Exposure reconstruction for the TCDD-exposed NIOSH cohort using a concentration- and age-dependent model of elimination

Aylward, Lesa L., Brunet, Robert C., Starr, Thomas B., Carrier, Gaetan, Delzell, Elizabeth, Cheng, Hong and Beall, Colleen (2005) Exposure reconstruction for the TCDD-exposed NIOSH cohort using a concentration- and age-dependent model of elimination. Risk Analysis, 25 4: 945-956. doi:10.1111/j.1539-6924.2005.00645.x

Author Aylward, Lesa L.
Brunet, Robert C.
Starr, Thomas B.
Carrier, Gaetan
Delzell, Elizabeth
Cheng, Hong
Beall, Colleen
Title Exposure reconstruction for the TCDD-exposed NIOSH cohort using a concentration- and age-dependent model of elimination
Journal name Risk Analysis   Check publisher's open access policy
ISSN 0272-4332
Publication date 2005-08
Sub-type Article (original research)
DOI 10.1111/j.1539-6924.2005.00645.x
Open Access Status Not yet assessed
Volume 25
Issue 4
Start page 945
End page 956
Total pages 12
Place of publication Hoboken, NJ, United States
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
Recent studies demonstrating a concentration dependence of elimination of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suggest that previous estimates of exposure for occupationally exposed cohorts may have underestimated actual exposure, resulting in a potential overestimate of the carcinogenic potency of TCDD in humans based on the mortality data for these cohorts. Using a database on U.S. chemical manufacturing workers potentially exposed to TCDD compiled by the National Institute for Occupational Safety and Health (NIOSH), we evaluated the impact of using a concentration- and age-dependent elimination model (CADM) (Aylward et al., 2005) on estimates of serum lipid area under the curve (AUC) for the NIOSH cohort. These data were used previously by Steenland et al. (2001) in combination with a first-order elimination model with an 8.7-year half-life to estimate cumulative serum lipid concentration (equivalent to AUC) for these workers for use in cancer dose-response assessment. Serum lipid TCDD measurements taken in 1988 for a subset of the cohort were combined with the NIOSH job exposure matrix and work histories to estimate dose rates per unit of exposure score. We evaluated the effect of choices in regression model (regression on untransformed vs. In-transformed data and inclusion of a nonzero regression intercept) as well as the impact of choices of elimination models and parameters on estimated AUCs for the cohort. Central estimates for dose rate parameters derived from the serum-sampled subcohort were applied with the elimination models to time-specific exposure scores for the entire cohort to generate AUC estimates for all cohort members. Use of the CADM resulted in improved model fits to the serum sampling data compared to the first-order models. Dose rates varied by a factor of 50 among different combinations of elimination model, parameter sets, and regression models. Use of a CADM results in increases of up to five-fold in AUC estimates for the more highly exposed members of the cohort compared to estimates obtained using the first-order model with 8.7-year half-life. This degree of variation in the AUC estimates for this cohort would affect substantially the cancer potency estimates derived from the mortality data from this cohort. Such variability and uncertainty in the reconstructed serum lipid AUC estimates for this cohort, depending on elimination model, parameter set, and regression model, have not been described previously and are critical components in evaluating the dose-response data from the occupationally exposed populations.
Keyword Dioxin
Occupational exposure reconstruction
Toxicokinetic models
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: National Research Centre for Environmental Toxicology Publications
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