Concentration-dependent TCDD elimination kinetics in humans: toxicokinetic modeling for moderately to highly exposed adults from Seveso, Italy, and Vienna, Austria, and impact on dose estimates for the NIOSH cohort.
Lesa L. Aylward,Robert C. Brunet,Gaétan Carrier,Sean M. Hays,Colleen A Cushing,Larry L. Needham,Donald G. Patterson,Pier Mario Gerthoux,Paolo Brambilla,Paolo Mocarelli +9 more
TLDR
Application of the model to serum sampling data from the cohort of US herbicide-manufacturing workers assembled by the National Institute of Occupational Safety and Health (NIOSH) indicates that previous estimates of peak serum lipid TCDD concentrations in dioxin-exposed manufacturing workers may have underestimated the maximum concentrations in these workers and other occupational cohorts by several-fold to an order of magnitude or more.Abstract:
Serial measurements of serum lipid 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations in 36 adults from Seveso, Italy, and three patients from Vienna, Austria, with initial serum lipid TCDD concentrations ranging from 130 to 144,000 ppt, were modeled using a modified version of a previously published toxicokinetic model for the distribution and elimination of dioxins. The original model structure accounted for a concentration-dependent increase in overall elimination rate for TCDD due to nonlinear distribution of TCDD to the liver (secondary to induction of the binding protein CYP1A2), from which elimination takes place via a first-order process. The original model structure was modified to include elimination due to lipid partitioning of TCDD from circulation into the large intestine, based on published human data. We optimized the fit of the modified model to the data by varying the hepatic elimination rate parameter for each of the 39 people. The model fits indicate that there is significant interindividual variability of TCDD elimination efficiency in humans and also demonstrate faster elimination in men compared to women, and in younger vs. older persons. The data and model results indicate that, for males, the mean apparent half-life for TCDD (as reflected in changes in predicted serum lipid TCDD level) ranges from less than 3 years at serum lipid levels above 10,000 ppt to over 10 years at serum lipid levels below 50 ppt. Application of the model to serum sampling data from the cohort of US herbicide-manufacturing workers assembled by the National Institute of Occupational Safety and Health (NIOSH) indicates that previous estimates of peak serum lipid TCDD concentrations in dioxin-exposed manufacturing workers, based on first-order back-extrapolations with half-lives of 7-9 years, may have underestimated the maximum concentrations in these workers and other occupational cohorts by several-fold to an order of magnitude or more. Such dose estimates, based on a single sampling point decades after last exposure, are highly variable and dependent on a variety of assumptions and factors that cannot be fully determined, including interindividual variations in elimination efficiency. Dose estimates for these cohorts should be re-evaluated in light of the demonstration of concentration-dependent elimination kinetics for TCDD, and the large degree of uncertainty in back-calculated dose estimates should be explicitly incorporated in quantitative estimates of TCDD's carcinogenic potency based on such data.read more
Citations
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Journal ArticleDOI
Dioxins: An overview
TL;DR: This review article summarizes what is known about human health following exposure to dioxins and is meant primarily for health professionals but was also written with the general public in mind.
Journal ArticleDOI
Dioxin Exposure, from Infancy through Puberty, Produces Endocrine Disruption and Affects Human Semen Quality
Paolo Mocarelli,Pier Mario Gerthoux,Donald G. Patterson,Silvano Milani,Giuseppe Limonta,Maria Bertona,Stefano Signorini,Pierluigi Tramacere,Laura Colombo,Carla Crespi,Paolo Brambilla,Cecilia Sarto,Vittorio Carreri,Eric J. Sampson,Wayman E. Turner,Larry L. Needham +15 more
TL;DR: Exposure to TCDD in infancy reduces sperm concentration and motility, and an opposite effect is seen with exposure during puberty, which is within one order of magnitude of those in the industrialized world in the 1970s and 1980s and may be responsible for the reported decrease in sperm quality.
Journal ArticleDOI
Apparent Half-Lives of Dioxins, Furans, and Polychlorinated Biphenyls as a Function of Age, Body Fat, Smoking Status, and Breast-Feeding
Meghan O. Milbrath,Yvan Wenger,C. W Chiung Wen Chang,Claude Emond,David H. Garabrant,Brenda W. Gillespie,Olivier Jolliet +6 more
TL;DR: The half-life of dioxin, furan, and polychlorinated biphenyl congeners named in the World Health Organization toxic equivalency factor scheme can be predicted using a linear relationship with age adjusted for body fat, smoking, and breast-feeding.
Journal ArticleDOI
Air pollution exposure assessment methods utilized in epidemiological studies.
TL;DR: This review critically reviewed 157 studies over 29 years that utilized one of five categories of exposure methods (proximity, air dispersion, hybrid, human inhalation, and biomarkers) and found proximity models were found to be a questionable technique.
Journal ArticleDOI
Risk for animal and human health related to the presence of dioxins and dioxin???like PCBs in feed and food
Helle Katrine Knutsen,Jan Alexander,Lars Barregård,Margherita Bignami,Beat Johannes Brüschweiler,Sandra Ceccatelli,Bruce Cottrill,Michael Dinovi,Lutz Edler,Bettina Grasl-Kraupp,Christer Hogstrand,Carlo Nebbia,Isabelle P. Oswald,Annette Petersen,Martin Rose,Alain-Claude Roudot,Tanja Schwerdtle,Christiane Vleminckx,Günter Vollmer,Heather M. Wallace,Peter Fürst,Helen Håkansson,Thorhallur I. Halldorsson,Anne-Katrine Lundebye,Raimo Pohjanvirta,Lars Rylander,Andrew Smith,Henk Van Loveren,Ine Waalkens-Berendsen,Marco J. Zeilmaker,Marco Binaglia,Jose Ángel Gómez Ruiz,Zsuzsanna Horvath,Eugen H. Christoph,Laura Ciccolallo,Luisa Ramos Bordajandi,Hans Steinkellner,Laurentius Hoogenboom +37 more
TL;DR: The CONTAM Panel was not able to identify reference values in most farm and companion animals with the exception of NOAELs for mink, chicken and some fish species, and the estimated exposure from feed for these species does not imply a risk.
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