@article{merwe_buur_riviere_2007, title={Physiologically based pharmacokinetic modeling}, DOI={10.1016/b978-012370467-2/50100-0}, journal={VETERINARY TOXICOLOGY: BASIC AND CLINICAL PRINCIPLES}, author={Merwe, Deon and Buur, Jennifer L. and Riviere, Jim E.}, year={2007}, pages={42–50} } @article{merwe_brooks_gehring_baynes_monteiro-riviere_riviere_2006, title={A physiologically based pharmacokinetic model of organophosphate dermal absorption}, volume={89}, ISSN={["1096-0929"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000233991000018&KeyUID=WOS:000233991000018}, DOI={10.1093/toxsci/kfj014}, abstractNote={The rate and extent of dermal absorption are important in the analysis of risk from dermal exposure to toxic chemicals and for the development of topically applied drugs, barriers, insect repellents, and cosmetics. In vitro flow-through cells offer a convenient method for the study of dermal absorption that is relevant to the initial processes of dermal absorption. This study describes a physiologically based pharmacokinetic (PBPK) model developed to simulate the absorption of organophosphate pesticides, such as parathion, fenthion, and methyl parathion through porcine skin with flow-through cells. Parameters related to the structure of the stratum corneum and solvent evaporation rates were independently estimated. Three parameters were optimized based on experimental dermal absorption data, including solvent evaporation rate, diffusivity, and a mass transfer factor. Diffusion cell studies were conducted to validate the model under a variety of conditions, including different dose ranges (6.3-106.9 microg/cm2 for parathion; 0.8-23.6 microg/cm2 for fenthion; 1.6-39.3 microg/cm2 for methyl parathion), different solvents (ethanol, 2-propanol and acetone), different solvent volumes (5-120 microl for ethanol; 20-80 microl for 2-propanol and acetone), occlusion versus open to atmosphere dosing, and corneocyte removal by tape-stripping. The study demonstrated the utility of PBPK models for studying dermal absorption, which can be useful as explanatory and predictive tools that may be used for in silico hypotheses generation and limited hypotheses testing. The similarity between the overall shapes of the experimental and model-predicted flux/time curves and the successful simulation of altered system conditions for this series of small, lipophilic compounds indicated that the absorption processes that were described in the model successfully simulated important aspects of dermal absorption in flow-through cells. These data have direct relevance to topical organophosphate pesticide risk assessments.}, number={1}, journal={TOXICOLOGICAL SCIENCES}, author={Merwe, D and Brooks, JD and Gehring, R and Baynes, RE and Monteiro-Riviere, NA and Riviere, JE}, year={2006}, month={Jan}, pages={188–204} } @article{merwe_riviere_2006, title={Cluster analysis of the dermal permeability and stratum corneum/solvent partitioning of ten chemicals in twenty-four chemical mixtures in porcine skin}, volume={19}, ISSN={["1660-5527"]}, DOI={10.1159/000093115}, abstractNote={Assumptions based on absorption from single solvent systems may be inappropriate for risk assessment when chemical mixtures are involved. We used K-means and hierarchical cluster analyses to identify clusters in stratum corneum partitioning and porcine skin permeability datasets that are distinct from each other based on mathematical indices of similarity and dissimilarity. Twenty-four solvent systems consisting of combinations of water, ethanol, propylene glycol, methyl nicotinate and sodium lauryl sulfate were used with 10 solutes, including phenol, p-nitrophenol, pentachlorophenol, methyl parathion, ethyl parathion, chlorpyrifos, fenthion, simazine, atrazine and propazine. Identifying the relationships between solvent systems that have similar effects on dermal absorption formed the bases for hypotheses generation. The determining influence of solvent polarity on the partitioning data structure supported the hypothesis that solvent polarity drives the partitioning of non-polar solutes. Solvent polarity could not be used to predict permeability because solvent effects on diffusivity masked the effects of partitioning on permeability. The consistent influence of the inclusion of propylene glycol in the solvent system supports the hypothesis that over-saturation due to solvent evaporation has a marked effect on permeability. These results demonstrated the potential of using cluster analysis of large datasets to identify consistent solvent and chemical mixture effects.}, number={4}, journal={SKIN PHARMACOLOGY AND PHYSIOLOGY}, author={Merwe, D. and Riviere, J. E.}, year={2006}, pages={198–206} } @article{luseba_van der merwe_2006, title={Ethnoveterinary medicine practices among Tsonga speaking people of South Africa}, volume={73}, number={2}, journal={Onderstepoort Journal of Veterinary Research}, author={Luseba, D. and Van Der Merwe, D.}, year={2006}, pages={115–122} } @article{merwe_riviere_2005, title={Comparative studies on the effects of water, ethanol and water/ethanol mixtures on chemical partitioning into porcine stratum corneum and silastic membrane}, volume={19}, ISSN={["0887-2333"]}, DOI={10.1016/j.tiv.2004.06.002}, abstractNote={The effects of water and ethanol vehicles on stratum corneum and silastic membrane partitioning of 11 industrial and agricultural compounds were studied to aid in characterizing and assessing risk from skin exposure. Zero percent, 50% and 100% aqueous ethanol solutions were used as solvents for (14)C labeled phenol, 4-nitrophenol, pentachlorophenol, dimethyl parathion, parathion, chloropyrifos, fenthion, triazine, atrazine, simazine and propazine. Compound partitioning between the solvents and porcine stratum corneum/silastic membrane were estimated. Stratum corneum was exposed to aqueous ethanol ranging from 0% to 100% v/v ethanol in 20% increments and Fourier transform infrared spectroscopy (FT-IR) was used to obtain an index of lipid disorder. Gravimetry and FT-IR were used to demonstrate lipid extraction in aqueous ethanol solutions. Partitioning patterns in silastic membranes resembled those in stratum corneum and were correlated with octanol/water partitioning. Partitioning was highest in water and was higher from 50% ethanol than from 100% ethanol, except for parathion, 4-nitrophenol, atrazine and propazine. Correlation existed between molecular weight and partitioning in water, but not in ethanol and ethanol/water mixtures. Lipid order, as reflected in FT-IR spectra, was not altered. These studies suggest that stratum corneum partitioning of the compounds tested is primarily determined by relative compound solubility between the stratum corneum lipids and the donor solvent. Linear relationships existed between octanol/water partitioning and stratum corneum partitioning. Partitioning was also correlated with molecular weight in water solvent systems, but not in ethanol and ethanol/water mixtures. Ethanol and ethanol/water mixtures altered the stratum corneum through lipid extraction, rather than through disruption of lipid order.}, number={1}, journal={TOXICOLOGY IN VITRO}, author={Merwe, D and Riviere, JE}, year={2005}, month={Feb}, pages={69–77} } @article{gehring_merwe_pierce_baynes_craigmill_riviere_2005, title={Multivariate meta-analysis of pharmacokinetic studies of ampicillin trihydrate in cattle}, volume={66}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.2005.66.108}, abstractNote={Abstract}, number={1}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Gehring, R and Merwe, D and Pierce, AN and Baynes, RE and Craigmill, AL and Riviere, JE}, year={2005}, month={Jan}, pages={108–112} }