Registration Dossier

Administrative data

Description of key information

Human related data on triclosan were recently reviewed, evaluated and summarized by the Scientific Committee on Consumer Products of the European Commission, Health & Consumer Protection DG Directorate C: Public Health and Risk Assessment Unit C7 - Risk Assessment Office in Brussel. The data were published 2009 in the SCCP  Opinion on triclosan COLIPA No. P32 Report No. SCCP/1192/08.

Additional information

Summary of human data on triclosan (as reported by the SCCP (2009):

Human Safety/Tolerability Data:

No serious adverse events have been reported for triclosan-containing toothpaste. The low number of reported non-serious adverse events for triclosan-containing toothpaste (frequency of 0.27 complaints/100,000 units sold) included reactions that were associated with the use of dentifrices in general, as identified during clinical testing (e.g., dry mouth, mouth irritation/burning, sensitive teeth, altered taste or oral sensation, exfoliation). Other non-serious adverse events were those that represented a variety of much more infrequently reported effects (i.e., usually reported by only one or two consumers, resulting in a reporting frequency of 0.09 complaints/100,000 units sold). These rare non-serious events, which may not have been related to the use of the triclosan-containing toothpaste, included stomach ache, belching, alopecia, anxiety, headache, black or coated tongue, dizziness, excess saliva, upper respiratory infection, increased urge to urinate, and shortness of breath. Thus, based on consumer use information for triclosan-containing toothpaste, which represents a wide-spread use that includes the potential for systemic exposure through the oral route, data indicate that triclosan can be used safely and with good tolerability at levels that also are found in personal care products.

Safety/Tolerability Data from Clinical Studies:

In addition to the indications of good tolerability and safety from historical and consumer use of personal care products containing triclosan, a number of clinical studies have investigated the safety and tolerability of triclosan. Four human studies have evaluated the safety of triclosan in toothpaste products. These studies tested triclosan-containing toothpaste preparations in study populations over periods ranging from 12 weeks to 3 years at concentrations of 0.2% triclosan [Colgate- Palmolive, 1994 (105)], 0.2% triclosan with 0.5% zinc citrate [Safford, 1991 (106); Barnes, 1992 (107)], and 0.3% triclosan with 0.243% fluoride [Fishman, 1994 (108)]. Endpoints measured included blood chemistry and haematological parameters in all 4 studies. In addition, urinalysis parameters were evaluated in 1 study [Fishman, 1994 (108)]. In all studies, there were no changes indicative of overt toxicity. Reported changes in haematological and/or clinical chemistry parameters that did occur could not be attributed to the use of the triclosan-containing toothpaste. In a separate study of pharmacokinetics and tolerability, consumption of escalating daily doses of triclosan in capsule form (0 to 30 mg/capsule) by 20 volunteers was reported to be without overt effects on ophthalmic, neurologic, cardiac, and lung function evaluations [Lucker et al., 1990 (109)]. There were slight increases in liver enzyme values of the treated subjects, but this is in contrast to the four human studies (described above) that reported a lack of findings in liver enzyme parameters. Five of the treated participants dropped out during the course of the study; however, the adverse events reported in these subjects could not be attributed to triclosan. One of the safety studies [Safford, 1991 (106)] reported on the concentrations of triclosan in the blood following the use of a toothpaste containing 0.2% triclosan and 0.5% zinc citrate. In this study of 112 participants, the average triclosan concentration in the blood of 15.5 ng/mL was reported to rise to 31.2 ng/mL after a period of 4 weeks on study. This concentration was reported to subsequently level off with further use of the triclosancontaining dentifrice. In summary, the human safety studies reviewed showed no signs of overt toxicity in over 3,000 subjects that used triclosan-containing toothpaste for 12 weeks to 3 years.

Human Pharmacokinetics and Metabolism:

Triclosan is very well absorbed following oral ingestion (up to 98% of the dose). However, under normal conditions of toothpaste use (i.e., expectoration and rinsing) or following percutaneous application of several different personal care products, there is only limited absorption (approximately 5 to 10% of the dose via either of these routes of administration). Based on plasma levels and percentage of dose absorbed, it is clear that low exposures to triclosan occur following either toothpaste use or soap/hand wash use and that, with repeated exposures using either route, low steady-state levels of triclosan are reached after approximately 7 to 10 days. Regardless of the formulation administered, only trace amounts of the parent compound are detected in the plasma following exposure to triclosan-containing products. Due to a pronounced first-pass effect, there is near total conversion of absorbed triclosan to glucuronic and sulphuric acid conjugates. The relative proportions of these metabolites vary depending on the plasma steady state concentration of total triclosan, with higher concentrations resulting in a shift from predominantly glucuronide- to predominantly sulphate-conjugates. Following ingestion, percutaneous application, or intravenous administration of triclosan, the predominant route of excretion is the urine, in which triclosan is present as the glucuronide conjugate. In contrast, triclosan excreted in the faeces is present as the free unchanged compound. Pharmacokinetic data, in particular, AUC values after single or repeated oral exposures (e.g., after toothpaste use), as well as plasma levels after dermal (soap application) exposures, indicate a lack of evidence of bioaccumulation of triclosan.

Human Irritation and Sensitisation:

The ability of triclosan to cause irritation to human skin or mucous membranes was evaluated in human volunteers. Triclosan (0.3%) was shown not to induce skin irritation in single patch tests in 10 subjects [Barkvoll and Rolla, 1994 (143)]. There was also no evidence of primary skin irritation in repeated patch tests with a bar soap formulation containing triclosan (concentration of triclosan not specified) in 106 female subjects [Colgate-Palmolive, 1972 (147)]. In this study, a total of 1,155 patch tests were conducted, including a challenge application 14 days after the 10th patch test in each subject. Although irritation effects were observed in a hand washing study using a commercial detergent containing a high concentration (2%) of triclosan, the irritation effects could not clearly be attributed to triclosan [Bendig, 1990 (162)]. Thus, taken altogether, the data indicated that triclosan showed low skin irritation potential in clinical irritation tests and, possibly, skin irritation in a commercial detergent formulation containing a high concentration of triclosan (2%). The effect of triclosan on skin and oral mucosa irritation produced by SLS was investigated in four studies. In the same patch test study in which triclosan was shown not to produce skin irritation, it was also shown to eliminate SLS-induced irritation [Barkvoll and Rolla, 1994 (143)]. In another study, the effects of triclosan in toothpaste formulations on SLSinduced irritation was tested in skin, with inconclusive, but suggestive, results with respect to a protective effect of triclosan [Skaare et al., 1997a (144)]. Studies of oral mucosal response to various mouth rinse or toothpaste formulations containing SLS (1.5 or 3%) with/without triclosan (0.15% or 0.3%) showed that formulations containing triclosan reduced or eliminated the severity and frequency of SLS-induced oral mucosal erythema and desquamation compared to formulations without triclosan [Skaare et al., 1997b (145); Skaare et al., 1996 (146)]. Taken altogether, the data from these studies indicate that triclosan has a protective effect against SLS-induced skin or oral mucosa irritation. While the effects of triclosan alone have not been evaluated in stand-alone tests in oral mucosa because triclosan was typically tested in combination with SLS, the lack of irritant effects of triclosan-containing test formulations in oral mucosa studies, together with the protective effects of triclosan against SLS-induced irritation, indicate that triclosan is not a mucosal irritant. In summary, the skin and oral mucosa irritation studies evaluating the effects of triclosan alone, or in combination with SLS, indicate that triclosan is not a skin or oral mucosal irritant.Referring to sensitisation, In total, triclosan was tested in 420 healthy subjects using variations and modifications to the Patch, Draize, and Maximisation Test methods at induction concentrations of up to 20% and challenge concentrations of up to 5%. There were no positive reactions in any of the test subjects, including after repeated patch testing [e.g., Colgate-Palmolive, 1972 (14); DeSalva et al., 1989 (1)]. No positive challenge results were observed, leading investigators to conclude that triclosan has a very low sensitisation potential. Taken altogether, the results from these studies indicate that triclosan has very low sensitisation potential in healthy subjects. Triclosan has also been tested in patients with contact dermatitis or suspected cosmetic allergy. The results of routine patch testing with triclosan as one of a series of preservative or antimicrobial ingredients tested in these patients showed that triclosan has a low potential to cause positive skin reactions in this sensitive population. Case reports of contact dermatitis due to triclosan use have been relatively rare (Campbell and Zirwas 2006, AR3), although a few cases have been reported following the use of a cream formulation containing a high concentration of triclosan (3%) together with 0.02% flumethasone pivalate. Three such cases were reported by Veronesi et al. [1986 (153)], and 2 by Steinkjer and Braathen [1988 (159)]. The reason for a third case of reported allergic contact reaction to triclosan was not discovered [Steinkjer and Braathen, 1988 (159)]. All 6 of these patients were found to have positive results in patch tests using 2% triclosan in petrolatum (see Table 41). Investigators concluded that low concentrations of triclosan in cosmetic products do not cause contact dermatitis; however, sensitisation may occur following the use of products containing higher concentrations [Veronesi et al., 1986 (153)]. Six studies investigated the photosensitising potential of triclosan. In one of the larger studies using a soap formulation containing triclosan (concentration not reported), only one positive reaction was observed following a second photochallenge with the soap formulation; however, this reaction was considered to be the result of scratching [Colgate- Palmolive, 1972 (147)]. There was no evidence of photosensitising potential of triclosan in two of the other studies that tested over 100 subjects per study, and only two of 745 patients tested positive for a photoallergic reaction in the largest study (0.27% of patients) [Wennersten et al., 1984 (160)]. There was also no evidence of phototoxicity or photoallergenic potential in two smaller studies (n#25) with triclosan at concentrations of up to 10% in petrolatum or 0.1% in methanol. In summary, data from the photosensitisation and patch testing studies performed with triclosan indicate that it is unlikely to produce phototoxicity or photosensitisation in human skin at levels used in personal care products. Triclosan was tested at concentrations of up to 10% in petrolatum in the photosensitisation studies.