Triclosan is a broad spectrum antibacterial agent used in many household products. Due to its structural similarity to polychlorobiphenylols, which are potent inhibitors of the sulfonation and glucuronidation of 3-hydroxy-benzo[a]pyrene, it was hypothesized that triclosan would inhibit these phase II enzymes. This study was designed to assess the interactions of triclosan as a substrate and inhibitor of 3′-phosphoadenosine 5′-phosphosulfate-sulfotransferases and UDP-glucuronosyltransferases in human liver cytosol and microsomes. Triclosan was sulfonated and glucuronidated in human liver. The apparent K_m and V_max values for triclosan sulfonation were 8.5 μM and 0.096 nmol/min/mg protein, whereas K_m and V_max values for glucuronidation were 107 μM and 0.739 nmol/min/mg protein. Triclosan inhibited the hepatic cytosolic sulfonation of 3-hydroxybenzo(a)pyrene (3-OH-BaP), bisphenol A, p-nitrophenol, and acetaminophen with IC₅₀ concentrations of 2.87, 2.96, 6.45, and 17.8 μM, respectively. Studies of 3-OH-BaP sulfonation by expressed human SULT1A1^*1, SULT1A1^*2, SULT1B1, and SULT1E1 showed that triclosan inhibited the activities of each of these purified enzymes with IC₅₀ concentrations between 2.09 and 7.5 μM. Triclosan was generally a less potent inhibitor of microsomal glucuronidation. IC₅₀ concentrations for triclosan with 3-OH-BaP, acetaminophen, and bisphenol A as substrates were 4.55, 297, and >200 μM, respectively. Morphine glucuronidation was not inhibited by 50 μM triclosan. The kinetics of 3-OH-BaP sulfonation and glucuronidation were examined in the presence of varying concentrations of triclosan: the inhibition of sulfonation was noncompetitive, whereas that of glucuronidation was competitive. These findings reveal that the commonly used bactericide triclosan is a selective inhibitor of the glucuronidation and sulfonation of phenolic xenobiotics.

The sulfotransferase (SULT) family comprises important phase II conjugation enzymes for the detoxification of xenobiotics and modulation of the activity of physiologically important endobiotics such as thyroid hormones, steroids, and neurotransmitters. SULT enzymes catalyze the transfer of a sulfuryl group, donated by 3-phosphoadenosine-5- phosphosulfate (PAPS), to an acceptor substrate that may be a hydroxy group or an amine group in a process originally called sulfation, but more correctly referred to as sulfonation or sulfurylation. SULT activity may be inhibited when humans are exposed to certain xenobiotics including drugs (mefenamic acid, salicylic acid, clomiphene, danazol etc.), dietary chemicals (catechins, food colorants, flavonoids and phytoestrogens etc.), and environmental chemicals (hydroxylated polychlorinated biphenyls, hydroxylated polyhalogenated aromatic hydrocarbons, pentachlorophenol, triclosan and bisphenol A, etc.). Inhibition of individual SULT isoforms may cause adverse effects on human health. For example, hydroxylated polychlorinated biphenyls have been shown to interfere with the transport of thyroid hormones, inhibit estradiol sulfonation, and inhibit thyroid hormone sulfonation, thereby potentially disrupting the thyroid hormone system. Formation of sulfate conjugates of toxic xenobiotics usually decreases their toxicity, so inhibition of this pathway may lead to prolonged exposure to the compounds. Conversely, some sulfate conjugates are chemically reactive, inhibition of their formation may protect from toxicity. This manuscript will review the literature concerning the inhibition of SULTs by xenobiotics including isoform-selective effects, inhibition kinetics and health effects resulting from the inhibition.

$^{14}$C-Labelled phenylacetic acid has been administered to man, 14 species of sub-human primates and 11 non-primate species and their urine examined for metabolites. Four amino acid conjugates of this acid have been found in various species, namely, phenacetyl-glutamine, phenacetylglycine, phenacetyltaurine and diphenacetylornithine, but their occurrence varies with species. In the primates the occurrence of the glutamine and glycine conjugates appears to be correlated with their evolutionary status. Man excretes exclusively the glutamine conjugate, the Old World monkeys the glutamine conjugate and very small amounts of the glycine conjugate, the New World monkeys the glutamine conjugate and significant amounts of the glycine conjugate and the prosimians the glycine conjugate only. The non-primate mammalian species excrete the glycine conjugate and no glutamine conjugate. The two avian species examined also differed, since the pigeon excreted the glycine conjugate, whereas the domestic hen excreted mainly the ornithine conjugate with small amounts of the glycine conjugate. The conjugation of phenylacetic acid with taurine is reported for the first time. It occurs in all the species examined except the vampire bat and domestic hen, but its quantitative occurrence is haphazard amongst the species examined. It was found in significant amounts in the pigeon, ferret, bushbaby, capuchin monkey, squirrel monkey, mona monkey and baboon, but in minor amounts in other species.