title: 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.
authors.affiliation: BioSimulation Consulting Inc., Newark, DE, USA; Department of Environmental and Occupational Health, University of Montreal, Quebec, Canada. Electronic address: claude.Emond@umontreal.ca.
authors.forename: C
authors.initials: C
authors.lastname: Emond
authors.affiliation: National Institute of Environmental Health Sciences, National Toxicology Program, Research Triangle Park, NC, USA.
authors.forename: M
authors.initials: M
authors.lastname: DeVito
authors.affiliation: School of Public Health, University of California, Berkeley, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Warner
authors.affiliation: School of Public Health, University of California, Berkeley, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Eskenazi
authors.affiliation: Department of Laboratory Medicine, University of Milano-Bicocca, School of Medicine, Hospital of Desio, Desio, Milano, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Mocarelli
authors.affiliation: National Cancer Institute, Research Triangle Park, NC, USA.
authors.forename: L S
authors.initials: LS
authors.lastname: Birnbaum
mesh_terms: D015331:Cohort Studies; D004781:Environmental Exposure / Q000032:analysis*; D004785:Environmental Pollutants / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005544:Forecasting; D006801:Humans; D007558:Italy; D007774:Lactation; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D008954:Models, Biological; D000072317:Polychlorinated Dibenzodioxins / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D011247:Pregnancy; D016387:Women's Health
chemical_list: D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins
keywords: Developmental; Dioxin; PBPK; Pharmacokinetics; TCDD