Aerosol physicochemical determinants of carbon black and ozone inhalation co-exposure induced pulmonary toxicity

Air pollution accounts for more than 7 million premature deaths worldwide. Using ultrafine carbon black (CB) and ozone (O-3) as a model for an environmental co-exposure scenario, the dose response relationships in acute pulmonary injury and inflammation were determined by generating, characterizing, and comparing stable concentrations of CB aerosols (2.5, 5.0, 10.0 mg/m(3)), O-3 (0.5, 1.0, 2.0 ppm) with mixture CB + O-3 (2.5 + 0.5, 5.0 + 1.0, 10.0 + 2.0). C57BL6 male mice were exposed for 3 h by whole body inhalation and acute toxicity determined after 24 h. CB itself did not cause any alteration, however, a dose response in pulmonary injury/inflammation was observed with O-3 and CB + O-3. This increase in response with mixtures was not dependent on the uptake but was due to enhanced reactivity of the particles. Benchmark dose modeling showed several-fold increase in potency with CB + O-3 compared with CB or O-3 alone. Principal component analysis provided insight into response relationships between various doses and treatments. There was a significant correlation in lung responses with charge-based size distribution, total/alveolar deposition, oxidant generation, and antioxidant depletion potential. Lung tissue gene/protein response demonstrated distinct patterns that are better predicted by either particle dose/aerosol responses (interleukin-1 beta, keratinocyte chemoattractant, transforming growth factor beta) or particle reactivity (thymic stromal lymphopoietin, interleukin-13, interleukin-6). Hierarchical clustering showed a distinct signature with high dose and a similarity in mRNA expression pattern of low and medium doses of CB + O-3. In conclusion, we demonstrate that the biological outcomes from CB + O-3 co-exposure are significantly greater than individual exposures over a range of aerosol concentrations and aerosol characteristics can predict biological outcome.

Automated summary

Air pollution leads to over 7 million premature deaths worldwide. A study using ultrafine carbon black and ozone as a model found that co-exposure to the mixture resulted in significantly greater lung injury and inflammation compared to individual exposures. The enhanced reactivity of the particles in the mixture was responsible for this increase. Lung tissue gene and protein responses could predict the biological effects.