Triclosan Under The Microscope

If you’ve ever used a product labeled as antibacterial, chances are you’ve encountered triclosan. Patented in the 1960s as an antimicrobial agent and first used in health care settings, triclosan became ubiquitous in the U.S. as consumers became increasingly germophobic. Companies added triclosan to soaps, bodywashes, deodorants, toothpaste, shaving gel, and cosmetics, as well as products such as dishwashing liquids, laundry detergents, cutting boards, toys, fabrics, shoes, and caulking compounds.

Triclosan became so pervasive, in fact, that one study found triclosan in three-quarters of urine samples from a group of people representative of the U.S. population (Environ. Health Perspect. 2008, DOI: 10.1289/ehp.10768).

Yet controversy about triclosan’s efficacy and safety in the consumer market has dogged the compound from the start. Many scientists question whether triclosan reduces disease enough to be beneficial in the face of concerns about its toxicity. Others are concerned that it may promote drug resistance. As a result, triclosan is currently the focus of several regulatory efforts, not the least of which is a ban on triclosan-containing soaps and cleaning products passed by Minnesota legislators last month.

When medical providers first started using triclosan as a surgical scrub, “it replaced some really scary compounds,” says Bruce D. Hammock, a toxicology professor in the department of entomology at the University of California, Davis. “Triclosan is much less toxic, more effective, and more biodegradable” than hexachlorophene and other common biocides of the time, Hammock says.

But then triclosan made its way out of the operating room and into mass consumer products. In that context, its toxicity profile and environmental lifetime make the cost-benefit analysis murkier. “To me that doesn’t say rush out and ban it,” but careful consideration should be given to whether it’s appropriate for mass use, Hammock says. For washing hands, plain soap and water likely fit most needs.

To a majority of people, the risks of triclosan are probably minimal. In a 2008 safety review, the Environmental Protection Agency concluded that there are no adverse effects at doses up to 40 mg/kg body weight. That figure was for long-term dermal exposure, based on a 90-day toxicity study in rats. For chronic dietary exposure, EPA used 30 mg/kg body weight, based on a yearlong study in baboons.

A pump or two of handwash containing less than 0.5% triclosan will yield only a few milligrams of the compound, and most of the material will be rinsed down the drain after a few seconds on the skin. But add in use of multiple personal care and other products, inhalation of contaminated dust, and consumption of residual amounts in water and food—including breast milk for infants—and exposure goes up. Nevertheless, EPA concluded in 2008 that aggregate exposure was within safe limits, based on analysis of urine levels.

But some people may be more susceptible to harm, such as those with genetic variations that reduce their ability to metabolize triclosan, leaving them with higher blood concentrations.

Triclosan can hinder cardiac and skeletal muscle contraction, according to a study in mice and fish by Hammock, UC Davis School of Veterinary Medicine professor of molecular biosciences Isaac N. Pessah, and colleagues (Proc. Natl. Acad. Sci. USA 2012, DOI: 10.1073/pnas.1215071109). The contraction-inhibiting effect occurs at blood plasma concentrations at the high end of those found in people.

Triclosan also appears to disrupt signaling of the endocrine system, affecting the function of estrogens, androgens, and thyroid hormones. The clinical effects of triclosan endocrine disruption are still unclear. Generally, our bodies can detoxify low levels of triclosan, says Margaret O. James, a professor of medicinal chemistry at the University of Florida. “My concern is during pregnancy when you have a developing fetus in which the hormonal environment is very critical.” In her own work, James has found that triclosan inhibits enzymes that sulfate estradiol and estrone in sheep placentas (Environ. Int. 2010, DOI: 10.1016/j.envint.2009.02.004).

In addition to concerns about human toxicity, scientists are also worried that broad use of triclosan will promote antibiotic resistance. When triclosan was first developed, scientists believed its antibacterial activity was nonspecific, perhaps akin to ethanol or isopropanol’s general ability to dehydrate cells and disrupt their membranes and proteins. Bacteria therefore wouldn’t develop resistance to the compound, as they don’t for the alcohols.

Then, in 1998, a group led by Tufts University microbiology professor Stuart B. Levy discovered that triclosan inhibits enoyl-acyl carrier protein reductase, a key enzyme in bacterial fatty acid synthesis (Nature, DOI: 10.1038/28970). Blocking the enzyme’s activity results in weakened cell membranes.

Levy and colleagues also found that overexpressing or mutating the gene for the enzyme can prevent triclosan action. Bacteria exposed to triclosan outside of the lab can similarly develop mutations to acquire resistance. Because bacteria also commonly transfer genetic material among themselves, they can share mutated regulatory or enzyme genes that pass on resistance not to just triclosan but possibly also to antibiotics that target the same enzyme.

Bacteria also defeat triclosan by pumping it out of cells. “All bacteria have genes for efflux pumps; some are narrow and some are broad in their targets,” Levy says. Gene mutations that increase production of a broadly effective pump or expand the capacity of a narrow one will also increase resistance to triclosan and antibiotics. Bacteria can share those genes as well.

Field studies of triclosan-resistant microbes show that there’s no more triclosan resistance in households that use products with the compound than there is in households that don’t. It’s unclear whether that is because microbes are not becoming resistant or the compound is so pervasive in the environment that triclosan resistance is universal, Levy says.

As for spread of antibiotic resistance to other compounds, laboratory studies of bacteria such as Escherichia coli, Salmonella enterica, and Pseudomonas aeruginosa show evidence of cross-resistance developing for triclosan and erythromycin, amoxicillin, chloramphenicol, ciprofloxacin, tetracycline, and trimethoprim (Clin. Infect. Dis. 2007, DOI: 10.1086/519255).

Beyond human toxicity and bacterial drug resistance are the potential effects of triclosan after it is washed down the drain. About half of the triclosan in wastewater survives treatment, according to work led by Rolf U. Halden, a professor of civil, environmental, and sustainable engineering at Arizona State University (Chemosphere 2007, DOI: 10.1016/j.chemosphere.2006.04.066). Of the triclosan detected after treatment, about 4% is discharged with water and 96% sits in sewage sludge.

Although the percentage of triclosan that makes it through to be discharged in water is small, aggregate use adds up. A U.S. Geological Survey study found that triclosan was one of the top five organic wastewater contaminants in stream water samples taken from 30 states in 1999–2000 (Environ. Sci. Technol. 2002, DOI: 10.1021/es011055j). The researchers found triclosan in nearly 60% of samples at concentrations ranging from 0.05 µg/L—the limit of detection—up to 2.3 µg/L.

What those levels mean for aquatic organisms is unclear. EPA in its 2008 assessment determined that about 270 µg/L will kill 50% of freshwater fish in 96 hours, and about 400 µg/L will kill 50% of freshwater invertebrates in 96 hours. Both values qualify triclosan as highly toxic to aquatic organisms. In the UC Davis muscle studies, the researchers found that concentrations of 150 µg/L impaired swimming of fathead minnows.

For freshwater aquatic plants, EPA noted that triclosan inhibited 50% of plant growth at 16 µg/L for freshwater diatoms, 1.2 µg/L for cyanobacteria, and as low as 0.7 µg/L for green algae.

Downstream from wastewater treatment plants, triclosan also gets deposited from water into sediments. A study of sediment cores in Lake Pepin, downstream from Minneapolis and St. Paul on the Mississippi River, showed triclosan first appearing in the 1960s and increasing to more than 10 ng/g dry sediment by the 1980s (Environ. Sci. Technol. 2010, DOI: 10.1021/es1001105). The research team, which was led by University of Minnesota, Twin Cities, chemical engineering professor William A. Arnold and Swiss Federal Institute of Technology (ETH), Zurich, environmental chemistry professor Kristopher McNeill, also observed chlorinated triclosan derivatives from water treatment and dioxin derivatives from photoreactions. Although dioxins are generally considered to be highly toxic persistent environmental pollutants, toxicity of the triclosan derivatives has not been evaluated.

Although the concentrations of triclosan in water and sediments are less than acutely toxic concentrations, chronic, low-level exposure for multiple generations may still cause ecosystem problems by interfering with species low on the food chain. Triclosan may also accumulate in fatty tissue in fish, ultimately causing harmful effects through endocrine disruption or other mechanisms. Researchers are calling for additional studies on the effects of triclosan on aquatic ecosystems, especially since it does not biodegrade easily. “The more long-lived a chemical is, the more opportunity it has to move around the ecosystem and find a place it can do harm,” Halden says.

There’s also the triclosan that adheres to sewage sludge. The compound survives as the sludge is converted into biosolids that are applied as fertilizer. In this environment, triclosan poses potential concerns for the microbial communities that cycle nutrients, as well as toxicity to organisms such as earthworms and plants. Triclosan may also migrate through the soil.

So far, such concerns seem minor. In one study of the effects of triclosan on microbial communities in agricultural soil, most changes appeared to be more due to the addition of biosolids or passage of time than to triclosan (Water Environ. Res. 2013, DOI: 10.2175/106143012x13560205144335). And although triclosan-contaminated fertilizer does interfere with nitrogen cycling, the benefit of the fertilizer outweighs the triclosan effect, says Thomas M. Young, a professor of civil and environmental engineering at UC Davis.

Other studies indicate that the amount of triclosan in biosolids is not toxic to either earthworms or plants and that plant uptake and bioaccumulation are “minimal” (Environ. Toxicol. Chem. 2012, DOI: 10.1002/etc.1721 and 10.1002/etc.1930). Another study also found minimal uptake into plants but that triclosan persisted in and migrated through soil (J. Am. Water Resour. Assoc. 2014, DOI: 10.1111/jawr.12163). As in the aquatic environment, more study would be helpful to enable researchers to fully understand triclosan’s fate and toxicity.

Looming over all the concerns about human and environmental toxicity of triclosan is one question: Does it provide a health benefit to those who use it?

Triclosan does kill bacteria. In one recent study, washing hands with a product containing 0.46% triclosan reduced Shigella flexneri bacterial counts by about an order of magnitude more than washing with a nonantibacterial product (J. Food Prot. 2014, DOI: 10.4315/0362-028x.jfp-13-366). Washing with a triclosan-containing product also reduced the number of bacteria subsequently transferred to melon balls. An earlier review of studies comparing antimicrobial and nonantimicrobial soaps indicated that antimicrobial soap worked about five times better to reduce bacterial counts than nonantimicrobial soaps (J. Food. Prot. 2011, DOI: 10.4315/0362-028x.jfp-11-122).

But reducing bacterial counts is not the same thing as demonstrating clinical benefit. Colgate-Palmolive successfully did that for 0.3% triclosan in toothpaste, which the Food & Drug Administration approved in 1997 for the prevention of cavities, plaque, and gum inflammation, all of which are caused by bacteria. In new proposed regulations for consumer antibacterial washes published in December 2013, however, FDA identified only two clinical studies of antiseptic handwashes (Lancet 2005, DOI: 10.1016/s0140-6736(05)66912-7 and Ann. Intern. Med. 2004, DOI: 10.7326/0003-4819-140-5-200403020-00007). Both concluded that triclosan failed to reduce infections.

The lack of clinical benefit leaves some scientists thinking triclosan is overused. “With many of the chemicals I look at, I find it difficult to make a decision about what we should do about them, because there are risks and there are benefits,” Young says. But for triclosan, “it seems like we’re putting chemicals in stuff just for the point of putting chemicals in stuff.”

Others disagree. If antimicrobial-containing products are useful in areas such as food production or medical clinics, then people should be able to choose to have them in their homes, argues Richard Sedlak, executive vice president of technical and international affairs at the industry trade group the American Cleaning Institute.

What will happen to triclosan-containing consumer products is an open question. A few states are considering following Minnesota’s lead. At the federal level, EPA is again reviewing the compound’s safety profile in plastics and other non-personal-care products. FDA is reviewing comments on its proposed regulations, which would require that consumer personal care products show a clinical benefit such as reduced infections.

One concern about the regulations is the time frame. Companies only have until December to submit safety and efficacy data, but high-quality population studies typically take years to plan and execute, Sedlak says. Meanwhile, companies such as Johnson & Johnson and Procter & Gamble have already chosen to start removing triclosan from their products.

Whatever transpires, Halden hopes that we won’t again just replace one problematic chemical with another. Pointing to triclosan in personal care products, polychlorinated biphenyls in coolants, and polybrominated diphenyl ether flame retardants used in furnishings, Halden says product developers need to think harder about toxicity and biodegradability from the start. He adds, “How often can we make the same mistake before we learn our lesson?”