Slow O-demethylation of methyl triclosan to triclosan, which is rapidly glucuronidated and sulfonated in channel catfish liver and intestine

• Published in: Aquatic toxicology 2012-11, Vol.124-125, p.72-82
• Main Authors: James, Margaret O., Marth, Christopher J., Rowland-Faux, Laura
• Format: Article
• Language: English
• Subjects: Animals; bacteria; bioaccumulation; Biotransformation; catfish; Channel catfish; cytochrome P-450; cytosol; Cytosol - metabolism; Diet; Dimethyl Sulfoxide - pharmacology; Enzyme Inhibitors - pharmacology; fish feeds; food chain; Free Radical Scavengers - pharmacology; Freshwater; Glucuronidation; Glucuronides - metabolism; Ictaluridae - metabolism; Ictalurus punctatus; Intestines - metabolism; invertebrates; liver; Liver - metabolism; liver microsomes; metabolism; Methyl triclosan; Methylation - drug effects; Microsomes - enzymology; Microsomes - metabolism; NADP (coenzyme); O-Demethylation; sediments; sewage sludge; sewage treatment; soil; Sulfonation; summer; Temperature; Triclosan - analogs & derivatives; Triclosan - chemistry; Triclosan - metabolism; Water Pollutants, Chemical - chemistry; Water Pollutants, Chemical - metabolism; water temperature
• ISSN: 0166-445X; 1879-1514
• DOI: 10.1016/j.aquatox.2012.07.009

► This is the first study of triclosan and methyl triclosan biotransformation in a fish species ► Methyl triclosan was very slowly O-demethylated in the channel catfish liver and intestine ► The demethylation was inhibited by DMSO, a solvent commonly used in toxicology studies ► Triclosan was rapidly conjugated by glucuronidation and sulfonation ► Our results suggest methyl triclosan, but not triclosan, will bioaccumulate in exposed catfish. The antibacterial personal care product triclosan is discharged in municipal waste, and converted in part by bacteria in sewage sludge and soil to its more lipid-soluble methyl ether, methyl triclosan. Triclosan and methyl triclosan have been detected in water, sediment, fish and invertebrates near sewage treatment facilities. Understanding the biotransformation of methyl triclosan and triclosan in a model food fish, the channel catfish, will be of value in assessing the likelihood that these compounds will bioaccumulate in exposed fish, and therefore potentially pass up the food chain. We hypothesize that cytochrome P450 will catalyze the O-demethylation of methyl triclosan to yield triclosan, which is likely to undergo glucuronidation or sulfonation of the phenolic hydroxyl group. Conversion of methyl triclosan to triclosan was measured by LC/MS/MS following aerobic incubation of varying concentrations of methyl triclosan with NADPH and hepatic and intestinal microsomes from untreated, 3-methylcholanthrene-treated (10mg/kg, i.p.) or PCB-126-treated (0.1mg/kg, i.p.) channel catfish (n=4 per treatment group). The Km values for methyl triclosan were similar for untreated, 3-methylcholanthrene-treated and PCB-126-treated catfish liver microsomes, ranging from 80 to 250μM. Vmax values for O-demethylation ranged from 30 to 150pmol/min/mg protein, with no significant differences between controls, PCB-126-treated or 3-methylcholanthrene-treated fish, suggesting that methyl triclosan O-demethylation was not a CYP1-catalyzed reaction. Methyl triclosan O-demethylation activities in intestinal microsomes were similar to or lower than those found with liver microsomes. The calculated rate of O-demethylation of methyl triclosan in catfish liver at 1μM, a concentration reported in exposed fish, and 21°C, an early summer water temperature, is 0.10pmol/min/mg protein. This slow rate of metabolism suggests that upon continued exposure, methyl triclosan may bioaccumulate in the channel catfish. Triclosan itself, however, was readily gl