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Dorman, David C., DVM, PhD, DABVT, ATS

david dormanProfessor of Toxicology

D.V.M.: Colorado State University

Ph.D./Residency: University of Illinois- Champaign Urbana
Post-doctoral Training: Chemical Industry Institute of Toxicology (CIIT)
Phone: (919) 513-6237
E-Mail: david_dorman@ncsu.edu

 

Research Areas:

My research areas focus on three broad areas: (a) toxicology; (b) canine cognition and olfaction; and (c) human risk assessments.

Toxicology: The primary objective of my research is to provide a refined understanding of potential toxicity in humans from exposure to chemicals. Our laboratory uses a combination of in vivo, in vitro, and modeling approaches to accomplish this aim. My research interests include evaluation of the effect of chemicals on neonates and other potentially sensitive subpopulations; examination of chemically-induced effects on behavior and cognitive development; and the application of dosimetry modeling and other pharmacokinetic methods to risk assessment. We have worked with a wide range of chemicals including manganese, tungsten, the organophosphate fenitrothion, di-butyl phthalate, acrolein, acetaldehyde, hydrogen sulfide, amongst others.

Cognition and Olfaction: Our laboratory has recently branched out to evaluate cognition and olfaction in military working dogs. This effort arose in part from our past work examining the effects of chemicals on nasal structure and function in rodents exposed to a variety of inhaled chemicals.  Ongoing work is directed at the improved selection of dogs for use in bomb detection, olfactory capabilities, and learning and memory in dogs.  We use a variety of tools including remote telemetry, field trials, and operant behavioral approaches. 

Human health risk assessment. This interest is reflected not only by our experimental research portfolio but also through my service on a variety of advisory committees. I am a Member of the National Toxicology Program Board of Scientific Counselors, the North Carolina Scientific Advisory Board on Toxic Air Pollutants, and am an advisor for the development of US EPA’s Provisional Advisory Levels.  I have also served on the following National Resource Council committees: Committee on Toxicology, Committee on Potential Health Risks from Recurrent Lead Exposure to DOD Firing Range, Committee to Review the IRIS Process, Draft IRIS Assessment for Formaldehyde, Emerging and Continuous Exposure Guidance Levels for Selected Submarine Contaminants, and the Committee on Animal Models for Testing Interventions Against Aerosolized Bioterrorism Agents.

Current Research:

Airborne particulate matter (PM) has been linked to a range of serious respiratory and cardiovascular health problems. Less attention however has been given to neurological and other health effects. One PM source of interest to our laboratory is Middle Eastern sand. Inhalation of sand dust has been associated with pneumonitis and other adverse health effects. Co-exposure to cigarette smoke is a known risk factor for some of these effects. We recently characterized the respiratory toxicity of inhaled sand collected from Camp Victory in Baghdad in animals with co-exposure to mainstream cigarette smoke. This study showed that the respiratory toxicity of Iraqi sand is qualitatively similar to or less than that seen following short-term silica exposure. We are extending this study to evaluate the respiratory toxicity of sand materials collected at distinct geographical regions within Iraq and Afghanistan. Another focus of our laboratory is examining the role that the olfactory system plays in transporting chemicals from the olfactory epithelium directly to the olfactory bulb and other brain structures (‘nose-to-brain’ transport). Our laboratory has most recently focused on the transport of manganese and tungsten. Our work with Middle East sand and tungsten has been performed in conjunction with the Naval Medical Research Unit in Dayton Ohio (http://www.med.navy.mil/sites/nmrc/Pages/namrud.htm).

Manganese Toxicity and Risk Assessment: As an essential element, manganese is required for normal function of the brain and other tissues. As with all other metals, manganese toxicity can occur with excessive exposure. A variety of clinical effects are associated with manganese toxicity, including manganism, a parkinsonian movement disorder that primarily affects dopaminergic and γ-aminobutyric acid (GABA)-containing mid-brain structures that control motor functions. These neurotoxic syndromes develop when either manganese intake is excessive (e.g., following high-dose oral, inhalation, or parenteral manganese exposure) or when hepatobiliary clearance of this metal is impaired. This observation suggests that the dose of manganese delivered to target regions within the brain is the primary determinant for manganese neurotoxicity. Our laboratory has completed an extensive set of pharmacokinetic studies in animals to better determine the dose-response relationship between manganese exposure and brain manganese concentration. For the past several years we have been collaborating with a team of scientists at The Hamner Institutes for Health Sciences (http://www.thehamner.org) to develop physiologically based pharmacokinetic (PBPK) models for manganese with application to human health risk assessment.

Canine Cognition and Olfaction: Improvised Explosive Devices (IEDs) are a leading cause of casualties in US Warfighters. The best detection system currently available is an IED Detector Dog (IDD) led by a qualified handler, but we still have much to learn with respect to canine detection capabilities, cognition, training, and canine-human communication. In response to this need, we are conducting research to better understand the mental capacities, olfactory function, and stress-related susceptibilities of IDDs during training and deployment. This effort involves veterinary researchers with expertise in animal behavior, laboratory animal medicine, and neuroscience.

Representative Publications:

Taylor MD, Clewell HJ 3rd, Andersen ME, Schroeter JD, Yoon M, Keene AM, Dorman DC.  Update on a Pharmacokinetic-Centric Alternative Tier II Program for MMT-Part II: Physiologically Based Pharmacokinetic Modeling and Manganese Risk Assessment.  J Toxicol. 2012;2012:791431.

Dorman DC, Andersen ME, Roper JM, Taylor MD.Update on a Pharmacokinetic-Centric Alternative Tier II Program for MMT-Part I: Program Implementation and Lessons Learned.  J Toxicol. 2012;2012:946742. Epub 2012 Mar 27.

Dorman DC, Mokashi V, Wagner DJ, Olabisi AO, Wong BA, Moss OR, Centeno JA, Guandalini G, Jackson DA, Dennis WE, Lewis JA, Thomas RS, Chapman GD.  Biological responses in rats exposed to cigarette smoke and Middle East sand (dust).  Inhal Toxicol. 2012;24(2):109-24.

Lucchini RG, Dorman DC, Elder A, Veronesi B.  Neurological impacts from inhalation of pollutants and the nose-brain connection.Neurotoxicology. 2012 Aug;33(4):838-41..

Yoon M, Schroeter JD, Nong A, Taylor MD, Dorman DC, Andersen ME, Clewell HJ 3rd.  Physiologically based pharmacokinetic modeling of fetal and neonatal manganese exposure in humans: describing manganese homeostasis during development.  Toxicol Sci. 2011 Aug;122(2):297-316..

Schroeter JD, Nong A, Yoon M, Taylor MD, Dorman DC, Andersen ME, Clewell HJ 3rd.  Analysis of manganese tracer kinetics and target tissue dosimetry in monkeys and humans with multi-route physiologically based pharmacokinetic models.  Toxicol Sci. 2011 Apr;120(2):481-98.

Andersen ME, Dorman DC, Clewell HJ 3rd, Taylor MD, Nong A. Multi-dose-route, multi-species pharmacokinetic models for manganese and their use in risk assessment.  J Toxicol Environ Health A. 2010;73(2):217-34.

Radcliffe PM, Leavens TL, Wagner DJ, Olabisi AO, Struve MF, Wong BA, Tewksbury E, Chapman GD, Dorman DC.  Pharmacokinetics of radiolabeled tungsten ((188)W) in male Sprague-Dawley rats following acute sodium tungstate inhalation.  Inhal Toxicol. 2010 Jan;22(1):69-76.

Yoon M, Nong A, Clewell HJ 3rd, Taylor MD, Dorman DC, Andersen ME.  Evaluating placental transfer and tissue concentrations of manganese in the pregnant rat and fetuses after inhalation exposures with a PBPK model. Toxicol Sci. 2009 Nov;112(1):44-58.

Yoon M, Nong A, Clewell HJ 3rd, Taylor MD, Dorman DC, Andersen ME.  Lactational transfer of manganese in rats: predicting manganese tissue concentration in the dam and pups from inhalation exposure with a pharmacokinetic model.Toxicol Sci. 2009 Nov;112(1):23-43.

Struve MF, Gaido KW, Hensley JB, Lehmann KP, Ross SM, Sochaski MA, Willson GA, Dorman DC.  Reproductive toxicity and pharmacokinetics of di-n-butyl phthalate (DBP) following dietary exposure of pregnant rats. Birth Defects Res B Dev Reprod Toxicol. 2009 Aug;86(4):345-54.

Radcliffe PM, Olabisi AO, Wagner DJ, Leavens T, Wong BA, Struve MF, Chapman GD, Wilfong ER, Dorman DC.  Acute sodium tungstate inhalation is associated with minimal olfactory transport of tungsten (188W) to the rat brain. Neurotoxicology. 2009 May;30(3):445-50.

Nong A, Taylor MD, Clewell HJ 3rd, Dorman DC, Andersen ME.  Manganese tissue dosimetry in rats and monkeys: accounting for dietary and inhaled Mn with physiologically based pharmacokinetic modeling.  Toxicol Sci. 2009 Mar;108(1):22-34.

Dorman DC, Struve MF, Norris A, Higgins AJ.Metabolomic analyses of body fluids after subchronic manganese inhalation in rhesus monkeys. Toxicol Sci. 2008 Nov;106(1):46-54.

Roberts ES, Thomas RS, Dorman DC. Gene expression changes following acute hydrogen sulfide (H2S)-induced nasal respiratory epithelial injury.  Toxicol Pathol. 2008 Jun;36(4):560-7.

Wetmore BA, Struve MF, Gao P, Sharma S, Allison N, Roberts KC, Letinski DJ, Nicolich MJ, Bird MG, Dorman DC.  Genotoxicity of intermittent co-exposure to benzene and toluene in male CD-1 mice. Chem Biol Interact. 2008 Jun 17;173(3):166-78.

Erikson KM, Dorman DC, Lash LH, Aschner M.  Duration of airborne-manganese exposure in rhesus monkeys is associated with brain regional changes in biomarkers of neurotoxicity.  Neurotoxicology. 2008 May;29(3):377-85.

Nong A, Teeguarden JG, Clewell HJ 3rd, Dorman DC, Andersen ME  Pharmacokinetic modeling of manganese in the rat IV: Assessing factors that contribute to brain accumulation during inhalation exposure.  J Toxicol Environ Health A. 2008;71(7):413-26.

Dorman DC, Struve MF, Wong BA, Gross EA, Parkinson C, Willson GA, Tan YM, Campbell JL, Teeguarden JG, Clewell HJ 3rd, Andersen ME.  Derivation of an inhalation reference concentration based upon olfactory neuronal loss in male rats following subchronic acetaldehyde inhalation. Inhal Toxicol. 2008 Feb;20(3):245-56.

Schroeter JD, Kimbell JS, Gross EA, Willson GA, Dorman DC, Tan YM, Clewell HJ 3rd.  Application of physiological computational fluid dynamics models to predict interspecies nasal dosimetry of inhaled acrolein.  Inhal Toxicol. 2008 Feb;20(3):227-43.

Lab Personnel:

Melanie Foster, Research Associate

melanie_foster@ncsu.edu

Beth Case, Research Assistant

beth_case@ncsu.edu

Lucia Lazarowski, Research Specialist

lucia_lazarowski@ncsu.edu