…”

“…The fact that one sample (A-DEPs) has been used extensively in pulmonary toxicity studies but never studied previously for mutagenicity, and virtually the opposite situation pertains for the other sample (SRM 2975), illustrates the need for scientists to engage in collaborative, multidisciplinary research efforts in this area. Similar to the mutagenic activities of these particles, the pulmonary toxicities of these two DEPs were also strikingly different (Singh et al 2004). These biologic data, combined with the physical and chemical features of these two DEPs (Singh et al 2004), provide a basis for comparing these two DEPs that was not available previously.…”

“…Hayakawa et al (1997) showed that as much as 53% of the mutagenicity of the DCM fraction of DEPs was due to nitroarenes. As summarized by Singh et al (2004), the two DEP samples had different physical properties, chemical compositions, and pulmonary toxicities. The mass and mutagenicity distributions of the two samples described here reflected clear differences in the chemical composition of these DEPs.…”

“…The results were expressed as the distribution of mass and mutagenicity among the fractions. Combined with physical and chemical features of these DEPs, as well as their pulmonary toxicities (Singh et al 2004), we propose that DEP samples should be characterized chemically, physically, and biologically at multiple end points to understand the mechanisms associated with the health effects of DEPs.…”