TRICLOSAN :
environmental exposure,
toxicity and mechanisms of action
Journal of Applied Toxicology 31: 285-311, 2011
Dann and Hontela
Innovation Lectures (INNOLEC)
Masaryk University, May 2012

Triclosan – identity, use
•   Broad spectrum antimicrobial
•personal care products – Irgasan, Aquasept,
•        Sapoderm, …
•EU Cosmetic Directive
•(0.1-0.3%)
•sport clothing –
•       Ultra-Fresh,
•       Microban,
•       Sanitized, …
•food packaging                Economy – Life style
•
•
TCS-multiple products.jpg

Triclosan – key issues
•Detected in surface water,
•    human plasma, breastmilk
•Bioaccumulation
•By-product formation
•Endocrine disruption
–Thyroid hormones
–Sex hormones
•Antibiotic resistance, efficacy
•
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•Antimicrobial action of TCS
multiple sites in bacteria,
blocks synthesis of FFA
•Structural similarity of TCS to Bisphenol A,
to DES
to thyroxine

1. Identity and mode of action

link to experimental studies



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WWTP – Waste Water Treatment Plant


3. 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
Environmental chemistry, Environmental fate

Buth et al. 2009 Environ Toxicology Chem 28: 2555-2563, 2009



4. Concentrations of Triclosan
in organisms
triclosan levels.bmp
(Adolfsson-Erici et al. 2002; Queckenberg et al. 2010; Dann & Hontela, 2011)

Bioaccumulation (?)









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

Foran et al. 2000
Mar Environ Res
Triclosan
weak androgenic action
in medaka, Oryzias latipes

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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
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•Estrogenic effects in male medaka
induction of Vtg
•Estrogenic activity of TCS enhanced by S9 activation




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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)

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North American bullfrog
Rana catesbeiana

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•Acceleration of development in tadpoles exposed to
    T3 and TCS
•T3 alone has no effect

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•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

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South African clawed frog
Xenopus laevis




Crofton et al. 2007
Environ Toxicol Pharmacol
Paul et al 2010
Toxicological Sciences
Inhibition of thyroid axis
in rats
exposed to Triclosan
Effect on Phase II
enzymes
(metabolism of thyroid
hormones)




Ahn et al. Environ Health Perspectives 2008
•Effects of Triclosan
    on intracellular Ca2+ homeostasis
•Interaction with estrogen

Binelli et al. 2009 Aquatic Toxicology, 2009
Zebra mussel hemocytes
genotoxic effects of Triclosan in vitro and in vivo
Micronuclei formation
Appoptosis

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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 ?
•
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Antibacterial control
hospitals
oral care
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Risk assessment for Triclosan
Ecosystem integrity
    (algal populations)
Endocrine disruption
    amphibians, fish
Antibacterial
    resistance
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