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Physiologically based pharmacokinetic toolkit to evaluate environmental exposures: Applications of the dioxin model to study real life exposures.

Abstract：

:Chlorinated dibenzo-p-dioxins (CDDs) are a series of mono- to octa-chlorinated homologous chemicals commonly referred to as polychlorinated dioxins. One of the most potent, well-known, and persistent member of this family is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). As part of translational research to make computerized models accessible to health risk assessors, we present a Berkeley Madonna recoded version of the human physiologically based pharmacokinetic (PBPK) model used by the U.S. Environmental Protection Agency (EPA) in the recent dioxin assessment. This model incorporates CYP1A2 induction, which is an important metabolic vector that drives dioxin distribution in the human body, and it uses a variable elimination half-life that is body burden dependent. To evaluate the model accuracy, the recoded model predictions were compared with those of the original published model. The simulations performed with the recoded model matched well with those of the original model. The recoded model was then applied to available data sets of real life exposure studies. The recoded model can describe acute and chronic exposures and can be useful for interpreting human biomonitoring data as part of an overall dioxin and/or dioxin-like compounds risk assessment.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Emond C,Ruiz P,Mumtaz M

doi

10.1016/j.taap.2016.12.007

subject

Has Abstract

pub_date

2017-01-15 00:00:00

pages

70-79

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(16)30379-9

journal_volume

315

pub_type

杂志文章

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