Dorman, David C., DVM, PhD, DABVT, ATS
Professor 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
My research and professional interests focus on three broad areas: (a) toxicology; (b) cognition and olfaction; and (c) human risk assessments.
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 has included 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 chemical 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.
Our laboratory examines 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 tungsten was performed in conjunction with the Naval Medical Research Unit in Dayton Ohio (http://www.med.navy.mil/sites/nmrc/Pages/namrud.htm).
Ongoing research has also centered on manganese toxicity and risk assessment. As an essential element, manganese is required for normal function of the brain and other tissues. As with 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.
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. Our recent work sought to improve selection of dogs for use in bomb detection and evaluate olfactory capabilities, learning, and memory in dogs. We use a variety of tools including remote telemetry, field trials, and operant behavioral approaches. Ongoing research is evaluating dietary manipulation and early scent exposure to improve scent detection of ammonium nitrate in rats.
Human Health Risk Assessment External Advisory Service
This interest is reflected not only by our experimental research portfolio but also through my service on a variety of advisory committees. These activities include:
- Member of the National Toxicology Program Board of Scientific Counselors
- Member of the North Carolina Scientific Advisory Board on Toxic Air Pollutants
- Advisor for the development of US EPA’s Provisional Advisory Levels
- Service on the following National Resource Council (NRC) committees:
- Board on Environmental Studies and Toxicology (Member)
- Committee on Toxicology (Member)
- Committee on Predictive-Toxicology Approaches for Military Assessments of Acute Exposures (Chairman)
- Committee on Design and Evaluation of Safer Chemical Substitutions - A Framework to Inform Government and Industry Decisions (Chairman)
- Committee to Review the IRIS Process (Member)
- Committee on Potential Health Risks from Recurrent Lead Exposure to DOD Firing Range Personnel (Chairman)
- Committee on Review of the Draft IRIS Assessment on Formaldehyde (Member)
- Subcommittee on Emerging and Continuous Exposure Guidance Levels for Selected Submarine Contaminants (Chairman/Member)
- Committee on Animal Models for Testing Interventions Against Aerosolized Bioterrorism Agents (Member)
I have primary responsibility for the teaching of the following NCSU courses:
- VMB 954: Veterinary Toxicology and Poisonous Plants
- VMB 991: What the Nose Knows: Olfaction
- BIO 183H: Introductory Biology: Cellular and Molecular Biology (Honors Undergraduate)
Lazarowski L, Dorman DC. A comparison of pet and purpose-bred research dog (Canis familiaris) performance on human-guided object-choice tasks. Behav Processes. 2014 (in press).
Bazzle LJ, Cubeta MA, Marks SL, Dorman DC. Feasibility of flotation concentration of fungal spores as a method to identify toxigenic mushrooms. Vet Med Res Reports 2014 (in press).
Lazarowski L, Dorman DC. Explosives detection by military working dogs: Olfactory generalization from components to mixtures. Appl Anim Behav Sci 2014 151: 84-93.
Istvan SA, Marks SL, Murphy LA, Dorman DC. Evaluation of a point-of-care anticoagulant rodenticide test for dogs. J Vet Emerg Crit Care (San Antonio). 2014 Mar-Apr;24(2):168-73.
Lazarowski L, Foster ML, Gruen ME, Sherman BL, Case BC, Fish RE, Milgram NW, Dorman DC. Acquisition of a visual discrimination and reversal learning task by Labrador retrievers. Anim Cogn. 2014 May;17(3):787-92.
Dorman DC. Toxicities from newer over-the-counter drugs. In: Kirk's Current Veterinary Therapy XV, Bonagura JD and Twedt D (Eds), Elsevier, Maryland Heights, MO 2014 pp 115-120.
Taylor K, Foster ML, Law JM, Centeno JA, Fornero E, Henderson MS, Trager SA, Stockelman MG, Dorman DC. Assessment of geographical variation in the respiratory toxicity of desert dust particles. Inhal Toxicol. 2013 Jun;25(7):405-16.
Dorman DC, Alpi KM, Chappell KH. Subject matter expert and public evaluations of a veterinary toxicology course brochure-writing assignment. J Vet Med Educ. 2013 Spring;40(1):19-28. doi: 10.3138/jvme.0912.082R.
Schroeter JD, Kimbell JS, Asgharian B, Tewksbury EW, Sochaski M, Foster ML, Dorman DC, Wong BA, Andersen ME. Inhalation dosimetry of hexamethylene diisocyanate vapor in the rat and human respiratory tracts. Inhal Toxicol. 2013 Feb;25(3):168-77.
Bolon B, Butt MT, Garman RH, Dorman DC. Nervous system. In: Haschek, W.M., Rousseaux, C.G., Wallig, M.A. (Eds.), Haschek and Rousseaux's Handbook of Toxicologic Pathology. Elsevier Inc., Academic Press, 2013 pp. 2005–2093.
Block ML, Elder A, Auten RL, Bilbo SD, Chen H, Chen JC, Cory-Slechta DA, Costa D, Diaz-Sanchez D, Dorman DC, Gold DR, Gray K, Jeng HA, Kaufman JD, Kleinman MT, Kirshner A, Lawler C, Miller DS, Nadadur SS, Ritz B, Semmens EO, Tonelli LH, Veronesi B, Wright RO, Wright RJ. The outdoor air pollution and brain health workshop. Neurotoxicology. 2012 Oct;33(5):972-84
Schroeter JD, Dorman DC, Yoon M, Nong A, Taylor MD, Andersen ME, Clewell HJ 3rd. Application of a multi-route physiologically based pharmacokinetic model for manganese to evaluate dose-dependent neurological effects in monkeys. Toxicol Sci. 2012 Oct;129(2):432-46.
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. 2012:791431.
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. 2012:946742.
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.
Little PB and Dorman DC. Toxicological neuropathology in veterinary practice. In: Fundamental Neuropathology for Pathologists and Toxicologists: Principles and Techniques. Bolon B and Butt MT (Eds). John Wiley & Sons, Hoboken, NJ 2011 pp 487-500.
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 (188W) in male Sprague-Dawley rats following acute sodium tungstate inhalation. Inhal Toxicol. 2010 Jan;22(1):69-76.
Melanie Foster, Research Associate