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HERO ID
5882998
Reference Type
Book/Book Chapter
Title
Physiologically based pharmacokinetic models in the risk assessment of developmental neurotoxicants
Author(s)
Krishnan, K
Year
2018
Journal
Reproductive and Developmental Toxicology
ISSN:
978-0-12-804239-7
Publisher
Academic Press
Location
Cambridge, MA
Book Title
Handbook of Developmental Neurotoxicology (Second Edition)
Page Numbers
539-557
Language
English
DOI
10.1016/B978-0-12-809405-1.00047-X
URL
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85081918844&doi=10.1016%2fB978-0-12-809405-1.00047-X&partnerID=40&md5=28d025279f9e69bed686b9ee8a77b89e
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Abstract
Health risk assessment for developmental neurotoxicants often requires the analysis and use of data collected in nonhuman mammalian species exposed to high doses, at different developmental stages, via exposure routes and scenarios different from anticipated human exposures. In such cases, the challenge of extrapolating from one test or exposure condition and dose level to another can be resolved on the basis of target tissue dose (e.g., area under the brain concentration vs. time curve and maximal brain concentration). Physiologically based pharmacokinetic (PBPK) models are scientifically sound tools that facilitate the simulation of target tissue dose for a number of developmental neurotoxicants (e.g., dioxins, polychlorinated biphenyls, organochlorine pesticides, metals, and organometallics). The construction and evaluation of PBPK models to account for prenatal and postnatal exposures is described in this chapter along with examples of their application in the risk assessment of methylmercury, atrazine, chlorpyriphos, and ethanol. The use of PBPK models in the risk assessment for developmental neurotoxicants will not only enhance the credibility of the process, but also provide a dynamic way of integrating new observations on the mode of action, biomonitoring, and high throughput screening assays as they emerge for diverse sets of developmental neurotoxicants.
Keywords
Brain dosimetry; Fetal exposure; Internal dose; Lactational exposure; PBPK models; Risk assessment
Edition
2nd
Editor(s)
Slikker, W, Jr; Paule, MG; Wang, C
Tags
IRIS
•
Methylmercury
Literature Search: Jan 1998 - March 2017
Human Data
ToxNet
ADME Search: Jan 1990 - Nov 2018
ToxNet
PBPK Search: Jan 2001-Oct 2019
Science Direct
Scopus
PBPK Text Review: October 2019
Supplement
ADME
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