Relative Toxicity of Air Pollution Mixtures

EPA Grant Number: R834798C001
Subproject: this is subproject number 001 , established and managed by the Center Director under grant R834798
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Air Pollution Mixtures: Health Effects across Life Stages
Center Director: Koutrakis, Petros
Title: Relative Toxicity of Air Pollution Mixtures
Investigators: Godleski, John J. , Koutrakis, Petros
Institution: Harvard University
EPA Project Officer: Ilacqua, Vito
Project Period: January 1, 2011 through December 31, 2015 (Extended to December 31, 2016)
RFA: Clean Air Research Centers (2009) RFA Text |  Recipients Lists
Research Category: Health Effects , Air


Project I, an inhalation toxicological animal exposure study, will investigate the relative toxicity of different component concentration combinations of air pollution mixtures. These components include both particles and gases that are emitted directly from sources (primary species) or are formed in the atmosphere through a series of reactions that are predominantly photochemical (secondary species) Using a novel integration of our ambient particle concentrator and photochemical chamber technologies to generate realistic mixtures, we will test these specific hypotheses: (i) secondary gaseous pollutants formed from the photochemical oxidation of Boston ambient gases can induce biological responses; (ii) aging Boston concentrated ambient particles (CAPs) in the photochemical chamber enhances their toxicity; (iii) toxicological effects of photochemically aged CAPs are exacerbated by coexposure to ozone and other secondary gases; and (iv) mixture composition and toxicity exhibit inter- and intra-seasonal variability due to changes in source emissions and weather conditions.


Toxicity will be assessed in Sprague-Dawley rats by changes in 1) in vivo oxidant response, 2) blood pressure, 3) measures of inflammation, and 4) vascular blood flow/resistance. Three concurrent exposures groups (Sham, Control Exposure and Exposure) will allow us to control for the variability in CAPs composition. With this design, there can always be a direct comparison between two exposure mixtures on every exposure day, making it possible to determine which mixture is more toxic. In studies of vascular blood flow/resistance using a crossover design, each animal will have multiple exposures that will include each of the three types, including baseline measurements. This will permit for control of inter-subject variability in the biological response. Exposure atmospheres will be chemically and physically characterized using a broad array of measurement techniques for CO. NOx, 03, PM, BC, particle count and size distribution, EC/OC, elemental composition, sulfate, formaldehyde, acetaldehyde and VOCs. For the biological effects observed during each exposure, inter-group differences will be assessed using multi-way analysis of variance. To determine the effect of PM composition on biological response, linear regression models containing exposure concentrations as predictors will be fitted to each response outcome measure. Multiple pollutant linear regressions will be used to assess the independent effects of multiple pollution components on biological response.

Expected Results:

The proposed study will differentiate the health effects of components of multi-pollutant exposure mixtures. We expect to add to our understanding of the exposure- response relationship, the interaction between particulate matter and photochemical gases, and the extent to which the resultant products exert toxicity. The biological outcomes assessed in this Project focus on responses important in oxidant initiation of pulmonary inflammation, and important functional measures of vascular and cardiovascular health.

Publications and Presentations:

Publications have been submitted on this subproject: View all 36 publications for this subprojectView all 359 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 14 journal articles for this subprojectView all 297 journal articles for this center

Supplemental Keywords:

Air pollution, concentrated ambient particles, vascular blood flow and resistance, inflammation, blood pressure, reactive oxygen species, oxidant response, atmospheric photochemistry,, Scientific Discipline, Air, air toxics, Environmental Chemistry, Health Risk Assessment, Air Pollution Effects, Biochemistry, Environmental Monitoring, ambient air quality, children's health, complex mixtures, health effects, particulates, sensitive populations, air pollutants, aerosol particles, biological sensitivities, exposure and effects, lung epithelial cells, susceptible populations, chemical composition, neurotoxicity, human exposure, toxicity, coronary artery disease, cardiopulmonary, cardiotoxicity, environmental effects, human health, mortality

Progress and Final Reports:

2010 Progress Report
2011 Progress Report
2012 Progress Report
2013 Progress Report
2014 Progress Report
Final Report

Main Center Abstract and Reports:

R834798    Air Pollution Mixtures: Health Effects across Life Stages

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834798C001 Relative Toxicity of Air Pollution Mixtures
R834798C002 Cognitive Decline, Cardiovascular Changes, and Biological Aging in Response to Air Pollution
R834798C003 Identifying the Cognitive and Vascular Effects of Air Pollution Sources and Mixtures in the Framingharn Offspring and Third Generation Cohorts
R834798C004 Longitudinal Effects of Multiple Pollutants on Child Growth, Blood Pressure and Cognition
R834798C005 A National Study to Assess Susceptibility, Vulnerability, and Effect Modification of Air Pollution Health Risks