A case study on the effects of TRICLOSAN: personal care products in the aquatic environment Alice Hontela University of Lethbridge Water Institute for Sustainable Environments (WISE) Lethbridge, Canada Dann and Hontela. 2011. J. Applied Toxicology 31: 285 Hontela and Habibi. 2013. Fish Physiology, Chap.3 Masaryk University, April 2013 Outline: Triclosan Synopsis 1. Chemical and physical characteristics 2. Sources 3. Exposure 4. Fate in the environment 5. Effects 6. Risk and Remediation Triclosan – Synopsis (identity, use) • Broad spectrum antimicrobial • personal care products: Irgasan, Aquasept, … •EU Cosmetic Directive •(0.1-0.3%) •sport clothing: • Ultra-Fresh, • Microban, • Sanitized, … •food packaging • • • TCS-multiple products.jpg Triclosan – key issues •Detected in water, • human plasma, • breast milk •Bioaccumulation •By-product formation •Endocrine disruption –Thyroid hormones –Sex hormones •Antibiotic resistance, • efficacy • triclosan levels.bmp (Adolfsson-Erici et al. 2002; Queckenberg et al. 2010; Dann & Hontela, 2011) •Structural similarity of TCS to Bisphenol A, to DES to thyroxine •Antimicrobial action of TCS : multiple sites in bacteria, blocks synthesis of FFA 1. Identity and mode of action Cl E:\imagesCA3GIPWW.jpg WWTP – Waste Water Treatment Plant 2. Sources link to experimental studies Bioaccumulation (?) 3. Concentrations of Triclosan in organisms 4. Fate in the environment Degradation products of TCS •Methyltriclosan biological methylation, Kow = 5.2 (TCS Kow = 4.7) used as marker of exposure to WWTP effluent more persistent than TCS •Dioxins generated during photodegradation of TCS at pH > 8 •Chloroform and chlorophenols generated in presence of chlorine or chloramine Buth et al. 2009 Environ Toxicology Chem 28: 2555, 2009 fate in the environment … Biotransformation of Triclosan catfish hepatocytes James et al. 2012 Aquat Toxicol 124: 72 5. Effects of Triclosan on aquatic organisms Toxicity of Triclosan •Algae are highly sensitive to TCS LC50 96 hr = 1- 4 µg/L •Invertebrates and fish average sensitivity •Amphibians - highly sensitive effects in tadpoles at 0.15 µg/L effects on thyroid status Binelli et al. 2009 Aquatic Toxicology, 2009 Zebra mussel hemocytes genotoxic effects of Triclosan in vitro and in vivo Micronuclei formation Appoptosis EFFECTS … Cherednichenko et al. 2012 PNAS 109:14159 •Reduction of cardiac function in mice treated with TCS in vivo •TCS impairs excitation-contraction coupling in isolated cardiomyocytes •damage to Ca++ channels Ahn et al. Environ Health Perspectives 2008 •Effects of Triclosan on intracellular Ca2+ homeostasis in myotubes •Interaction with estrogen Fritsch et al 2013 Env Science and Technology Triclosan alters DHPR and RyR protein expression in fish larvae Effect of Triclosan on •swimming performance •feeding behaviour D:\FHM.jpg Pimephales promelas, fathead minnow E:\medaka[1].gif Medaka, Oryzias latipes Japanese killifish Isihibashi et al. 2004 Chemosphere Increase in GSI in male Medaka Lower hatchability of eggs in female Raut and Angus 2010 Env Toxicol Chem Decrease in sperm count in Mosquitofish Gambusia affinis E:\1-s2.0-S0166445X03002522-gr1[1].gif E:\1-s2.0-S0166445X03002522-gr3[1].gif E:\1-s2.0-S0166445X03002522-gr4[1].gif E:\1-s2.0-S0166445X03002522-gr6[1].gif •Estrogenic effects in male medaka induction of Vtg •Estrogenic activity of TCS enhanced by S9 activation D:\1-s2_0-S0166445X06003407-gr1.jpg Veldhoen et al. 2006, Aquat Toxicol Effects of Triclosan on amphibian metamorphosis Effects of Triclosan on thyroid axis In vivo Exposure of tadpoles (Rana catesbeiana) In vitro Exposure of XTC-2 cells (Xenopus laevis cells) E:\775px-North-American-bullfrog1[1].jpg North American bullfrog Rana catesbeiana D:\1-s2_0-S0166445X06003407-gr2.gif •Acceleration of development in tadpoles exposed to T3 and TCS •T3 alone has no effect D:\1-s2_0-S0166445X06003407-gr5.jpg E:\1-s2.0-S0166445X06003407-gr4[1].jpg •Relative mRNA expression of TH-regulated genes •Transcripts levels affected by Triclosan at a sensitive life stage of anuran development •No evidence for estrogenic effects ( no VTG induction) In vitro In vivo E:\Chamonix-Mont-Blanc1[1].jpg E:\images[3].jpg Effects of Triclosan in human ? Cell –based assays •estrogenic and androgenic effects in MCF37 breast cancer cells •weak AhR activity In vivo effects ??? Efficacy of Triclosan •Use in oral hygiene +++ •Use in clinical setting as soap +++ •Use in personal care ? •Use in food wrapping ? •Use in sport clothing ? • E:\TriclosanNYT[1].jpg Antibacterial control hospitals oral care E:\meat[1].jpg E:\decorative_soaps[1].jpg Risk assessment for Triclosan Ecosystem integrity (algal populations) Endocrine disruption amphibians, fish Antibacterial resistance C:\Users\alice.hontela\Pictures\2011-10-16, Oct15,2011Grasmere\Oct15,2011Grasmere 013.jpg Torres-Duarte 2012 Appl Biochem Biotechnol 168: 864 Remediation – inactivationl of Triclosan by enzymatic degradation •Vtg mRNA in zebrafish • • •ER activity C:\Users\alice.hontela\Pictures\2012_01_02\IMG_7317.JPG