Bioconcentration, metabolism and excretion of triclocarban in larval Qurt medaka (Oryzias latipes)

Schebb, Nils Helge; Flores, Ida; Kurobe, Tomofumi; Franze, Bastian; Ranganathan, Anupama; Hammock, Bruce D.; Teh, Swee J.

doi:10.1016/j.aquatox.2011.07.020

Cited by 45 publications

(44 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, conjugation with glucuronic acid plays a key role in both renal and biliary elimination of TCC. In a recent study, it was also shown that glucuronides of phase I metabolites are the major metabolites in fish (Schebb et al, 2011a). However, no information is available about the UDP-glucuronosyltransferases (UGTs) involved in the conjugation of TCC and its metabolites, as well as the biochemistry and kinetics of the conversion.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In Vitro Glucuronidation of the Antibacterial Triclocarban and Its Oxidative Metabolites

Schebb¹,

Franze²,

Maul³

et al. 2011

Drug Metab Dispos

View full text Add to dashboard Cite

ABSTRACT:Triclocarban (3,4,4-trichlorocarbanilide; TCC) is widely used as an antibacterial in bar soaps. During use of these soaps, a significant portion of TCC is absorbed by humans. For the elimination from the body, glucuronidation plays a key role in both biliary and renal clearance. To investigate this metabolic pathway, we performed microsomal incubations of TCC and its hydroxylated metabolites 2-OH-TCC, 3-OH-TCC, and 6-OH-TCC. Using a new liquid chromatography-UV-mass spectrometry method, we could show a rapid glucuronidation for all OH-TCCs by the uridine-5-diphosphate-glucuronosyltransferases (UGT) present in liver microsomes of humans (HLM), cynomolgus monkeys (CLM), rats (RLM), and mice (MLM). Among the tested human UGT isoforms, UGT1A7, UGT1A8, and UGT1A9 showed the highest activity for the conjugation of hydroxylated TCC metabolites followed by UGT1A1, UGT1A3, and UGT1A10. Due to this broad pattern of active UGTs, OH-TCCs can be efficiently glucuronidated in various tissues, as shown for microsomes from human kidney (HKM) and intestine (HIM). The major renal metabolites in humans, TCC-N-glucuronide and TCC-N-glucuronide, were formed at very low conversion rates (<1%) by microsomal incubations. Low amounts of N-glucuronides were generated by HLM, HIM, and HKM, as well as by MLM and CLM, but not by RLM, according to the observed species specificity of this metabolic pathway. Among the human UGT isoforms, only UGT1A9 had activity for the N-glucuronidation of TCC. These results present an anomaly where in vivo the predominant urinary metabolites of TCC are N and N-glucuronides, but these compounds are slowly produced in vitro.

show abstract

Section: Introductionmentioning

confidence: 99%

“…Rats received a dose of 1 mg/kg b.wt., and mice received a dose of 5 mg/kg b.wt. After administration, urine was collected between 0 to 24 and 24 to 48 h. Urine was analyzed using online-LC-MS, as described previously (Schebb et al, 2011a).…”

mentioning

confidence: 99%

In Vitro Glucuronidation of the Antibacterial Triclocarban and Its Oxidative Metabolites

Schebb¹,

Franze²,

Maul³

et al. 2011

Drug Metab Dispos

View full text Add to dashboard Cite

show abstract

“…Due to its lipophilicity, TCC bioconcentrates in the aquatic environment and is one of the most abundant anthropogenic compounds found in sewage sludge (Langford et al, 2011). Moreover, significant TCC bioconcentration in aquatic organisms such as algae, snails (Coogan et al, 2007;Coogan and La Point, 2008), and fish (Schebb et al, 2011a) has been reported.…”

Section: Introductionmentioning

confidence: 99%

“…The main phase 1 metabolites in all species are monohydroxylated-TCC derivatives bearing the hydroxyl group ortho to the aniline group, namely 29-OH-TCC and 69-OH-TCC (Birch et al, 1978;Baumann et al, 2010;Schebb et al, 2012b). In addition, hydroxylation in the meta position (39-OH-TCC) and substitution of a chlorine atom by a hydroxyl group occurs, yielding 3,4-dichloro-49-hydroxycarbanilide (DHC) [for the structures of metabolites see Schebb et al (2011a)]. All hydroxylated metabolites undergo extensive phase II conjugation by UDP-glucuronosyl transferases (Schebb et al, 2012b).…”

Section: Introductionmentioning

confidence: 99%

Metabolic Activation of the Antibacterial Agent Triclocarban by Cytochrome P450 1A1 Yielding Glutathione Adducts

et al. 2014

Self Cite

View full text Add to dashboard Cite

Triclocarban (3,4,49-trichlorocarbanilide; TCC) is an antibacterial agent used in personal care products such as bar soaps. Small amounts of chemical are absorbed through the epidermis. Recent studies show that residues of reactive TCC metabolites are bound covalently to proteins in incubations with keratinocytes, raising concerns about the potential toxicity of this antimicrobial agent. To obtain additional information on metabolic activation of TCC, this study characterized the reactive metabolites trapped as glutathione conjugates. Incubations were carried out with 14 C-labeled TCC, recombinant CYP1A1 or CYP1B1, coexpressed with cytochrome P450 reductase, glutathione-S-transferases (GSH), and an NADPHgenerating system. Incubations containing CYP1A1, but not 1B1, led to formation of a single TCC-GSH adduct with a conversion rate of 1% of parent compound in 2 hours. Using high-resolution mass spectrometry and diagnostic fragmentation, the adduct was tentatively identified as 3,4-dichloro-39-glutathionyl-49-hydroxycarbanilide. These findings support the hypothesis that TCC is activated by oxidative dehalogenation and oxidation to a quinone imine. Incubations of TCDD-induced keratinocytes with 14 C-TCC yielded a minor radioactive peak coeluting with TCC-GSH. Thus, we conclude that covalent protein modification by TCC in TCDDinduced human keratinocyte incubations is mainly caused by activation of TCC by CYP1A1 via a dehalogenated TCC derivative as reactive species.

show abstract

“…The remaining proportion of the total loss was shared by the advection export. It is likely that a certain percentage of the target chemicals can accumulate in aquatic organisms, 15,19,43,[49][50][51] as found in the multimedia model for the sh. However, without adequate vegetation and aquatic biota quantity data, the current model failed to catch the inuence of biological accumulation.…”

mentioning

confidence: 99%

Multimedia modeling of the fate of triclosan and triclocarban in the Dongjiang River Basin, South China and comparison with field data

Zhang

Zhao

Liu

et al. 2013

Environ. Sci.: Processes Impacts

View full text Add to dashboard Cite

Triclosan (TCS) and triclocarban (TCC) are two active ingredients widely used in many home and personal care products. Multimedia fate of TCS and TCC in the Dongjiang River basin, South China were addressed by the developed level III fugacity model based on their usage. Under the assumption of steady state, the concentrations in air, water, soil, sediment, suspended particulate matter (SPM) and fish as well as transfer flux across the interface between the compartments were simulated. The measured concentrations for the two compounds in water, SPM, and sediment from field monitoring campaigns were then compared to validate the model. The results showed that the model predicted reasonably accurate concentrations and the differences between the measured and modeled concentrations were all less than 0.7 log units. TCS and TCC had a tendency to distribute into the sediment phase, which accounted for more than 66.3% and 90.3% of the total masses, respectively. Wastewater discharge was the main source for the occurrence of the two compounds in the aquatic environment, while degradation was the primary process for the loss in the study area, followed by the advection export.Sensitivity analysis showed that the most influential parameters for the fate of the target chemicals were source term, degradation rates and adsorption coefficients. Monte Carlo simulation could well describe the modeling uncertainty and variability. Environmental impactPersonal care products are widely used in everyday life. Aer use, they are discharged into the receiving environments directly or indirectly. Their detection in the environment has become an increasing concern due to their potential impacts on the ecosystem. This paper developed a modied level III fugacity model to assess the multimedia fate of two personal care products (triclosan and triclocarban) in a river basin based on their usage data and evaluated the model by eld monitoring data in the Dongjiang River Basin. The modied steady state fugacity model can be used to evaluate contamination of personal care products at the basin scale based on their usage. This tool could be adopted by various decision-makers in the management of chemicals in river basins.

show abstract

Bioconcentration, metabolism and excretion of triclocarban in larval Qurt medaka (Oryzias latipes)

Cited by 45 publications

References 34 publications

In Vitro Glucuronidation of the Antibacterial Triclocarban and Its Oxidative Metabolites

In Vitro Glucuronidation of the Antibacterial Triclocarban and Its Oxidative Metabolites

Metabolic Activation of the Antibacterial Agent Triclocarban by Cytochrome P450 1A1 Yielding Glutathione Adducts

Multimedia modeling of the fate of triclosan and triclocarban in the Dongjiang River Basin, South China and comparison with field data

Contact Info

Product

Resources

About