Triclosan, allergies and the "hygiene hypothesis"

When I talk to people about drug-resistant organisms and how to protect yourself against them, hand-washing and hand hygiene — for individuals and especially for health-care workers — are at the top of my list. Inevitably, I’ll get asked next about hand sanitizers, the alcohol-based gels that now are just about everywhere: outside hospital rooms, in public bathrooms, near elevators in public buildings, and in cute little bottles in bins next to the cash register in almost any drug store.

Hand sanitizer is a good thing: If it’s used properly, it kills reliably. (Except for Clostridium difficile; you need proper hand-washing to keep that down, because alcohol can’t penetrate the hard wall of the spore that the bacterium forms.) That observation usually moves the conversation pretty quickly to the more-is-better impulse that seems so central to American culture. If it’s protective to use regular hand sanitizer, surely highly antibacterial, super-duper-extra-protective, Kills Everything Smaller Than Your Head ™ sanitizer would be better?

The answer to that, counter-intuitively, is no. When it comes to the rise of resistant organisms, topical-antiseptic hand sanitizers seem likely to be part of the problem. And very new research published over the Thanksgiving holiday suggests that they may be problematic in more dimensions than we know.

The chemicals that antibacterial products use for bacterial killing work on organisms in a manner similar to antibiotics’ effect, though they are less potent — and just as organisms have evolved resistance to antibiotic compounds, they have begun to develop resistance to antibacterial compounds too. Which would be a risk worth taking if the compounds provided necessary protection; but studies show that in regular household use, regular soap provides the same amount of protection against disease organisms that antibacterial soaps do.

The most suspect compound in this emerging understanding is triclosan (2,4,4’-trichloro-2’-hydroxy-dipenyl ether), an antibacterial that is found in hundreds of household products: hand sanitizers, but also liquid soaps, bar soaps, toothpaste, acne ointments, deodorant, mouthwash, cutting boards and socks.

The compound’s safety has been under close scrutiny for years, primarily as an endocrine disruptor but also as a possible stimulator of resistance. In the European Union, triclosan has been restricted in products where it would come in contact with food, such as storage containers. The question of whether it should be removed from personal-care products has been debated but not resolved in EU reports in 2002, 2006, 2009 and in March and June of this year. In June, the EU’s Scientific Committee on Consumer Safety (SCCS) said:

Based on the available scientific information including recent data from in vitro investigations (proteomic and genomic analyses), it is not possible to quantify the risk associated with triclosan (including its use in cosmetics) in terms of development of antimicrobial resistance… In view of the concentrations of triclosan reported to trigger resistance in vitro, some of the environmental concentrations found in a number of geographical distinct areas are high enough to suggest that bacterial resistance could be triggered… The applications of triclosan which contribute to those high environmental concentrations cannot be properly identified nor quantified at present and the presence of other chemicals (e.g. antibiotics, surfactants, other biocides, etc.) in the environment, which may also affect microbial populations, would preclude assessing the effects of triclosan independently. Due to the limited number of in situ studies of resistance induced by triclosan to date, SCCS can only recommend the prudent use of triclosan, for example in applications where a health benefit can be demonstrated. However, conclusions from in vitro studies cannot be ignored, notably the role of triclosan (and other biocides) in triggering resistance. (pp.36-37)

Triclosan got a free pass for a long time in the United States. It’s one of the tens of thousands of chemical compounds that were never independently tested for safety before release, and despite a variety of studies suggesting it could be problematic, no research has ever isolated  and characterized its effects enough to make an unshakeable case for its being removed from the market. Consequently, concerns voiced about it by citizen and environmental groups took a long time to take hold.

Last March, Rep. Edward J. Markey (D-MA), chair of the energy and environment subcommittee of the House of Representatives’ Energy and Commerce Committee, released documentation from the Environmental Protection Agency and Food and Drug Administration showing that the two agencies were beginning to be concerned about the compound, based on new research results from the past several years. Markey pressed the agencies, and also manufacturers, to restrict triclosan’s use in “consumer soaps and handwashes, products intended for use by children, and products intended to come in contact with food.” In April, the FDA and EPA announced that they were beginning to take a second look at how widely triclosan is used.

So far, so (unfortunately) normal: Possibly problematic compound, lack of testing at the front end, unclear research results, insufficient federal oversight, powerful commercial interests.

But a week ago, a fresh evaluation by researchers from University of Michigan and City University of New York , published in Environmental Health Perspectives, tossed new fuel into the smoldering debate.

Using data gathered by the National Health and Nutrition Examination Survey (NHANES), the massive CDC dataset of interviews and physical exams collected every few years from thousands of Americans, the researchers looked for any evidence that  triclosan and bisphenol A are having an immune-disrupting effect. Because the NHANES results include blood and urine samples and analysis, the researchers were able to make some direct, though circumstantial, associations between individuals’ concentrations of the two endocrine disruptors and their health status.

The results for BPA deserve separate discussion (two controversial compounds in one blog post is too much). The triclosan results are provocative enough: Up to 75 percent of Americans carried some measurable amount of triclosan in their urine, fat tissue and breast milk. And the higher the urine concentration of the chemical, the more likely that person was to also have a diagnosis of allergy and hay fever. The association with allergy persisted after adjusting the data for age, sex, race, weight/body mass index, family income, and amount of education — the social and economic factors that are known to play a role in whether children develop allergic diseases.

Here’s why that’s interesting: For more than 20 years, there’s been an evolving concept in immunology known as the “hygiene hypothesis.” It contends that experiencing an environment that is “too clean” — with a lower microbial burden than the environments we evolved in, and lived in for most of human history — upsets the mutually regulated balance between two arms of the immune system and tips that balance toward a predilection for allergy.

The hypothesis was first proposed in 1989, as part of an observation that hay fever rates rose in Britain as families got smaller. It expanded (and was refined — and is still being re-argued) via observations that allergies were less common among children who had older siblings, attended day care, lived on farms or had pets — in other words, children who were more likely to have been exposed early in life to bacterial and viral diseases, and/or to soil organisms and commensal bacteria. Children who didn’t have such exposures were more likely to develop allergies as they got older.

In most iterations of the hygiene hypothesis, conscious decision-making gets blamed for hyper-cleanliness: having just one or two children, living in condos, buying antibacterial products, not letting kids play in the dirt. This newest addition suggests that there’s an inadvertent, undetected factor as well: that the pervasive distribution of triclosan, not just in in commercial products but in soil and and water, might be sterilizing our environments or our own microbiota enough to exert an immune-system effect that could be lifelong.

It’s purely an association, and it’s clearly meant to be provocative. But it’s enough to make you want to look really hard at the ingredients list of the next hand sanitizer you buy.

Cite: Clayton EMR, Todd M, Dowd JB, Aiello AE. The Impact of Bisphenol A and Triclosan on Immune Parameters in the US Population, NHANES 2003-2006. Environmental Health Perspectives. Nov 29 2010. doi:10.1289/ehp.1002883

Image courtesy of Flickr user bunchofpants under CC


Leave a Reply

Your email address will not be published. Required fields are marked *