Abstract
A large percentage of flunixin, a nonsteroidal anti-inflammatory drug widely used for treating livestock, is excreted in intact form and thus potentially available for environmental transport. As the fate of flunixin in the environment is unknown, our objective was to quantify sorption, desorption, and transformation in five agricultural soils and manure using batch equilibrium methods. Concentrations of flunixin and degradation products were determined by high performance liquid chromatography time of flight mass spectrometry. For all studied soils, sorption of flunixin exhibited linear character, with both linear and Freundlich models providing adequate fit. Linear sorption coefficients varied from 8 to 112 L kg−1. The strongest Pearson correlations with sorption coefficients were for clay content (r = 0.8693), total nitrogen (r = 0.7998), and organic carbon (r = 0.6291). Desorption of the reversibly bound fraction (3–10% of total sorbed flunixin) from all five studied soils exhibited non-hysteretic character suggesting low affinity of this fraction of flunixin to soil. Flunixin degradation in soils was relatively slow, exhibiting half-lives of 39–203 days, thus providing time for off-site transport and environmental contamination. The biological impacts of flunixin at environmentally relevant concentrations must be determined given its environmental behavior and extensive use as a nonsteroidal anti-inflammatory drug in livestock.
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References
Al-Khazrajy OS, Boxall A (2016) Impacts of compound properties and sediment characteristics on the sorption behaviour of pharmaceuticals in aquatic systems. J Hazard Mater 317:198–209. https://doi.org/10.1016/j.jhazmat.2016.05.065
Azzouz A, Ballesteros E (2013) Influence of seasonal climate differences on the pharmaceutical, hormone and personal care product removal efficiency of a drinking water treatment plant. Chemosphere 93:2046–2054. https://doi.org/10.1016/j.chemosphere.2013.07.037
Baert K, Backer P (2003) Comparative pharmacokinetics of three non-steroidal anti-inflammatory drugs in five bird species. Comp Biochem Physiol C Toxicol Pharmacol 134:25–33. https://doi.org/10.1016/S1532-0456(02)00184-9
Barker SA (2008) Drug contamination of the equine racetrack environment: a preliminary examination. J Vet Pharmacol Ther 31:466–471. https://doi.org/10.1111/j.1365-2885.2008.00978.x
Batrawi N, Naseef-Shtaya H, Al-Rimawi F (2017) Development and validation of a stability-indicating HPLC method for the simultaneous determination of florfenicol and flunixin meglumine combination in an injectable solution. J Anal Methods Chem 2017:7. https://doi.org/10.1155/2017/1529280
Bhadra B, Seo P, Jhung S (2016) Adsorption of diclofenac sodium from water using oxidized activated carbon. Chem Eng J 301:27–34. https://doi.org/10.1016/j.cej.2016.04.143
Biel-Maeso M, González-González C, Lara-Martin PA, Corada-Fernández C (2019) Sorption and degradation of contaminants of emerging concern in soils under aerobic and anaerobic conditions. Sci Total Environ 666:662–671. https://doi.org/10.1016/j.scitotenv.2019.02.279
Borisover M (2018) Accumulated Gibbs free energy as a quantitative measure of desorption hysteresis associated with the formation of metastable states. Chemosphere 215:490–499. https://doi.org/10.1016/j.chemosphere.2018.10.051
Bublitz CM, Mzyk DA, Mays T, Fajt VR, Hairgrove T, Baynes RE (2019) Comparative plasma and urine concentrations of flunixin and meloxicam in goats. Small Rumin Res 174:40–46. https://doi.org/10.1016/j.smallrumres.2019.01.013
Bui T, Choi H (2010) Influence of ionic strength, anions, cations, and natural organic matter on the adsorption of pharmaceuticals to silica. Chemosphere 80:681–686. https://doi.org/10.1016/j.chemosphere.2010.05.046
Cuthbert R, Parry-Jones J, Green R, Pain D (2007) NSAIDs and scavenging birds: potential impacts beyond Asia’s critically endangered vultures. Biol Lett 3:90–93. https://doi.org/10.1098/rsbl.2006.0554
Day P (1956) Report of the committee on physical analyses, 1954–55, soil science Society of America. Soil Sci Soc Am J 20:167–169. https://doi.org/10.2136/sssaj1956.03615995002000020007x
De Oliveira T, Guegan R (2016) Coupled organoclay/micelle action for the adsorption of diclofenac. Environ Sci Technol 50:10209–10215. https://doi.org/10.1021/acs.est.6b03393
Drillia P, Stamatelatou K, Lyberatos G (2005) Fate and mobility of pharmaceuticals in solid matrices. Chemosphere 60:1034–1044. https://doi.org/10.1016/j.chemosphere.2005.01.032
EMEA (1999) Committee for the veterinary medicinal products. Flunixin - summary report. The European agency for the evaluation of medicinal products, veterinary medicines evaluation unit. 661/99. London, UK
Facey SJ, Nebel BA, Kontny L, Allgaier M, Hauer B (2017) Rapid and complete degradation of diclofenac by native soil microorganisms. Environ Technol Innov 10:55–61. https://doi.org/10.1016/j.eti.2017.12.009
Galbraith EA, Mckellar Q (1996) Protein binding and in vitro serum thromboxane B2 inhibition by flunixin meglumine and meclofenamic acid in the dog. Res Vet Sci 61:78–81. https://doi.org/10.1016/S0034-5288(96)90115-0
Gu X, Meleka-Boules M, Chen CL, Ceska DM, Tiffany DM (1997) Determination of flunixin in equine urine and serum by capillary electrophoresis. J Chromatogr B 692:187–198. https://doi.org/10.1016/S0378-4347(96)00393-3
Hairgrove TB, Mask JW, Mayas TP, Fajt VR, Bentke AL, Warner JL, Baynes RE (2019) Detection of flunixin in the urine of untreated pigs housed with pigs treated with flunixin meglumine at labeled doses. Transl Anim Sci 3:1399–1404
Honeycutt R (1994) Mechanisms of pesticide movement into ground water. CRC Press, Boca Raton. https://doi.org/10.1201/9781351074346
Hill DN, Popova IE, Hammel JE, Morra MJ (2018) Transport of potential manure hormone and pharmaceutical contaminants through intact soil columns. J Environ Qual 48:47–56. https://doi.org/10.2134/jeq2018.06.0233
Intervet (2017) Banamine, product information, Madison
Jaffrezic A, Jardé E, Soulier A, Carrera L, Marengue E, Cailleau A, Le Bot B (2017) Veterinary pharmaceutical contamination in mixed land use watersheds: from agricultural headwater to water monitoring watershed. Sci Total Environ 609:992–1000. https://doi.org/10.1016/j.scitotenv.2017.07.206
Kissell L, Baynes R, Riviere J, Smith G (2013) Occurrence of flunixin residues in bovine milk samples from the USA. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 30:1513–1516. https://doi.org/10.1080/19440049.2013.803604
Leavens T, Tell L, Kissell L, Smith G, Smith D, Wagner S, Shelver W, Wu H, Baynes R, Riviere J (2014) Development of a physiologically based pharmacokinetic model for flunixin in cattle (Bos taurus). Food Addit Contam Part A Chem Anal Control Expo Risk Assess 31:1–16. https://doi.org/10.1080/19440049.2014.938363
Lin A, Plumlee M, Reinhard M (2006) Natural attenuation of pharmaceuticals and alkylphenol polyethoxylate metabolites during river transport: photochemical and biological transformation. Environ Toxicol Chem 25:1458–1464. https://doi.org/10.1897/05-412R.1
Liu S (2015) Cooperative adsorption on solid surfaces. J colloid Interface Sci 450:224–238.://doi.org/10.1016/j.jcis.2015.03.013
Matamoros V, García J, Bayona J (2008) Organic micropollutant removal in a full-scale surface flow constructed wetland fed with secondary effluent. Water Res 42:653–660. https://doi.org/10.1016/j.watres.2007.08.016
Milne R (2000) Drugs: synonyms and properties. Ashgate Publ Co. 1280pp
Morra M, Blank R, Freeborn L, Shafii B (1991) Size fractionation of soil organo-mineral complexes using ultrasonic dispersion. Soil Sci 152:294–303. https://doi.org/10.1097/00010694-199110000-00008
O’Keefe M, Muñiz Ortiz J (2015) United States national residue program for meat, poultry, and egg products - 2015 residue sampling plans
Odensvik K, Johansson I (1995) An HPLC method for determination of flunixin in bovine plasma and pharmacokinetics after single and repeated dosage. Am J Vet Res 56:489–495
OECD (2014) OECD guideline for the testing of chemicals. Sect. 4 heal. Eff. 425, 1–26
Radovic TT, Grujic SD, Kovacevic SR, Lausevic MD, Dimkic MA (2016) Sorption of selected pharmaceuticals and pesticides on different river sediments. Environ Sci Pollut Res 23:25232–25244. https://doi.org/10.1007/s11356-016-7752-4
Revitt M, Jones H (2015) Sorption behaviours and transport potentials for selected pharmaceuticals and triclosan in two sterilised soils. J Soils Sediments 15:594–606. https://doi.org/10.1007/s11368-014-1025-y
Rocca LM, Gentili A, Caretti F, Curini R, Perez-Fernandez V (2015) Occurrence of non-steroidal anti-inflammatory drugs in surface waters of Central Italy by liquid chromatography-tandem mass spectrometry. Int J Environ Anal Chem 95:685–697. https://doi.org/10.1080/03067319.2015.1046059
Salvia MV, Vulliet E, Wiest L, Baudot R, Cren-Olivé C (2012) Development of a multi-residue method using acetonitrile-based extraction followed by liquid chromatography–tandem mass spectrometry for the analysis of ateroids and veterinary and human drugs at trace levels in soil. J Chromatogr A 1245:122–133. https://doi.org/10.1016/j.chroma.2012.05.034
Site A (2001) Factors affecting sorption of organic compounds in natural sorbent/water systems and sorption coefficients for selected pollutants: a review. J Phys Chem Ref Data 30:187–439. https://doi.org/10.1063/1.1347984
Smith D, Shelver W, Baynes R, Tell L, Gehring R, Li M, Dutko T, Schroeder JW, Herges G, Riviere J (2015) Excretory, secretory, and tissue residues after label and extra-label administration of flunixin meglumine to saline- or lipopolysaccharide-exposed dairy cows. J Agric Food Chem 63:4893–4901. https://doi.org/10.1021/acs.jafc.5b01509
Sparks DL, Page AL, Helmke PA, Loeppert RH, Nelson D, Sommers L (1996) Total carbon, organic carbon, and organic matter. In: methods of soil analysis. https://doi.org/10.2136/sssabookser5.3.c34
Watanabe N, Bergamaschi B, Loftin K, Meyer M, Harter T (2010) Use and environmental occurrence of antibiotics in freestall dairy farms with manured forage fields. Environ Sci Technol 44:6591–6600. https://doi.org/10.1021/es100834s
Wauchope RD, Yeh S, Linders JBHJ, Kloskowski R, Tanaka K, Rubin B, Katayama A, Kordel W, Gerstl Z, Lane M, Unsworth JB (2002) Pesticide soil sorption parameters: theory, measurement, uses, limitations and reliability. Pest Manag Sci 58:419–445. https://doi.org/10.1002/ps.489
Yamamoto H, Nakamura Y, Moriguchi S, Nakamura Y, Honda Y, Tamura I, Hirata Y, Hayashi A, Sekizawa J (2008) Persistence and partitioning of eight selected pharmaceuticals in the aquatic environment: laboratory photolysis, biodegradation, and sorption experiments. Water Res 43:351–362. https://doi.org/10.1016/j.watres.2008.10.039
Yu Z, Luo X, Guo F, Zhang Z, Peng L (2019) Determination of flunixin in swine plasma, urine and feces by UPLCMS/ MS and its application in the real samples. Curr Pharm Anal 15:51–60. https://doi.org/10.2174/1573412913666170918163625
Zederfeldt B, Borg I, Haeger K (1977) Efficacy and tolerance of flunixin (SCH 14714) in the treatment of postoperative pain, with observations on the methodology of postoperative pain studies. Br J Anaesth 49:467–471. https://doi.org/10.1093/bja/49.5.467
Zhang Y, Price G, Jamieson R, Burton D, Khosravi K (2017) Sorption and desorption of selected non-steroidal anti-inflammatory drugs in an agricultural loam-textured soil. Chemosphere 174:628–637. https://doi.org/10.1016/j.chemosphere.2017.02.027
Zoetis (2015) Safety data sheet for flunixin, Kalamazoo
Zoetis (2014) Flunixamine, Product information. In: ANADA 200–387, Kalamazoo
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This project was supported by the Agriculture and Food Research Initiative competitive grant 2013-67019-21375 from the USDA National Institute of Food and Agriculture.
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Popova, I.E., Morra, M.J. Fate of the nonsteroidal, anti-inflammatory veterinary drug flunixin in agricultural soils and dairy manure. Environ Sci Pollut Res 27, 19746–19753 (2020). https://doi.org/10.1007/s11356-020-08438-4
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DOI: https://doi.org/10.1007/s11356-020-08438-4