title: TCDD exposure-response analysis and risk assessment.
abstract: We examined the relation between cancer mortality and time-dependent cumulative exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) estimated from a concentration- and age-dependent kinetic model of elimination, and we estimated incremental cancer risks at age 75. Data from the National Institute for Occupational Safety and Health study of 3,538 workers with occupational exposure to TCDD were analyzed using standardized mortality ratios and Cox regression procedures. Analyses adjusted for potential confounding by age, year of birth, and race and considered exposure lag periods of 0, 10, or 15 years. Other potential confounders including smoking and other occupational exposures were evaluated indirectly. To explore the influence of extreme values of cumulative TCDD ppt-years, we restricted the analysis to observations with exposure below the 95th percentile or used logarithmic (ln) transformed exposure values. We applied penalized smoothing splines to examine variation in the exposure-response relation across the exposure range. TCDD was not statistically significantly associated with cancer mortality using the full data set, regardless of the lag period. When we restricted the analysis to observations with exposure below the 95th percentile, TCDD was associated positively with cancer mortality, particularly when a 15-year lag was applied (untransformed exposure data: regression coefficient , standard error (s.e.) = 1.4 x 10(-6), p < 0.05; ln-transformed exposure data: , s.e. = 2.9 x 10(-2), p < 0.05). The estimated incremental lifetime risk of mortality at age 75 from all cancers was about 6 to more than 10 times lower than previous estimates derived from this cohort using exposure models that did not consider the age and concentration dependence of TCDD elimination.
authors.affiliation: Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, USA. hcheng@ms.soph.uab.edu
authors.forename: Hong
authors.initials: H
authors.lastname: Cheng
authors.forename: Lesa
authors.initials: L
authors.lastname: Aylward
authors.forename: Colleen
authors.initials: C
authors.lastname: Beall
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Starr
authors.forename: Robert C
authors.initials: RC
authors.lastname: Brunet
authors.forename: Gaétan
authors.initials: G
authors.lastname: Carrier
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Delzell
mesh_terms: D000368:Aged; D002617:Chemical Industry; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008954:Models, Biological; D009369:Neoplasms / Q000139:chemically induced / Q000401:mortality; D016273:Occupational Exposure; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage* / Q000633:toxicity*; D016016:Proportional Hazards Models; D018570:Risk Assessment; D014481:United States / Q000453:epidemiology
chemical_list: D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins