triclosan
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Triclosan (sometimes abbreviated as TCS) is an
antibacterial An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
and
antifungal An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as crypto ...
agent present in some consumer products, including toothpaste,
soap Soap is a salt of a fatty acid used in a variety of cleansing and lubricating products. In a domestic setting, soaps are surfactants usually used for washing, bathing, and other types of housekeeping. In industrial settings, soaps are use ...
s,
detergent A detergent is a surfactant or a mixture of surfactants with cleansing properties when in dilute solutions. There are a large variety of detergents, a common family being the alkylbenzene sulfonates, which are soap-like compounds that are more ...
s, toys, and surgical cleaning treatments. It is similar in its uses and
mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targe ...
to
triclocarban Triclocarban (sometimes abbreviated as TCC) is an antibacterial chemical once common in, but now phased out of, personal care products like soaps and lotions. It was originally developed for the medical field. Although the mode of action is unkn ...
. Its efficacy as an
antimicrobial agent An antimicrobial is an agent that kills microorganisms or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals ar ...
, the risk of
antimicrobial resistance Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. ...
, and its possible role in disrupted hormonal development remains controversial. Additional research seeks to understand its potential effects on organisms and environmental health. Triclosan was developed in 1966. A 2006 study recommended showering with 2% triclosan as a regimen in surgical units to rid patients' skin of methicillin-resistant ''Staphylococcus aureus'' (MRSA). While finding benefit for consumers and no proven risk to human health, but assumed risk of antibiotic resistance, in December 2017, the
FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
announced that "consumer antiseptic washes" containing triclosan or 23 other ingredients marketed as antimicrobials were prohibited without pre-market approval. The FDA did find that triclosan in Colgate Total toothpaste helped prevent gingivitis.


Uses

Triclosan was used as a hospital scrub in the 1970s. Since then, it has expanded commercially and is now a common ingredient in soaps (0.10–1.00%),
shampoo Shampoo () is a hair care product, typically in the form of a viscous liquid, that is used for cleaning hair. Less commonly, shampoo is available in solid bar format. Shampoo is used by applying it to wet hair, massaging the product into the ...
s,
deodorant A deodorant is a substance applied to the body to prevent or mask body odor due to bacterial breakdown of perspiration or vaginal secretions, for example in the armpits, groin, or feet. A subclass of deodorants, called antiperspirants, prevents s ...
s,
toothpaste Toothpaste is a paste or gel dentifrice used with a toothbrush to clean and maintain the aesthetics and health of teeth. Toothpaste is used to promote oral hygiene: it is an abrasive that aids in removing dental plaque and food from the teeth, a ...
s,
mouthwash Mouthwash, mouth rinse, oral rinse, or mouth bath is a liquid which is held in the mouth passively or swilled around the mouth by contraction of the perioral muscles and/or movement of the head, and may be gargling, gargled, where the head is ti ...
es, cleaning supplies, and
pesticide Pesticides are substances that are meant to control pests. This includes herbicide, insecticide, nematicide, molluscicide, piscicide, avicide, rodenticide, bactericide, insect repellent, animal repellent, microbicide, fungicide, and lampri ...
s. It is part of consumer products, including kitchen utensils, toys, bedding, socks, and trash bags. As of 2017, there were five registrations for triclosan with the EPA. The antimicrobial active ingredient is added to a variety of products where it acts to slow or stop the growth of bacteria, fungi, and mildew. In commercial, institutional, and industrial equipment uses, triclosan is incorporated in conveyor belts, fire hoses, dye bath vats, or ice-making equipment as an antimicrobial. Triclosan may be directly applied to commercial
HVAC Heating, ventilation, and air conditioning (HVAC) is the use of various technologies to control the temperature, humidity, and purity of the air in an enclosed space. Its goal is to provide thermal comfort and acceptable indoor air quality. HV ...
coils, where it prevents microbial growth that contributes to product degradation. In the United States, by 2000, triclosan and
triclocarban Triclocarban (sometimes abbreviated as TCC) is an antibacterial chemical once common in, but now phased out of, personal care products like soaps and lotions. It was originally developed for the medical field. Although the mode of action is unkn ...
(TCC) could be found in 75% of liquid soaps and 29% of bar soaps, and triclosan was used in more than 2,000 consumer products. In healthcare, triclosan is used in surgical scrubs and hand washes. Use in surgical units is effective with a minimum contact time of approximately two minutes. More recently, showering with 2% triclosan has become a recommended regimen in surgical units for the
decolonization Decolonization or decolonisation is the undoing of colonialism, the latter being the process whereby imperial nations establish and dominate foreign territories, often overseas. Some scholars of decolonization focus especially on separatism, in ...
of patients whose skin carries methicillin-resistant ''Staphylococcus aureus'' (MRSA). Two small uncontrolled case studies reported the use of triclosan correlated with reduction in MRSA infections. Triclosan is also used in the coatings for some
surgical sutures A surgical suture, also known as a stitch or stitches, is a medical device used to hold body tissues together and approximate wound edges after an injury or surgery. Application generally involves using a needle with an attached length of threa ...
. There is good evidence these triclosan coated sutures reduce the risk of surgical site infection. The World Health Organization, the American College of Surgeons and the Surgical Infection Society point out the benefit of triclosan-coated sutures in reducing the risk for surgical site infection. Triclosan has been employed as a selective agent in molecular cloning. A bacterial host transformed by a
plasmid A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...
harboring a triclosan-resistant mutant ''FabI'' gene (mFabI) as a selectable marker can grow in presence of high dose of triclosan in growth media.


Effectiveness

In surgery, triclosan coated sutures reduce the risk of surgical site infection. Some studies suggest that antimicrobial hand soaps containing triclosan provide a slightly greater bacterial reduction on the hands compared to plain soap. , the US
FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
had found clear benefit to health for some consumer products containing triclosan, but not in others; for example the FDA had no evidence that triclosan in antibacterial soaps and body washes provides any benefit over washing with regular soap and water. A
Cochrane review Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health professi ...
of 30 studies concluded that triclosan/copolymer-containing toothpastes produced a 22% reduction in both
dental plaque Dental plaque is a biofilm of microorganisms (mostly bacteria, but also fungi) that grows on surfaces within the mouth. It is a sticky colorless deposit at first, but when it forms tartar, it is often brown or pale yellow. It is commonly found bet ...
and
gingival inflammation Gingivitis is a non-destructive disease that causes inflammation of the gums. The most common form of gingivitis, and the most common form of periodontal disease overall, is in response to bacterial biofilms (also called plaque) that is attached ...
when compared with fluoride toothpastes without triclosan/copolymer. There was weak evidence of a reduction in tooth cavities, and no evidence of reduction in
periodontitis Periodontal disease, also known as gum disease, is a set of inflammatory conditions affecting the tissues surrounding the teeth. In its early stage, called gingivitis, the gums become swollen and red and may bleed. It is considered the main caus ...
. A study of triclosan toothpastes did not find any evidence that it causes an increase in serious adverse cardiac events such as heart attacks. A study by
Colgate-Palmolive Colgate-Palmolive Company is an American multinational consumer products company headquartered on Park Avenue in Midtown Manhattan, New York City. The company specializes in the production, distribution, and provision of household, health car ...
found a significant reduction in gingivitis, bleeding, and plaque with the use of triclosan-containing toothpaste. An independent review by the Cochrane group suggests that the reduction in gingivitis, bleeding, and plaque is
statistically significant In statistical hypothesis testing, a result has statistical significance when it is very unlikely to have occurred given the null hypothesis (simply by chance alone). More precisely, a study's defined significance level, denoted by \alpha, is the p ...
(unlikely to occur by chance) but not
clinically significant In medicine and psychology, clinical significance is the practical importance of a treatment effect—whether it has a real genuine, palpable, noticeable effect on daily life. Types of significance Statistical significance Statistical significance ...
(unlikely to provide noticeable effects). Triclosan is used in
food storage Food storage is a way of decreasing the variability of the food supply in the face of natural, inevitable variability. p.507 It allows food to be eaten for some time (typically weeks to months) after harvest rather than solely immediately. I ...
containers although. This use is banned in the
European Union The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been des ...
since 2010.
Veterinary Veterinary medicine is the branch of medicine that deals with the prevention, management, diagnosis, and treatment of disease, disorder, and injury in animals. Along with this, it deals with animal rearing, husbandry, breeding, research on nutri ...
use as a biocidal product in the EU is governed by the
Biocidal Products Directive The Biocidal Products Directive (BPD) also known as the Biocides Directive is European Union Directive, (98/8/EC), which concerns biocides. It is officially known as Directive 98/8/EC of the European Parliament and of the Council of 16 February 1 ...
.


Chemical structure and properties

This
organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...
is a white powdered
solid Solid is one of the State of matter#Four fundamental states, four fundamental states of matter (the others being liquid, gas, and Plasma (physics), plasma). The molecules in a solid are closely packed together and contain the least amount o ...
with a slight aromatic, phenolic odor. Categorized as a
polychloro phenoxy phenol Polychloro phenoxy phenols (polychlorinated phenoxy phenols, PCPPs) are a group of organic polyhalogenated compounds. Among them include triclosan Triclosan (sometimes abbreviated as TCS) is an antibacterial and antifungal agent present in s ...
, triclosan is a
chlorinated In chemistry, halogenation is a chemical reaction that entails the introduction of one or more halogens into a compound. Halide-containing compounds are pervasive, making this type of transformation important, e.g. in the production of polymers, ...
aromatic compound Aromatic compounds, also known as "mono- and polycyclic aromatic hydrocarbons", are organic compounds containing one or more aromatic rings. The parent member of aromatic compounds is benzene. The word "aromatic" originates from the past grouping ...
that has
functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the rest ...
s representative of both
ether In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again be c ...
s and
phenol Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it req ...
s. Phenols often demonstrate antibacterial properties. Triclosan is soluble in
ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...
,
methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical and the simplest aliphatic alcohol, with the formula C H3 O H (a methyl group linked to a hydroxyl group, often abbreviated as MeOH). It is a ...
,
diethyl ether Diethyl ether, or simply ether, is an organic compound in the ether class with the formula , sometimes abbreviated as (see Pseudoelement symbols). It is a colourless, highly volatile, sweet-smelling ("ethereal odour"), extremely flammable liq ...
, and strongly
basic BASIC (Beginners' All-purpose Symbolic Instruction Code) is a family of general-purpose, high-level programming languages designed for ease of use. The original version was created by John G. Kemeny and Thomas E. Kurtz at Dartmouth College ...
solution Solution may refer to: * Solution (chemistry), a mixture where one substance is dissolved in another * Solution (equation), in mathematics ** Numerical solution, in numerical analysis, approximate solutions within specified error bounds * Soluti ...
s such as a 1 M
sodium hydroxide Sodium hydroxide, also known as lye and caustic soda, is an inorganic compound with the formula NaOH. It is a white solid ionic compound consisting of sodium cations and hydroxide anions . Sodium hydroxide is a highly caustic base and alkali ...
solution, but only slightly soluble in water. Triclosan can be synthesized from 2,4-dichlorophenol.


Synthesis

Under a reflux process, 2,4,4'-trichloro-2'-methoxydiphenyl ether is treated with
aluminium chloride Aluminium chloride, also known as aluminium trichloride, is an inorganic compound with the formula . It forms hexahydrate with the formula , containing six water molecules of hydration. Both are colourless crystals, but samples are often contam ...
. The United States Pharmacopeia formulary has published a monograph for triclosan that sets purity standards.


Mechanism of action

At high concentrations, triclosan acts as a
biocide A biocide is defined in the European legislation as a chemical substance or microorganism intended to destroy, deter, render harmless, or exert a controlling effect on any harmful organism. The US Environmental Protection Agency (EPA) uses a slig ...
with multiple
cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
ic and
membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. B ...
targets. However, at the lower concentrations seen in commercial products, triclosan appears
bacteriostatic A bacteriostatic agent or bacteriostat, abbreviated Bstatic, is a biological or chemical agent that stops bacteria from reproducing, while not necessarily killing them otherwise. Depending on their application, bacteriostatic antibiotics, disinfect ...
, and it targets bacteria primarily by inhibiting
fatty acid synthesis In biochemistry, fatty acid synthesis is the creation of fatty acids from acetyl-CoA and NADPH through the action of enzymes called fatty acid synthases. This process takes place in the cytoplasm of the cell. Most of the acetyl-CoA which is conve ...
. Triclosan binds to bacterial
enoyl-acyl carrier protein reductase Enoyl-acyl carrier protein reductase (or ENR) (), is a key enzyme of the type II fatty acid synthesis (FAS) system. ENR is an attractive target for narrow-spectrum antibacterial drug discovery because of its essential role in metabolism and its seq ...
(ENR) enzyme,The WHO Guidelines on Hand Hygiene in Healthcare (Advanced Draft)
WHO, 2006, p. 37. "9.9 Triclosan"
which is encoded by the gene ''fabI''. This binding increases the enzyme's affinity for
nicotinamide adenine dinucleotide Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an aden ...
(NAD+). This results in the formation of a stable, ternary complex of ENR-NAD+-triclosan, which is unable to participate in
fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, fr ...
synthesis. Fatty acids are necessary for building and reproducing cell membranes. Humans do not have an ENR enzyme and thus are not affected by this mode of action.


Endocrine disruptor

Triclosan has been found to be a weak
endocrine disruptor Endocrine disruptors, sometimes also referred to as hormonally active agents, endocrine disrupting chemicals, or endocrine disrupting compounds are chemicals that can interfere with endocrine (or hormonal) systems. These disruptions can cause c ...
, though the relevance of this to humans is uncertain. The compound has been found to bind with low
affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...
to both the
androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in th ...
and the
estrogen receptor Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen ( 17β-estradiol). Two classes of ER exist: nuclear estrogen receptors (ERα and ERβ), which are members of the ...
, where both
agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
ic and antagonistic responses have been observed.


Efflux pump inducer

Triclosan may upregulate or induce efflux pumps in bacteria causing them to become resistant against variety of other antibiotics.


Exposure

Humans are exposed to triclosan through skin absorption when washing hands or in the shower, brushing teeth, using mouthwash or doing dishes, and through ingestion when swallowed. When triclosan is released into the environment, additional exposure to the chemical is possible through ingesting plants grown in soil treated with
sewage sludge Sewage sludge is the residual, semi-solid material that is produced as a by-product during sewage treatment of industrial or municipal wastewater. The term "septage" also refers to sludge from simple wastewater treatment but is connected to si ...
, or eating fish exposed to it. An article from the
American Society of Agronomy The American Society of Agronomy (ASA) is a scientific and professional society of agronomists and scientists of related disciplines, principally in the United States but with many non-U.S. members as well. About It was founded December 13, 190 ...
refers to a study done by Monica Mendez ''et al.'', in which the researchers irrigated plants with water containing triclosan and months later found it in all edible parts of
tomato The tomato is the edible berry of the plant ''Solanum lycopersicum'', commonly known as the tomato plant. The species originated in western South America, Mexico, and Central America. The Mexican Nahuatl word gave rise to the Spanish word ...
and
onion An onion (''Allium cepa'' L., from Latin ''cepa'' meaning "onion"), also known as the bulb onion or common onion, is a vegetable that is the most widely cultivated species of the genus ''Allium''. The shallot is a botanical variety of the onion ...
plants. Triclosan is found to kill a wide spectrum of bacteria, and the researchers are also concerned about the effect it has on the beneficial bacteria in soil.


Distribution, metabolism, and elimination

Once absorbed, triclosan is metabolized by humans primarily through conjugation reactions into
glucuronide A glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond. The glucuronides belong to the glycosides. Glucuronidation, the conversion of chemical compounds to glucur ...
and sulfate conjugates that are excreted in feces and urine. Pharmacokinetic studies demonstrate that triclosan sulfate and glucuronide may be formed in the liver at approximately equal rates at the environmentally relevant concentration of 1 to 5 microMolar. When concentrations of triclosan are below 1 microMolar,
sulfonation Aromatic sulfonation is an organic reaction in which a hydrogen atom on an arene is replaced by a sulfonic acid functional group in an electrophilic aromatic substitution. Aryl sulfonic acids are used as detergents, dye, and drugs. Stoichiometry an ...
is expected to be the major metabolic pathway for elimination.


Health concerns

Because of potential health concerns, due to the possibility of antimicrobial resistance, endocrine disruption and other issues as listed below, triclosan has been designated as a "contaminant of emerging concern (CEC)", meaning it is under investigation for public health risk. "Emerging contaminants" can be broadly defined as any synthetic or naturally occurring chemical or any microorganism that is not commonly monitored in the environment but has the potential to enter the environment and cause known or suspected adverse ecological or human health effects. Triclosan is thought to accumulate in wastewater and return to drinking water, thus propagating a buildup that could cause increasing effects with ongoing use. In the United States, after a decades-long review of the potential health issues from this contaminant of emerging concern, the FDA ruled on September 6, 2016, that 19 active ingredients including triclosan are not generally recognized as safe and effective (GRAS/GRAE). (See
policy Policy is a deliberate system of guidelines to guide decisions and achieve rational outcomes. A policy is a statement of intent and is implemented as a procedure or protocol. Policies are generally adopted by a governance body within an organ ...
section below).


Allergic

Triclosan has been associated with a higher risk of
food allergy A food allergy is an abnormal immune response to food. The symptoms of the allergic reaction may range from mild to severe. They may include itchiness, swelling of the tongue, vomiting, diarrhea, hives, trouble breathing, or low blood pressure ...
. This may be because exposure to bacteria reduces
allergies Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...
, as predicted by the
hygiene hypothesis In medicine, the hygiene hypothesis states that early childhood exposure to particular microorganisms (such as the gut flora and helminth parasites) protects against allergic diseases by contributing to the development of the immune system. In pa ...
, and not caused by toxicology of triclosan itself. This effect may also occur with
chlorhexidine gluconate Chlorhexidine (CHX) (commonly known by the salt forms chlorhexidine gluconate and chlorhexidine digluconate (CHG) or chlorhexidine acetate) is a disinfectant and antiseptic that is used for skin disinfection before surgery and to sterilize surgi ...
and PCMX, among other antibacterial agents. * Other studies have linked triclosan to allergic
contact dermatitis Contact dermatitis is a type of acute or chronic inflammation of the skin caused by exposure to chemical or physical agents. Symptoms of contact dermatitis can include itchy or dry skin, a red rash, bumps, blisters, or swelling. These rashes are ...
in some individuals. Additionally, triclosan concentrations have been associated with allergic sensitization, especially inhalant and seasonal allergens, rather than food allergens.


By-product exposure

Triclosan can react with the free
chlorine Chlorine is a chemical element with the Symbol (chemistry), symbol Cl and atomic number 17. The second-lightest of the halogens, it appears between fluorine and bromine in the periodic table and its properties are mostly intermediate betwee ...
in chlorinated tap water to produce lesser amounts of other compounds, such as 2,4-dichlorophenol. Some of these intermediates convert into
dioxins Dioxin may refer to: * 1,2-Dioxin or 1,4-Dioxin, two unsaturated heterocyclic 6-membered rings where two carbon atoms have been replaced by oxygen atoms, giving the molecular formula C4H4O2 *Dibenzo-1,4-dioxin, the parent compound also known as ...
upon exposure to UV radiation (from the sun or other sources). The dioxins that can form from triclosan are not considered to be congeners of toxicologic concern for mammals, birds and fish.


Hormonal

Concerns on the health effects of triclosan have been raised after it was detected in human breast milk, blood, and urine samples. Studies on rats have shown that triclosan exposure modulates estrogen-dependent responses. There have been many studies performed over the years both in vivo and in vitro, in male and female fish and rats and they support the conclusion that triclosan possesses (anti)estrogenic and (anti)androgenic properties depending on species, tissues, and cell types. Human studies on triclosan and hormone effects are fewer in number than those on animals, but are being conducted. In a 2017 study on 537 pregnant women in China, prenatal triclosan exposure was associated with increased cord
testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
levels in the infants. A 2020 study using the 2011–12 NHANES database found that either triclosan concentrations are too low in the human body to cause a significant impact on male serum testosterone levels or that there is no association between triclosan and male serum testosterone levels. With regards to non-sex hormones such as TSH, a South Korean study published in 2019 found a statistically-significant positive association between triclosan exposure and serum TSH concentrations in Korean women, but no association between triclosan exposure and serum TSH in Korean men, and no association between triclosan exposure and serum
thyroxine File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4 rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus rect 66 216 386 25 ...
or
triiodothyronine Triiodothyronine, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate. Production of T3 and its prohormone thyroxine ( ...
in either sex.


History

Triclosan (TCS) was patented in 1964 by Swiss company
Ciba-Geigy Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...
. The earliest known safety testing began in 1968. It was introduced the next year, mainly for use in hospitals, and was in worldwide production and use by the early 1970s. In 1997 Ciba-Geigy merged with another Swiss company,
Sandoz Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...
, to form
Novartis Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...
. During the merger, Ciba-Geigy's chemical business was spun off to become
Ciba Specialty Chemicals Ciba was a chemical company based in and near Basel, Switzerland. "Ciba" stood for "Chemische Industrie Basel" (Chemical Industries Basel). It was formed as the non-pharmaceuticals elements of Novartis were spun out in 1997, following the merger ...
, which was acquired in 2008 by chemical giant
BASF BASF Societas Europaea, SE () is a German multinational corporation, multinational chemical company and the List of largest chemical producers, largest chemical producer in the world. Its headquarters is located in Ludwigshafen, Germany. The ...
. BASF currently manufactures TCS under the brand name Irgasan DP300.


Environmental concerns


Treatment and disposal

Exposure to triclosan in personal product use is relatively short. Upon disposal, triclosan is sent to municipal
sewage treatment Sewage treatment (or domestic wastewater treatment, municipal wastewater treatment) is a type of wastewater treatment which aims to remove contaminants from sewage to produce an effluent that is suitable for discharge to the surrounding envir ...
plants, where, in the United States, about 97–98% of triclosan is removed. Studies show that substantial quantities of triclosan (170,000–970,000 kg/yr) can escape from wastewater treatment plants and damage algae on surface waters. In a study on
effluent Effluent is wastewater from sewers or industrial outfalls that flows directly into surface waters either untreated or after being treated at a facility. The term has slightly different meanings in certain contexts, and may contain various pollut ...
from wastewater treatment facilities, approximately 75% of triclocarban was present in
sewage sludge Sewage sludge is the residual, semi-solid material that is produced as a by-product during sewage treatment of industrial or municipal wastewater. The term "septage" also refers to sludge from simple wastewater treatment but is connected to si ...
. This poses a potential environmental and ecological hazard, particularly for aquatic systems. The volume of triclosan, in the United States, re-entering the environment in
sewage Sewage (or domestic sewage, domestic wastewater, municipal wastewater) is a type of wastewater that is produced by a community of people. It is typically transported through a sewer system. Sewage consists of wastewater discharged from residenc ...
sludge after initial successful capture from wastewater is 44,000 ± 60,000 kg/yr. Triclosan can attach to other substances suspended in aquatic environments, which potentially endangers marine organisms and may lead to further bioaccumulation.
Ozone Ozone (), or trioxygen, is an inorganic molecule with the chemical formula . It is a pale blue gas with a distinctively pungent smell. It is an allotrope of oxygen that is much less stable than the diatomic allotrope , breaking down in the lo ...
is considered to be an effective tool for removing triclosan during sewage treatment. As little triclosan is released through
plastic Plastics are a wide range of synthetic or semi-synthetic materials that use polymers as a main ingredient. Their plasticity makes it possible for plastics to be moulded, extruded or pressed into solid objects of various shapes. This adaptab ...
and textile household consumer products, these are not considered to be major sources of triclosan contamination. During wastewater treatment, a portion of triclosan is degraded, while the remaining adsorbs to sewage
sludge Sludge is a semi-solid slurry that can be produced from a range of industrial processes, from water treatment, wastewater treatment or on-site sanitation systems. For example, it can be produced as a settled suspension obtained from conventiona ...
or exits the plant as effluent. A mass balance in Athens (Greece) Sewage Treatment Plant (2013) showed that 43% of triclosan is accumulated to the primary and secondary sludge, 45% is lost due to degradation while the rest 12% is discharged to the environment via the secondary treated wastewater. In the environment, triclosan may be degraded by microorganisms or react with sunlight, forming other compounds, which include chlorophenols and
dioxins Dioxin may refer to: * 1,2-Dioxin or 1,4-Dioxin, two unsaturated heterocyclic 6-membered rings where two carbon atoms have been replaced by oxygen atoms, giving the molecular formula C4H4O2 *Dibenzo-1,4-dioxin, the parent compound also known as ...
. During 1999 to 2000, US Geological Survey detected TCS in 57.6% of streams and rivers sampled.


Bioaccumulation

While studies using semi-permeable membrane devices have found that triclosan does not strongly
bioaccumulate Bioaccumulation is the gradual accumulation of substances, such as pesticides or other chemicals, in an organism. Bioaccumulation occurs when an organism absorbs a substance at a rate faster than that at which the substance is lost or eliminated ...
, methyl-triclosan is comparatively more stable and
lipophilic Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipop ...
and thus poses a higher risk of bioaccumulation. The ability of triclosan to bioaccumulate is affected by its ionization state in different environmental conditions.
Global warming In common usage, climate change describes global warming—the ongoing increase in global average temperature—and its effects on Earth's climate system. Climate change in a broader sense also includes previous long-term changes to E ...
may increase uptake and effects of triclosan in aquatic organisms.


Ecotoxicity

Triclosan is toxic to aquatic bacteria at levels found in the environment. It is highly toxic to various types of algae and has the potential to affect the structure of algal communities, particularly immediately downstream of effluents from
wastewater treatment Wastewater treatment is a process used to remove contaminants from wastewater and convert it into an effluent that can be returned to the water cycle. Once returned to the water cycle, the effluent creates an acceptable impact on the environme ...
facilities that treat household wastewaters. Triclosan has been observed in multiple organisms, including algae, aquatic blackworms, fish, and
dolphin A dolphin is an aquatic mammal within the infraorder Cetacea. Dolphin species belong to the families Delphinidae (the oceanic dolphins), Platanistidae (the Indian river dolphins), Iniidae (the New World river dolphins), Pontoporiidae (the ...
s. It has also been found in land animals including earthworms and species higher up the
food chain A food chain is a linear network of links in a food web starting from producer organisms (such as grass or algae which produce their own food via photosynthesis) and ending at an apex predator species (like grizzly bears or killer whales), det ...
. In toxicity experiments with ''Vibrio fischeri'' marine bacterium, an EC50 value of TCS equal to 0.22 mg/L has been determined. Few data are available for the long-term toxicity of TCS to algae, daphnids and fish, while enough data are available for its acute toxicity on these groups of organisms. A 2017 study that used risk quotient (RQ) methodology and evaluated the ecological threat due to the discharge of wastewater containing TCS in European rivers, reported that the probability that RQ values exceeds 1 ranged from 0.2% (for rivers with dilution factor of 1000) to 45% (for rivers with dilution factor 2). Triclosan favors anaerobic conditions which is typical in soil and sediment. The antimicrobial properties of Triclosan are resistant to anaerobic degradation which is the main contributor to its persistence in the environment.


Resistance concerns

Concern pertains to the potential for
cross-resistance Cross-resistance is when something develops resistance to several substances that have a similar mechanism of action. For example, if a certain type of bacteria develops resistance to one antibiotic, that bacteria will also have resistance to sev ...
(or co-resistance) to other antimicrobials. Numerous studies have been performed and there have been results indicating that the use of biocidal agents, such as triclosan, can cause cross-resistance. A study done in a wide range of bacteria and different classes of antibiotics showed that ''
Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. aerugi ...
'' and ''
Stenotrophomonas maltophilia ''Stenotrophomonas maltophilia'' is an aerobic, nonfermentative, Gram-negative bacterium. It is an uncommon bacterium and human infection is difficult to treat. Initially classified as ''Bacterium bookeri'', then renamed ''Pseudomonas maltophil ...
'', already resistant to triclosan, had increased resistance against antibiotics tetracycline and norfloxacin when exposed to triclosan. Results from a study published in ''The American Journal of Infection Control'' showed that exposure to triclosan was associated with a high risk of developing resistance and cross-resistance in ''
Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive ...
'' and ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
''. This was not observed with exposure to
chlorhexidine Chlorhexidine (CHX) (commonly known by the salt forms chlorhexidine gluconate and chlorhexidine digluconate (CHG) or chlorhexidine acetate) is a disinfectant and antiseptic that is used for skin disinfection before surgery and to sterilize surg ...
or a hydrogen
peroxide In chemistry, peroxides are a group of compounds with the structure , where R = any element. The group in a peroxide is called the peroxide group or peroxo group. The nomenclature is somewhat variable. The most common peroxide is hydrogen p ...
-based agent (during the conditions in said study).


Alternatives

A comprehensive
meta-analysis A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...
published in 2007 indicated that, in community settings, plain soap was no less effective than soaps containing triclosan for "preventing infectious illness symptoms and reducing bacterial levels on the hands.". Nonorganic antibiotics and organic biocides are effective alternatives to triclosan, such as silver and copper ions and
nanoparticle A nanoparticle or ultrafine particle is usually defined as a particle of matter that is between 1 and 100 nanometres (nm) in diameter. The term is sometimes used for larger particles, up to 500 nm, or fibers and tubes that are less than 1 ...
s.


Policy

In the US, triclosan is regulated as a pesticide by EPA and as a drug by FDA. EPA generally regulates uses on solid surfaces, and FDA regulations cover uses in personal care products. In 1974, the US FDA began the drug review monograph process for "over-the-counter (OTC) topical antimicrobial products", including triclosan and triclocarban. The advisory panel first met on June 29, 1972, and the agency published its proposed rule on Sept 13, 1974. The initial rule applied to, "OTC products containing antimicrobial ingredients for topical human use, which includes soaps, surgical scrubs, skin washes, skin cleansers, first aid preparations and additional products defined by the panel." The proposed rule lists dozens of products that were already on the market at the time and the firms that produced them. In 1978 FDA published a tentative final monograph (TFM) for topical antimicrobial products. The record was re-opened in March 1979 to take into account six comments the agency received during the period for submitting objections to the TFM, including new data submitted by Procter & Gamble on the safety and effectiveness of triclocarban and by Ciba-Geigy on the proliferation of use of triclosan. The document states that, "significant amounts of new and previously unconsidered data were submitted with each of the above petitions." It was re-opened again in October of that year to permit interested persons to submit further data establishing conditions for the safety, effectiveness and labeling of over-the-counter topical antimicrobial products for human use. The next document issued was a proposed rule dated June 17, 1994, which states, "FDA is issuing a notice of proposed rulemaking in the form of an amended tentative final monograph that would establish conditions under which OTC topical health-care antiseptic drug products are generally recognized as safe and effective and not misbranded. FDA is issuing this notice of proposed rulemaking on topical antimicrobial drug products after considering the public comments on that notice and other information in the administrative record for this rulemaking. FDA is also requesting data and information concerning the safety and effectiveness of topical antimicrobials for use as hand sanitizers or dips." In the 1994 update to the rule, TCS was effectively removed from the drug category which made it available for use in consumer products. In 2010, the
Natural Resources Defense Council The Natural Resources Defense Council (NRDC) is a United States-based 501(c)(3) non-profit international environmental advocacy group, with its headquarters in New York City and offices in Washington D.C., San Francisco, Los Angeles, Chicago, Bo ...
forced the FDA to review triclosan after suing the agency for its inaction. Because the FDA prohibited
hexachlorophene Hexachlorophene, also known as Nabac, is an organochlorine compound that was once widely used as a disinfectant. The compound occurs as a white odorless solid, although commercial samples can be off-white and possess a slightly phenolic odor. It ...
, a compound similar to triclosan, Halden and others argued that the FDA should also ban triclosan. On December 17, 2013, the FDA issued a draft rule revoking the generally recognized as safe status of triclosan as an ingredient in hand wash products, citing the need for additional studies of its potential endrocrine and developmental effects; impact on bacterial resistance; and carcinogenic potential. On September 6, 2016, 44 years after its initial proposed rule, the FDA issued a final rule establishing that 19 active ingredients, including triclosan and triclocarban, used in over-the-counter (OTC) consumer antiseptic products intended for use with water (aka consumer antiseptic washes) are not generally recognized as safe and effective (GRAS/GRAE) and are misbranded, and are new drugs for which approved applications under section 505 of the FD&C Act are required for marketing. Companies have one year to reformulate products without these ingredients, take them off the market or submit a New Drug Application (NDA) for the products. The 19 ingredients are: * Cloflucarban * Fluorosalan *
Hexachlorophene Hexachlorophene, also known as Nabac, is an organochlorine compound that was once widely used as a disinfectant. The compound occurs as a white odorless solid, although commercial samples can be off-white and possess a slightly phenolic odor. It ...
*
Hexylresorcinol Hexylresorcinol is an organic compound with local anaesthetic, antiseptic, and anthelmintic properties. It is available for use topically on small skin infections, or as an ingredient in throat lozenges. It is marketed as S.T.37 by Numark Labora ...
* Iodine complex (ammonium ether sulfate and polyoxyethylene sorbitan monolaurate) * Iodine complex (phosphate ester of alkylaryloxy polyethylene glycol) * Methylbenzethonium chloride * Nonylphenoxypoly (ethyleneoxy) ethanoliodine *
Phenol Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it req ...
(greater than 1.5 percent) * Phenol (less than 1.5 percent) *
Poloxamer Poloxamers are nonionic triblock copolymers composed of a central hydrophobic chain of polyoxypropylene (poly(propylene oxide)) flanked by two hydrophilic chains of polyoxyethylene (poly(ethylene oxide)). The word was coined by BASF inventor, I ...
-iodine complex *
Povidone-iodine Povidone-iodine (PVP-I), also known as iodopovidone, is an antiseptic used for skin disinfection before and after surgery. It may be used both to disinfect the hands of healthcare providers and the skin of the person they are caring for. It may a ...
5 to 10 percent * Secondary amyltricresols * Sodium oxychlorosene *
Tribromsalan Salicylanilide is a chemical compound which is the amide of salicylic acid and aniline. It is classified as both a salicylamide and an anilide. Derivatives of salicylanilide have a variety of pharmacological uses. Chlorinated derivatives inclu ...
*
Triclocarban Triclocarban (sometimes abbreviated as TCC) is an antibacterial chemical once common in, but now phased out of, personal care products like soaps and lotions. It was originally developed for the medical field. Although the mode of action is unkn ...
* Triclosan * Triple dye (an antiseptic applied to the
umbilical region The umbilical region, is one of the nine regions of the abdomen. It is the region that surrounds the area around the umbilicus and is placed approximately half way between the xiphoid process and the pubic symphysis. This region of the abdomen c ...
of newborn infants) * Undecoylium chloride iodine complex In 2015 and 2016 FDA also issued proposed rules to amend the 1994 TFM regarding the safety and effectiveness of OTC health care antiseptics and OTC consumer antiseptic rubs. The state of Minnesota took action against triclosan in advance of a federal rule. In May 2014, the governor signed a bill banning triclosan-containing products in the state. A ''CNN'' article quotes the new law, "In order to prevent the spread of infectious disease and avoidable infections and to promote best practices in sanitation, no person shall offer for retail sale in Minnesota any cleaning product that contains triclosan and is used by consumers for sanitizing or hand and body cleansing." The law goes into effect on January 1 2017. The exceptions to this rule are individual products that have received approval from the US Food and Drug Administration for consumer use. In light of mounting evidence on the human health and ecotoxic effects of triclosan, some companies reformulated to remove it in advance of regulation: Colgate-Palmolive removed it from Palmolive Dish Soap and Softsoap in 2011 (but it remained in Colgate Total toothpaste until late 2018 or early 2019); Johnson & Johnson removed it from baby products in 2012 and all products in 2015; Procter & Gamble from all products in 2014; in 2014 it was removed from Clearasil and Avon began phasing it out; and Unilever removed it from skin care and cleansing products in 2015, and says oral care by 2017. In Canada, triclosan is allowed in cosmetics, though FDA's recent announcement has prompted Health Canada spokeswoman Maryse Durette to state in an e-mail to Toronto newspaper ''The Globe and Mail'' that, "the government will publish a final assessment of the safety of triclosan 'in the near future' and take further action 'if warranted. Health Canada maintains a Cosmetic Ingredient Hotlist, including hundreds of chemicals that are not allowed or whose use is restricted in cosmetics. The list states that triclosan is currently allowed in cosmetics up to 0.3%, and 0.03% in mouthwashes and other oral products with required warnings to avoid swallowing and not for use in children under the age of 12. Triclosan was not approved by the European Commission as an active substance for use in biocidal products for product-type 1 in January 2016. In the United States, manufacturers of products containing triclosan must indicate its presence on the label. In Europe, triclosan is regulated as a cosmetic preservative and must be listed on the label. Usage of triclosan in cosmetic products was restricted by the EU commission in 2014.Commission Regulation (EU) No 358/2014 of 9 April 2014


See also


References

{{Estrogen receptor modulators Antibiotics Antifungals Chloroarenes Endocrine disruptors Phenol ethers Selective androgen receptor modulators Steroid sulfotransferase inhibitors Xenoestrogens