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An assessment of dioxin exposure across gestation and lactation using a PBPK model and new data from Seveso
Abstract On July 10, 1976, an explosion at a chemical plant in Seveso, Italy, released up to 30kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)—the most potent dioxin congener. Twenty years later, the Seveso Women's Health Study (SWHS) initiated a follow-up assessment of a cohort of female Seveso residents. Researchers collected serial blood, measured for TCDD levels, and recorded information about the women's medical history after the explosion. The study's aims were to: 1) modify the human PBPK model for TCDD (Emond et al. 2004; Emond et al. 2005; NCEA-USEPA, 2010) to include repetitive gestation and lactation; 2) simulate TCDD blood concentrations during different life stages including pregnancy and lactation, under different exposure scenarios; and 3) use this PBPK model to compare the influence of gestation and lactation on elimination of TCDD. After optimization of the model, it was assessed using data from the SWHS cohort. The 23 women in Subcohort A, were 4–39years old and in Subcohort B, the 18 women were 3–17years old when the explosion occurred. The model accurately predicted the blood concentrations during the 20years post-exposure, including periods of pregnancy and lactation. The model was also used to analyze the contribution of gestation and lactation to the mother's elimination of TCDD. The results suggest that gestation and lactation do not significantly impact TCDD blood elimination. Future efforts will focus on using additional data to evaluate the PBPK model and improving the mathematical descriptions of lactation and multiple gestations.
Highlights PBPK modeling can help to determine what influence the TCDD elimination. The PBPK model accurately reproduces the exposure profiles of the Seveso women. A small impact for the mother, but significant ones for the fetus and newborn. The importance of gestation/lactation was overrated in the old literature of TCDD. The PBPK model is an important quantification tool for human risk assessments.
An assessment of dioxin exposure across gestation and lactation using a PBPK model and new data from Seveso
Abstract On July 10, 1976, an explosion at a chemical plant in Seveso, Italy, released up to 30kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)—the most potent dioxin congener. Twenty years later, the Seveso Women's Health Study (SWHS) initiated a follow-up assessment of a cohort of female Seveso residents. Researchers collected serial blood, measured for TCDD levels, and recorded information about the women's medical history after the explosion. The study's aims were to: 1) modify the human PBPK model for TCDD (Emond et al. 2004; Emond et al. 2005; NCEA-USEPA, 2010) to include repetitive gestation and lactation; 2) simulate TCDD blood concentrations during different life stages including pregnancy and lactation, under different exposure scenarios; and 3) use this PBPK model to compare the influence of gestation and lactation on elimination of TCDD. After optimization of the model, it was assessed using data from the SWHS cohort. The 23 women in Subcohort A, were 4–39years old and in Subcohort B, the 18 women were 3–17years old when the explosion occurred. The model accurately predicted the blood concentrations during the 20years post-exposure, including periods of pregnancy and lactation. The model was also used to analyze the contribution of gestation and lactation to the mother's elimination of TCDD. The results suggest that gestation and lactation do not significantly impact TCDD blood elimination. Future efforts will focus on using additional data to evaluate the PBPK model and improving the mathematical descriptions of lactation and multiple gestations.
Highlights PBPK modeling can help to determine what influence the TCDD elimination. The PBPK model accurately reproduces the exposure profiles of the Seveso women. A small impact for the mother, but significant ones for the fetus and newborn. The importance of gestation/lactation was overrated in the old literature of TCDD. The PBPK model is an important quantification tool for human risk assessments.
An assessment of dioxin exposure across gestation and lactation using a PBPK model and new data from Seveso
Emond, C. (author) / DeVito, M. (author) / Warner, M. (author) / Eskenazi, B. (author) / Mocarelli, P. (author) / Birnbaum, L.S. (author)
Environmental International ; 92-93 ; 23-32
2016-03-14
10 pages
Article (Journal)
Electronic Resource
English
acslX® , Advanced Continuous Simulation Language , AhR , aryl hydrocarbon receptor , AUC , area under the curve , CYP1A , Cytochrome P4501A , CYP1A2 , Cytochrome P4501A2 , CYP1B , Cytochrome P4501B , EPA , U.S. Environmental Protection Agency , GI , gastrointestinal , ICMESA , Industrie Chimiche Meda Società Azionaria , NCEA , National Center for Environmental Assessment , NIH , National Institutes of Health , NIEHS , National Institute of Environmental Health Sciences , PBPK , physiologically based pharmacokinetic , PCB , polychlorinated biphenyl , R<sup>2</sup> , R-squared , TCDD , 2,3,7,8-tetrachlorodibenzo-p-dioxin , Pharmacokinetics , Dioxin , Developmental
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