title: Modeling and analysis of personal exposures to VOC mixtures using copulas.
abstract: Environmental exposures typically involve mixtures of pollutants, which must be understood to evaluate cumulative risks, that is, the likelihood of adverse health effects arising from two or more chemicals. This study uses several powerful techniques to characterize dependency structures of mixture components in personal exposure measurements of volatile organic compounds (VOCs) with aims of advancing the understanding of environmental mixtures, improving the ability to model mixture components in a statistically valid manner, and demonstrating broadly applicable techniques. We first describe characteristics of mixtures and introduce several terms, including the mixture fraction which represents a mixture component's share of the total concentration of the mixture. Next, using VOC exposure data collected in the Relationship of Indoor Outdoor and Personal Air (RIOPA) study, mixtures are identified using positive matrix factorization (PMF) and by toxicological mode of action. Dependency structures of mixture components are examined using mixture fractions and modeled using copulas, which address dependencies of multiple variables across the entire distribution. Five candidate copulas (Gaussian, t, Gumbel, Clayton, and Frank) are evaluated, and the performance of fitted models was evaluated using simulation and mixture fractions. Cumulative cancer risks are calculated for mixtures, and results from copulas and multivariate lognormal models are compared to risks calculated using the observed data. Results obtained using the RIOPA dataset showed four VOC mixtures, representing gasoline vapor, vehicle exhaust, chlorinated solvents and disinfection by-products, and cleaning products and odorants. Often, a single compound dominated the mixture, however, mixture fractions were generally heterogeneous in that the VOC composition of the mixture changed with concentration. Three mixtures were identified by mode of action, representing VOCs associated with hematopoietic, liver and renal tumors. Estimated lifetime cumulative cancer risks exceeded 10(-3) for about 10% of RIOPA participants. Factors affecting the likelihood of high concentration mixtures included city, participant ethnicity, and house air exchange rates. The dependency structures of the VOC mixtures fitted Gumbel (two mixtures) and t (four mixtures) copulas, types that emphasize tail dependencies. Significantly, the copulas reproduced both risk predictions and exposure fractions with a high degree of accuracy, and performed better than multivariate lognormal distributions. Copulas may be the method of choice for VOC mixtures, particularly for the highest exposures or extreme events, cases that poorly fit lognormal distributions and that represent the greatest risks.
authors: Environmental Health Sciences, School of Public Health, University of Michigan, USA.
authors: Feng-Chiao
authors: FC
authors: Su
authors: Biostatistics, School of Public Health, University of Michigan, USA.
authors: Bhramar
authors: B
authors: Mukherjee
authors: Environmental Health Sciences, School of Public Health, University of Michigan, USA. Electronic address: stuartb@umich.edu.
authors: Stuart
authors: S
authors: Batterman
mesh_terms: D000393:Air Pollutants / Q000032:analysis* / Q000633:toxicity; D016902:Air Pollution, Indoor; D045424:Complex Mixtures / Q000737:chemistry* / Q000633:toxicity; D004781:Environmental Exposure / Q000706:statistics & numerical data*; D005260:Female; D019337:Hematologic Neoplasms / Q000453:epidemiology; D006801:Humans; D007680:Kidney Neoplasms / Q000453:epidemiology; D008113:Liver Neoplasms / Q000453:epidemiology; D008297:Male; D015233:Models, Statistical; D011336:Probability; D016008:Statistical Distributions; D055549:Volatile Organic Compounds / Q000032:analysis* / Q000633:toxicity; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D045424:Complex Mixtures; D055549:Volatile Organic Compounds
keywords: Copula; Cumulative effects; Exposure determinants; Mixture; RIOPA; VOC