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Toxicology Reflections

What risk does triclosan pose to human health?

10 Comments

Triclosan is an antimicrobial chemical first used in surgical disinfectants in the early 1970’s but its use has steadily increased and can now be found in a variety of personal care and consumer products (e.g., antibacterial soap, mouthwash, deoderant, textiles, plastic kitchenware). Triclosan has received a great deal of attention from the media and interest groups due to studies indicating that triclosan exposure may cause adverse effects to human health. A few examples of triclosan in the media are linked below.

http://www.huffingtonpost.com/2013/05/02/triclosan-safety-antibacterial-soap-safe-fda_n_3202847.html

http://www.ctvnews.ca/environmental-group-urges-ban-on-triclosan-1.823706

http://www.theglobeandmail.com/life/health-and-fitness/ottawa-to-review-safety-of-key-ingredient-in-anti-bacterial-soaps/article555607/#dashboard/follows/

The media and interest groups identify a number of pathways in which triclosan may cause adverse effects to human health. The most common adverse effect mentioned is the ability of triclosan to act as an endocrine disruptor. It has also been mentioned that triclosan in water can be transformed into chloroform (known human carcinogen) due to the chlorination of drinking water or various dioxins due to UV light exposure. There is also a concern that triclosan may indireclty affect human health by promoting antibiotic resistance in bacteria.

What I hope to do in these series of posts is to quantify the risk that realistic daily exposure to triclosan poses to human health, and thus determine whether a ban of triclosan, which many are callign for, is based in science or public fear created by interest groups and the media.

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10 thoughts on “What risk does triclosan pose to human health?

  1. I think several posts on the discussion board outline a similar issue with respect to public perceptions of risk versus actual risk (e.g. fluoride, 2,4-D, triclosan). Clearly, there is a gap between the public perception of risk and actual risk posed by a chemical. Could this gap be largely corrected with increased and more effective methods of risk communication? The article by Sirota and Juanchich (2012) suggests there should be “evidence-based risk communication guidelines” to ensure that risks are communicated in a way that are relevant to societal perceptions. In class, we discussed the connectivity between risk assessment and risk management; however, in my opinion, it appears as though a lot of resources are utilized to precisely determine and review the risk versus the education and effective communication of risk to the general public.

    Sirota, M. and J. Juanchich. 2012. Risk communication on shaky ground. Science. 338(6112):1286-1287.

  2. This is a great topic Ryan, one that involves the assessment of the cost and benefit of a chemical product on human health. It is interesting that there are such opposing views regarding the safety and use of triclosan (TCS). I think Lorelei is right in thinking this gap arises from the publics perception of risk versus the actual risk.

    With regard to the multiple effects TCS are associated with, is the largest concern of TCS use its effects as an endocrine disruptor, chloroform creation, or its promotion of antibiotic resistant bacteria? Would the risk of TCS transformation into chloroform be comparable to the risk associated with the use of chlorine in the treatment of municipal water? An interesting point regarding the resistance of bacteria is that it is often difficult to confine exposure to only one drug/toxicant at a time that may be producing this resistance because this is a rare event in the real world (Jones et al., 2004). This is similar to the case I presented on depleted uranium (DU) exposure in which there is a difficulty in establishing a causal pathway between human parental DU exposure and the birth defects of offspring due to exposure to other teratogens.

    The precautionary principal approach seems to be the leading viewpoint for the banning of TCS use and for those in the media that oppose its use. It is also interesting that evidence used to support the banning of TCS arise from the use of animal studies, many of which demonstrate conflicting conclusions of adverse effects or lackthereof (Sandborgh-Englund et al., 2006, Sullivan et al., 2003, Li et al., 2010, Dayan, 2007). Sullivan et al. (2003) concluded that no adverse effects have been established in humans with regard to TCS resistant bacteria, but recommended that TCS should not be added to oral hygiene products until the mechanisms of action and potential risk of development of multidrug resistance are fully understood. Uncertainty in results arise with regard to some of the listed effects, particularly with the application of animal studies to human health impacts. Thus, more population based studies may be required to gain a better understanding of exposure and effects from TCS containing products in order to make decisions on TCS use.

    Dayan, A., 2007. Risk assessment of triclosan [Irgasan®] in human breast milk. Food and chemical toxicology 45, 125-129. http://www.aseanfood.info/Articles/11020405.pdf

    Jones, O., Voulvoulis, N., Lester, J., 2004. Potential ecological and human health risks associated with the presence of pharmaceutically active compounds in the aquatic environment. Crit. Rev. Toxicol. 34, 335-350. http://informahealthcare.com/doi/pdf/10.1080/10408440490464697

    Li, X., Ying, G., Su, H., Yang, X., Wang, L., 2010. Simultaneous determination and assessment of 4-nonylphenol, bisphenol A and triclosan in tap water, bottled water and baby bottles. Environ. Int. 36, 557-562. http://www.sciencedirect.com/science/article/pii/S0160412010000619

    Sandborgh-Englund, G., Adolfsson-Erici, M., Odham, G., Ekstrand, J., 2006. Pharmacokinetics of triclosan following oral ingestion in humans. Journal of Toxicology and Environmental Health, Part A 69, 1861-1873. http://www.tandfonline.com/doi/pdf/10.1080/15287390600631706

    Sullivan, Å, Wretlind, B., Nord, C., 2003. Will triclosan in toothpaste select for resistant oral streptococci? Clinical microbiology and infection 9, 306-309. http://onlinelibrary.wiley.com/doi/10.1046/j.1469-0691.2003.00486.x/full

  3. My first thought after reading this and sourcing Health Canada1 is if there are populations that are more prone to exposure. In risk assessment characterizing exposure is an important step as certain populations may be at increased risk because of increased exposure.

    Health Canada says that triclosan is present in soap, deodorant, eye and face make-up, lotion, body-wash/shower gel, shampoo, toothpaste, mouthwash, non-prescription medication and health products1. Immediately I wonder if the exposure is greater in women who presumably use more of these products (specifically make-up) than men. However, the only study that I could find on gender-related exposure differences was by Allmyr et al. in Australia and this study actually found the opposite trend occurring2. That is, exposure was slightly, but significantly, higher in males relative to females2. During your search to quantify risk may be you can find evidence that contradicts this study and/or identifies other potential at risk groups.

    Health Canada.(2013). The Safety or Triclosan. Healthy Canadians. Government of Canada. http://healthycanadians.gc.ca/environment-environnement/home-maison/triclosan-eng.php

    Allmyr M., Harden F., Toms L.M.L., Mueller J.F., McLachlan M.S., Adolfsson-Erici M., Sandborgh-Englund G. (2008). The influence of age and gender on triclosan concentrations in Austrailain human blood serum. Science of the Total Environment. 393: 162 – 167

  4. She makes a really good point. Her point leads nicely into the next step of my assessment of the risk that triclosan poses to human health, which is characterization human exposure.

    The potential pathways of exposure of humans to triclosan is via consumer products through dermal absorption or involuntary consumption, drinking water, household dust, and/or breast milk (1). The Scientific Committee on Consumer Products (SCCP) in Europe reviewed pharmacokinetic studies to examine the proportion of triclosan exposure that is abosrbed into the body (2). The review found that approximately all consumed triclosan is absorbed into the bloodstream but absorption through the mouth and skin is very limited (2). Only trace amounts of triclosan are detected in the blood as the majority of absorbed triclosan is converted to glucuronic and sulfuric acid conjugates (2). The major pathway of excretion is through the urine and the majority of excreted triclosan is conjugated with glucuronic acid (2).

    The United States Environmental Protection Agency (USEPA) conducted an assessment of exposure to the general population using data from the United States National Health and Nutrition Examination Survey (NHANES), which was collected by the US Center for Disease Control and Prevention (CDC) (1). NHANES provided data on concentration of triclosan in urine and patterns of use of consumer products known to contain triclosan (3). At this time, there is no Canadian exposure data of this nature but apparently Health Canada is conducting biomonitoring surveys to assess triclosan exposure to the general Canadian population. These studies are expected to be completed in 2013 but have not been released yet, so the US data will have to be used to represents Canadian exposure.

    In 2007-2008, NHANES found that 82% of urine samples of participants greater than or equal to 6 years of age had detectable levels of triclosan. This indicates that the majority of individuals in the general population are being exposed to triclosan. Concentration in urine now needs to be expressed as a daily dose. USEPA used mean and 95th centile of daily urine volume (L/kg/day) that was reported by Lentner (4) to estimate daily dose (5). Studies show that the percentage of triclosan excreted in urine can range from 24% to 87% (2). In order to account for incomplete excreation, USEPA used the median value of 54% to adjust all estimates by a factor of 0.54 (5).

    There are a number of uncertainties associated with using urine concentration to estimate daily dose. Firstly, urine volume varies widely across the age group of ≥6 years. Therefore, using the 95th centile probably overestimates the average daily dose. Secondly, pharmcokinetics varies between individuals and varies within individuals over time and the majority of pharmokinetic data is based on oral dosing. However, studies consistently show that dermal exposure accounts for very little absorption into the blood and excretion percetages based on intravenous studies (~65%) are close to the median value of 54% (2). In order to account for pharmcokinetic uncertainties, USEPA used 95th centile of urine concentrations, as well as mean concentrations, to determine dose (5). Another source of uncertainity is the lack of Canadian data but products containing triclosan and usage pattens are very similar to the US, so it is not unreasonable to use the US NHANES data.

    The estimated daily dose for adults and children (≥6 years) based on 95th centile urine concentration and 95th centile daily urine volume data was 0.0222 mg/kg bw/day. The lowest estimated dialy dose was 0.0148 mg/kg bw/dayfor female individuals of 50 years and above. The highest estimated daily dose was 0.0356 mg/kg bw/day for female individuals from 6 to 12 years. To address Breda’s point, the estimated daily dose for all males and all females was the same, 0.222 mg/kg bw/day. However, men aged 12 to 59 years was 0.0243 mg/kg bw/day and women aged 13 to 49 years was 0.0284 mg/kg bw/day. As mentioned, estimated daily dose for women aged 6 to 12 years was 0.0356 mg/kg bw/day but men aged 6 to 11 years was 0.0200 mg/kg bw/day. There is some indication that for certain age groups there is a higher exposure in women as opposed to men.

    In my next post, I’m going to discuss exposure in the <6 years age group and in further posts I'm going to characterize the effects of triclosan. So Sarah, don't be a spoiler!!!

    References:

    USEPA. 2008. Triclosan reregistration eligibility decision (RED) document. List B Case No. 2340. Washington (DC): USEPA, Office of Prevention, Pesticides and Toxic Substances. http://www.epa.gov/oppsrrd1/REDs/2340red.pdf

    SCCP. 2009. Opinion on triclosan (COLIPA No. P32). Europe Commission. Health & Consumer Protection Directorate-General, Scientific Committee on Consumer Products. http://ec.europa.eu/health/ph_risk/committees/04_sccp/docs/sccp_o_166.pdf

    CDC. 2011. Fourth national report on human exposure to environmental chemicals: updated tables, February 2011. Atlanta (GA): CDC. http://www.cdc.gov/exposurereport/

    Lentner C, editor. 1981. Geigy scientific tables volumes 1: Units of measurement, body fluids, composition of the body, nutrition, 8th ed. Basil (CH): Ciba-Geigy Ltd.

    USEPA. 2011. Draft triclosan residential exposure and illustratve risk assessment. May 4, 2011. Washington (DC): USEPA, Office of Pesticides Programs, Antimicrobials Division.

  5. I was reading you post and a comment raised my interests. It is really curious why men presented a higher exposure to triclosan than women (Allmyr et al. 2008), but somehow debatable.
    However, your post made me think of another question. I am observing that different behaviour and activities influence the exposure to PAH. Have you identified any characteristic occupation or behaviour that might be influencing on the age association to exposure to triclosan?

    Allmyr M., Harden F., Toms L.M.L., Mueller J.F., McLachlan M.S., Adolfsson-Erici M., Sandborgh-Englund G. (2008). The influence of age and gender on triclosan concentrations in Austrailain human blood serum. Science of the Total Environment.
    393: 162 – 167

  6. I thought of your reflection when I was reading a communication put out by the CDC this week about the growing threats of antibiotic resistance (Antibiotic Resistance Threats in the US). It is possible that the anibiotic resistance-producing threat posed by Triclosan itself might be small compared to the indiscriminate use of antibiotics (especially in animal production but also in people), and it would likely be impossible to quantify the relative contributions of different animicrobials to the resistance issue, especially because microbes tend to transfer and adapt their resistance mechanisms. One study did find an outbreak of multi-drug resistant Psuedomonas traced back to a single soap dispenser (in which a triclosan based soap was alternated with a chlorhexidine-based soap. The bacteria was highly resistant to Triclosan (but not chlorhexidine) and it was hypothesized that the selection for triclosan-resistant bacteria in the soap dispenser enhanced resistance to a suite of other antibitoics which are affected by the same resistance mechanism (D’Arezzo, 2012). The chronic background low levels of triclosan in the environment due to their widespread use in personal and household products would seem to pose some level of risk in terms of antibiotic resistance. It seems to me the utility of risk assessments based on endpoints of toxicity or carcinogenesis are somewhat limiting due to the complexity of issues we are facing.

    Also to touch on Lorelei’s comment about risk perceptions vs reality, research has been done on the inverse relationship between perceived risks and benefits (Alakhami and Slovic, 2006) where things that are perceived as beneficial are perceived as less risky. I think for me that kind of applies to this one. Triclosan has its benefits as a disinfectant, but I question its use in personal care products where its benefits are less clear. The potential risks from such widespread use may not be huge, but maybe the benefits are not worth the risks, however small those risks are?

  7. You raise some great points. I wanted to comment first on the issue of antibiotic resistance. The antimicrobial mechanism of triclosan comes from it’s ability to hinder fatty acid synthesis in bacteria and fungi (Heath et al. 1999). Specifically, triclosan inhibits the enoyl-acyl carrier protein reductase (Fabl) step in fatty acid synthesis (Heath et al. 1999). If bacteria were able to alter the protein that is inhibited in this reaction, they may become resistant to triclosan but I wonder if this would translate into resistance to other antibiotics, particularly compounds used in human and veterinary medicine? I think you raise a good point about whether antibiotics used in humans and livestock pose a much greater threat in terms of antibiotic resistance than triclosan and other antimicrobial used in personal care products but it would be difficult to determine the contribution of each chemical group to resistance.

    Lianne also points out the influence of perceived benefit on perceived risk. I am playing the devil’s advocate a little bit here. There are studies showing that triclosan is effective at controlling certain strains of bacteria that have been shown to be very dangerous to human health. For example, two studies have shown the triclosan was very effective at controlling an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals (Brady et al. 1990, Zafar et al. 1995). I think we can agree that the risk to human health from exposure to MRSA is much greater than from exposure to triclosan? My biggest question is should we ban the use of triclosan? Is a ban based in science? Could we reserve the use of triclosan for certain high risk situations? Thoughts are welcomed.

    Heath et al. 1999. Mechanism of triclosan inhibition of bacterial fatty acid synthesis. Journal of Biological Chemistry, 274:11110-11114.

    Brady et al. 1990. Succesful control of endemic MRSA in a cardiothoracic surgical unit. Medical Journal of Australia, 152:240-245.

    Zafar et al. 1995. Use of 0.3% triclosan to eradicate an outbreak of methicillin-resistant Staphylococcus aureus in a neonatal nursery. American Journal of Infectous Control, 23:200-208.

  8. The structure of my posts are attempting to follow Health Canada’s risk assessment approach presented in class. My first and second posts made up a very basic problem formulation, while the second and third posts are attempting to assess exposure to different groups within the population. In my last post I attempted to characterize exposure to adults and children (≥6 years). In this post I want to address exposure to individuals less than 6 years of age.

    The concentration of triclosan in urine data from US NHANES, mentioned in my last post, was not collected for indivduals less than 6 years of age but it has been reported in other studies. However, the small dataset is a cource of uncertainity when characterizing the exposure of this age group. Only two studies report urine concentration in children less than 6 years of age. Calafat et al. (2009) reported 42 samples from premature infants in the US and Li et al. (2011) reported 56 samples from children ranging in age from 3 to 6 years. Health Canada has collected some data on children less than 7 days old (n=44) and 2 to 3 months old (n=46) (Health Canada).

    Using the same method to convert urine concentrations to dose used in individuals ≥6 years of age indicates that infants of age 2 to 3 months have the greatest exposure, ranging from 0.0064 to 0.0185 mg/kg bw/day. The uncertainties applied to urine concentraiton-to-dose calculations mentioend in my last post apply here but there is added uncertainity in that there is very little pharmacokinetic data for children or data providing a comparison between adults and children (SCCP 2009). Another method to address exposure other than urine concentrations is to exposure from the individual major pathways and add them to get a cumulative exposure.

    A number of studies have measured triclosan concentrations in breast milk (Dayan 2007; Allmyr et al. 2006; Azzouz et al. 2011; Wang et al. 2011). The highest concentration reported was 0.084 mg/kg which translates into a dose of 0.011 mg/kg bw/day for infants ≤6 months and 0.006 mg/kg bw/day for infants 6 to 12 months using USEPA assumptions for milk intake, milk density, and body weight (USEPA 2011). Health Canada (2012) reports conservative estimated daily doses from hand-in-mouth exposure to be 0.00000124 mg/kg bw/day for infants 6 to 12 months and object-in-mouth exposure to be 0.0068 mg/kg bw/day.

    Infants (6 – 12 months of age) will probably have the highest exposure to triclosan of indivduals less than 6 years of age due to a number of activities they perform that are not present in other groups (e.g., nursing and objects and hands being placed in the mouth). Objects- and hands-in-mouth exposure are less of an issue in infants less than 6 months of age and nursing is less frequent in infants greater than 1 year of age. Therefore the cumulative exposure of infants aged 6 to 12 months from nursing and hand/object-in-mouth is 0.0128 mg/kg bw/day. However, based on the Health Canada data, infants aged 2 to 3 months are exposed to 0.0185 mg/kg bw/day based on urine concentrations. This supports uncertainty related to exposure to children <6 years of age. More data needs to be collected on urine concentrations in these different age groups below 6 years.

    The data would indicate that infant exposure is lower than individuals greater than 6 years of age. If you rememberin my last post, in women aged 6 to 12 years, the daily exposure was 0.0356 mg/kg bw. In my next post, I'd like to start to characterize the hazard that triclosan may pose to human health.

    Calafat et al. 2009. Exposure of bisphenol A and other phenols in neonatal intensive care unit premature infants. Environmental Health Perspective, 117:639-644.

    Li et al. 2011. 4-nonylphenol, bisphenol-A and triclosan level in human urine of children and students in China, and the effects of drinking these bottled materials on the levels. Environmental International

    Health Canada. 2012. Preliminary Assessment of Triclosan. pp 137

    SCCP. 2009. Opinion on triclosan (COLIPA No. P32). Europe Commission. Health & Consumer Protection Directorate-General, Scientific Committee on Consumer Products.

    Dayan. 2007. Risk assessment of triclosan [Irgasan] in human breast milk. Food Chemistry and Toxicology, 45:125-129.

    Allmyr et al. 2006. Triclosan in plasma and milk from Swedish nursing mothers and their exposure via personal care products. Science of the Total Environment, 372:87-93.

    Azzouz et al. 2011. Simultaneous determination of 20 pharmacologically active substances in cow’s milk, goat’s milk, and human breast milk by gas chromatography-mass spectrometry. Journal of Agricultural and Food Chemistry, 59:5125-5132.

    Wang et al. 2011. Simultaneous analysis of synthetic musks and triclosan in human breast milk by gas chromatography tandem mass spectrometry. Journal of Chromatrography B, 879:1861-1869.

    USEPA. 2011. Exposure factors handbook. Washington DC: USEPA, National Center for Environmental Assessment, Office of Reserach and Development.

  9. I remember that one of the issues in risk assessment that we discussed in class is how to ask the public for information or provide them with information without unnecessarily frightening them. I know that a request for urine samples from infants would be met with several questions from the parents and/or guardians and likely an assumption by the parent that whatever you were testing for, if found in the urine, would pose an immediete and dangerous threat to their child.

    One of the problems you mention is that additonal data needs to be collected before you can accurately determine exposure in children <6 years or age but how do you collect those samples without sending the parents into a frenzy. Is there any ideas you have as to how Health Canada can acquire more samples? My guess is they don't have as many samples for that group of people compared to others because of the sensitivity associated with collecting samples from children.

  10. You make an important point. Certain groups (e.g., adults) of the population are easier to collect information on relative to other groups (e.g., infants). Consequently, our ability to assess exposure and, as an extension, our ability to assess risk to human health varies among groups. This could have profound consequences for particularly sensitive groups that are challenging to collect information on. As mentioned in class, the quality of risk assessment is driven by the quality and quantity of data available.

    To address the question, studies that are attempting to quantify exposure to infants will require parent participation. Many parents may not want to participate because information on exposure can disconcerting. However, I think many parents would want to help to collect information on their child’s exposure to certain chemicals of interest. For example, Health Canada recruited 80 pregnant women in 2008 for a “Plastic and Personal-Care Product Use in Pregnancy” study (Health Canada 2012). The women have agreed to keep a detailed diary of consumer product and food packaging use, as well as collected maternal and infant urine, meconium (feces first excreted by newborn after birth), and breast milk samples. Triclosan is one of the chemicals that will be included in the analysis of samples. The information is being collected to better define the estimated daily doses for infants. Interestingly the study is examining the use of meconium samples to measure in utero exposure due to meconium being composed of materials ingested while the baby was in the uterus (Ostrea et al. 2009). There is definitely fewer participants in a study of this nature compared to a similar study involving adults. I would guess, logistically it is more challenging to find infant participants and once you have infant participants, collect the required samples. You are also relying on mothers to recall potential exposure, in this case exposure to personal care products. Another form of uncertainty to consider. Ideally the study would want to link measure of exposure, such as urine concentration, with actual use of products that contain the chemical of interest but this is clearly an added challenge.

    Health Canada. 2012. Preliminary Assessment of Triclosan. pp 137.

    Ostrea et al. 2009. Combined analysis of prenatal (maternal hair and blood) and neonatal (infant hair, cord blood and meconium) matrices to detect fetal exposure to environmental pesticides. Environmental Research, 109:116-122.

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