At 50 and 100 μM, triclosan (1-100 μM; 24 hours) decreases cell viability in a dose- and time-dependent manner. A 50 μM dose of triclosan dramatically raises the protein Bax and cleaved caspase 3, while lowering Bcl-2[2]. Phosphorylated p38 and JNK proteins are more highly expressed when exposed to 50 μM triclosan for 1-3 hours [2]. In cultured NSCs, triclosan (10–50 μM; 3 hours) at 50 μM decreases GSH activity and raises ROS generation to around 40% [2].

Triclosan (5, 50, and 500 mg/kg; oral gavage, five days a week for four weeks) induced the production of IL-4, IL-13, and anti-Der f IgE [3].

Cell Viability Assay[2]
Cell Types: Neural stem wells
Tested Concentrations: 1, 10, 20, 30, 50 and 100 μM
Incubation Duration: 24 h
Experimental Results: Initiated the decreases in cell viability in dose and time dependent manners with 50 and 100 μM.

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Western Blot Analysis[2]
Cell Types: Neural stem wells
Tested Concentrations: 50 μM
Incubation Duration: 1, 3 h
Experimental Results: Did not affect the expressions of MAPK signaling proteins per se. Differentially induced the increased expressions of both phosphorylated p38 and JNK proteins .

Animal/Disease Models: Wild type BALB/cJ mice[3]
Doses: 5, 50, 500 mg/kg
Route of Administration: po (oral gavage), five days a week for a total of four weeks
Experimental Results: Caused an increase in the production of anti-dermatophagoides farinae (Der f) IgE, IL‐4, and IL‐13, and this resulted in the aggravation of airway hyperresponsiveness in aeroallergen‐exposed wild type mice.

Absorption, Distribution and Excretion
A 2000 study showed that small amounts of triclosan can be absorbed through the skin and enter the bloodstream. Triclosan is rapidly absorbed and distributed in the human body, reaching maximum concentrations within three hours of oral administration. However, the compound is also rapidly metabolized and excreted. In one study, after topical application of a 64.5 mM solution of [(3)H]triclosan alcohol to the skin of rats, 12% of the radioactivity was recovered in feces, 8% in the carcass, 1% in urine, 30% in the stratum corneum, and 26% was washed out of the skin surface after 24 hours. The number of personal hygiene products containing triclosan has increased rapidly over the past decade, and triclosan is currently one of the most commonly used antimicrobial compounds in toothpaste. However, the extent of triclosan exposure has not been fully described. The potential risk of developing triclosan-resistant pathogens or screening for resistant strains is a cause for concern. This study aimed to (1) obtain baseline information on triclosan levels in plasma and urine, and (2) investigate the pharmacokinetic pattern after a single dose of triclosan. Ten healthy volunteers took a single oral dose of 4 mg triclosan via mouthwash. Triclosan levels in plasma and urine were monitored before and for up to 8 days after administration. Plasma triclosan levels rose rapidly, reaching peak concentrations within 1 to 3 hours, with a terminal plasma half-life of 21 hours. Most of the drug was excreted within the first 24 hours. Urinary excretion varied among subjects, with 24% to 83% of the oral dose excreted within the first 4 days after administration. In summary, triclosan appears to be readily absorbed from the gastrointestinal tract and rapidly metabolized in the human body. Its high lipid solubility raises questions about its distribution characteristics and accumulation. The results of this study lay the foundation for a deeper understanding of the toxicokinetics of triclosan in humans.
/Milk/ One study reported that the triclosan content in breast milk ranged from <20 to 300 micrograms per kilogram of lipids, while another study reported <5 to 2100 micrograms per kilogram of lipids. One study compared the triclosan levels in the breast milk of women who used products containing triclosan with those who did not, showing that the former had 0.022 to 0.95 micrograms per kilogram of lipids in their breast milk, while the latter had 0.018 to 0.35 micrograms per kilogram of lipids.
Oral and dermal routes (humans and rodents): Triclosan glucuronide is primarily excreted in urine, while triclosan is primarily excreted in feces. In humans, hamsters, rabbits, and monkeys, the concentration of triclosan administered orally and dermally was higher in urine than in feces. The opposite was true in rats, mice, and dogs. Up to 87% of triclosan (via an unspecified route) is absorbed by the human body and excreted in the urine, with the majority excreted within 72 hours of administration. A preliminary study and a 90-day rhesus monkey study investigated the dermal absorption of unlabeled triclosan. In the preliminary study, triclosan was detected in all blood samples following a single skin contact with a soap solution containing triclosan (1 mg/mL, 0.1%), with blood concentrations persisting for up to 24 hours, peaking between 8 and 12 hours. In the 90-day study, glucuronide and sulfate conjugates were detected only in blood samples, with glucuronide dominating in early blood samples (days 1-2) and triclosan sulfate dominating in all subsequent blood samples (samples were collected daily during the 90-day study). Triclosan is primarily excreted in the urine as glucuronide conjugates and in the feces primarily as free or unconjugated forms. Low concentrations of triclosan were detected in tissues. The results of this monkey study indicate that triclosan can be absorbed through the skin after 90 consecutive days of washing with 15 mL of soap (1 mg triclosan/mL), and that the ratio of glucuronide to sulfate conjugates in plasma changed with long-term administration. For more complete data on the absorption, distribution, and excretion of triclosan (14 items in total), please visit the HSDB record page.
Metabolism/Metabolites
Triclosan is readily metabolized in phase II by sulfonyltransferases and glucuronyltransferases (Wang et al., 2004). In humans, the resulting conjugates are primarily excreted in the urine.
Oral and dermal routes (humans and rodents): Triclosan absorbed through the gastrointestinal tract undergoes extensive first-pass metabolism, primarily involving glucuronide and sulfate conjugates. In humans and rodents, at higher plasma triclosan concentrations, metabolism shifts from primarily producing glucuronide conjugates to producing sulfate conjugates. Due to the extensive first-pass metabolism of triclosan, the bioavailability of unconjugated triclosan after oral exposure may be limited. Triclosan is also metabolized through the skin into glucuronide and sulfate conjugates. Triclosan was once widely used as a disinfectant in human health products. Although the chemical itself has low toxicity, its biotransformation products can be toxic to humans. Therefore, understanding the pharmacokinetics and metabolism of triclosan in animals and humans is crucial. Plasma samples collected from SD rats after oral administration of 5 mg/kg triclosan were analyzed… The results showed pharmacokinetic data of triclosan in rats, including an elimination half-life of (48.5 ± 10.5) hours, indicating slow elimination of triclosan in rats. Two hydroxylated and sulfonated triclosans, one glucuroninated triclosan, and one sulfonated triclosan were identified in rat plasma samples. …Irgasan DP 300 is excreted unchanged in feces and urine (partially as conjugates), but can also be hydroxylated into five different monohydroxy metabolites, which are found in urine; three of these are also present in feces.
The known human metabolites of triclosan include triclosan sulfate and (2S,3S,4S,5R)-6-[5-chloro-2-(2,4-dichlorophenoxy)phenoxy]-3,4,5-trihydroxyoxacyclohexane-2-carboxylic acid.
Triclosan is readily metabolized in phase II by sulfonyltransferases and glucuronyltransferases (Wang et al., 2004). In humans, the resulting conjugates are mainly excreted in urine (Sandborgh-Englund et al., 2006).
In one study, after topical application of a 64.5 mM solution of [(3)H]triclosan alcohol to the skin of rats, 12% of the radioactivity was recovered in feces 24 hours later, 8% in the carcass, 1% in urine, 30% in the stratum corneum, and 26% was washed away from the skin surface. (A7866)
The terminal plasma half-life of triclosan is 21 hours (Sandborgh-Englund et al., 2006).
Biological half-life
The terminal plasma half-life of triclosan is 21 hours.
In 12 healthy volunteers (aged 19–37 years), oral retention and pharmacokinetics of (3)H-triclosan in toothpaste containing 0.2% (3)H-triclosan were measured. …After using 1 gram of toothpaste, the retention rate of (3)H-triclosan was 36.3 ± 1.4%. …The salivary decay curve of (3)H-triclosan conformed to a two-phase model, with half-lives of 0.45 hours and 2.42 hours, respectively. …Ten healthy volunteers took 4 mg of triclosan orally via mouthwash. Plasma and urine levels of triclosan were monitored before and for 8 days after exposure. Plasma triclosan levels rapidly increased, reaching peak concentrations within 1 to 3 hours, with a terminal plasma half-life of 21 hours. Following intravenous (IV, 5 mg/kg, dissolved in polyethylene glycol-400) or intravaginal (IVg, 5 mg/kg, dissolved in corn oil) administration, the blood half-life of 14C-triclosan in the β phase was 8.8 ± 0.6 hours, with a blood clearance rate of 77.5 ± 11.3 mL/kg/hour. Plasma samples collected from SD rats after oral administration of 5 mg/kg triclosan were analyzed… This paper provides pharmacokinetic data of triclosan in rats, including an elimination half-life of (48.5 ± 10.5) hours, indicating slow elimination of triclosan in rats. Two hydroxylated and sulfonated triclosans, one glucuroninated triclosan, and one sulfonated triclosan were identified in rat plasma samples.

Toxicity Summary
Identification and Uses: Triclosan is a white to off-white crystalline powder. It is used as a fungicide and bacteriostatic agent. It is highly active against Staphylococcus aureus and is used as an active ingredient in deodorants and antibacterial soaps. It is also used as a material preservative for industrial and household plastics and textiles. Human Studies: 50 subjects were treated with a 0.5% triclosan solution (dissolved in a 1% soap solution). The study found that triclosan was not sensitizing, and its irritant properties depended on the concentration. Tests also showed that triclosan was not photosensitizing. Exposure to triclosan may lead to spontaneous abortion; this may be due to inhibition of estrogen sulfotransferase activity, leading to placental thrombosis. In terms of estrogenic activity, triclosan can displace (3)H-estradiol from the estrogen receptor (ER) on MCF7 human breast cancer cells as well as recombinant human ERα/ERβ. In children, triclosan exposure is associated with anaphylactic sensitization, particularly of inhaled and seasonal allergens, rather than food allergens. Currently, rhinitis is most strongly correlated with triclosan concentrations, while no correlation has been found with asthma. Animal studies: Triclosan applied to the ocular mucosa of rabbits can cause mild primary eye irritation. Triclosan has an extremely low sensitization index in guinea pigs. Intravenous injection of 10, 20, and 30 (rat only) mg/kg body weight of triclosan into mice and rats resulted in mild spasms, exophthalmos (mice only), mydriasis (rat only), dyspnea, and prone position, which recovered within 24 to 48 hours after administration. In an 18-month bioassay for carcinogenicity in mice, five groups of male and female mice (70 mice per sex per dose) were fed triclosan in their diet at doses of 0, 10, 30, 100, or 200 mg/kg/day. Fifty mice per sex per dose were fed triclosan for 18 consecutive months, while the remaining 20 mice were fed triclosan for only 6 months before being sacrificed. After 18 months of exposure, the incidence of hepatocellular adenomas and/or carcinomas was statistically significantly increased in both male and female mice at daily doses of 100 mg/kg or higher. The incidence in both sexes was positively correlated with the dose. In a mouse developmental toxicity study, starting from days 6–15 of gestation, 25 female mice in each group were fed triclosan at target dose levels of 0, 10, 25, 75, or 350 mg/kg/day via diet. Maternal toxicity was observed in the 75 mg/kg/day dose group, manifested as an increase in both absolute and relative liver weight in one female mouse, as well as the appearance of brownish-red patches on the liver. Developmental toxicity was observed at the target dose levels of 75 and 350 mg/kg/day, manifested as an increased rate of variation (reversible irregular ossification of the skull in the 75 and 350 mg/kg/day dose groups, and reversible irregular ossification of the phalanges in the 350 mg/kg/day dose group). At target dose levels of 75 and 350 mg/kg/day, fetal body weight decreased by 14% and 18%, respectively. Triclosan reduced androgen synthesis, leading to decreased spermatogenesis in the tested male rats. In rats, pups were administered triclosan orally at doses of 50 or 150 mg/kg body weight/day from day 3 to day 16 postnatally. Results showed significantly reduced T4 levels in 16-day-old pups in both dose groups. Triclosan was tested against Salmonella Typhimurium strains TA1537, TA100, TA98, TA1535, and TA1538 with or without metabolic activation. No treatment-related increase in gene mutations was observed at any dose. In mouse models, dermal contact with triclosan stimulated the immune system. Ecotoxicity studies: At environmentally relevant concentrations (<2 μg/L), triclosan may lead to a decline in fish populations. Triclosan in aquatic environments may affect algal growth, chlorophyll synthesis, oxidative stress responses, and cause biochemical changes. This study exposed adult male western mosquitofish (Gambusia affinis) to triclosan at concentrations of 100, 200, and 350 nM for 35 days. Results showed that the 350 nM triclosan treatment group had significantly increased vitellogenin mRNA expression, significantly reduced sperm count, and significantly increased hepatosome ratio. This study suggests that triclosan may have an endocrine disrupting effect on male mosquitofish. Furthermore, in the North American bullfrog (Rana catesbeiana), low-concentration triclosan exposure interferes with the expression of thyroid hormone-related genes and may alter the thyroid hormone-mediated post-embryonic tailless amphibian development rate. Triclosan can induce systemic toxicity in C. elegans. At practical application concentrations, triclosan acts as a bactericide targeting various cytoplasmic and cell membrane sites. However, at lower concentrations, triclosan exhibits antibacterial activity, primarily through its mechanism of action targeting bacteria by inhibiting fatty acid synthesis. Triclosan binds to bacterial enoyl-acyl carrier protein reductase (ENR), an enzyme encoded by the Fabi gene. This binding increases the enzyme's affinity for nicotinamide adenine dinucleotide (NAD+). This results in the formation of a stable ENR-NAD+-triclosan ternary complex, which is unable to participate in fatty acid synthesis. Fatty acids are essential for cell proliferation and cell membrane construction. Humans do not possess the ENR enzyme and are therefore unaffected.

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Toxicity Data
Oral LD50 in rats: 3700 mg/kg; Dermal LD50 in rabbits: 9300 mg/kg

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Interactions
Humans are frequently exposed to a variety of environmental chemicals, including tetrabromobisphenol A (TBBPA; a flame retardant), triclosan (an antibacterial agent), and bisphenol A (BPA; a polycarbonate plastic). These chemicals are readily absorbed and may interact with each other. We aimed to determine whether the use of TBBPA alone or in combination with triclosan could modulate the concentrations of BPA and 17β-estradiol (E2). Female and male CF-1 mice were subcutaneously injected with 0–27 mg TBBPA, with or without the injection of 0.33 mg triclosan, followed by dietary administration of 50 μg/kg body weight of (14)C-BPA. Radioactivity in serum and tissues was measured by liquid scintillation counting. In subsequent experiments, female and male CF-1 mice were subcutaneously injected with 0 or 1 mg TBBPA, and urinary E2 levels were measured 2–12 hours after injection. Dose as low as 1 mg of TBBPA significantly increased (14)C-BPA concentrations in the uterus and ovaries of female mice, and in the testes, epididymis, seminal vesicle coagulation glands, and prepuce glands of male mice, as well as in the serum, heart, lungs, and kidneys of both male and female mice; urinary E2 concentrations were also increased. Lower doses of TBBPA or triclosan alone had no effect on (14)C-BPA concentrations, but when both were administered co-administered, they increased (14)C-BPA concentrations. These data suggest that TBBPA, triclosan, and BPA interact in vivo, consistent with evidence that TBBPA and triclosan inhibit enzymes crucial for BPA and E2 metabolism. Atrazine is a herbicide with a number of known toxicologically relevant effects, including interactions with other chemicals. Atrazine increases the toxicity of a variety of organophosphates and has been shown to reduce the toxicity of triclosan to Daphnia magna in a concentration-dependent manner. In vitro studies have shown that atrazine is a potent activator of the xenobiotic-sensing nuclear receptor HR96, which is associated with the vertebrate constitutive androstenedione receptor (CAR) and pregnane X receptor (PXR). We performed RNA sequencing (RNAseq) to determine whether atrazine induces phase I–III detoxification enzymes in vivo and to assess its potential mixture interactions. RNA sequencing analysis revealed that the expression of glutathione S-transferases (GSTs), cytochrome P450 (CYPs), glucosyltransferases (UDPGTs), and exogenous substance transporters was induced, some of which were validated by qPCR. Pathway analysis indicated alterations in drug, glutathione, and sphingolipid metabolism, suggesting HR96 activation. Based on RNA sequencing data, we hypothesized which environmentally relevant chemicals might exhibit altered toxicity upon co-exposure to atrazine. We performed acute toxicity tests to determine the LC50 and Hillslope values for each substance and conducted toxicity tests on binary mixtures containing atrazine. We used the Computational Method for Mixture Toxicity Assessment (CATAM) to compare the observed mixture toxicity with model-predicted mixture toxicity to assess whether atrazine exhibited antagonistic, additive, or synergistic toxicity, thus validating our hypotheses. As expected, the atrazine-triclosan mixture showed reduced toxicity; the atrazine-parathion, atrazine-endosulfan, and atrazine-nonylphenol mixtures (to a lesser extent) showed increased toxicity. In summary, exposure to atrazine activates HR96 and induces phase I-III detoxification genes, which may be involved in the interaction of the mixture. This study aimed to investigate whether triclosan could alleviate clinical symptoms of nickel exposure in an allergic patch test (APR) model. Ten nickel-allergic women underwent an APR test using 1% nickel sulfate. Results showed that applying triclosan to the skin significantly reduced nickel APR symptoms in sensitized patients compared to saline and alcohol solutions (p<0.05). This study also aimed to investigate whether triclosan affects skin inflammation induced by intradermal histamine injection. Nine female volunteers participated in a double-blind study and underwent two skin patch tests. In the first test, the skin was pretreated with triclosan for 1 hour before histamine was applied. In the second test, a histamine response was induced first, followed by triclosan application. The study measured the effect of triclosan on wheals formed on the skin after histamine stimulation. The results showed that applying triclosan after wheal formation significantly reduced the area of the wheals, while skin pretreatment had little effect. ...In the Endocrine Disruptor Screening Program (EDSP) puberty protocol and the weaned rat uterine nutrition test (3-day exposure), the effects of triclosan were assessed in female Wistar rats after 21 days of exposure. In the puberty study, triclosan at a dose of 150 mg/kg advanced the age of vaginal opening and increased uterine weight, indicating estrogen-like effects. In the uterine nutrition test, rats were orally administered different doses of triclosan (1.18, 2.35, 4.69, 9.37, 18.75, 37.5, 75, 150, and 300 mg/kg), 3 μg/kg ethinylestradiol (EE), or triclosan (at the same dose) combined with 3 μg/kg EE. Compared with the control group, the EE group (positive control group) showed an increase in uterine weight, while triclosan alone had no such effect. However, compared with the EE alone group, the uterine weight in the EE combined with triclosan (≥4.69 mg/kg) group was significantly increased in a dose-dependent manner, indicating that EE enhanced the effect of estrogen on uterine weight. This result is closely related to the enhanced estrogen-induced histological changes in the uterus. In this study, triclosan also suppressed serum thyroid hormone concentrations, which is similar to the results found in other studies on male and female rats. In summary, triclosan affected the estrogen-mediated response in adolescent and weaned female rats and suppressed thyroid hormone levels in both studies. In rodent models, the lowest effective concentrations were approximately 10-fold (estrogen) and 40-fold (thyroid hormone) higher than the highest concentrations reported in human plasma, respectively.

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Non-human toxicity values
Rat intravenous LD50: 19 mg/kg
Rat subcutaneous LD50: 3900 mg/kg
Rat dermal LD50: 9300 mg/kg
Rat oral LD50: 3700 mg/kg
For more non-human toxicity values (complete data) for triclosan (7 items in total), please visit the HSDB records page.

[1]. Weatherly LM, et al. Triclosan exposure, transformation, and human health effects. J Toxicol Environ Health B Crit Rev. 2017;20(8):447-469.
[2]. Ley C, et al. Triclosan and triclocarban exposure and thyroid function during pregnancy-A randomized intervention. Reprod Toxicol. 2017 Dec;74:143-149.

Therapeutic Uses
Topical anti-infective; fatty acid synthesis inhibitor. ClinicalTrials.gov is a registry and results database that indexes human clinical studies funded by public and private institutions worldwide. The website is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each record on ClinicalTrials.gov includes a summary of the study protocol, including: the disease or condition; the intervention (e.g., the medical product, behavior, or procedure under investigation); the title, description, and design of the study; participation requirements (eligibility criteria); the location of the study; contact information for the study location; and links to relevant information from other health websites, such as the NLM's MedlinePlus (for providing patient health information) and PubMed (for providing citations and abstracts of academic articles in the medical field). Triclosan is indexed in the database. In surgical wards, methicillin-resistant Staphylococcus aureus (MRSA) infections have been successfully controlled through measures including handwashing and bathing with triclosan. Triclosan is a chlorinated bisphenol disinfectant effective against Gram-positive bacteria and most Gram-negative bacteria, but its activity against Pseudomonas spp. is poor or unstable. It is also effective against fungi. Concentrations up to 2% triclosan are commonly used in soaps, creams, and solutions for hand and wound disinfection, as well as for skin disinfection before surgery, injections, or intravenous punctures. It is also used in oral hygiene products and acne preparations. For more complete data on the therapeutic uses of triclosan (out of 7), please visit the HSDB record page.

C12H7CL3O2

289.54178071022

287.951

3380-34-5

Triclosan-d3;1020719-98-5

5564

White to off-white solid powder

1.5±0.1 g/cm3

344.6±42.0 °C at 760 mmHg

56-60 °C(lit.)

162.2±27.9 °C

0.0±0.8 mmHg at 25°C

1.632

5.17

1

2

2

17

252

0

XEFQLINVKFYRCS-UHFFFAOYSA-N

InChI=1S/C12H7Cl3O2/c13-7-1-3-11(9(15)5-7)17-12-4-2-8(14)6-10(12)16/h1-6,16H

5-chloro-2-(2,4-dichlorophenoxy)phenol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

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

DMSO : ≥ 100 mg/mL (~345.38 mM)
H2O : ~1 mg/mL (~3.45 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.63 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 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 2: ≥ 2.5 mg/mL (8.63 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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 (Please use freshly prepared in vivo formulations for optimal results.)