Bacterial

Rat thymocytes exposed to 300 µM H2O2 have greater cytotoxicity when treated with triclocarban (300 nM). Triclocarban (300 nM) promotes the process of H2O2-induced cell death, which leads to an additional increase in the population of dead cells[1]. It does not itself increase the population of death cells. Triclocarban exhibits its estrogenic effects by stimulating luciferase activity in an ER reporter gene assay, encouraging MCF-7 cell proliferation, up-regulating pS2 expression, and down-regulating ERα expression in MCF-7 cells at both the mRNA and protein levels.

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Triclocarban at concentrations ranging from 30 nM to 300 nM did not affect the number of dead cells (cell lethality) in rat thymocytes after 4 hours of incubation.
At 300 nM, triclocarban potentiated the cytotoxicity of 300 µM H₂O₂, leading to a further increase in the population of dead cells.
Triclocarban at 300 nM slightly increased the population of living cells with exposed phosphatidylserine (an early apoptotic marker) without changing overall cell lethality.
Triclocarban at concentrations of 300 nM or higher significantly decreased the cellular content of nonprotein thiol (presumably glutathione) in rat thymocytes after 1 hour of incubation.
The simultaneous application of 300 nM triclocarban and 300 µM H₂O₂ further attenuated cellular nonprotein thiol content compared to H₂O₂ alone.[1]

Human subjects' use of soap during showering causes triclocarbaban to be absorbed significantly; its Cmax in their whole blood ranges from 23 nM to 530 nM[1]. Exposure to triclocarban during gestation does not impact a mother's ability to carry her offspring to term, but exposure to triclocarban during lactation negatively impacts the offspring's survival[3].

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Exposure to Triclocarban during lactation significantly reduces neonate survival in Sprague Dawley rats.
At 0.5% w/w in maternal diet, no offspring survived beyond postnatal day (PND) 8.
At 0.2% w/w, only 13% of offspring survived beyond weaning.[3]
Gestational exposure alone did not affect survival; all pups nursed by control dams survived regardless of in utero exposure.[3]
Mammary gland involution was observed in TCC-exposed dams after litter loss, but this was secondary to reduced suckling stimulation, not a primary effect of TCC.[3]
TCC levels in milk were approximately 4 times higher than in maternal serum, indicating milk as a significant exposure route for neonates.[3]

Cell lethality was assessed using propidium iodide staining. Rat thymocytes were incubated with triclocarban (30 nM to 10 µM), H₂O₂ (100 µM or 300 µM), or both for 4 hours. Propidium iodide (final concentration 5 µM) was added at least 2 minutes before measurement. Fluorescence was measured using a flow cytometer with excitation at 488 nm and emission detection at 600±20 nm.
Apoptosis/phosphatidylserine exposure was detected using annexin V-FITC. Cells were incubated with annexin V-FITC (10 µl/ml) for 30 minutes and with 5 µM propidium iodide for 2 minutes before measurement. Fluorescence was measured with excitation at 488 nm and emission at 530±20 nm.
Cellular nonprotein thiol content was monitored using 5-chloromethylfluorescein diacetate (5-CMF-DA). Cells were incubated with 1 µM 5-CMF-DA for 30 minutes before measurement. Fluorescence was measured in living cells with intact membranes using excitation at 488 nm and emission at 530±15 nm.[1]

Rats: In three experiments that limited exposure to critical growth periods—gestation, gestation and lactation, or lactation only (cross-fostering)—Sprague Dawley rats are given control, 0.2% weight/weight (w/w), or 0.5% w/w triclocarban-supplemented chow. The goal was to identify the susceptible windows of exposure for developmental consequences.[3]

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Pregnant Sprague Dawley rats were exposed to Triclocarban via diet supplemented at 0.2% or 0.5% w/w from gestational day (GD) 5 through lactation.
Control groups received unsupplemented chow.[3]
Cross-fostering experiments were conducted to separate gestational and lactational exposure effects.
Pups were exchanged between control and TCC-exposed dams on PND 0, 1, 3, 6, and 9 to maintain suckling stimulation.[3]
Milk bands were scored daily to assess milk transfer.
Dams and pups were sacrificed at various time points for tissue collection, histology, and biofluid analysis.[3]
Blood, milk, and amniotic fluid were collected for TCC quantification using LC-MS/MS.[3]

Absorption, Distribution and Excretion
A small-scale human exposure study in a few subjects showed that some triclocarban (TCC) present in bar soaps can be absorbed through the skin and excreted in the urine as N-glucuronide. Due to its widespread production and use in various products, it is likely absorbed by the general population. A human pharmacokinetic study estimated the absorption rate of triclocarban (70 ± 15 mg) from the soap used to be 0.6%. The concentration of triclocarban-N-glucuronide in the urine of the subjects varied considerably, and steady-state excretion levels were achieved with continued daily use of the soap. The metabolism of (14)C-TCC (3,4,4'-triclocarbanirib) after oral administration of 2.2 μmol/kg has been investigated in humans. Fecal excretion (70% of the dose) was completed 120 hours after administration; urinary excretion (27% of the dose) was completed 80 hours after administration. Urinary glucuronide appears to be an effective biomarker for triclocarban exposure. In human pharmacokinetic studies, after intravenous injection of propylene glycol containing 14C-triclocarban, the radioactive material was rapidly cleared from the blood, with a blood clearance half-life of 8.6 hours. /MILK/ ... Through a series of three experiments, Sprague Dawley rats were fed a control group, a diet supplemented with 0.2% (w/w), or 0.5% (w/w) triclocarban. These experiments limited exposure time to critical growth periods: gestation, gestation and lactation, or lactation only (cross-lactation) to determine the susceptible exposure window for developmental consequences. ... The average concentration of TCC in breast milk was almost four times the corresponding maternal serum concentration. The results indicate that TCC exposure during gestation does not affect the mother's ability to carry to full term, but TCC exposure during lactation adversely affects offspring survival, although the mechanism of reduced survival is currently unclear. These findings highlight the importance of assessing the safety of TCC use in personal care products and the impact of early-life exposure.
The antibacterial agent triclocarban (TCC) is primarily enriched in the cellular components of blood. Therefore, the concentration of TCC in plasma is at least twice that in blood. A study in a small number of subjects showed that TCC from soap during showering is absorbed in small but significant amounts via whole blood sampling.
Researchers also investigated the excretion pathway and rate of the antibacterial agent (14)C-triclocarban (formerly known as triclocarbanilide) administered via parenteral injection in rats. This study compared blood concentrations based on radiometric and chemical assays after parenteral injection with blood concentrations after topical application of (14)C-triclocarban (dissolved in soap and dimethylformamide (DMF)) to the closed skin of rats. In addition, the application of other soaps and hand sanitizers containing (14)C-triclocarban to the unclosed skin of rats was investigated, and the effects of exposure time, concentration, and solubilizer use were examined. In humans, the absorption of triclocarban through the skin was investigated by chemical analysis of blood and urine after 28 days of daily showering. Data showed that rats rapidly and completely eliminated triclocarban primarily through feces. Low plasma concentrations were observed after parenteral injection, and comparisons of radiometric and chemometric assays indicated rapid triclocarban metabolism. Plasma concentrations based on (14)C-triclocarban were very low after dermal application. Absorption of (14)C-triclocarban from the skin of blocked rats via DMF was higher than via soap. On unblocked rat skin, soap absorption was less and concentration-dependent, but not time-dependent. The use of a solubilizer did not increase dermal absorption. Measurable levels of triclocarban (below 25 ppb) were not detected in blood and urine samples from volunteers during or shortly after the 28-day intensive bathing regimen. The metabolism and distribution of (14)C-TCC (3,4,4'-triclocarbanirib) in humans following oral administration of 2.2 μmol/kg body weight were evaluated. Fecal excretion (70% of the dose) was completed within 120 hours after administration; urinary excretion (27% of the dose) was completed within 80 hours. Peak plasma concentration occurred 2.8 hours after administration, at 3.7 nmol equivalent of TCC per gram of plasma (approximately 1.2 ppm). The biotransformation of triclocarban (TCC) is rapid, but does not appear to involve the cleavage of its basic structure. The major plasma metabolites are N- and N'-glucuronides of TCC, which are excreted in the urine with a half-life of approximately 2 hours; and 2'-hydroxy-TCC sulfate and 6-hydroxy-TCC sulfate (ortho-hydroxy-TCC sulfate), which are excreted with a half-life of approximately 20 hours (presumably via bile). ...
For more complete data on absorption, distribution, and excretion of triclocarban (10 items in total), please visit the HSDB record page.

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Metabolism/Metabolites
Plasma concentrations were low after parenteral injection, and comparisons of radiometric and chemical assays indicated rapid metabolism of triclocarban. The metabolic pathways of TCC in the human body include direct glucuronidation to N- and N'-glucuronides, and cyclic hydroxylation to 2'-hydroxy-TCC and 6-hydroxy-TCC, the latter of which are further metabolized to sulfate and glucuronide conjugates. Following a single oral dose of TCC, approximately 27% of the dose is excreted in the urine within 80 hours and approximately 70% in the feces within 5 days. The main urinary metabolite is N-glucuronide (average level 30 ng/mL), and the main plasma metabolite is the sulfate conjugate of 2'-OH-TCC (level range 0-20 ng/mL). Peak plasma concentrations occurred 2.8 hours after administration, at 3.7 nmol equivalent TCC per gram of plasma (approximately 1.2 ppm). The biotransformation of TCC is rapid but does not appear to involve the cleavage of the basic TCC structure. The main plasma metabolites are N- and N'-glucuronides of TCC, which are excreted in the urine with a half-life of about 2 hours; and 2'-hydroxy-TCC sulfate and 6-hydroxy-TCC sulfate (ortho-hydroxy-TCC sulfate), which are excreted with a half-life of about 20 hours (presumably via bile).
(14) The metabolism and distribution of C-TCC (3,4,4'-triclocabanibrine) were evaluated in humans at an oral dose of 2.2 μmol/kg body weight. Fecal excretion (70% of the dose) was completed 120 hours after administration; urinary excretion (27% of the dose) was completed within 80 hours. …Biotransformation of TCC is rapid but does not appear to involve the cleavage of the basic TCC structure. The main plasma metabolites are N- and N'-glucuronides of TCC, which are excreted in urine with a half-life of approximately 2 hours; and 2'-hydroxy-TCC sulfate and 6-hydroxy-TCC sulfate (ortho-hydroxy-TCC sulfate), which have a half-life of approximately 20 hours (presumably excreted in bile). …The uptake and metabolism of emerging organic pollutants (such as personal care products) by plants may pose potential risks to human health. In this study, we cultured plants of Capsicum annuum (jalapeno pepper). Plants were exposed to labeled and unlabeled triclocarban (TCC) in hydroponic media to investigate the accumulation, distribution, and metabolism of TCC after uptake. The results showed that TCC was detected in all plant tissues; after 12 weeks, the TCC concentrations in root, stem, leaf, and fruit tissues were 19.74 ± 2.26, 0.26 ± 0.04, 0.11 ± 0.01, and 0.03 ± 0.01 mg/kg dry weight, respectively. More importantly, a significant portion of the TCC absorbed by plants was metabolized, especially in stems, leaves, and fruits. Hydroxylated TCC (e.g., 2'-OH TCC and 6-OH TCC) and glycosylated OH-TCC were the main phase I and phase II metabolites in plant tissues, respectively. The amount of bound (or non-extractable) TCC residues accounted for approximately 0.5% of the total plant tissue. 44.6%, 85.6%, 69.0%, and 47.5% of TCC species accumulated in roots, stems, leaves, and fruits, respectively. After 12 weeks, the concentration of TCC metabolites in the aboveground tissues of pepper plants was more than 20 times higher than the concentration of TCC itself; notably, approximately 95.6% of TCC existed in the fruit as metabolites. Therefore, considering plant metabolism, the amount of TCC humans are exposed to through consuming pepper fruit is expected to increase significantly. Previous studies on triclocarban have shown that its biotransformation may produce active metabolites that can form protein adducts. Since the skin is the primary route of triclocarban exposure, this study explored this possibility in cultured human keratinocytes. The results showed that significant biotransformation and protein adduct formation occurred when cytochrome P450 activity was induced in the cells. 2,3,7,8-Tetrachlorodibenzo-p-dioxin is a typical aromatic hydrocarbon acceptor ligand. Due to the difficulty in detecting low concentrations of adducts in cells and tissues, we employed a novel method: accelerator mass spectrometry. Utilizing the high sensitivity of this method, we confirmed that under the P450-induced conditions, a significant portion of triclocarban forms adducts with keratinocyte proteins. Following repeated oral administration of 3,4,4'-triclocarban (TCC), bile metabolites were isolated and identified. The dominant TCC bile metabolite was 2'-hydroxy-TCC. This compound was primarily isolated from the unconjugated and glucuronide fractions. Other abundant metabolites included 6-hydroxy-TCC and 2',6-dihydroxy-TCC, primarily in glucuronide form, and 3'-hydroxy-TCC, primarily in sulfate conjugate form. Small amounts of 3',6-dihydroxy-TCC were isolated from the fractions. Unmetabolized TCC was not found in bile. Only trace amounts of other metabolites were found; no N-hydroxylation products were observed. For more complete metabolite/metabolite data on triclocarban (7 metabolites in total), please visit the HSDB record page.

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Biological half-life
10 hours
The metabolism and distribution of (14)C-TCC (3,4,4'-triclocarban) in humans after oral administration of 2.2 μmol/kg body weight have been evaluated. ……The major plasma metabolites are N- and N'-glucuronides of TCC, which are excreted in the urine with a half-life of about 2 hours; and 2'-hydroxy-TCC sulfate and 6-hydroxy-TCC sulfate (ortho-hydroxy-TCC sulfate), which are excreted with a half-life of about 20 hours (presumably in the urine). Bile). ……
……After intravenous injection of 14C-triclocarban in propylene glycol, the radioactive material is rapidly cleared from the blood with a blood clearance half-life of 8.6 hours. Approximately 54% of the dose is excreted in the feces and 21% in the urine, with a urinary elimination half-life of 10 hours. ...

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Triclocarban was detected in maternal serum, amniotic fluid, breast milk, and fetal serum after dietary exposure. [3]
In breast milk, the concentration of triclocarban was about 4 times higher than in maternal serum (e.g., 917.8 ng/mL in breast milk and 230.3 ng/mL in serum at 0.5% w/w). [3]
Triclocarban can cross the placenta and was detected in amniotic fluid at concentrations of 11.10 ng/mL (0.2% w/w) and 14.64 ng/mL (0.5% w/w). [3]

Toxicity Summary
Identification and Uses: Triclocarban (TCC) is a solid. It possesses antibacterial activity and is widely used globally in various personal care products, including deodorant soaps, detergents, cleansers, and wipes. In North America, TCC is used only as an antibacterial agent and preservative in solid soaps, liquid soaps, and shower gels. Human Studies: Human studies have shown no evidence of skin sensitization or severe irritation. Vaseline (0.1 mL) containing 0%, 1%, 3%, 6%, and 9% TCC was applied continuously to 10 men for 21 days. Mild skin irritation was observed at the 9% concentration. No evidence of skin sensitization was found in volunteers tested with TCC (1.5% and 10%). One study investigated the potential effects of TCC exposure on fetal malformations in 39 pregnant women diagnosed with fetal or postnatal malformations. Significantly elevated TCC levels were detected in the serum of mothers with abnormal deliveries. TCC's endocrine-disrupting effects have also been investigated. TCC exerts estrogenic activity by inducing luciferase activity in ER reporter gene assays, promoting MCF-7 cell proliferation, upregulating pS2 expression in MCF-7 cells, and downregulating ERα expression at both the mRNA and protein levels. In prostate cancer cell lines LNCaP and C4-2B, TCC enhances androgenic activity through androgen receptor-dependent mechanisms. Animal experiments: TCC is non-irritating to guinea pig and rabbit skin. TCC does not cause skin sensitization in guinea pigs. A 4% concentration of TCC did not show photosensitivity in guinea pigs. In rabbit eye tests, no significant irritation caused by TCC was observed in the rinse group, while only mild irritation was observed in the unrinsed group. In a two-year chronic feeding trial, 80 Sprague Dawley rats (half male and half female) were treated with doses of 0, 25, 75, and 250 mg/kg body weight/day, respectively. For most of the study period, the mean body weight of male rats in the 250 mg/kg body weight/day dose group and female rats in the 75 and 250 mg/kg body weight/day dose groups was slightly lower than that of the control group. Male rats in the 75 and 250 mg/kg body weight/day dose groups and female rats in the 250 mg/kg body weight/day dose group developed anemia. Blood biochemistry analysis showed slight increases in alkaline phosphatase, blood urea nitrogen, glucose, and total bilirubin levels in male rats in the high-dose group at different time points. No dose-related increase in tumor incidence was found in any site. The long-term effects of TCC on rats were also tested in a three-generation reproductive study. At the highest TCC dose level, the average number of live offspring in the F0 generation was lower than that in the control group. No similar trend was observed in the F1 and F2 generations. In vitro experiments showed that TCC enhanced testosterone induction and enlarged accessory organs in castrated male rats. TCC was negative for inducing chromosomal structural and numerical abnormalities in CHO cells. In the Ames test (Salmonella Typhimurium strains TA98, TA100, TA1535, and TA1537), TCC was considered non-mutagenic regardless of metabolic activation. Ecotoxicity studies: TCC has been detected in aquatic ecosystems, and toxicity studies indicate a potential environmental risk. TCC can induce systemic toxicity in C. elegans. Triclocarban (TCC) exhibits reproductive toxicity in fish at concentrations close to or equal to those measured in surface water. This study investigated the effects of TCC on mortality, population growth, lifespan, and reproductive capacity of the monogenean rotifer Brachionus koreanus using cellular reactive oxygen species (ROS) levels, glutathione S-transferase (GST) activity, and defensin gene expression. Results showed that TCC exposure led to stunted growth and decreased reproductive capacity in Brachionus koreanus, potentially adversely affecting its life cycle. Furthermore, TCC exposure resulted in increased ROS levels and GST activity over time. In a reproductive experiment on the New Zealand mud snail Potamopyrgus antipodarum, all tested concentrations of TCC, except for the 0.170 μg/L group, significantly increased embryo number. Triclocarban (TCC) inhibited the growth of Tetrahymena thermophila, and damage to its plasma membrane was observed 2 hours after exposure to TCC. Furthermore, notably, at environment-associated concentrations (1.0 μg/L), TCC caused statistically significant DNA damage in Tetrahymena thermophila, but no growth inhibition or changes in cell viability were observed. In Potamopyrgus antipodarum, exposure to environment-associated concentrations of TCC (1.6 to 10.5 μg/L) for four weeks resulted in a significant increase in the number of unmolted embryos, while exposure at 0.2, 1.6, and 10.5 μg/L significantly increased the number of shelled embryos.

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Interactions
Triclocarban (TCC) is a common antimicrobial agent in surface water and is presumed to interact with the vertebrate endocrine system. This study investigated the effects of triclocarban (TCC) alone and in combination with the model endocrine disruptor 17β-trenbolone (TRB) on reproductive function in fish. Adult channel catfish (Pimephales promelas) were continuously exposed to 1 μg/L or 5 μg/L TCC, 0.5 μg/L TRB, or a mixture of 5 μg/L TCC and 0.5 μg/L TRB (MIX) for 22 days, and various reproductive and endocrine-related indicators were measured. Results showed that exposure to TRB, MIX, or 5 μg/L TCC significantly reduced cumulative fertility in channel catfish. Exposure to 1 μg/L TCC had no effect on reproduction. Overall, TRB and MIX treatments induced similar physiological effects, leading to significant decreases in plasma vitellogenin, estradiol, and testosterone levels in females, and significant increases in plasma estradiol levels in males. Based on ovarian transcriptome analysis, both TRB and TCC treatments shared some common potential pathway effects. However, in most cases, these pathways are more likely associated with differences in reproductive status than with androgen-specific function. Overall, TCC exhibits reproductive toxicity in fish at concentrations at or near those measured in surface water. There is little evidence that TCC induces reproductive toxicity through specific endocrine or reproductive mechanisms of action, nor is there evidence that it enhances the androgenic effects of TRB. Nevertheless, the relatively small safety margins between some measured environmental and effective concentrations warrant attention. Many widely used health products contain disinfectants, and the persistent presence of these disinfectants in aquatic environments, soil, and sediments can lead to ecosystem contamination and adverse effects on wildlife. In recent years, the effects of high and low doses of pollutants, as well as mixtures of multiple chemicals, have become a focus of attention. This study used Caenorhabditis elegans to test the toxicity of the disinfectants triclosan (TCS) and triclocarban (TCC) in aquatic test media. First, single-substance toxicity tests (96-hour exposure) were performed on nominal concentrations of TCS and TCC, focusing on their effects on nematode growth and reproduction. Then, based on the half-maximal effective concentration (EC50) obtained from single-substance tests, five different ratios of TCS:TCC mixtures were prepared, all exhibiting the same toxicity. Finally, six dilutions of each mixture ratio were tested to assess their effect on the reproduction of C. elegans. In the single-substance tests, TCC was approximately 30 times more toxic than TCS in terms of growth effect and approximately 50 times more toxic than TCS in terms of reproduction effect. The toxic effects of both substances on reproduction were more significant than their toxic effects on growth. Low doses of triclocarban (TCS, 1–10 μmol/L) increased reproductive capacity by up to 301% compared to the control group, possibly due to endocrine disruption or other stress-related compensatory responses (excitatory effects). Neither disinfectant stimulated growth. In the mixtures, increasing the concentration of triclocarban (TCC) inhibited the stimulatory effect of TCS on reproduction. Furthermore, the interaction between TCS and TCC was antagonistic, therefore the toxicity of the mixtures was lower than expected, while, based on the principle of concentration addition, the toxicity of the TCS and TCC mixtures may be higher. The effects of environmentally relevant concentrations of chemical mixtures on the endocrine systems of aquatic organisms warrant attention. Triclocarban (TCC) and inorganic mercury (Hg2+) are widely present in aquatic environments and are known to interfere with endocrine pathways through different toxic mechanisms. However, the effects of mixtures of these two pollutants on aquatic organisms and the associated molecular mechanisms remain unclear. This study investigated the effects of 21 days of exposure to a binary mixture of TCC and Hg2+ on the histopathological and biochemical changes in the reproductive organs of zebrafish (Danio rerio). The results showed that: 1) Within the studied concentration range, TCC alone had a relatively small effect on liver tissue, but TCC exacerbated Hg2+-induced liver damage through indirect mechanisms such as disrupting homeostasis and altering hormone concentrations; 2) Individuals exposed to the binary mixture, especially males, exhibited more severe histological damage to the gonads. Exposure to TCC alone (2.5 or 5 μg/L) (measured concentrations of 140 or 310 ng/L) or Hg2+ alone (5 μg/L or 10 μg/L) (measured concentrations of 367 or 557 ng/L) slightly inhibited oocyte development, while simultaneous exposure to nominal concentrations of 5 μg/L TCC and 10 μg/L Hg2+ promoted oocyte maturation. In male fish, exposure to TCC or Hg2+ alone slightly delayed sperm maturation, while combined exposure resulted in reduced testicular volume and sperm count compared to fish exposed to either contaminant alone; 3) the lesions observed in fish exposed to the binary mixture may be due to transcriptional alterations and concentration regulation of genes involved in steroid production (such as cyp19a, 3β-HSD, cyp17, 17β-HSD). Plasma testosterone and estradiol levels. The observed results further confirm the complexity of toxic responses in fish exposed to low concentrations of binary chemical mixtures. Since it is impossible to gather empirical information on all possible combinations of toxins through controlled studies, applying omics approaches may help improve the predictive power for outcomes of single classes of chemicals. Estrogen regulates a variety of developmental and physiological processes. Most of its effects are mediated by the estrogen receptor (ER), which acts as a ligand-regulated transcription factor. Estrogen also regulates the activity of the membrane-associated G protein-coupled receptor GPR30. Many different types of environmental pollutants can activate the ER; some pollutants can also bind to GPR30. There is growing concern that exposure to certain compounds known as exogenous estrogens can interfere with the behavior and reproductive capacity of many wild animals and affect human health. This study investigated how two common environmental chemicals affect the in vivo expression of aromatase AroB, a known estrogen target gene, in the brain during zebrafish embryonic development. AroB converts androgens into estrogens. We demonstrated that, similar to estrogen, the well-studied isoestrogen bisphenol A (BPA, a plastic monomer) can induce brain-specific overexpression of aromatase. Experiments using selective regulators of the ER and GPR30 showed that this induction was primarily mediated through the nuclear ER. BPA induced significant overexpression of AroB RNA in the same subregion of the developing brain, with effects similar to those of estrogen. The antibacterial agent triclocarban (TCC) itself only mildly stimulated AroB expression, but TCC significantly enhanced exogenous estrogen-induced AroB overexpression. Therefore, both BPA and TCC may increase the level of aromatase in the developing brain, thereby increasing endogenous estrogen levels. Unlike estrogen, TCC inhibited BPA-induced AroB overexpression. These results suggest that exposure to a combination of certain hormonally active contaminants can lead to outcomes that are difficult to predict based on their individual effects. For more complete data on interactions of the six triclocarbans, please visit the HSDB record page.

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Non-human toxicity values
Rabbit dermal LD50 >10,000 mg/kg body weight
Mice oral LD50 >5,000 mg/kg body weight
Mice intraperitoneal LD50 2100 mg/kg body weight
Rats oral LD50 >2,000 mg/kg body weight

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10 µM triclocarban significantly increased the cell death rate of rat thymocytes (32.2 ± 4.0%) after 4 hours of incubation.
300 nM triclocarban increased the sensitivity of rat thymocytes to… H₂O₂-induced oxidative stress promotes cell death. Simultaneous application of 300 µM H₂O₂ and 300 nM triclocarban significantly inhibited the increase in cell death rate, while 3 µM TPEN (an intracellular Zn²⁺ chelator) significantly inhibited this increase. [1]

[1]. Nanomolar concentration of triclocarban increases the vulnerability of rat thymocytes to oxidative stress. J Toxicol Sci. 2013 Feb;38(1):49-55.

[2]. The in vitro estrogenic activities of triclosan and triclocarban. J Appl Toxicol. 2014 Sep;34(9):1060-7.

[3]. Early life triclocarban exposure during lactation affects neonate rat survival. Reprod Sci. 2015 Jan;22(1):75-89.

Triclocarban appears as white flakes or a white powder. (NTP, 1992)
Triclocarban belongs to the phenylurea class of compounds. Its structure is a urea group, with 4-chlorophenyl and 3,4-dichlorophenyl groups substituted at positions 1 and 3, respectively. It can be used as a disinfectant, preservative, antibacterial agent, environmental pollutant, and exogenous substance. It is a dichlorobenzene, belonging to the monochlorobenzene and phenylurea classes. Its structure is similar to 1,3-diphenylurea.
Triclocarban, with the chemical formula C13H9Cl3N2O, is an antibacterial agent, particularly effective against Gram-positive bacteria such as Staphylococcus aureus. It is an antimicrobial compound commonly found in antibacterial soaps and other personal care products. In 2017, the U.S. Food and Drug Administration (FDA) banned the sale of over-the-counter (OTC) antibacterial laundry products containing triclocarban due to its potential to cause adverse health effects such as bacterial resistance or hormonal imbalances. Triclocarban is an analogue of triclosan and possesses antibacterial properties. Triclocarban works by inhibiting the activity of acyl-(acylcarrier protein) (ACP) reductase, an enzyme widely found in bacteria, fungi, and plants. ACP reductase catalyzes the final step in the elongation cycle of each fatty acid in the type II fatty acid synthase system. Therefore, the drug interferes with cell membrane synthesis, thereby inhibiting bacterial growth.

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Drug Indications
Triclocarban (TCC), also known as 3,4,4'-triclocarbanilide, is an antibacterial agent used in solid and liquid soaps and shower gels.

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Mechanism of Action
Triclocarban is an analogue of triclosan and possesses antibacterial activity. Triclocarban works by inhibiting the activity of acyl-(acylcarrier protein) (ACP) reductase, an enzyme widely found in bacteria, fungi, and various plants. ACP reductase catalyzes the final step in the elongation cycle of each fatty acid in the type II fatty acid synthase system. Therefore, the drug interferes with cell membrane synthesis, thereby inhibiting bacterial growth.
As a cabanilide compound, triclocarban can be classified as a membrane-active compound based on its antibacterial mechanism. Its mode of action can be described as non-specific adsorption onto the cell membrane, interfering with the function of intercellular proteins and/or disrupting the semi-permeability of the cell membrane, leading to the release of ions and organic molecules. Its antibacterial or bactericidal effect depends on the concentration. At standard application concentrations, triclocarban primarily inhibits the growth of Gram-positive bacteria, but also inhibits the growth of Gram-negative bacteria. Unlike antibiotics, membrane-active antibacterial substances such as triclocarban can take effect in a short time.

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Therapeutic Uses
Preservatives, disinfectants.
/EXPL THER/ The increasing use of the antibacterial agent triclocarban in personal care products has raised concerns about environmental pollution. Triclocarban is a potent soluble epoxide hydrolase (sEH) inhibitor. sEH inhibitors (sEHI) have shown anti-inflammatory, antihypertensive, and cardioprotective effects in various animal models. However, there have been no reports on the expected role of triclocarban in sEHI in vivo. This study confirmed the anti-inflammatory effect of triclocarban in a mouse model. We used a lipopolysaccharide (LPS)-induced mouse model and examined plasma levels of systolic blood pressure, various inflammatory cytokines and chemokines, as well as the metabolomics characteristics of plasma oxidized lipids. The results showed that triclocarban significantly reversed LPS-induced pathological hypotension in a time-dependent manner and significantly inhibited the increased release of inflammatory cytokines and chemokines induced by LPS. Furthermore, triclocarban significantly altered the oxylipin profile in vivo in a time-dependent manner, directing it towards inflammation resolution, consistent with the expected role of sEHI. These results indicate that triclocarban has an anti-inflammatory effect in the mouse model at the administered dose. This study suggests that due to its potent inhibitory effect on sEH, triclocarban may possess other beneficial effects in addition to its antibacterial activity. This could be a promising starting point for developing novel, low-dose, high-value applications of triclocarban. However, these biological effects also serve as a reminder of the potential overuse of triclocarban in personal care products.

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Pharmacodynamics
The antibacterial mechanism of triclocarban’s bacteriostatic and bactericidal effects is thought to be its nonspecific adsorption to the cell membrane and interference with its function. As a result, the growth of both Gram-positive and Gram-negative bacteria is inhibited.

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Triclocarban is an antibacterial agent used in personal care products. Triclocarban can be absorbed through the skin, and nanomolar concentrations of triclocarban can be detected in human blood after bathing with soap containing triclocarban. Studies have shown that nanomolar concentrations (300 nM or higher) of triclocarban may affect cellular function by reducing the content of nonprotein thiols in cells and increasing sensitivity to oxidative stress, although no direct adverse effects on humans have been confirmed so far. [1]

C13H9CL3N2O

315.5824

313.978

C, 49.48; H, 2.87; Cl, 33.70; N, 8.88; O, 5.07

101-20-2

Triclocarban-d4;1219799-29-7

7547

Fine white plates
Fine plates
Fine, white to off-white powder

1.4±0.1 g/cm3

475.3±55.0 °C at 760 mmHg

254-256 °C(lit.)

241.2±31.5 °C

0.0±1.2 mmHg at 25°C

1.630

5.66

2

1

2

19

308

0

ClC1=C(C([H])=C([H])C(=C1[H])N([H])C(N([H])C1C([H])=C([H])C(=C([H])C=1[H])Cl)=O)Cl

ICUTUKXCWQYESQ-UHFFFAOYSA-N

InChI=1S/C13H9Cl3N2O/c14-8-1-3-9(4-2-8)17-13(19)18-10-5-6-11(15)12(16)7-10/h1-7H,(H2,17,18,19)

Carbanilide, 3,4,4'-trichloro-

3,4,4′-Trichlorocarbanilide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : 63100 mg/mL ( 199.63~316.88 mM )
Ethanol : ~5 mg/mL

Solubility in Formulation 1: 2.5 mg/mL (7.92 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 2.5 mg/mL (7.92 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (7.92 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline:2.5 mg/mL (7.92 mM)

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 (Please use freshly prepared in vivo formulations for optimal results.)