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TCDD Exposure‐Response Analysis and Risk Assessment
Author(s) -
Cheng Hong,
Aylward Lesa,
Beall Colleen,
Starr Thomas B.,
Brunet Robert C.,
Carrier Gaétan,
Delzell Elizabeth
Publication year - 2006
Publication title -
risk analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.972
H-Index - 130
eISSN - 1539-6924
pISSN - 0272-4332
DOI - 10.1111/j.1539-6924.2006.00800.x
Subject(s) - percentile , confounding , medicine , linear regression , regression analysis , demography , proportional hazards model , confidence interval , standard error , coefficient of variation , statistics , toxicology , mathematics , biology , sociology
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 × 10 −6 , p < 0.05; ln‐transformed exposure data: , s.e. = 2.9 × 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.