Air pollution combustion emissions: Characterization of causative agents and mechanisms associated with cancer, reproductive, and cardiovascular effects

Abstract

Combustion emissions account for over half of the fine particle (PM_2.5) air pollution and most of the primary particulate organic matter. Human exposure to combustion emissions including the associated airborne fine particles and mutagenic and carcinogenic constituents (e.g., polycyclic aromatic compounds (PAC), nitro-PAC) have been studied in populations in Europe, America, Asia, and increasingly in third-world counties. Bioassay-directed fractionation studies of particulate organic air pollution have identified mutagenic and carcinogenic polycyclic aromatic hydrocarbons (PAH), nitrated PAH, nitro-lactones, and lower molecular weight compounds from cooking. A number of these components are significant sources of human exposure to mutagenic and carcinogenic chemicals that may also cause oxidative and DNA damage that can lead to reproductive and cardiovascular effects. Chemical and physical tracers have been used to apportion outdoor and indoor and personal exposures to airborne particles between various combustion emissions and other sources. These sources include vehicles (e.g., diesel and gasoline vehicles), heating and power sources (e.g., including coal, oil, and biomass), indoor sources (e.g., cooking, heating, and tobacco smoke), as well as secondary organic aerosols and pollutants derived from long-range transport.

Biomarkers of exposure, dose and susceptibility have been measured in populations exposed to air pollution combustion emissions. Biomarkers have included metabolic genotype, DNA adducts, PAH metabolites, and urinary mutagenic activity. A number of studies have shown a significant correlation of exposure to PM_2.5 with these biomarkers. In addition, stratification by genotype increased this correlation. New multivariate receptor models, recently used to determine the sources of ambient particles, are now being explored in the analysis of human exposure and biomarker data.

Human studies of both short- and long-term exposures to combustion emissions and ambient fine particulate air pollution have been associated with measures of genetic damage. Long-term epidemiologic studies have reported an increased risk of all causes of mortality, cardiopulmonary mortality, and lung cancer mortality associated with increasing exposures to air pollution. Adverse reproductive effects (e.g., risk for low birth weight) have also recently been reported in Eastern Europe and North America. Although there is substantial evidence that PAH or substituted PAH may be causative agents in cancer and reproductive effects, an increasing number of studies investigating cardiopulmonary and cardiovascular effects are investigating these and other potential causative agents from air pollution combustion sources.

Introduction

Combustion products of coal (soot and tars) were the first recognized chemical carcinogens. The earliest discovery that coal soot caused cancer in human chimney sweeps was reported Percival Pott in 1775 followed by studies in animals in the 1920s and the discovery of carcinogenic polycyclic aromatic hydrocarbons (PAH), e.g., benzo[a]pyrene (BaP), in the 1930s [1]. In the early 1970s, advances in the identification and evaluation of carcinogens resulted in the initiation of the International Agency for Research on Cancer (IARC) that conducted research and international assessment programs to identify and evaluate the carcinogenic risks to humans from chemicals and complex human exposure mixtures [2], [3], [4], [5], [6], [7], [8], [9]. The development of new methods and approaches to more efficiently identify potential carcinogens [10], [11], [12] in complex mixtures through the use of a bacterial mutagenesis bioassay [10] combined with bioassay-directed fractionation and chemical characterization was applied to complex combustion source emissions and air pollution [11], [12]. Using this approach, the identification of mutagens in particles from diesel exhaust and urban air, not only confirmed the contribution of PAH to mutagenic activity, but also led to the discovery of highly mutagenic nitroarenes (e.g., nitro-PAH and nitro-lactones) in diesel and urban air particles [11], [12], [13]. The IARC Monograph program has evaluated the carcinogenic risk of chemicals to humans, including the carcinogenicity of PAH [2], [3], [7] and nitro-PAH [6] (http://monographs.iarc.fr). The third monograph evaluated the cancer risk of PAH and heterocyclic compounds [2] found in coal-tars and other combustion products. Later, monographs in this series have evaluated air pollution combustion emissions and related complex mixtures of PAH and polycyclic aromatic compounds (PAC) [3], [4], [5], [6], aluminum and coke production industries [4], coal-tars and soot [5], diesel and gasoline engine exhausts and nitro-PAH [6]. The two most recent evaluations are summarized in Lancet Oncology, included PAH [7] and household solid fuel combustion (coal and biomass) and high-temperature frying [8]. The IARC Monograph program has evaluated a wide range of combustion emissions includes industrial sources [4], [5], motor vehicles [6], and residential combustion sources such as cooking emissions and indoor heating sources [8], and tobacco smoke [9].

The role of air pollution in human cancer has been reported in a number of reviews [14], [15], [16] and recent studies in the U.S. and Europe [17], [18]. This review addresses the chemical, mechanistic, animal, and human evidence for a link between particulate air pollution from combustion sources and a series of adverse health effects that may be linked by common causative agents and mechanisms. These health outcomes include cancer, reproductive effects, cardiovascular disease, and related intermediate effects.