Investigation of human exposure to triclocarban after showering and preliminary evaluation of its biological effects.

The antibacterial soap additive triclocarban (TCC) is widely used in personal care products. TCC has a high environmental persistence. We developed and validated a sensitive online solid-phase extraction-LC-MS/MS method to rapidly analyze TCC and its major metabolites in urine and other biological samples to assess human exposure. We measured human urine concentrations 0-72 h after showering with a commercial bar soap containing 0.6% TCC. The major route of renal elimination was excretion as N-glucuronides. The absorption was estimated at 0.6% of the 70±15 mg of TCC in the soap used. The TCC-N-glucuronide urine concentration varied widely among the subjects, and continuous daily use of the soap led to steady state levels of excretion. In order to assess potential biological effects arising from this exposure, we screened TCC for the inhibition of human enzymes in vitro. We demonstrate that TCC is a potent inhibitor of the enzyme soluble epoxide hydrolase (sEH), whereas TCC's major metabolites lack strong inhibitory activity. Topical administration of TCC at similar levels to rats in a preliminary in vivo study, however, failed to alter plasma biomarkers of sEH activity. Overall the analytical strategy described here revealed that use of TCC soap causes exposure levels that warrant further evaluation.

[1]  B. Hammock,et al.  Development of an ultra fast online-solid phase extraction (SPE) liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS) based approach for the determination of drugs in pharmacokinetic studies. , 2011, Analytical methods : advancing methods and applications.

[2]  U. Karst,et al.  Electrochemistry-Mass Spectrometry Unveils the Formation of Reactive Triclocarban Metabolites , 2010, Drug Metabolism and Disposition.

[3]  Paul D. Jones,et al.  1-Aryl-3-(1-acylpiperidin-4-yl)urea inhibitors of human and murine soluble epoxide hydrolase: structure-activity relationships, pharmacokinetics, and reduction of inflammatory pain. , 2010, Journal of medicinal chemistry.

[4]  L. Nováková,et al.  A review of current trends and advances in modern bio-analytical methods: chromatography and sample preparation. , 2009, Analytica chimica acta.

[5]  C. Gagnon,et al.  On-line solid-phase extraction of large-volume injections coupled to liquid chromatography-tandem mass spectrometry for the quantitation and confirmation of 14 selected trace organic contaminants in drinking and surface water. , 2009, Journal of chromatography. A.

[6]  Jun Yang,et al.  Quantitative profiling method for oxylipin metabolome by liquid chromatography electrospray ionization tandem mass spectrometry. , 2009, Analytical chemistry.

[7]  Bruce D. Hammock,et al.  Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases , 2009, Nature Reviews Drug Discovery.

[8]  M. Denison,et al.  Toxicology in the Fast Lane: Application of High-Throughput Bioassays to Detect Modulation of Key Enzymes and Receptors , 2009, Environmental health perspectives.

[9]  I. González-Mariño,et al.  Simultaneous determination of parabens, triclosan and triclocarban in water by liquid chromatography/electrospray ionisation tandem mass spectrometry. , 2009, Rapid communications in mass spectrometry : RCM.

[10]  Alison M. Cupples,et al.  Detection of the antimicrobials triclocarban and triclosan in agricultural soils following land application of municipal biosolids. , 2009, Water research.

[11]  Paul D. Jones,et al.  Soluble epoxide hydrolase and epoxyeicosatrienoic acids modulate two distinct analgesic pathways , 2008, Proceedings of the National Academy of Sciences.

[12]  T. L. Point,et al.  Snail bioaccumulation of triclocarban, triclosan, and methyltriclosan in a north texas, usa, stream affected by wastewater treatment plant runoff , 2008, Environmental toxicology and chemistry.

[13]  B. Hammock,et al.  Triclocarban enhances testosterone action: a new type of endocrine disruptor? , 2008, Endocrinology.

[14]  M. D. Hernando,et al.  Application of high-performance liquid chromatography–tandem mass spectrometry with a quadrupole/linear ion trap instrument for the analysis of pesticide residues in olive oil , 2007, Analytical and bioanalytical chemistry.

[15]  B. Hammock,et al.  Measurement of Soluble Epoxide Hydrolase (sEH) Activity , 2007, Current protocols in toxicology.

[16]  Leimin Fan,et al.  Recent advances in high-throughput quantitative bioanalysis by LC-MS/MS. , 2007, Journal of pharmaceutical and biomedical analysis.

[17]  B. Venables,et al.  Algal bioaccumulation of triclocarban, triclosan, and methyl-triclosan in a North Texas wastewater treatment plant receiving stream. , 2007, Chemosphere.

[18]  B. Hammock,et al.  Development of highly sensitive fluorescent assays for fatty acid amide hydrolase. , 2007, Analytical biochemistry.

[19]  Wayne M Mullett,et al.  Determination of drugs in biological fluids by direct injection of samples for liquid-chromatographic analysis. , 2007, Journal of biochemical and biophysical methods.

[20]  A. Sapkota,et al.  Detection of triclocarban and two co-contaminating chlorocarbanilides in US aquatic environments using isotope dilution liquid chromatography tandem mass spectrometry. , 2007, Environmental research.

[21]  B. Hammock,et al.  Inhibition of soluble epoxide hydrolase reduces LPS-induced thermal hyperalgesia and mechanical allodynia in a rat model of inflammatory pain. , 2006, Life sciences.

[22]  Xiaoyun Ye,et al.  Measuring environmental phenols and chlorinated organic chemicals in breast milk using automated on-line column-switching-high performance liquid chromatography-isotope dilution tandem mass spectrometry. , 2006, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[23]  Paul D. Jones,et al.  Fluorescent substrates for soluble epoxide hydrolase and application to inhibition studies. , 2005, Analytical biochemistry.

[24]  P. Beroza,et al.  Identification and characterization of novel benzil (diphenylethane-1,2-dione) analogues as inhibitors of mammalian carboxylesterases. , 2005, Journal of medicinal chemistry.

[25]  R. Halden,et al.  Co-occurrence of triclocarban and triclosan in U.S. water resources. , 2005, Environmental science & technology.

[26]  R. Halden,et al.  Analysis of triclocarban in aquatic samples by liquid chromatography electrospray ionization mass spectrometry. , 2004, Environmental science & technology.

[27]  Xiang Fang,et al.  Epoxyeicosatrienoic acids (EETs): metabolism and biochemical function. , 2004, Progress in lipid research.

[28]  B. Hammock,et al.  Development of sensitive esterase assays based on alpha-cyano-containing esters. , 2001, Analytical biochemistry.

[29]  B D Hammock,et al.  Potent urea and carbamate inhibitors of soluble epoxide hydrolases. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[30]  B D Hammock,et al.  Mechanism of mammalian soluble epoxide hydrolase inhibition by chalcone oxide derivatives. , 1998, Archives of biochemistry and biophysics.

[31]  B. Hammock,et al.  cDNA cloning and expression of a soluble epoxide hydrolase from human liver. , 1993, Archives of biochemistry and biophysics.

[32]  L. Gruenke,et al.  Synthesis and hydrolytic behavior of the sulfate conjugate of 2'-hydroxy-3,4,4'-trichlorocarbanilide. , 1989, Drug metabolism and disposition: the biological fate of chemicals.

[33]  H. Maibach,et al.  A selected ion monitoring GC/MS assay for 3,4,4'-trichlorocarbanilide and its metabolites in biological fluids. , 1987, Journal of analytical toxicology.

[34]  R. Mosteller Simplified calculation of body-surface area. , 1987, The New England journal of medicine.

[35]  B. Hammock,et al.  Radiometric assays for mammalian epoxide hydrolases and glutathione S-transferase. , 1983, Analytical biochemistry.

[36]  J. Fouts,et al.  A rapid method for assaying the metabolism of 7-ethoxyresorufin by microsomal subcellular fractions. , 1980, Analytical biochemistry.

[37]  R. Hiles,et al.  The metabolism and disposition of 3,4,4'-trichlorocarbanilide in the intact and bile duct-cannulated adult and in the newborn rhesus monkey (M. mulatta). , 1978, Toxicology and applied pharmacology.

[38]  R. Hiles,et al.  Nonlinear metabolism and disposition of 3,4,4'-trichlorocarbanilide in the rat. , 1978, Toxicology and applied pharmacology.

[39]  R. Hiles,et al.  The absorption, excretion, and biotransformation of 3,4,4'-trichlorocarbanilide in humans. , 1978, Drug metabolism and disposition: the biological fate of chemicals.

[40]  A. Jeffcoat,et al.  Biotransformation products of 3,4,4'-trichlorocarbanilide in rat, monkey, and man. , 1978, Drug metabolism and disposition: the biological fate of chemicals.

[41]  D. E. Carter,et al.  Identification of the metabolites of trichlorocarbanilide in the rat. , 1978, Drug metabolism and disposition: the biological fate of chemicals.

[42]  A. Jeffcoat,et al.  The metabolism and toxicity of halogenated carbanilides. Biliary metabolites of 3,4,4'-trichlorocarbanilide and 3-trifluoromethyl-4,4'-dichlorocarbanilide in the rat. , 1977, Drug metabolism and disposition: the biological fate of chemicals.

[43]  D. Howes,et al.  Percutaneous absorption of triclocarban in rat and man. , 1976, Toxicology.

[44]  D. Howes,et al.  Skin deposition and penetration of trichlorocarbanilide. , 1975, Toxicology.

[45]  H. Maibach,et al.  Percutaneous penetration and disposition of triclocarban in man: body showering. , 1975, Archives of environmental health.

[46]  W B Jakoby,et al.  Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. , 1974, The Journal of biological chemistry.

[47]  P. J. Hurley,et al.  Demonstration of individual variation in constancy of 24-hour urinary creatinine excretion. , 1968, Clinica chimica acta; international journal of clinical chemistry.

[48]  H. Husdan,et al.  Estimation of creatinine by the Jaffe reaction. A comparison of three methods. , 1968, Clinical chemistry.