@article{holland_fogle_blikslager_curling_barlow_schirmer_davis_2014, title={Pharmacokinetics and pharmacodynamics of three formulations of firocoxib in healthy horses}, volume={38}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/jvp.12177}, DOI={10.1111/jvp.12177}, abstractNote={The objectives of this study were to compare the pharmacokinetics and COX selectivity of three commercially available formulations of firocoxib in the horse. Six healthy adult horses were administered a single dose of 57 mg intravenous, oral paste or oral tablet firocoxib in a three‐way, randomized, crossover design. Blood was collected at predetermined times for PGE2 and TXB2 concentrations, as well as plasma drug concentrations. Similar to other reports, firocoxib exhibited a long elimination half‐life (31.07 ± 10.64 h), a large volume of distribution (1.81 ± 0.59L/kg), and a slow clearance (42.61 ± 11.28 mL/h/kg). Comparison of the oral formulations revealed a higher Cmax, shorter Tmax, and greater AUC for the paste compared to the tablet. Bioavailability was 112% and 88% for the paste and tablet, respectively. Maximum inhibition of PGE2 was 83.76% for the I.V. formulation, 52.95% for the oral paste formulation, and 46.22% for the oral tablet formulation. Pharmacodynamic modeling suggests an IC50 of approximately 27 ng/mL and an IC80 of 108 ng/ mL for COX2 inhibition. Inhibition of TXB2 production was not detected. This study indicates a lack of bioequivalence between the oral formulations of firocoxib when administered as a single dose to healthy horses.}, number={3}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Holland, B. and Fogle, C. and Blikslager, A. T. and Curling, A. and Barlow, B. M. and Schirmer, J. and Davis, J. L.}, year={2014}, month={Nov}, pages={249–256} }
 @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{davis_kruger_lafevers_barlow_schirmer_breuhaus_2014, title={Effects of quinapril on angiotensin converting enzyme and plasma renin activity as well as pharmacokinetic parameters of quinapril and its active metabolite, quinaprilat, after intravenous and oral administration to mature horses}, volume={46}, ISSN={["2042-3306"]}, DOI={10.1111/evj.12206}, abstractNote={SummaryReasons for performing studyAngiotensin converting enzyme (ACE) inhibitors improve survival and quality of life in human patients and small animals with cardiovascular and renal disease. There is limited information regarding their effects in horses.ObjectivesThe purpose of this study was to determine the pharmacokinetics of quinapril and its effects on ACE and renin in horses.Study designExperimental study using healthy mature horses.MethodsSix healthy horses were administered quinapril at 120 mg i.v., 120 mg per os and 240 mg per os in a 3‐way crossover design. Blood was collected for measurement of quinapril and quinaprilat concentrations using ultra‐high pressure liquid chromatography with mass spectrometry. Angiotensin converting enzyme activity and renin activity were measured using a radioenzymatic assay. Noncompartmental pharmacokinetic modelling and statistical analyses were performed.ResultsNo adverse effects were observed during the study period. Intravenous and oral administration significantly inhibited ACE activity. Renin concentrations increased in all groups, but this increase was not statistically significant. Following i.v. administration of quinapril, mean terminal half‐life was 0.694 h and 1.734 h for quinapril and quinaprilat, respectively. The mean volume of distribution and clearance for quinapril were 0.242 l/kg bwt and 11.93 ml/kg bwt/min, respectively. Maximum concentration for quinaprilat was 145 ng/ml at 0.167 h. Bioavailability of quinapril following oral administration was <5%. Quinaprilat was detected in all horses following oral administration of quinapril; however, it was below the limit of quantification of the assay (2.5 ng/ml) for most horses in the 120 mg dosing group.ConclusionsThese results suggest that, despite low plasma concentrations, quinapril has sufficient oral absorption to produce inhibition of ACE in healthy horses. Controlled studies in clinically affected horses are indicated. Quinapril provides a potential treatment alternative for horses with cardiovascular and renal disease.}, number={6}, journal={EQUINE VETERINARY JOURNAL}, author={Davis, J. L. and Kruger, K. and LaFevers, D. H. and Barlow, B. M. and Schirmer, J. M. and Breuhaus, B. A.}, year={2014}, month={Nov}, pages={729–733} }
 @article{newman_prange_jennings_barlow_davis_2013, title={Pharmacokinetics of tobramycin following intravenous, intramuscular, and intra-articular administration in healthy horses}, volume={36}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12048}, abstractNote={The objectives of this study were to examine the pharmacokinetics of tobramycin in the horse following intravenous (IV), intramuscular (IM), and intra‐articular (IA) administration. Six mares received 4 mg/kg tobramycin IV, IM, and IV with concurrent IA administration (IV+IA) in a randomized 3‐way crossover design. A washout period of at least 7 days was allotted between experiments. After IV administration, the volume of distribution, clearance, and half‐life were 0.18 ± 0.04 L/kg, 1.18 ± 0.32 mL·kg/min, and 4.61 ± 1.10 h, respectively. Concurrent IA administration could not be demonstrated to influence IV pharmacokinetics. The mean maximum plasma concentration (Cmax) after IM administration was 18.24 ± 9.23 μg/mL at 1.0 h (range 1.0–2.0 h), with a mean bioavailability of 81.22 ± 44.05%. Intramuscular administration was well tolerated, despite the high volume of drug administered (50 mL per 500 kg horse). Trough concentrations at 24 h were below 2 μg/mL in all horses after all routes of administration. Specifically, trough concentrations at 24 h were 0.04 ± 0.01 μg/mL for the IV route, 0.04 ± 0.02 μg/mL for the IV/IA route, and 0.02 ± 0.02 for the IM route. An additional six mares received IA administration of 240 mg tobramycin. Synovial fluid concentrations were 3056.47 ± 1310.89 μg/mL at 30 min after administration, and they persisted for up to 48 h with concentrations of 14.80 ± 7.47 μg/mL. Tobramycin IA resulted in a mild chemical synovitis as evidenced by an increase in synovial fluid cell count and total protein, but appeared to be safe for administration. Monte Carlo simulations suggest that tobramycin would be effective against bacteria with a minimum inhibitory concentration (MIC) of 2 μg/mL for IV administration and 1 μg/mL for IM administration based on Cmax:MIC of 10.}, number={6}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Newman, J. C. and Prange, T. and Jennings, S. and Barlow, B. M. and Davis, J. L.}, year={2013}, month={Dec}, pages={532–541} }
 @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{messenger_davis_lafevers_barlow_posner_2011, title={Intravenous and sublingual buprenorphine in horses: pharmacokinetics and influence of sampling site}, volume={38}, ISSN={["1467-2995"]}, DOI={10.1111/j.1467-2995.2011.00613.x}, abstractNote={OBJECTIVE
To describe the pharmacokinetics and adverse effects of intravenous (IV) and sublingual (SL) buprenorphine in horses, and to determine the effect of sampling site on plasma concentrations after SL administration.


STUDY DESIGN
Randomized crossover experiment; prospective study.


ANIMALS
Eleven healthy adult horses between 6 and 20 years of age and weighing 487-592 kg.


METHODS
In the first phase; buprenorphine was administered as a single IV or SL dose (0.006 mg kg(-1)) and pharmacokinetic parameters were determined for each route of administration using a noncompartmental model. In the second phase; the jugular and lateral thoracic veins were catheterized for simultaneous venous blood sampling, following a dose of 0.006 mg kg(-1) SL buprenorphine. For both phases, plasma buprenorphine concentrations were measured using ultra-performance liquid chromatography with mass spectrometry. At each sampling period, horses were assessed for behavioral excitement and gastrointestinal motility.


RESULTS
Following IV administration, buprenorphine mean ± SD half-life was 5.79 ± 1.09 hours. Systemic clearance (Cl) following IV administration was 6.13 ± 0.86 mL kg(-1) minute(-1) and volume of distribution at steady-state was 3.16 ± 0.65 L kg(-1). Following IV administration, horses showed signs of excitement. Gastrointestinal sounds were decreased following both routes of administration; however, none of the horses exhibited signs of colic. There was a significant discrepancy between plasma buprenorphine concentrations measured in the jugular vein versus the lateral thoracic vein following phase 2, thus pharmacokinetic parameters following SL buprenorphine are not reported.


CONCLUSIONS AND CLINICAL RELEVANCE
Buprenorphine has a long plasma half-life and results in plasma concentrations that are consistent with analgesia in other species for up to 4 hours following IV administration of this dose in horses. While buprenorphine is absorbed into the circulation following SL administration, jugular venous sampling gave a false measurement of the quantity absorbed and should not be used to study the uptake from SL administration.}, number={4}, journal={VETERINARY ANAESTHESIA AND ANALGESIA}, author={Messenger, Kristen M. and Davis, Jennifer L. and LaFevers, Douglas H. and Barlow, Beth M. and Posner, Lysa P.}, year={2011}, month={Jul}, pages={374–384} }
 @article{davis_messenger_lafevers_barlow_posner_2011, title={Pharmacokinetics of intravenous and intramuscular buprenorphine in the horse}, volume={35}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2011.01284.x}, abstractNote={Davis, J. L., Messenger, K. M., LaFevers, D. H., Barlow, B. M., Posner, L. P. Pharmacokinetics of intravenous and intramuscular buprenorphine in the horse.J. vet. Pharmacol. Therap. 35, 52–58.The purpose of this study was to determine the pharmacokinetics of buprenorphine following intravenous (i.v.) and intramuscular (i.m.) administration in horses. Six horses received i.v. or i.m. buprenorphine (0.005 mg/kg) in a randomized, crossover design. Plasma samples were collected at predetermined times and horses were monitored for adverse reactions. Buprenorphine concentrations were measured using ultra‐performance liquid chromatography with electrospray ionization mass spectrometry. Following i.v. administration, clearance was 7.97 ± 5.16 mL/kg/min, and half‐life (T1/2) was 3.58 h (harmonic mean). Volume of distribution was 3.01 ± 1.69 L/kg. Following i.m. administration, maximum concentration (Cmax) was 1.74 ± 0.09 ng/mL, which was significantly lower than the highest measured concentration (4.34 ± 1.22 ng/mL) after i.v. administration (P < 0.001). Time to Cmaxwas 0.9 ± 0.69 h andT1/2was 4.24 h. Bioavailability was variable (51–88%). Several horses showed signs of excitement. Gut sounds were decreased 10 ± 2.19 and 8.67 ± 1.63 h in the i.v. and i.m. group, respectively. Buprenorphine has a moderateT1/2in the horse and was detected at concentrations expected to be therapeutic in other species after i.v. and i.m. administration of 0.005 mg/kg. Signs of excitement and gastrointestinal stasis may be noted.}, number={1}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Davis, J.L. and Messenger, K.M. and Lafevers, D.H. and Barlow, B.M. and Posner, L.P.}, year={2011}, month={Mar}, pages={52–58} }
 @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 (11.12 h) 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 9.44 h 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 4 days 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{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
Objective—To determine elimination kinetics of tilmicosin in milk following intramammary administration in lactating dairy cattle.
Design—Prospective pharmacokinetic study.
Animals—6 lactating dairy cows.
Procedures—Following collection of baseline milk samples, 1,200 mg (4 mL) of tilmicosin was infused into the left front and right rear mammary glands of each cow. Approximately 12 hours later, an additional 1,200 mg of tilmicosin was infused into the left front and right rear glands after milking. Milk samples were then collected from each gland at milking time for 40 days. Concentration of tilmicosin was determined by means of ultraperformance liquid chromatography–mass spectrometry, and a milk withdrawal interval for tilmicosin was calculated on the basis of the tolerance limit method.
Results—Although there was considerable variation between glands, concentration of tilmicosin was high in milk from treated glands and had a long half-life in treated and untreated glands. Tilmicosin was detected in all treated glands for the entire 40-day study period and was detected in untreated glands for approximately 30 to 35 days.
Conclusions and Clinical Relevance—Findings indicated that tilmicosin should not be administered by the intramammary route in lactating dairy cows. Milk from all glands of any cows accidentally treated should be discarded for a minimum of 82 days following intramammary administration.}, 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{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{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{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{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{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{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_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} }