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1 

## Triclosan

White Paper prepared by The Alliance for the Prudent Use of Antibiotics (APUA ) January 2011

Alliance for the Prudent Use of Antibiotics
75 Kneeland Street, 2 nd Floor
Boston, MA 02111

www.apua.org

617 636 3911

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2 Antimicrobial agents (substances that kill or inhibit the growth of microorganisms such as bacteria
, fungi
, or protozoans ) are common ingredients in many everyday household, personal care and co n sumer products. There are growing concern s about the emergence of these chemical s in the environment and their potential negative effects on human and animal health. Triclosan is a synthetic, broad

- spectrum antimicrobial agent that in recent years has exploded onto the consumer market in a wide variety of antibacterial soaps, deodoran ts, toothpastes, cosmetics, fabrics, plastics, and other products. There is a current debate on the safety, effectiveness and regulation of use of triclosan. We have reviewed the state of knowledge regarding triclosan, and it is the purpose of this white p aper to consider the following aspects that pertain to this issue: (i) the mode of action of triclosan; (ii) current usage of triclosan; (iii) the potential impact of triclosan on human and animal health; (iv) the possible association between triclosan us age and antibiotic resistance; (v) the potential impact of triclosan on the environment; (vi) current regulatory scrutiny of triclosan; and ( v ii ) potential alternatives and next steps

.

_______________________________________________________________________ _______ ______ 

### 1. Introduction Triclosan possesses mostly antibacterial properties ( kills or slows down the growth of bacteria ) , but also some antifungal and antiviral properties. Triclosan is most often used to kill bacteria on the skin and other surfaces, although it sometimes is used to preserve the product against deterioration due to microbes. Its use began in the US in the 1970s in soaps, and its uses have risen dramatically in the past few years. Triclosan, as well as other antibacterial agents and their degrad ation by

- products, are now found throughout the environment, including surface waters, soil, fis h tissue, and human breast milk (1 ). Furthermore, the American Medical Association (AMA) has concerns about the use of these chemicals and has:

e ncouraged the U.S. Food and Drug Ad ministration to study the issue,

s tated that they will monitor the progress of the current FDA evaluation of the safety and effectiveness of antimicrobials fo r consumer use,
e ncouraged continued research on the use of common antimicrobials as ingredients in consumer products and their impact on health, the environment and the major public health problem of antimicrobial resistance.
In 2009, the American Public Health Association (APHA) proposed that i t would endorse the banning of t riclosan for household and non

- medica l uses. At the time of writing, this proposal has not yet been taken any further.
Despite current and pressing efforts to review and regulate th e appropriate use of triclosan, a scientific debate continues regarding its potential negative impact on human health, the environment and potential link to resistance to antibiotics.



### 2. What is Triclosan and How Does It W ork?
Triclosan is a phenylether
, or chlorinated bisphenol
, with a broad

- spec trum antimicrobial action which is classified as a Class III drug by the FDA ( Class III drugs are compounds with high solubility and low permeability) (2 )

.

### Supported by an unrestricted education grant from the Clorox Company

3 Triclosan (2,4,4′

- trichloro

- 2′

- hydroxy

- diphenyl ether )

It is manufactured by Ciba Specialty Chemical Products under their trade names Irgasan ® and Irgacare ®

. Triclosan (generic) is also produced by a number of other manufacturers outside of the U.S. located in Switzerland, the Netherlands, China, India, So uth Korea and else where (3 )

. Triclosan usually comes in the solid form of white powder. It has a faint aromatic, phenolic scent as it is a chlorinated aromatic compound. Triclosan can come in either ether or phenol form though the phenol forms are more po pularly used as they have antibacterial properties. In addition, under the trade name of Microban ®, triclosan is used as a built

- in antimicrobial for product protection.
As a result of the potential for the formation of ultra

- trace un wanted by

- products whi ch can a ff ect the safety and efficacy of t ri closan, the United States Pharmacopeia ( USP ) has issued a monograph fo r the specific testing of bulk t riclosan. In addition to setting product specification standards and pro cedures to assay the purit y and phys ical identity of t riclosan, it also defines the limits and methods of testing for these unwanted ultra

- trace by

- products, which may be present (3 ).
2.1. Target organisms

Triclosan has a broad range of activity that encompasses many, but not all, types of G ram
- positive and Gram

- negative non

- spo rulating bacteria, some fungi (4 )
, Plasmodium falciparum and Toxoplasma gondii (5 ). It is bacteriostatic (it stops the growth of microorganisms) at low concentrations, but higher concentrations are bactericidal (it kil ls microorganisms)

. The most sensitive organisms to triclosan are staphylococci, some streptococci, some mycobacteria, Escherichia coli and Proteus spp. (against which triclosan is effective at concentrations that range from 0.01 mg/L to 0.1 mg/L). Methici llin

- resistant Staphylococcus aureus (MRSA) strains are also sensitive to triclosan (6, 7 ) and may or may not have an increased resistance to triclosan (it is sensitive to concentrations of triclosan in the range of of 0.1

– 2 mg/L )

. S howering or bathing wit h 2% triclosan has been shown to be an effective regimen for the decolonization of patients whose skin is carrying MRSA (8)

. Enterococci are much less su sceptible than staphylococci (9 ) and Pseudomonas aeruginosa is highly resistant (9 ). The microorgani sm Clostridium difficile presents a particularly hard to combat situation in hospitals. The noninfectious form, called a spore, can survive in hospitals, nursing homes, extended

- care facilities, and newborns' nurseries. The spores cannot cause infection, b ut when they are ingested, they transform into the active virulent form. In severe cases, C. difficile can cause critical illness and death in elderly or immune

- compromised patients (10) . Studies have found spores on hospital items such as over

- bed tables, side curtains, lab coats, scrubs, plants and cut flowers, computer keyboards (especially computers on wheels), bedpans, furniture, toilet seats, linens, telephones, stethoscopes, jewelry, diaper pails, and under fingernails; even physician's neck ties can be contaminated with C. difficile. (10)
Some researchers, like Dr. Dale Gerding, associate chief of staff research and development coordinator at Edward Hines Jr. VA Hospital, in Hines, Illinois, have proposed that, similar to anthrax spores, C. difficil e spores have an ― exosporium ‖

— sticky chains of protein

- containing substances

— that confers a particular adherence , or stickiness, and they stick on hands. Dr. Gerding and colleagues assessed several commercially available hand washes for C. difficile s pore removal, and concluded that care should be taken in assessing C. difficile spore claims from hand

- hygiene manufacturers, which might not be supported by scientific evidence. In their analysis, the only agent that achieved a reduction in C.difficile sp ores was t he heavy

- duty printer's ink hand cleaner. Thus, there is a c le ar need for an ef fective way to combat the sticki ness of C.difficile (10).
Table 1. Germs that are destroyed by triclosan Staphylococci Streptococci

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4 Methicillin

- resistant Staphyloc occus aureus (MRSA) Enterococci: Escherichia coli
, Klebsiella pneumonia
, Klebsiella spp, Enterobacter spp Proteus spp Acinetobacter spp Mycobacteria Proteus mirabilis

Table 2. Germs that are NOT destroyed by triclosan Pseudomonas aeruginosa Clo stridium difficile

2. 2 . Mechanism of Action
Triclosan works by blocking the active site of the enoyl

- acyl carrier protein reductase enzyme (ENR), which is an essential enzyme in fatty acid synthesis in bacteria (1 1 ) . By blocking the active site, triclosa n inhibits the enzyme, and therefore prevents the bacteria from synthesizing fatty acid, which is necessary for building cell membranes and for reproducing. Since humans do not have this ENR enzyme, triclosan has long been thought to be fairly harmless to them. Triclosan is a very potent inhibitor, and only a small amount is needed for powerful antibacterial action.
2. 3 . Uses of Triclosan

Triclosan has been used since 1972, and is now found in the following products:

soap s h and

- washes d ish

- washing products l aundry detergents and softeners p lastics (e.g., toys, cutting boards , kitchen utensils ) t oothpaste and mouth washes d eodorants and antiperspirants
c osmetics and shaving creams
a cne treatment products h air conditioners bedding trash bags apparel like sock s and undershirts hot tubs, plastic lawn furniture i mpregnated sponges surgical scrubs implantable medical devices pesticides

Triclosan is used in hundreds of common commercial prod ucts

. At this time, in the United States, manufacturers of products containing triclosan must say so somewhere on the label. So if tricl osan is of
concern , one must look for claims of a product being 'anti

- bacterial', and then check the label for triclosan. T riclosan is used as a built

- in antimicrobial product protection, under the trade name of Microban®
, in antimicrobial solutions for consumer, industrial and medical products around the world. The Microban® technology is engineered into a breadth of materials including: polymers, texti les, coatings, ceramics, paper and adhesives. Microban® controls microbial growth and odors within the impregnated surface but does not offer the user any significant protection from infectious microbes on the exterior surfaces of those ite ms. This could p otentially crea te a false sense of securit y , and cause the user to relax other efforts to keep surfaces clean.

### Supported by an unrestricted education grant from the Clorox Company

5 Table 3. List of product s containing triclosan (1 2 ) SOAPS: Dial® Liquid Soap; Softsoap® Antibacterial Liquid Hand Soap; Tea Tree TherapyTM Liquid Soap; Provon® Soap; Clearasil® Daily Face Wash; Dermatologica ® Skin Purifying Wipes; Clean & Clear Oil Free Foaming Facial Cleanser; DermaKleenTM Antibacterial Lotion S oap; Naturade Aloe Vera 80® Antibacterial Soap; CVS Antibacterial Soap, pHisoderm Antibacterial Skin Cleanser, Dawn® Complete Antibacterial Dish Liquid, Ajax® Antibacterial Dish Liquid. DENTAL CARE: Colgate Total®; BreezeTM Triclosan Mouthwash; Reach® Anti bacterial Toothbrush; Janina Diamond Whitening Toothpaste COSMETICS: Supre® Café BronzerTM; TotalSkinCare Makeup Kit; Garden Botanika® Powder Foundation; Mavala Lip Base; Jason Natural Cosmetics; Blemish Cover Stick; Movate® Skin Litening Cream HQ; Paul Mi tchell Detangler Comb, Revlon ColorStay LipSHINE Lipcolor Plus Gloss, Dazzle DEODORANT: Old Spice High Endurance Stick Deodorant, Right Guard Sport Deodorant Queen Helene® Tea Trea Oil Deodorant and Aloe Deodorant; Nature De France Le Stick Natural Stick Deodorant; DeCleor Deodorant Stick; Epoch® Deodorant with Citrisomes; X Air Maximum Strength Deodorant OTHER PERSONAL CARE PRODUCTS : Gillette® Complete Skin Care MultiGel Aerosol Shave Gel; Murad Acne Complex® Kit, ®; Diabet

- xTM Cream; T.TaioTM sponges and wipes, Aveeno Therapeutic Shave Gel. FIRST AID: SyDERMA® Skin Protectant plus First Aid Antiseptic; Solarcaine® First Aid Medicated Spray;NexcareTM First Aid, Skin Crack Care; First Aid/Burn Cream; HealWell® Night Splint; Splint 11

- 1X1: Universal Cervical Collar with Microban KITCHENWARE: Farberware® Microban Steakknife Set and Cutting Boards; Franklin Machine Products FMP Ice Cream S coop SZ 20 Microban; Hobart Semi

- Automatic Slicer; Chix® Food Service Wipes with Microban; Compact Web Foot® Wet Mop Heads COMPUTER EQUIPMENT: Fellowes Cordless Microban Keyboard and Microban Mouse Pad CLOTHES: Teva® Sandals; Merrell Shoes; Sabatier Chef ‘s Apron; Dickies Socks; Biofresh® socks CHILDRENS TOYS: Playskool®: Stack  ̳n Scoop Whale, Rockin‘ Radio, Hourglass, Sounds Around Driver, Roll  ̳n Rattle Ball, Animal Sounds Phone, Busy Beads Pal, Pop  ̳n Spin Top, Lights  ̳n Surprise Laptop OTHER: Bionare

® Cool Mist Humidifier; Microban® All Weather Reinforced Hose; Thomasville® Furniture; Deciguard AB Ear Plugs; Bauer® 5000 Helmet; Aquatic Whirlpools; Miller Paint Interior Paint; QVC® Collapsible 40

- Can Cooler; Holmes Foot BuddyTM Foot Warmer, Blue Mountai n Wall Coverings, California Paints®, EHC AMRail Escalator Handrails, DupontTM Air Filters, DurelleTM Carpet Cushions, Advanta One Laminate Floors, San Luis Blankets, J Cloth® towels, JERMEX mops

2.4. Effectiveness considerations

A variety of methods are av ailable for evaluation of the antimicrobial activity of antiseptic and disinfectant agents. An important but often overlooked variable in this type of studies is adequate neutralization of the chemical compund. Neutralization is essential to stop the antim icrobial activity and misleading interpretation of results. Triclosan is difficult to neutralize, therefore incomplete neutralization may overestimate the efficacy of triclosan

- containing products (13).

While all antimicrobial hand soaps have demonstrated acceptable levels of effectiveness in accordance with the Topical Antiseptic Drug Monograph as measured by the Heal thcare Personnel Handwash test (14) , all are hampered to some degree by the interaction of the active ingredient with the surfactants (or cl e a n ing agents) u sed. The triclosan molecules get encaged by the cleaning surfactant molecules, which help to keep the active triclosan from settling out in the solution. During lathering, a small percentage o f the active ingredient is deli vered to the skin, bu t th e rest is simply washed down the drain, trapped in these cage

- like structures. To address this problem an approach termed ―activated triclosan‖ has been applied to triclo san
- containing soaps to boost their performance. The activated triclosan uses a combination of different surfactants

- - sodium xylenesulfonate and dipropylene glycol

- - to keep the triclosan in solution and prevent its settling out in the soap (14)

. 

### 3 . Health Impacts
Data from the 2003

– 2004 National Health and Nutrition Examination Su rvey showed triclosan in 75% of urine samples analyzed (15 )

. Triclosan also has been found in rivers and streams and in sewag e s ludge applied to agriculture (16 ). Studies have yielded conflicting fi ndings regarding links between triclosan and adverse health effects in humans and animals.

### Supported by an unrestricted education grant from the Clorox Company

6 Acute Toxicity. In classical toxicological terms, triclosan is relatively non

- toxic to humans and other mammals. However, there have been reports (17) of contact de rmatitis, or skin irritation, from exposure to triclosan. There is also evidence (18) that triclosan may cause photoallergic contact dermatitis (PACD), which occurs when the part of the skin exposed to triclosan is also exposed to sunlight. PACD can cause an eczematous rash, usually on the face, neck, the back of the hands, and on the sun

- exposed areas of the arms. Manufacturers of a number of triclosan

- containing toothpaste and soap products claim that the active ingredient continues to work for as long as 12 hours after use. Thus, consumers are exposed to triclosan for much longer than the 20 seconds it takes to wash their hands or brush their teeth.

Chronic Health Effects. A Swedish study (1) found high levels triclosan in three out of five human milk
sa mples, indicating that triclosan does in fact get absorbed into the body, often in high quantities. Additionally, triclosan is lipophilic, so it can bioaccumulate in fatty tissues. Triclosan has not clearly been found to have carcinogenic, mutagenic, or te ratogenic effects.
Concerns over triclosan interfering with the body‘s thyroid hormone metabolism led to a study that found that triclosan had a marked hypothermic effect, lowering the body temperature, and overall causing a ―nonspecific depressant effect on the central nervous system‖ of mice (19). A nother study associated exposure to low levels (0.03 microg/L) of triclosan with disrupted thyroid hormone

– associated gene expression in tadpoles, which encouraged them to prematurely change into frogs (20), wh ile another linked triclosan exposure with reduced sperm production in male rats (21). The hypothesis proposed is that triclosan blocks the metabolism of thyroid hormone, because it chemically mimics thyroid hormone, and binds to the hormone receptor sites , blocking them, so that endogenous hormones cannot be used. Although the chemical structure of triclosan closely resembles certain estrogens, a study on a Japanese species of fish did not demonstrate estrogenic effects. However, it did find that triclosan is weakly androgenic, causing changes in fin length and sex ratios (22)

. A more recent paper in Environment International (23) shows that triclosan can hinder estrogen sulfotransferase in sheep placenta, an enzyme which helps metabolize the hormone and tr ansport it to the developing fetus. The suspicion is that triclosan would be dangerous in pregnancy if enough of it gets through to the placenta to affect the enzyme.
Although information in humans from chronic usage of personal care products is not availa ble, triclosan has been extensively studied in laboratory animals. When evaluated in chronic oncogenicity studies in mice, rats, and hamsters, treatment

- related tumors were found only in the liver of male and female mice (24). Application of the Human Rele vance Framework suggested that these tumors arose by way of a mode of action not considered to be relevant to humans (24)

. Another area of debate involves the hypothesis that triclosan enhances the production of chloroform. A study published in 2007 illus trated that, under some circumstances, triclosan triggered the production of chloroform in amounts up to 40% higher than background levels in chlorine

- treated tap water (25). But another study published the same year showed no formation of detectable chlor oform levels over a range of expected tooth

- brushing durations among subjects using toothpaste with triclosan and normal chlorinated tap water (26). The U.S. EPA classifies chloroform as a probable human carcinogen. As a result, triclosan was the target o f a UK cancer alert, even though the study (26) showed that the amount of chloroform generated was less than is normally present in treated, chlorinated water and required brushing your teeth or washing your hands for times on the order of two hours or mor e.

Dioxin L ink. There has been a number of concerns about triclosan and its link to dioxins. Dioxin s can be highly carcinogenic and can cause health problems as severe as weakening of the immune system, decreased fertility, altered sex hormones, miscarri age, birth defects, and cancer. It needs to be clarified that ―dioxin‖ is not one compound, but a family of compounds of widely ranging toxicity. Of the 210 dioxin family compounds, only 17 are considered to be of public health concern (27). Two dioxins, 2 ,8

- dichlorodibenzo

- p
- dioxin (2,8

- DCDD) and 2,4

- dichlorophenol (2,4

- DCP), are produced following photochemical degradation of triclosan , when chemical by

- products are exposed to UV radiation after the reaction of triclosan with chlorine water (25). These di oxins could be formed in river water after exposure to sunlight of chlorinated triclosan, or even in treatment of triclosan

- tainted water at water treatment

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7 plants. Despite these concerns, it was concluded in a study by University of Minnesota researchers that dioxin compounds formed from triclosan are not of public health concern because of the low concentrations of reactive oxygen species in natural waters and the low efficiency of the direct photolysis of triclosan (28).



### 4 . Antibiotic Resistance

Scient ists worldwide are concerned that the overuse and misuse of antibiotics and antimicrobials may lead to increased resistance among bacteria to these agents . Based on a review of published studies triclosan may, or may not, encourage the development of antib iotic resistance i n pathogenic bacteria.

4 .1. Bacterial resistance to triclosan In the laboratory, triclosan

- resistant bacteria can be produced fairly readily by serial passage in increasing triclosan concentrations or by isolation of resistant colonies w ithin growth inhibition zones around a paper disc containing triclosan (29 ). In E. coli r esistance may be due to overproduction of the enzyme enoyl reductase, or to changes in cellular permeability (29 ). While most resistant bacteria grow more slowly than sensitive bacteria, E. coli strains that are resistant to triclosan actually have increased growth rates. Constant exposure to triclosan will cause these resistant strains to tolerate it better, become increasingly hardy, and ever more resistant. In P. a eruginosa , which is intrinsically resistant to triclosan, resistance could be due to a non

- susceptible enoyl reductase (both triclosan

- susceptible and

- non
- suscept ible enzymes have been found (30 ), an outer membrane permeability barrier or a pumping of the drug from the cell interior to its exterior. The latter has been stated to be the major reason for triclosa n non
susceptibility (31

- 33 ). MRSA strains may or may not show decreased sensitivity to triclosan (34). Fan and colleagues (35 ) found that all S. au reus strains with decreased sensitivity overproduced the enzyme FabI by three

- to five

- fold, and the most resistant strains had mutations in FabI.
4 .2. Possible association between triclosan and antibiotic resistance
A number of recent studies have raised serious concerns that triclosan and other similar products may promote the emergence of bacteria resistant to antibiotics. One concern is that bacteria will become resistant to antibacterial products like triclosan, rendering the products useless to those who actually need them, such as people with compromised immune systems. Scientists also worry that because triclosan‘s mode of action and target site in the bacteria is similar to antibiotics, bacteria that become resistant to triclosan will also become r esistant to antibiotics. Triclosan does not actually cause a mutation in the bacteria, but by killing the normal bacteria, it creates an environment where mutated bacteria that are resistant to triclosan are more likely to survive and reproduce. An article coauthored by Dr. Stuart Levy i n 1998 (36 ) warned that triclosan's overuse could cause the development of cross

- resi stance to antibiotics, and thereby result in the em e rgence of strains of bacteria resistant to both triclosan and antibiotics. In 2003, th e Scottish Sunday Herald reported that some UK supermarkets and other retailers were considering phasing out products containing triclosan mostly due to the belief that it contributes to
a ntibiotic resistance. It has since been shown that the laboratory method used by Dr. Levy does not translate into predicting bacterial resistance to biocide s like triclosan in the environment

. At least seven peer
- reviewed and published studies have been conducted demonstrating that triclosan is not significantly associated with bacterial resistance over the short term, including one stu dy coauthored by Dr. Levy (37

- 43 )

. Susceptibility of MRSA strains to triclosan has changed little over a 10 year period (8) , and there does not seem to be any association between triclosan response in MRSA and other strains of S. aureus and antibiotic susceptibility or resistance (7 ). It has been emphasized that laboratory studies have a useful role to play in evaluating mecha nisms of action of and resistance to biocides, including triclosan, but that these should, wherever possible, be related to the clinical and ot her uses of these agents (44, 29 ). Do biocides therefore select for antibiotic resistance? Certainly, there are some similarities in the manner in which ba cteria resist the action of antibiotics and biocides (45 ). Several authors have purported to show a relationship between the use of

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8 triclosan (and other biocides) and antibiotic resistance (46

- 48 ). Others have cas t doubt on this proposal (49, 50 ) while emphasizing that, like all biocides, triclosan should be used only when appropriate. Some recent surveys on the use of triclosan and other biocides add weight to these doubts. In a survey (51 ) conducted over a 10 ye ar period, it was found that there was no relationship between triclosan usage and antibiotic resistance in MRSA and P. aeruginosa . Another survey (52) showed that there were no significant differences in overall titers of bacteria or frequencies of antibi otic resistance in a snap
- shot analysis of homes that did or did not use surface antibacterial agents. A comprehensive survey by Cole et al . (53 ) found no relationship between the use of triclosan and other biocides and antibiotic resistance in homes where biocidal products were or were not being used.
What about the incorporation of triclosan into oral products? Will the use of triclosan in dental hygiene products result in the development of triclosan

- resistant bacteria with reduced susceptibility to imp ortant antibiotics? An Expert Panel review concluded in 2000 that there was no evidence of resistant, opportunistic or pathogenic microorganisms developing subsequent to the introduction of triclosan (54 ). The short

- term use of triclosan had no major impac t on normal oral microflora or on the susceptibility of streptococci to antibiotics. Chronic exposure to triclosan did not demonstrate significant decreases in antibiotic susceptibi lity in dental bacteria (55 ). In general terms, the use of antimicrobial ag ents in dental care products in order to reduce plaque i s considered to be justified (56 ). While triclosan resistance in laboratory experiments may be associated with changes in antibiotic susceptibility, comprehensive environmental surveys have not yet cl early demonstrated any association between triclosan usage and antibiotic resistance. Triclosan has several important uses, and the future aim must be to retain these applications while eliminating the unnecessary ones.
Bacterial resistance to disinfectant s in general is most certainly not a new phenomenon, and there are known examples of reduced susceptibility being d escribed over a century ago (57 )

. Triclosan, of course, is of more recent vintage. Consequently, it is necessary to continue to monitor wheth er reduced susceptibility to it and to antibiotics occurs. Although it is sometimes stated that resistance to triclosan and other biocides is increasing (58 ) this conclusion is generally based upon minimum inhibitory concentrations in lab settings rather t han bactericidal estimations.
Since resi s tan ce often builds in a step

- wise f ashion, it is prudent to conserve use and continue surveillance of susceptibility to both antibiotics and to biocides like triclosan.



### 5. Triclosan in the Environment

Triclosan, a s well as other antibacterial agents and their degradation byproducts, are now found throughout the environment, including surface waters, soil, fish tissue, and human breast milk (1 ). Swiss researchers found three out of five samples of human breast milk contained measurable concentrations of triclosan ( at concentrations up to 30 μg/kg lipid weight )

. Over 95% of the uses of triclosan are in consumer products that are disposed of in residential drains. In a U.S. Geological Survey study of 95 different organ ic wastewater contaminants in U.S. streams, triclosan was one of the most frequently detected compounds, and in some of the highest concentrations. A study of triclosan in bodies of water in Switzerland also found high concentrations of the chemic al in sev eral lakes and rivers (12).

In a 1999

- 2000 study by the U.S. Geological Survey, triclosan was found in 57 percent of the 139 U.S. waterways that were thought to be susceptible to agr iculture or urban activities (59 ). Triclosan has been found in both surfa ce water and wastewater. Surface water sources may include wastewater treatment plant effluent, urban stormwater, rural stormwater, and agricultural runoff. When domestic wastewater is treated before discharge to surface waters, there is evidence that up t o 95 percent of triclosan is removed via the wastew ater treatment plant process (60 ). This removal efficiency is dependent on treatment plant operations. Swiss researchers observed a 94 percent removal rate of triclosan at wastewater treatment operations that employed mechanical clarification, biological treatment or nitrification, flocculation and filtration. The researchers estimated that 79 percent of the triclosan was removed via biological degradation while 15 percent adsorbed to the sludge. The remai ning 6 percent in the effluent resulted in a concentration of 42 ng/Liter (61 ).

### Supported by an unrestricted education grant from the Clorox Company

9 The transport of triclosan to wastewater treatment plants occurs when people: w ash hands with antibacterial soap , h and wash dishes with antibacterial soap , c lean with antibact erial products , u se antibacterial products in a dishwasher , b athe or shower with antibacterial soap or shampoo , b rush teeth with toothpaste containing antibacterial products , w ash clothes with antibacterial products , w ash antibacterial cutting boards , etc. Unlike wastewater, most runoff that enters storm drains is untreated and directly flows into creeks, rivers and ultimately to the ocean . Triclosan may be transported into the stormwater system through commercial or residential washing of equipment outdoor s with antibacterial soaps

. While our current understanding of triclosan‘s environmental effects is limited, there is evidence that triclosan can be toxi c to aquatic organisms (62

- 64 ). T he presence of triclosan may influence both the structure and the fu nction of algal communities in stream ecosystems receiv ing treated wastewater effluent (65 ). These changes could result in shifts in both the nutrient processing capacity and the natural food web structure of these streams

. According to a literature review by the Danish Environmental Protection Agency, tr iclosan bioaccumulates in fish (66) and the concentrations found in fish are thousands of times higher than w hat is found in the water

. Furthermore, at least one transformation product of triclosan

- methyl triclosan

- is stable in the environment, making it also available for bioaccumulation. Once methylated, the lipophilicity of triclosan increases, meaning that it will be more likely to accumulate in fatty tissue and is not likely to photodegrade. In a Swi ss study, the lipid

- based concentrations of methyl triclosan detected in fish were considerably higher than the concentrations in lake water, suggesting significant bioaccumulation of the compound. For aquatic organisms, the potential uptake mechanisms of lipophilic contaminants are direct uptake from water through exposed surfaces, mainly gills , and uptake through the consumpti on of food (67 ).


### 6. Regulation of Triclosan U se
At the present time, triclosan is coming under close scrutiny. In March 2010, the European Union banned triclosan from any products that may come into contact with food, and i n August 2009 the Canadian Medical Association asked the Canadian government to ban triclosan use in household products under concerns of creating bacterial resistance and producing dangerous side products. In the U

. S

. , Federal agencies are reviewing triclosan‘s safety but haven‘t called for altered usage yet.

In the U.S. if an ant imicrobial product is intended for use on the human body, it falls under the jurisdiction of the Food and Drug Administration (FDA). The FDA categorizes triclosan based on use and product claims. If a product makes a health related claim, such as ―kills ge rms‖ (soap, first aid creams, etc.), FDA registers it as a drug. If it makes no claim at all or if its claims are cosmetic, such as ―fights odors‖ or ―improves skin‖ (deodorant, makeup, shaving cream), it is registered as a cosmetic. All uses not applied t o the human body (bathroom and kitchen cleaners, hospital disinfectants), that make pesticidal claims, such as ―kills bacteria and mildew‖ are regulated by the Environmental Protection Agency (EPA) as a pesticide

. The FDA regulates drugs similar to the way that the EPA regulates pesticides, using a risk

benefit analysis based on data gathered from animal studies and human clinical trials. The manufacturer must prove that: the drug is safe and effective in its proposed use(s), and that the benefits of the dr ug outweigh the risks; the drug‘s proposed labeling is appropriate; and the manufacturing methods used are able to maintain the drug ‘s quality, identity, strength , and purity. On the other hand, the FDA is only able to regulate cosmetics after products are released on the marketplace. Neither cosmetic products nor cosmetic ingredients are reviewed or approved by the FDA before they are sold to the public. The FDA cannot require companies to do safety testing of their cosmetic products before marketing. Howe ver, if the safety of a cosmetic product has not been substantiated, the product‘s label must read: ―WARNING: The safety of this product has not been determined.‖ FDA does not require, but maintains a voluntary data collection program. If cosmetic products are found to present a hazard, recalls are also voluntary.

O n December 8 2010, the EPA published in the Federal Register a petition filed by 82 public health and environmental groups, led by Beyond Pesticides and Food and Water Watch, to ban triclosan fo r non
medical use (71)

. The Federal Register notice ( 72) invited the public to comment until February 7, 2011 on the need to ban triclosan under numerous federal statutes. The petition identifies pervasive and

### Supported by an unrestricted education grant from the Clorox Company

10 widespread use of triclo san and a failure of the EPA to address the impacts posed by triclosan's degradation products on hum an health and the environment, to conduct separate assessment for triclosan residues in contaminated dr inking water and food, and to evaluate concerns related to antibacterial r esistance and endocrine disruption. The petition cites violations of numerous environmental statutes, including laws on pesticide registration, the Clean Water Act, Safe Drinking Water Act, and Endangered Species Act. It also documents that triclosan is no more effective than regular soap and water in removing germs and therefore creates an unnecessary hazardous exposure for people and the environment.
On April 2010 the FDA announced it is conducting a scientific and regulatory review of triclosan in FDA

r egulated products, with publication of results expected in spring 2011 (73). The agency also is collaborating with the EPA specifically to study the potential endocrine

- disrupting effects of the compound (74). The FDA indicated that it currently has no evi dence that triclosan is hazardous to humans and does not recommend consumers avoid it. However, the agency said there is no evidence that soap with triclosan is superior to soap without the ingredient. The FDA agreed to look into the safety of triclosan a t the request of Congressman Edward Markey, D

- Mass. According to the congressman‘s letter, his office contacted more than a dozen companies that make soaps, cutlery and other consumer goods, asking them to voluntarily remove triclosan from their products. The majority of companies said they would not change their products until the FDA issues its review. However, several companies are already phasing the chemical out, including Colgate

- Palmolive, which plans to reformulate its dishwashing formula. Reckitt Benckiser, maker of Lysol spray along with several soap products, said it plans to reformulate its triclosan

- containing products by 2011. Acme United Corp. and Victorinox both said they have already removed triclosan from their knives as a result of recent regulations passed in Europe.
In 2008, the EPA completed a Re

- registration Eligibility Decision (RED) document for triclosan. This RED document described the conclusions of EPA‘s comprehensive review of the potential risks to human health and the environ ment resulting from the registered pesticidal uses of triclosan. In conducting the review for the RED, the EPA considered all available data on triclosan, including data on endocrine effects, developmental and reproductive toxicity, chronic toxicity, and c arcinogenicity (74) . The 2008 EPA assessment also relied in part on 2003

– 2004 biomonitoring data available from the National Health and Nutrition Examination Survey (NHANES) which reported measurements of urinary concentrations of triclosan in the U.S. pop ulation. Therefore, the 2008 EPA assessment was inclusive of all triclosan

- related exposures (i.e., EPA and FDA regulated uses). The 2008 RED also considered new research data on the thyroid effects of triclosan in laboratory animals made available through the EPA‘s Office of Research and Development (ORD). Since the 2008 assessment, additional data on effects of triclosan on estrogen have also been made available from ORD. The ORD studies on the thyroid and estrogen effects led the EPA to determine that ad ditional research on the potential health consequences of endocrine effects of triclosan is warranted. This research is underway and will help characterize the human relevance and potential risk of the results observed from initial laboratory animal studie s. The Agency will pay close attention to the ongoing research and will amend the regulatory decision if the science supports such a change. Also, the Agency has previously indicated that because of the amount of research being planned and currently in pro gress, it will undertake another comprehensive review of triclosan beginning in 2013.
In 1997, the EPA acted to prevent the manufacturer of Playskool toys, Hasbro, Inc. (which sells toys made with Microban® plastic containing triclosan), from making fals e claims about protecting children from microbial infections. Hasbro could no longer claim that toys treated with triclosan protect children from infectious diseases caused by bacteria because it did not prove efficacy to EPA. Labels and advertisements for the toys suggested that the treatment protects children from health risks, when in fact it protects only the plastic in the toy. The company is prevented from making such claims due to a lack of reliable data to support them. Under the agreement, Hasbro h ad to publish large advertisements in certain newspapers and magazines about misrepresentation of the public health claim.

The current reali ty pertaining to regulation of triclosan in the U.S. is that w e are in a conundrum, where there are data that show that triclosan is safe, and data that show its potential harm ful effects

. The challenge for the FDA and the EPA will be to figure out where the se apparent conflicting data intersect.

### Supported by an unrestricted education grant from the Clorox Company

11 

### 7. Do We Have A lternatives to Triclosan?

When used in hospitals and o ther health care settings, or for persons with weakened immune systems, triclosan represents an important health care and sanitary tool. But outside of these settings, t he American Medical Association has not endorsed the necessity or efficacy of triclosan and other antibacterial agents in personal care products , household products and commercial consumer products

. According to the Centers for Disease Control and Prevention (CDC), vigorous hand washing in warm water with plain soap for at least 10 seconds i s sufficient to fight germs in most cases, even for healthcare workers ( 75 ). For extra assurance, use of an alcohol

- or peroxide

- based hand sanitizer product is a good option

. Regarding the use of cutting boards, the following quote from the Mayo Clinic web site indicates that cutting boards impregnated with triclosan are ineffectual: “There's no evidence that cutting boards containing triclosan, an antibacterial agent, prevent the spread of food

- borne infections. These boards also may give a false sense of security and cause you to relax other efforts to keep the board clean. In addition, triclosan

- treated boards don't kill germs. Antibacterial compounds only slow reproduction of microorganisms. Germs will die, but slowly enough to still contaminate other food or hands that come int o contact with the board” (76 ). For alternatives to triclosan

- containing cutting boards, the Center for Food Safety and Applied Nutrition recommends that households use a two cutting board system. Use one board for cutting foods that will be cooked (e.g., raw meats, poultry, fish, vegetables) and one for ready

to

- eat foods (e.g., breads, fresh fruits).

In a recent interview (77) Dr. Stuart B. Levy (President and F ounder of The Alliance for the Prudent Use of Antibiotics
, Directo r of the Center for Adaptation Genetics and Drug Resistance and Professor of Medicine at the Tufts University School of Medicine ) indicated ―

... alcohol

- based disinfectants are the way to go if you don‘t have an area to go wash hands with soap and water [..

. ] I‘m big on antibacterial products that don‘t leave a r esidue

... that is those that contain alcohol, peroxide, or bleach . Let‘s say you bring in your meat and it‘s got salmonella, and you‘ve been washing it on the counter. You may take peroxide or alcoho l to clean it. That gets rid of both good and bad [bacteria]. The surface is now available for good and bad, and generally if you haven‘t brought more meat in, it‘s the good in the environment that take over. If you use a product with triclosan what‘s left on the counter, or in the sink, is a small and increasing amount of residue of that chemical. Now, bacteria come and sit down. Only the resistant ones can live on that environment. So you kind of help them to take over the world ‖

.

APUA published and dis tributed information to consumers regarding the use of antibacterials in household products and has made some recommendations as to alternatives to triclosan (78). These are guidelines on keeping clean without triclosan:
Wash hands frequently and thoroug hly. Regular soaps lower the surface tension of water, and thus wash away unwanted bacteria. Lather hands for at least 10 to 15 seconds and then rinse off in warm water. Dry hands with a clean towel to help brush off any germs that did not get washed down the drain

. Complement with alcohol

- containing hand sanitizers. Wash surfaces that come in contact with food with a detergent and water , or with bleach. Wash children‘s hands and toys regularly to prevent infection. When selecting products such as hand soa p, toothpaste, and deodorants, it is recommended to read the label. If the product states "antibacterial" one should locate the active ingredients list to see if the product contains triclosan or other antibacterial agents. Consumers may opt to purchase pr oducts that either are not labeled ―antibacterial‖ or contain alcohol or hydrogen peroxide as the antibacterial agent. In addition, non
- organic antibiotics and organic biocides are effective alternatives to triclosan

.

### Supported by an unrestricted education grant from the Clorox Company

12 

### 8. Conclusions and Next Steps

The re are growing concerns about the emergence and spread of triclosan residues in the environment, and its potential negative impact on human and animal health. However, the scientific debate continues regarding the safety and efficacy of its application in personal care and household products. Triclosan has several important medical uses, and the future aim must be to retain these applications while eliminating the more frivolous and unnecessary ones. It would be wise to restrict the use of triclosan to area s where it has been shown to be effective and most needed

. 

### Below are the suggested next steps:

1. Follow the upcoming decisions by the FDA and the EPA in 2011, after their review of safety and efficacy data is concluded.

2. Support scientific and public healt h research on the cumulative effects and chronic use of triclosan

.
3. Continue to follow scientific literature for additional information regarding heath impact s and environmental fate of triclosan and its by

- products.

4. Adopt a precautionary principle attit ude towards the use of triclosan (78). Coordinate with appropriate agencies and groups to develop a public factsheet as well as concise messages that resonate with the public and specific audiences. Possible messages include:

- Antibacterial product residues are found in the environment

- The use of antibacterial products may provide a false sense of security and lead to inadequate hand

- washing practices

- Effective a lternatives include washing hands with soap and water and using alcohol or peroxide based hand ge l sanitizing agents for extra assurance

- Minimize use of antibacterial

- containing cleaning products and personal care products; for surfaces
, bleach

- containing products are an alternative

- Avoid antibacterial cutting boards

5. Review opportunities to include m essages from water quality outreach efforts to specific audiences. Such audiences might include:

- Primary purchasing agents in households and commercial institutions

- Purchasing departments of public institutions

- Health care and veterinary professionals

- Par ents and teachers

- Manufacturers and distributors

6. Consider developing State and Federal legislation to limit the use of triclosan in consumer products.

7. Support advocacy initiatives that through the gathering of new knowledge and offering of solutions promote the prudent use of triclosan (78).

8. Support initiatives to gather relevant agencies and public health stake holders to engage in face

to

- face conversations on the implementation of appropriate use of triclosan (78)

.

### Supported by an unrestricted education grant from the Clorox Company

1 3 

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18