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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.

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.

There is no FDA approved therapy for the treatment of celiac disease (CeD), aside from avoidance of dietary gluten. Larazotide acetate (LA) is a first in class oral peptide developed as a tight junction regulator, which is a lead candidate for management of CeD. A delayed release formulation was tested in vitro and predicted release in the mid duodenum and jejunum, the target site of CeD. The aim of this study was to follow the concentration versus time profile of orally administered LA in the small intestine using a porcine model. A sensitive liquid chromatography/tandem mass spectrometry method was developed to quantify LA concentrations in porcine intestinal fluid samples. Oral dosing of LA (1 mg total) in overnight fasted pigs resulted in time dependent appearance of LA in the distal duodenum and proximal jejunum. Peak LA concentrations (0.32–1.76 μM) occurred at 1 hour in the duodenum and in proximal jejunum following oral dosing, with the continued presence of LA (0.02–0.47 μM) in the distal duodenum and in proximal jejunum (0.00–0.43 μM) from 2 to 4 hours following oral dosing. The data shows that LA is available in detectable concentrations at the site of CeD.

Background The objective of this study was to determine the renal clearance of flunixin and meloxicam in pigs and compare plasma and urine concentrations and tissue residues. Urine clearance is important for livestock show animals where urine is routinely tested for these drugs. Fourteen Yorkshire/Landrace cross pigs were housed in individual metabolism cages to facilitate urine collection. This is a unique feature of this study compared to other reports. Animals received either 2.2 mg/kg flunixin or 0.4 mg/kg meloxicam via intramuscular injection and samples analyzed by mass spectrometry. Pigs were euthanized when drugs were no longer detected in urine and liver and kidneys were collected to quantify residues. Results Drug levels in urine reached peak concentrations between 4 and 8 h post-dose for both flunixin and meloxicam. Flunixin urine concentrations were higher than maximum levels in plasma. Urine concentrations for flunixin and meloxicam were last detected above the limit of quantification at 120 h and 48 h, respectively. The renal clearance of flunixin and meloxicam was 4.72 ± 2.98 mL/h/kg and 0.16 ± 0.04 mL/h/kg, respectively. Mean apparent elimination half-life in plasma was 5.00 ± 1.89 h and 3.22 ± 1.52 h for flunixin and meloxicam, respectively. Six of seven pigs had detectable liver concentrations of flunixin (range 0.0001–0.0012 µg/g) following negative urine samples at 96 and 168 h, however all samples at 168 h were below the FDA tolerance level (0.03 µg/g). Meloxicam was detected in a single liver sample (0.0054 µg/g) at 72 h but was below the EU MRL (0.065 µg/g). Conclusions These data suggest that pigs given a single intramuscular dose of meloxicam at 0.4 mg/kg or flunixin at 2.2 mg/kg are likely to have detectable levels of the parent drug in urine up to 2 days and 5 days, respectively, after the first dose, but unlikely to have tissue residues above the US FDA tolerance or EU MRL following negative urine testing. This information will assist veterinarians in the therapeutic use of these drugs prior to livestock shows and also inform livestock show authorities involved in testing for these substances.

OBJECTIVE: To evaluate tissue levels, safety, and efficacy of topical ophthalmic 0.5% and 1% pirfenidone in decreasing subconjunctival fibrosis. ANIMAL STUDIED: Twelve normal beagle dogs PROCEDURES: A 5 × 1 mm diameter silicone disk was implanted subconjunctivally in one eye, and then dogs were treated with topical 0.5% pirfenidone (n = 9) in artificial tears or artificial tears alone (n = 3) for 28 days. To evaluate tissue drug levels, a single sample of tears, conjunctiva, and aqueous humor was collected 30 (n = 3), 90 (n = 3), and 180 min (n = 3) following administration of the last drop of pirfenidone, respectively. Fibrous capsule thickness and staining for Ki67 and fibroblast activation protein alpha (FAPα) were evaluated histologically. After a 2‐week washout, the experiment was repeated in the opposite eye and using 1% pirfenidone. RESULTS: Treatment with pirfenidone resulted in thinner fibrous capsules and decreased staining for FAPα with no adverse effects. The implant in one dog treated with pirfenidone extruded. There was no difference in tissue levels, capsular thickness, or staining for Ki67 or FAPα between dogs treated with 0.5% or 1% pirfenidone. CONCLUSIONS: Pirfenidone may decrease fibrosis following glaucoma shunt surgery and can potentially be used indefinitely due to minimal side effects.

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.

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 dial...

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

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.

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].

Identifying individual genetic variation in drug metabolism pathways is of importance not only in livestock, but also in humans in order to provide the ultimate goal of giving the right drug at the right dose at the right time. Our objective was to identify individual genes and gene networks involved in metabolizing fenbendazole (FBZ) and flunixin meglumine (FLU) in swine liver. The population consisted of female and castrated male pigs that were sired by boars represented by 4 breeds. Progeny were randomly placed into groups: no drug (UNT), FLU or FBZ administered. Liver transcriptome profiles from 60 animals with extreme (i.e. fast or slow drug metabolism) pharmacokinetic (PK) profiles were generated from RNA sequencing. Multiple cytochrome P450 (CYP1A1, CYP2A19 and CYP2C36) genes displayed different transcript levels across treated versus UNT. Weighted gene co-expression network analysis identified 5 and 3 modules of genes correlated with PK parameters and a portion of these were enriched for biological processes relevant to drug metabolism for FBZ and FLU, respectively. Genes within identified modules were shown to have a higher transcript level relationship (i.e. connectivity) in treated versus UNT animals. Investigation into the identified genes would allow for greater insight into FBZ and FLU metabolism.

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.

Occupational and environmental exposures to chemicals are major potential routes of exposure for direct skin toxicity and for systemic absorption. The majority of these exposures are to complex mixtures, yet most experimental studies to assess topical chemical absorption are conducted neat or in simple aqueous vehicles. A component of many industrial mixtures is surfactants that solubilize ingredients and stabilize mixtures of oily components when present in aqueous vehicles. The purpose of this series of experiments was to use two well-developed experimental techniques to assess how solution interactions present in a pure nonbiological in vitro system (membrane coated fibers, MCF) compare to those seen in a viable ex vivo biological preparation (isolated perfused porcine skin flap, IPPSF). Two widely encountered anionic surfactants, sodium lauryl sulfate (SLS) and linear alkylbenzene sulfonate (LAS), were studied in 10% solutions. The rank orders of absorption were: water: pentachlorophenol (PCP) > 4-nitrophenol (PNP) > parathion > fenthion > simazine > propazine; SLS: PNP > PCP > parathion > simazine > fenthion > propazine; and LAS: PNP > PCP > simazine > parathion > fenthion > propazine. For all penetrants, absorption was greater in SLS compared to LAS mixtures, a finding consistent with smaller micelle sizes seen with SLS. For these low-water-solubility compounds, absorption was greater from aqueous solutions in nearly every case. The inert three-fiber MCF array predicted absorptive fluxes seen in the ex vivo IPPSF, suggesting lack of any biological effects of the surfactants on skin.

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.

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+vV where 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.

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.

Objective—To determine the elimination kinetics of ceftiofur hydrochloride in milk after intramammary administration in lactating dairy cows. Design—Prospective study. Animals—5 lactating dairy cows. Procedure—After collection of baseline milk samples, 300 mg (6 mL) of ceftiofur was infused into the left front and right rear mammary gland quarters of each cow. Approximately 12 hours later, an additional 300 mg of ceftiofur was administered into the same mammary gland quarters after milking. Milk samples were collected from each mammary gland quarter every 12 hours for 10 days. Concentrations of ceftiofur and its metabolites in each milk sample were determined to assess the rate of ceftiofur elimination. Results—Although there were considerable variations among mammary gland quarters and individual cows, ceftiofur concentrations in milk from all treated mammary gland quarters were less than the tolerance (0.1 µg/mL) set by the FDA by 168 hours (7 days) after the last intramammary administration of ceftiofur. No drug concentrations were detected in milk samples beyond this period. Ceftiofur was not detected in any milk samples from nontreated mammary gland quarters throughout the study. Conclusions and Clinical Relevance—Ceftiofur administered by the intramammary route as an extralabel treatment for mastitis in dairy cows reaches concentrations in milk greater than the tolerance set by the FDA. Results indicated that milk from treated mammary gland quarters should be discarded for a minimum of 7 days after intramammary administration of ceftiofur. Elimination of ceftiofur may be correlated with milk production, and cows producing smaller volumes of milk may have prolonged withdrawal times. (J Am Vet Med Assoc 2004;224:1827–1830)

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 stimulant 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 micrograms/cm2/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.

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 micro g/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 x 10(-5)+/-0.54 x 10(-5) cm/h.

Every year, 10 million workers are exposed to metalworking fluids (MWFs) that may be toxic. There are four types of MWFs: neat oils and three water-based MWFs (soluble oil, semisynthetic and synthetic), which are diluted with water and whose composition varies according to the mineral oils ratio. MWFs also contain various additives. To determine the absorption of six amines used as corrosion inhibitors and biocides in MWFs, porcine skin flow-through diffusion cell experiments were conducted with hydrophilic ethanolamines (mono-, di- and triethanolamine, MEA, DEA and TEA respectively) and a mixture of lipophilic amines (dibutylethanolamine, dicyclohexylamine and diphenylamine). The six amines were dosed in four vehicles (water and three generic water-based MWF formulations) and analyzed using a scintillation counter or gas chromatography/mass spectrometry. These 24 h studies showed that dermal absorption significantly (P0.05) increased from water for the six amines (e.g. 1.15 ± 0.29% dose; DEA in water) compared to other formulations (e.g. 0.13 ± 0.01% dose; DEA in semisynthetic MWF) and absorption was greatest for dibutylethanolamine in all the formulations. The soluble oil formulation tended to increase the dermal absorption of the hydrophilic amines. The permeability coefficient was significantly higher (P0.05) with TEA relative to the other hydrophilic amines (e.g. 4.22 × 10(-4) ± 0.53 × 10(-4) cm h(-1) [TEA in synthetic MWF] vs. 1.23 × 10(-4) ± 0.10 × 10(-4) cm h(-1) [MEA in synthetic MWF]), except for MEA in soluble oil formulation. Future research will confirm these findings in an in vivo pig model along with dermatotoxicity studies. These results should help MWF industries choose safer additives for their formulations to protect the health of metalworkers.

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 14 C-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.

This is an abstract concerning: Stereselective Absorption of Permethrin Through Silastic Membrane and Excised Porcine Skin In Vitro Flow Through Diffusion System.