Toxic effects of triclosan on a zebrafish (Danio rerio) liver cell line, ZFL.

Triclosan (TCS, 5-chloro-2-(2,4-dichlorophenoxy) phenol) is an antimicrobial agent widely used in personal care products. It has been detected in surface water, soil, aquatic species, and even humans. In this study, we used zebrafish (Danio rerio) as a model to test the hypothesis that TCS exhibits toxic effects by interacting with thyroid hormone receptor β (TRβ) and aryl hydrocarbon receptor (AhR) and by inducing the transcription of thyroid hormone (TH)-associated genes and affecting phase I and phase II enzymes. The median lethal concentrations (LC50) of TCS in zebrafish embryos/larvae and a zebrafish liver cell line (ZFL) were first determined. Hatched larvae were most sensitive to TCS exposure, with LC50 values ranging from 1.26 to 1.46μM for 96h after hatching exposure. The major effect of TCS was delayed hatching which occurred from 1.13μM. The constructed GFP-zfTRβ fusion protein revealed the subcellular location of zfTRβ as the nucleus in both T3-induced and uninduced states, adding to the difficulty of studying TCS action on thyroid hormone receptors in ZFL cells. TCS had neither agonistic nor antagonistic effects on zfTRβLBD or AhR from the reporter gene systems. Ethoxyresorufin-o-deethylase (EROD) assay suggested that TCS is a weak P4501a (Cyp1a) agonist at 5μM and that it inhibits cytochrome Cyp1a activity induced by benzo(a)pyrene (BaP). In time course-based mRNA profiling in ZFL cells, 4-h exposure to TCS caused a significant (up to 37.5-fold) inhibition of Cyp1a at 2.5μM. An overall inhibition of liver phase I and II gene transcription at 4h exposure indicates the possible quick catabolism of TCS. Our findings suggest that TCS is not a TH mimic that affects TH-related gene expression. The impairment of Cyp1a mRNA expression could be due to stimulation by other stressors such as oxidative stress, warranting further investigation into the underlying mechanism in zebrafish.

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