Cefic-lri Programme | European Chemical Industry Council

HBM2-DOW: Development of a Tiered Set of Modelling Tools for Derivation of Biomonitoring Guidance Values

Principal Investigator

Dr. Michael Bartels
Toxicology and Environmental Research & Consulting
1803 Building
Midland, Michigan, 48674, USA
Tel: +1 989 636 9057
Fax: +1 989 638 9305

Collaborators

Dr. George Loizou, Dr. Martin Spendiff, Dr. John Cocker – Health & Safety Laboratory (HSL), UK
Nicholas Ball – Dow Europe, Switzerland
Paul Price, Dr. Scott Arnold – Dow, USA

Description

Current determinations of the exposures that correspond with biomonitoring data (parent/metabolite in blood/urine) are generally conducted with chemical-specific pharmacokinetic models that are physiologically-based (PBPK), to best simulate xenobiotic disposition in complex mammalian systems. While these models are necessary to accurately determine exposure, there is a lack of standardization in their design and implementation. These issues have limited broad acceptance of this technique in determining acceptable exposure levels for chemicals.

Working towards this direction, a suite of tools would provide the best approach for forward- and reverse-dosimetry estimations of xenobiotic exposure. A tiered approach of simple, arithmetic pharmacokinetic (PK) models, as well as more standardized PBPK models, would promote the use of human biomonitoring data in the development of appropriate biomonitoring guidance values (BGVs). The output of these evaluations are potentially useful in setting hazard/exposure riteria, such as the Derived No-Effect Level Values under the EU REACH program.

 

Related Publications

Papers:

McNally K., Cotton R., Cocker J., Jones K., Bartels M., Rick D., Price P., Loizou G. (2012). Reconstruction of Exposure to m-Xylene from Human Biomonitoring Data Using PBPK Modellin, Bayesian Inference, and Markov Chain Monte Carlo Simulation. Journal of Toxicology, Epub April 2012.

Bartels M., Rick D., Lowe E., Loizou G., Price P., Spendiff M., Arnold S., Cocker J., Ball N. (2012).  Development of PK- and PBPK-based Modeling Tools for Derivation of Biomonitoring Guidance Values, Computer Methods Programs Biomedicine, 108(2):773-88.

Presentations:

Bartels M., Loizou G., Price P., Spendiff M., Arnold S., Cocker J., Ball N. (2009).  Development of a Tiered Set of Modelling Tools for Derivation of Biomonitoring Guidance Values, 45th Congress of the European Societies of Toxicology, 13-16 September 2009, Dresden Germany, Toxicology Letters: 189S, S57-S273.

Poster Presentations:

Michael J. Bartels, David Rick, Paul Price, Scott Arnold, Nicholas Ball, George Loizou, Martin Spendiff, John Cocker (2009).  Development of a Tiered Set of Modeling Tools for Derivation of Biomonitoring Guidance Values.  19th Annual meeting of the International Society of Exposure Science (abstract 2009-A-508-ISES), 2-7 November, Minneapolis, Minnesota, US.

M. Bartels, G. Loizou, P. Price, D. Rick, M. Spendiff, S. Arnold, J. Cocker, N. Ball (2010).  Development of PK- and PBPK-based modeling tools for derivation of biomonitoring guidance values, XII International Congress of Toxicology, 29-12 July 2010, Barcelona Spain (abstract P101-018), Toxicology Letters: 196S, S37-S351.

 

Michael J. Bartels, David Rick, Paul Price, Scott Arnold, Nicholas Ball, George Loizou, Martin Spendiff, John Cocker (2010).  Development of a Tiered Set of Modeling Tools for Derivation of Biomonitoring Guidance Values.  Cefic-LRI 12th Annual Workshop 2010 Reduction of Uncertainty Enabling Decision Making, 17-18 November 2010 Radisson Blu Royal Hotel, Brussels, Belgium

Timeline: January 2008 > June 2010

LRI funding: €300,000

Cefic-Lri Programme Responsible Care

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