The National Environmental Respiratory Center (NERC) experiment in multi-pollutant air quality health research: IV. Vascular effects of repeated inhalation exposure to a mixture of five inorganic gases

Inhal Toxicol. 2014 Sep;26(11):691-6. doi: 10.3109/08958378.2014.947448.


An experiment was conducted to test the hypothesis that a mixture of five inorganic gases could reproduce certain central vascular effects of repeated inhalation exposure of apolipoprotein E-deficient mice to diesel or gasoline engine exhaust. The hypothesis resulted from preceding multiple additive regression tree (MART) analysis of a composition-concentration-response database of mice exposed by inhalation to the exhausts and other complex mixtures. The five gases were the predictors most important to MART models best fitting the vascular responses. Mice on high-fat diet were exposed 6 h/d, 7 d/week for 50 d to clean air or a mixture containing 30.6 ppm CO, 20.5 ppm NO, 1.4 ppm NO₂, 0.5 ppm SO₂, and 2.0 ppm NH₃ in air. The gas concentrations were below the maxima in the preceding studies but in the range of those in exhaust exposure levels that caused significant effects. Five indicators of stress and pro-atherosclerotic responses were measured in aortic tissue. The exposure increased all five response indicators, with the magnitude of effect and statistical significance varying among the indicators and depending on inclusion or exclusion of an apparent outlying control. With the outlier excluded, three responses approximated predicted values and two fell below predictions. The results generally supported evidence that the five gases drove the effects of exhaust, and thus supported the potential of the MART approach for identifying putative causal components of complex mixtures.

Keywords: Air pollution; ammonia; carbon monoxide; cardiovascular; nitric oxide; nitrogen dioxide; nitrogen oxides; sulfur dioxide.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Air Pollutants / chemistry*
  • Air Pollutants / toxicity
  • Ammonia / chemistry
  • Ammonia / toxicity
  • Animals
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Carbon Monoxide / chemistry
  • Carbon Monoxide / toxicity
  • Cardiovascular Diseases / chemically induced*
  • Dose-Response Relationship, Drug
  • Gases / chemistry*
  • Gases / toxicity
  • Gasoline / analysis*
  • Mice
  • Mice, Knockout
  • Nitric Oxide / chemistry
  • Nitric Oxide / toxicity
  • Nitrous Oxide / chemistry
  • Nitrous Oxide / toxicity
  • Oxides / chemistry
  • Oxides / toxicity
  • Sulfur Compounds / chemistry
  • Sulfur Compounds / toxicity
  • Vehicle Emissions / analysis*
  • Vehicle Emissions / toxicity


  • Air Pollutants
  • Apolipoproteins E
  • Gases
  • Gasoline
  • Oxides
  • Sulfur Compounds
  • Vehicle Emissions
  • sulfur monoxide
  • Nitric Oxide
  • Ammonia
  • Carbon Monoxide
  • Nitrous Oxide