How can biologically-based modeling of arsenic kinetics and dynamics inform the risk assessment process? - A workshop review

Elaina M. Kenyon, Walter Klimecki, Hisham El-Masri, Rory B. Conolly, Harvey J. Clewell, Barbara D. Beck

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Quantitative biologically-based models describing key events in the continuum from arsenic exposure to the development of adverse health effects provide a framework to integrate information obtained across diverse research areas. For example, genetic polymorphisms in arsenic metabolizing enzymes can lead to differences in target tissue dosimetry for key metabolites causative in toxic and carcinogenic response. This type of variation can be quantitatively incorporated into pharmacokinetic (PK) models and used together with population-based modeling approaches to evaluate the impact of genetic variation in methylation capacity on dose of key metabolites to target tissue. The PK model is an essential bridge to the pharmacodynamic (PD) models. A particular benefit of PD modeling for arsenic is that alternative models can be constructed for multiple proposed modes of action for arsenicals. Genomics data will prove useful for identifying the key pathways involved in particular responses and aid in determining other types of data needed for quantitative modeling. These models, when linked with PK models, can be used to better understand and explain dose- and time-response behaviors. This in turn assists in prioritizing modes of action with respect to their risk assessment relevance and future research. This type of integrated modeling approach can form the basis for a highly informative mode-of-action directed risk assessment for inorganic arsenic (iAs). This paper will address both practical and theoretical aspects of integrating PK and PD data in a modeling framework, including practical barriers to its application.

Original languageEnglish (US)
Pages (from-to)359-368
Number of pages10
JournalToxicology and Applied Pharmacology
Volume232
Issue number3
DOIs
StatePublished - Nov 1 2008

Fingerprint

Arsenic
Risk assessment
Pharmacokinetics
Education
Kinetics
Pharmacodynamics
Arsenicals
Poisons
Genetic Polymorphisms
Genomics
Methylation
Metabolites
Tissue
Health
Enzymes
Research
Population
Polymorphism
Dosimetry

Keywords

  • Arsenic
  • Modeling
  • Pharmacodynamics
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

How can biologically-based modeling of arsenic kinetics and dynamics inform the risk assessment process? - A workshop review. / Kenyon, Elaina M.; Klimecki, Walter; El-Masri, Hisham; Conolly, Rory B.; Clewell, Harvey J.; Beck, Barbara D.

In: Toxicology and Applied Pharmacology, Vol. 232, No. 3, 01.11.2008, p. 359-368.

Research output: Contribution to journalArticle

Kenyon, Elaina M. ; Klimecki, Walter ; El-Masri, Hisham ; Conolly, Rory B. ; Clewell, Harvey J. ; Beck, Barbara D. / How can biologically-based modeling of arsenic kinetics and dynamics inform the risk assessment process? - A workshop review. In: Toxicology and Applied Pharmacology. 2008 ; Vol. 232, No. 3. pp. 359-368.
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