Effects of fuel components and combustion particle physicochemical properties on toxicological responses of lung cells

Abstract

The physicochemical properties of combustion particles that promote lung toxicity are not fully understood, hindered by the fact that combustion particles vary based on the fuel and combustion conditions. Real-world combustion-particle properties also continually change as new fuels are implemented, engines age, and engine technologies evolve. This work used laboratory-generated particles produced under controlled combustion conditions in an effort to understand the relationship between different particle properties and the activation of established toxicological outcomes in human lung cells (H441 and THP-1). Particles were generated from controlled combustion of two simple biofuel/diesel surrogates (methyl decanoate and dodecane/BD, and butanol and dodecane/AD) and compared to a widely studied reference diesel particle (NIST SRM2975/RD). BD, AD, and RD particles exhibited differences in size, surface area, extractable chemical mass, and the content of individual polycyclic aromatic hydrocarbons (PAHs). Some of these differences were directly associated with different effects on biological responses. BD particles had the greatest surface area, amount of extractable material and oxidizing potential. These particles and extracts induced cytochrome P450 1A1 and 1B1 enzyme mRNA in lung cells. AD particles and extracts had the greatest total PAH content and also caused CYP1A1 and 1B1 mRNA induction. The RD extract contained the highest relative concentration of 2-ring PAHs and stimulated the greatest level of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNFα) cytokine secretion. Finally, AD and RD were more potent activators of TRPA1 than BD, and while neither the TRPA1 antagonist HC-030031 nor the antioxidant N-acetylcysteine (NAC) affected CYP1A1 or 1B1 mRNA induction, both inhibitors reduced IL-8 secretion and mRNA induction. These results highlight that differences in fuel and combustion conditions affect the physicochemical properties of particles, and these differences, in turn, affect commonly studied biological/toxicological responses.

Oxidative Potential Versus Biological Effects: A Review on the Relevance of Cell-Free/Abiotic Assays as Predictors of Toxicity from Airborne Particulate Matter

“…Statistical significant associations between OP and biological effects were reported in 22 of the 29 independent studies were statistical analysis were applied [29,32,43,44,49,52,57,58,59,60,63,65,66,74,75,76,77,78,79,80,81,82,83,84]: 10 independent studies reported that at least one OP measure was statistically significantly associated with all endpoints examined [43,49,52,57,63,66,78,79,80,81,83], while additional 12 independent studies reported that at least one OP measure was significantly associated with at least one effect outcome [29,32,44,58,59,60,65,74,75,76,77,82,84]. By contrast, seven studies reported no significant correlation/association between any OP measures and any biological effects [50,55,56,64,65,67,68,69,70,71,72,73] (Figure 1, and Tables S1 and S2, supplementary materials).…”

“…Of the 22 studies that reported a statistically significant association between at least one OP measure and at least one or more biological effects, were 10 experimental in vitro or in vivo studies in cells or animals [29,32,43,44,49,50,52,55,56,57,58,59,60], and 11 epidemiological or clinical studies in humans [49,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84] (Figure 1). Of the seven independent studies reporting no statistical significant association between any OP measure and any biological effects were three independent experimental in vitro or in vivo studies [50,55,56], and four independent epidemiological or clinical studies [64,65,67,68,69,70,71,72,73] (Figure 1).…”

“…It seems likely that this at least in part could be the reason for the general assumption often encountered in the literature, that OP may provide a good prediction PM toxicity. However, an alternative way to present this is that 19 of the 29 studies (65%) showed that OP was not statistically significantly associated with at least one or more biological effects examined [29,32,44,50,55,56,58,59,60,64,65,67,68,69,70,71,72,73,74,75,76,77,82,84].…”

“…In total 58 studies were identified exploring both the OP and biological effects of PM and/or combustion particles in cells, animals or humans [27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84]. Among these were three cases of multiple studies based on the same particle samples and measurements of OP: Two studies on in vitro and in vivo effects of a set of wood smoke and PM samples [45,46], and six studies from a series of PM exposures of human volunteers under the RAPTES (Risk of Airborne Particles: A Toxicological–Epidemiological Hybrid Study) project [67,68,69,70,71,72], and three epidemiolo...…”

“…In cases where no statistical analysis was available, the studies were marked with either “possible association” or “no apparent association” based on a comparison of the rank order of OP and rank order of potency to induce biological effects induced by the different particulates tested in the study (Tables S1 and S2, supplementary materials). Importantly, the main conclusions of this review have been based on the 29 studies were correlation between OP and biological effects was assessed by statistical analysis [29,32,43,44,49,50,52,55,56,57,58,59,60,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84].…”