Quantitative Risk Analysis of Particulate Matter in the Air: Interspecies Extrapolation with Bioassay and Mathematical Models

We analyzed the health risk of particulate matters in the air to humans using bioassay data and a mathematical model. We designed an original dosimetry model to estimate the particle concentration in human respiratory organs, and the concentration of the inhaled particles at the target organ was used for interspecies extrapolation from rat to human. Our model is based on the conventional dosimetry model and deposition model in the previous literature, but clearance parameters have been newly introduced for the simulation of long-term exposure. Lung cancer was set as the risk endpoint in our risk study, and the dose-response relationship at the target organ (lung) was quantitatively analyzed by the benchmark dose (BMD) method. For interspecies extrapolation based on target organ concentration, we assumed benchmark concentration (BMC) related to 1% excess cancer in rats and humans, and the human equivalent concentration (HEC) was searched by back-estimation using our model. The obtained HEC was 948 to 1098 mg/m3, and the unit risk to humans was 9.11 to 10.5 × 10−9 per 1 μ g/m3 of particulate matter. The estimated cancer risk for Japanese people in general was estimated as approximately 9–10 persons per 100,000,000 when the particle concentration in the air is 10 μg/m3.

[1]  Annie M Jarabek,et al.  Dosimetric Adjustments for Interspecies Extrapolation of Inhaled Poorly Soluble Particles (PSP) , 2005, Inhalation toxicology.

[2]  James S. Brown,et al.  Dosimetric Comparisons of Particle Deposition and Retention in Rats and Humans , 2005, Inhalation toxicology.

[3]  J L Mauderly,et al.  Health Effects of Subchronic Exposure to Environmental Levels of Diesel Exhaust , 2004, Inhalation toxicology.

[4]  K. Broman,et al.  Particle Effects on Heart-Rate Regulation in Senescent Mice , 2004, Inhalation toxicology.

[5]  Isao Yoshimura,et al.  Effects of Particulate Matter on Daily Mortality in 13 Japanese Cities , 2003, Journal of epidemiology.

[6]  J Pekkanen,et al.  Effects of fine and ultrafine particles on cardiorespiratory symptoms in elderly subjects with coronary heart disease: the ULTRA study. , 2003, American journal of epidemiology.

[7]  Ravi P Subramaniam,et al.  Analysis of Lobar Differences in Particle Deposition in the Human Lung , 2003, Inhalation toxicology.

[8]  Chang-Chuan Chan,et al.  Effects of submicrometer particle compositions on cytokine production and lipid peroxidation of human bronchial epithelial cells. , 2002, Environmental health perspectives.

[9]  R. Burnett,et al.  Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. , 2002, JAMA.

[10]  M. Selgrade,et al.  Air pollutant-enhanced respiratory disease in experimental animals. , 2001, Environmental Health Perspectives.

[11]  W. Hofmann,et al.  Particle Deposition in a Multiple-Path Model of the Human Lung , 2001 .

[12]  S Perz,et al.  Increases in heart rate during an air pollution episode. , 1999, American journal of epidemiology.

[13]  J Schwartz,et al.  Air pollution and hospital admissions for heart disease in eight U.S. counties. , 1998, Epidemiology.

[14]  A. Cohen,et al.  Inappropriate use of daily mortality analyses to estimate longer-term mortality effects of air pollution. , 1998, International journal of epidemiology.

[15]  B. Ostro,et al.  Assessing the health benefits of reducing particulate matter air pollution in the United States. , 1998, Environmental research.

[16]  Y. Kawabata,et al.  Lung tumor induced by long-term inhalation or intratracheal instillation of diesel exhaust particles. , 1997, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[17]  D. Taylor,et al.  Human Respiratory Tract Model for Radiological Protection , 1996 .

[18]  B. Asgharian,et al.  A multiple-path model of particle deposition in the rat lung. , 1995, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[19]  J L Mauderly,et al.  Comparative Pulmonary Toxicities and Carcinogenicities of Chronically Inhaled Diesel Exhaust and Carban Black in F344 Rats , 1995, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[20]  D. Dockery,et al.  Epidemiologic studies on short-term effects of low levels of major ambient air pollution components. , 1995, Environmental health perspectives.

[21]  D. Dockery,et al.  An association between air pollution and mortality in six U.S. cities. , 1993, The New England journal of medicine.

[22]  B. Ostro,et al.  The association of air pollution and mortality: examining the case for inference. , 1993, Archives of environmental health.

[23]  J Schwartz,et al.  Air pollution and daily mortality: associations with particulates and acid aerosols. , 1992, Environmental research.

[24]  Y. Kawabata,et al.  Risk Assessment for Human Lung Cancer due to Diesel Exhaust Particles , 1992 .

[25]  D. Dockery,et al.  Acute health effects of PM10 pollution on symptomatic and asymptomatic children. , 1992, The American review of respiratory disease.

[26]  J Schwartz,et al.  Increased mortality in Philadelphia associated with daily air pollution concentrations. , 1992, The American review of respiratory disease.

[27]  Tadao Suzuki,et al.  Long-term Inhalation Experiments on the Health Effects of Diesel Exhaust , 1990 .

[28]  D. Dockery,et al.  Chronic obstructive pulmonary disease mortality in six U.S. cities. , 1989, The American review of respiratory disease.

[29]  C. P. Yu,et al.  Predicted deposition of diesel particles in young humans , 1987 .

[30]  R. McClellan,et al.  Diesel exhaust is a pulmonary carcinogen in rats exposed chronically by inhalation. , 1987, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[31]  K S Crump,et al.  A new method for determining allowable daily intakes. , 1984, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[32]  D. E. Seizinger,et al.  Mutagenicity of diesel exhaust particle extracts: influence of car type. , 1981, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[33]  H C Yeh,et al.  Anatomic Models of the tracheobronchial and pulmonary regions of the rat , 1979, The Anatomical record.

[34]  G. J. Newton,et al.  Deposition of inhaled monodisperse aerosols in small rodents. , 1975, Inhaled particles.

[35]  Benoit Nemery,et al.  Size effect of intratracheally instilled particles on pulmonary inflammation and vascular thrombosis. , 2003, Toxicology and applied pharmacology.

[36]  J Schwartz,et al.  Air pollution and incidence of cardiac arrhythmia. , 2000, Epidemiology.

[37]  K S Crump,et al.  Lung cancer mortality and diesel exhaust: reanalysis of a retrospective cohort study of U.S. railroad workers. , 1999, Inhalation toxicology.

[38]  J. Pearl,et al.  Causal diagrams for epidemiologic research. , 1999, Epidemiology.

[39]  U. Epa.  Air Quality Criteria for Particulate Matter , 1996 .

[40]  J Schwartz,et al.  What are people dying of on high air pollution days? , 1994, Environmental research.

[41]  J. Schwartz,et al.  Mortality and air pollution in London: a time series analysis. , 1990, American journal of epidemiology.

[42]  F. T. Cross,et al.  The current approach of the ICRP Task Group for modeling doses to respiratory tract tissues. , 1989, Health physics.

[43]  R. McClellan,et al.  Retention patterns for inhaled particles in the lung: comparisons between laboratory animals and humans for chronic exposures. , 1989, Health physics.

[44]  J. Heyder,et al.  Deposition of particles in the human respiratory tract in the size range 0.005–15 μm , 1986 .

[45]  T. Suzuki,et al.  Long-term inhalation studies on effects of exhaust from heavy and light duty diesel engines on F344 rats. , 1986, Developments in toxicology and environmental science.

[46]  R. Hertzberg,et al.  A new method for determining allowable daily intakes. , 1986, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[47]  C. Davies.  Deposition of particles in the human lungs as a function of particle size and breathing pattern: an empirical model. , 1982, The Annals of occupational hygiene.

[48]  H. Yeh,et al.  Models of human lung airways and their application to inhaled particle deposition. , 1980, Bulletin of mathematical biology.