@article{giles_ferdous_halleran_yeatts_baynes_mzyk_2024, title={Flunixin meglumine tissue residues after intravenous administration in goats}, volume={10}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2023.1341779}, abstractNote={BackgroundFlunixin is commonly used in goats in an extra-label manner, indicating a significant need to determine withdrawal intervals for edible tissues.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Giles, Claire B. and Ferdous, Farha and Halleran, Jennifer L. and Yeatts, Jim L. and Baynes, Ronald E. and Mzyk, Danielle A.}, year={2024}, month={Jan} }
 @article{halleran_sylvester_jacob_callahan_baynes_foster_2024, title={Impact of florfenicol dosing regimen on the phenotypic and genotypic resistance of enteric bacteria in steers}, volume={14}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-024-55591-8}, abstractNote={Abstract}, number={1}, journal={SCIENTIFIC REPORTS}, author={Halleran, Jennifer and Sylvester, Hannah and Jacob, Megan and Callahan, Benjamin and Baynes, Ronald and Foster, Derek}, year={2024}, month={Feb} }
 @article{wiloch_enomoto_smith_baynes_messenger_2024, title={Pharmacokinetics of intranasal and intramuscular flunixin in healthy grower pigs}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.13426}, abstractNote={Abstract}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Wiloch, Emily E. and Enomoto, Hiroko and Smith, Lilly and Baynes, Ronald E. and Messenger, Kristen M.}, year={2024}, month={Jan} }
 @article{elliot_enomoto_petritz_crespo_yeatts_fricke_singleton_thomson_baynes_2024, title={Pharmacokinetics of intravenously and trans-dermally administered fluralaner in healthy laying shaver hens: fluralaner in chickens}, volume={103}, ISSN={["1525-3171"]}, DOI={10.1016/j.psj.2023.103362}, abstractNote={Ectoparasite infestations negatively affect both backyard and commercial chicken flocks in the United States. Fluralaner is an isoxazoline shown to be efficacious in treating mite and bed bug infestations in poultry. Fluralaner is approved to treat fleas and ticks in dogs and cats in the United States and to treat mite infestations of chickens in Europe and Australia; however, the use of fluralaner in poultry is not yet approved in the United States. This study aimed to investigate the plasma fluralaner pharmacokinetic profile of intravenous and transdermal routes and apparent bioavailability of fluralaner administered trans-dermally in healthy shaver hens. A total of 12 individually housed healthy shaver hens received a single dose of either intravenous technical grade fluralaner at 0.5 mg/kg, or transdermal fluralaner (Bravecto (fluralaner transdermal solution) for dogs, 280 mg/mL, Merck Animal Health) at mean 58.7 mg/kg. Plasma from each hen was collected from the jugular, ulnar, or medial metatarsal vein at multiple intervals. Fluralaner concentrations in plasma were determined using Ultra Performance Liquid Chromatography with Mass Spectrometry (UPLC/MS). Noncompartmental analysis revealed that the geometric mean elimination half-life for intravenous and transdermal routes were 80.5 and 179.6 h, respectively. The geometric mean apparent bioavailability of transdermal routes was estimated as 3.4%. Prolonged fluralaner concentration in plasma above minimum inhibitory concentration of bed bugs following the single dose was observed in healthy shaver hens for both routes. It is important to understand the pharmacokinetic profile could be useful in determining the appropriate treatment strategy.}, number={3}, journal={POULTRY SCIENCE}, author={Elliot, Baxter A. and Enomoto, Hiroko and Petritz, Olivia and Crespo, Rocio and Yeatts, James and Fricke, Isabel and Singleton, Abby and Thomson, Andrea and Baynes, Ronald E.}, year={2024}, month={Mar} }
 @article{chou_tell_baynes_davis_cheng_maunsell_riviere_lin_2023, title={Development and application of an interactive generic physiologically based pharmacokinetic (igPBPK) model for adult beef cattle and lactating dairy cows to estimate tissue distribution and edible tissue and milk withdrawal intervals for per- and polyfluoroalkyl substances (PFAS)}, volume={181}, ISSN={["1873-6351"]}, DOI={10.1016/j.fct.2023.114062}, abstractNote={Humans can be exposed to per- and polyfluoroalkyl substances (PFAS) through dietary intake from milk and edible tissues from food animals. This study developed a physiologically based pharmacokinetic (PBPK) model to predict tissue and milk residues and estimate withdrawal intervals (WDIs) for multiple PFAS including PFOA, PFOS and PFHxS in beef cattle and lactating dairy cows. Results showed that model predictions were mostly within a two-fold factor of experimental data for plasma, tissues, and milk with an estimated coefficient of determination (R2) of >0.95. The predicted muscle WDIs for beef cattle were <1 day for PFOA, 449 days for PFOS, and 69 days for PFHxS, while the predicted milk WDIs in dairy cows were <1 day for PFOA, 1345 days for PFOS, and zero day for PFHxS following a high environmental exposure scenario (e.g., 49.3, 193, and 161 ng/kg/day for PFOA, PFOS, and PFHxS, respectively, for beef cattle for 2 years). The model was converted to a web-based interactive generic PBPK (igPBPK) platform to provide a user-friendly dashboard for predictions of tissue and milk WDIs for PFAS in cattle. This model serves as a foundation for extrapolation to other PFAS compounds to improve safety assessment of cattle-derived food products.}, journal={FOOD AND CHEMICAL TOXICOLOGY}, author={Chou, Wei-Chun and Tell, Lisa A. and Baynes, Ronald E. and Davis, Jennifer L. and Cheng, Yi-Hsien and Maunsell, Fiona P. and Riviere, Jim E. and Lin, Zhoumeng}, year={2023}, month={Nov} }
 @article{zad_tell_ramachandran_xu_riviere_baynes_lin_maunsell_davis_jaberi-douraki_2023, title={Development of machine learning algorithms to estimate maximum residue limits for veterinary medicines}, volume={179}, ISSN={["1873-6351"]}, DOI={10.1016/j.fct.2023.113920}, abstractNote={Establishing maximum-residue limits (MRLs) for veterinary medicine helps to protect the human food supply. Guidelines for establishing MRLs are outlined by regulatory authorities that drug sponsors follow in each country. During the drug approval process, residue limits are targeted for specific animal species and matrices. Therefore, MRLs are commonly not established for other species. This study demonstrates unestablished MRLs can be reliably predicted for under-represented food commodity groups using machine learning (ML). Classification methods with imbalanced data were used to analyze MRL data from multiple countries by implementing resampling techniques in different ML classifiers. Afterward, we developed and evaluated a data-mining method for predicting unestablished MRLs. Seven different ML classifiers such as support vector classifier, multi-layer perceptron (MLP), random forest, decision tree, k-neighbors, Gaussian NB, and AdaBoost have been selected in this baseline study. Among these, the neural network MLP classifier reliably scored the highest average-weighted F1 score (accuracy >99% with markers and ≈88% without markets) in predicting unestablished MRLs. This provides the first study to apply ML algorithms in regulatory food animal medicine. By predicting and estimating MRLs, we can potentially decrease the use and cost of live animals and the overall research burden of determining new MRLs.}, journal={FOOD AND CHEMICAL TOXICOLOGY}, author={Zad, Nader and Tell, Lisa A. and Ramachandran, Remya Ampadi and Xu, Xuan and Riviere, Jim E. and Baynes, Ronald and Lin, Zhoumeng and Maunsell, Fiona and Davis, Jennifer and Jaberi-Douraki, Majid}, year={2023}, month={Sep} }
 @article{mzyk_giles_baynes_smith_2023, title={Milk residues following multiple doses of meloxicam and gabapentin in lactating dairy cattle}, volume={261}, ISSN={["1943-569X"]}, url={http://dx.doi.org/10.2460/javma.23.06.0329}, DOI={10.2460/javma.23.06.0329}, abstractNote={Abstract}, number={12}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, publisher={American Veterinary Medical Association (AVMA)}, author={Mzyk, Danielle A. and Giles, Claire B. and Baynes, Ronald E. and Smith, Geof W.}, year={2023}, month={Dec}, pages={1873–1879} }
 @article{petritz_enomoto_meyer_thomson_baynes_flammer_2023, title={Pharmacokinetics and Safety of Sulfamethoxazole-Trimethoprim After Oral Administration of Single and Multiple Doses to Rhode Island Red Chickens (<i>Gallus gallus domesticus</i>)}, volume={37}, ISSN={["1938-2871"]}, DOI={10.1647/22-00020}, abstractNote={Abstract: Sulfamethoxazole-trimethoprim (SMZ-TMP), a commonly prescribed antibiotic for backyard hens, is neither Food and Drug Administration approved nor prohibited in laying hens in the United States. The aim of this study was to determine whether plasma concentrations above targeted minimum inhibitory concentration breakpoint values for Enterobacteriaceae could be achieved with oral dosing. Five Rhode Island red hens (Gallus gallus domesticus) were administered a single dose of 96 mg/kg SMZ-TMP (80 mg/kg SMZ and 16 mg/kg TMP) IV followed by the same dose orally after a washout period. Following oral dosing, mean SMZ concentrations exceeded the target breakpoint for approximately 12 hours; however, TMP only briefly exceeded the target breakpoint. Bioavailability was 60.5% for SMZ and 82.0% for TMP. Ten naïve birds were allocated into control (n = 4) and treatment (n = 6) groups for a 7-day multi-dose study. Treatment birds received an oral suspension dosed at 16 mg/kg TMP and 80 mg/kg SMZ every 48 hours (on days 1, 3, 5, and 7); TMP tablets were additionally dosed at 25 mg/bird on days 1, 3, 5, and 7, and 50 mg/bird on days 2, 4, and 6. Plasma SMZ-TMP concentrations were measured on a multiple time interval by ultraperformance liquid chromatography–mass spectrometry, and pharmacokinetic analyses were performed using a noncompartmental model. No accumulation for either drug was noted following repeated dosing, and no statistical differences in biochemical values, packed cell volumes, or weight were found between pre- and posttreatment in either the treatment or control groups. Sulfamethoxazole (80 mg/kg q48h PO) and TMP (24.1–28.0 mg/kg q24h PO) maintained therapeutic plasma concentrations at or exceeding the minimum inhibitory concentration breakpoint of Enterobacteriaceae for 72 and 24 hours for TMP and SMZ, respectively, without evidence of adverse effects or drug accumulation. Further studies are needed to refine this dosage regimen and evaluate adverse effects in ill birds.}, number={1}, journal={JOURNAL OF AVIAN MEDICINE AND SURGERY}, author={Petritz, Olivia A. and Enomoto, Hiroko and Meyer, Emma G. and Thomson, Andrea and Baynes, Ronald E. and Flammer, Keven}, year={2023}, month={Mar}, pages={1–12} }
 @article{gonzalez-morales_thomson_yeatts_enomoto_haija_santangelo_petritz_crespo_schal_baynes_2023, title={Pharmacokinetics of fluralaner as a systemic drug to control infestations of the common bed bug, <i>Cimex lectularius</i>, in poultry facilities}, volume={16}, ISSN={["1756-3305"]}, url={https://doi.org/10.1186/s13071-023-05962-3}, DOI={10.1186/s13071-023-05962-3}, abstractNote={Abstract}, number={1}, journal={PARASITES & VECTORS}, author={Gonzalez-Morales, Maria A. and Thomson, Andrea E. and Yeatts, James and Enomoto, Hiroko and Haija, Ahmed and Santangelo, Richard G. and Petritz, Olivia A. and Crespo, Rocio and Schal, Coby and Baynes, Ronald}, year={2023}, month={Sep} }
 @article{yuan_chou_richards_tell_baynes_davis_riviere_lin_2022, title={A web-based interactive physiologically based pharmacokinetic (iPBPK) model for meloxicam in broiler chickens and laying hens}, volume={168}, ISSN={["1873-6351"]}, DOI={10.1016/j.fct.2022.113332}, abstractNote={Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) commonly used in food-producing animals, including chickens in an extralabel manner. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model for meloxicam in broiler chickens and laying hens to facilitate withdrawal interval (WDI) estimations. The model structure for broiler chickens contained six compartments including plasma, muscle, liver, kidney, fat and rest of body, while an additional compartment of ovary was included for laying hens. The model adequately simulated available pharmacokinetic data of meloxicam in plasma of broiler chickens as well as tissue and egg data of laying hens. The model was converted to a web-based interface and used to predict WDIs following extralabel administrations. The results showed that the estimated WDIs were 50, 44, 11, 3, 3, 22 and 4 days for liver, kidney, muscle, fat, ovary, yolk and white, respectively in laying hens after 14 repeated oral administrations of meloxicam (1 mg/kg) at 24-h intervals. This model provides a useful and flexible tool for risk assessment and management of residues for meat and eggs from chickens treated with meloxicam and will serve as a basis for extrapolation to other NSAID drugs and other poultry species to aid animal-derived food safety assessment.}, journal={FOOD AND CHEMICAL TOXICOLOGY}, author={Yuan, Long and Chou, Wei-Chun and Richards, Emily D. and Tell, Lisa A. and Baynes, Ronald E. and Davis, Jennifer L. and Riviere, Jim E. and Lin, Zhoumeng}, year={2022}, month={Oct} }
 @article{chou_tell_baynes_davis_maunsell_riviere_lin_2022, title={An Interactive Generic Physiologically Based Pharmacokinetic (igPBPK) Modeling Platform to Predict Drug Withdrawal Intervals in Cattle and Swine: A Case Study on Flunixin, Florfenicol, and Penicillin G}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/kfac056}, abstractNote={Abstract}, journal={TOXICOLOGICAL SCIENCES}, author={Chou, Wei-Chun and Tell, Lisa A. and Baynes, Ronald E. and Davis, Jennifer L. and Maunsell, Fiona P. and Riviere, Jim E. and Lin, Zhoumeng}, year={2022}, month={Jun} }
 @article{werners_karasek_butler_yeatts_enomoto_baynes_2022, title={Control of ticks on horses using abamectin-impregnated ear tags. A pharmacokinetic and pharmacodynamic study}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.13084}, abstractNote={Abstract}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Werners, Arno and Karasek, Inga and Butler, Catherine and Yeatts, James and Enomoto, Hiroko and Baynes, Ronald}, year={2022}, month={Jun} }
 @article{mercer_davis_riviere_baynes_tell_jaberi-douraki_maunsell_lin_2022, title={Mechanisms of toxicity and residue considerations of rodenticide exposure in food Animals-a FARAD perspective}, volume={260}, ISSN={["1943-569X"]}, DOI={10.2460/javma.21.08.0364}, abstractNote={T Food Animal Residue Avoidance Databank (also known as the Food Animal Residue Avoidance and Depletion Program; FARAD) frequently receives requests for withdrawal interval (WDI) recommendations following inadvertent exposure of food animals to various environmental contaminants and pesticides such as rodenticides (Table 1). Rodenticide exposure in food animals typically occurs as a result of widespread use on farms for rodent control, contamination of waterways, or malicious intent. The Environmental Protection Agency (EPA) is the regulatory body that oversees rodenticides in the US, with 11 rodenticide chemicals currently carrying numerous active commercially registered products. The principal challenges when recommended WDIs are formulated for animals exposed to anticoagulant rodenticides and rodenticides with other mechanisms of action are numerous. These challenges include a lack of robust tissue pharmacokinetic data (particularly limited tissue half-lives) in many species, the low number of animal subjects enrolled in pharmacokinetic studies that may not represent population variations, and incomplete knowledge of dose exposure in affected animals. For most rodenticides, marker residues can be present in tissues such as the liver, pancreas, and kidney for years following oral exposure, whereas other more commonly consumed tissues may have declining residues over a period of months. Therefore, despite clinical resolution of rodenticide toxicosis in affected animals, extremely Mechanisms of toxicity and residue considerations of rodenticide exposure in food Animals—a FARAD perspective}, number={5}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Mercer, Melissa A. and Davis, Jennifer L. and Riviere, Jim E. and Baynes, Ronald E. and Tell, Lisa A. and Jaberi-Douraki, Majid and Maunsell, Fiona P. and Lin, Zhoumeng}, year={2022}, month={Mar}, pages={514–523} }
 @article{nixon_chittenden_baynes_messenger_2022, title={Pharmacokinetic/pharmacodynamic modeling of ketoprofen and flunixin at piglet castration and tail-docking}, volume={7}, ISSN={["1365-2885"]}, url={https://doi.org/10.1111/jvp.13083}, DOI={10.1111/jvp.13083}, abstractNote={Abstract}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, publisher={Wiley}, author={Nixon, Emma and Chittenden, Jason T. and Baynes, Ronald E. and Messenger, Kristen M.}, year={2022}, month={Jul} }
 @article{meira_wiloch_nixon_yeatts_sheela_smith_baynes_2022, title={The pharmacokinetics of transdermal flunixin in lactating dairy goats}, volume={105}, ISSN={["1525-3198"]}, url={https://doi.org/10.3168/jds.2021-20460}, DOI={10.3168/jds.2021-20460}, abstractNote={Flunixin is a nonsteroidal anti-inflammatory drug approved for use in cattle to manage pyrexia associated with bovine respiratory disease, mastitis, and endotoxemia. In the United States, no nonsteroidal anti-inflammatory drugs are approved for use in goats, but analgesics are needed for management of painful conditions to improve animal welfare. The objective of this study was to evaluate the pharmacokinetics of transdermal flunixin in dairy goats to determine a milk withdrawal interval (WDI) to avoid violative residue contamination in the food supply. Six adult lactating dairy goats received 3.3 mg/kg of transdermal flunixin before milk, interstitial fluid (ISF), and blood samples were collected at various time points for 360 h. The samples were analyzed using tandem mass spectrometry to detect flunixin as well as the flunixin marker metabolite, 5-hydroxyflunixin followed by a pharmacokinetic WDI calculation using the US Food and Drug Administration tolerance limit method to propose safe residue levels in goat milk. The mean flunixin apparent plasma half-life was 21.63 h. The apparent milk half-life for 5-hydroxyflunixin was 17.52 h. Our findings provide a milk WDI of 60 h using the US Food and Drug Administration tolerance of 0.002 µg/mL (established for bovine milk) and a more conservative WDI of 96 h using a limit of quantification of 0.001 µg/mL following the extralabel use of transdermal flunixin in dairy goats.}, number={1}, journal={JOURNAL OF DAIRY SCIENCE}, publisher={American Dairy Science Association}, author={Meira, Enoch B. de S., Jr Jr and Wiloch, Emily E. and Nixon, Emma and Yeatts, James L. and Sheela, Farha Ferdous and Smith, Geof W. and Baynes, Ronald E.}, year={2022}, month={Jan}, pages={549–559} }
 @article{halleran_papich_li_lin_davis_maunsell_riviere_baynes_foster_2022, title={Update on withdrawal intervals following extralabel use of procaine penicillin G in cattle and swine}, volume={260}, ISSN={["1943-569X"]}, DOI={10.2460/javma.21.05.0268}, abstractNote={IntroductionExtralabel drug use (ELDU) is defined as the use of an FDA-approved medication in a manner that differs from what is provided on the label of the medication.1 Administration of the medication to a different species or at a different dose, volume, route, duration, indication, or frequency than indicated on the label is considered ELDU. Extralabel drug use also requires an extended withdrawal period to avoid violative residues, and practitioners can get advice on withdrawal intervals (WDIs) following ELDU from the Food Animal Residue Avoidance and Depletion Program (FARAD). Penicillin is one of the most commonly used}, number={1}, journal={Journal of the American Veterinary Medical Association}, author={Halleran, J.L. and Papich, M.G. and Li, M. and Lin, Z. and Davis, J. and Maunsell, F. and Riviere, J. and Baynes, R. and Foster, D.M.}, year={2022}, month={Jan}, pages={50–55} }
 @article{nixon_carlson_routh_hernandez_almond_baynes_messenger_2021, title={Comparative effects of nonsteroidal anti-inflammatory drugs at castration and tail-docking in neonatal piglets}, volume={16}, ISSN={["1932-6203"]}, url={https://doi.org/10.1371/journal.pone.0254409}, DOI={10.1371/journal.pone.0254409}, abstractNote={This study assessed the efficacy of meloxicam, flunixin, and ketoprofen in piglets undergoing routine castration and tail-docking. Six-day-old male piglets (8/group) received one of five randomized treatments: intramuscular saline (SAL PROC), meloxicam (MEL; 0.4 mg/kg), flunixin (FLU; 2.2 mg/kg), ketoprofen (KETO; 3.0 mg/kg) or sham (SAL SHAM; saline injection, no processing). Two hours post-dose, piglets were castrated and tail-docked. Plasma cortisol, interstitial fluid (ISF) prostaglandin E2 (PGE2) and activity levels via Actical® monitoring were used to estimate pain. SAL SHAM and FLU exhibited lower cortisol concentrations than SAL PROC at the time of processing (p = 0.003 and p = 0.049, respectively), and all NSAIDs exhibited lower PGE2 than SAL PROC at 3.69 hours (MEL p = 0.050; FLU p = 0.043 and KETO p = 0.031). While not statistically significant, PGE2 was higher in SAL PROC piglets vs. other treatment groups at most time points. There was also a high degree of variability between piglets, especially for SAL PROC. Activity levels were significantly decreased at multiple time points in SAL PROC and MEL piglets following processing. However, FLU and KETO piglets had increased activity levels closer to that of the SAL SHAM group, suggesting that these NSAIDs are more effective than MEL in providing analgesia. These results demonstrate that management strategies including administration of intramuscular flunixin or ketoprofen to reduce pain associated with processing will likely improve piglet health and welfare in the United States.}, number={11}, journal={PLOS ONE}, author={Nixon, Emma and Carlson, Alexandra R. and Routh, Patricia A. and Hernandez, Liliana and Almond, Glen W. and Baynes, Ronald E. and Messenger, Kristen M.}, editor={Loor, Juan J.Editor}, year={2021}, month={Nov} }
 @article{halleran_minch_slyvester_jacob_prange_baynes_foster_2021, title={Comparison of the Intestinal Pharmacokinetics of Two Different Florfenicol Dosing Regimens and Its Impact on the Prevalence and Phenotypic Resistance of E. coli and Enterococcus over Time}, volume={9}, ISSN={["2076-2607"]}, DOI={10.3390/microorganisms9091835}, abstractNote={In order to mitigate the food animal sector’s role in the growing threat of antimicrobial resistance (AMR), the World Health Organization (WHO) suggests the use of lower tier antimicrobials, such as florfenicol. Florfenicol has two dosing schemes used to treat primarily bovine respiratory disease. In this study, the objective was to characterize the plasma and gastrointestinal pharmacokinetics of each dosing regimen and assess the effect of these dosing regimens on the prevalence of resistant indicator bacteria over time. Twelve steers underwent abdominal surgery to facilitate the placement of ultrafiltration probes within the lumen of the ileum and colon, as well as placement of an interstitial probe. Following surgery, cattle were dosed with either 20 mg/kg IM every 48 h of florfenicol given twice (n = 6) or a single, subcutaneous dose (40 mg/kg, n = 6). Plasma, interstitial fluid, gastrointestinal ultrafiltrate, and feces were collected. Pharmacokinetic analysis demonstrated high penetration of florfenicol within the gastrointestinal tract for both the high and low dose group (300%, 97%, respectively). There was no significant difference noted between dosing groups in proportion or persistence of phenotypically resistant bacterial isolates; however, the percent of resistant isolates was high throughout the study period. The recommendation for the use of a lower tier antimicrobial, such as florfenicol, may allow for the persistence of co-resistance for antibiotics of high regulatory concern.}, number={9}, journal={MICROORGANISMS}, author={Halleran, Jennifer L. and Minch, Ryker and Slyvester, Hannah J. and Jacob, Megan E. and Prange, Timo and Baynes, Ronald and Foster, Derek M.}, year={2021}, month={Sep} }
 @article{riad_baynes_tell_davis_maunsell_riviere_lin_2021, title={Development and Application of an interactive Physiologically Based Pharmacokinetic (iPBPK) Model to Predict Oxytetracycline Tissue Distribution and Withdrawal Intervals in Market-Age Sheep and Goats}, volume={183}, ISSN={1096-6080 1096-0929}, url={http://dx.doi.org/10.1093/toxsci/kfab095}, DOI={10.1093/toxsci/kfab095}, abstractNote={Abstract}, number={2}, journal={Toxicological Sciences}, publisher={Oxford University Press (OUP)}, author={Riad, Mahbubul H and Baynes, Ronald E and Tell, Lisa A and Davis, Jennifer L and Maunsell, Fiona P and Riviere, Jim E and Lin, Zhoumeng}, year={2021}, month={Jul}, pages={253–268} }
 @article{smith_bublitz_nixon_yeatts_ball_baynes_2021, title={EVALUATION OF THE PHARMACOKINETIC BEHAVIOR OF TULATHROMYCIN (DRAXXIN) IN FLORIDA MANATEES (TRICHECHUS MANATUS LATIROSTRIS) UNDERGOING MEDICAL REHABILITATION}, volume={52}, ISSN={["1937-2825"]}, url={http://dx.doi.org/10.1638/2021-0025}, DOI={10.1638/2021-0025}, abstractNote={Abstract: Florida manatees (Trichechus manatus latirostris) frequently present to rehabilitation care facilities for various conditions, including boat strike trauma, cold stress syndrome, and brevetoxicosis. Throughout the course of treatment, antimicrobial use to treat respiratory disease is frequently warranted. To date, clinicians have extrapolated dosages based on established information available in bovine and equine medicine. The routes of administration, efficacy, and treatment intervals are considerations in dealing with critical wild animals. The use of tulathromycin, a triamilide antibiotic, has been studied in multiple domestic species of economic importance, including cattle, small ruminants, and swine, and has revealed efficacy against respiratory diseases. Given this information, this antibiotic has also been used in manatees with positive clinical outcomes. This study employed sparse sampling and evaluated banked plasma samples at various time intervals post–tulathromycin administration obtained during the clinical treatment course of nine animals during their rehabilitation. Preliminary pharmacokinetic analysis following administration of a single dose estimated a half-life of 33.75 h and volume of distribution per fraction absorbed (Vz/F = 4.29 L/kg). The pharmacokinetic behavior of tulathromycin in Florida manatees can be used to optimize dosage regimens in this species.}, number={3}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, publisher={American Association of Zoo Veterinarians}, author={Smith, Lauren N. and Bublitz, Claire and Nixon, Emma and Yeatts, James and Ball, Ray L. and Baynes, Ronald E.}, year={2021}, month={Sep}, pages={880–885} }
 @article{enomoto_petritz_thomson_flammer_ferdous_meyer_tell_baynes_2021, title={Egg residue and depletion in Rhode Island Red hens (Gallus gallus domesticus) following multiple oral doses of trimethoprim-sulfamethoxazole}, volume={123}, ISSN={["1096-0295"]}, url={https://doi.org/10.1016/j.yrtph.2021.104941}, DOI={10.1016/j.yrtph.2021.104941}, abstractNote={Sulfamethoxazole-Trimethoprim residues in eggs can cause risks to human health. The most common cause of residues in eggs results from failure to meet an appropriate withdrawal interval. The aim of this study was to determine the quantity and duration of sulfamethoxazole-trimethoprim residues in eggs and evaluate the drug elimination parameters in egg components and whole egg to better estimate the withdrawal interval of sulfamethoxazole and trimethoprim following oral administration for 7 days at a purposed dosage regimen (time average 46 mg kg-1 day-1 for sulfamethoxazole, time average 25 mg kg-1 day-1 for trimethoprim). Residues of sulfamethoxazole and trimethoprim in albumen and yolk were analyzed by ultra-performance liquid chromatography mass spectrometry. A greater percentage of sulfamethoxazole was distributed into the albumen (91.53-96.74%) and a greater percentage of trimethoprim was distributed into yolk (63.92-77.36%) during treatment. The residues levels in whole egg declined below or reached the limit of quantification until 13 days for SMZ and TMP respectively. The withdrawal interval for SMZ and TMP were 43 days and 17 days respectively using the FDA tolerance method.}, journal={REGULATORY TOXICOLOGY AND PHARMACOLOGY}, publisher={Elsevier BV}, author={Enomoto, Hiroko and Petritz, Olivia A. and Thomson, Andrea E. and Flammer, Keven and Ferdous, Farha and Meyer, Emma and Tell, Lisa A. and Baynes, Ronald E.}, year={2021}, month={Jul} }
 @article{wagner_nixon_robles_baynes_coetzee_pairis-garcia_2021, title={Non-Steroidal Anti-Inflammatory Drugs: Pharmacokinetics and Mitigation of Procedural-Pain in Cattle}, volume={11}, ISSN={["2076-2615"]}, url={https://www.mdpi.com/2076-2615/11/2/282}, DOI={10.3390/ani11020282}, abstractNote={Common routine management practices in cattle, such as castration and disbudding, are recognized as being painful. In the United States (U.S.), these procedures are frequently performed without pain mitigation and there are currently no drugs federally approved for such use. Non-steroidal anti-inflammatory drugs, such as meloxicam, flunixin meglumine and aspirin, are the most commonly used analgesics in U.S. food-animal production systems. However, the body of research investigating the effectiveness of these pharmaceuticals to control pain in cattle at castration and disbudding has not been comprehensively evaluated. Therefore, this review examined existing literature to summarize meloxicam, flunixin and aspirin (1) pharmacokinetics (PK) and (2) administration outcome in regard to pain control during castration and disbudding procedures, in cattle. Following systematic searches and screening, 47 PK and 44 publications were extracted for data and are presented. The sample size contained notable variability and a general deficiency of validated and replicated methodologies for assessing pain in cattle remain substantial challenges within this research area. Future research should prioritize replication of pain assessment methodologies across different experimental conditions to close knowledge gaps identified by the present study and facilitate examination of analgesic efficacy.}, number={2}, journal={ANIMALS}, publisher={MDPI AG}, author={Wagner, Brooklyn K. and Nixon, Emma and Robles, Ivelisse and Baynes, Ronald E. and Coetzee, Johann F. and Pairis-Garcia, Monique D.}, year={2021}, month={Feb} }
 @misc{wang_li_tell_baynes_davis_vickroy_riviere_lin_2021, title={Physiological parameter values for physiologically based pharmacokinetic models in food-producing animals. Part II: Chicken and turkey}, volume={44}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12931}, abstractNote={Abstract}, number={4}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Wang, Yu-Shin and Li, Miao and Tell, Lisa A. and Baynes, Ronald E. and Davis, Jennifer L. and Vickroy, Thomas W. and Riviere, Jim E. and Lin, Zhoumeng}, year={2021}, month={Jul}, pages={423–455} }
 @article{robles_arruda_nixon_johnstone_wagner_edwards-callaway_baynes_coetzee_pairis-garcia_2021, title={Producer and Veterinarian Perspectives towards Pain Management Practices in the US Cattle Industry}, volume={11}, ISSN={["2076-2615"]}, url={https://www.mdpi.com/2076-2615/11/1/209}, DOI={10.3390/ani11010209}, abstractNote={Producers and veterinarians are considered responsible for improving animal welfare, as they are responsible for implementing practices that directly impact the animal’s well-being. Most husbandry procedures performed in cattle do not include pain mitigation, and understanding challenges faced by these stakeholders to use analgesics is key in improving on-farm pain management strategies. Therefore, the objectives of this study were to explore producer and veterinarian perspectives on pain management practices by (1) exploring inquires received by Food Animal Residue Avoidance Databank (FARAD) regarding analgesic use in cattle and (2) using a survey instrument to identify factors that impact pain management implementation in the US cattle industry. Albeit analgesia use increased in the past ten years for some producers and the majority of veterinarians, administering analgesics for pain management on US cattle farms remains a challenge. From a producer perspective, drug cost, availability and logistics for administration. From a veterinarian perspective, lack of Food and Drug Administration (FDA) products hinders the support of on-farm protocols requiring extra-label drug use. Future steps to improve analgesic use on-farm include identifying and approving drugs that demonstrate efficacy for managing pain in cattle and disseminating educational resources to support stakeholders in both the implementation and drug withdrawal process.}, number={1}, journal={ANIMALS}, author={Robles, Ivelisse and Arruda, Andreia G. and Nixon, Emma and Johnstone, Elizabeth and Wagner, Brooklyn and Edwards-Callaway, Lily and Baynes, Ronald and Coetzee, Johann and Pairis-Garcia, Monique}, year={2021}, month={Jan} }
 @misc{baeumer_baynes_2021, title={Surface distribution of pyrethroids following topical application to veterinary species: Implications for lateral transport}, volume={44}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12907}, abstractNote={Abstract}, number={1}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Baeumer, Wolfgang and Baynes, Ronald}, year={2021}, month={Jan}, pages={1–10} }
 @misc{karasek_butler_baynes_werners_2020, title={A review on the treatment and control of ectoparasite infestations in equids}, volume={43}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12874}, abstractNote={Ectoparasites infestations are a growing concern to horse owners and equine veterinarians alike. Ectoparasites cause significant health and welfare issues and can potentially can serve as vectors for a variety of pathogens. The prevalence of ectoparasites increases around the world, and especially in horses information on the successful prevention and treatment of ectoparasite infestations in scarce and in many instances anecdotal. This poses a challenge to the equine veterinarian and off‐label use of drugs can lead to detrimental effects in horses. In this review we describe the current available evidence for the prevention and treatment of ectoparasite infestations in horses. Only a very limited number of products is approved for the use in horses and fortunately many of the other products that are used in an off‐label manner appear to be safe in horses. Future research in this area should aim at providing PK/PD modelling data to assure appropriate and safe dose regimen to prevent and treat ectoparasite infestations in horses.}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Karasek, Inga and Butler, Catherine and Baynes, Ronald and Werners, Arno}, year={2020}, month={Sep}, pages={421–428} }
 @article{nixon_almond_baynes_messenger_2020, title={Comparative Plasma and Interstitial Fluid Pharmacokinetics of Meloxicam, Flunixin, and Ketoprofen in Neonatal Piglets}, volume={7}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2020.00082}, abstractNote={Piglet castration and tail-docking are routinely performed in the United States without analgesia. Pain medications, predominately non-steroidal anti-inflammatory drugs, are used in the EU/Canada to decrease pain associated with processing and improve piglet welfare, however, past studies have shown the efficacy and required dose remain controversial, particularly for meloxicam. This study assessed the pharmacokinetics of three NSAIDs (meloxicam, flunixin, and ketoprofen) in piglets prior to undergoing routine castration and tail-docking. Five-day-old male piglets (8/group) received one of 3 randomized treatments; meloxicam (0.4 mg/kg), flunixin (2.2 mg/kg), ketoprofen (3.0 mg/kg). Two hours post-dose, piglets underwent processing. Drug concentrations were quantified in plasma and interstitial fluid (ISF) and pharmacokinetic parameters were generated by non-compartmental analysis. Time to peak concentration (Tmax) of meloxicam, flunixin, and S(–)-ketoprofen in plasma were 1.21, 0.85, and 0.59 h, compared to 2.81, 3.64, and 2.98 h in the ISF, respectively. The apparent terminal half-life of meloxicam, flunixin and S(–)-ketoprofen were 4.39, 7.69, and 3.50 h, compared to 11.26, 16.34, and 5.54 h, respectively in the ISF. If drug concentrations in the ISF are more closely related to efficacy than the plasma, then the delay between the Tmax in plasma and ISF may be relevant to the timing of castration in order to provide the greatest analgesic effect.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Nixon, Emma and Almond, Glen W. and Baynes, Ronald E. and Messenger, Kristen M.}, year={2020}, month={Feb} }
 @misc{lin_li_wang_tell_baynes_davis_vickroy_riviere_2020, title={Physiological parameter values for physiologically based pharmacokinetic models in food-producing animals. Part I: Cattle and swine}, volume={43}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12861}, abstractNote={Abstract}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Lin, Zhoumeng and Li, Miao and Wang, Yu-Shin and Tell, Lisa A. and Baynes, Ronald E. and Davis, Jennifer L. and Vickroy, Thomas W. and Riviere, Jim E.}, year={2020}, month={Sep}, pages={385–420} }
 @article{nixon_mays_routh_yeatts_fajt_hairgrove_baynes_2020, title={Plasma, urine and tissue concentrations of Flunixin and Meloxicam in Pigs}, volume={16}, ISSN={["1746-6148"]}, DOI={10.1186/s12917-020-02556-4}, abstractNote={Abstract}, number={1}, journal={BMC VETERINARY RESEARCH}, author={Nixon, Emma and Mays, Travis P. and Routh, Patricia A. and Yeatts, James L. and Fajt, Virginia R. and Hairgrove, Thomas and Baynes, Ronald E.}, year={2020}, month={Sep} }
 @article{bublitz_mzyk_mays_fajt_hairgrove_baynes_2019, title={Comparative plasma and urine concentrations of flunixin and meloxicam in goats}, volume={174}, ISBN={1879-0941}, DOI={10.1016/j.smallrumres.2019.01.013}, abstractNote={The objective of this study was to compare plasma and urine concentrations of flunixin and meloxicam, in order to determine withdrawal intervals for animals at livestock shows where urine is routinely tested. Eleven goats were housed in individual metabolism cages to facilitate complete urine collection. All animals were randomly divided into one of two treatment groups and received either a single dose of 2.2 mg/kg flunixin in the muscle (n = 5) or 0.5 mg/kg meloxicam by mouth (n = 6). Flunixin meglumine was given via an intramuscular injection to evaluate the effect of extra label administration on the disposition of flunixin in goats. The information from this study represents a potential worst-case scenario for urine depletion and helps determine the withdrawal intervals needed for flunixin meglumine in show goats when administered in this extra label manner. Plasma and urine samples were collected over 360 h and analyzed by tandem mass spectrometry (UPLC-MS-MS). Goats were euthanized at the end of the study, and liver samples were collected at necropsy 15 days post dose in order to quantify any potential residues. Drug levels in urine reached peak concentrations between 8 and 16 h after dosing for both drugs. Flunixin urine concentrations were higher than maximum levels determined in plasma. Urine concentrations for both flunixin and meloxicam fell below the limit of detection (LOD) of 1.0 ng/mL by 240 h in all goats. Calculated harmonic mean apparent elimination half-life in plasma based on non-compartmental analysis was 5.4 ± 0.001 h and 10.3 ± 0.001 h for flunixin and meloxicam respectively. Five of six liver samples for goats administered meloxicam fell below the limit of quantification (LOQ) of 5.0 ng/mL by 15 days. Four out of five liver samples for goats administered flunixin fell below the LOQ (5.0 ng/mL) by 15 days. Flunixin and meloxicam administered to healthy goats exhibited longer elimination from urine than plasma, but followed a similar and linear depletion profile. Urine concentrations did not correlate with liver residues. This study provides useful information that can assist livestock show authorities and veterinarians determine an appropriate withdrawal interval for show animals whose urine may be tested prior to competition.}, journal={SMALL RUMINANT RESEARCH}, author={Bublitz, Claire M. and Mzyk, Danielle A. and Mays, Travis and Fajt, Virginia R. and Hairgrove, Thomas and Baynes, Ronald E.}, year={2019}, month={May}, pages={40–46} }
 @article{hairgrove_mask_mays_fajt_bentke_warner_baynes_2019, title={Detection of flunixin in the urine of untreated pigs housed with pigs treated with flunixin meglumine at labeled doses}, volume={3}, ISSN={["2573-2102"]}, DOI={10.1093/tas/txz099}, abstractNote={Abstract}, number={4}, journal={TRANSLATIONAL ANIMAL SCIENCE}, author={Hairgrove, Thomas B. and Mask, Joe W. and Mays, Travis P. and Fajt, Virginia R. and Bentke, Ashley L. and Warner, Jacob L. and Baynes, Ronald E.}, year={2019}, month={Jul}, pages={1399–1404} }
 @article{yang_lin_riviere_baynes_2019, title={Development and application of a population physiologically based pharmacokinetic model for florfenicol and its metabolite florfenicol amine in cattle}, volume={126}, ISSN={["1873-6351"]}, DOI={10.1016/j.fct.2019.02.029}, abstractNote={Florfenicol (FF) is used in cattle to treat respiratory diseases but could result in tissue residues. This study aimed to develop a population physiologically based pharmacokinetic (PBPK) model to predict the concentrations of FF and its metabolite, florfenicol amine (FFA), in cattle after four different routes of administration, and to calculate and compare the withdrawal intervals (WDIs) with approved withdrawal times based on different marker residues and their MRLs or tolerances. A flow-limited PBPK model including both FF and FFA sub-models were developed with published data using acslXtreme. This model predicted FF and FFA concentrations in tissues and plasma/serum after intramuscular or subcutaneous administration. Based on the model, the WDIs of 46 and 58 days were calculated to ensure that total residue concentrations (FF + FFA) in 95th percentile of the population after intramuscular and subcutaneous administration were below the MRL, respectively. WDIs were calculated as 44 and 47 days to ensure that FFA concentrations after intramuscular and subcutaneous administration fell below tolerances in 99th percentile of the population, respectively. WDIs were longer than the corresponding label in China, US, and EU. This model provides a useful tool to predict tissue residues of FF and FFA in cattle to improve food safety.}, journal={FOOD AND CHEMICAL TOXICOLOGY}, author={Yang, Fan and Lin, Zhoumeng and Riviere, Jim E. and Baynes, Ronald E.}, year={2019}, month={Apr}, pages={285–294} }
 @article{mzyk_bublitz_martinez_davis_baynes_smith_2019, title={Impact of bovine respiratory disease on the pharmacokinetics of danofloxacin and tulathromycin in different ages of calves}, volume={14}, ISSN={["1932-6203"]}, url={http://dx.doi.org/10.1371/journal.pone.0218864}, DOI={10.1371/journal.pone.0218864}, abstractNote={Pneumonia is one of the most economically important respiratory diseases of calves and knowledge of the impact of clinical disease on pharmacokinetics (PK) in young calves is limited. This study was undertaken to investigate the efficacy and PK of two antibiotics, tulathromycin and danofloxacin, in two age groups of calves experimentally infected with Pasteurella multocida. Both danofloxacin, a fluoroquinolone antibiotic, and tulathromycin, a macrolide antibiotic is approved for the treatment of bovine respiratory disease (BRD). To evaluate potential influences of age and disease on drug distribution and elimination in calves, plasma, interstitial fluid (ISF), and pulmonary epithelial lining fluid (PELF) were analyzed for drug concentrations. Concentrations for both drugs in the PELF were estimated by a urea dilution assay of the collected bronchoalveolar lavage fluids. Age was determined to be a significant covariate for calves administered danofloxacin and tulathromycin for plasma PK parameters. For calves administered danofloxacin, the area under the curve (AUC) in the plasma was lower in 6-month old calves (18.9 ± 12.6 hr* μg/mL) vs. 3-week old calves (32.0 ± 8.2 hr* μg/mL). Clearance (CL/F) of danofloxacin was higher in 6-month old calves. In contrast, tulathromycin plasma concentrations were higher in 6 month old calves and CL/F was higher in 3-week old calves. Age did not significantly influence the ISF concentrations of danofloxacin or tulathromycin in calves with respiratory disease, unlike previous studies which reported higher ISF concentrations of danofloxacin and tulathromycin in 6-month old calves when compared to younger calves. PELF concentrations were higher than plasma and ISF for both danofloxacin and tulathromycin, but did not differ between age groups. Potential reasons for age-related differences on plasma concentration–time profiles and the impact of disease on the partitioning of the drug from the blood to the lungs and ISF as a function of age are explored.}, number={6}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={Mzyk, Danielle A. and Bublitz, Claire M. and Martinez, Marilyn N. and Davis, Jennifer L. and Baynes, Ronald E. and Smith, Geof W.}, editor={Gladue, DouglasEditor}, year={2019}, month={Jun} }
 @article{li_cheng_chittenden_baynes_tell_davis_vickroy_riviere_lin_2019, title={Integration of Food Animal Residue Avoidance Databank (FARAD) empirical methods for drug withdrawal interval determination with a mechanistic population-based interactive physiologically based pharmacokinetic (iPBPK) modeling platform: example for flunixin meglumine administration}, volume={93}, ISSN={0340-5761 1432-0738}, url={http://dx.doi.org/10.1007/s00204-019-02464-z}, DOI={10.1007/s00204-019-02464-z}, abstractNote={Violative chemical residues in animal-derived food products affect food safety globally and have impact on the trade of international agricultural products. The Food Animal Residue Avoidance Databank program has been developing scientific tools to provide appropriate withdrawal interval (WDI) estimations after extralabel drug use in food animals for the past three decades. One of the tools is physiologically based pharmacokinetic (PBPK) modeling, which is a mechanistic-based approach that can be used to predict tissue residues and WDIs. However, PBPK models are complicated and difficult to use by non-modelers. Therefore, a user-friendly PBPK modeling framework is needed to move this field forward. Flunixin was one of the top five violative drug residues identified in the United States from 2010 to 2016. The objective of this study was to establish a web-based user-friendly framework for the development of new PBPK models for drugs administered to food animals. Specifically, a new PBPK model for both cattle and swine after administration of flunixin meglumine was developed. Population analysis using Monte Carlo simulations was incorporated into the model to predict WDIs following extralabel administration of flunixin meglumine. The population PBPK model was converted to a web-based interactive PBPK (iPBPK) framework to facilitate its application. This iPBPK framework serves as a proof-of-concept for further improvements in the future and it can be applied to develop new models for other drugs in other food animal species, thereby facilitating the application of PBPK modeling in WDI estimation and food safety assessment.}, number={7}, journal={Archives of Toxicology}, publisher={Springer Science and Business Media LLC}, author={Li, Miao and Cheng, Yi-Hsien and Chittenden, Jason T. and Baynes, Ronald E. and Tell, Lisa A. and Davis, Jennifer L. and Vickroy, Thomas W. and Riviere, Jim E. and Lin, Zhoumeng}, year={2019}, month={Apr}, pages={1865–1880} }
 @article{westermeyer_salmon_baynes_yeatts_khattab_oh_mowat_2019, title={Safety and efficacy of topically applied 0.5% and 1% pirfenidone in a canine model of subconjunctival fibrosis}, volume={22}, ISSN={["1463-5224"]}, url={https://doi.org/10.1111/vop.12619}, DOI={10.1111/vop.12619}, abstractNote={Abstract}, number={4}, journal={VETERINARY OPHTHALMOLOGY}, author={Westermeyer, Hans D. and Salmon, Beth and Baynes, Ronald and Yeatts, James and Khattab, Ahlam and Oh, Annie and Mowat, Freya}, year={2019}, month={Jul}, pages={502–509} }
 @article{udiani_mason_smith_mzyk_gehring_tell_riviere_baynes_2018, title={Automation and applications of the tolerance limit method in estimating meat withdrawal periods for veterinary drugs}, volume={146}, ISSN={["1872-7107"]}, url={http://dx.doi.org/10.1016/j.compag.2018.02.005}, DOI={10.1016/j.compag.2018.02.005}, abstractNote={A program was written in R to facilitate the implementation of the tolerance limit method (TLM) for establishing regulatory withdrawal times for limiting drug residues in meat, milk, and eggs. The developed computer source code can use pharmacokinetic and regulatory data to calculate the drug withdrawal period according to United States Food and Drug Administration (U.S. FDA) guidelines. The code called the “Withdrawal Time Calculator (WTC)” applied this TLM method to meat samples. The program was tested with the data provided by the U.S. FDA guidance and other published data collected from in vivo studies. Additional algorithm validation data were flunixin and sulfamethazine liver concentration data from peer-reviewed publications generated by our laboratory. This manuscript reports the withdrawal period results from testing the developed WTC code. Moreover, the source code for the WTC contains a data removal algorithm, constructed according to U.S. FDA data elimination recommendations if the user chooses. The power of the WTC is that it bypasses the use of multiple platforms typically required to perform the TLM, including standard commercial spreadsheet software (i.e., Microsoft Excel) and Statistical Analysis System (SAS) while providing speed and usability. This novel program provides a platform to calculate a withdrawal period recommendation for any drug in any class of animal for various regulatory body standards and could be very helpful in cases of extra-label drug use in food animals.}, journal={COMPUTERS AND ELECTRONICS IN AGRICULTURE}, publisher={Elsevier BV}, author={Udiani, O. and Mason, S. and Smith, G. and Mzyk, D. and Gehring, R. and Tell, L. and Riviere, J. E. and Baynes, R. E.}, year={2018}, month={Mar}, pages={125–135} }
 @article{mason_mullen_washburn_anderson_baynes_2018, title={Comparison of the pharmacokinetics of plant-based treatments in milk and plasma of USDA organic dairy cattle with and without mastitis}, volume={35}, ISSN={["1944-0057"]}, DOI={10.1080/19440049.2018.1502475}, abstractNote={ABSTRACT Organic dairy products are the second largest sector of the organic food market. Organic dairy products come from United States Department of Agriculture (USDA) certified organic dairy cattle that meet USDA organic standards. Organic dairy cattle in the US cannot be treated with antibiotics for mastitis, one of the costliest diseases of dairy cattle, and thus effective alternatives are needed. When any compound (medication or other non-food product) is used in a food producing animal, a withhold time for that compound that meets US Food and Drug Administration (FDA) standards for food safety must be applied to the animal and its products (like milk). However, there are no US FDA products approved for mastitis that maintain USDA certified organic dairy cattle’s organic status. Thus, we studied the pharmacokinetics of 3 compounds (garlic, thymol and carvacrol) used on organic both healthy and mastitic organic dairy cattle. We also used this information to estimate a milk withhold time using methods consistent with US FDA requirements. For thymol intra-mammary and carvacrol intra-mammary or topical administration, all compounds were partially absorbed into the body from the milk or skin. Thymol and carvacrol are measurable in plasma (at 0.0183 and 0.0202 µg/mL, respectively) after intramammary administration with similar elimination half lives of 1.7 h. Milk concentrations of thymol and carvacrol are much higher at 2.958 and 4.487 µg/mL in healthy cattle, respectively. Concentrations are not significantly different in cows with mastitis as compared to those in healthy cows. Despite these compounds being natural products, they should have a withhold time for milk of at least 24 h after administration. For garlic, levels remained below the limit of detection in milk and plasma and thus no withdrawal time appears to be needed for milk.}, number={9}, journal={FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT}, author={Mason, Sharon E. and Mullen, Keena A. E. and Washburn, Steven P. and Anderson, Kevin L. and Baynes, Ronald E.}, year={2018}, pages={1716–1727} }
 @article{stafford_tell_lin_davis_vickroy_riviere_baynes_2018, title={Consequences of fipronil exposure in egg-laying hens}, volume={253}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.253.1.57}, DOI={10.2460/javma.253.1.57}, number={1}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Stafford, Emma G. and Tell, Lisa A. and Lin, Zhoumeng and Davis, Jennifer L. and Vickroy, Thomas W. and Riviere, Jim E. and Baynes, Ronald E.}, year={2018}, month={Jul}, pages={57–60} }
 @article{mullen_lyman_washburn_baynes_anderson_2018, title={Effect of 3 phytoceutical products on elimination of bacteria in experimentally induced Streptococcus uberis clinical mastitis}, volume={101}, ISSN={["1525-3198"]}, DOI={10.3168/jds.2017-14279}, abstractNote={Our objective was to assess the ability of 3 herbal products to eliminate experimentally induced Streptococcus uberis mastitis. These herbal products, also known as phytoceuticals, are used in organically managed dairy cattle to maintain or promote udder health. The products tested were an intramammary product, a topical product, and a product applied to the vulvar area. These products are not approved by the US Food and Drug Administration for treatment of mastitis but they are sold to enhance milk quality or for maintenance or improvement of udder health. Each of the products contains at least one component shown to have antibacterial activity. In this study, we successfully challenge-inoculated 25 lactating dairy cows maintained under organic conditions with an isolate of S. uberis. All challenged cows were positive for S. uberis by milk culture after challenge. When cows met predefined criteria indicating the presence of clinical mastitis, treatment with 1 of the 3 products was initiated based upon a predetermined random allocation. Culture of aseptically collected quarter milk samples was performed before, during, and following challenge with S. uberis. Eight, 8, and 9 cows received the intravulvar, intramammary, and topical treatments, respectively. Milk from all cows that were treated with phytoceuticals were culture-positive for S. uberis at every time point following treatment through 168 h following the last phytoceutical treatment. Based upon the presence of clinical signs and for humane reasons, 2 intravulvar-treated cows, 1 topical-treated, and 4 intramammary-treated cows received intramammary antibiotic therapy. We concluded that the phytoceuticals tested, as dosed and used in this trial, did not produce bacterial cures in S. uberis-induced mastitis.}, number={11}, journal={JOURNAL OF DAIRY SCIENCE}, author={Mullen, K. A. E. and Lyman, R. L. and Washburn, S. P. and Baynes, R. E. and Anderson, K. L.}, year={2018}, month={Nov}, pages={10409–10413} }
 @article{mzyk_bublitz_hobgood_martinez_davis_smith_baynes_2018, title={Effect of age on plasma protein binding of several veterinary drugs in dairy Check for calves 2}, volume={121}, ISSN={["1532-2661"]}, DOI={10.1016/j.rvsc.2018.09.004}, abstractNote={The intent of this study was to determine what influence, if any, increasing age has on the binding of drugs to plasma proteins in cattle. Plasma from three different cohorts of calves were used. The first group (n = 20) had plasma samples taken at 1, 7 and 21 days of age. These were compared to results from a second group of calves at 8 weeks and third group sampled at 6 months of age. The plasma protein binding of danofloxacin, florfenicol, flunixin meglumine and tulathromycin was determined in vitro via microcentrifugation using three different drug concentrations spiked into the individual plasma samples derived from each calf. Albumin concentrations were lowest at 1 day of age as compared to plasma samples taken from 2 month old and 6 month old calves. There were significant decreases in alpha1-acid glycoprotein in calves until 21 days of age. However, statistically significant age-effects on plasma protein binding were not observed for any of the drugs evaluated in this study. Findings from these calves suggest that age is not an important factor in the binding of these drugs to plasma proteins.}, journal={RESEARCH IN VETERINARY SCIENCE}, author={Mzyk, Danielle A. and Bublitz, Claire M. and Hobgood, Ginger D. and Martinez, Marilyn N. and Davis, Jennifer L. and Smith, Geof W. and Baynes, Ronald E.}, year={2018}, month={Dec}, pages={59–64} }
 @article{martin_clapham_davis_baynes_lin_vickroy_riviere_tell_2018, title={Extralabel drug use in small ruminants}, volume={253}, ISSN={["1943-569X"]}, DOI={10.2460/javma.253.8.1001}, abstractNote={SEARCH AVMA Journals Both journals JAVMA AJVR Advanced Search Saved Searches JAVMA News Classified Ads Register Activate Individual Institution AVMA Home Journals Home Contact Us Help}, number={8}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Martin, Krysta L. and Clapham, Maaike O. and Davis, Jennifer L. and Baynes, Ronald E. and Lin, Zhoumeng and Vickroy, Thomas W. and Riviere, Jim E. and Tell, Lisa A.}, year={2018}, month={Oct}, pages={1001–1009} }
 @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{ehling_baynes_baeumer_2018, title={Impact of synthetic canine cerumen on in vitro penetration of auricular skin of dogs by florfenicol, terbinafine, and betamethasone acetate}, volume={79}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.79.3.333}, abstractNote={Abstract}, number={3}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Ehling, Sarah and Baynes, Ronald E. and Baeumer, Wolfgang}, year={2018}, month={Mar}, pages={333–341} }
 @article{mzyk_bublitz_sylvester_mullen_hobgood_baynes_foster_2018, title={Short communication: Use of an ultrafiltration device in gland cistern for continuous sampling of healthy and mastitic quarters of lactating cattle for pharmacokinetic modeling.}, volume={101}, url={https://doi.org/10.3168/jds.2018-14849}, DOI={10.3168/jds.2018-14849}, abstractNote={Pharmacokinetic studies of the drugs in the milk are often limited due to infrequent sampling associated with milking. Alternatively, frequent sample collection with repeated milking may increase drug elimination. The objective of this study was to determine the feasibility of continuously sampling the udder using ultrafiltration. An ultrafiltration probe was placed into the gland cisterns through mammary parenchyma of normal and mastitic quarters of 6 mature mid-lactation Jersey cows with naturally occurring subclinical mastitis. An ultrafiltration probe was secured to the caudal or lateral aspect of the udder depending on the quarter being sampled. The timed interval samples were collected at 0, 2, 4, 6, 8, 12, 18, 24, 28, 32, 36, 48, 60, 72, 84, and 96 h after drug administration. Plasma samples were collected at the same time points. Each cow received 2.2 mg/kg of flunixin intravenously before milking at time 0. All cows were routinely milked by machine every 12 h. Flunixin concentrations in plasma, whole milk, and milk ultrafiltrates were analyzed by use of ultra-high-performance liquid chromatography with mass spectrometric detection. We found no significant effects on the appearance of the milk or the ability to milk the cows after implantation of the ultrafiltration probes. The concentration of flunixin collected from the ultrafiltration probes in the mastitic quarters tended to be greater than that of the healthy quarters. We concluded that collection of ultrafiltration samples from the mammary gland of cows provides a viable means to continuously assess drug concentrations in the milk while continuing to milk the cow normally. This study demonstrates the utility of continuous sampling of milk via ultrafiltration for future pharmacokinetic studies in cattle.}, number={11}, journal={Journal of dairy science}, author={Mzyk, D. A. and Bublitz, C. M. and Sylvester, H. and Mullen, K. A. E. and Hobgood, G. D. and Baynes, R. E. and Foster, Derek}, year={2018}, month={Sep}, pages={10414–10420} }
 @article{hughes-oliver_xu_baynes_2018, title={Skin Permeation of Solutes from Metalworking Fluids to Build Prediction Models and Test A Partition Theory}, volume={23}, ISSN={["1420-3049"]}, DOI={10.3390/molecules23123076}, abstractNote={Permeation of chemical solutes through skin can create major health issues. Using the membrane-coated fiber (MCF) as a solid phase membrane extraction (SPME) approach to simulate skin permeation, we obtained partition coefficients for 37 solutes under 90 treatment combinations that could broadly represent formulations that could be associated with occupational skin exposure. These formulations were designed to mimic fluids in the metalworking process, and they are defined in this manuscript using: one of mineral oil, polyethylene glycol-200, soluble oil, synthetic oil, or semi-synthetic oil; at a concentration of 0.05 or 0.5 or 5 percent; with solute concentration of 0.01, 0.05, 0.1, 0.5, 1, or 5 ppm. A single linear free-energy relationship (LFER) model was shown to be inadequate, but extensions that account for experimental conditions provide important improvements in estimating solute partitioning from selected formulations into the MCF. The benefit of the Expanded Nested-Solute-Concentration LFER model over the Expanded Crossed-Factors LFER model is only revealed through a careful leave-one-solute-out cross-validation that properly addresses the existence of replicates to avoid an overly optimistic view of predictive power. Finally, the partition theory that accompanies the MCF approach is thoroughly tested and found to not be supported under complex experimental settings that mimic occupational exposure in the metalworking industry.}, number={12}, journal={MOLECULES}, author={Hughes-Oliver, Jacqueline M. and Xu, Guangning and Baynes, Ronald E.}, year={2018}, month={Dec} }
 @article{adrian_papich_baynes_stafford_lascelles_2018, title={The pharmacokinetics of gabapentin in cats}, volume={32}, ISSN={["1939-1676"]}, url={https://dx.doi.org/10.1111/jvim.15313}, DOI={10.1111/jvim.15313}, abstractNote={BackgroundGabapentin is the most commonly prescribed medication for the treatment of chronic musculoskeletal pain in cats. Despite this common and chronic usage, clinically relevant pharmacokinetic data is lacking.}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, publisher={Wiley}, author={Adrian, Derek and Papich, Mark G. and Baynes, Ronald and Stafford, Emma and Lascelles, B. Duncan X.}, year={2018}, pages={1996–2002} }
 @article{sidhu_gehring_mzyk_marmulak_tell_baynes_vickroy_riviere_2017, title={Avoiding violative flunixin meglumine residues in cattle and swine}, volume={250}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.250.2.182}, DOI={10.2460/javma.250.2.182}, number={2}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Sidhu, Pritam K. and Gehring, Ronette and Mzyk, Danielle A. and Marmulak, Tara and Tell, Lisa A. and Baynes, Ronald E. and Vickroy, Thomas W. and Riviere, Jim E.}, year={2017}, month={Jan}, pages={182–189} }
 @article{mzyk_gehring_tell_vickroy_riviere_ragan_baynes_smith_2017, title={Considerations for extralabel drug use in calves}, volume={250}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.250.11.1275}, DOI={10.2460/javma.250.11.1275}, abstractNote={1275 Calfhood diseases have major negative economic consequences on beef and dairy operations owing to costs associated with treatment, long-term effects on growth and performance, and death of affected calves.1–3 The number of drugs approved for the treatment of diseased calves by the FDA is limited; however, veterinarians have the authority to administer drugs in an extralabel manner to that class of animals under provisions established by AMDUCA.4 Nevertheless, drug labels that state, “a withdrawal period has not been established for this product in preruminating calves” can cause confusion about whether those drugs can or cannot be administered to young calves. Pharmacokinetic and residue depletion studies for very few drugs have been performed in young calves, and extrapolation of drug WDTs established for adult cattle to calves might not be appropriate or adequate to avoid violative tissue residues, which makes ELDU in calves problematic and potentially difficult to justify. The purpose of this digest is to provide veterinarians with a summary of the considerations for ELDU in both beef and dairy calves as well as calves intended for veal production.}, number={11}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Mzyk, Danielle A. and Gehring, Ronette and Tell, Lisa A. and Vickroy, Thomas W. and Riviere, Jim E. and Ragan, Gail and Baynes, Ronald E. and Smith, Geof W.}, year={2017}, month={Jun}, pages={1275–1282} }
 @article{draughn_allen_routh_stone_kirker_boegli_schuchman_linder_baynes_james_et al._2017, title={Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections}, volume={11}, journal={Drug Design Development and Therapy}, author={Draughn, G. L. and Allen, C. L. and Routh, P. A. and Stone, M. R. and Kirker, K. R. and Boegli, A. and Schuchman, R. M. and Linder, K. E. and Baynes, R. E. and James, G. and et al.}, year={2017}, pages={153–162} }
 @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{riviere_tell_baynes_vickroy_gehring_2017, title={Guide to FARAD resources: historical and future perspectives}, volume={250}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.250.10.1131}, DOI={10.2460/javma.250.10.1131}, number={10}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Riviere, Jim E. and Tell, Lisa A. and Baynes, Ronald E. and Vickroy, Thomas W. and Gehring, Ronette}, year={2017}, month={May}, pages={1131–1139} }
 @article{mason_mullen_anderson_washburn_yeatts_baynes_2017, title={Pharmacokinetic analysis of thymol, carvacrol and diallyl disulfide after intramammary and topical applications in healthy organic dairy cattle}, volume={34}, ISSN={1944-0049 1944-0057}, url={http://dx.doi.org/10.1080/19440049.2017.1285056}, DOI={10.1080/19440049.2017.1285056}, abstractNote={ABSTRACT Mastitis is among the most costly concerns for dairy producers whether cattle are managed conventionally or organically. Unfortunately, there are no USFDA-approved mastitis treatments that allow dairy cows in the United States to maintain organic dairy status. We investigated the plasma pharmacokinetics of three organic mastitis products currently used by organic producers and organic dairy veterinarians. Those products include intramammary, topical and intravaginal preparations, each dosed at two levels. Additionally, tissue data were collected for kidney, liver and fat in order to estimate a withholding time for each of the products. The lower limit of quantification (LOQ) and lower limit of detection (LOD) were 0.001 and 0.0005 µg ml–1, respectively, in plasma and all tissues except fat for both thymol and carvacrol. Fat had an LOQ of 0.01 µg ml–1 and an LOD of 0.005 µg ml–1 for thymol and carvacrol. Diallyl disulfide had an LOQ of 0.005 µg ml–1 and LOD of 0.001 µg ml–1 in all tissues. For diallyl disulfide (garlic), no levels above 0.001 µg ml–1 were measurable in plasma or tissues. For topical and intramammary products, levels were measurable in the plasma, liver, kidney and fat up to 72 h after the last dose. The plasma half-lives were short for thymol (approximately 1.6 h) and carvacrol (approximately 1.5 h), whereas the estimated half-lives for these substances in tissues ranged from 13.9 to 31.5 h for thymol and from 16.9 to 25 h for carvacrol. The predicted amount of time that the molecules would be found in the body based on the slowest depletion time of liver tissue was 13 days for thymol and 10 days for carvacrol. The apparent half-life of topically applied carvacrol was approximately 4.5 h in plasma, with an estimated withhold time of 10 days. These times were calculated using the USFDA’s tolerance limit method for meat withdrawal times.}, number={5}, journal={Food Additives & Contaminants: Part A}, publisher={Informa UK Limited}, author={Mason, Sharon E. and Mullen, Keena A. E. and Anderson, Kevin L. and Washburn, Steven P. and Yeatts, James L. and Baynes, Ronald E.}, year={2017}, month={Feb}, pages={1–10} }
 @article{mzyk_baynes_messenger_martinez_smith_2017, title={Pharmacokinetics and distribution in interstitial and pulmonary epithelial lining fluid of danofloxacin in ruminant and preruminant calves}, volume={40}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12346}, abstractNote={The objective of this study was to compare active drug concentrations in the plasma vs. different effector compartments including interstitial fluid (ISF) and pulmonary epithelial lining fluid (PELF) of healthy preruminating (3‐week‐old) and ruminating (6‐month‐old) calves. Eight calves in each age group were given a single subcutaneous (s.c.) dose (8 mg/kg) of danofloxacin. Plasma, ISF, and bronchoalveolar lavage (BAL) fluid were collected over 96 h and analyzed by high‐pressure liquid chromatography. PELF concentrations were calculated by a urea dilution assay of the BAL fluids. Plasma protein binding was measured using a microcentrifugation system. For most preruminant and ruminant calves, the concentration–time profile of the central compartment was best described by a two‐compartment open body model. For some calves, a third compartment was also observed. The time to maximum concentration in the plasma was longer in preruminating calves (3.1 h) vs. ruminating calves (1.4 h). Clearance (CL/F) was 385.15 and 535.11 mL/h/kg in preruminant and ruminant calves, respectively. Ruminant calves maintained higher ISF/plasma concentration ratios throughout the study period compared to that observed in preruminant calves. Potential reasons for age‐related differences in plasma concentration–time profiles and partitioning of the drug to lungs and ISF as a function of age are explored.}, number={2}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Mzyk, D. A. and Baynes, R. E. and Messenger, K. M. and Martinez, M. and Smith, G. W.}, year={2017}, month={Apr}, pages={179–191} }
 @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{mullen_beasley_rizzo_washburn_baynes_mason_anderson_2017, title={Potential of phytoceuticals to affect antibiotic residue detection tests in cow milk in a randomised trial}, volume={4}, ISSN={2052-6113}, url={http://dx.doi.org/10.1136/vetreco-2016-000214}, DOI={10.1136/vetreco-2016-000214}, abstractNote={Mastitis is a costly disease for dairy farmers. Some dairy farmers use herbal products, or phytoceuticals, to treat mastitis. Phytoceuticals have not been approved for this use by the United States Food and Drug Administration, and have not been tested to determine how they impact antibiotic residue detection testing. The current study tested the potential for phytoceuticals to cause positive results on two milk antibiotic residue screening tests, the Delvotest P and Charm SL Beta‐lactam test, or to interfere with the detection of antibiotics by these tests.}, number={1}, journal={Veterinary Record Open}, publisher={BMJ}, author={Mullen, Keena AE and Beasley, Erin and Rizzo, Julio Q and Washburn, Steven P and Baynes, Ronald E and Mason, Sharon E and Anderson, Kevin L}, year={2017}, month={Aug}, pages={e000214} }
 @article{armorini_yeatts_mullen_mason_mehmeti_anderson_washburn_baynes_2016, title={Development of a HS-SPME-GC-MS/MS Method for the Quantitation of Thymol and Carvacrol in Bovine Matrices and To Determine Residue Depletion in Milk and. Tissues}, volume={64}, ISSN={["1520-5118"]}, DOI={10.1021/acs.jafc.6b02899}, abstractNote={Thymol and carvacrol may be present in several phytoceutical products but there are no well-defined methods to measure these compounds in meat and milk from treated animals. U.S. regulatory authorities deem their presence as an adulteration of food. A rapid and sensitive HS-SPME-GC-MS/MS method was developed for the detection of thymol and carvacrol in bovine milk, plasma, liver, kidney, and fat. Inter- and intraday precision values were all less than 15.7 and 20.2% for thymol and carvacrol, respectively. The accuracy was in ranges of 69.9-111.8% for thymol and 74.0-119.2% for carvacrol. With the exception of fat tissue, stability studies showed that both compounds are stable over a 2 month period. A pilot pharmacokinetic study was conducted to evaluate the developed analytical method and to provide initial estimates of thymol and carvacrol depletion in plasma, milk, and several tissues. Treatment of lactating dairy cattle with phytoceutical products containing these substances resulted in low but measurable residue levels at 96 h for liver and 36 h for milk with very short apparent plasma and milk half-lives (<3.0 h).}, number={41}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, author={Armorini, Sara and Yeatts, James E. and Mullen, Keena A. E. and Mason, Sharon E. and Mehmeti, Elmira and Anderson, Kevin L. and Washburn, Steve P. and Baynes, Ronald E.}, year={2016}, month={Oct}, pages={7856–7865} }
 @article{baynes_dedonder_kissell_mzyk_marmulak_smith_tell_gehring_davis_riviere_2016, title={Health concerns and management of select veterinary drug residues}, volume={88}, ISSN={0278-6915}, url={http://dx.doi.org/10.1016/J.FCT.2015.12.020}, DOI={10.1016/J.FCT.2015.12.020}, abstractNote={The aim of this manuscript is to review the potential adverse health effects in humans if exposed to residues of selected veterinary drugs used in food-producing animals. Our other objectives are to briefly inform the reader of why many of these drugs are or were approved for use in livestock production and how drug residues can be mitigated for these drugs. The selected drugs include several antimicrobials, beta agonists, and phenylbutazone. The antimicrobials continue to be of regulatory concern not only because of their acute adverse effects but also because their use as growth promoters have been linked to antimicrobial resistance. Furthermore, nitroimidazoles and arsenicals are no longer approved for use in food animals in most jurisdictions. In recent years, the risk assessment and risk management of beta agonists, have been the focus of national and international agencies and this manuscript attempts to review the pharmacology of these drugs and regulatory challenges. Several of the drugs selected for this review can cause noncancer effects (e.g., penicillins) and others are potential carcinogens (e.g., nitroimidazoles). This review also focuses on how regulatory and independent organizations manage the risk of these veterinary drugs based on data from human health risk assessments.}, journal={Food and Chemical Toxicology}, publisher={Elsevier BV}, author={Baynes, Ronald E. and Dedonder, Keith and Kissell, Lindsey and Mzyk, Danielle and Marmulak, Tara and Smith, Geof and Tell, Lisa and Gehring, Ronette and Davis, Jennifer and Riviere, Jim E.}, year={2016}, month={Feb}, pages={112–122} }
 @article{kissell_brinson_gehring_tell_wetzlich_baynes_riviere_smith_2016, title={Pharmacokinetics and tissue elimination of flunixin in veal calves}, volume={77}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.77.6.634}, DOI={10.2460/ajvr.77.6.634}, abstractNote={Abstract}, number={6}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Kissell, Lindsey W. and Brinson, Patrick D. and Gehring, Ronette and Tell, Lisa A. and Wetzlich, Scott E. and Baynes, Ronald E. and Riviere, Jim E. and Smith, Geof W.}, year={2016}, month={Jun}, pages={634–640} }
 @article{shelver_smith_tell_baynes_schroeder_riviere_2016, title={Screening and Confirmatory Analyses of Flunixin in Tissues and Bodily Fluids after Intravenous or Intramuscular Administration to Cull Dairy Cows with or without Lipopolysaccharide Challenge}, volume={64}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/acs.jafc.5b04793}, DOI={10.1021/acs.jafc.5b04793}, abstractNote={Twenty cull dairy cows (645 ± 83 kg) were treated with 2.2 mg/kg bw flunixin by intravenous (IV) or intramuscular (IM) administration with, or without, exposure to lipopolysaccharide in a two factor balanced design. The usefulness of screening assays to identify violative flunixin levels in a variety of easily accessible ante-mortem fluids in cattle was explored. Two animals with violative flunixin liver residue and/or violative 5-hydroxy flunixin milk residues were correctly identified by a flunixin liver ELISA screen. Oral fluid did not produce anticipated flunixin concentration profiles using ELISA determination. One cow that had liver and milk violative residues, and one cow that had a milk violation at the prescribed withdrawal period were correctly identified by flunixin milk lateral flow analyses. The ratio of urinary flunixin and 5-hydroxy flunixin may be useful for predicting disruption of metabolism caused by disease or other factors potentially leading to violative liver flunixin residues.}, number={1}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Shelver, Weilin L. and Smith, David J. and Tell, Lisa A. and Baynes, Ronald E. and Schroeder, J. W. and Riviere, Jim E.}, year={2016}, pages={336–345} }
 @article{kissell_leavens_baynes_riviere_smith_2015, title={Comparison of pharmacokinetics and milk elimination of flunixin in healthy cows and cows with mastitis}, volume={246}, ISSN={["1943-569X"]}, DOI={10.2460/javma.246.1.118}, abstractNote={Abstract}, number={1}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Kissell, Lindsey W. and Leavens, Teresa L. and Baynes, Ronald E. and Riviere, Jim E. and Smith, Geof W.}, year={2015}, month={Jan}, pages={118–125} }
 @article{howard_o’nan_maltecca_baynes_ashwell_2015, title={Differential Gene Expression across Breed and Sex in Commercial Pigs Administered Fenbendazole and Flunixin Meglumine}, volume={10}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0137830}, DOI={10.1371/journal.pone.0137830}, abstractNote={Characterizing the variability in transcript levels across breeds and sex in swine for genes that play a role in drug metabolism may shed light on breed and sex differences in drug metabolism. The objective of the study is to determine if there is heterogeneity between swine breeds and sex in transcript levels for genes previously shown to play a role in drug metabolism for animals administered flunixin meglumine or fenbendazole. Crossbred nursery female and castrated male pigs (n = 169) spread across 5 groups were utilized. Sires (n = 15) of the pigs were purebred Duroc, Landrace, Yorkshire or Hampshire boars mated to a common sow population. Animals were randomly placed into the following treatments: no drug (control), flunixin meglumine, or fenbendazole. One hour after the second dosing, animals were sacrificed and liver samples collected. Quantitative Real-Time PCR was used to measure liver gene expression of the following genes: SULT1A1, ABCB1, CYP1A2, CYP2E1, CYP3A22 and CYP3A29. The control animals were used to investigate baseline transcript level differences across breed and sex. Post drug administration transcript differences across breed and sex were investigated by comparing animals administered the drug to the controls. Contrasts to determine fold change were constructed from a model that included fixed and random effects within each drug. Significant (P-value <0.007) basal transcript differences were found across breeds for SULT1A1, CYP3A29 and CYP3A22. Across drugs, significant (P-value <0.0038) transcript differences existed between animals given a drug and controls across breeds and sex for ABCB1, PS and CYP1A2. Significant (P <0.0038) transcript differences across breeds were found for CYP2E1 and SULT1A1 for flunixin meglumine and fenbendazole, respectively. The current analysis found transcript level differences across swine breeds and sex for multiple genes, which provides greater insight into the relationship between flunixin meglumine and fenbendazole and known drug metabolizing genes.}, number={9}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={Howard, Jeremy T. and O’Nan, Audrey T. and Maltecca, Christian and Baynes, Ronald E. and Ashwell, Melissa S.}, editor={Kobeissy, Firas HEditor}, year={2015}, month={Sep}, pages={e0137830} }
 @article{marmulak_tell_gehring_baynes_vickroy_riviere_2015, title={Egg residue considerations during the treatment of backyard poultry}, volume={247}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.247.12.1388}, DOI={10.2460/javma.247.12.1388}, abstractNote={The purpose of this digest was to provide US veterinarians guidance on the responsible treatment of backyard poultry flocks. The treatment of backyard poultry can be a daunting task for veterinarians because only limited resources are available; however, it is likely to become an increasingly common task owing to the increasing popularity of backyard poultry throughout the United States, especially in urban and suburban areas. Although backyard poultry flock owners may consider their birds pets, the FDA considers them food-producing animals, and veterinarians should follow all regulations that pertain to food-producing animals when administering or prescribing drugs to those birds. The lack of FDA-approved drugs for use in laying hens frequently necessitates the use of drugs in an extralabel manner in backyard poultry. Unfortunately, information regarding the depletion of drug residues in eggs from hens treated with various drugs in an extralabel manner is sparse or lacking, and veterinarians need to be cognizant of this issue, especially when the eggs from treated hens are intended for human consumption.}, number={12}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Marmulak, Tara and Tell, Lisa A. and Gehring, Ronette and Baynes, Ronald E. and Vickroy, Thomas W. and Riviere, Jim E.}, year={2015}, month={Dec}, pages={1388–1395} }
 @article{smith_shelver_baynes_tell_gehring_li_dutko_schroeder_herges_riviere_2015, title={Excretory, Secretory, and Tissue Residues after Label and Extra-label Administration of Flunixin Meglumine to Saline- or Lipopolysaccharide-Exposed Dairy Cows}, volume={63}, ISSN={0021-8561 1520-5118}, url={http://dx.doi.org/10.1021/acs.jafc.5b01509}, DOI={10.1021/acs.jafc.5b01509}, abstractNote={Twenty lactating dairy cattle were intravenously infused with either lipopolysaccharide (LPS) (n = 10) or sterile saline (n = 10). Five cattle in each group received three doses of flunixin meglumine administered by either intravenous infusion or intramuscular injection at 24 h intervals. Milk, urine, and tissues were collected. Thirty-six hours after the last flunixin administration, milk from six cows contained 5-hydroxyflunixin (5OHF) levels greater than the milk tolerance of 2 ng/mL; by 48 h, milk from two cows, a saline and a LPS-treated animal, had violative milk concentrations of 5OHF. A single animal treated with LPS and intramuscular flunixin contained violative flunixin residues in liver. The ratio of urinary flunixin/5OHF was correlated (P < 0.01; R(2) = 0.946) with liver flunixin residues in LPS-treated animals, but not (P = 0.96; R(2) = 0.003) in cows treated with saline in lieu of LPS. Violative residues of flunixin in dairy cattle may be related to LPS inhibition of flunixin metabolism.}, number={19}, journal={Journal of Agricultural and Food Chemistry}, publisher={American Chemical Society (ACS)}, author={Smith, David J. and Shelver, Weilin L. and Baynes, Ronald E. and Tell, Lisa and Gehring, Ronette and Li, Mengjie and Dutko, Terry and Schroeder, J. W. and Herges, Grant and Riviere, Jim E.}, year={2015}, month={May}, pages={4893–4901} }
 @article{lindquist_baynes_smith_2015, title={Short communication: Pharmacokinetics of intramammary hetacillin in dairy cattle milked 3 times per day}, volume={98}, ISSN={0022-0302}, url={http://dx.doi.org/10.3168/jds.2014-8715}, DOI={10.3168/jds.2014-8715}, abstractNote={Mastitis remains a critical disease in the dairy industry and the use of intramammary antibiotics plays a critical role in mastitis treatment. Hetacillin is currently approved as an intramammary antibiotic that is used to treat mastitis in dairy cows. It is approved for once a day administration and can be used for a total of 3 d. An increasing number of dairy farms are milking 3 times per day (instead of the traditional 2 times per day) and very little pharmacokinetic data exists on the use of intramammary drugs in a 3×system. The primary purpose of this study was to determine if once a day intramammary infusion of hetacillin is sufficient to maintain therapeutic drug concentrations in cattle milked 3 times per day. Eight Holstein cattle milked 3 times per day were used in this study. After collecting a baseline milk sample, each cow received intramammary infusions of hetacillin in the left front and right rear quarters once a day for 3 d. Milk samples from each of the treated quarters were collected at each milking and frozen until analysis. Milk samples were analyzed for ampicillin concentrations using an ultra-performance liquid chromatography method. All treated quarters had antibiotic concentrations well above the minimum inhibitory concentration (MIC) for gram-positive mastitis pathogens at 8 and 16 h postinfusion. Milk concentrations had fallen well below the MIC by the 24-h period (before the next infusion). All 8 cows in this study consistently had individual quarter milk ampicillin concentrations below the FDA tolerance of 0.01 μg/mL (10 ppb) within 48 h of the last infusion. Based on this study, milk ampicillin concentrations exceed the minimum inhibitory concentration required to inhibit the growth of 90% of organisms (MIC90) for at least 65% of the dosing interval, which is sufficient for once-daily dosing with most cases of gram-positive mastitis. Therefore, intramammary hetacillin should be an effective treatment for the vast majority of gram-positive mastitis pathogens when used according to label (once per day) in cows milked 3 times per day.}, number={3}, journal={Journal of Dairy Science}, publisher={American Dairy Science Association}, author={Lindquist, Danielle A. and Baynes, Ronald E. and Smith, Geof W.}, year={2015}, month={Mar}, pages={1856–1861} }
 @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{mason_wu_yeatts_baynes_2015, title={Tissue concentrations of sulfamethazine and tetracycline hydrochloride of swine (Sus scrofa domestica) as it relates to withdrawal methods for international export}, volume={71}, ISSN={["1096-0295"]}, DOI={10.1016/j.yrtph.2015.02.013}, abstractNote={The use of water medications is a common practice in the US swine industry to treat and prevent infections in swine herds with minimal labor and without risk of needle breakage. There are concerns that FDA-approved withdrawal times (WDT) may be inadequate for several water medications when exporting pork products to countries where MRLs (maximum residue limits) are lower than US tolerance levels. In this study, withdrawal intervals (WDI) were estimated for pigs when dosed with tetracycline and sulfamethazine in water. The WDI were calculated using the FDA tolerance method (TLM) and a population-based pharmacokinetic method (PopPK). The estimated WDIs (14–16 days using TLM) were similar to the approved WDT of 15 days for sulfamethazine. However, the PopPK method extended WDIs for both sulfamethazine (19–20 days) and tetracycline (12 days) compared to the currently approved WDTs in the U.S. This study also identified potential differences in WDI between weanling and finisher pigs. In conclusion, the TLM may not always provide adequate WDT for foreign export markets especially when MRLs differ from tolerance levels approved for US markets. However, PopPK methods can provide conservative WDIs in situations with considerable variability in medication exposure such as with administration in water.}, number={3}, journal={REGULATORY TOXICOLOGY AND PHARMACOLOGY}, author={Mason, Sharon E. and Wu, Huali and Yeatts, Jim E. and Baynes, Ronald E.}, year={2015}, month={Apr}, pages={590–596} }
 @article{leavens_tell_kissell_smith_smith_wagner_shelver_wu_baynes_riviere_et al._2014, title={Development of a physiologically based pharmacokinetic model for flunixin in cattle (Bos taurus)}, volume={31}, ISSN={["1944-0057"]}, DOI={10.1080/19440049.2014.938363}, abstractNote={Frequent violation of flunixin residues in tissues from cattle has been attributed to non-compliance with the USFDA-approved route of administration and withdrawal time. However, the effect of administration route and physiological differences among animals on tissue depletion has not been determined. The objective of this work was to develop a physiologically based pharmacokinetic (PBPK) model to predict plasma, liver and milk concentrations of flunixin in cattle following intravenous (i.v.), intramuscular (i.m.) or subcutaneous (s.c.) administration for use as a tool to determine factors that may affect the withdrawal time. The PBPK model included blood flow-limited distribution in all tissues and elimination in the liver, kidney and milk. Regeneration of parent flunixin due to enterohepatic recirculation and hydrolysis of conjugated metabolites was incorporated in the liver compartment. Values for physiological parameters were obtained from the literature, and partition coefficients for all tissues but liver and kidney were derived empirically. Liver and kidney partition coefficients and elimination parameters were estimated for 14 pharmacokinetic studies (including five crossover studies) from the literature or government sources in which flunixin was administered i.v., i.m. or s.c. Model simulations compared well with data for the matrices following all routes of administration. Influential model parameters included those that may be age or disease-dependent, such as clearance and rate of milk production. Based on the model, route of administration would not affect the estimated days to reach the tolerance concentration (0.125 mg kg−1) in the liver of treated cattle. The majority of USDA-reported violative residues in liver were below the upper uncertainty predictions based on estimated parameters, which suggests the need to consider variability due to disease and age in establishing withdrawal intervals for drugs used in food animals. The model predicted that extravascular routes of administration prolonged flunixin concentrations in milk, which could result in violative milk residues in treated cattle.}, number={9}, journal={FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT}, author={Leavens, Teresa and Tell, L. A. and Kissell, L. W. and Smith, G. W. and Smith, D. J. and Wagner, S. A. and Shelver, W. L. and Wu, H. L. and Baynes, R. E. and Riviere, J. E. and et al.}, year={2014}, month={Sep}, pages={1506–1521} }
 @article{li_gehring_tell_baynes_huang_riviere_2014, title={Interspecies Mixed-Effect Pharmacokinetic Modeling of Penicillin G in Cattle and Swine}, volume={58}, ISSN={0066-4804 1098-6596}, url={http://dx.doi.org/10.1128/aac.02806-14}, DOI={10.1128/aac.02806-14}, abstractNote={ABSTRACT}, number={8}, journal={Antimicrobial Agents and Chemotherapy}, publisher={American Society for Microbiology}, author={Li, Mengjie and Gehring, Ronette and Tell, Lisa and Baynes, Ronald and Huang, Qingbiao and Riviere, Jim E.}, year={2014}, month={May}, pages={4495–4503} }
 @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{shelver_tell_wagner_wetzlich_baynes_riviere_smith_2013, title={Comparison of ELISA and LC-MS/MS for the Measurement of Flunixin Plasma Concentrations in Beef Cattle after Intravenous and Subcutaneous Administration}, volume={61}, ISSN={["1520-5118"]}, DOI={10.1021/jf304773p}, abstractNote={Eight cattle (288 ± 22 kg) were treated with 2.2 mg/kg of body weight of flunixin free acid in a crossover design by subcutaneous (SC) and intravenous (IV) administration. After a minimum 1:10 dilution with 50 mM phosphate buffer, a commercial immunoassay was adapted to determine plasma concentrations of flunixin. The limit of detection was 0.42 ng/mL and the working range was 0.76-66.4 ng/mL when adjusted with the dilution factor. Plasma samples were extracted using mixed-mode cation exchange solid phase extraction prior to the LC-MS/MS analyses. The linear calibration curve for LC-MS/MS was 0.5-2000 ng/mL with a limit of detection of 0.1 ng/mL for flunixin and 0.3 ng/mL for 5-hydroxy flunixin. Flunixin concentrations determined using the ELISAs were compared to concentrations derived from the same samples using LC-MS/MS analyses. Pharmacokinetic parameters of time versus concentration data from each analysis were estimated and compared. Differences (P < 0.05) in estimates of area under the curve, volume of distribution, and clearance were apparent between ELISA and LC-MS/MS analyses after IV dosing; after SC dosing, however, there were no differences among the estimated parameters between the two methods. Quantitative immunoassay was a satisfactory method of flunixin analysis and that it would be difficult to differentiate routes of administration in healthy beef cattle based on the plasma elimination profile of flunixin after IV or SC administration.}, number={11}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, author={Shelver, Weilin L. and Tell, Lisa A. and Wagner, Sarah and Wetzlich, Scott E. and Baynes, Ronald E. and Riviere, Jim E. and Smith, David J.}, year={2013}, month={Mar}, pages={2679–2686} }
 @article{dedonder_gehring_baynes_tell_vickroy_apley_riviere_2013, title={Effects of new sampling protocols on procaine penicillin G withdrawal intervals for cattle}, volume={243}, DOI={10.2460/javma.243.10.1408}, number={10}, journal={Journal of the American Veterinary Medical Association}, author={DeDonder, K. D. and Gehring, R. and Baynes, R. E. and Tell, L. A. and Vickroy, T. W. and Apley, M. D. and Riviere, J. E.}, year={2013}, pages={1408–1412} }
 @article{kissell_baynes_riviere_smith_2013, title={Occurrence of flunixin residues in bovine milk samples from the USA}, volume={30}, ISSN={1944-0049 1944-0057}, url={http://dx.doi.org/10.1080/19440049.2013.803604}, DOI={10.1080/19440049.2013.803604}, abstractNote={5-Hydroxy-flunixin concentrations in milk samples were quantified by two commercially available screening assays – CHARM® and enzyme-linked immunoabsorbant assay (ELISA) – to determine whether any concentrations could be detected above the tolerance limit of 2 ng g−1 from different regions in the United States. Milk samples came from large tanker trucks hauling milk to processing plants, and had already been screened for antibiotics. Positive results for flunixin residues based on a screening assay were confirmed by ultra-HPLC with mass spectrometric detection. Of the 500 milk samples analysed in this study, one sample was found to have a 5-hydroxy-flunixin concentration greater than the tolerance limit. The results of this study indicate that flunixin residues in milk are possible. Regulatory agencies should be aware that such residues can occur, and should consider incorporating or expanding flunixin screening tests as part of routine drug monitoring in milk. Larger studies are needed to determine the true prevalence of flunixin residues in milk from other regions in the United States as well as different countries.}, number={9}, journal={Food Additives & Contaminants: Part A}, publisher={Informa UK Limited}, author={Kissell, L.W. and Baynes, R.E. and Riviere, J.E. and Smith, G.W.}, year={2013}, month={Sep}, pages={1513–1516} }
 @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} }
 @article{wu_baynes_tell_riviere_2013, title={Prediction of flunixin tissue residue concentrations in livers from diseased cattle}, volume={62}, ISSN={0278-6915}, url={http://dx.doi.org/10.1016/j.fct.2013.10.018}, DOI={10.1016/j.fct.2013.10.018}, abstractNote={Flunixin, a widely used non-steroidal anti-inflammatory drug, was a leading cause of violative residues in cattle. The objective of this analysis was to explore how the changes in pharmacokinetic (PK) parameters that may be associated with diseased animals affect the predicted liver residue of flunixin in cattle. Monte Carlo simulations for liver residues of flunixin were performed using the PK model structure and relevant PK parameter estimates from a previously published population PK model for flunixin in cattle. The magnitude of a change in the PK parameter value that resulted in a violative residue issue in more than one percent of a cattle population was compared. In this regard, elimination clearance and volume of distribution affected withdrawal times. Pathophysiological factors that can change these parameters may contribute to the occurrence of violative residues of flunixin.}, journal={Food and Chemical Toxicology}, publisher={Elsevier BV}, author={Wu, H. and Baynes, R.E. and Tell, L.A. and Riviere, J.E.}, year={2013}, month={Dec}, pages={876–879} }
 @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{wu_baynes_leavens_tell_riviere_2013, title={Use of population pharmacokinetic modeling and Monte Carlo simulation to capture individual animal variability in the prediction of flunixin withdrawal times in cattle}, volume={36}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/j.1365-2885.2012.01420.x}, DOI={10.1111/j.1365-2885.2012.01420.x}, abstractNote={The objective of this study was to develop a population pharmacokinetic (PK) model and predict tissue residues and the withdrawal interval (WDI) of flunixin in cattle. Data were pooled from published PK studies in which flunixin was administered through various dosage regimens to diverse populations of cattle. A set of liver data used to establish the regulatory label withdrawal time (WDT) also were used in this study. Compartmental models with first‐order absorption and elimination were fitted to plasma and liver concentrations by a population PK modeling approach. Monte Carlo simulations were performed with the population mean and variabilities of PK parameters to predict liver concentrations of flunixin. The PK of flunixin was described best by a 3‐compartment model with an extra liver compartment. The WDI estimated in this study with liver data only was the same as the label WDT. However, a longer WDI was estimated when both plasma and liver data were included in the population PK model. This study questions the use of small groups of healthy animals to determine WDTs for drugs intended for administration to large diverse populations. This may warrant a reevaluation of the current procedure for establishing WDT to prevent violative residues of flunixin.}, number={3}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Wu, H. and Baynes, R. E. and Leavens, T. and Tell, L. A. and Riviere, J. E.}, year={2013}, month={Jun}, pages={248–257} }
 @article{baynes_riviere_franz_monteiro riviere_lehman_peyrou_toutain_2012, title={Challenges obtaining a biowaiver for topical veterinary dosage forms}, volume={35}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/j.1365-2885.2012.01381.x}, DOI={10.1111/j.1365-2885.2012.01381.x}, abstractNote={Baynes, R., Riviere, J., Franz, T., Monteiro‐Riviere, N., Lehman, P., Peyrou, M., Toutain, P.‐L. Challenges obtaining a biowaiver for topical veterinary dosage forms. J. vet. Pharmacol. Therap.35 (Suppl. 1), 103–114.}, number={SUPPL. 1}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Baynes, R. and Riviere, J. and Franz, T. and Monteiro Riviere, N. and Lehman, P. and Peyrou, M. and Toutain, P. L.}, year={2012}, month={Mar}, pages={103–114} }
 @article{leavens_tell_clothier_griffith_baynes_riviere_2012, title={Development of a physiologically based pharmacokinetic model to predict tulathromycin distribution in goats}, volume={35}, ISSN={["1365-2885"]}, DOI={10.1111/j.1365-2885.2011.01304.x}, abstractNote={Leavens, T. L., Tell, L. A., Clothier, K. A., Griffith, R. W., Baynes, R. E., Riviere, J. E. Development of a physiologically based pharmacokinetic model to predict tulathromycin distribution in goats. J. vet. Pharmacol. Therap. 35, 121–131.}, number={2}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Leavens, T. L. and Tell, L. A. and Clothier, K. A. and Griffith, R. W. and Baynes, R. E. and Riviere, J. E.}, year={2012}, month={Apr}, pages={121–131} }
 @article{mason_almond_riviere_baynes_2012, title={Evaluation of factors important in modeling plasma concentrations of tetracycline hydrochloride administered in water in swine}, volume={73}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.73.10.1641}, abstractNote={Abstract}, number={10}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Mason, Sharon E. and Almond, Glen W. and Riviere, Jim E. and Baynes, Ronald E.}, year={2012}, month={Oct}, pages={1641–1649} }
 @article{romanet_smith_leavens_baynes_wetzlich_riviere_tell_2012, title={Pharmacokinetics and tissue elimination of tulathromycin following subcutaneous administration in meat goats}, volume={73}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.73.10.1634}, abstractNote={Abstract}, number={10}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Romanet, Jessica and Smith, Geof W. and Leavens, Teresa L. and Baynes, Ronald E. and Wetzlich, Scott E. and Riviere, Jim E. and Tell, Lisa A.}, year={2012}, month={Oct}, pages={1634–1640} }
 @article{baynes_2012, title={Quantitative Risk Assessment Methods for Cancer and Noncancer Effects}, volume={112}, ISBN={["978-0-12-415813-9"]}, ISSN={["1877-1173"]}, DOI={10.1016/b978-0-12-415813-9.00009-x}, abstractNote={Human health risk assessments have evolved from the more qualitative approaches to more quantitative approaches in the past decade. This has been facilitated by the improvement in computer hardware and software capability and novel computational approaches being slowly recognized by regulatory agencies. These events have helped reduce the reliance on experimental animals as well as better utilization of published animal toxicology data in deriving quantitative toxicity indices that may be useful for risk management purposes. This chapter briefly describes some of the approaches as described in the guidance documents from several of the regulatory agencies as it pertains to hazard identification and dose-response assessment of a chemical. These approaches are contrasted with more novel computational approaches that provide a better grasp of the uncertainty often associated with chemical risk assessments.}, journal={TOXICOLOGY AND HUMAN ENVIRONMENTS}, author={Baynes, Ronald E.}, year={2012}, pages={259–283} }
 @article{clothier_leavens_griffith_wetzlich_baynes_riviere_tell_2012, title={Tulathromycin assay validation and tissue residues after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus)}, volume={35}, ISSN={["1365-2885"]}, DOI={10.1111/j.1365-2885.2011.01300.x}, abstractNote={Clothier, K. A., Leavens, T., Griffith, R. W., Wetzlich, S. E., Baynes, R. E., Riviere, J. E., Tell, L. A. Tulathromycin assay validation and tissue residues after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus). J. vet. Pharmacol. Therap. 35, 113–120.}, number={2}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Clothier, K. A. and Leavens, T. and Griffith, R. W. and Wetzlich, S. E. and Baynes, R. E. and Riviere, J. E. and Tell, L. A.}, year={2012}, month={Apr}, pages={113–120} }
 @article{mcphee_anderson_yeatts_mason_barlow_baynes_2011, title={Hot topic: Milk and plasma disposition of thymol following intramammary administration of a phytoceutical mastitis treatment}, volume={94}, ISSN={["1525-3198"]}, DOI={10.3168/jds.2010-3988}, abstractNote={Despite the recent growth of the organic dairy industry, organic producers and veterinarians have limited information when choosing mastitis treatments for animals in organic dairy production. Organic producers commonly administer homeopathic or other plant-based products without having research evaluating the efficacy of these products and using estimated or no withholding times to treat mastitis and other health problems in their herds. In this pilot study, we attempted to identify several active ingredients of Phyto-Mast (Penn Dutch Cow Care, Narvon, PA), a plant-based mastitis treatment used on organic dairy farms, and to quantify the product residue in milk and plasma after intramammary administration. We developed an assay to quantify thymol (one of the active ingredients in Phyto-Mast) in milk and plasma using gas chromatography and mass spectrometry (GC-MS). Thymol is a volatile aromatic compound with antiinflammatory properties. As a model for dairy cows, 5 healthy, lactating alpine dairy goats were given 5 mL of Phyto-Mast per udder half. For 10 d following treatment, we analyzed blood and milk samples for thymol residues using GC-MS. The GC-MS assay was very sensitive for thymol detection, to a concentration of 0.01 μg/mL in plasma. Using thymol as a marker, Phyto-Mast was detectable and quantifiable in plasma beginning with the 15-min posttreatment sample, but was no longer detectable in the 4-h posttreatment sample. Thymol residues were only detected in the 12-h posttreatment milk sample. An inflammatory response was not evident in the udder following phytoceutical administration. Although this study provides information about the elimination of thymol, the product contains several other active chemicals, which may have different pharmacokinetic behaviors. Further analysis and additional study animals will help to determine a milk withholding time for Phyto-Mast. Given the recent growth of the organic dairy industry, understanding the pharmacokinetics of therapeutics used in organic production and developing accurate withholding recommendations will help to ensure milk safety.}, number={4}, journal={JOURNAL OF DAIRY SCIENCE}, author={McPhee, C. S. and Anderson, K. L. and Yeatts, J. L. and Mason, S. E. and Barlow, B. M. and Baynes, R. E.}, year={2011}, month={Apr}, pages={1738–1743} }
 @article{clothier_leavens_griffith_wetzlich_baynes_riviere_tell_2011, title={Pharmacokinetics of tulathromycin after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus)}, volume={34}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2010.01261.x}, abstractNote={Clothier, K. A., Leavens, T., Griffith, R. W., Wetzlich, S. E., Baynes, R. E., Riviere, J. E., Tell, L. A. Pharmacokinetics of tulathromycin after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus). J. vet. Pharmacol. Therap.34, 448–454.}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Clothier, K. A. and Leavens, T. and Griffith, R. W. and Wetzlich, S. E. and Baynes, R. E. and Riviere, J. E. and Tell, L. A.}, year={2011}, month={Oct}, pages={448–454} }
 @article{young_smith_leavens_wetzlich_baynes_mason_riviere_tell_2011, title={Pharmacokinetics of tulathromycin following subcutaneous administration in meat goats}, volume={90}, ISSN={["0034-5288"]}, DOI={10.1016/j.rvsc.2010.06.025}, abstractNote={Tulathromycin is a triamilide antibiotic that maintains therapeutic concentrations for an extended period of time. The drug is approved for the treatment of respiratory disease in cattle and swine and is occasionally used in goats. To investigate the pharmacokinetics of tulathromycin in meat goats, 10 healthy Boer goats were administered a single 2.5 mg/kg subcutaneous dose of tulathromycin. Plasma concentrations were measured by ultra-high pressure liquid chromatography tandem mass spectrometry (UPLC–MS/MS) detection. Plasma maximal drug concentration (Cmax) was 633 ± 300 ng/ml (0.40 ± 0.26 h post-subcutaneous injection). The half-life of tulathromycin in goats was 110 ± 19.9 h. Tulathromycin was rapidly absorbed and distributed widely after subcutaneous injection 33 ± 6 L/kg. The mean AUC of the group was 12,500 ± 2020 h ng/mL for plasma. In this study, it was determined that the pharmacokinetics of tulathromycin after a single 2.5 mg/kg SC injection in goats were very similar to what has been previously reported in cattle.}, number={3}, journal={RESEARCH IN VETERINARY SCIENCE}, author={Young, Gabrielle and Smith, Geof W. and Leavens, Teresa L. and Wetzlich, Scott E. and Baynes, Ronald E. and Mason, Sharon E. and Riviere, Jim E. and Tell, Lisa A.}, year={2011}, month={Jun}, pages={477–479} }
 @article{baynes_barlow_mason_riviere_2010, title={Disposition of melamine residues in blood and milk from dairy goats exposed to an oral bolus of melamine}, volume={48}, ISSN={["0278-6915"]}, DOI={10.1016/j.fct.2010.04.040}, abstractNote={There have been numerous reports of melamine-related illnesses following oral exposure to this contaminant. These studies have been in monogastrics, but there are few reports of adverse effects and pharmacokinetics of melamine in ruminants. The purpose of this project was to determine how melamine is systemically cleared from the blood and milk in lactating animals. Five lactating goats were given a single oral dose of 40 mg/kg body weight. Milk and blood samples were collected for 144 h and analyzed to determine key pharmacokinetic parameters. The apparent plasma half-life (11.12h) was 3 times longer in these ruminants than that reported in monogastrics and the apparent volume of distribution was more than 6 times greater than that reported in monogastrics. The milk had an apparent half-life of 9.44h and less than 0.4% of the melamine dose was eliminated in milk. All milk samples were below the LOQ at 4 days (96 h) after exposure. In summary, the pharmacokinetics of melamine in ruminants is not predictive from monogastrics and milk from similarly exposed animals should be condemned for at least 4days after the last exposure to avoid violation of proposed MRLs or safe levels for milk.}, number={8-9}, journal={FOOD AND CHEMICAL TOXICOLOGY}, author={Baynes, Ronald E. and Barlow, Beth and Mason, Sharon E. and Riviere, Jim E.}, year={2010}, pages={2542–2546} }
 @article{buur_baynes_smith_riviere_2009, title={A physiologically based pharmacokinetic model linking plasma protein binding interactions with drug disposition}, volume={86}, ISSN={["0034-5288"]}, DOI={10.1016/j.rvsc.2008.07.003}, abstractNote={Combination drug therapy increases the chance for an adverse drug reactions due to drug–drug interactions. Altered disposition for sulfamethazine (SMZ) when concurrently administered with flunixin meglumine (FLU) in swine could lead to increased tissue residues. There is a need for a pharmacokinetic modeling technique that can predict the consequences of possible drug interactions. A physiologically based pharmacokinetic model was developed that links plasma protein binding interactions to drug disposition for SMZ and FLU in swine. The model predicted a sustained decrease in total drug and a temporary increase in free drug concentration. An in vivo study confirmed the presence of a drug interaction. Neither the model nor the in vivo study revealed clinically significant changes that alter tissue disposition. This novel linkage approach has use in the prediction of the clinical impact of plasma protein binding interactions. Ultimately it could be used in the design of dosing regimens and in the protection of the food supply through prediction and minimization of tissue residues.}, number={2}, journal={RESEARCH IN VETERINARY SCIENCE}, author={Buur, J. L. and Baynes, R. E. and Smith, G. W. and Riviere, J. E.}, year={2009}, month={Apr}, pages={293–301} }
 @article{vijay_white_kaminski_riviere_baynes_2009, title={Dermal Permeation of Biocides and Aromatic Chemicals in Three Generic Formulations of Metalworking Fluids}, volume={72}, ISSN={["1087-2620"]}, DOI={10.1080/15287390902800421}, abstractNote={Metalworking fluids (MWF) are complex mixtures consisting of a variety of components and additives. A lack of scientific data exists regarding the dermal permeation of its components, particularly biocides. The aim of this study was to evaluate the dermal permeation of biocides and other aromatic chemicals in water and in three generic soluble oil, semi-synthetic, and synthetic MWF types in order to evaluate any differences in their permeation profiles. An in vitro flow-through diffusion cell study was performed to determine dermal permeation. An infinite dose of different groups of chemicals (6 biocides and 29 aromatic chemicals) was applied to porcine skin, with perfusate samples being collected over an 8-h period. Perfusate samples were analyzed by gas chromatography/mass spectrometry (GC-MS) and ultra-performance liquid chromatography/mass spectroscopy (UPLC-MS), and permeability was calculated from the analysis of the permeated chemical concentration–time profile. In general, the permeation of chemicals was highest in aqueous solution, followed by synthetic, semi-synthetic, and soluble oil MWF. The absorption profiles of most of the chemicals including six biocides were statistically different among the synthetic and soluble oil MWF formulations, with reduced permeation occurring in oily formulations. Permeation of almost all chemicals was statistically different between aqueous and three MWF formulation types. Data from this study show that permeation of chemicals is higher in a generic synthetic MWF when compared to a soluble oil MWF. This indicates that a soluble oil MWF may be safer than a synthetic MWF in regard to dermal permeation of chemicals to allow for an increased potential of systemic toxicity. Therefore, one may conclude that a synthetic type of formulation has more potential to produce contact dermatitis and induce systemic toxicological effects. The dilution of these MWF formulations with water may increase dermal permeability of biocides, allowing for an enhanced risk for systemic toxicological effects and dermatitis potential.}, number={13}, journal={JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES}, author={Vijay, Vikrant and White, Eugene M. and Kaminski, Michael D., Jr. and Riviere, Jim E. and Baynes, Ronald E.}, year={2009}, pages={832–841} }
 @article{smith_davis_baynes_yeatts_barlow_riviere_2009, title={Elimination kinetics of tilmicosin following intramammary administration in lactating dairy cattle}, volume={234}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.234.2.245}, DOI={10.2460/javma.234.2.245}, abstractNote={Abstract}, number={2}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Smith, Geof W. and Davis, Jennifer L. and Baynes, Ronald E. and Yeatts, James L. and Barlow, Beth M. and Riviere, Jim E.}, year={2009}, month={Jan}, pages={245–248} }
 @article{mason_baynes_almond_riviere_scheidt_2009, title={Pharmacology of tetracycline water medication in swine}, volume={87}, ISSN={["1525-3163"]}, DOI={10.2527/jas.2009-1877}, abstractNote={Medicating drinking water with tetracycline is commonly used in swine production systems to treat and prevent disease outbreaks. However, little information is known of the pharmacokinetics of this medication in water formulations. Twenty-four barrows, divided into 1 control group (of nontreated animals) and 3 equally sized treatments groups (n = 6/group), were treated with tetracycline water medication for 5 d at 125, 250, and 500 mg/L. Blood samples were collected at 0 (prestudy), 4, 8, 12, 24, 32, 48, 56, 72, 80, 96, and 104 h after exposure. Data analyses consisted of a noncompartmental pharmacokinetic analysis and statistical analysis of steady state concentrations with repeated measures ANOVA and multiple-comparison testing to determine whether plasma concentrations differed among groups. Derived pharmacokinetic parameters were consistent with previously published feed and intravenous data. Plasma tetracycline concentrations at steady state were 0, 0.33, 0.47, and 0.77 microg/mL for 0-, 125-, 250-, and 500-mg/L exposures, respectively. Treatment group steady-state plasma concentrations were significantly different from plasma concentrations in control animals (P < 0.0001); however, whereas the 125- and 250-mg/L groups were significantly different from the 500-mg/L group (P < 0.0001), their mean plasma tetracycline concentrations did not differ from one another. Furthermore, the study showed that tetracycline oral bioavailability is very small. The dose response curve also shows that concentrations of plasma tetracycline increase linearly, yet not in a 1 to 1 ratio, to the direct increase in water medication dose.}, number={10}, journal={JOURNAL OF ANIMAL SCIENCE}, author={Mason, S. E. and Baynes, R. E. and Almond, G. W. and Riviere, J. E. and Scheidt, A. B.}, year={2009}, month={Oct}, pages={3179–3186} }
 @article{vijay_baynes_young_riviere_2009, title={Selection of Appropriate Training Set of Chemicals for Modeling Dermal Permeability Using Uniform Coverage Design}, volume={28}, ISSN={["1611-020X"]}, DOI={10.1002/qsar.200960088}, abstractNote={Abstract}, number={11-12}, journal={QSAR & COMBINATORIAL SCIENCE}, author={Vijay, Vikrant and Baynes, Ronald E. and Young, S. Stanley and Riviere, Jim E.}, year={2009}, month={Dec}, pages={1478–1486} }
 @article{davis_smith_baynes_tell_webb_riviere_2009, title={Update on drugs prohibited from extralabel use in food animals}, volume={235}, ISSN={["0003-1488"]}, DOI={10.2460/javma.235.5.528}, number={5}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Davis, Jennifer L. and Smith, Geof W. and Baynes, Ronald E. and Tell, Lisa A. and Webb, Alistair I. and Riviere, Jim E.}, year={2009}, month={Sep}, pages={528–534} }
 @article{dorr_nemechek_scheidt_baynes_gebreyes_almond_2009, title={Water-flow variation and pharmacoepidemiology of tetracycline hydrochloride administration via drinking water in swine finishing farms}, volume={235}, ISSN={["0003-1488"]}, DOI={10.2460/javma.235.3.299}, abstractNote={Abstract}, number={3}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Dorr, Paul M. and Nemechek, Megan S. and Scheidt, Alan B. and Baynes, Ronald E. and Gebreyes, Wondwossen A. and Almond, Glen W.}, year={2009}, month={Aug}, pages={299–304} }
 @article{baynes_xia_vijay_riviere_2008, title={A solvatochromatic approach to quantifying formulation effects on dermal permeability}, volume={19}, ISSN={["1029-046X"]}, DOI={10.1080/10629360802551026}, abstractNote={Dermal risk assessments are most often concerned with the occupational and environmental exposure to a single chemical and then determining solute permeability through in vitro or in vivo experimentation with various animal models and/or computational approaches. Oftentimes, the skin is exposed to more than one chemical that could potentially modulate dermal permeability of the chemical that could cause adverse health effects. The focus of this article is to demonstrate that these formulation effects on dermal permeability can occur with simple solvent formulations or complex industrial formulations and that these effects can be modeled within the context of a linear solvation energy relationship (LSER). This research demonstrated that formulation-specific strength coefficients (r p a b v) predicted (r 2 = 0.75–0.83) changes in the dermal permeability of phenolic compounds when formulated with commercial metal-working fluid (MWF) formulations or 50% ethanol. Further experimentation demonstrated that chemical-induced changes in skin permeability with 50% ethanol are strongly correlated (r 2 = 0.91) to similar changes in an inert membrane-coated fiber (MCF) array system consisting of three chemically diverse membranes. Changes in specific strength coefficients pertaining to changes in hydrogen donating ability (Δb) and hydrophobicity (Δv) across membrane systems were identified as important quantitative interactions associated with ethanol mixtures. This solvatochromatic approach along with the use of a MCF array system holds promise for predicting dermal permeability of complex chemical formulations in occupational exposures where performance additives can potentially modulate permeability of potential toxicants. †Presented at the 13th International Workshop on QSARs in the Environmental Sciences (QSAR 2008), 8–12 June 2008, Syracuse, USA.}, number={7-8}, journal={SAR AND QSAR IN ENVIRONMENTAL RESEARCH}, author={Baynes, R. E. and Xia, X-R. and Vijay, V. and Riviere, J. E.}, year={2008}, pages={615–630} }
 @inbook{monteiro-riviere_baynes_riviere_2008, place={New York}, edition={2nd}, title={Animal skin morphology and dermal absorption}, ISBN={0849375916}, booktitle={Dermal absorption and toxicity assessment}, publisher={Informa Healthcare}, author={Monteiro-Riviere, N. A. and Baynes, R. E. and Riviere, J. E.}, editor={Roberts, M.S. and Walters, K.A.Editors}, year={2008}, pages={17–35} }
 @article{yeatts_baynes_xia_riviere_2008, title={Application of linear solvation energy relationships to a custom-made polyaniline solid-phase microextraction fiber and three commercial fibers}, volume={1188}, ISSN={["1873-3778"]}, DOI={10.1016/j.chroma.2008.02.057}, abstractNote={The term linear solvation energy relationships, LSERs, is considered to be a specific subset of a larger group of thermodynamic relationships called linear free energy relationships. Overall, the LSERs model represents a three-step thermodynamic process. The most recently accepted notation for the LSER equation, proposed by Abraham is given as follows:SP=c+eE+sS+aA+bB+vVwhere SP is any free energy related property of a solute, such as log K, and each term in the equation represents a specific type of chemical interaction. In this work, LSERs were applied to a custom-made polyaniline (PANI) solid-phase microextraction fiber and three commercial fibers immersed in water in order to aid in the assessment of a diverse series of solutes’ partitioning behavior. By experimentally determining the log K for a series of solutes with known solute descriptors (E, S, A, B, and V) and performing multi-linear regression, the unknown system coefficients (e, s, a, b, and v) were obtained. The sign and magnitude of the system coefficients reflect the relative strengths of chemical interactions that affect partitioning between the two phases (fiber and water). The LSER study showed that the system properties having the greatest influence on log K were ease of cavity formation and hydrogen bond donating ability. The differences in dipolarity/polarizability as well as in hydrogen bond accepting ability further showed that all four fibers offer a unique environment for solute partitioning. The PANI fiber may offer greater flexibility in the choice of fibers to use for solid-phase microextraction.}, number={2}, journal={JOURNAL OF CHROMATOGRAPHY A}, author={Yeatts, James L., Jr. and Baynes, Ronald E. and Xia, Xin-Rui and Riviere, Jim E.}, year={2008}, month={Apr}, pages={108–117} }
 @article{buur_baynes_riviere_2008, title={Estimating meat withdrawal times in pigs exposed to melamine contaminated feed using a physiologically based pharmacokinetic model}, volume={51}, ISSN={["1096-0295"]}, DOI={10.1016/j.yrtph.2008.05.003}, abstractNote={Recently melamine was found to have contaminated the feed of multiple food production species leading to concern over the ability to establish an appropriate withdrawal interval and protect the safety of the food supply. To establish an appropriate withdrawal interval, a physiologically based pharmacokinetic (PBPK) model for melamine was developed for rats and extrapolated to pigs. The rat model underpredicted plasma concentrations, but better predicted tissue residues. Correlation values for plasma, kidney, and liver were 0.59, 0.76, and 0.73, respectively. The pig model underpredicted early plasma time points but had greater accuracy at later time points which is relevant to withdrawal times. Correlation (R2) between predicted and observed plasma values was 0.89 with a negative intercept of −0.76. The pig model estimated a withdrawal interval (based on kidney tissue residues) of 19.2 and 20.9 h for single oral exposures of 3.0 and 5.12 mg/kg of melamine, respectively. Chronic oral dosing (3.0 and 5.12 mg/kg twice daily for 7 days) yielded withdrawal intervals of 20 and 21.3 h, respectively. PBPK models, such as this one, provide evidence of the usefulness in species extrapolation over a range of dosing scenarios and can be used to protect the food supply after accidental exposure in the face of little in the target species.}, number={3}, journal={REGULATORY TOXICOLOGY AND PHARMACOLOGY}, author={Buur, Jennifer L. and Baynes, Ronald E. and Riviere, Jim E.}, year={2008}, month={Aug}, pages={324–331} }
 @article{baynes_smith_mason_barrett_barlow_riviere_2008, title={Pharmacokinetics of melamine in pigs following intravenous administration}, volume={46}, DOI={10.1016/j.fct.2007.11.013}, abstractNote={Melamine-contaminated pet food was recently added as a supplement to livestock feed. There is little or no information concerning the pharmacokinetics of melamine in livestock, and the aim of this study was to obtain pharmacokinetic parameters for this contaminant in pigs. Melamine was administered intravenously to five weanling pigs at a dose of 6.13 mg/kg and plasma samples were collected over 24 h, extracted for melamine, and then analyzed by HPLC-UV. The data was shown to best fit a one-compartment model with melamine's half-life of 4.04 (+/- 0.37) h, clearance of 0.11 (+/- 0.01) L/h/kg, and volume of distribution of 0.61 (+/- 0.04) L/kg. These data are comparable to the only mammalian study in rats and suggests that melamine is readily cleared by the kidney and there is unlikely to be significant tissue binding. Further tissue residue studies are required to assess the depletion kinetics of this contaminant in the pig which will determine whether residue levels in the kidney should be of public health concern if pigs were exposed to a similar dose.}, number={3}, journal={Food and Chemical Toxicology}, author={Baynes, R. E. and Smith, Geof and Mason, S. E. and Barrett, E. and Barlow, B. M. and Riviere, J. E.}, year={2008}, pages={1196–1200} }
 @article{baynes_xia_irman_riviere_2008, title={Quantification of chemical mixture interactions modulating dermal absorption using a multiple membrane fiber array}, volume={21}, ISSN={["1520-5010"]}, DOI={10.1021/tx7002118}, abstractNote={Dermal exposures to chemical mixtures can potentially increase or decrease systemic bioavailability of toxicants in the mixture. Changes in dermal permeability can be attributed to changes in physicochemical interactions between the mixture, the skin, and the solute of interest. These physicochemical interactions can be described as changes in system coefficients associated with molecular descriptors described by Abraham's linear solvation energy relationship (LSER). This study evaluated the effects of chemical mixtures containing either a solvent (ethanol) or a surfactant (sodium lauryl sulfate, SLS) on solute permeability and partitioning by quantifying changes in system coefficients in skin and a three-membrane-coated fiber (MCF) system, respectively. Regression analysis demonstrated that changes in system coefficients in skin were strongly correlated ( R2 = 0.89-0.98) to changes in system coefficients in the three-membrane MCF array with mixtures containing either 1% SLS or 50% ethanol. The PDMS fiber appeared to play a significant role (R2 = 0.84-0.85) in the MCF array in predicting changes in solute permeability, while the WAX fiber appeared to contribute less (R2 = 0.59-0.77) to the array than the other two fibers. On the basis of changes in system coefficients that are part of a LSER, these experiments were able to link physicochemical interactions in the MCF with those interactions in skin when either system is exposed to 1% SLS or 50% ethanol. These experiments further demonstrated the utility of a MCF array to adequately predict changes in dermal permeability when skin is exposed to mixtures containing either a surfactant or a solvent and provide some insight into the nature of the physiochemical interactions that modulate dermal absorptions.}, number={3}, journal={CHEMICAL RESEARCH IN TOXICOLOGY}, author={Baynes, Ronald E. and Xia, Xin Rui and Irman, Mudassar and Riviere, Jim E.}, year={2008}, month={Mar}, pages={591–599} }
 @article{mason_baynes_buur_riviere_almond_2008, title={Sulfamethazine water medication pharmacokinetics and contamination in a commercial pig production unit}, volume={71}, ISSN={["1944-9097"]}, DOI={10.4315/0362-028X-71.3.584}, abstractNote={Sulfamethazine is often used to treat disease in the swine industry. Sulfamethazine is available as water or feed medication and historically (over the past 40 years) has been associated with residue violations in both the United States and Europe. Despite sulfamethazine's approval for use as a water medication, little research on the pharmacokinetics of the water formulation is available. Therefore, a pilot study was performed to determine the plasma levels of an approved sulfamethazine water medication. Plasma levels in pigs treated with an oral bolus (250 mg/kg), which is equivalent to the total drug consumed within a 24-h period, achieved therapeutic concentrations (50 microg/ml). Noncompartmental-based pharmacokinetic model parameters for clearance, half-life, and volume of distribution were consistent with previously published values in swine. However, the above treatment resulted in exposure of pen mates to sulfamethazine at levels currently above tolerance (0.1 ppm). Using a physiologically based pharmacokinetic model, the treatment dose simulation was compared with observed plasma levels of treated pigs. Flexibility of the physiologically based pharmacokinetic model also allowed simulation of control-pig plasma levels to estimate contamination exposure. A simulated exposure to 0.15 mg/kg twice within approximately 8 h resulted in detectable levels of sulfamethazine in the control pigs. After initial exposure, a much lower dose of 0.059 mg/kg maintained the contamination levels above tolerance for at least 3 days. These results are of concern for producers and veterinarians, because in commercial farms, the entire barn is often treated,and environmental contamination could result in residues of an unknown duration.}, number={3}, journal={JOURNAL OF FOOD PROTECTION}, author={Mason, Sharon E. and Baynes, Ronald E. and Buur, Jennifer L. and Riviere, Jim E. and Almond, Glen W.}, year={2008}, month={Mar}, pages={584–589} }
 @article{ardente_barlow_burns_goldman_baynes_2008, title={Vehicle effects on in vitro transdermal absorption of sevoflurane in the bullfrog, Rana catesbeiana}, volume={25}, ISSN={["1382-6689"]}, DOI={10.1016/j.etap.2007.12.001}, abstractNote={The experimental objectives were to identify a vehicle which produces a homogenous formulation when combined with the anesthetic solution sevoflurane and understand the dermal absorption of sevoflurane in silastic membranes and amphibian skin in vitro utilizing a flow-through diffusion system. Seven vehicles were evaluated in varying ratios with 5 formulations resulting in the desired homogenous consistency for practical application. Sevoflurane diffusion across silastic membranes was influenced by pluronic/lecithin organogel (PLO), pluronic F 127 20% gel, and sterile lube. Flux and permeability across silastic membranes were significantly greater in sterile lube than in the other formulations. While no significant vehicle effects were observed in bullfrog skin, the flux-time profiles suggest that sevoflurane diffusion in bullfrog skin may be positively influenced by PLO. Future in vivo studies are required to assess sevoflurane retention after removal of these formulations to more accurately control the plane of anesthesia in amphibians.}, number={3}, journal={ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY}, author={Ardente, Amanda J. and Barlow, Beth M. and Burns, Patrick and Goldman, Rebecca and Baynes, Ronald E.}, year={2008}, month={May}, pages={373–379} }
 @article{xia_baynes_monteiro-riviere_riviere_2007, title={A system coefficient approach for quantitative assessment of the solvent effects on membrane absorption from chemical mixtures}, volume={18}, ISSN={["1062-936X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000249294000006&KeyUID=WOS:000249294000006}, DOI={10.1080/10629360701428540}, abstractNote={A system coefficient approach is proposed for quantitative assessment of the solvent effects on membrane absorption from chemical mixtures. The complicated molecular interactions are dissected into basic molecular interaction forces via Abraham's linear solvation energy relationship (LSER). The molecular interaction strengths of a chemical are represented by a set of solute descriptors, while those of a membrane/chemical mixture system are represented by a set of system coefficients. The system coefficients can be determined by using a set of probe compounds with known solute descriptors. Polydimethylsiloxane (PDMS) membrane-coated fibres and 32 probe compounds were used to demonstrate the proposed approach. When a solvent was added into the chemical mixture, the system coefficients were altered and detected by the system coefficient approach. The system coefficients of the PDMS/water system were (0.09, 0.49, −1.11, −2.36, −3.78, 3.50). When 25% ethanol was added into the PDMS/water system, the system coefficients were altered significantly (0.38, 0.41, −1.18, −2.07, −3.40, 2.81); and the solvent effect was quantitatively described by the changes in the system coefficients (0.29, −0.08, −0.07, 0.29, 0.38, −0.69). The LSER model adequately described the experimental data with a correlation coefficient (r 2) of 0.995 and F-value of 1056 with p-value less than 0.0001.}, number={5-6}, journal={SAR AND QSAR IN ENVIRONMENTAL RESEARCH}, author={Xia, X. R. and Baynes, R. E. and Monteiro-Riviere, N. A. and Riviere, J. E.}, year={2007}, pages={579–593} }
 @article{xia_baynes_monteiro-riviere_riviere_2007, title={An experimentally based approach for predicting skin permeability of chemicals and drugs using a membrane-coated fiber array}, volume={221}, ISSN={["1096-0333"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000247278800007&KeyUID=WOS:000247278800007}, DOI={10.1016/j.taap.2007.03.026}, abstractNote={A membrane-coated fiber (MCF) array approach is proposed for predicting the percutaneous absorption of chemicals and drugs from chemical or biological mixtures. Multiple MCFs were used to determine the partition coefficients of compounds (logKMCF). We hypothesized that one MCF will characterize one pattern of molecular interactions and therefore the skin absorption process can be simulated by a multiple MCF array having diverse patterns of molecular interactions. Three MCFs, polydimethylsiloxane (PDMS), polyacrylate (PA) and CarboWax (Wax), were used to determine the logKMCF values for a set of calibration compounds. The skin permeability log(kp) of the compounds was measured by diffusion experiments using porcine skin. The feasibility of the MCF array approach for predicting skin permeability was demonstrated with the three MCFs. A mathematical model was established by multiple linear regression analysis of the log(kp) and logKMCF data set: log(kp) = − 2.34–0.124 logKpdms + 1.91 logKpa − 1.17 logKwax (n = 25, R2 = 0.93). The MCF array approach is an alternative animal model for skin permeability measurement. It is an experimentally based, high throughput approach that provides high prediction confidence and does not require literature data nor molecular structure information in contrast to the existing predictive models.}, number={3}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Xia, Xin-Rui and Baynes, Ronald E. and Monteiro-Riviere, Nancy A. and Riviere, Jim E.}, year={2007}, month={Jun}, pages={320–328} }
 @article{needham_webb_baynes_riviere_craigmill_tell_2007, title={Current update on drugs for game bird species}, volume={231}, ISSN={["1943-569X"]}, DOI={10.2460/javma.231.10.1506}, abstractNote={JAVMA, Vol 231, No. 10, November 15, 2007 T USDA considers game bird species to include grouse, guineafowl, partridges, pigeons (squabs), quail, pheasants, ducks, geese, and wild turkey. According to USDA regulations, although these game bird species may not be hunted in the wild for the purpose of being sold for human consumption, they may be sold for food when raised in captivity. In the United States, over 8 billion chickens and 220 million domestic turkeys are sold for human food consumption on an annual basis. In comparison, 37 million quail, 4 million chukars, 10 million pheasants, and 1 million mallard ducks are reportedly sold for food. Veterinarians who treat game birds need access to therapeutic drugs and need to be able to provide appropriate WDIs to ensure that drug residues will not enter the food chain. The purpose of this digest is to familiarize veterinarians with the few drugs that are approved for use in game birds and to provide information on the status of ELDU in these species.}, number={10}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Needham, Martha L. and Webb, Alistair I. and Baynes, Ronald E. and Riviere, Jim E. and Craigmill, Arthur L. and Tell, Lisa A.}, year={2007}, month={Nov}, pages={1506–1508} }
 @article{riviere_baynes_xia_2007, title={Membrane-coated fiber array approach for predicting skin permeability of chemical mixtures from different vehicles}, volume={99}, DOI={10.1093/toxsci/kfm155}, abstractNote={A membrane-coated fiber (MCF) array approach was developed for quantitative assessment of skin absorption from chemical mixtures, which was based on the similarity in the absorption mechanisms of the MCF membrane and the stratum corneum of the skin. A set of probe compounds were used to detect the relative molecular interaction strengths of chemicals with the vehicle and the membranes, which provided a linkage between the skin permeability (log k) and MCF partition coefficients (log KF). A predictive model was established via multiple linear regression analysis of the data matrix of experimentally measured log k value and log KFm values; log k=a0+a1 log KF1+a2 log KF2+...+an log KFm, where m is the number of diverse MCFs. Twenty-five probe compounds and three MCFs (polydimethylsiloxane for lipophilic, polyacrylate for polarizable, and CarboWax for polar interactions) were used to demonstrate the model development processes in the MCF array approach. The skin permeability of the probe compounds was measured with conventional diffusion cell experiments using dermatomed porcine skin. Three predictive models were established for skin permeability prediction from chemical mixtures in water, 50% ethanol, and 1% sodium lauryl sulfate (SLS) with R2 values of 93, 91, and 83, respectively. The log k and log KF values were considerably altered by the addition of ethanol or SLS into the dose vehicle; however, their correlations to skin permeability remained strong under various conditions. These results suggested that the experimentally based MCF array approach can be used to predict skin absorption from chemical mixtures in different vehicles or formulations.}, number={1}, journal={Toxicological Sciences}, author={Riviere, J. E. and Baynes, R. E. and Xia, X. R.}, year={2007}, pages={153–161} }
 @article{baynes_xia_barlow_riviere_2007, title={Partitioning behavior of aromatic components in jet fuel into diverse membrane-coated fibers}, volume={70}, ISSN={["1528-7394"]}, DOI={10.1080/15287390701549146}, abstractNote={Jet fuel components are known to partition into skin and produce occupational irritant contact dermatitis (OICD) and potentially adverse systemic effects. The purpose of this study was to determine how jet fuel components partition (1) from solvent mixtures into diverse membrane-coated fibers (MCFs) and (2) from biological media into MCFs to predict tissue distribution. Three diverse MCFs, polydimethylsiloxane (PDMS, lipophilic), polyacrylate (PA, polarizable), and carbowax (CAR, polar), were selected to simulate the physicochemical properties of skin in vivo. Following an appropriate equilibrium time between the MCF and dosing solutions, the MCF was injected directly into a gas chromatograph/mass spectrometer (GC-MS) to quantify the amount that partitioned into the membrane. Three vehicles (water, 50% ethanol–water, and albumin-containing media solution) were studied for selected jet fuel components. The more hydrophobic the component, the greater was the partitioning into the membranes across all MCF types, especially from water. The presence of ethanol as a surrogate solvent resulted in significantly reduced partitioning into the MCFs with discernible differences across the three fibers based on their chemistries. The presence of a plasma substitute (media) also reduced partitioning into the MCF, with the CAR MCF system being better correlated to the predicted partitioning of aromatic components into skin. This study demonstrated that a single or multiple set of MCF fibers may be used as a surrogate for octanol/water systems and skin to assess partitioning behavior of nine aromatic components frequently formulated with jet fuels. These diverse inert fibers were able to assess solute partitioning from a blood substitute such as media into a membrane possessing physicochemical properties similar to human skin. This information may be incorporated into physiologically based pharmacokinetic (PBPK) models to provide a more accurate assessment of tissue dosimetry of related toxicants.}, number={22}, journal={JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES}, author={Baynes, Ronald E. and Xia, Xin-Rui and Barlow, Beth M. and Riviere, Jim E.}, year={2007}, pages={1879–1887} }
 @article{vijay_yeatts_riviere_baynes_2007, title={Predicting dermal permeability of biocides in commercial cutting fluids using a LSER approach}, volume={175}, DOI={10.1016/j.toxiet.2007.09.005}, number={1-3}, journal={Toxicology Letters}, author={Vijay, V. and Yeatts, J. L. and Riviere, J. E. and Baynes, R. E.}, year={2007}, pages={34–43} }
 @article{vijay_yeattsjr_riviere_baynes_2007, title={Predicting dermal permeability of biocides in commercial cutting fluids using a LSER approach}, volume={175}, ISSN={0378-4274}, url={http://dx.doi.org/10.1016/j.toxlet.2007.09.005}, DOI={10.1016/j.toxlet.2007.09.005}, abstractNote={The aim of this study is to predict dermal permeability of four phenolic biocides in four different formulations using a linear solvation energy relationship (LSER) approach, with a calibrated flow through diffusion cell system. Mathematical descriptors were determined in the laboratory, by mathematical computations, and by statistical methods. Infinite doses of 4 biocides and 25 probe chemicals in water, 17% methanol and 2 commercial metalworking fluids namely Astrocut–C® and Tapfree 2® were applied to porcine skin flow through diffusion cells. The strength coefficients for the 25 probe compounds for each system were determined from multiple linear regression analysis and plugged into the Abraham's LSER equation to predict permeability values for biocides. Biocide permeability significantly decreased in methanol, Astrocut–C® and Tapfree 2® when compared to water. The strength coefficients revealed that hydrophobicity played an important role in explaining the reduced permeability in vehicles compared to water. This finding is important for selection of biocides and cutting fluids formulation. The R2 between experimental and predicted log Kp of probe solutes for water, methanol, Astrocut–C® and Tapfree 2® were 0.70, 0.78, 0.89 and 0.84, respectively. In conclusion, the LSER approach adequately predicted the dermal permeability of four biocides in commercial cutting fluids and also shed light on the chemical interactions resulting in reduced permeability.}, number={1-3}, journal={Toxicology Letters}, publisher={Elsevier BV}, author={Vijay, V and Yeattsjr, J and Riviere, J and Baynes, R}, year={2007}, month={Dec}, pages={34–43} }
 @book{riviere_monteiro-riviere_baynes_xia_2007, title={Quantitating the absorption, partitioning and toxicity of hydrocarbon components of JP-8 jet fuel}, number={FA9550-04-1-0376}, author={Riviere, J. E. and Monteiro-Riviere, N. A. and Baynes, R. E. and Xia, X. R.}, year={2007} }
 @article{kong_shea_baynes_riviere_xia_2007, title={Regression method of the hydrophobicity for determining octanol/water partition ruler approach coefficients of very hydrophobic compounds}, volume={66}, ISSN={["0045-6535"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33751246493&partnerID=MN8TOARS}, DOI={10.1016/j.chemosphere.2006.06.060}, abstractNote={A regression method was developed for the hydrophobicity ruler approach, which is an indirect method for determining the octanol/water partition coefficients of very hydrophobic compounds. Two constants introduced into the mathematical model were obtained by regression of the absorption data sampled before the partition equilibrium. A water miscible organic solvent was used to increase the solubility of the very hydrophobic compounds in the aqueous solution so that the hydrophobicity scale was reduced and the equilibration was accelerated. Polydimethylsiloxane/methanol aqueous solution and a series of 21 polychlorinated biphenyls (PCBs) were used to demonstrate the regression method. The PCB compounds with known experimental logK(o/w) values served as reference compounds, while the PCB compounds without known logK(o/w) values were determined. The distribution coefficients (logK(p/s)), uptake and elimination rate constants were obtained from the two regression constants for each compound (reference or unknown). The correlation of the logK(p/s) values of the reference PCB compounds with their logK(o/w) values was linear (logK(o/w)=2.69logK(p/s)+0.76, R(2)=0.97). The logK(o/w) values were compared with literature values and suggested that some values from the literature far off the calibration line could be inaccurate. The critical experimental factors, the merits of the regression method were discussed.}, number={6}, journal={CHEMOSPHERE}, author={Kong, Xiang Q. and Shea, Damian and Baynes, Ronald E. and Riviere, Jim E. and Xia, Xin-Rui}, year={2007}, month={Jan}, pages={1086–1093} }
 @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{gehring_baynes_riviere_2006, title={Application of risk assessment and management principles to the extralabel use of drugs in food-producing animals}, volume={29}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2006.00707.x}, abstractNote={A risk assessment of the food safety implications of drugs used in food‐producing animals is an essential component of the regulatory approval process for products containing these drugs. This ensures that there is negligible risk to human health if these drugs are used according to the instructions that appear on the approved label. A relative paucity of approved products for veterinary species; however, forces veterinarians worldwide to use drugs in an extralabel manner to treat disease and alleviate suffering in animals. In food‐producing animals, this may result in residues that are potentially harmful to the human consumer. This review describes how risk assessment principles can be extended to evaluate the risks posed by different classes of extralabel drug use. Risk management practices in the United States and Europe are summarized and contrasted to illustrate the application of these principles.}, number={1}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Gehring, R and Baynes, RE and Riviere, JE}, year={2006}, month={Feb}, pages={5–14} }
 @article{monteiro-riviere_inman_barlow_baynes_2006, title={Dermatotoxicity of cutting fluid mixtures: In vitro and in vivo studies}, volume={25}, ISSN={["1556-9535"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000242997200001&KeyUID=WOS:000242997200001}, DOI={10.1080/15569520601013137}, abstractNote={Cutting fluids are widely used in the metal-machining industry to lubricate and reduce heat generation when metals are cut by a metal-cutting tool. These cutting fluids have caused occupational irritant contact dermatitis (OICD), and many of the additives used in these cutting fluid mixtures are thought to be responsible for OICD in workers. The purpose of this study was to assess single or various combinations of these additives in initiating the OICD response following an acute 8-hour exposure in porcine skin in vivo and in vitro using the isolated perfused porcine skin flap (IPPSF) and human epidermal keratinocytes (HEK). Pigs (n = 4) were exposed to 5% mineral oil (MO) or 5% polyethylene glycol (PEG) aqueous mixtures containing various combinations of 2% triazine (TRI), 5% triethanolamine (TEA), 5% linear alkylbenzene sulfonate (LAS), or 5% sulfurized ricinoleic acid (SRA). Erythema and edema were evaluated and skin biopsies for histopathology were obtained at 4 and 8 hours. IPPSFs (n = 4) were exposed to control MO or PEG mixtures and complete MO or PEG mixtures, and perfusate samples were collected hourly to determine interleukin- (IL-) 8 release. The only significant (p < 0.05) mixture effects observed in IPPSFs were with SRA + MO that caused an increase in IL-8 release after 1 or 2 hours' exposure. In vivo exposure to TRI alone appeared to increase erythema, edema, and dermal inflammation compared to the other additives, while SRA alone was least likely to initiate a dermal inflammatory response. In 2-component mixture exposures, the presence of TRI appeared to increase the dermal inflammatory response at 4 and 8 hours especially with the PEG mixtures. In the 3- and 4-component mixtures, MO mixtures are more likely to incite an inflammatory response than PEG mixtures. TRI exhibited the highest toxicity toward HEK, which correlates well to the in vivo irritation and morphology results. In summary, these preliminary studies suggest that the biocide, TRI, is the more potent of the 4 performance additives in causing dermal irritation, and this may vary depending on whether the worker is exposed to a synthetic (PEG)- or MO-based fluid. These findings will however require further clinical studies to validate these acute dermal effects as well as human cumulative irritation following exposure to similar cutting fluid formulations in the workplace.}, number={4}, journal={CUTANEOUS AND OCULAR TOXICOLOGY}, author={Monteiro-Riviere, Nancy A. and Inman, Alfred O. and Barlow, Beth M. and Baynes, Ronald E.}, year={2006}, pages={235–247} }
 @article{willens_stoskopf_baynes_lewbart_taylor_kennedy-stoskopf_2006, title={Percutaneous malathion absorption by anuran skin in flow-through diffusion cells}, volume={22}, ISSN={["1872-7077"]}, DOI={10.1016/j.etap.2006.04.010}, abstractNote={There is increased concern about the sublethal effects of organophosphorous (OP) compounds on human and animal health, including the potential role of OP compounds in the global decline of amphibian populations. Malathion is one of the most widely used OP pesticides with numerous agricultural and therapeutic applications, and exposure to environmentally applied malathion can lead to adverse systemic effects in anurans. Cutaneous absorption is considered a potentially important route of environmental exposure to OP compounds for amphibians, especially in aquatic environments. One in vitro system commonly used to determine the absorption kinetics of xenobiotics across the skin is the two-compartment Teflon flow-through diffusion cell system. To establish cutaneous absorption kinetics of malathion, six full thickness skin samples taken from both the dorsal and ventral surfaces of each of three bullfrogs (Rana catesbeiana) and three marine toads (Bufo marinus) were placed into two-compartment Teflon flow-through diffusion cells perfused with modified amphibian Ringer's solution. A 26 μg/cm2 dose of malathion-2,3-14C diluted in 100% ethanol was applied to each sample (0.44–0.45 μCi). Perfusate was collected at intervals over a 6 h period and analyzed for 14C in a scintillation counter. At the end of 6 h, surface swabs, tape strips, biopsy punches of the dosed area of skin, and peripheral samples were oxidized and analyzed for residue effects. Malathion absorption was greater across the ventral skin compared to dorsal skin in both bullfrogs and marine toads.}, number={3}, journal={ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY}, author={Willens, Scott and Stoskopf, Michael K. and Baynes, Ronald E. and Lewbart, Gregory A. and Taylor, Sharon K. and Kennedy-Stoskopf, Suzanne}, year={2006}, month={Nov}, pages={255–262} }
 @article{willens_stoskopf_baynes_lewbart_taylor_kennedy-stoskopf_2006, title={Percutaneous malathion absorption in the harvested perfused anuran pelvic limb}, volume={22}, ISSN={["1872-7077"]}, DOI={10.1016/j.etap.2006.04.009}, abstractNote={The objective of this study was to establish an accurate in vitro model for cutaneous absorption in anurans. The harvested perfused anuran pelvic limb (HPAPL) model maintains the anatomic and physiologic integrity of the skin from the pelvic limb, including the intact capillary network. Radiolabeled malathion was applied to the skin of the dorsal thigh, and perfusate was collected over a 6h period. Residues from the skin surface, stratum externum, and dosed area beneath the stratum externum were analyzed. Kinetic parameters were calculated from these data. Absorption was significantly less for the HPAPL than previously reported for Teflon flow-through diffusion cells. However, partitioning effects were comparable. The HPAPL is an appropriate in vitro model for examining cutaneous absorption kinetics in the bullfrog.}, number={3}, journal={ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY}, author={Willens, Scott and Stoskopf, Michael K. and Baynes, Ronald E. and Lewbart, Gregory A. and Taylor, Sharon K. and Kennedy-Stoskopf, Suzanne}, year={2006}, month={Nov}, pages={263–267} }
 @article{buur_baynes_smith_riviere_2006, title={Pharmacokinetics of flunixin meglumine in swine after intravenous dosing}, volume={29}, ISSN={["1365-2885"]}, DOI={10.1111/j.1365-2885.2006.00788.x}, abstractNote={Journal of Veterinary Pharmacology and TherapeuticsVolume 29, Issue 5 p. 437-440 Pharmacokinetics of flunixin meglumine in swine after intravenous dosing J. L. BUUR, J. L. BUUR Food Animal Residue Avoidance Databank, Center for Chemical Toxicology Research and Pharmacokinetics, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USASearch for more papers by this authorR. E. BAYNES, R. E. BAYNES Food Animal Residue Avoidance Databank, Center for Chemical Toxicology Research and Pharmacokinetics, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USASearch for more papers by this authorG. SMITH, G. SMITH Food Animal Residue Avoidance Databank, Center for Chemical Toxicology Research and Pharmacokinetics, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USASearch for more papers by this authorJ. E. RIVIERE, J. E. RIVIERE Food Animal Residue Avoidance Databank, Center for Chemical Toxicology Research and Pharmacokinetics, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USASearch for more papers by this author J. L. BUUR, J. L. BUUR Food Animal Residue Avoidance Databank, Center for Chemical Toxicology Research and Pharmacokinetics, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USASearch for more papers by this authorR. E. BAYNES, R. E. BAYNES Food Animal Residue Avoidance Databank, Center for Chemical Toxicology Research and Pharmacokinetics, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USASearch for more papers by this authorG. SMITH, G. SMITH Food Animal Residue Avoidance Databank, Center for Chemical Toxicology Research and Pharmacokinetics, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USASearch for more papers by this authorJ. E. RIVIERE, J. E. RIVIERE Food Animal Residue Avoidance Databank, Center for Chemical Toxicology Research and Pharmacokinetics, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USASearch for more papers by this author First published: 06 September 2006 https://doi.org/10.1111/j.1365-2885.2006.00788.xCitations: 36 Ronald E. Baynes, 4700 Hillsborough St, Raleigh, NC 27606, USA. E-mail: ronald_baynes@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 onFacebookTwitterLinked InRedditWechat Citing Literature Volume29, Issue5October 2006Pages 437-440 RelatedInformation}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Buur, J. L. and Baynes, R. E. and Smith, G. and Riviere, J. E.}, year={2006}, month={Oct}, pages={437–440} }
 @article{buur_baynes_smith_riviere_2006, title={Use of probabilistic modeling within a physiologically based pharmacokinetic model to predict sulfamethazine residue withdrawal times in edible tissues in swine}, volume={50}, ISSN={["1098-6596"]}, DOI={10.1128/AAC.01355-05}, abstractNote={ABSTRACT}, number={7}, journal={ANTIMICROBIAL AGENTS AND CHEMOTHERAPY}, author={Buur, Jennifer and Baynes, Ronald and Smith, Geof and Riviere, Jim}, year={2006}, month={Jul}, pages={2344–2351} }
 @article{buur_baynes_yeatts_davidson_defrancesco_2005, title={Analysis of diltiazem in Lipoderm (R) transdermal gel using reversed-phase high-performance liquid chromatography applied to homogenization and stability studies}, volume={38}, ISSN={["0731-7085"]}, DOI={10.1016/j.jpba.2004.11.053}, abstractNote={A simple and novel method for the extraction and quantification of diltiazem hydrochloride was developed and applied to homogenization and stability studies. The method used solid phase extraction coupled with reversed-phase high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Validation showed inter-day recoveries ranging from 84.00 to 96.52% with relative standard deviations ranging from 12.01 to 15.94%. Intra-day recoveries ranged from 67.95 to 106.1% with relative standard deviations less than 5%. The method showed excellent linearity from 50 to 250 mg/ml in undiluted gel (R2 = 0.996). The homogenization study showed good homogenization using both 50 and 100 depression techniques. Diltiazem was stable at a concentration of 246 mg/ml for 30 days and at a concentration of 99.6 mg/ml for 60 days no matter the storage conditions explored in this study.}, number={1}, journal={JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS}, author={Buur, JL and Baynes, RE and Yeatts, JL and Davidson, G and DeFrancesco, TC}, year={2005}, month={Jun}, pages={60–65} }
 @article{xia_baynes_monteiro-riviere_riviere_2005, title={Determination of the partition coefficients and absorption kinetic parameters of chemicals in a lipophilic membrane/water system by using a membrane-coated fiber technique}, volume={24}, ISSN={["0928-0987"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000226717800002&KeyUID=WOS:000226717800002}, DOI={10.1016/j.ejps.2004.09.004}, abstractNote={The absorption kinetics of chemicals in a lipophilic membrane/water system was studied with a membrane-coated fiber (MCF) technique, in which the partition coefficient, membrane diffusivity and boundary layer adjacent to the membrane were taken into account. The cumulative amount permeated into the membrane was expressed as a function of absorption time in an exponential equation. Two constants were introduced into the model. Both of them were clearly defined by the physiochemical parameters of the system and were obtained by regression of the experimental data sampled over a limited time. The partition and diffusion coefficients, as well as the thickness of the boundary layer, were calculated from the two constants. The kinetic model adequately described the absorption kinetics of the MCF technique. All of the theoretical predictions were supported by the experimental results. The measured partition coefficients correlated well with the published octanol/water partition coefficient (R(2)=0.91). The thickness of the boundary layer was 5.2 microm in a solution stirred at 400 rpm. An inference of the kinetic model revealed that the contribution of the boundary layer to the absorption kinetics is significant for lipophilic chemicals by a lipophilic membrane. It suggested that the absorption rate of a very lipophilic compound could be controlled by the boundary layer even though the diffusivity of the compound in the membrane is lower than that in the solution. It was demonstrated that the MCF technique could be used to determine the partition, diffusion and permeation coefficients, as well as the thickness of the boundary layer in a lipophilic membrane/water system.}, number={1}, journal={EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES}, author={Xia, XR and Baynes, RE and Monteiro-Riviere, NA and Riviere, JE}, year={2005}, month={Jan}, pages={15–23} }
 @article{buur_baynes_craigmill_riviere_2005, title={Development of a physiologic-based pharmacokinetic model for estimating sulfamethazine concentrations in swine and application to prediction of violative residues in edible tissues}, volume={66}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.2005.66.1686}, abstractNote={Abstract}, number={10}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Buur, JL and Baynes, RE and Craigmill, AL and Riviere, JE}, year={2005}, month={Oct}, pages={1686–1693} }
 @article{muhammad_monteiro-riviere_baynes_riviere_2005, title={Effect of in vivo jet fuel exposure on subsequent in vitro dermal absorption of individual aromatic and aliphatic hydrocarbon fuel constituents}, volume={68}, ISSN={["1087-2620"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000229475900004&KeyUID=WOS:000229475900004}, DOI={10.1080/15287390590925456}, abstractNote={The percutaneous absorption of topically applied jet fuel hydrocarbons (HC) through skin previously exposed to jet fuel has not been investigated, although this exposure scenario is the occupational norm. Pigs were exposed to JP-8 jet fuel-soaked cotton fabrics for 1 and 4 d with repeated daily exposures. Preexposed and unexposed skin was then dermatomed and placed in flow-through in vitro diffusion cells. Five cells with exposed skin and four cells with unexposed skin were dosed with a mixture of 14 different HC consisting of nonane, decane, undecane, dodecane, tridecane, tetradecane, pentadecane, hexadecane, ethyl benzene, o-xylene, trimethyl benzene (TMB), cyclohexyl benzene (CHB), naphthalene, and dimethyl naphthalene (DMN) in water + ethanol (50:50) as diluent. Another five cells containing only JP-8-exposed skin were dosed solely with diluent in order to determine the skin retention of jet fuel HC. The absorption parameters of flux, diffusivity, and permeability were calculated for the studied HC. The data indicated that there was a two-fold and four-fold increase in absorption of specific aromatic HC like ethyl benzene, o-xylene, and TMB through 1- and 4-dJP-8 preexposed skin, respectively. Similarly, dodecane and tridecane were absorbed more in 4-d than 1-dJP-8 preexposed skin experiments. The absorption of naphthalene and DMN was 1.5 times greater than the controls in both 1- and 4-d preexposures. CHB, naphthalene, and DMN had significant persistent skin retention in 4-d preexposures as compared to 1-d exposures that might leave skin capable of further absorption several days postexposure. The possible mechanism of an increase in HC absorption in fuel preexposed skin may be via lipid extraction from the stratum corneum as indicated by Fourier transform infrared (FTIR) spectroscopy. This study suggests that the preexposure of skin to jet fuel enhances the subsequent in vitro percutaneous absorption of HC, so single-dose absorption data for jet fuel HC from naive skin may not be optimal to predict the toxic potential for repeated exposures. For certain compounds, persistent absorption may occur days after the initial exposure. This work was supported by U.S. Air Force Office of Scientific Research, grant F49620-01-1-0080.}, number={9}, journal={JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES}, author={Muhammad, F and Monteiro-Riviere, NA and Baynes, RE and Riviere, JE}, year={2005}, month={May}, pages={719–737} }
 @article{xia_baynes_monteiro-riviere_riviere_2005, title={Membrane uptake kinetics of jet fuel aromatic hydrocarbons from aqueous solutions studied by a membrane-coated fiber technique}, volume={15}, ISSN={["1537-6524"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000230827300008&KeyUID=WOS:000230827300008}, DOI={10.1080/15376520590968888}, abstractNote={The absorption of aromatic hydrocarbons from aqueous media is a critical step involved in many biological processes after occupational and environmental exposures to jet fuel. A membrane-coated fiber (MCF) technique was used to study the uptake kinetics. A flow-through system was used to provide a constant concentration for the prolonged permeation experiments. Polydimethylsiloxane (PDMS) and polyacrylate (PA) MCFs were used to study the differential absorptivity of the aromatic compounds between the two membrane materials. The equilibrium absorption amount and a kinetic parameter describing the absorption kinetics were obtained by the regression of the permeation profiles of the aromatic compounds with a mathematical model. The partition coefficients, uptake, and elimination rate constants were determined for six benzene and three naphthalene derivatives. The PDMS/water partition coefficients of the benzene and naphthalene derivatives were linearly correlated with their logKo/w (LogKpdms/w = 0.871LogKo/w − 0.241, R2 = 0.995). The PA/water partition coefficients of the benzene derivatives and the naphthalene derivatives were correlated differently with their logKo/w. The correlation equations for benzene and naphthalene derivatives were LogKpa/w = 0.865LogKo/w + 0.0045, R2 = 0.997 and LogKpa/w = 0.763LogKo/w + 0.911, R2 = 1.00, respectively. These results suggest that the MCF technique can detect subtle differences in molecular interactions of the two group derivatives between the two membrane/water systems and may be used to study the absorption and permeation properties of closely related compounds. Finally, the regression method is a particularly useful tool to determine partition coefficients of very lipophilic compounds.}, number={4}, journal={TOXICOLOGY MECHANISMS AND METHODS}, author={Xia, XR and Baynes, RE and Monteiro-Riviere, NA and Riviere, JE}, year={2005}, pages={307–316} }
 @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} }
 @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{xia_baynes_monteiro-riviere_riviere_2004, title={A Compartment Model for the Membrane-Coated Fiber Technique Used for Determining the Absorption Parameters of Chemicals into Lipophilic Membranes}, volume={21}, ISSN={0724-8741}, url={http://dx.doi.org/10.1023/b:pham.0000036907.02901.f7}, DOI={10.1023/B:PHAM.0000036907.02901.f7}, abstractNote={{"Label"=>"PURPOSE", "NlmCategory"=>"OBJECTIVE"} The purpose of this work was to develop a compartment model for the membrane-coated fiber (MCF) technique for determining the absorption parameters of chemicals into lipophilic membranes. {"Label"=>"METHODS", "NlmCategory"=>"METHODS"} A polymer membrane coated onto a section of inert fiber was used as a permeation membrane in the MCF technique. When MCFs were immersed into a donor solution, the compounds in the solution partitioned into the membrane. At a given permeation time, a fiber was removed from the solution and transferred into a gas chromatography injector for quantitative analysis. The permeation process of a given chemical from the donor phase into the membrane was described by a one-compartment model by assuming first-order kinetics. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} A mathematical model was obtained that describes the cumulative amount of a chemical permeated into the membrane as a function of the permeation time in an exponential equation. Two constants were introduced into the compartment model that were clearly defined by the physiochemical parameters of the system (a kinetic parameter and the equilibrium absorption amount) and were obtained by regression of the experimental data sampled over a limited time before equilibrium. The model adequately described the permeation kinetics of the MCF technique. All theoretical predictions were supported by the experimental results. The experimental data correlated well with the mathematical regression results. The partition coefficients, initial permeation rate, uptake, and elimination rate constants were calculated from the two constants. {"Label"=>"CONCLUSIONS", "NlmCategory"=>"CONCLUSIONS"} The compartment model can describe the absorption kinetics of the MCF technique. The regression method based on the model is a useful tool for the determination of the partition coefficients of lipophilic compounds when it takes too long for them to reach permeation equilibrium. The kinetic parameter and the initial permeation rate are unique parameters of the MCF technique that could be used in the development of quantitative structure-activity relationship models.}, number={8}, journal={Pharmaceutical Research}, publisher={Springer Science and Business Media LLC}, author={Xia, Xin-Rui and Baynes, Ronald E. and Monteiro-Riviere, Nancy A. and Riviere, Jim E.}, year={2004}, month={Aug}, pages={1345–1352} }
 @article{gehring_baynes_wang_craigmill_riviere_2004, title={A web-based decision support system to estimate extended withdrawal intervals}, volume={44}, ISSN={["1872-7107"]}, DOI={10.1016/j.compag.2004.05.002}, abstractNote={All drugs approved for use in food-producing animals have a withdrawal interval to prevent residues in food of animal origin that are potentially harmful to consumers. These withdrawal times must be appropriately extended if the drug is used in an extralabel manner. This paper describes a web-based application that was developed to facilitate the calculation of extended withdrawal intervals based on information in the databases maintained by members of the Food Animal Residue Avoidance Databank (FARAD) and using the Extrapolated Withdrawal Interval Estimator (EWE) algorithm. The implementation of this application was illustrated using a group of antimicrobials that are used in cattle and swine. The use of this application has been limited to staff veterinarians working for FARAD since limitations in the available pharmacokinetic data require that results are interpreted by personnel with in-depth knowledge of the pharmacokinetics of drugs in food-producing animals.}, number={2}, journal={COMPUTERS AND ELECTRONICS IN AGRICULTURE}, author={Gehring, R and Baynes, RE and Wang, J and Craigmill, AL and Riviere, JE}, year={2004}, month={Aug}, pages={145–151} }
 @article{xia_baynes_monteiro-riviere_riviere_2004, title={Characterization of polyacrylate membrane-coated fibers used in chemical absorption studies with programmed thermal treatment and FT-IR microscopy}, volume={76}, ISSN={["0003-2700"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000222706400053&KeyUID=WOS:000222706400053}, DOI={10.1021/ac0355146}, abstractNote={A polyacrylate (PA) film was coated onto a fused-silica fiber as a permeation membrane in a membrane-coated fiber (MCF) technique and a solid-phase microextraction technique. The molecular changes of the PA membrane after different temperature treatments were studied with FT-IR microscopy. The absorption bands of the PA aliphatic backbone at 2902, 2795, and 2740 cm(-)(1) remained unchanged over the elevated thermal treatments, indicating that the polymer backbone was stable over these conditions. The spectra of the PA membrane remained unchanged when the thermal treatment temperature was under 150 degrees C. When the temperature was 250 degrees C, the O-H stretching band in the -COOH groups of the poly(acrylic acid) at 3315 cm(-)(1) was significantly reduced. When the temperature was higher than 280 degrees C, this O-H band disappeared. These evidences suggested that the PA membrane underwent dehydroxyl reaction to form an anhydride when the thermal treatments were higher than 250 degrees C. Thermal treatments of a deuterated PA MCF confirmed the anhydride formation mechanism. The anhydride formation explained the absorption property of PA MCFs in GC applications where they must be preconditioned at 300 degrees C. The absorption data suggest that a PA fiber does not preferably absorb polar compounds (with permanent dipole moment); instead, it absorbs preferably aromatic compounds.}, number={14}, journal={ANALYTICAL CHEMISTRY}, author={Xia, XR and Baynes, RE and Monteiro-Riviere, NA and Riviere, JE}, year={2004}, month={Jul}, pages={4245–4250} }
 @article{muhammad_baynes_monteiro-riviere_xia_riviere_2004, title={Dose related absorption of JP-8 jet fuel hydrocarbons through porcine skin with quantitative structure permeability relationship analysis}, volume={14}, ISSN={["1537-6524"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000220690300003&KeyUID=WOS:000220690300003}, DOI={10.1080/15376520490429319}, abstractNote={The effects of dosage on the percutaneous absorption of jet fuel hydrocarbons is not clear, yet is essential for human risk assessment. The present study is an ongoing approach to assess the dose-related percutaneous absorption of a number of aliphatic and aromatic hydrocarbons. The first treatment (1X) was comprised of mixtures containing undecane (4.1%), dodecane (4.7%), tridecane (4.4%), tetradecane (3%), pentadecane (1.6%), naphthalene (1.1%), and dimethyl naphthalene (1.3% of jet fuels) in hexadecane solvent using porcine skin flow through diffusion cell. Other treatments (n = 4 cells) were 2X and 5X concentrations. Perfusate samples were analyzed with gas chromatography-flame ionization detector (GC-FID) using head space solid phase micro-extraction fiber technique. We have standardized the assay to have a good linear correlation for all the tested components in media standards. Absorption parameters including diffusivity, permeability, steady state flux, and percent dose absorbed were estimated for all the tested hydrocarbons. This approach provides a baseline to access component interactions among themselves and with the diluent (solvents). A quantitative structure permeability relationship (QSPR) model was derived to predict the permeability of unknown jet fuel hydrocarbons in this solvent system by using their physicochemical parameters. Our findings suggested a dose related increase in absorption for naphthalene and dimethyl naphthalene (DMN).}, number={3}, journal={TOXICOLOGY MECHANISMS AND METHODS}, author={Muhammad, F and Baynes, RE and Monteiro-Riviere, NA and Xia, XR and Riviere, JE}, year={2004}, pages={159–166} }
 @article{webb_baynes_craigmill_riviere_haskell_2004, title={Drugs approved for small ruminants}, volume={224}, ISSN={["0003-1488"]}, DOI={10.2460/javma.2004.224.520}, abstractNote={JAVMA, Vol 224, No. 4, February 15, 2004 F the purpose of this FARAD Digest, small ruminants are considered to include sheep, goats, deer, and camelids. In the United States, the small ruminant population is low, and they are all considered minor species under the Food, Drug, and Cosmetics Act (Table 1). Minor species are defined by exclusion from major species (ie, cats, dogs, horses, swine, cattle, chickens, and turkeys). In the United States, sheep were only considered to be minor species in regard to efficacy and target animal safety requirements and remained a major species when human food safety was being evaluated. This exception was attributed to the high consumption of lamb and mutton at the time of the original classification in 1983. It was not until August 2002 that the sheep drug approval process was amended so that sheep were reclassified as a minor species with regard to human food safety requirements. Classification as a minor species allows the FDA flexibility in permitting new drug applications when FARAD Digest}, number={4}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Webb, AI and Baynes, RE and Craigmill, AL and Riviere, JE and Haskell, SRR}, year={2004}, month={Feb}, pages={520–523} }
 @article{smith_gehring_riviere_yeatts_baynes_2004, title={Elimination kinetics of ceftiofur hydrochloride after intramammary administration in lactating dairy cows}, volume={224}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2004.224.1827}, DOI={10.2460/javma.2004.224.1827}, abstractNote={Abstract}, number={11}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Smith, Geof W. and Gehring, Ronette and Riviere, Jim E. and Yeatts, James L. and Baynes, Ronald E.}, year={2004}, month={Jun}, pages={1827–1830} }
 @article{gehring_baynes_craigmill_riviere_2004, title={Feasibility of using half-life multipliers to estimate extended withdrawal intervals following the extralabel use of drugs in food-producing animals}, volume={67}, ISSN={["0362-028X"]}, DOI={10.4315/0362-028X-67.3.555}, abstractNote={Under the Animal Medicinal Drug Use Clarification Act of 1994, veterinarians are legally allowed to use drugs in food-producing animals in an extralabel manner. This could potentially lead to violative residues in food of animal origin. It is therefore essential that an appropriately extended withdrawal interval be established. Ideally, these extended withdrawal intervals should be calculated on the basis of the tissue half-life of the drug in the target animal. However, these data are not readily available for all drugs of extralabel use in food-producing animals. For this reason, the use of a half-life multiplier has been proposed as a simple alternative method to estimate the effective tissue half-life of a drug. Extended withdrawal intervals, estimated using various half-life multipliers, were compared with the withdrawal intervals calculated using actual tissue half-lives. For the group of drugs investigated, a half-life multiplier of 5 resulted in estimates of extended withdrawal intervals that were potentially inadequate to prevent violative tissue residues for drugs that had relatively long tissue half-lives, high tolerances, or both. This is possibly because fewer half-lives are required for these drugs to reach the target tissue concentrations following administration at label doses. Use of a smaller half-life multiplier (in this case 3) is therefore suggested to ensure that extended withdrawal intervals are adequate to prevent violative tissue residues.}, number={3}, journal={JOURNAL OF FOOD PROTECTION}, author={Gehring, R and Baynes, RE and Craigmill, AL and Riviere, JE}, year={2004}, month={Mar}, pages={555–560} }
 @article{baynes_2004, title={In vitro dermal disposition of abarnectin (avermectin B-1) in livestock}, volume={76}, ISSN={["0034-5288"]}, DOI={10.1016/j.rvsc.2003.10.006}, abstractNote={Many avermectins are approved for topical application in domestic animals. However, extralabel use may result in significant dermal absorption and consequently the potential for adverse effects or violative residues. The primary aim of this study was to assess dermal disposition of abamectin in vitro in bovine, caprine, ovine, and porcine skin dosed in 100% isopropanol, commercial alcohol-based (Ivomec), or oil-based (Eprinex) formulations. Skin sections were perfused in a flow-through diffusion cell system for 8 h, and the disposition of radiolabel abamectin was determined from perfusate and skin samples. Abamectin absorption ranged from 0.09% to 0.20% dose and there were no significant differences between formulations in each species. Isopropanol significantly increased skin deposition in all species when compared to the oil formulation. Absorption was significantly greater in bovine skin than in porcine skin for the isopropanol-containing formulations, but there were no significant species differences for the oil formulation. While significant levels (11.69–50.23% dose) remained on the skin surface, the highest levels deposited in viable skin were observed in caprine skin (28.09% dose) and the lowest levels were in porcine skin (1.50% dose) which could lead to systemic absorption. In summary, these 8-h experiments demonstrated that the alcohol-based formulations compared to oil-based formulations enhanced abamectin absorption and skin deposition in several animal species, and this effect is more likely to be observed in ruminant species than in porcine species.}, number={3}, journal={RESEARCH IN VETERINARY SCIENCE}, author={Baynes, RE}, year={2004}, month={Jun}, pages={235–242} }
 @article{baynes_riviere_2004, title={Mixture additives inhibit the dermal permeation of the fatty acid, ricinoleic acid}, volume={147}, ISSN={0378-4274}, url={http://dx.doi.org/10.1016/j.toxlet.2003.09.014}, DOI={10.1016/j.toxlet.2003.09.014}, abstractNote={Ricinoleic acid (RA) like many of the ingredients in machine cutting fluids and other industrial formulations are potential dermal irritants, yet very little is known about its permeability in skin. 3H-ricinoleic acid mixtures were formulated with three commonly used cutting fluid additives; namely, triazine (TRI), linear alkylbenzene sulfonate (LAS), and triethanolamine (TEA) and topically applied to inert silastic membranes and porcine skin in vitro as aqueous mineral oil (MO) or polyethylene glycol (PEG) mixtures. These additives significantly decreased ricinoleic acid partitioning from the formulation into the stratum corneum (SC) in PEG-based mixtures. Except for LAS, all other additives produced a more basic formulation (pH = 9.3-10.3). In silastic membranes and porcine skin, individual additives or combination of additives significantly reduced ricinoleic permeability. This trend in ricinoleic acid disposition in both membranes suggests that the mixture interaction is more physicochemical in nature and probably not related to the chemical-induced changes in the biological membrane as may be assumed with topical exposures to potentially irritant formulations.}, number={1}, journal={Toxicology Letters}, publisher={Elsevier BV}, author={Baynes, R.E and Riviere, J.E}, year={2004}, month={Feb}, pages={15–26} }
 @article{xia_baynes_monteiro-riviere_leidy_shea_riviere_2003, title={A novel in-vitro technique for studying percutaneous permeation with a membrane-coated fiber and gas chromatography/mass spectrometry: Part I. Performances of the technique and determination of the permeation rates and partition coefficients of chemical mixtures}, volume={20}, ISSN={["0724-8741"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0037331884&partnerID=MN8TOARS}, DOI={10.1023/A:1022287524024}, abstractNote={{"Label"=>"PURPOSE", "NlmCategory"=>"OBJECTIVE"} To develop a novel in-vitro technique for rapid assessment of percutaneous absorption of chemical mixtures. {"Label"=>"METHODS", "NlmCategory"=>"METHODS"} A silastic membrane was coated on to a fiber to be used as a permeation membrane. The membrane-coated fiber was immersed in the donor phase to partition the compounds into the membrane. At a given partition time, the membrane-coated fiber was transferred into a GC injector to evaporate the partitioned compounds for quantitative and qualitative analyses. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} This technique was developed and demonstrated to study the percutaneous permeation of a complex mixture consisting of 30 compounds. Each compound permeated into the membrane was identified and quantified with GC/MS. The standard deviation was less than 10% in 12 repeated permeation experiments. The partition coefficients and permeation rates in static and stirred donor solution were obtained for each compound. The partition coefficients measured by this technique were well correlated (R2 = 0.93) with the reported octanol/water partition coefficients. {"Label"=>"CONCLUSIONS", "NlmCategory"=>"CONCLUSIONS"} This technique can be used to study the percutaneous permeation of chemical mixtures. No expensive radiolabeled chemicals are required. Each compound permeated into the membrane can be identified and quantified. The initial permeation rate and equilibrium time can be obtained for each compound, which could serve as characteristic parameters regarding the skin permeability of the compound.}, number={2}, journal={PHARMACEUTICAL RESEARCH}, author={Xia, XR and Baynes, RE and Monteiro-Riviere, NA and Leidy, RB and Shea, D and Riviere, JE}, year={2003}, month={Feb}, pages={275–282} }
 @article{baynes_barlow_riviere_2003, title={Dermal disposition of triazine in cutting fluid mixtures}, volume={22}, ISSN={["0731-3829"]}, DOI={10.1081/CUS-120026301}, abstractNote={Triazine is often added as a biocide/preservative to cutting fluids formulations that are used in the metal machine industry. Workers involved in metal machining are not only exposed to components in these cutting fluids, but also to biocides such as triazine that have been implicated in occupational irritant dermatitis. Very little is known about how these cutting fluids and their ingredients influence the dermal disposition of triazine. The purpose of this study was to assess 14C‐triazine membrane transport when topically applied to inert silastic membranes and porcine skin in an in vitro flow‐through diffusion cell system as aqueous mineral oil (MO) or aqueous polyethylene glycol (PEG) mixtures. 14C‐triazine mixtures were formulated with three commonly used cutting fluid additives; namely, 0% or 5% linear alkylbenzene sulfonate (LAS), 0% or 5% triethanolamine (TEA), and 0% or 5% sulfurized ricinoleic acid (SRA). Triazine partitioning from the formulation into the stratum corneum (SC) was reduced significantly by the presence of LAS, while SRA significantly reduced the pH of the formulation. Triazine absorption ranged from 2.2% to 3.9% dose in porcine skin and 12.6% to 18.6% dose in silastic membranes. In silastic membranes, the complete mixture reduced triazine absorption significantly in MO‐based mixtures, while in PEG‐based mixtures triazine absorption and apparent permeability were significantly increased. In porcine skin, triazine permeability was significantly increased for both MO‐ and PEG‐based complete mixtures with a trend towards greater triazine absorption in more complex PEG‐based mixtures. Interestingly, SRA + TEA significantly increased triazine permeability absorption in MO‐ and PEG‐based mixtures, but this interaction appears to be more additive than synergistic. Although the physicochemical experiments suggest otherwise, triazine readily permeates a homogenous lipid membrane such as the SC, while triazine permeability was significantly enhanced by the complete mixture, especially in PEG‐based mixtures.}, number={4}, journal={JOURNAL OF TOXICOLOGY-CUTANEOUS AND OCULAR TOXICOLOGY}, author={Baynes, RE and Barlow, BM and Riviere, JE}, year={2003}, pages={215–229} }
 @article{wang_gehring_baynes_webb_whitford_payne_fitzgerald_craigmill_riviere_2003, title={Evaluation of the advisory services provided by the Food Animal Residue Avoidance Databank}, volume={223}, ISSN={["0003-1488"]}, DOI={10.2460/javma.2003.223.1596}, abstractNote={JAVMA, Vol 223, No. 11, December 1, 2003 A part of its mission to help ensure that foods of animal origin are free of violative chemical residues, the Food Animal Residue Avoidance Databank (FARAD) offers 2 advisory services to veterinary practitioners. The first is a comprehensive online database (VetGRAM) of drugs approved by the US FDA/Center for Veterinary Medicine (CVM) for the treatment of food-producing animals. Second, FARAD offers expert-mediated advice on residue avoidance and mitigation for chemical contamination incidents and the extralabel use of drugs. This service is provided by FARAD pharmacologists and toxicologists, who can be reached by e-mail as well as a toll-free telephone number.}, number={11}, journal={JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Wang, JM and Gehring, R and Baynes, RE and Webb, AI and Whitford, C and Payne, MA and Fitzgerald, K and Craigmill, AL and Riviere, JE}, year={2003}, month={Dec}, pages={1596–1598} }
 @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}, ISSN={1528-7394 1087-2620}, url={http://dx.doi.org/10.1080/15287390306400}, DOI={10.1080/15287390306400}, abstractNote={Exposure to N,N-diethyl-m-toluamide (DEET) commonly occurs in the general population and has been implicated as a contributory factor to the Gulf War Illness. The focus of the present studies was to determine the effect of coexposure factors, potentially encountered in a military environment, that could modulate transdermal flux of topically applied DEET. Factors investigated were vehicle, dose, coexposure to permethrin, low-level sulfur mustard, occlusion, and simultaneous systemic exposure to pyridostigmine bromide and the nerve agent simulant diisopropylfluorophosphate (DFP). Studies were conducted using the isolated perfused porcine skin flap (IPPSF), with a few mechanistically oriented studies conducted using in vitro porcine skin and silastic membrane diffusion cells. DEET was quantitated using high-performance liquid chromatography. The vehicle-control transdermal DEET flux in the IPPSF was approximately 2 w g/cm 2 /h for both 7.5 and 75% DEET concentrations, a value similar to that reported in humans. DEET absorption was enhanced by coinfusion of pyridostigmine bromide and DFP, by the presence of sulfur mustard, or by dosing under complete occlusion. The greatest increase in baseline flux was fivefold. In vitro diffusion cell studies indicated that silastic membranes had two orders of magnitude greater permeability than porcine skin, and showed vehicle effects on flux that were not detected in the IPPSF. These results suggest that coexposure to a number of chemicals that potentially could be encountered in a military environment may modulate the percutaneous absorption of topically applied DEET beyond that seen for normal vehicles at typically applied concentrations.}, number={2}, journal={Journal of Toxicology and Environmental Health, Part A}, publisher={Informa UK Limited}, author={Riviere, Jim and Baynes, Ronald and Brooks, James and Yeatts, James and Monteiro-Riviere, Nancy}, year={2003}, month={Jan}, pages={133–151} }
 @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{monteiro-riviere_baynes_riviere_2003, title={Pyridostigmine bromide modulates topical irritant-induced cytokine release from human epidermal keratinocytes and isolated perfused porcine skin}, volume={183}, ISSN={["0300-483X"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000180799100002&KeyUID=WOS:000180799100002}, DOI={10.1016/s0300-483x(02)00421-3}, abstractNote={Gulf War personnel were given pyridostigmine bromide (PB) as a prophylactic treatment against organophosphate nerve agent exposure, and were exposed to the insecticide permethrin and the insect repellent N,N-diethyl-m-toluamide (DEET). The purpose of this study was to assess the effects of PB to modulate release of inflammatory biomarkers after topical chemical exposure to chemical mixtures containing permethrin and DEET applied in ethanol or water vehicles. Treatments were topically applied to isolated perfused porcine skin flaps (IPPSFs). Concentrations of interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E(2) (PGE(2)) were assayed in perfusate to probe for potential inflammatory effects after complex mixture application. IPPSFs (n=4/treatment) were topically dosed with mixtures of permethrin, DEET, and permethrin/DEET, in ethanol. Each treatment was repeated with perfusate spiked with 50 ng/ml of PB. Perfusate was also spiked with 30 ng/ml diisopropylfluorophosphate to simulate low level organophosphate nerve agent exposure. Timed IPPSF venous effluent samples (0.5,1,2,4, and 8 h) were assayed by ELISA for IL-8 and TNF-alpha and by EIA for PGE(2). Overall, PB infusion caused a decrease or IL-8 and PGE(2) release. Effects on TNF-alpha were vehicle dependent. To probe the potential mechanism of this PB effect, human epidermal keratinocyte HEK cell cultures were exposed to permethrin DEET permethrin/DEET, with and without PB in DMSO. IL-8 was assayed at 1, 2, 4, 8, 12 and 24 h. PB suppressed IL-8 in permethrin and ethanol treatment from 4 to 24 h confirming the IPPSF results. In conclusion, these studies suggest that systemic exposure to PB suppressed IL-8 release at multiple time points in two skin model systems. This interaction merits further study.}, number={1-3}, journal={TOXICOLOGY}, author={Monteiro-Riviere, NA and Baynes, RE and Riviere, JE}, year={2003}, month={Feb}, pages={15–28} }
 @article{haskell_gehring_payne_craigmill_webb_baynes_riviere_2003, title={Update on FARAD food animal drug withholding recommendations}, volume={223}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2003.223.1277}, DOI={10.2460/javma.2003.223.1277}, number={9}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Haskell, Scott R. R. and Gehring, Ronette and Payne, Michael A. and Craigmill, Arthur L. and Webb, Alistair I. and Baynes, Ronald E. and Riviere, Jim E.}, year={2003}, month={Nov}, pages={1277–1278} }
 @article{baynes_yeatts_riviere_2002, title={Analysis of N,N-diethyl-m-toluamide in porcine skin perfusates using solid-phase extraction disks and reversed-phase high-performance liquid chromatography}, volume={780}, ISSN={["1570-0232"]}, DOI={10.1016/S1570-0232(02)00412-9}, abstractNote={N,N-Diethyl-m-toluamide (DEET) is frequently used as an insect repellent by military and civilian populations. Because dermal exposure has resulted in several cases of DEET toxicosis, there is a need to rapidly and reliably determine DEET concentrations in biological matrices. An improved method for the analysis of DEET was developed for determining transdermal diffusion of low levels of DEET following application to an in vitro porcine skin flow-through diffusion cell system. The technical improvement involved the use of disk solid-phase extraction (SPE) instead of packed-bed SPE. The disk SPE method required small volumes of preconditioning, wash, and elution solvent (0.5–1 ml) to extract DEET from perfusate samples containing bovine serum albumin (BSA). The limit of quantitation (LOQ) was estimated as 0.08 μg/ml DEET and recoveries from BSA media samples spiked with DEET ranged from 90.1 to 117% with relative standard deviation (RSD) ranging from 2.0 to 13.1%. This method was used to analyze perfusate samples from skin (n=4) topically exposed to DEET–ethanol formulations. The data from these analyses determined that DEET permeability in porcine skin was 2.55×10−5±0.54×10−5 cm/h.}, number={1}, journal={JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES}, author={Baynes, RE and Yeatts, JL and Riviere, JE}, year={2002}, month={Nov}, pages={45–52} }
 @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{martin-jimenez_baynes_craigmill_riviere_2002, title={Extrapolated withdrawal-interval estimator (EWE) algorithm: A quantitative approach to establishing extralabel withdrawal times}, volume={36}, ISSN={["0273-2300"]}, DOI={10.1006/rtph.2002.1544}, abstractNote={The extralabel use of drugs can be defined as the use of drugs in a manner inconsistent with their FDA-approved labeling. The passage of the Animal Medicinal Drug Use Clarification Act (AMDUCA) in 1994 and its implementation by the FDA-Center for Veterinary Medicine in 1996 has allowed food animal veterinarians to use drugs legally in an extralabel manner, as long as an appropriate withdrawal period is established. The present study introduces and validates with simulated and experimental data the Extrapolated Withdrawal-Period Estimator (EWE) Algorithm, a procedure aimed at predicting extralabel withdrawal intervals (WDIs) based on the label and pharmacokinetic literature data contained in the Food Animal Residue Avoidance Databank (FARAD). This is the initial and first attempt at consistently obtaining WDI estimates that encompass a reasonable degree of statistical soundness. Data on the determination of withdrawal times after the extralabel use of the antibiotic oxytetracycline were obtained both with simulated disposition data and from the literature. A withdrawal interval was computed using the EWE Algorithm for an extralabel dose of 25 mg/kg (simulation study) and for a dose of 40 mg/kg (literature data). These estimates were compared with the withdrawal times computed with the simulated data and with the literature data, respectively. The EWE estimates of WDP for a simulated extralabel dose of 25 mg/kg was 39 days. The withdrawal time (WDT) obtained for this dose on a tissue depletion study was 39 days. The EWE estimate of WDP for an extralabel intramuscular dose of 40 mg/kg in cattle, based on the kinetic data contained in the FARAD database, was 48 days. The withdrawal time experimentally obtained for similar use of this drug was 49 days. The EWE Algorithm can obtain WDI estimates that encompass the same degree of statistical soundness as the WDT estimates, provided that the assumptions of the approved dosage regimen hold for the extralabel dosage regimen. Population models could be fitted to fragmentary data to predict residue concentrations in tissues, validate the EWE estimates, and obtain WDI estimates.}, number={1}, journal={REGULATORY TOXICOLOGY AND PHARMACOLOGY}, author={Martin-Jimenez, T and Baynes, RE and Craigmill, A and Riviere, JE}, year={2002}, month={Aug}, pages={131–137} }
 @article{riviere_monteiro-riviere_baynes_2002, title={Gulf War related exposure factors influencing topical absorption of 14C-permethrin}, volume={135}, ISSN={0378-4274}, url={http://dx.doi.org/10.1016/s0378-4274(02)00239-4}, DOI={10.1016/S0378-4274(02)00239-4}, abstractNote={Topical exposure to permethrin has often been implicated as a mitigating factor in the illnesses reported in Gulf War veterans. These studies were designed to assess the effect of co-exposure to low level sulfur mustard, JP-8 jet fuel, N,N-diethyl-m-toluamide (DEET) and fabric occlusion on the percutaneous absorption and skin disposition of topically applied 14C-permethrin (40 μg/cm2) in the isolated perfused porcine skin flap (IPPSF) model. Extent of dermal absorption in vehicle controls in the IPPSF was comparable to literature values for humans. These studies demonstrated a two-fold increased 14C-permethrin percutaneous absorption and almost three-fold increased penetration when JP-8 was present, compared to a one-third decreased permethrin flux in the presence of sulfur mustard. Complete occlusion slightly increased 14C-permethrin absorption, while occlusion with fabric showed no significant effect. A previously noted effect of DEET to inhibit permethrin absorption was still seen in the presence of sulfur mustard exposure. These studies suggest that co-exposure to JP-8 or sulfur mustard may modulate transdermal flux of 14C-permethrin. However, the JP-8 increase in absorption and penetration was less than the five-fold increase previously seen with arterial infusion of pyridostigmine bromide and diisopropylfluorophosphate in the IPPSF. The toxicologic significance of this moderate increase in permethrin absorption remains unclear.}, number={1-2}, journal={Toxicology Letters}, publisher={Elsevier BV}, author={Riviere, Jim E and Monteiro-Riviere, Nancy A and Baynes, Ronald E}, year={2002}, month={Sep}, pages={61–71} }
 @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{baynes_monteiro-riviere_riviere_2002, title={Pyridostigmine bromide modulates the dermal disposition of [C-14]permethrin}, volume={181}, ISSN={["1096-0333"]}, url={http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=ORCID&SrcApp=OrcidOrg&DestLinkType=FullRecord&DestApp=WOS_CPL&KeyUT=WOS:000176540200002&KeyUID=WOS:000176540200002}, DOI={10.1006/taap.2002.9412}, abstractNote={The cause of the Gulf War Syndrome may be related to soldiers being exposed to insecticides (e.g., permethrin (P)), insect repellents (e.g., N,N-diethyl-m-toluamide (DEET)), an organophosphate nerve agent simulant (e.g., diisopropyl fluorpohosphate (DFP)), and/or prophylactic treatment (e.g., pyridostigmine bromide (PB)) against potential nerve gas attacks. The purpose of this study was to assess the dermal disposition of [14C]permethrin in ethanol or ethanol:water (3:2) in the isolated perfused porcine skin flap (IPPSF) model with simultaneous dermal exposure to DEET or DFP. These IPPSFs were also simultaneously perfused arterially with or without PB, DFP, or DFP + PB. The results indicated that DFP + PB significantly increased [14C]permethrin absorption compared to controls (1.06% dose vs 0.14% dose). PB significantly increased [14C]permethrin disposition in the stratum corneum (SC) in aqueous mixtures only (9.40 vs 3.35% dose), while topical DEET or topical DFP reduced [14C]permethrin levels in the SC especially in nonaqueous mixtures. PB also significantly enhanced [14C]permethrin penetration into all skin tissues and perfusate in aqueous mixtures, while DEET reversed this effect. PB appeared to influence [14C]permethrin disposition in flowthrough diffusion cells, suggesting that the mechanism of this interaction may be associated predominantly with epidermal permeability, although muscarinic effects in the vasculature in IPPSFs should not be ruled out and requires further investigation. These experiments suggest that intraarterial perfusion of PB and/or DFP and topical application of DFP or DEET can alter the disposition of [14C]permethrin in skin and possibly its bioavailability in soldiers simultaneously exposed to these chemicals.}, number={3}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Baynes, RE and Monteiro-Riviere, NA and Riviere, JE}, year={2002}, month={Jun}, pages={164–173} }
 @book{baynes_riviere_smith_monteiro-riviere_freeman_2001, title={Dermal absorption cutting fluids}, journal={Annual report 1R010H03669-01A2}, author={Baynes, R. E. and Riviere, J. E. and Smith, C. E. and Monteiro-Riviere, N. A. and Freeman, B.}, year={2001}, month={May} }
 @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} }
 @inbook{baynes_riviere_2001, title={Pesticide disposition: dermal absorption}, ISBN={9780124262614}, DOI={10.1016/b978-012426260-7.50025-2}, abstractNote={Percutaneous absorption is reported as the possible route of entry in 65-85% of all cases of occupational exposure with pesticides. This chapter focuses on mechanisms and pathways of dermal absorption and experimental models used to assess dermal absorption by in vitro, ex vivo, and in vivo methods. The effects of biological variability, pesticide chemistry and formulations, and environmental variables that influence dermal absorption are discussed. The skin is relatively impermeable to aqueous solutions and ions, but it may be permeable in varying degrees to a large number of drugs or xenobiotics. Drug or xenobiotic delivery pathways can hypothetically involve intercellular and intracellular passive diffusion across the epidermis and dermis and/or transappendageal routes via hair follicles and sweat pores. Regional variation in skin permeability in different body sites may be related to skin thickness, number of cell layers, cell size of the epidermis and stratum corneum, and distribution of hair follicles and sweat pores.}, booktitle={Handbook of Pesticide Toxicology (2nd ed.)}, publisher={San Diego: Academic Press}, author={Baynes, R. and Riviere, J. E.}, year={2001}, pages={515–530} }
 @article{baynes_payne_martin-jimenez_abdullah_anderson_webb_craigmill_riviere_2000, title={Extralabel use of ivermectin and moxidectin in food animals}, volume={217}, ISSN={["0003-1488"]}, DOI={10.2460/javma.2000.217.668}, number={5}, journal={JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Baynes, RE and Payne, M and Martin-Jimenez, T and Abdullah, AR and Anderson, KL and Webb, AI and Craigmill, A and Riviere, JE}, year={2000}, month={Sep}, pages={668–671} }
 @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} }
 @misc{riviere_martin-jimenez_baynes_craigmill_2000, title={Methods, systems and products for determining drug withdrawal intervals}, volume={6,066,091}, number={2000 May 23}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Riviere, J. E. and Martin-Jimenez, T. and Baynes, R. E. and Craigmill, A. L.}, year={2000}, month={May} }
 @article{baynes_lyman_anderson_brownie_1999, title={A preliminary survey of antibiotic residues and viable bacteria in milk from three Caribbean basin countries}, volume={62}, ISSN={["1944-9097"]}, DOI={10.4315/0362-028X-62.2.177}, abstractNote={There is widespread concern about the presence of antimicrobial drugs in milk. The presence of drug residues in milk may have public health implications. Milk samples (n = 25 to 65/country) were collected from bulk tanks and commercial vendors in Barbados, Costa Rica, and Jamaica between February 1996 and August 1997. Bulk tank samples were collected from high milk-producing regions of Jamaica and Costa Rica and from 26 dairy farms in Barbados. Milk pH, bacterial growth (total CFU/ml and the presence of Streptococcus agalactiae and Staphylococcus aureus), and the presence of antimicrobials were determined. Milk samples were tested by a microbial inhibition test (Delvotest-P, Gist-Brocades Food Ingredients, Inc.) to screen for antimicrobial drugs. All positives were retested for the presence of beta-lactam antibiotics after incubating with penicillinase and some positives were identified by high-pressure liquid chromatography-UV. Mean pH values ranged from 6.5 to 6.7. S. aureus was identified in bulk tank samples from Costa Rica (52%), Barbados (44%), and Jamaica (46%). S. agalactiae was identified in bulk tank samples from Costa Rica (28%), Barbados (8 and 16%), and Jamaica (18%). Antimicrobial residues were detected in some bulk tank samples from Barbados (8%) and Jamaica (10%) but not in samples from Costa Rica. All positives in milk from Jamaica and Barbados were determined to be beta-lactams. No residues were detected in pasteurized milk samples from Barbados or ultrahigh-temperature milk from Jamaica. The presence of beta-lactam residues in some of these samples suggests the appropriateness of testing milk prior to processing for consumption.}, number={2}, journal={JOURNAL OF FOOD PROTECTION}, author={Baynes, RE and Lyman, R and Anderson, KL and Brownie, CF}, year={1999}, month={Feb}, pages={177–180} }
 @article{payne_baynes_sundlof_craigmill_webb_riviere_1999, title={Drugs prohibited from extralabel use in food animals}, volume={215}, number={1}, journal={Journal of the American Veterinary Medical Association}, author={Payne, M. A. and Baynes, R. E. and Sundlof, S. F. and Craigmill, A. and Webb, A. I. and Riviere, J. E.}, year={1999}, month={Jul}, pages={28–32} }
 @article{baynes_martin-jimenez_craigmill_riviere_1999, title={Estimating provisional acceptable residues for extralabel drug use in livestock}, volume={29}, ISSN={["1096-0295"]}, DOI={10.1006/rtph.1999.1302}, abstractNote={In 1996, the United States Congress passed legislation (Animal Medicinal Drug Use Clarification Act, AMDUCA), which allows some veterinary or human drugs to be used off label in food-producing animals. In order to implement this Act and protect the U.S. consumer, tolerances or safe concentrations are required before a withdrawal time can be estimated for extralabel drug use. Use of foreign MRLs to satisfy these data needs may not be applicable because of differences in safety standards between the U.S. and other countries. This paper presents strategies that can be used to derive equivalent safe concentrations, referred to as provisional acceptable residues (PARs), that may then be used to estimate drug withdrawal times. Health-based methods are proposed for calculating a PAR for a tissue. Procedure A partitions 50% of the acceptable daily intake (ADI) to edible tissues and reserves the remainder for milk. Procedure B equally partitions the ADI into all edible tissues. Procedure C partitions 50% of the ADI to milk and equally partitions the remaining 50% ADI into edible tissues. Simulations were performed for florfenicol, tetracycline, dexamethasone, azaperone, ivermectin, eprinomectin, and doramectin. In general, these simulations resulted in derivation of conservative PARs, which did not result in daily intakes of residues greater than the health-based ADI. These simulations demonstrated that provided the safe concentrations or equivalent PARs are based on rigorous toxicology safety data (e.g., NOELs, ADIs), the safety of food animal products will not be compromised. It is proposed that these PARs can be used for estimating withdrawal times after extralabel drug use or inadvertent exposure to an environmental contaminant where no approved withdrawal time exists. Finally, implementing similar transparent methods could have a positive impact on international harmonization and trade.}, number={3}, journal={REGULATORY TOXICOLOGY AND PHARMACOLOGY}, author={Baynes, RE and Martin-Jimenez, T and Craigmill, AL and Riviere, JE}, year={1999}, month={Jun}, pages={287–299} }
 @article{payne_craigmill_riviere_baynes_webb_sundlof_1999, title={The Food Animal Residue Avoidance Databank (Farad): Past, Present and Future}, volume={15}, ISSN={0749-0720}, url={http://dx.doi.org/10.1016/s0749-0720(15)30208-5}, DOI={10.1016/S0749-0720(15)30208-5}, abstractNote={The Food Animal Residue Avoidance Databank (FARAD) was created in 1982 as a cooperative state and federal educational outreach program. FARAD's mission has remained unchanged in the last fifteen years: to assist producers, veterinarians, and allied professionals in the production of animal foods free of illegal chemical contaminants. At its core, FARAD is a collection of databases that users can efficiently access with the assistance of program experts. In order to meet emerging challenges related to technical and trade issues in food safety, current FARAD projects include inter-species data extrapolation, novel kinetic modeling, and international information exchange.}, number={1}, journal={Veterinary Clinics of North America: Food Animal Practice}, publisher={Elsevier BV}, author={Payne, Michael A. and Craigmill, Arthur L. and Riviere, Jim E. and Baynes, Ronald E. and Webb, Alistair I. and Sundlof, Stephen F.}, year={1999}, month={Mar}, pages={75–88} }
 @article{baynes_riviere_1998, title={Influence of inert ingredients in pesticide formulations on dermal absorption of carbaryl}, volume={59}, number={2}, journal={American Journal of Veterinary Research}, author={Baynes, R. E. and Riviere, J. E.}, year={1998}, month={Feb}, pages={168–175} }
 @article{baynes_monteiro-riviere_qiao_riviere_1997, title={Cutaneous toxicity of the benzidine dye direct red 28 applied as mechanistically-defined chemical mixtures (MDCM) in perfused porcine skin}, volume={93}, ISSN={0378-4274}, url={http://dx.doi.org/10.1016/s0378-4274(97)00083-0}, DOI={10.1016/S0378-4274(97)00083-0}, abstractNote={Complex chemical mixtures at hazardous waste sites can potentially consist of a marker chemical and several other chemicals, each of which can have different modulating actions on the dermatotoxicity of the marker chemical and/or other components in the mixture. A total of 16 mixtures, consisting of a marker chemical direct red 28 (DR28), a solvent (80% acetone or DMSO in water), a surfactant (0 or 10% sodium lauryl sulfate, SLS), a vasodilator (0 or 180 μg methyl nicotinate, MN) and a reducing agent (0 or 2% stannous chloride, SnCl2) were selected. Isolated perfused porcine skin flaps (IPPSFs), which have been proven to be an in vitro model for assessing absorption and toxicity, were utilized. These mixtures did not cause severe dermatotoxicity. However, light microscopic observations depicted minor alterations (intracellular and intercellular epidermal edema) with DMSO mixtures than with acetone mixtures. The presence of SLS caused an alteration in the stratum corneum. Enzyme histochemical staining for alkaline phosphatase (ALP) and nonspecific esterase (NSE) revealed no significant treatment effects, but increased staining for acid phosphatase (ACP) in the stratum basale was significant when associated with SLS or SLS+MN in DMSO mixtures. At 8 h post-dose, only DMSO mixtures containing SL+MN, SL+SnCl2, or SLS+MN+SnCl2 significantly increased transepidermal water loss. In conclusion, this study demonstrated that various mixtures, especially those containing SLS alter the epidermal barrier differently with complex interactions occurring simultaneously.}, number={2-3}, journal={Toxicology Letters}, publisher={Elsevier BV}, author={Baynes, Ronald E and Monteiro-Riviere, Nancy A and Qiao, Gui L and Riviere, Jim E}, year={1997}, month={Dec}, pages={159–169} }
 @article{baynes_craigmill_riviere_1997, title={Residue avoidance after topical application of veterinary drugs and parasiticides}, volume={210}, number={9}, journal={Journal of the American Veterinary Medical Association}, author={Baynes, R. E. and Craigmill, A. L. and Riviere, Jim E.}, year={1997}, pages={1288–1289} }
 @article{baynes_halling_riviere_1997, title={The influence of diethyl-m-toluamide (DEET) on the percutaneous absorption of permethrin and carbaryl}, volume={144}, ISSN={["0041-008X"]}, DOI={10.1006/taap.1997.8156}, abstractNote={Simultaneous exposure to DEET and permethrin was recently proposed to be associated with the "Gulf War Syndrome." However, no studies have reported the percutaneous absorption of DEET and permethrin when applied simultaneously to the skin as a mixture, the relevant route of exposure in the Persian Gulf. The present study quantitates percutaneous absorption of DEET and permethrin after coadministration to rodent and pig skin in vitro. Dosing solutions were also prepared with either acetone, dimethyl sulfoxide (DMSO), or ethanol to compare vehicle effects on percutaneous absorption of permethrin and DEET. The influence of DEET on carbaryl absorption and dermal disposition was also assessed in pig studies to statistically demonstrate DEET effects in acetone or DMSO and different solvent concentrations. Topical application of permethrin + DEET resulted in absorption of DEET (1-20% dose), but no permethrin. Permethrin (1.2-1.7% dose) was detected only when mouse skin was dosed solely with permethrin, a finding suggesting that DEET decreased permethrin absorption. DEET also inhibited carbaryl absorption in acetone mixtures, but had no effect on DMSO mixtures. Irrespective of solvent, DEET did not enhance carbaryl penetration into skin. For DEET, absorption was greater in mouse skin (10.7-20.6% dose) than in rat skin (1.1-5.2% dose) and pig skin (2.8% dose). The extent of DEET absorption was greater with DMSO and acetone than with ethanol in rat and mouse skin. These studies support DEET, but not permethrin or carbaryl, as having sufficient systemic exposure to potentially cause signs of toxicity when simultaneously applied with pesticides. Furthermore, these studies demonstrated that DEET does not necessarily enhance dermal absorption of all toxicants as was originally hypothesized.}, number={2}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Baynes, RE and Halling, KB and Riviere, JE}, year={1997}, month={Jun}, pages={332–339} }
 @article{baynes_brownie_freeman_riviere_1996, title={In vitro percutaneous absorption of benzidine in complex mechanistically defined chemical mixtures}, volume={141}, ISSN={["0041-008X"]}, DOI={10.1006/taap.1996.0315}, abstractNote={Little work has been done on the topical absorption of the bladder carcinogen benzidine. Since humans are more likely to be exposed to chemical mixtures than to a single chemical, a program was developed in these laboratories to examine the cumulative effect of complex mixtures on percutaneous absorption of important toxicants such as benzidine. In this investigation, a mixture is defined as a physical combination consisting of a marker chemical and several other chemicals, each of which can have independent and/or synergistic effects on dermal penetration and absorption of the marker chemical. Ten mixtures, consisting of a marker chemical (benzidine, B), a solvent (acetone, A or DMSO, D), a surfactant (0 or 10% sodium lauryl sulfate, SL), a vasodilator (0 or 180 microg methyl nicotinate, M), and a reducing agent (0 or 2% SnCl2, s) were employed in this study. Isolated perfused porcine skin flaps (IPPSFs), which have proven to be a suitable in vitro model for assessing dermal absorption and toxicity, and flow-through diffusion cell systems were utilized. The extent of benzidine absorption in skin sections dosed with either B + A (0.94% dose) or B + D (1.01% dose) was similar to that when IPPSFs were dosed with either B + A (0.54% dose) or B + D (1.31% dose). However, flux vs time profiles were different when the two in vitro methods were compared. For mixtures containing (1) DMSO only or acetone only or (2) solvents containing SL + M, benzidine absorption was enhanced when compared with other mixtures. Compared to acetone, DMSO appears to enhance dermal penetration of benzidine in most of the mixtures. Compared to other mixtures evaluated, SnCl2 inhibited benzidine absorption irrespective of solvent present. SnCl2 also appears to inhibit benzidine penetration in DMSO mixtures containing SL only, but not in acetone mixtures. It is proposed that chemical-chemical interactions between benzidine and SnCl2 may be inhibiting benzidine absorption and chemical-biological interactions between M + SL and skin may be enhancing benzidine absorption. Across all mixtures, maximum observed benzidine absorption was almost 3% of the topical dose over 8 hr, but maximum penetration was 22% over the same time period which would suggest a potential for greater systemic exposure over longer time frames. This work underscores the need to study potentially toxic chemicals in mixture exposure scenarios since the interactions observed would confound risk assessment based on single chemical data.}, number={2}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Baynes, RE and Brownie, C and Freeman, H and Riviere, JE}, year={1996}, month={Dec}, pages={497–506} }
 @inbook{xia_baynes_riviere, title={A novel system coefficient approach for systematic assessment of dermal absorption from chemical mixtures}, ISBN={0415700361}, booktitle={Dermal absorption models in toxicology and pharmacology}, publisher={New York: Taylor and Francis / CRC Press}, author={Xia, X. R. and Baynes, R. E. and Riviere, J. E.}, pages={69–86} }
 @article{bublitz_mzyk_mays_fajt_hairgrove_baynes, title={Comparative urine residues of flunixin and meloxicam in show goats}, volume={41}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Bublitz, C. M. and Mzyk, D. A. and Mays, T. and Fajt, V. R. and Hairgrove, T. and Baynes, R. E.}, pages={24–24} }
 @article{monteiro-riviere_baynes_riviere, title={Epidermal cytotoxicity of topically-applied chemical mixtures in porcine skin}, volume={20}, number={1997}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Monteiro-Riviere, N. A. and Baynes, R. and Riviere, J.}, pages={255–256} }
 @inproceedings{martin-jimenez_baynes_craigmill_riviere, title={Extralabel Withdrawal-interval Estimator (EWE) algorithm. An automated approach to establishing extralabel withdrawal times}, volume={11}, booktitle={Proceedings of the 11th Biennial Symposium of American Acadamic Veterinary Pharmacologic Therapeutics}, author={Martin-Jimenez, T. and Baynes, R. and Craigmill, A. and Riviere, J.}, pages={49–63} }
 @misc{baynes_dedonder_kissell_mzyk_marmulak_smith_tell_gehring_davis_riviere, title={Health concerns and management of select veterinary drug residues}, volume={88}, journal={Food and Chemical Toxicology}, author={Baynes, R. E. and Dedonder, K. and Kissell, L. and Mzyk, D. and Marmulak, T. and Smith, G. and Tell, L. and Gehring, R. and Davis, J. and Riviere, J. E.}, pages={112–122} }
 @article{mzyk_bublitz_martinez_davis_baynes_smith, title={Impact of bovine respiratory disease on the pharmacokinetics of danofloxacin and tulathromycin in different ages of calves}, volume={41}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Mzyk, D. A. and Bublitz, C. M. and Martinez, M. N. and Davis, J. L. and Baynes, R. E. and Smith, G. W.}, pages={33–33} }
 @misc{riviere_xia_baynes_monteiro-riviere, title={Method and apparatus for determining a molecular descriptor of absorption for a candidate compound}, volume={7,517,693}, number={2009 Apr. 14}, author={Riviere, J. E. and Xia, X. R. and Baynes, R. E. and Monteiro-Riviere, N. A.} }
 @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} }
 @book{riviere_monteiro-riviere_baynes, title={Percutaneous absorption of chemical mixtures relevant to the Gulf War}, journal={Technical report USAMRMC DAMD 17-99C-9047}, author={Riviere, J. E. and Monteiro-Riviere, N. A. and Baynes, R. E.}, pages={1–162} }
 @book{riviere_baynes_monteiro-riviere, title={Percutaneous absorption of chemical mixtures relevant to the Gulf War}, journal={USAMRMC, DAMD17-99C-9047. Technical Report ADB253401}, author={Riviere, J. E. and Baynes, R. E. and Monteiro-Riviere, N. A.}, pages={1–30} }
 @book{riviere_baynes_monteiro-riviere, title={Percutaneous absorption of chemical mixtures relevant to the Gulf War. II.}, journal={Technical report ADB, USAMRMC, DAMD17-99-C-9047}, author={Riviere, J. E. and Baynes, R. E. and Monteiro-Riviere, N. A.}, pages={1–34} }
 @book{riviere_baynes_monteiro-riviere, title={Quantitating absorption of complex chemical mixtures}, journal={Final report, CDC OH 007555}, institution={Atlanta: Center for Disease Control}, author={Riviere, J. E. and Baynes, R. E. and Monteiro-Riviere, N. A.}, pages={1–27} }
 @book{riviere_baynes_smith_monteiro-riviere, title={Quantitating the percutaneous absorption of mechanistically defined chemical mixtures}, journal={NTIS report, AFOSR GF 49620-98-1-0105}, author={Riviere, J. E. and Baynes, R. E. and Smith, C. E. and Monteiro-Riviere, N. A.}, pages={1–109} }
 @book{riviere_montiero-riviere_baynes_xia_smith, title={Quantitating the percutaneous absorption of mechanistically-defined chemical mixtures}, volume={34}, author={Riviere, J. E. and Montiero-Riviere, N. A. and Baynes, R. E. and Xia, X. R. and Smith, C. E.}, pages={1} }
 @misc{dedonder_gehring_riviere_baynes_tell_vickroy, title={Residue concerns following exposure of livestock to oil and petroleum products}, volume={248}, number={2}, journal={Journal of the American Veterinary Medical Association}, author={DeDonder, K. D. and Gehring, R. and Riviere, J. E. and Baynes, R. E. and Tell, L. A. and Vickroy, T. W.}, pages={145–146} }
 @article{mason_suyemoto_baynes_almond, title={Stability and bioactivity of tetracycline hydrochloride water medication in a swine production unit}, volume={19}, number={2}, journal={Journal of Swine Health and Production}, author={Mason, S. E. and Suyemoto, M. and Baynes, R. and Almond, G.}, pages={107–111} }
 @book{rbaynes_riviere, title={Strategies for reducing drug and chemical residues in food animals: International approaches to residue avoidance, management, and testing}, publisher={Hoboken, New Jersey: Wiley} }
 @inbook{riviere_baynes, title={Veterinary dermal absorption and toxicity assessment}, ISBN={0824701542}, booktitle={Dermal absorption and toxicity assessment}, publisher={New York: Marcel Dekker}, author={Riviere, J. E. and Baynes, R.}, pages={625–645} }