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Population Health and Pathobiology
Pharmacology and Risk Assessment

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Ronald E. Baynes, DVM, PhD

Associate Professor of Pharmacology

B.Sc., University of the West Indies
DVM, Tuskegee University,
M.S, University of Georgia
Ph.D, North Carolina State University

Phone 919.513.6261
Fax 919.513.6358
Email: Ronald_Baynes@ncsu.edu

Center for Chemical Toxicology Research and Pharmacokinetics

FARAD (Food Animal Residue Avoidance Databank)

Research Area

Dermal Absorption Assessment

Skin represents a significant surface area over which humans and animals may be exposed to hazardous chemicals. Occupational exposure to hazardous chemicals via skin can result in local effects (e.g., irritant dermatitis) or systemic toxicity. Unfortunately, workers are not exposed to a single chemical, but rather chemical mixtures and therefore quantitative risk assessment in any work place scenario should take this into account. The focus of my research is to determine physiochemical and chemical-biological interactions in epidermal corneocytes and intercellular lipids in the epidermis that can influence dermal absorption of complex mixtures.

Identification of these interactions in in vitro flow-through porcine skin and inert membranes and ex vivo porcine skin models allows one to predict mixture effects on the dermal disposition of hazardous chemicals in human skin. Because porcine skin is physiologically and biochemically similar to human skin, chemical transport mechanisms are comparable and reduces uncertainty in the risk assessment process.

Current research activities are focused on assessing the dermal disposition of cutting fluid and jet fuel additives and pesticides. This research is providing some understanding of the physicochemical factors influencing dermal absorption of these pesticides and formulation additives that cause occupational irritant dermatitis. Other work is focused on understanding transdermal delivery of avermectins across skin various food animal species. HPLC and GC analytical methods are continually being developed.

Residue Pharmacology and Risk Assessment of Veterinary Drugs:

FARAD is a multi-institutional project funded in part by the North Carolina State University, University of Florida, and University of California and the US Department of Agriculture (USDA).

The mission of FARAD is to maintain a drug and chemical database that can be used to prevent harmful residues from occurring in livestock products. Livestock farmers, veterinarians, extension personnel and related government specialist consult with FARAD to determine what drugs are approved for use in livestock and what are safe levels and safe withdrawal times for approved and unapproved/accidental use. The ultimate aim is to utilize relevant regulatory and pharmacokinetic data to provide farmers and veterinarians with food safety information so that they can produce meat and milk free of residues and reduce the risk of the public from being exposed to contaminated food.

Current Research and Extension Activities are focused on providing expert consultation to veterinarians and livestock farmers about drug/chemical residues in livestock, development of algorithms for estimating safe withdrawal times, development of provisional acceptable residues as temporary safe levels in animal-derived food, and development of residue monitoring and residue avoidance programs internationally (gFARAD). The laboratory has been active in HPLC analytical method development for antibiotic residues in milk.

Selected Publications

Baynes, R. E., Monteiro-Riviere, N. A., Riviere, J. E. (2002). Pyridostigmine bromide modulates dermal disposition of C14-permethrin. Toxicol. Appl. Pharmacol. 181: 164-173.

Baynes R. E., Yeatts J. L., Riviere J. E. (2002): Analysis of N,N-diethyl-m-toluamide in porcine skin perfusates using solid-phase extraction disks and reversed-phased high-performance liquid chromatography. J. Chromatog. B 780: 45-52

Martin-Jiménez, T., Baynes, R. E., Craigmill, A., and Riviere, J. E. (2002). Extrapolated withdrawal-period estimator (EWE) algorithm. A quantitative approach to establishing extra-label withdrawal times. Regul. Toxicol. Pharmacol. 36: 131-137

Baynes, R. E., Brooks JD, Mumtaz M, Rivier JE. (2002). Effect of chemical interactions in pentachlorophenol mixtures on skin and membrane transport. Toxicol. Sci. 69, 295-305, 2002.

Riviere J. E., Monteiro-Riviere N.A., Baynes R. E. (2002) Gulf War related exposure factors influencing topical absorption of C14 - permethrin. Toxicol Lett 135: 61-71, 2002.

Monteiro-Riviere, N. A., Baynes, R. E., Riviere, J. E. (2003). Pyridostigmine bromide modulates topical irritant-induced cytokine release from human epidermal keratinocytes and isolated perfused skin. Toxicol 183:15-28.

Riviere, J. E., Baynes, R. E., Brooks, J. D., Yeatts, J. L., Monteiro-Riviere, N. A. (2003). Percutaneous Absorption of Topical N,N-Diethyl-m-toluamide (DEET): Effects of Exposure Variables and Coadministered Toxicants. J. Toxicol. Environ. Health A. 66(2): 133-151.

Xia, X. R., Baynes, R. E., Monteiro-Riviere, N. A., Leidy, R. B., Shea, D., and Riviere, J. E. (2003). A novel in vitro technique for studying percutaneous permeation with a membrane-caoted fiber and gas chromatography/mass spectrometry: Part I. Performances of the technique and determination of the permeation rates and partition coefficients of chemical mixtures. Pharm Res. 20:272-279.

Baynes RE, Brooks, J. D., Barlow, B., and Riviere, J. E. (2002). Physicochemical determinants of linear alkylbenzene sulfonate (LAS) disposition in skin exposed to aqueous cutting fluid mixtures. Toxicol. Industr. Health 18(5): 237-248.

Baynes RE, Barlow, B., and Riviere, J. E. (2003). Dermal disposition of triazine in cutting fluid mixtures. J. Toxicol. Cut. and Ocular Toxicol 22(4): 215-229.

Muhammad F, Baynes RE, Monteiro-Riviere NA, Xia XR, Riviere JE. (2004). Dose related absorption of JP-8 jet fuel hydrocarbons through porcine skin with quantitative structure permeability relationship analysis. Toxicol. Mechanisms and Methods 14: 159-166, 2004.

Wang, J., Gehring, R, Riviere, J. E., Baynes RE, Payne, M., Craigmill, A. L., Fitzgrald, K, Webb, A. I., Whitford, C. (2003). Evaluation of the advisory services provided by the Food Animal Residue Avoidance Databank (FARAD). J. Am. Vet. Med. Assoc. 223(11): 1596-1598.

Smith, G., Gehring, R., Riviere, J., Baynes RE. (2004). Elimination kinetics of ceftiofur hydrochloride after intramammary administration in lactating dairy cows. J. Am. Vet. Med. Assoc. 224(11): 1827-1830.

Baynes RE, Riviere, JE. (2004). Mixture additives inhibit the dermal permeation of the fatty acid, ricinoleic acid. Toxicol. Lett. 147(1): 15-26.

Baynes RE. (2004). In Vitro Dermal Disposition of Abamectin (Avermectin B1) in Livestock. Res. Vet. Sci. 76(3):235-242.

Gehring, R., Baynes RE, Riviere, J. E., and Craigmill, A. L. (2004). A comparison of two proposed methods for estimating extended withdrawal intervals following the extralabel use of drugs in food-producing animals. J. Food. Protect. 67(3): 555-560.

Xia, Xin R., Baynes RE., Monteiro-Riviere, NA., Riviere, J.E. (2004). Characterization of polyacrylate membrane-coated fibers used in chemical absorption studies with programmed thermal treatment and FT-IR microscopy. Anal. Chem. 76(14):4245-4250.

Xia XR, Baynes RE, Monteiro-Riviere NA, Riviere JE. (2004). A compartment model for the membrane-coated fiber technique used for determining the absorption parameters of chemicals into lipophilic membranes. Pharm Res. 21(8): 1345-52.

Gehring R, Baynes RE, Wang J, Craigmill AL, Riviere JE. (2004). A web-based decision support system to estimate extended withdrawal intervals. Comp. Electron. Agric 44: 145-151.

Xia, Xin R., Baynes, R.E., Monteiro-Riviere, N.A., and Riviere, J.E. (2005). Determination of the partition coefficients and absorption kinetic parameters of chemicals in a lipophilic membrane/water system by using a membrane-coated fiber technique. Eur. J. Pharm. Sci. 24: 15-23.

Gehring, R., van der Merwe, D., Pierce, A., Baynes, R.E., Craigmill, A.L., and Riviere, J. (2005). Multivariate meta-analysis of pharmacokinetic studies of ampicillin trihydrate in cattle. Am. J. Vet. Res. 66: 108-112.

Muhammad, F., Monteiro-Riviere, N.A., Baynes, R.E., and Riviere, J.E. (2005). Effect of in vivo jet fuel exposure on subsequent in vitro dermal absorption of individual aromatic and aliphatic hydrocarbon fuel constituents. J. Toxicol. Environ Health. (in press).

Buur JL, Baynes RE., Craigmill A., Riviere JE. (2005). A physiologic based pharmacokinetic model of sulfamethazine in swine applied to tissue residues. Am J. Vet. Res. (in press).

Buur, J.L, Baynes, RE., James L. Yeatts, J.L., Davidson, G., and DeFrancesco, T. (2005). Analysis of diltiazem in LipodermŽ transdermal gel using reversed-phase high-performance liquid chromatography applied to homogenization and stability studies. Journal of Pharmaceutical and Biomedical Analysis. (in press).


From left to right:
Mr. Jim Yeatts, Analytical Chemists (BS, MS Chemistry), Ms. Beth Barlow, Research Technician (BS Biology/Chemistry), and Dr. Baynes

Ms. Beth Barlow and Mr. Jim Yeatts

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NC State College of Veterinary Medicine
Population Health and Pathobiology
4700 Hillsborough Street
Raleigh, NC 27606