A pharmacokinetic analysis of interspecies extrapolation in dioxin risk assessment

Lawrence, Gary S.; Gobas, Frank A.P.C.

doi:10.1016/s0045-6535(97)00108-2

Cited by 22 publications

(12 citation statements)

References 51 publications

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“…All of the mathematical equations and descriptions of the symbol are presented in Supplemental Materials Section A and B. Anatomical, physiological, and biochemical parameters (e.g., tissue volumes, cardiac output, blood flows, partition coefficients, and permeability constants) were extracted from the literature (Emond et al 2004; Krishnan and Andersen 2008; Lawrence and Gobas 1997; Poiger and Schlatter 1986; Wang et al 1997). Other parameters such as fetal weight or adipose tissue content during pregnancy were described as functions using data from literature.…”

Section: Methodsmentioning

confidence: 99%

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An assessment of dioxin exposure across gestation and lactation using a PBPK model and new data from Seveso

Emond

DeVito

Warner

et al. 2016

Environment International

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On July 10, 1976, an explosion at a chemical plant in Seveso, Italy, released up to 30 kg 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 4–39 years old and in Subcohort B, the 18 women were 3–17 years old when the explosion occurred. The model accurately predicted the blood concentrations during the 20 years 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.

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Section: Methodsmentioning

confidence: 99%

“… a Units for human non-gestational parameters are L and kg. b (Krishnan and Andersen 2008) c Units are L/kg/day. d (Wang et al 1997) e Optimized. f (Emond et al 2004) g (Lawrence and Gobas 1997) …”

Section: Figmentioning

confidence: 99%

An assessment of dioxin exposure across gestation and lactation using a PBPK model and new data from Seveso

Emond

DeVito

Warner

et al. 2016

Environment International

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show abstract

“…8.6). Level 1 models by Lawrence and Gobas (1997) and Leung et al (1988) feature two specific binding proteins (i.e., cytosolic AhR and microsomal CYP1A2) in the liver, with or without consideration of CYP1A1/2 induction. The Leung et al (1988) model was later subjected to modifications, such as incorporation of extrahepatic AhR-binding sites (muscle and skin) (Leung et al 1990b) and CYP1A1/2 induction (Leung et al 1990a).…”

Section: Pbpk Models Of Tcdd In Rodentsmentioning

confidence: 99%

“…To study TCDD internal distribution patterns in different species and their impact on risk assessment, Lawrence and Gobas (1997) developed PBPK models for rodents (rats and mice) and humans. The human model had blood, muscle, viscera, skin, fat, kidney, liver, and gut (divided into gut tissue and gut lumen) compartments.…”

Section: Reference Man Lifetime Exposure Modelmentioning

confidence: 99%

Dioxin and Related Compounds

2005

Physiologically Based Pharmacokinetic Modeling

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“…The physiologically based toxicokinetic (PBTK) models have previously been used to quantify the magnitude of UF AH for few chemicals (Clewell III and Jarnot, 1994 Gobas, 1997;Pelekis, 1998). The interspecies toxicokinetic uncertainty factors (UF AH-TK ) derived in these studies are appropriate only when steady-state conditions or lifetime exposures have been simulated.…”

Section: Introductionmentioning

confidence: 99%

Magnitude and mechanistic determinants of the interspecies toxicokinetic uncertainty factor for organic chemicals

Pelekis¹,

Krishnan²

2004

Regulatory Toxicology and Pharmacology

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A pharmacokinetic analysis of interspecies extrapolation in dioxin risk assessment

Cited by 22 publications

References 51 publications

An assessment of dioxin exposure across gestation and lactation using a PBPK model and new data from Seveso

An assessment of dioxin exposure across gestation and lactation using a PBPK model and new data from Seveso

Dioxin and Related Compounds

Magnitude and mechanistic determinants of the interspecies toxicokinetic uncertainty factor for organic chemicals

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