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Firefighters face significant risks of exposure to toxic chemicals, such as polycyclic aromatic hydrocarbons (PAHs), during fire suppression activities. PAHs have been found in the air, on the gear and equipment, and in biological samples such as the skin, breath, urine, and blood of firefighters after fire response. However, the extent to which exposure occurs via inhalation, dermal absorption, or ingestion is unclear. In this study, three PAHs, naphthalene, phenanthrene, and benzo[a]pyrene, were applied to porcine skin in vitro in an artificial sweat solution to better gauge firefighters’ dermal exposures while mimicking their sweaty skin conditions using an artificial sweat dosing vehicle. Multiple absorption characteristics were calculated, including cumulative absorption, percent dose absorbed, diffusivity, flux, lag time, and permeability. The absorption of the PAHs was greatly influenced by their molecular weight and solubility in the artificial sweat solution. Naphthalene had the greatest dose absorption efficiency (35.0 ± 4.6% dose), followed by phenanthrene (6.8 ± 3.2% dose), and lastly, benzo[a]pyrene, which had the lowest absorption (0.03 ± 0.04% dose). The lag times followed a similar trend. All chemicals had a lag time of approximately 60 min or longer, suggesting that chemical concentrations on the skin may be reduced by immediate skin cleansing practices after fire exposure.

ABSTRACT: 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.

Abstract 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.

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.

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.

Porcine reproductive and respiratory syndrome viruses (PRRSV) are responsible for one of the most economically important diseases affecting the global pig industry. On-farm high-efficiency particulate air (HEPA) filtration systems can effectively reduce airborne transmission of PRRSV and the incidence of PRRS, but they are costly, and their adoption is limited. Therefore, there is a need for low-cost alternatives, such as antimicrobial filters impregnated with antiviral nanoparticles (AVNP). During the past 10 years, tailored intermetallic/multi-elemental AVNP compositions have demonstrated effective performance against human viruses. In this study, a panel of five AVNP was evaluated for viricidal activity against PRRSV. Three AVNP materials: AVNP2, copper nanoparticles (CuNP), and copper oxide nanoparticles (CuONP), were shown to exert a significant reduction (>99.99%) in virus titers at 1.0% (w/v) concentration. Among the three, CuNP was the most effective at lower concentrations. Further experiments revealed that AVNP generated significant reductions in viral titers within just 1.5 min. For an optimal reduction in viral titers, direct contact between viruses and AVNP was required. This was further explained by the inert nature of these AVNP, where only negligible leaching concentrations of Ag/Cu ions (0.06–4.06 ppm) were detected in AVNP supernatants. Real-time dynamic light scatting (DLS) and transmission electron microscopic (TEM) analyses suggested that the mono-dispersive hydrodynamic behavior of AVNPs may have enhanced their antiviral activity against PRRSV. Collectively, these data support the further evaluation of these AVNP as candidate nanoparticles for incorporation into antimicrobial air-filtration systems to reduce transmission of PRRSV and other airborne pathogens.

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.

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.