Tcdd Exposure-Response Analysis and Risk Assessment

13 Pages Posted: 7 Nov 2006  

Hong Cheng

affiliation not provided to SSRN

Lesa Aylward

affiliation not provided to SSRN

Colleen Beall

affiliation not provided to SSRN

Thomas B. Starr

TBS Associates

Robert C. Brunet

University of Montreal - Department of Mathematics and Statistics

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 × 10, p < 0.05; ln-transformed exposure data: , s.e. = 2.9 × 10, 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.

Suggested Citation

Cheng, Hong and Aylward, Lesa and Beall, Colleen and Starr, Thomas B. and Brunet, Robert C., Tcdd Exposure-Response Analysis and Risk Assessment. Risk Analysis, Vol. 26, Issue 4, pp. 1059-1071, August 2006. Available at SSRN: https://ssrn.com/abstract=943285 or http://dx.doi.org/10.1111/j.1539-6924.2006.00800.x

Hong Cheng (Contact Author)

affiliation not provided to SSRN

No Address Available

Lesa Aylward

affiliation not provided to SSRN

No Address Available

Colleen Beall

affiliation not provided to SSRN

No Address Available

Thomas B. Starr

TBS Associates ( email )

7500 Rainwater Road
Raleigh, NC 27615
United States

Robert C. Brunet

University of Montreal - Department of Mathematics and Statistics ( email )

Montreal, Quebec H3C 3J7
Canada

HOME PAGE: http://www.bio.net/bionet/mm/toxicol/2005-June/003588.html

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