Harvey J. Clewell III, Ph.D., DABT

Senior Investigator and Director, Center for Human Health Assessment

hclewell@thehamner.org
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Education

B.A., chemistry, Bradley University, Peoria, Illinois, 1969.

M.A., physical chemistry, Washington University, St. Louis, Missouri, 1971.

Ph.D., toxicology, University of Utrecht, Utrecht, The Netherlands, 2007.

Diplomate, American Board of Toxicology.

Research

My research interests are in the areas of biological modeling, toxicology, and chemical safety/risk assessment. The focus of my work is on in vitro to in vivo extrapolation of cell-based toxicity assays, modeling of nanoparticle disposition and effects, incorporation of genomic dose-response information in risk assessment, and application of systems biology approaches to understand drug induced liver toxicity.

Selected Publications - click to view

Reddy, M.B., Clewell, H.J., Andersen, M.E., Lave, T.  2010.  Physiologically Based Pharmacokinetic Modeling in Drug Development: Past, Present, and Future.  Current Opinion in Drug Discovery Development, in press.

Bois FY, Jamei M, Clewell HJ.  2010.  PBPK modelling of inter-individual variability in the pharmacokinetics of environmental chemicals.  Toxicology, in press.

Boellmann F, Zhang L, Clewell HJ, Schroth GP, Kenyon EM, Andersen ME, Thomas RS.  2010.  Genome wide analysis of DNA methylation and gene expression changes in the mouse lung following subchronic arsenate exposure.  Toxicol Sci, 117(2):404-417.

Anders MW, Andersen ME, Clewell HJ 3rd, Gargas ML, Guengerich FP, Reitz RH.  2010.  Comment on M.V. Evans and J.C. Caldwell: Evaluation of two different metabolic hypotheses for dichloromethane toxicity using physiologically based pharmacokinetic modeling of in vivo gas uptake data exposure in female B6C3F1 mice, Toxicol. Appl. Pharmacol., 244, 280-290, 2010.  Toxicol Sci, 248(1):63-64.

Rotroff DM, Wetmore BA, Dix DJ, Ferguson SS, Clewell HJ, Houck KA, Lecluyse EL, Andersen ME, Judson RS, Smith CM, Sochaski MA, Kavlock RJ, Boellmann F, Martin MT, Reif DM, Wambaugh JF, Thomas RS.  2010.  Incorporating Human Dosimetry and Exposure into High-Throughput In Vitro Toxicity Screening.  Toxicol Sci, 117(2):348-358.

Yang, Y., Allen, B.C., Tan, Y.M., Liao, K.H., and Clewell, H.J. III  2010.  Markov Chain Monte Carlo Analysis of a Rat Formaldehyde-DPX Model.  J. Tox Environ Health, 73:787-806.

Meng, F., Bermudez, E., Andersen, M.E., Clewell, H.J., III, McKinzie P.B., Parsons, B.L.  2010.   Measurement of tumor-associated mutations in the nasal mucosa of rats exposed to varying doses of formaldehyde.  Reg Toxicol Pharmacol 57(2-3):274-283..

Andersen, M.E., Dorman, D.C., Clewell, H.J. 3rd, Taylor, M.D., Nong, A. 2010.  Multi-dose-route, multi-species pharmacokinetic models for manganese and their use in risk assessment.  J Toxicol Environ Health A 73(2):217-234.

Gentry, P.R., McDonald, T.B., Sullivan, d.e., Shipp, A.M., Yager, J.W., and Clewell, H.J., III.  2010.  Analysis of genomic dose-response information on arsenic to inform key events in a mode of action for carcinogenicity.  Environmental and Molecular Mutagenesis 51:1-14.

Yoon, M., Nong, A., Clewell, H.J. 3rd, Taylor, M.D., Dorman, D.C., and Andersen, M.E.  2009.  Evaluating placental transfer and tissue concentrations of manganese in the pregnant rat and fetuses after inhalation exposures with a PBPK model. Toxicol Sci. 112(1):44-58.

Yoon, M., Nong, A., Clewell, H.J. 3rd, Taylor, M.D., Dorman, D.C., and Andersen, M.E.  2009.  Lactational transfer of manganese in rats: Predicting manganese tissue concentration in the dam and pups from inhalation exposure with a pharmacokinetic model. Toxicol Sci. 112(1):23-43.

Clewell, R.A., Campbell, J.L., Ross, S.M., Gaido, K.W., Clewell, H.J. 3rd, and Andersen, M.E.  2009.  Assessing the relevance of in vitro measures of phthalate inhibition of steroidogenesis for in vivo response. Toxicol In Vitro, 24(1):327-34.

Sweeney, L.M., Kirman, C.R., Albertini, R.J., Tan, Y.M., Clewell, H.J., Filser, J.G., Csanády, G., Pottenger, L.H., Banton, M.I., Graham, C.J., Andrews, L.S., Papciak, R.J., Gargas, M.L.  2009.  Derivation of inhalation toxicity reference values for propylene oxide using mode of action analysis: Example of a threshold carcinogen. Crit Rev Toxicol. 39(6):462-86.

Nong, A., Taylor, M.D., Clewell, H.J. III, Dorman, D.C., Andersen, M.E.  2008.  Manganese tissue dosimetry in rats and monkeys: accounting for dietary and inhaled Mn with physiologically-based pharmacokinetic modeling. Toxicol. Sci., 108(1):22-34.

Kenyon, E.M., Hughes, M.F., Adair, B.M., Highfill1, J.H., Crecelius, E.A., Clewell, H.J., andYager, J.W.  2008.  Tissue distribution and urinary excretion of inorganic arsenic and its methylated metabolites in C57BL6 mice following subchronic exposure to arsenate in drinking water.  Toxicol. Appl. Pharmacol., 232(3):448-455.

Andersen, M.E., Clewell, H.J.. 3rd, Bermudez, E., Willson, G.A., and Thomas, R.S.  2008.  Genomic Signatures and Dose Dependent Transitions in Nasal Epithelial Responses to Inhaled Formaldehyde in the Rat. Toxicol Sci., 105(2):368-383.

Kenyon, E.M., Klimecki, W.T., El-Masri, H., Conolly, R.B., Clewell, H.J., and Beck, B.D.  2008.  How can biologically-based modeling of arsenic kinetics and dynamics inform the risk assessment process? - A workshop review. Toxicol Appl Pharmacol., 232(3):359-368.

Nong, A., Tan, Y.-M., Krolski, M., Wang, J., Lunchick, C., Conolly, R.B., and Clewell, H.J.  2008.  Bayesian calibration of a physiologically based pharmacokinetic/ pharmacodynamic model of carbaryl cholinesterase inhibition.  J. Toxicol. Environ. Health, 71(20):1363-1381.

Clewell, H.J., Andersen, H.J., and Blaauboer, B.J.  2008.  On the incorporation of chemical-specific information in risk assessment.  Toxicology Letters, 180:100-109.

Clewell, H. J., Tan, Y. M., Campbell, J.L., and Andersen, M.E.  2008.  Quantitative interpretation of human biomonitoring data.  Tox. Appl. Pharmacol., 231:122-133.

Bogen, K.T., Benson, J.M., Yost, G.S., Morris, J.B., Dahl, A.R., Clewell, H.J. 3rd, Krishnan, K., and Omiecinski, C.J. (2008). Naphthalene metabolism in relation to target tissue anatomy, physiology, cytotoxicity and tumorigenic mechanism of action. Reg Tox Pharm. 51(2), Suppl 1:27-36.

Zhang Q., Pi J., Woods C.G., Jarabek A.M., Clewell H.J. III, and Andersen M.E. ((2008)). Hormesis and Adaptive Cellular Control Systems. Dose-Response. 6(2):196-208.

Loizou G, Spendiff M, Barton HA, Bessems J, Bois FY, d'Yvoire MB, Buist H, Clewell HJ 3rd, Meek B, Gundert-Remy U, Goerlitz G, Schmitt W. (2008). Development of good modelling practice for physiologically based pharmacokinetic models for use in risk assessment: The first steps. Regul Toxicol Pharmacol. 50:400-411.

Nong, A., Teeguarden, J.G., Clewell, H.J., 3rd, Dorman, D.C., and Andersen, M.E. (2008). Pharmacokinetic modeling of manganese in the rat IV: Assessing factors that contribute to brain accumulation during inhalation exposure. J Toxicol Environ Health A. 71(7):413-426.

Dorman DC, Struve MF, Wong BA, Gross EA, Parkinson C, and Willson GA, Tan YM, Campbell JL, Teeguarden JG, Clewell HJ III, and Andersen ME. (2008). Derivation of an inhalation reference concentration based upon olfactory neuronal loss in male rats following subchronic acetaldehyde inhalation. Inhal. Toxicol. 20(3):245-256.

Schroeter JD, Kimbell JS, Gross EA, Willson GA, Dorman DC, Tan YM, and Clewell HJ III. (2008). Application of physiological computational fluid dynamics models to predict interspecies nasal dosimetry of inhaled acrolein. Inhal. Toxicol. 20(3):227-244.

Tan, Y.M, Clewell, H.J., and Andersen, M.E. (2008). Time dependencies in perfluorooctylacids disposition in rat and monkeys: A kinetic analysis. Toxicology Letters 177(1):38-47.

Clewell, R.A. and Clewell, H.J. (2008). Development and Specification of Physiologically Based Pharmacokinetic Models for Use in Risk Assessment. Reg. Tox. Pharm., 50:129-143.

Liao, K.H., Tan, Y.-M., Conolly, R.B., and Clewell, H.J. (2007). Bayesian estimation of pharmacokinetic and pharmacodynamic parameters in a mode-of-action based cancer risk assessment for chloroform. Risk Anal., 27(6):1535-1551.

Liao, K.H., Tan, Y.-M., and Clewell, H.J. (2007). Development of a screening approach to interpret human biomonitoring data on volatile organic compounds (VOCs). Risk Anal., 27(5):1223-1236.

Tan, Y.-M., Liao, K.H., and Clewell, H.J. (2007). Reverse dosimetry: Interpreting trihalomethanes biomonitoring data using physiologically based pharmacokinetic modeling. J. of Exposure Science and Environmental Epidemiology, 17:591-603.

Clewell, H.J., Thomas, R.S., Gentry, P.R., Crump, K.S., Kenyon, E.M., El-Masri, H.A., Yager, J.W. (2007). Research toward the development of a biologically based dose response assessment for inorganic arsenic carcinogenicity: A progress report. Toxicol. Appl. Pharmacol. 222:388-398.

Bahadori, T., Phillips, R.D., Money, C.D., Quackenboss, J.J., Clewell, H.J., Bus, J.S., Robison, S.H., Humphris, C.J., Parekh, A.A., Osborn, K., Kauffman, R.M. (2007). Making sense of human biomonitoring data: Findings and recommendations of a workshop. J Expo Sci Environ Epidemiol. (4):308-313.

Thomas, R.S., Allen, B.C., Nong, A., Yang, L., Bermudez, E., Clewell, H.J. 3rd, and Andersen, M.E. (2007). A Method to Integrate Benchmark Dose Estimates with Genomic Data to Assess the Functional Effects of Chemical Exposure. Toxicol Sci. 98(1):240-248

Clewell, R. A., Merrill, E. A., Gearhart, J. M., Robinson, P. J., Sterner, T. R., Mattie, D. R., and Clewell, H. J. III. (2007). Perchlorate and radioiodide kinetics across life-stages in the human: Using PBPK models to predict dosimetry and thyroid inhibition and sensitive subpopulations based on developmental stage. J. Toxicol. Environ. Health, Part A 70(5), 408-428.

Hack, C. E., Covington, T. R., Lawrence, G., Shipp, A. M., Gentry, P. R., Yager, J. A., and Clewell, H. J. III. (2007). A pharmacokinetic model of the intracellular dosimetry of inhaled nickel. J. Toxicol. Environ. Health, Part A 70, 445-464.

Andersen, M. E., Clewell, H. J., Tan, Y.-M., Butenhoff, J. L., and Olsen, G. W. (2006). Pharmacokinetic modeling of saturable, renal resorption of perfluoroalkylacids in monkeys - Probing the determinants of long plasma half-lives. Toxicology 227(1-2), 156-164.

Dorman, D. C., Struve. M. F., Clewell, H. J. 3rd, and Andersen, M. E. (2006). Application of pharmacokinetic data to the risk assessment of inhaled manganese. Neurotoxicology 27, 752-764.

Tan, Y.-M., Liao, Kai H., Conolly, R. B., Blount, B. C., Mason, A. M., and Clewell, H. J. (2006). Use of a physiologically based pharmacokinetic model to identify exposures consistent with human biomonitoring data for chloroform. J. Toxicol. Environ. Health Part A 69, 1727-1756.

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