Konferensartikel

Modeling and Simulation of Triclosan Kinetics and Distribution in Humans Using a PBPK Model

Samee Maharjan
Telemark University College, Norway

Roshan Sharma
Telemark University College, Norway

Trine Husøy
Dept. of Food, Water and Cosmetics; Norwegian Institute of Public Health (NIPH)

Hubert Dirven
Dept. of Food, Water and Cosmetics; Norwegian Institute of Public Health (NIPH)

Monica Andreassen
Dept. of Food, Water and Cosmetics; Norwegian Institute of Public Health (NIPH)

Bernt Lie
Telemark University College, Norway

Ladda ner artikelhttp://dx.doi.org/10.3384/ecp15119279

Ingår i: Proceedings of the 56th Conference on Simulation and Modelling (SIMS 56), October, 7-9, 2015, Linköping University, Sweden

Linköping Electronic Conference Proceedings 119:28, s. 279-288

Visa mer +

Publicerad: 2015-11-25

ISBN: 978-91-7685-900-1

ISSN: 1650-3686 (tryckt), 1650-3740 (online)

Abstract

Personal care products (PCPs) such as soaps, perfumes, toothpastes, lotions, etc. contain various chemicals. Triclosan (TCS) is widely used as an antibacterial additive in PCPs. Traces of TCS are found in human plasma and milk indicating absorption through the skin and/or after oral ingestion. In this paper, a Physiologically Based Pharmacokinetic or Toxicokinetic (PBPK/TK) model is developed to assess the behavior of TCS in human body after exposure to PCPs orally or through the skin. The model will describe metabolism, kinetics and distribution in human organs. The developed model is based on available literature data on biotransformation in rodents and humans, and is simulated using MATLAB and/or Modelica. The intention of the work is to further develop the model and fit model parameters to experimental data, and to develop a PBPK model useful for human risk assessment of TCS.

Nyckelord

Modeling; Simulation; PBPK; Triclosan; Kinetics; Distribution; Humans

Referenser

Barter, ZE, Bayliss, MK, Beaune, PH, Boobis, AR, Carlile, DJ, & Reisfeld, Brad. (2007). "Scaling Factors for the Extrapolation of In Vivo Metabolic Drug Clearance From In Vitro Data: Reaching a Consensus on Values of Human Microsomal Protein and Hepatocellularity Per Gram of Liver". Current Drug Metabolism, 8, 33-45.

Beard, Daniel A. (2012). Biosimulation Simulation of Living Systems. Cambridge United Kingdom: Cambridge University Press.

Cubitt, Helen E., Houston, J. Brian, & Galetin, Aleksandra. (2009). "Prediction of Human Drug Clearance by Multiple Metabolic Pathways: Integration of Hepatic and Intestinal Microsomal and Cytosolic Data". Drug Metabolism and Disposition, 39, 864-873.

Ekstrom, Per-Anders. (2005). "Eikos: A Simulation Toolbox for Sensitivity Analysis in MATLAB". FACILIA AB.

Fang, JL, Stingley, RL, Beland, FA, Harrouk, W, Lumpkins, DL, & Howard, P. (2010). "Occurrence, efficacy, metabolism, and toxicity of triclosan". Journal of Environmental Science and Health, 28(3), 147-171.

Johnson, Trevor N., Tucker, Geoffrey T., Tanner, M. Stuart, & Rostami-Hodjegan, Amin. (2005)."Changes in Liver Volume from Birth to Adulthood: A Meta-Analysis". Liver Transplantation, 12(11), 1481-1493.

Mielke, Hans, Abraham, Klaus, Gotz, Mario, Vieth, Barbel, Lampen, Alfonso, Luch, Andreas,& Gundert-Remy, Ursula. (2011). "Physiologically based toxicokinetic modelling as a tool to assess target organ toxicity in route-to-route extrapolation- The case of courmarin". Toxicology Letters, 202, 100-110.

Mielke, Hans, & Gundert-Remy, Ursula. (2012)."Physiologically Based Toxicokinetic Modelling as a Tool to Support Risk Assessment :Three Case Studies". Journal of Toxicology, 2012, 11.

Morris, Max D. (1991). "Factorial Sampling Plans for Preliminary Computational Experiments". Technometrics, 33, 161-174.

Moss, T, Howes, D, & Williams, F. M. (2000)."Percutaneous Penetration and Dermal Metabolism of Triclosan (2,4,4’-Trichloro-2’-hydroxydiphenyl Ether)". Food and Chemical Toxicology, 30, 360-370.

Rodricks, Joseph V, Swenberg, James A, Borzelleca, Joseph F, Maronpot, Robert R, & Shipp, Annette M. (2010). "Triclosan: A critical review of the experimental data and development of margins of safety for consumer products". Critical Reviews in Toxicology, 40, 422-484.

Wang, Li-Quan, Falany, Charles N., & James, Margaret O. (2004). "Triclosan as a substrate and inhibitor of 3’-phosphoadenosine 5’- phosphosulfate-sulfotransferase and udpglucuronosyl transferase in human liver fractions". Drug Metabolism and Disposition, 32, 1162-1169.

Citeringar i Crossref