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Physiologically based pharmacokinetic modeling of cyclohexane as a tool for integrating animal and human test data.
Int J Toxicol. 2009 Nov-Dec; 28(6):498-509.IJ

Abstract

This report describes a physiologically based pharmacokinetic model for cyclohexane and its use in comparing internal doses in rats and volunteers following inhalation exposures. Parameters describing saturable metabolism of cyclohexane are measured in rats and used along with experimentally determined partition coefficients. The model is evaluated by comparing predicted blood and brain concentrations to data from studies in rats and then allometrically scaling the results to humans. Levels of cyclohexane in blood and exhaled air are measured in human volunteers and compared with model values. The model predicts that exposure of volunteers to cyclohexane at levels of 4100 mg/m(3) (approximately 1200 ppm) will result in brain levels similar to those in rats exposed to 8000 mg/m(3) (the no-effect level for acute central nervous system effects). There are no acute central nervous system effects in humans exposed to 860 mg/m(3), consistent with model predictions that current occupational exposure levels for cyclohexane protect against acute central nervous system effects.

Authors+Show Affiliations

TNO Quality of Life, Zeist, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19966142

Citation

Hissink, A M., et al. "Physiologically Based Pharmacokinetic Modeling of Cyclohexane as a Tool for Integrating Animal and Human Test Data." International Journal of Toxicology, vol. 28, no. 6, 2009, pp. 498-509.
Hissink AM, Kulig BM, Kruse J, et al. Physiologically based pharmacokinetic modeling of cyclohexane as a tool for integrating animal and human test data. Int J Toxicol. 2009;28(6):498-509.
Hissink, A. M., Kulig, B. M., Kruse, J., Freidig, A. P., Verwei, M., Muijser, H., Lammers, J. H., McKee, R. H., Owen, D. E., Sweeney, L. M., & Salmon, F. (2009). Physiologically based pharmacokinetic modeling of cyclohexane as a tool for integrating animal and human test data. International Journal of Toxicology, 28(6), 498-509. https://doi.org/10.1177/1091581809348718
Hissink AM, et al. Physiologically Based Pharmacokinetic Modeling of Cyclohexane as a Tool for Integrating Animal and Human Test Data. Int J Toxicol. 2009 Nov-Dec;28(6):498-509. PubMed PMID: 19966142.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Physiologically based pharmacokinetic modeling of cyclohexane as a tool for integrating animal and human test data. AU - Hissink,A M, AU - Kulig,B M, AU - Kruse,J, AU - Freidig,A P, AU - Verwei,M, AU - Muijser,H, AU - Lammers,J H C M, AU - McKee,R H, AU - Owen,D E, AU - Sweeney,L M, AU - Salmon,F, PY - 2009/12/8/entrez PY - 2009/12/8/pubmed PY - 2010/2/18/medline SP - 498 EP - 509 JF - International journal of toxicology JO - Int J Toxicol VL - 28 IS - 6 N2 - This report describes a physiologically based pharmacokinetic model for cyclohexane and its use in comparing internal doses in rats and volunteers following inhalation exposures. Parameters describing saturable metabolism of cyclohexane are measured in rats and used along with experimentally determined partition coefficients. The model is evaluated by comparing predicted blood and brain concentrations to data from studies in rats and then allometrically scaling the results to humans. Levels of cyclohexane in blood and exhaled air are measured in human volunteers and compared with model values. The model predicts that exposure of volunteers to cyclohexane at levels of 4100 mg/m(3) (approximately 1200 ppm) will result in brain levels similar to those in rats exposed to 8000 mg/m(3) (the no-effect level for acute central nervous system effects). There are no acute central nervous system effects in humans exposed to 860 mg/m(3), consistent with model predictions that current occupational exposure levels for cyclohexane protect against acute central nervous system effects. SN - 1092-874X UR - https://www.unboundmedicine.com/medline/citation/19966142/Physiologically_based_pharmacokinetic_modeling_of_cyclohexane_as_a_tool_for_integrating_animal_and_human_test_data_ L2 - https://journals.sagepub.com/doi/10.1177/1091581809348718?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -