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Boyes WK, Simmons JE, Eklund C, et al. Applications of dosimetry modeling to assessment of neurotoxic risk. Environ Toxicol Pharmacol. 2005;19(3):599-605doi: 10.1016/j.etap.2004.12.025.
Boyes, W. K., Simmons, J. E., Eklund, C., Benignus, V. A., Janssen, P., & Bushnell, P. J. (2005). Applications of dosimetry modeling to assessment of neurotoxic risk. Environmental toxicology and pharmacology, 19(3), 599-605. https://doi.org/10.1016/j.etap.2004.12.025
Boyes, William K, et al. "Applications of dosimetry modeling to assessment of neurotoxic risk." Environmental toxicology and pharmacology vol. 19,3 (2005): 599-605. doi: https://doi.org/10.1016/j.etap.2004.12.025
Boyes WK, Simmons JE, Eklund C, Benignus VA, Janssen P, Bushnell PJ. Applications of dosimetry modeling to assessment of neurotoxic risk. Environ Toxicol Pharmacol. 2005 May;19(3):599-605. doi: 10.1016/j.etap.2004.12.025. PMID: 21783532.
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Environ Toxicol Pharmacol. 2005 May;19(3):599-605. doi: 10.1016/j.etap.2004.12.025.

Applications of dosimetry modeling to assessment of neurotoxic risk.

Environmental toxicology and pharmacology

William K Boyes, Jane Ellen Simmons, Christopher Eklund, Vernon A Benignus, Paul Janssen, Philip J Bushnell

Affiliations

  1. National Health and Environmental Effects Research Laboratory, B105-05, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.

PMID: 21783532 DOI: 10.1016/j.etap.2004.12.025

Abstract

Risk assessment procedures can be improved through better understanding and use of tissue dose information and linking tissue dose level to adverse outcomes. For volatile organic compounds, such as toluene and trichloroethylene (TCE), blood and brain concentrations can be estimated with physiologically based pharmacokinetic (PBPK) models. Acute changes in the function of the nervous system can be linked to the concentration of test compounds in the blood or brain at the time of neurological assessment. This set of information enables application to a number of risk assessment situations. For example, we have used this approach to recommend duration adjustments for acute exposure guideline levels (AEGLs) for TCE such that the exposure limits for each exposure duration yield identical tissue concentrations at the end of the exposure period. We have also used information on tissue concentration at the time of assessment to compare sensitivity across species, adjusting for species-specific pharmacokinetic differences. Finally this approach has enabled us to compare the relative sensitivity of different compounds on a tissue dose basis, leading to expression of acute solvent effects as ethanol-dose equivalents for purposes of estimating cost-benefit relationships of various environmental control options.

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