Mathematical Modeling and Trichloroethylene

Chapter
Part of the Molecular and Integrative Toxicology book series (MOLECUL)

Abstract

Mathematical modeling has been used extensively to quantify and characterize the disposition, fate, and risk associated with the volatile organic chemical trichloroethylene (TCE). Here, we summarize many of these models that have been developed and applied across the exposure-dose-effect continuum, ranging from pharmacokinetic and pharmacodynamic models to quantitative structure-activity relationships. We conclude by reviewing some future directions in computational modeling that are increasingly used to inform an understanding of the adverse health effects associated with exposure to TCE, and introduce elements of a first-generation systems biology model of TCE-induced autoimmune disease.

Keywords

Mathematical modeling Computational modeling Exposure Pharmacokinetics Pharmacodynamics QSAR Systems biology Omics Dose response 

Acronyms and Abbreviations

ADME

Absorption, distribution, metabolism, and excretion

AIH

Autoimmune hepatitis

ARR

Arrest of mitosis in Aspergillus nidulans

AUC

Area under the curve

BBDR

Biologically-based dose response

BBPD

Biologically-based pharmacodynamic

BDM

Benchmark dose method

BEI

Biological exposure index

CNS

Central nervous system

CPK

Compartmental pharmacokinetic

D37

Measure of lethality in Aspergillus nidulans

DCA

Dichloroacetic acid

DCVC

S-(1,2-dichlorovinyl)-L-cysteine

DCVG

S-(1,2-dichlorovinyl)glutathione

DIFF

Difference between the highest occupied molecular orbital and the lowest unoccupied molecular orbital

DNAPL

Dense nonaqueous phase liquid

EDR

Exposure-dose-response

EPA

US Environmental Protection Agency

HBA

H-bonding acceptor ability

HBD

H-bonding donor ability

IC50

Chemical concentration that inhibits some endpoint in 50 % of the test animals in a given time

IRIS

Integrated Risk Information System

Kow

Octanol-water partition coefficient

LC50

Chemical concentration that kills 50 % of the test animals in a given time

LCA

Life cycle assessment

LEC

Induction of chromosome malsegregation leading to aneuploidy in Aspergillus nidulans

LOEC

Lowest observed effect concentration

logP

The log of the ratio of concentration of neutral species in octanol divided the concentration of neutral species in water

MCL

Maximum contaminant level

MOE

Margin of exposure

MR

Molar refractivity

MRL

Minimal risk level

NAPL

Non-aqueous phase liquid

NCPK

Non-compartmental pharmacokinetic

PBPK

Physiologically-based pharmacokinetic

PC

Partition coefficient

PCE

Tetrachloroethylene, perchloroethylene

PD

Pharmacodynamics

PEL

Permissible exposure limit

PK

Pharmacokinetics

QSAR

Quantitative structure activity relationship

RfC

Reference concentration

t1/2

Chemical half life

TAI

TCE-induced autoimmunity

TBARS

Thiobarbituric acid reactive substance

TCA

Trichloroacetic acid

TCE

Trichloroethylene

TCOH

Trichloroethanol

TLV

Threshold limit value

VOC

Volatile organic compound

Notes

Acknowledgements

The authors thank Dr. Arthur N. Mayeno for his contribution to the materials contained in this chapter.

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© Springer-Verlag London 2014

Authors and Affiliations

  1. 1.Department of Chemical and Biological Engineering and School of Biomedical EngineeringColorado State UniversityFort CollinsUSA
  2. 2.Department of Chemical and Biological EngineeringColorado State UniversityFort CollinsUSA

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