@article{howard_ashwell_baynes_brooks_yeatts_maltecca_2018, title={Genetic Parameter Estimates for Metabolizing Two Common Pharmaceuticals in Swine}, volume={9}, ISSN={1664-8021}, url={http://dx.doi.org/10.3389/fgene.2018.00040}, DOI={10.3389/fgene.2018.00040}, abstractNote={In livestock, the regulation of drugs used to treat livestock has received increased attention and it is currently unknown how much of the phenotypic variation in drug metabolism is due to the genetics of an animal. Therefore, the objective of the study was to determine the amount of phenotypic variation in fenbendazole and flunixin meglumine drug metabolism due to genetics. The population consisted of crossbred female and castrated male nursery pigs (n = 198) that were sired by boars represented by four breeds. The animals were spread across nine batches. Drugs were administered intravenously and blood collected a minimum of 10 times over a 48 h period. Genetic parameters for the parent drug and metabolite concentration within each drug were estimated based on pharmacokinetics (PK) parameters or concentrations across time utilizing a random regression model. The PK parameters were estimated using a non-compartmental analysis. The PK model included fixed effects of sex and breed of sire along with random sire and batch effects. The random regression model utilized Legendre polynomials and included a fixed population concentration curve, sex, and breed of sire effects along with a random sire deviation from the population curve and batch effect. The sire effect included the intercept for all models except for the fenbendazole metabolite (i.e., intercept and slope). The mean heritability across PK parameters for the fenbendazole and flunixin meglumine parent drug (metabolite) was 0.15 (0.18) and 0.31 (0.40), respectively. For the parent drug (metabolite), the mean heritability across time was 0.27 (0.60) and 0.14 (0.44) for fenbendazole and flunixin meglumine, respectively. The errors surrounding the heritability estimates for the random regression model were smaller compared to estimates obtained from PK parameters. Across both the PK and plasma drug concentration across model, a moderate heritability was estimated. The model that utilized the plasma drug concentration across time resulted in estimates with a smaller standard error compared to models that utilized PK parameters. The current study found a low to moderate proportion of the phenotypic variation in metabolizing fenbendazole and flunixin meglumine that was explained by genetics in the current study.}, number={FEB}, journal={Frontiers in Genetics}, publisher={Frontiers Media SA}, author={Howard, Jeremy T. and Ashwell, Melissa S. and Baynes, Ronald E. and Brooks, James D. and Yeatts, James L. and Maltecca, Christian}, year={2018}, month={Feb} }
 @article{howard_ashwell_baynes_brooks_yeatts_maltecca_2017, title={Gene co-expression network analysis identifies porcine genes associated with variation in metabolizing fenbendazole and flunixin meglumine in the liver}, volume={7}, ISSN={2045-2322}, url={http://dx.doi.org/10.1038/s41598-017-01526-5}, DOI={10.1038/s41598-017-01526-5}, abstractNote={Abstract}, number={1}, journal={Scientific Reports}, publisher={Springer Nature}, author={Howard, Jeremy T. and Ashwell, Melissa S. and Baynes, Ronald E. and Brooks, James D. and Yeatts, James L. and Maltecca, Christian}, year={2017}, month={May} }
 @article{nixon_brooks_routh_chittenden_baynes_2017, title={Pharmacokinetics of C-14-ortho-phenylphenol following intravenous administration in pigs}, volume={37}, ISSN={["1099-1263"]}, url={https://doi.org/10.1002/jat.3380}, DOI={10.1002/jat.3380}, abstractNote={Abstract}, number={4}, journal={JOURNAL OF APPLIED TOXICOLOGY}, author={Nixon, Emma and Brooks, James D. and Routh, Patricia A. and Chittenden, Jason T. and Baynes, Ronald E.}, year={2017}, month={Apr}, pages={508–512} }
 @article{roux_brooks_yeatts_baynes_2015, title={Skin absorption of six performance amines used in metalworking fluids}, volume={35}, ISSN={["1099-1263"]}, DOI={10.1002/jat.3056}, abstractNote={Abstract}, number={5}, journal={JOURNAL OF APPLIED TOXICOLOGY}, author={Roux, Lauriane N. and Brooks, James D. and Yeatts, James L. and Baynes, Ronald E.}, year={2015}, month={May}, pages={520–528} }
 @article{chittenden_brooks_riviere_2014, title={Development of a Mixed-Effect Pharmacokinetic Model for Vehicle Modulated In Vitro Transdermal Flux of Topically Applied Penetrants}, volume={103}, ISSN={["1520-6017"]}, DOI={10.1002/jps.23862}, abstractNote={Transient flux profiles from in vitro flow-through cell experiments exhibit different characteristics depending upon the properties of the penetrants and vehicle mixtures applied. To enable discrimination of the chemical properties contributing to these differences, a consistent mathematical model should first be developed. A mixed effects modeling framework was used so that models can be estimated with as few parameters as possible, while also quantifying variability and accounting for correlation in the data. The models account for diffusion and binding within the membrane as well as dynamics on the diffusion coefficient. The models explain key features of the data, such as: lag time, sharp peaks in flux, two terminal phases, and low flux profiles. The models with dynamic diffusivity fit the data better than those without-particularly the sharp peaks. The significance of changing diffusivity over time suggests that vehicle effects are transient and are more accurately estimated when dynamics are modeled.}, number={3}, journal={JOURNAL OF PHARMACEUTICAL SCIENCES}, author={Chittenden, Jason T. and Brooks, James D. and Riviere, Jim E.}, year={2014}, month={Mar}, pages={1002–1012} }
 @article{guth_riviere_brooks_dammann_fabian_ravenzwaay_schaefer-korting_landsiedel_2014, title={In silico models to predict dermal absorption from complex agrochemical formulations}, volume={25}, ISSN={["1029-046X"]}, DOI={10.1080/1062936x.2014.919358}, abstractNote={Dermal absorption is a critical part in the risk assessment of complex mixtures such as agrochemical formulations. To reduce the number of in vivo or in vitro absorption experiments, the present study aimed to develop an in silico prediction model that considers mixture-related effects. Therefore, an experimental ‘real-world’ dataset derived from regulatory in vitro studies with human and rat skin was processed. Overall, 56 test substances applied in more than 150 mixtures were used. Descriptors for the substances as well as the mixtures were generated and used for multiple linear regression analysis. Considering the heterogeneity of the underlying data set, the final model provides a good fit (r² = 0.75) and is able to estimate the influence of a newly composed formulation on dermal absorption of a well-known substance (predictivity Q²Ext = 0.73). Application of this model would reduce animal and non-animal testings when used for the optimization of formulations in early developmental stages, or would simplify the registration process, if accepted for read-across.}, number={7}, journal={SAR AND QSAR IN ENVIRONMENTAL RESEARCH}, author={Guth, K. and Riviere, J. E. and Brooks, J. D. and Dammann, M. and Fabian, E. and Ravenzwaay, B. and Schaefer-Korting, M. and Landsiedel, R.}, year={2014}, pages={565–588} }
 @article{riviere_brooks_collard_deng_rose_mahabir_merritt_marchiondo_2014, title={Prediction of formulation effects on dermal absorption of topically applied ectoparasiticides dosed in vitro on canine and porcine skin using a mixture-adjusted quantitative structure permeability relationship}, volume={37}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12121}, abstractNote={Topical application of ectoparasiticides for flea and tick control is a major focus for product development in animal health. The objective of this work was to develop a quantitative structure permeability relationship (QSPeR) model sensitive to formulation effects for predicting absorption and skin deposition of five topically applied drugs administered in six vehicle combinations to porcine and canine skin in vitro. Saturated solutions (20 μL) of 14C‐labeled demiditraz, fipronil, permethrin, imidacloprid, or sisapronil were administered in single or binary (50:50 v/v) combinations of water, ethanol, and transcutol (6 formulations, n = 4–5 replicates per treatment) nonoccluded to 0.64 cm2 disks of dermatomed pig or dog skin mounted in flow‐through diffusion cells. Perfusate flux over 24 h and skin deposition at termination were determined. Permeability (logKp), absorption, and penetration endpoints were modeled using a four‐term Abrahams and Martin (hydrogen‐bond donor acidity and basicity, dipolarity/polarizability, and excess molar refractivity) linear free energy QSPeR equation with a mixture factor added to compensate for formulation ingredient interactions. Goodness of fit was judged by r2, cross‐validation coefficient, coefficients (q2s), and Williams Plot to visualize the applicability domain. Formulation composition was the primary determinant of permeation. Compounds generally penetrated dog skin better than porcine skin. The vast majority of permeated penetrant was deposited within the dosed skin relative to transdermal flux, an attribute for ectoparasiticides. The best QSPeR logKp model for pig skin permeation (r2 = 0.86, q2s = 0.85) included log octanol/water partition coefficient as the mixture factor, while for dogs (r2 = 0.91, q2s = 0.90), it was log water solubility. These studies clearly showed that the permeation of topical ectoparasiticides could be well predicted using QSPeR models that account for both the physical–chemical properties of the penetrant and formulation components.}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Riviere, J. E. and Brooks, J. D. and Collard, W. T. and Deng, J. and Rose, G. and Mahabir, S. P. and Merritt, D. A. and Marchiondo, A. A.}, year={2014}, month={Oct}, pages={435–444} }
 @article{lindquist_wu_mason_yeatts_brooks_barlow_schill_baynes_2014, title={Tetracycline Residues in Porcine Stomach after Administration via Drinking Water on a Swine Farm}, volume={77}, ISSN={["1944-9097"]}, DOI={10.4315/0362-028x.jfp-13-199}, abstractNote={Tetracycline is a broad-spectrum antibiotic used to treat infections in swine. The maximum residue levels of tetracycline in pork stomach tissue in Russia, Europe, and the United States are 10, 200, and 2,000 ppb, respectively. This difference in accepted safety levels may be the reason why stomach tissues that the United States exports continue to be residue violators in overseas markets. In this study, 30 pigs at two different stages of production (weanling and finisher) were treated with tetracycline at 22 mg/kg of body weight per day for a total of 5 days via a water medicator. Blood samples were collected at 0, 72, 78, 96, and 102 h after the start of medication. The medication was stopped at 120 h, and blood samples were again collected at 126, 144, 168, 192, and 216 h after exposure. Five animals were slaughtered for stomach tissue 0, 24, 48, 96, and 192 h after the drug was flushed from the water line. All blood and tissue samples were analyzed by high-performance liquid chromatography-UV methods. The tetracycline levels in plasma were below the level of detection after the U.S.-labeled withdrawal time of 4 days. The stomach tissue residues averaged 671.72, 330.31, 297.77, 136.36, and 268.08 ppb on withdrawal days 0, 1, 2, 4, and 8, respectively. Using the U.S. Food and Drug Administration tolerance limit method and a population-based pharmacokinetic model with Monte Carlo simulation, a withdrawal interval was estimated. This study demonstrated that tetracycline residues are still detectable in the stomach tissues after the established United States withdrawal time of 4 days. These residue levels may explain why stomach tissues tested in Russia and Europe show positive residues for tetracycline, even though the meat may pass inspection here in the United States prior to export.}, number={1}, journal={JOURNAL OF FOOD PROTECTION}, author={Lindquist, Danielle and Wu, Huali and Mason, Sharon and Yeatts, Jim and Brooks, Jim and Barlow, Beth and Schill, Kaitlyn and Baynes, Ronald}, year={2014}, month={Jan}, pages={122–126} }
 @article{howard_baynes_brooks_yeatts_bellis_ashwell_routh_o'nan_maltecca_2014, title={The effect of breed and sex on sulfamethazine, enrofloxacin, fenbendazole and flunixin meglumine pharmacokinetic parameters in swine}, volume={37}, ISSN={["1365-2885"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84911423325&partnerID=MN8TOARS}, DOI={10.1111/jvp.12128}, abstractNote={Drug use in livestock has received increased attention due to welfare concerns and food safety. Characterizing heterogeneity in the way swine populations respond to drugs could allow for group‐specific dose or drug recommendations. Our objective was to determine whether drug clearance differs across genetic backgrounds and sex for sulfamethazine, enrofloxacin, fenbendazole and flunixin meglumine. Two sires from each of four breeds were mated to a common sow population. The nursery pigs generated (n = 114) were utilized in a random crossover design. Drugs were administered intravenously and blood collected a minimum of 10 times over 48 h. A non‐compartmental analysis of drug and metabolite plasma concentration vs. time profiles was performed. Within‐drug and metabolite analysis of pharmacokinetic parameters included fixed effects of drug administration date, sex and breed of sire. Breed differences existed for flunixin meglumine (P‐value<0.05; Cl, Vdss) and oxfendazole (P‐value<0.05, AUC0→∞). Sex differences existed for oxfendazole (P‐value < 0.05; Tmax) and sulfamethazine (P‐value < 0.05, Cl). Differences in drug clearance were seen, and future work will determine the degree of additive genetic variation utilizing a larger population.}, number={6}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Howard, J. T. and Baynes, R. E. and Brooks, J. D. and Yeatts, J. L. and Bellis, B. and Ashwell, M. S. and Routh, P. and O'Nan, A. T. and Maltecca, C.}, year={2014}, month={Dec}, pages={531–541} }
 @article{karadzovska_brooks_riviere_2013, title={Modeling the effect of experimental variables on the in vitro permeation of six model compounds across porcine skin}, volume={443}, ISSN={0378-5173}, url={http://dx.doi.org/10.1016/j.ijpharm.2013.01.002}, DOI={10.1016/j.ijpharm.2013.01.002}, abstractNote={A majority of quantitative structure–permeability relationships (QSPeRs) predict the permeability coefficient (kp) of compounds topically applied as infinite, saturated doses from water vehicles. Alternate delivery vehicles and other experimental variables are rarely incorporated in such models. This research presents the development and statistical validation of QSPeR models that incorporate the effects of penetrant, vehicle, and experimental conditions such as dose volume (finite/infinite), and saturation level (saturated/unsaturated). A composite parameter, a mixture factor (MF), was also included to account for the physicochemical properties of the compound/vehicle mixture components. The resultant models effectively described skin flux and absorption, identifying the summation of hydrogen bond acidity and basicity, excess molar refractivity, dose volume, saturation level, and vehicle as the most prominent factors influencing flux values. The main factors influencing absorption values were the summation of hydrogen bond basicity, dipolarity/polarizability, the McGowan characteristic volume, dose volume, saturation level, and vehicle. The same MF (inverse of the melting point) was considered suitable to describe both flux and absorption. For endpoints involving skin deposition, log propylene glycol solubility was a more suitable MF. Such models show potential for use in drug delivery and toxicology research, specifically in assessing percutaneous absorption data collected under different experimental conditions.}, number={1-2}, journal={International Journal of Pharmaceutics}, publisher={Elsevier BV}, author={Karadzovska, Daniela and Brooks, James D. and Riviere, Jim E.}, year={2013}, month={Feb}, pages={58–67} }
 @article{xu_hughes-oliver_brooks_baynes_2013, title={Predicting skin permeability from complex chemical mixtures: incorporation of an expanded QSAR model}, volume={24}, ISSN={1062-936X 1029-046X}, url={http://dx.doi.org/10.1080/1062936X.2013.792875}, DOI={10.1080/1062936x.2013.792875}, abstractNote={Quantitative structure–activity relationship (QSAR) models have been widely used to study the permeability of chemicals or solutes through skin. Among the various QSAR models, Abraham’s linear free-energy relationship (LFER) model is often employed. However, when the experimental conditions are complex, it is not always appropriate to use Abraham’s LFER model with a single set of regression coefficients. In this paper, we propose an expanded model in which one set of partial slopes is defined for each experimental condition, where conditions are defined according to solvent: water, synthetic oil, semi-synthetic oil, or soluble oil. This model not only accounts for experimental conditions but also improves the ability to conduct rigorous hypothesis testing. To more adequately evaluate the predictive power of the QSAR model, we modified the usual leave-one-out internal validation strategy to employ a leave-one-solute-out strategy and accordingly adjust the Q2 LOO statistic. Skin permeability was shown to have the rank order: water > synthetic > semi-synthetic > soluble oil. In addition, fitted relationships between permeability and solute characteristics differ according to solvents. We demonstrated that the expanded model (r2 = 0.70) improved both the model fit and the predictive power when compared with the simple model (r2 = 0.21).}, number={9}, journal={SAR and QSAR in Environmental Research}, publisher={Informa UK Limited}, author={Xu, G. and Hughes-Oliver, J.M. and Brooks, J.D. and Baynes, R.E.}, year={2013}, month={Sep}, pages={711–731} }
 @misc{karadzovska_brooks_monteiro-riviere_riviere_2013, title={Predicting skin permeability from complex vehicles}, volume={65}, ISSN={["1872-8294"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84873522106&partnerID=MN8TOARS}, DOI={10.1016/j.addr.2012.01.019}, abstractNote={It is now widely accepted that vehicle and formulation components influence the rate and extent of passive chemical absorption through skin. Significant progress, over the last decades, has been made in predicting dermal absorption from a single vehicle; however the effect of a complex, realistic mixture has not received its due attention. Recent studies have aimed to bridge this gap by extending the use of quantitative structure–permeation relationship (QSPR) models based on linear free energy relationships (LFER) to predict dermal absorption from complex mixtures with the inclusion of significant molecular descriptors such as a mixture factor that accounts for the physicochemical properties of the vehicle/mixture components. These models have been compiled and statistically validated using the data generated from in vitro or ex vivo experimental techniques. This review highlights the progress made in predicting skin permeability from complex vehicles.}, number={2}, journal={ADVANCED DRUG DELIVERY REVIEWS}, author={Karadzovska, Daniela and Brooks, James D. and Monteiro-Riviere, Nancy A. and Riviere, Jim E.}, year={2013}, month={Feb}, pages={265–277} }
 @article{xu_hughes-oliver_brooks_yeatts_baynes_2013, title={Selection of appropriate training and validation set chemicals for modelling dermal permeability by U-optimal design}, volume={24}, ISSN={1062-936X 1029-046X}, url={http://dx.doi.org/10.1080/1062936X.2012.742458}, DOI={10.1080/1062936x.2012.742458}, abstractNote={Quantitative structure-activity relationship (QSAR) models are being used increasingly in skin permeation studies. The main idea of QSAR modelling is to quantify the relationship between biological activities and chemical properties, and thus to predict the activity of chemical solutes. As a key step, the selection of a representative and structurally diverse training set is critical to the prediction power of a QSAR model. Early QSAR models selected training sets in a subjective way and solutes in the training set were relatively homogenous. More recently, statistical methods such as D-optimal design or space-filling design have been applied but such methods are not always ideal. This paper describes a comprehensive procedure to select training sets from a large candidate set of 4534 solutes. A newly proposed ‘Baynes’ rule’, which is a modification of Lipinski's ‘rule of five’, was used to screen out solutes that were not qualified for the study. U-optimality was used as the selection criterion. A principal component analysis showed that the selected training set was representative of the chemical space. Gas chromatograph amenability was verified. A model built using the training set was shown to have greater predictive power than a model built using a previous dataset [1].}, number={2}, journal={SAR and QSAR in Environmental Research}, publisher={Informa UK Limited}, author={Xu, G. and Hughes-Oliver, J.M. and Brooks, J.D. and Yeatts, J.L. and Baynes, R.E.}, year={2013}, month={Feb}, pages={135–156} }
 @article{riviere_leavens_brooks_monteiro-riviere_2012, title={Acute vascular effects of nanoparticle infusion in isolated perfused skin}, volume={8}, ISSN={1549-9634}, url={http://dx.doi.org/10.1016/j.nano.2012.02.016}, DOI={10.1016/j.nano.2012.02.016}, abstractNote={The majority of studies on the effect of nanomaterials on biological function involves either isolated in vitro cell systems or are concerned with in vivo effects after inhalational or dermal exposure. The current work reports on an intriguing observation of the vascular effects seen in an ex vivo perfused tissue preparation, the isolated perfused porcine skin flap (IPPSF), in studies conducted to assess nanomaterial biodistribution. Compared with a relatively large dataset involving organic chemical infusions (n = 53), infusion of six different nanoparticles of diverse sizes and composition (silica or dextran coated Fe(2)O(3), silica or citrate coated silver, PEG or carboxylated quantum dots [QD]) resulted in statistically significant post-infusion flap weight gain and an increase in arterial perfusion pressure (especially with QD-PEG). In contrast, infusion with nC(60) nanoparticles did not produce these effects. These observations suggest certain nanoparticle infusions may be associated with acute vascular physiologic effects that merit further attention.In this study utilizing a perfused porcine skin flap, specific nanoparticle infusions were demonstrated to be associated with significant acute vascular physiological effects.}, number={4}, journal={Nanomedicine: Nanotechnology, Biology and Medicine}, publisher={Elsevier BV}, author={Riviere, Jim E. and Leavens, Teresa L. and Brooks, James D. and Monteiro-Riviere, Nancy A.}, year={2012}, month={May}, pages={428–431} }
 @article{karadzovska_brooks_riviere_2012, title={Experimental factors affecting in vitro absorption of six model compounds across porcine skin}, volume={26}, ISSN={0887-2333}, url={http://dx.doi.org/10.1016/j.tiv.2012.06.009}, DOI={10.1016/j.tiv.2012.06.009}, abstractNote={This comparative study evaluated the effect of several experimental variables on the absorption of six model [14C]-labeled compounds (caffeine, cortisone, diclofenac sodium, mannitol, salicylic acid, and testosterone) through porcine skin. Using static and flow-through diffusion cells, finite or infinite, saturated or unsaturated doses were applied in one of three vehicles: propylene glycol, water, and ethanol following a full factorial experimental design. The flux of each compound into the receptor phase, with or without bovine serum albumin (BSA), was monitored over 24 h. Levels of radioactivity were also determined in the stratum corneum by tape stripping and in the remaining skin. Apparent permeability coefficients (Kp) and dose absorbed were calculated and compared. The overall results emphasize the importance of experimental design and confirm previous findings that identified dose volume, saturation level and vehicle as the main sources of variation in the in vitro assessment of dermal absorption, whilst diffusion cell model and the presence/absence of BSA in the receptor phase had minimal effect. Although the acquired data do not directly reveal new mechanistic information on dermal absorption, the unique and complete study design has provided a suitable data source for the development of dermal absorption prediction models.}, number={7}, journal={Toxicology in Vitro}, publisher={Elsevier BV}, author={Karadzovska, Daniela and Brooks, James D. and Riviere, Jim E.}, year={2012}, month={Oct}, pages={1191–1198} }
 @article{leavens_monteiro-riviere_inman_brooks_oldenburg_riviere_2012, title={In vitro biodistribution of silver nanoparticles in isolated perfused porcine skin flaps}, volume={32}, ISSN={["0260-437X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84866866954&partnerID=MN8TOARS}, DOI={10.1002/jat.2750}, abstractNote={ABSTRACT}, number={11}, journal={JOURNAL OF APPLIED TOXICOLOGY}, author={Leavens, Teresa L. and Monteiro-Riviere, Nancy A. and Inman, Alfred O. and Brooks, James D. and Oldenburg, Steven J. and Riviere, Jim E.}, year={2012}, month={Nov}, pages={913–919} }
 @article{riviere_brooks_2011, title={Predicting Skin Permeability from Complex Chemical Mixtures: Dependency of Quantitative Structure Permeation Relationships on Biology of Skin Model Used}, volume={119}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/kfq317}, abstractNote={Dermal absorption of topically applied chemicals usually occurs from complex chemical mixtures; yet, most attempts to quantitate dermal permeability use data collected from single chemical exposure in aqueous solutions. The focus of this research was to develop quantitative structure permeation relationships (QSPR) for predicting chemical absorption from mixtures through skin using two levels of in vitro porcine skin biological systems. A total of 16 diverse chemicals were applied in 384 treatment mixture combinations in flow-through diffusion cells and 20 chemicals in 119 treatment combinations in isolated perfused porcine skin. Penetrating chemical flux into perfusate from diffusion cells was analyzed to estimate a normalized dermal absorptive flux, operationally an apparent permeability coefficient, and total perfusate area under the curve from perfused skin studies. These data were then fit to a modified dermal QSPR model of Abraham and Martin including a sixth term to account for mixture interactions based on physical chemical properties of the mixture components. Goodness of fit was assessed using correlation coefficients (r²), internal and external validation metrics (q²L00, q²L25%, q²EXT), and applicable chemical domain determinations. The best QSPR equations selected for each experimental biological system had r² values of 0.69-0.73, improving fits over the base equation without the mixture effects. Different mixture factors were needed for each model system. Significantly, the model of Abraham and Martin could also be reduced to four terms in each system; however, different terms could be deleted for each of the two biological systems. These findings suggest that a QSPR model for estimating percutaneous absorption as a function of chemical mixture composition is possible and that the nature of the QSPR model selected is dependent upon the biological level of the in vitro test system used, both findings having significant implications when dermal absorption data are used for in vivo risk assessments.}, number={1}, journal={TOXICOLOGICAL SCIENCES}, author={Riviere, Jim E. and Brooks, James D.}, year={2011}, month={Jan}, pages={224–232} }
 @article{ghafourian_samaras_brooks_riviere_2010, title={Modelling the effect of mixture components on permeation through skin}, volume={398}, ISSN={["1873-3476"]}, DOI={10.1016/j.ijpharm.2010.07.014}, abstractNote={A vehicle influences the concentration of penetrant within the membrane, affecting its diffusivity in the skin and rate of transport. Despite the huge amount of effort made for the understanding and modelling of the skin absorption of chemicals, a reliable estimation of the skin penetration potential from formulations remains a challenging objective. In this investigation, quantitative structure–activity relationship (QSAR) was employed to relate the skin permeation of compounds to the chemical properties of the mixture ingredients and the molecular structures of the penetrants. The skin permeability dataset consisted of permeability coefficients of 12 different penetrants each blended in 24 different solvent mixtures measured from finite-dose diffusion cell studies using porcine skin. Stepwise regression analysis resulted in a QSAR employing two penetrant descriptors and one solvent property. The penetrant descriptors were octanol/water partition coefficient, log P and the ninth order path molecular connectivity index, and the solvent property was the difference between boiling and melting points. The negative relationship between skin permeability coefficient and log P was attributed to the fact that most of the drugs in this particular dataset are extremely lipophilic in comparison with the compounds in the common skin permeability datasets used in QSAR. The findings show that compounds formulated in vehicles with small boiling and melting point gaps will be expected to have higher permeation through skin. The QSAR was validated internally, using a leave-many-out procedure, giving a mean absolute error of 0.396. The chemical space of the dataset was compared with that of the known skin permeability datasets and gaps were identified for future skin permeability measurements.}, number={1-2}, journal={INTERNATIONAL JOURNAL OF PHARMACEUTICS}, author={Ghafourian, T. and Samaras, E. G. and Brooks, J. D. and Riviere, J. E.}, year={2010}, month={Oct}, pages={28–32} }
 @misc{riviere_brooks_2010, title={Riviere and Brooks pig skin flow-through  [data file]}, author={Riviere, J. L. and Brooks, J. D.}, year={2010} }
 @article{riviere_brooks_yeatts_koivisto_2010, title={Surfactant Effects on Skin Absorption of Model Organic Chemicals: Implications for Dermal Risk Assessment Studies}, volume={73}, ISSN={["1528-7394"]}, DOI={10.1080/15287391003614026}, abstractNote={Occupational and environmental exposures to chemicals are major potential routes of exposure for direct skin toxicity and for systemic absorption. The majority of these exposures are to complex mixtures, yet most experimental studies to assess topical chemical absorption are conducted neat or in simple aqueous vehicles. A component of many industrial mixtures is surfactants that solubilize ingredients and stabilize mixtures of oily components when present in aqueous vehicles. The purpose of this series of experiments was to use two well-developed experimental techniques to assess how solution interactions present in a pure nonbiological in vitro system (membrane coated fibers, MCF) compare to those seen in a viable ex vivo biological preparation (isolated perfused porcine skin flap, IPPSF). Two widely encountered anionic surfactants, sodium lauryl sulfate (SLS) and linear alkylbenzene sulfonate (LAS), were studied in 10% solutions. The rank orders of absorption were: water: pentachlorophenol (PCP) > 4-nitrophenol (PNP) > parathion > fenthion > simazine > propazine; SLS: PNP > PCP > parathion > simazine > fenthion > propazine; and LAS: PNP > PCP > simazine > parathion > fenthion > propazine. For all penetrants, absorption was greater in SLS compared to LAS mixtures, a finding consistent with smaller micelle sizes seen with SLS. For these low-water-solubility compounds, absorption was greater from aqueous solutions in nearly every case. The inert three-fiber MCF array predicted absorptive fluxes seen in the ex vivo IPPSF, suggesting lack of any biological effects of the surfactants on skin.}, number={11}, journal={JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES}, author={Riviere, Jim E. and Brooks, James D. and Yeatts, James L. and Koivisto, Elisha L.}, year={2010}, pages={725–737} }
 @article{ghafourian_samaras_brooks_riviere_2010, title={Validated models for predicting skin penetration from different vehicles}, volume={41}, ISSN={["1879-0720"]}, DOI={10.1016/j.ejps.2010.08.014}, abstractNote={The permeability of a penetrant though skin is controlled by the properties of the penetrants and the mixture components, which in turn relates to the molecular structures. Despite the well-investigated models for compound permeation through skin, the effect of vehicles and mixture components has not received much attention. The aim of this Quantitative Structure Activity Relationship (QSAR) study was to develop a statistically validated model for the prediction of skin permeability coefficients of compounds dissolved in different vehicles. Furthermore, the model can help with the elucidation of the mechanisms involved in the permeation process. With this goal in mind, the skin permeability of four different penetrants each blended in 24 different solvent mixtures were determined from diffusion cell studies using porcine skin. The resulting 96 kp values were combined with a previous dataset of 288 kp data for QSAR analysis. Stepwise regression analysis was used for the selection of the most significant molecular descriptors and development of several regression models. The selected QSAR employed two penetrant descriptors of Wiener topological index and total lipole moment, boiling point of the solvent and the difference between the melting point of the penetrant and the melting point of the solvent. The QSAR was validated internally, using a leave-many-out procedure, giving a mean absolute error of 0.454 for the log kp value of the test set.}, number={5}, journal={EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES}, author={Ghafourian, Taravat and Samaras, Eleftherios G. and Brooks, James D. and Riviere, Jim E.}, year={2010}, month={Dec}, pages={612–616} }
 @article{riviere_brooks_2009, title={Determination of the effective dermal penetration barrier pH of porcine skin}, volume={32}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2008.01055.x}, abstractNote={Journal of Veterinary Pharmacology and TherapeuticsVolume 32, Issue 4 p. 407-410 Determination of the effective dermal penetration barrier pH of porcine skin J. E. RIVIERE, J. E. RIVIERE Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, NC, USASearch for more papers by this authorJ. D. BROOKS, J. D. BROOKS Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, NC, USASearch for more papers by this author J. E. RIVIERE, J. E. RIVIERE Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, NC, USASearch for more papers by this authorJ. D. BROOKS, J. D. BROOKS Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, NC, USASearch for more papers by this author First published: 08 July 2009 https://doi.org/10.1111/j.1365-2885.2008.01055.xCitations: 5 Dr Jim Riviere, Center for Chemical Toxicology Research and Pharmacokinetics, 4700 Hillsborough Street, North Carolina State University, Raleigh, NC 27606, USA. E-Mail:jim_riviere@ncsu.edu Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume32, Issue4August 2009Pages 407-410 RelatedInformation}, number={4}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Riviere, J. E. and Brooks, J. D.}, year={2009}, month={Aug}, pages={407–410} }
 @article{riviere_brooks_2007, title={Prediction of dermal absorption from complex chemical mixtures: incorporation of vehicle effects and interactions into a QSPR framework}, volume={18}, ISSN={["1029-046X"]}, DOI={10.1080/10629360601033598}, abstractNote={Significant progress has been made on predicting dermal absorption/penetration of topically applied compounds by developing QSPR models based on linear free energy relations (LFER). However, all of these efforts have employed compounds applied to the skin in aqueous or single solvent systems, a dosing scenario that does not mimic occupational, environmental or pharmaceutical exposure. We have explored using hybrid QSPR equations describing individual compound penetration based on the molecular descriptors for the compound modified by a mixture factor (MF) which accounts for the physicochemical properties of the vehicle/mixture components. The MF is calculated based on percentage composition of the vehicle/mixture components and physical chemical properties selected using principal components analysis. This model has been applied to 12 different compounds in 24 mixtures for a total of 288 treatment combinations obtained from flow-through porcine skin diffusion cells and in an additional dataset of 10 of the same compounds in five mixtures for a total of 50 treatment combinations in the ex vivo isolated perfused porcine skin flap. The use of the MF in combination with a classic LFER based on penetrant properties significantly improved the ability to predict dermal absorption of compounds dosed in complex chemical mixtures. †Presented at the 12th International Workshop on Quantitative Structure--Activity Relationships in Environmental Toxicology (QSAR2006), 8--12 May 2006, Lyon, France.}, number={1-2}, journal={SAR AND QSAR IN ENVIRONMENTAL RESEARCH}, author={Riviere, J. E. and Brooks, J. D.}, year={2007}, pages={31–44} }
 @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{baynes_yeatts_brooks_riviere_2005, title={Pre-treatment effects of trichloroethylene on the dermal absorption of the biocide, triazine}, volume={159}, ISSN={["0378-4274"]}, DOI={10.1016/j.toxlet.2005.05.012}, abstractNote={Triazine is often added to cutting-fluid formulations in the metal-machining industry as a preservative. Trichloroethylene (TCE) is a solvent used for cleaning the cutting fluid or oil from the metal product. The purpose of this study was to examine the effect of TCE on the dermal absorption of triazine in an in vitro flow-through diffusion cell system. Skin sections were dosed topically with aqueous mixtures containing mineral oil or polyethylene glycol (PEG) spiked with 14C-triazine. Some skin sections were simultaneously exposed to TCE while other skin sections were pre-treated with TCE daily for 4 days in vivo and then exposed to these mixtures in vitro. TCE pre-treatment almost doubled triazine permeability, but this pre-treatment had no effect on triazine diffusivity. The pre-treatment effects of TCE on triazine permeability appear to be more important in PEG-based mixtures than in the mineral oil-based mixtures. Simultaneous single exposure to TCE had little or no effect on triazine absorption. TCE absorption was significantly less than triazine absorption; however, cutting fluid additives had a more significant effect on TCE absorption than on triazine absorption. In summary, this study demonstrated that TCE pre-treatment can significantly alter the dermal permeability to triazine, and workers who are chronically exposed to this or similar cleansers may be at increased risk of absorbing related skin irritants.}, number={3}, journal={TOXICOLOGY LETTERS}, author={Baynes, RE and Yeatts, JL and Brooks, JD and Riviere, JE}, year={2005}, month={Dec}, pages={252–260} }
 @article{riviere_brooks_2005, title={Predicting skin permeability from complex chemical mixtures}, volume={208}, ISSN={["1096-0333"]}, DOI={10.1016/j.taap.2005.02.016}, abstractNote={Occupational and environmental exposure to topical chemicals is usually in the form of complex chemical mixtures, yet risk assessment is based on experimentally derived data from individual chemical exposures from a single, usually aqueous vehicle, or from computed physiochemical properties. We present an approach using hybrid quantitative structure permeation relationships (QSPeR) models where absorption through porcine skin flow-through diffusion cells is well predicted using a QSPeR model describing the individual penetrants, coupled with a mixture factor (MF) that accounts for physicochemical properties of the vehicle/mixture components. The baseline equation is log k(p) = c + mMF + a sigma alpha2(H) + b sigma beta2(H) + s pi2(H) + rR2 + vV(x) where sigma alpha2(H) is the hydrogen-bond donor acidity, sigma beta2(H) is the hydrogen-bond acceptor basicity, pi2(H) is the dipolarity/polarizability, R2 represents the excess molar refractivity, and V(x) is the McGowan volume of the penetrants of interest; c, m, a, b, s, r, and v are strength coefficients coupling these descriptors to skin permeability (k(p)) of 12 penetrants (atrazine, chlorpyrifos, ethylparathion, fenthion, methylparathion, nonylphenol, rho-nitrophenol, pentachlorophenol, phenol, propazine, simazine, and triazine) in 24 mixtures. Mixtures consisted of full factorial combinations of vehicles (water, ethanol, propylene glycol) and additives (sodium lauryl sulfate, methyl nicotinate). An additional set of 4 penetrants (DEET, SDS, permethrin, ricinoleic acid) in different mixtures were included to assess applicability of this approach. This resulted in a dataset of 16 compounds administered in 344 treatment combinations. Across all exposures with no MF, R2 for absorption was 0.62. With the MF, correlations increased up to 0.78. Parameters correlated to the MF include refractive index, polarizability and log (1/Henry's Law Constant) of the mixture components. These factors should not be considered final as the focus of these studies was solely to determine if knowledge of the physical properties of a mixture would improve predicting skin permeability. Inclusion of multiple mixture factors should further improve predictability. The importance of these findings is that there is an approach whereby the effects of a mixture on dermal absorption of a penetrant of interest can be quantitated in a standard QSPeR model if physicochemical properties of the mixture are also incorporated.}, number={2}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Riviere, JE and Brooks, JD}, year={2005}, month={Oct}, pages={99–110} }
 @article{muhammad_brooks_riviere_2004, title={Comparative mixture effects of JP-8(100) additives on the dermal absorption and disposition of jet fuel hydrocarbons in different membrane model systems}, volume={150}, ISSN={["1879-3169"]}, DOI={10.1016/j.toxlet.2004.02.012}, abstractNote={Jet fuel are complex mixtures of hydrocarbon fuel components and performance additives. Three different membrane systems, silastic, porcine skin and the isolated perfused porcine skin flap (IPPSF) were used to gain insight into the possible mechanism for additive interactions on hydrocarbon component absorption. Influence of JP-8(100) additives on the dermal kinetics of 14C-naphthalene and 14C/3H-dodecane as markers of hydrocarbon absorption, were evaluated using analysis of means (ANOM) and analysis of variance (ANOVA). This study indicated that the naphthalene absorption through silastic membrane was significantly different with JP-8 plus individual additives as compared to controls, i.e. JP-8 and JP-8(100). The porcine skin data indicated that neither individual nor combinations of additives affected naphthalene absorption. The third membrane system (IPPSF) showed that only MDA and BHT were important additives altering naphthalene absorption. MDA was a significant suppressor while BHT was a significant enhancer of naphthalene absorption. MDA significantly decreased dodecane absorption in skin flaps. All individual and combinations of two additives with JP-8 affected naphthalene and dodecane surface retention in silastic membrane. The IPPSF indicated that only 8Q405 is a significant modulator of surface retention for both marker hydrocarbons. The 8Q405 significantly reduced naphthalene contents in dosed silastic and skin indicating a direct interaction between additive and marker hydrocarbons. The MDA and BHT, which significantly retained naphthalene in the stratum corneum of porcine skin individually, led to a statistical decrease in its retention in the stratum corneum when in combination (MDA+BHT) suggesting a potential biological interaction. These observations demonstrate that the single membrane system may not be suitable for the final prediction of complex additive interactions in jet fuels. Rather a combination of different membrane systems may provide the insight to elucidate the possible mechanism for additive interactions. Finally, it is important to assess all components of a chemical mixture since the effects of single components administered alone or as pairs may be confounded when all are present in the complete mixture.}, number={3}, journal={TOXICOLOGY LETTERS}, author={Muhammad, F and Brooks, JD and Riviere, JE}, year={2004}, month={May}, pages={351–365} }
 @article{monteiro-riviere_van miller_simon_joiner_brooks_riviere_2003, title={In vitro percutaneous absorption of nonylphenol (NP) and nonylphenol ethoxylates (NPE-4 and NPE-9) in isolated perfused skin}, volume={22}, ISSN={["0731-3829"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000182704200001&KeyUID=WOS:000182704200001}, DOI={10.1081/CUS-120019325}, abstractNote={Skin contact with nonylphenol ethoxylates (NPE), a group of widely used surfactants, is the primary source of human exposure. Previous studies have shown that the absorption of NPE through human and animal skin in vitro is limited (<1% over 8 hr) [Monteiro-Riviere et al. Toxicol Indust Health 2000; 16:49–57]. The purpose of this study was to examine the percutaneous absorption of NPE and the chemical precursor, nonylphenol (NP), in the isolated perfused porcine skin flap (IPPSF) model for comparison to the in vitro porcine skin flow through (PSFT) diffusion studies. The IPPSF model is considered to accurately predict absorption of chemicals through human skin. The IPPSF was dosed with 100 μl of 1% 14C ring-labeled NP, 14C ring-labeled NPE-4, or 14C ring-labeled NPE-9 in aqueous polyethylene glycol (PEG-400) solution and perfused for 8 hr. All three chemicals were minimally absorbed, with only approximately 0.1% of the applied dose found in the perfusate over the 8-hr collection. This absorbed material represents the systemic exposure expected following skin contact in humans. In addition, less than 1% of the applied dose penetrated into the stratum corneum and underlying dermis, but remained within the skin and did not go through to the perfusate. Thus, the overall potential systemic exposure to these chemicals from skin contact, using a model considered similar to human skin in vivo, is less than 1%. The absorption results of this study were consistent with previous studies in the PSFT model. The penetration of NPEs and NP in the IPPSF was less than the PSFT and is probably more predictive of in vivo human absorption as this model is physiologically closer to human skin. This suggests that the overall potential for skin absorption of these chemicals in humans is even lower than previous estimates.}, number={1-2}, journal={JOURNAL OF TOXICOLOGY-CUTANEOUS AND OCULAR TOXICOLOGY}, author={Monteiro-Riviere, NA and Van Miller, JP and Simon, GS and Joiner, RL and Brooks, J and Riviere, JE}, year={2003}, pages={1–11} }
 @article{inman_still_jederberg_carpenter_riviere_brooks_monteiro-riviere_2003, title={Percutaneous absorption of 2,6-di-tert-butyl-4-nitrophenol (DBNP) in isolated perfused porcine skin}, volume={17}, ISSN={["0887-2333"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000183738100006&KeyUID=WOS:000183738100006}, DOI={10.1016/S0887-2333(03)00015-8}, abstractNote={DBNP (2,6-di-tert-butyl-4-nitrophenol) has been reported as a potential contaminant in submarines. This yellow substance forms when lubrication oil mist containing the antioxidant additive 2,6-di-tert-butylphenol passes through an electrostatic precipitator and is nitrated. Percutaneous absorption of 14C-DBNP was assessed in the isolated perfused porcine skin flap (IPPSF). Four treatments were studied (n=4 flaps/treatment): 40.0 μg/cm2 in 100% ethanol; 40.0 μg/cm2 in 85% ethanol/15% H2O; 4.0 μg/cm2 in 100% ethanol; and 4.0 μg/cm2 in 85% ethanol/15% water. DBNP absorption was minimal across all treatment groups, with the highest absorption detected being only 1.08% applied dose in an aqueous ethanol group. The highest mass of 14C-DBNP absorbed was only 0.5 μg. The majority of the applied dose remained on the surface of the skin. This suggests that there is minimal dermal exposure of DBNP when exposed topically to skin.}, number={3}, journal={TOXICOLOGY IN VITRO}, author={Inman, AO and Still, KR and Jederberg, WW and Carpenter, RL and Riviere, JE and Brooks, JD and Monteiro-Riviere, NA}, year={2003}, month={Jun}, pages={289–292} }
 @article{riviere_baynes_brooks_yeatts_monteiro-riviere_2003, title={Percutaneous absorption of topical N,N-diethyl-m-toluamide (DEET): Effects of exposure variables and coadministered toxicants}, volume={66}, DOI={10.1080/15287390390155796}, number={2}, journal={Journal of Toxicology and Environmental Health. Part A}, author={Riviere, J. E. and Baynes, R. E. and Brooks, J. D. and Yeatts, J. L. and Monteiro-Riviere, N.A.}, year={2003}, pages={133–151} }
 @article{baynes_brooks_mumtaz_riviere_2002, title={Effect of chemical interactions in pentachlorophenol mixtures on skin and membrane transport}, volume={69}, ISSN={["1096-6080"]}, DOI={10.1093/toxsci/69.2.295}, abstractNote={Pentachlorophenol (PCP) has been widely used as a pesticide, and topical exposure to a chemical mixture can alter its dermal absorption. The purpose of this study was to evaluate the influence of single and binary solvent systems (ethanol, EtOH, and water), a surfactant (6% sodium lauryl sulfate, SLS), and a rubifacient/vasodilator (1.28% methyl nicotinate, MNA) on PCP membrane transport, and to correlate these effects with physiochemical characteristics of the PCP mixtures. Partitioning, diffusion, and absorption parameters of (14)C-PCP at low (4 microg/cm(2)) and high (40 microg/cm(2)) doses were assessed in porcine skin and silastic membranes in vitro. In these 8-h, flow-through diffusion studies, PCP was dosed with the following vehicles: 100% EtOH, 100% water, 40% EtOH + 60% water, 40% EtOH + 60% water + SLS, 40% EtOH + 60% water + MNA, and 40% EtOH + 60% water + SLS + MNA. PCP absorption ranged from 1.55-15.62% for the high dose and 0.43-7.20% for the low dose. PCP absorption, flux, and apparent permeability were influenced by PCP solubility, and PCP apparent permeability was correlated with log PC (r2 = 0.66). Although PCP was very soluble in pure ethanol (100%), this vehicle evaporated very rapidly, and PCP absorption in ethanol was the lowest with this vehicle when compared to pure water (100%) or aqueous ethanol mixtures in general. MNA had no significant effect on membrane absorption or relative permeability R(P) in aqueous ethanol solutions, but the presence of the surfactant, SLS, significantly reduced PCP absorption and R(P) in both membrane systems. In conclusion, these studies demonstrated that modification in mixture composition with either a solvent and/or a surfactant can influence PCP diffusion in skin. Physicochemical interactions between these mixture components on the skin surface and stratum corneum contributed significantly to PCP transport, and these interactions were identified by simultaneously assessing chemical diffusion in biological and inert membrane systems.}, number={2}, journal={TOXICOLOGICAL SCIENCES}, author={Baynes, RE and Brooks, JD and Mumtaz, M and Riviere, JE}, year={2002}, month={Oct}, pages={295–305} }
 @article{baynes_brooks_barlow_riviere_2002, title={Physicochemical determinants of linear alkylbenzene sulfonate (LAS) disposition in skin exposed to aqueous cutting fluid mixtures}, volume={18}, ISSN={["1477-0393"]}, DOI={10.1191/0748233702th147oa}, abstractNote={ Linear alkylbenzene sulfonate (LAS) is added to cutting fluid formulations to enhance the performance of metal machining operations, but this surfactant can cause contact dermatitis in workers involved in these operations. The purpose of this study was to determine how cutting fluid additives influence dermal disposition of 14C-LAS in mineral oil-or polyethylene glycol 200 (PEG)-based mixtures when topically applied to silastic membranes and porcine skin in an in vitroflow-through diffusion cell system. 14C-LAS mixtures were formulated with three commonly used cutting fluid additives; 0 or 2% triazine (TRI), 0 or 5% triethanolamine (TEA), and 0 or 5% sulfurized ricinoleic acid (SRA). LAS absorption was limited to less than a 0.5% dose and the additives in various combinations influenced the physicochemical characteristics of the dosing mixture. LAS was more likely to partition into the stratum corneum (SC) in mineral oil mixtures, and LAS absorption was significantly greater in the complete mixture. TRI enhanced LAS transport, and the presence of SRA decreased LAS critical micelle concentration (CMC) which reduced LAS monomers available for transport. TEA increased mixture viscosity, and this may have negated the apparent enhancing properties of TRI in several mixtures. In summary, physicochemical interactions in these mixtures influenced availability of LAS for absorption and distribution in skin, and could ultimately influence toxicological responses in skin. }, number={5}, journal={TOXICOLOGY AND INDUSTRIAL HEALTH}, author={Baynes, RE and Brooks, JD and Barlow, BM and Riviere, JE}, year={2002}, pages={237–248} }
 @article{riviere_qiao_baynes_brooks_mumtaz_2001, title={Mixture component effects on the in vitro dermal absorption of pentachlorophenol}, volume={75}, DOI={10.1007/s002040100242}, abstractNote={Interactions between chemicals in a mixture and interactions of mixture components with the skin can significantly alter the rate and extent of percutaneous absorption, as well as the cutaneous disposition of a topically applied chemical. The predictive ability of dermal absorption models, and consequently the dermal risk assessment process, would be greatly improved by the elucidation and characterization of these interactions. Pentachlorophenol (PCP), a compound known to penetrate the skin readily, was used as a marker compound to examine mixture component effects using in vitro porcine skin models. PCP was administered in ethanol or in a 40% ethanol/60% water mixture or a 40% ethanol/60% water mixture containing either the rubefacient methyl nicotinate (MNA) or the surfactant sodium lauryl sulfate (SLS), or both MNA and SLS. Experiments were also conducted with 14C-labelled 3,3',4,4'-tetrachlorobiphenyl (TCB) and 3,3',4,4',5-pentachlorobiphenyl (PCB). Maximal PCP absorption was 14.12% of the applied dose from the mixture containing SLS, MNA, ethanol and water. However, when PCP was administered in ethanol only, absorption was only 1.12% of the applied dose. There were also qualitative differences among the absorption profiles for the different PCP mixtures. In contrast with the PCP results, absorption of TCB or PCB was negligible in perfused porcine skin, with only 0.14% of the applied TCB dose and 0.05% of the applied PCB dose being maximally absorbed. The low absorption levels for the PCB congeners precluded the identification of mixture component effects. These results suggest that dermal absorption estimates from a single chemical exposure may not reflect absorption seen after exposure as a chemical mixture and that absorption of both TCB and PCB are minimal in this model system.}, number={6}, journal={Archives of Toxicology}, author={Riviere, J. E. and Qiao, G. L. and Baynes, R. E. and Brooks, J. D. and Mumtaz, M.}, year={2001}, pages={329–334} }
 @article{baynes_brooks_budsaba_smith_riviere_2001, title={Mixture effects of JP-8 additives on the dermal disposition of jet fuel components}, volume={175}, ISSN={["1096-0333"]}, DOI={10.1006/taap.2001.9259}, abstractNote={Aliphatic and aromatic components in formulated jet fuels can cause occupational dermatitis. However, the influence of JP-8 performance additives (DIEGME, 8Q21, and Stadis450) on the dermal disposition of fuel components is not well understood. These additives are formulated with commercial Jet-A to form military JP-8 fuel. The purpose of this study is to assess the influence of these additives on the dermal disposition of marker aromatic and aliphatic components, naphthalene and dodecane, respectively. Porcine skin sections in an in vitro system were used to characterize chemical-biological interactions that modulate diffusion of jet fuel components and isolated perfused porcine skin flaps (IPPSFs) were used to evaluate diffusion in a viable skin model with an intact microvasculature. In these 5-h studies, Jet-A, Jet-A + DIEGME, Jet-A + 8Q21, and Jet-A + Stadis450, Jet-A + DIEGME + 8Q21, Jet-A + DIEGME + Stadis450, Jet-A + 8Q21 + Stadis450, and JP-8 mixtures were tested. In general, naphthalene absorption (0.76-2.39% dose) was greater than dodecane absorption (0.10-0.84% dose), while the IPPSFs alone demonstrated that dodecane absorption was significantly greater in JP-8 than in Jet-A. Synergistic interactions with 8Q21 + Stadis450 appear to enhance systemic absorption of either naphthalene or dodecane, while DIEGME + Stadis450 increased naphthalene (1.88% dose) and dodecane (2.02% dose) penetration into the skin and fat tissues of IPPSFs. These findings were supported by the fact that 8Q21 + Stadis450 significantly increased dodecane flux and permeability in porcine skin sections, but 8Q21 alone reduced marker diffusion in both membrane systems. Furthermore, dodecane is more likely than naphthalene to remain in the stratum corneum and skin surface at 5 h, and DIEGME mixtures played a significant role in skin and surface retention of both markers. In summary, the data suggest that various combinations of these three performance additives in JP-8 can potentially alter the dermal disposition of aromatic and aliphatic fuel components in skin. More importantly, products of two-factor interactions were not predictable from single-factor exposures and, by extension, cannot be extrapolated to three-factor interactions.}, number={3}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Baynes, RE and Brooks, JD and Budsaba, K and Smith, CE and Riviere, JE}, year={2001}, month={Sep}, pages={269–281} }
 @article{riviere_smith_budsaba_brooks_olajos_salem_monteiro-riviere_2001, title={Use of methyl salicylate as a simulant to predict the percutaneous absorption of sulfur mustard}, volume={21}, ISSN={["1099-1263"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000167916500002&KeyUID=WOS:000167916500002}, DOI={10.1002/jat.718}, abstractNote={Abstract}, number={2}, journal={JOURNAL OF APPLIED TOXICOLOGY}, author={Riviere, JE and Smith, CE and Budsaba, K and Brooks, JD and Olajos, EJ and Salem, H and Monteiro-Riviere, NA}, year={2001}, pages={91–99} }
 @article{monteiro-riviere_miller_simon_joiner_brooks_riviere_2000, title={Comparative in vitro percutaneous absorption of nonylphenol and nonylphenol ethoxylates (NPE-4 and NPE-9) through human, porcine and rat skin}, volume={16}, DOI={10.1191/074823300678827654}, number={2}, journal={Toxicology and Industrial Health}, author={Monteiro-Riviere, N.A. and Miller, J. P. Van and Simon, G. and Joiner, R. L. and Brooks, J. D. and Riviere, J. E.}, year={2000}, pages={49–57} }
 @article{qiao_chang_brooks_riviere_2000, title={Dermatotoxicokinetic modeling of p-nitrophenol and its conjugation metabolite in swine following topical and intravenous administration}, volume={54}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/54.2.284}, abstractNote={The development of a dermatotoxicokinetic (dTK) model for p-nitrophenol (PNP), a common metabolite from a variety of compounds and a biomarker of organophosphate (OP) insecticide exposure, may facilitate the kinetic modeling and risk assessment strategy for its parent compounds. In order to quantify and then clarify in vivo-in vitro correlation of PNP disposition, multicom- partment kinetic models were formulated. Female weanling pigs were dosed with ( 14 14 C quantitation in many other samples. Disposition pa- rameters (rate constants, Ftop ,T 1/2 ,T 1/2Ka, AUC, Vss, Clp, MAT, and MRT) and the simulated chemical mass-time profiles on the dosed skin surface and in the local, systemic, and excretory compart- ments were also determined. Total recoveries of 97.17 6 4.18% and 99.80 6 2.41% were obtained from topical and intravenous experiments, respectively. Ninety-six hours after topical and in- travenous application, 70.92 6 9.72% and 98.65 6 2.43% of the dose were excreted via urine, and 0.55 6 0.16% and 0.51 6 0.10% via the fecal route, respectively. Peak excretion rate and time were also determined. It was suggested by experimental observation and modeling that urinary 14 C excretion correlates with the systemic tissue depletion profile well and may be used as a biomarker of PNP exposure. This study also supports the strategy of using urinary PNP as a biomonitoring tool for OP pesticide exposure, although some precautions have to be taken. The strategy used in this study will be useful in comprehensive dTK modeling in der-}, number={2}, journal={TOXICOLOGICAL SCIENCES}, author={Qiao, GL and Chang, SK and Brooks, JD and Riviere, JE}, year={2000}, month={Apr}, pages={284–294} }
 @article{baynes_brooks_riviere_2000, title={Membrane transport of naphthalene and dodecane in jet fuel mixtures}, volume={16}, DOI={10.1191/074823300678839264}, number={6}, journal={Toxicology and Industrial Health}, author={Baynes, R. E. and Brooks, J. D. and Riviere, J. E.}, year={2000}, pages={225–238} }
 @article{riviere_brooks_qiao_2000, title={Methods of assessing the percutaneous absorption of volatile chemicals in isolated perfused skin: Studies with chloropentafluorobenzene and dichlorobenzene}, volume={10}, ISSN={["1051-7235"]}, DOI={10.1080/105172300750048746}, abstractNote={The experimental determination of dermal absorption of volatile chemicals is fraught with difficulties. The isolated perfused porcine skin flap (IPPSF) is a biologically intact, perfused skin preparation that has been employed to predict dermal absorption of chemicals in humans. The purpose of this work was to explore various experimental dosing strategies for volatile chemicals using dichlorobenzene (DCB) and chloropentafluorobenzene (CPFB) as model compounds. Effects of complete occlusion and various strategies of vapor trapping, vapor dosing, and solvent effects were explored. The results suggest that dosing methodology is a major determinant of dermal absorption and could easily skew results obtained from different systems. A biologically sensitive system such as the IPPSF is particularly sensitive to the manipulations required to ensure precise dosing of these compounds. An interesting finding was that the effects of solvents on compound absorption that are routinely described in liquid dosing scenarios were also detected when both the compound and solvent were exposed during the vapor phase.}, number={4}, journal={TOXICOLOGY METHODS}, author={Riviere, JE and Brooks, JD and Qiao, GL}, year={2000}, pages={265–281} }
 @article{riviere_brooks_monteiro-riviere_budsaba_smith_1999, title={Dermal Absorption and Distribution of Topically Dosed Jet Fuels Jet-A, JP-8, and JP-8(100)}, volume={160}, ISSN={0041-008X}, url={http://dx.doi.org/10.1006/taap.1999.8744}, DOI={10.1006/taap.1999.8744}, abstractNote={Dermal exposure to jet fuels has received increased attention with the recent release of newer fuels with novel performance additives. The purpose of these studies was to assess the percutaneous absorption and cutaneous disposition of topically applied (25 microl/5 cm(2)) neat Jet-A, JP-8, and JP-8(100) jet fuels by monitoring the absorptive flux of the marker components 14C naphthalene and (3)H dodecane simultaneously applied nonoccluded to isolated perfused porcine skin flaps (IPPSF) (n = 4). Absorption of 14C hexadecane was estimated from JP-8 fuel. Absorption and disposition of naphthalene and dodecane were also monitored using a nonvolatile JP-8 fraction reflecting exposure to residual fuel that might occur 24 h after a jet fuel spill. In all studies, perfusate, stratum corneum, and skin concentrations were measured over 5 h. Naphthalene absorption had a clear peak absorptive flux at less than 1 h, while dodecane and hexadecane had prolonged, albeit significantly lower, absorption flux profiles. Within JP-8, the rank order of absorption for all marker components was (mean +/- SEM % dose) naphthalene (1.17 +/- 0.07) > dodecane (0.63 +/- 0.04) > hexadecane (0.18 +/- 0.08). In contrast, deposition within dosed skin showed the reverse pattern. Naphthalene absorption into perfusate was similar across all fuel types, however total penetration into and through skin was highest with JP-8(100). Dodecane absorption and total penetration was greatest from JP-8. Absorption of both markers from aged JP-8 was lower than other fuels, yet the ratio of skin deposition to absorption was greatest for this treatment group. In most exposure scenarios, absorption into perfusate did not directly correlate to residual skin concentrations. These studies demonstrated different absorption profiles for the three marker compounds, differential effects of jet fuel types on naphthalene and dodecane absorption, and uncoupling of perfusate absorption from skin disposition.}, number={1}, journal={Toxicology and Applied Pharmacology}, publisher={Elsevier BV}, author={Riviere, Jim E. and Brooks, James D. and Monteiro-Riviere, Nancy A. and Budsaba, Kamon and Smith, Charles E.}, year={1999}, month={Oct}, pages={60–75} }
 @article{qiao_brooks_riviere_1997, title={Pentachlorophenol dermal absorption and disposition from soil in swine: Effects of occlusion and skin microorganism inhibition}, volume={147}, ISSN={["1096-0333"]}, DOI={10.1006/taap.1997.8288}, abstractNote={Residue of the environmentally relevant biocide pentachlorophenol (PCP) is found mainly in soil, making dermal contact one of the primary routes for PCP exposure. To quantify exposure effects on dermal absorption and systemic disposition, [14C-UL]PCP was dosed nonocclusively or occlusively at 40 micrograms/cm2 in a soil-based mixture in an in vivo swine model. Additionally, antibiotics were also codosed with occlusive PCP in soil to examine the impacts of skin microbial PCP biodegradation on total dermal absorption. Under nonocclusive, occlusive, and occlusive-antibiotic conditions, total radiolabel absorption by 408 hr was 29.08, 100.72, and 86.21% dose, respectively. Tissue accumulation of PCP and its labeled metabolite(s) was very significant in swine since one-half to two-thirds of the absorbed dose was still present in tissues by 17 days after PCP dermal exposure. High 14C concentrations were found in liver, kidney, lung, ovary, and uterus. Urine and fecal routes were equally important for label excretion from the body. Occlusion enhanced total dermal absorption and changed the shape of the absorption profiles in the blood and plasma. Skin microorganism inhibition retarded 14C dermal absorption, altered local and systemic tissue distribution, and increased plasma/blood concentration ratios, suggesting skin microbial PCP degradation might play an important role in the altered absorption and disposition by occlusion. This study demonstrated significant dermal absorption and extensive tissue persistence of PCP after soil exposure. Occlusion and skin microflora growth may greatly impact dermal absorption, cutaneous disposition, and systemic toxic input. Therefore, exposure-specific PCP absorption and disposition profiles must be taken into consideration in risk analysis.}, number={2}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Qiao, GL and Brooks, JD and Riviere, JE}, year={1997}, month={Dec}, pages={234–246} }
 @book{riviere_brooks_qiao_monteiro-riviere_1997, title={Percutaneous absorption of volatile chemicals}, DOI={10.21236/ada332910}, abstractNote={Abstract : The purpose of this project was to assess the percutaneous absorption of two volatile organic compounds, chloropentafluorobenzene (CPFB) and dichlorobenzene (DCB) in the isolated perfused porcine skin flap (IPPSF) model. An independent theoretical goal was to begin to develop a mathematical framework to assess vehicle-compound interactions which occur during dermal exposure. Assessment of the percutaneous absorption and penetration of volatile compounds is difficult. The process of studying these compounds involved 5 steps: (1) development of an IPPSF cradle chamber to trap the evaporated compound in the area next to the skin, (2) assessment of the mass of CPFB that was absorbed into the perfusate from CPFB which was evaporated from excised skin, (3) exposure of the IPPSF to neat test compounds and test compounds in a vehicle, (4) assessment of the mass of the test compound in the perfusate is a result of exposure to the volatile compound vapor, and (5) development of a dosing dome that allowed dosing a vapor without vapor uptake directly into the perfusate. Relevant absorption parameters were then determined. These studies demonstrated dose-dependent absorption of CPFB and DCB in skin which was further modulated by concomitant exposure to vehicle. The data obtained could be used as direct input into a systemic risk assessment model.}, journal={(NTIS report AFOSR G49620-95-1-0017)}, institution={Bethesda, MD: Cambridge Scientific Abstracts}, author={Riviere, J. E. and Brooks, J. D. and Qiao, G. L. and Monteiro-Riviere, N.A.}, year={1997}, pages={1–23} }
 @article{riviere_brooks_williams_mcgown_francoeur_1996, title={Cutaneous metabolism of isosorbide dinitrate after transdermal administration in isolated perfused porcine skin}, volume={127}, ISSN={["0378-5173"]}, DOI={10.1016/0378-5173(95)04213-X}, abstractNote={The purpose of this study was to determine whether isosorbide dinitrate (ISDN) was metabolized by the skin during transdermal delivery. In order to assess this, the isolated perfused porcine skin flap (IPPSF) was utilized since this in vitro model possesses a viable epidermis and intact vasculature, two attributes ideal for studying the biotransformation of a vasoactive drug. ISDN transdermal systems (20 cm2) were applied onto IPPSFs and the venous efflux sampled repeatedly over 16 h. ISDN, isosorbide-2-mononitrate (IS-2-MN), and isosorbide-5-mononitrate (IS-5-MN) fluxes were determined using gas chromatography. Approximately 14% of parent ISDN was metabolized to IS-2-MN and 10% to IS-5-MN. These observations are important as they indicate that a fraction of ISDN is biotransformed during transdermal delivery.}, number={2}, journal={INTERNATIONAL JOURNAL OF PHARMACEUTICS}, author={Riviere, JE and Brooks, JD and Williams, PL and McGown, E and Francoeur, ML}, year={1996}, month={Feb}, pages={213–217} }
 @article{brooks_riviere_1996, title={Quantitative percutaneous absorption and cutaneous distribution of binary mixtures of phenol and para-nitrophenol in isolated perfused porcine skin}, volume={32}, ISSN={["0272-0590"]}, DOI={10.1006/faat.1996.0126}, abstractNote={Chemical exposure to skin remains an important route by which systemic toxicity may occur. However, chemicals are seldom contacted singly in neat form and generally are present as a mixture. A total of 56 8-hr isolated perfused porcine skin flap (IPPSF) topical experiments were used to study the percutaneous absorption and cutaneous distribution of binary mixtures (solute/solvent) of14C-labeled phenol vsp-nitrophenol (PNP) at two concentrations (4 μg/cm2vs 40 μg/cm2) in two vehicles (acetone vs ethanol) under occluded vs nonoccluded dosing conditions. Pertinent comparisons were made to determine if dose, vehicle, or occlusion had a significant effect on absorption, localization of the test compounds, or total recoveries. Total recoveries were much greater in all cases for PNP than phenol. Absorption, penetration into tissues, and total recoveries of phenol were greater under occluded conditions than nonoccluded. Absorption and penetration of phenol into tissues were greater with ethanol than with acetone under nonoccluded conditions, but the opposite was observed under occluded conditions. Percentage of applied dose penetration into tissues was greater from low-dose phenol in acetone than high-dose, suggesting a fixed absorption rate. This was also seen for PNP, but only under occluded conditions. Neither phenol dose, vehicle, or occlusion had any significant effect on the labeled phenol seen in the stratum corneum or on time of peak flux, a finding which limits the usefulness of noninvasive stratum corneum sampling to assess topical penetration. There was greater absorption and penetration into tissues of PNP from acetone than from ethanol. PNP dose had a significant effect on time of peak dose, with low-dose PNP taking longer to reach its peak. Neither PNP dose, vehicle, nor occlusion had any significant effect on total recovery of labeled PNP. The results suggest that comparative absorption of phenol and PNP are vehicle-, occlusion-, and penetrant-dependent. These factors must be considered when comparing absorption data between studies. These findings suggest that single chemical data (the compound applied neat) is not predictive of even binary mixtures and that exposure conditions further modulate disposition.}, number={2}, journal={FUNDAMENTAL AND APPLIED TOXICOLOGY}, author={Brooks, JD and Riviere, JE}, year={1996}, month={Aug}, pages={233–243} }
 @article{qiao_brooks_baynes_monteiroriviere_williams_riviere_1996, title={The use of mechanistically defined chemical mixtures (MDCM) to assess component effects on the percutaneous absorption and cutaneous disposition of topically exposed chemicals .1. Studies with parathion mixtures in isolated perfused porcine skin}, volume={141}, ISSN={["0041-008X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1996WC22200015&KeyUID=WOS:A1996WC22200015}, DOI={10.1006/taap.1996.0313}, abstractNote={Recently, attention has been directed to the risk assessment of cutaneous exposure to chemical mixtures rather than to only a single compound since this is the exposure scenario in the environment, residence, and work place. Using acetone or dimethylsulfoxide (DMSO) (80% in water) as a vehicle, percutaneous absorption and cutaneous disposition of parathion (PA) were studied following PA (40 microg/cm2) dosing on isolated perfused porcine skin as mechanistically defined chemical mixtures (MDCM) consisting of the surfactant sodium lauryl sulfate (SLS), the rubefacient methyl nicotinate (MNA), and the reducing agent stannous chloride (SnCl2). A full 2 x 4 factorial design was used to asses treatment effects and potential interactions. More radiolabel was absorbed with DMSO than with acetone albeit an earlier peak flux time but lower peak flux was observed with acetone than with DMSO. The absorption flux rate profiles with DMSO continued increasing but bipeak-featured profiles were observed with acetone. SLS enhanced PA absorption with both DMSO and acetone. The presence of MNA in both vehicles blunted the absorption rate curves without significantly changing total absorption. SnCl2 blocked PA absorption and increased residue level on the skin surface and in the stratum corneum (SC). The venous flux profiles were mixture-dependent and highly reproducible within treatment groups. Higher level interactions were also noted. This study indicated multiple levels of interactive effects on PA absorption which must be incorporated into any effort to identify critical mechanisms which affect risk assessment of topically exposed mixtures. It was suggested that the chemicals selected in a topically applied mixture may have significant effects on the penetration/distribution pattern and percutaneous absorption profile of a toxicant/drug in the mixture. The MDCM approach may be useful in a screening or triage approach to identify mixture components which affect marker chemical absorption as well as identify potential mechanisms which deserve further attention. Risk assessment efforts could then be focused on those mixtures, containing these critical components, which would be expected to have the greatest penetration and absorption.}, number={2}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Qiao, GL and Brooks, JD and Baynes, RE and MonteiroRiviere, NA and Williams, PL and Riviere, JE}, year={1996}, month={Dec}, pages={473–486} }
 @article{chang_brooks_monteiroriviere_riviere_1995, title={ENHANCING OR BLOCKING EFFECT OF FENVALERATE ON THE SUBSEQUENT PERCUTANEOUS-ABSORPTION OF PESTICIDES IN-VITRO}, volume={51}, ISSN={["0048-3575"]}, DOI={10.1006/pest.1995.1021}, abstractNote={Abstract The percutaneous absorption of pesticides has been receiving much research attention. However, most work is conducted with single exposures and potential interactions of previous pesticide exposure have received little attention. In the present study, the effect of in vivo pretreatment of the skin with a 3% fenvalerate in ethanol or a 3% parathion in ethanol solution on carbaryl, fenvalerate, lindane, and parathion absorption was studied in vitro using weanling pig skin in a flowthrough diffusion cell system. Concentrations of 40 or 400 μg/cm2 of carbaryl, fenvalerate, lindane, and parathion in ethanol were applied topically. Environmental conditions of air and perfusate temperature (37°C), relative humidity (60%), flow rate (4 ml/hr), and Kreb′s-Ringer bicarbonate buffer with 4.5% bovine serum albumin medium were controlled. The total absorption of these pesticides, both ethanol control and fenvalerate or parathion pretreated, increased proportionally with the dose; however, the absorption efficiency (fraction of applied dose absorbed) decreased as the dose increased. At both doses, fenvalerate pretreatment had little or no effect on carbaryl and fenvalerate absorption; however, parathion absorption was significantly decreased in fenvalerate-pretreated skin (P}, number={3}, journal={PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY}, author={CHANG, SK and BROOKS, JD and MONTEIRORIVIERE, NA and RIVIERE, JE}, year={1995}, month={Mar}, pages={214–219} }
 @article{riviere_brooks_williams_monteiroriviere_1995, title={TOXICOKINETICS OF TOPICAL SULFUR MUSTARD PENETRATION, DISPOSITION, AND VASCULAR TOXICITY IN ISOLATED-PERFUSED PORCINE SKIN}, volume={135}, ISSN={["0041-008X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:A1995TD76100004&KeyUID=WOS:A1995TD76100004}, DOI={10.1006/taap.1995.1205}, abstractNote={Sulfur mustard bis(2-chloroethyl) sulfide (HD) is a bifunctional alkylating agent that causes cutaneous vesication. The isolated perfused porcine skin flap is an in vitro model that has been used to study this toxic response. The purpose of this study was to formulate a toxicokinetic model of HD penetration and cutaneous disposition as an aid in correlating critical steps in the pathogenesis of vesication to HD concentrations in different regions of skin. [14C]HD was dosed topically in ethanol at 10.0 mg/ml in a 7.5-cm2 dosing site and venous efflux samples were collected over 2, 4, or 8 hr. At the termination of the experiment, stratum corneum tape strips, core biopsies for serial sections, and the entire skin flap were collected for radioassay. Peak 14C-radiolabel flux occurred within 5 to 60 min in all skin flaps, much earlier than signs of HD-induced toxicity. A toxicokinetic model was used to quantitate the time profile of HD disposition in different skin compartments. Estimates of vascular and extracellular volume changes due to topical HD toxicity were estimated using radiolabeled albumin and inulin infusions. A second toxicokinetic model, with a time-variant distribution rate, was used to simulate volume changes. In order to accurately predict HD disposition, it was necessary to add another compartment as a reservoir for slowly released metabolites of HD. This model provides a quantitative profile of the time course of HD (or metabolites) disposition within skin which would aid in the interpretation of mechanistic studies of vesication as well as in designing interventive antivesicant drug strategies.}, number={1}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={RIVIERE, JE and BROOKS, JD and WILLIAMS, PL and MONTEIRORIVIERE, NA}, year={1995}, month={Nov}, pages={25–34} }
 @article{william_brooks_inman_monteiro-riviere_riviere_1994, title={Determination of physicochemical properties of phenol, p-nitrophenol, acetone and ethanol relevant to quantitating their percutaneous absorption in porcine skin}, volume={83}, journal={Research Communications in Chemical Pathology and Pharmacology}, author={William, P. L. and Brooks, J. D. and Inman, A. O. and Monteiro-Riviere, N. A. and Riviere, J. E.}, year={1994}, pages={61–75} }
 @book{monteiro-riviere_zhang_inman_brooks_riviere_1994, title={Mechanisms of cutaneous vesication}, volume={114}, journal={DAMD17-92-C-2071; NTIS, ADA283085}, institution={DAMD 17-92-C-2071, NTIS Report, ADA 283085}, author={Monteiro-Riviere, N. A. and Zhang, J. Z. and Inman, A. O. and Brooks, J. D. and Riviere, J. E.}, year={1994}, pages={1–114} }
 @inproceedings{bristol_riviere_monteiro-riviere_brooks_rogers_1992, title={Effect of vehicle and application site on absorption of chemicals through equine skin}, volume={38}, booktitle={Proceedings, 38th Annual Convention of the American Association of Equine Practitioners}, author={Bristol, D. G. and Riviere, J. E. and Monteiro-Riviere, N. A. and Brooks, J. D. and Rogers, R. A.}, year={1992}, pages={725} }
 @article{baynes_brooks_barlow_riviere, title={NDELA and nickel modulation of triazine disposition in skin}, volume={21}, number={9}, journal={Toxicology and Industrial Health}, author={Baynes, R. E. and Brooks, J. D. and Barlow, B. M. and Riviere, J. E.}, pages={197–205} }