title: Multiple classes of environmental chemicals are associated with liver disease: NHANES 2003-2004.
abstract: Biomonitoring studies show that humans carry a body burden of multiple classes of contaminants which are not often studied together. Many of these chemicals may be hepatotoxic. We used the 2003-2004 National Health and Nutrition Examination Survey to evaluate the relationship between alanine aminotransferase (ALT) and 37 environmental contaminants, comprising heavy metals, non-dioxin-like polychlorinated biphenyls (PCBs), and dioxin-like compounds, using a novel method. Linear regression models were constructed for each chemical separately, then as a class, using quartiles to represent exposure and adjusting for age, sex, race, income, and BMI. We then used an optimization approach to compile a weighted sum of the quartile scores, both within and across chemical classes. Using the optimization approach to construct weighted quartile scores, the dioxin like PCB, the non-dioxin like PCB and metal class-level scores were significantly associated with elevated ALT. A significant interaction was detected between the class-level score for metals, and the score for non-dioxin-like PCBs. When including all chemicals in one model, 3 chemicals accounted for 78% of the weight (mercury, PCB 180, 3,3',4,4',5-PNCB) with the remaining 22% associated with 4 chemicals (a dioxin and 3 PCBs). Validation with a holdout dataset indicated that the weighted quartile sum estimator efficiently identifies reproducible significant associations.
authors.affiliation: U.S. Environmental Protection Agency, Mailstop 8623P, 1200 Pennsylvania Avenue NW, Washington, DC 20460, USA. Electronic address: Christensen.Krista@epa.gov.
authors.forename: Krista L
authors.initials: KL
authors.lastname: Yorita Christensen
authors.forename: Caroline K
authors.initials: CK
authors.lastname: Carrico
authors.forename: Arun J
authors.initials: AJ
authors.lastname: Sanyal
authors.forename: Chris
authors.initials: C
authors.lastname: Gennings
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology*; D002648:Child; D004147:Dioxins / Q000009:adverse effects*; D004781:Environmental Exposure / Q000009:adverse effects*; D004785:Environmental Pollutants / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008628:Mercury / Q000009:adverse effects; D019216:Metals, Heavy / Q000009:adverse effects*; D008875:Middle Aged; D009749:Nutrition Surveys; D011078:Polychlorinated Biphenyls / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D004147:Dioxins; D004785:Environmental Pollutants; D019216:Metals, Heavy; D011078:Polychlorinated Biphenyls; D000410:Alanine Transaminase; D008628:Mercury
keywords: ALT; Biomonitoring; Cumulative; Liver; Mixtures