Abstracts from peer-reviewed journal articles on the health effects associated with Triclosan

From medline search, 2/2/99

TITLE: Triclosan: cytotoxicity, mode of action, and induction of apoptosis in human gingival cells in vitro.

AUTHORS: Zuckerbraun HL; Babich H; May R; Sinensky MC

AUTHOR AFFILIATION: Department of Biology, Stern College for Women, Yeshiva University, New York, NY 10016, USA.

SOURCE: Eur J Oral Sci 1998 Apr;106(2 Pt 1):628-36

CITATION IDS: PMID: 9584909 UI: 98244300

ABSTRACT: The in vitro cytotoxicology of triclosan, the active ingredient in some mouthrinses and dentifrices used in the prevention and treatment of gingivitis and plaque, was studied using the Smulow-Glickman (S-G) human gingival epithelial cell line. The 24 h midpoint cytotoxicity value was 0.05-0.06 mM triclosan as assessed with the neutral red (NR) assay. Triclosan is used in dentifrices in combination with either zinc citrate or sodium fluoride (NaF). The sequence of potencies of these test agents, as assessed with the NR assay, was triclosan>zinc citrate>>NaF; combinations of triclosan + zinc citrate and triclosan + NaF were additive in their toxicities. Damage to the integrity of the plasma membrane, as assessed by the leakage of lactic acid dehydrogenase during a 3-h exposure, was initially evident with 0.1 mM triclosan. When exposed to triclosan for 3 d, a lag in the growth kinetics of the S-G cells was first observed at 0.01 mM triclosan. A reduction in attachment of S-G cells to dentin chips, previously exposed to triclosan for 1 h, was noted at 0.25 mM triclosan and greater. Triclosan-induced cell death was apparently by apoptosis, as noted by fluorescence microscopy and DNA agarose gel electrophoresis of extracted oligonucleosomal fragments.

TITLE: Sodium lauryl sulfate and triclosan: in vitro cytotoxicity studies with gingival cells.

AUTHORS: Babich H; Babich JP

AUTHOR AFFILIATION: Stern College for Women, Yeshiva University, Department of Biology, New York, NY 10016, USA. babich@yu1.yu.edu

SOURCE: Toxicol Lett 1997 May 16;91(3):189-96

CITATION IDS: PMID: 9217239 UI: 97360211

ABSTRACT: Triclosan and sodium lauryl sulfate (SLS) are antimicrobial agents used, both singularly and in combination, in dentifrices and mouth- rinses. Studies by Waaler et al. (Scand. J. Dent. Res. 101 (1993) 192- 195) with human volunteers showed that the adverse side-effects induced by SLS in mouth-rinses, i.e. desquamation of oral epithelium and a burning sensation, were lessened by the addition of triclosan. However, Baert et al. (Int. J. Exp. Pathol. 77 (1996) 73-78) showed that triclosan did not protect the hamster cheek pouch mucosa from irritation caused by SLS. The studies presented herein further evaluated, using a cell culture system, the triclosan-SLS interaction. The in vitro cytotoxicities of triclosan and SLS, alone and in combination, were determined with human gingival S-G epithelial cells and GF fibroblasts. The 24-h midpoint (NR50) cytotoxicity values towards the S-G cells were 0.052 mM triclosan and 0.0075% SLS and for the GF fibroblasts the respective values were 0.095 mM triclosan and 0.0127% SLS. Both agents at their NR50 values induced vacuolization. Coexposures of triclosan and SLS were additive in their cytotoxicities towards the S-G epithelial cells and GF fibroblasts. Pretreatment with triclosan potentiated the toxicity of a subsequent exposure of SLS to the S-G cells; a similar pretreatment of the GF fibroblasts with triclosan had no effect on a subsequent challenge with SLS.

TITLE: Skin reactions and irritation potential of four commercial toothpastes.

AUTHORS: Skaare A; Kjaerheim V; Barkvoll P; Rolla G

AUTHOR AFFILIATION: Department of Oral Surgery and Oral Medicine, Faculty of Dentistry, University of Oslo, Norway.

SOURCE: Acta Odontol Scand 1997 Apr;55(2):133-6

CITATION IDS: PMID: 9176662 UI: 97319769

ABSTRACT: Skin reactions to 4 toothpastes were tested in 19 healthy dental students in a double-blind study. The hypothesis was that common toothpaste brands with and without sodium lauryl sulfate (SLS) and triclosan and with different additives/emulgators differ in irritation potential. An occlusion test system on human skin was used. The toothpastes tested were A) Zendium (non-ionic detergent), B) Solidox F (SLS/polyethylene glycol), C) Colgate Total (triclosan/copolymer/SLS/propylene glycol), and D) Solidox G (triclosan/zinc citrate/SLS/polyethylene glycol). Toothpaste C was the greatest irritant, causing skin erythema in 16 of the 19 subjects, whereas toothpaste D gave no reactions. Toothpaste B provoked three reactions (two severe), whereas toothpaste A caused only one mild reaction. Although this study was carried out on skin and hence not directly applicable to the oral cavity, these and previous results may indicate that a toothpaste without propylene glycol and SLS may be preferred by susceptible persons.

TITLE: Interaction of 2,4,4'-trichloro-2'-hydroxydiphenyl ether with microsomal cytochrome P450-dependent monooxygenases in rat liver.

AUTHORS: Hanioka N; Omae E; Nishimura T; Jinno H; Onodera S; Yoda R; Ando M

AUTHOR AFFILIATION: Division of Environmental Chemistry, National Institute of Health Sciences, Tokyo, Japan.

SOURCE: Chemosphere 1996 Jul;33(2):265-76

CITATION IDS: PMID: 8696774 UI: 96290869

ABSTRACT: We studied the effects of 2,4,4'-trichloro-2'-hydroxydiphenyl ether (Irgasan DP300) on the kinetics of the cytochrome P450 (P450)-dependent monooxygenases in rat liver microsomes. The activities of 7- ethoxyresorufin O-deethylase (EROD) and 7-pentoxyresorufin O- depentylase (PROD) in rat liver microsomes exposed to 3- methylcholanthrene (MC) and phenobarbital (PB) respectively, were substantially inhibited by Irgasan DP300. The inhibition profile of EROD was competitive, whereas that of PROD was noncompetitive; the Ki values from Hanes plots were 0.24 and 1.48 microM for EROD and PROD, respectively. Phenacetin O-deethylase (PCOD) and 4-nitrophenol hydroxylase (4NPH) activities in rats exposed to PB were also inhibited by Irgasan DP300, at Ki values lower than those for other microsomes. Irgasan DP300 slightly inhibited testosterone 6 beta-hydroxylase (TS6BH) activities in some microsomes. No effect of Irgasan DP300 on lauric acid omega-hydroxylase (LAOH) activity was evident in any microsomal preparations. These results indicated that Irgasan DP300 inhibits MC- and PB-inducible P450-dependent monoxygenase in vitro competitively or noncompetitively, and that the P450 enzymes of the CYP1A or CYP2B subfamily may contribute to Irgasan DP300 toxicity.

TITLE: Triclosan: applications and safety.

AUTHORS: Bhargava HN; Leonard PA

AUTHOR AFFILIATION: Division of Pharmaceutical Sciences, Massachusetts College of Pharmacy and Allied Health Sciences, Boston 02115, USA.

SOURCE: Am J Infect Control 1996 Jun;24(3):209-18

CITATION IDS: PMID: 8807001 UI: 96400625

ABSTRACT: Triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) is a nonionic, broad spectrum, antimicrobial agent that, because of its favorable safety profile, has been incorporated into a variety of many personal care products, including deodorant soaps, underarm deodorants, shower gels, and health care personnel handwashes. Triclosan exhibits a moderate degree of substantivity to the skin, and, in many products, it imparts a remnant antimicrobial effect. Although direct contact with the material under exaggerated exposure conditions causes dermal irritation in laboratory animals, it has only rarely been associated with skin irritation or sensitization in human being in formulated products. Acute, subacute/subchronic, and chronic toxicity profiles have been established to determine that triclosan is neither an acute oral toxicant nor that it acts as a carcinogen, mutagen, or teratogen. A new application for triclosan is in oral dentifrices for plaque control. Currently under investigation in the United States, it is approved for oral care application in Canada and many European countries.

TITLE: The effect of sodium lauryl sulphate and triclosan on hamster cheek pouch mucosa.

AUTHORS: Baert JH; Veys RJ; Ampe K; De Boever JA

AUTHOR AFFILIATION: Interdisciplinary Research Center, Katholieke Universiteit Leuven, Belgium.

SOURCE: Int J Exp Pathol 1996 Apr;77(2):73-8

CITATION IDS: PMID: 8762865 UI: 96296339

ABSTRACT: It has recently been shown that triclosan protects the human skin from the inflammation that may be caused by exposure to sodium lauryl sulphate (SLS). The aim of the present study was to examine whether triclosan can protect the hamster cheek pouch mucosa from the irritation caused by exposure to SLS. After four daily applications of a paste containing SLS, the epithelium of the hamster cheek pouch showed consistently prominent structural changes, especially basal hyperplasia, acanthosis, hypergranulosis, and hyperkeratosis. Identical morphological changes were also observed after applications of a paste containing SLS together with triclosan. In contrast, after applications of a paste containing triclosan alone, the cheek pouch mucosa revealed a histological structure essentially similar to the non-treated control mucosa. From these results, we may conclude that SLS, but not triclosan, irritates the hamster cheek pouch epithelium. Moreover, triclosan does not protect the cheek pouch mucosa against structural changes induced by SLS. It must be taken into account that triclosan does not always offer protection against the side-effects of SLS.

TITLE: Newborn conjunctivitis associated with triclosan 0.5% antiseptic intrinsically contaminated with Serratia marcescens.

AUTHORS: McNaughton M; Mazinke N; Thomas E

SOURCE: Can J Infect Control 1995 Spring;10(1):7-8

CITATION IDS: PMID: 7620192 UI: 95345500

ABSTRACT: In February 1994, three cases of conjunctivitis with Serratia marcescens occurred in infants in the newborn nursery. An epidemiological investigation was conducted including environmental sampling. S marcescens was isolated from the bottle of triclosan 0.5% antiseptic soap that was in use in the nursery and from an unopened bottle on the pharmacy shelf. The manufacturer confirmed that this contaminant was dislodged from the air purification system during a filter change while the packaging was being completed in an adjoining room. The product was withdrawn from use in the nursery and replaced by individual bar soap. No further cases of infection with S marcescens have been identified following the withdrawal of the triclosan 0.5% soap.

TITLE: Frequency of sensitization to 13 common preservatives in Switzerland. Swiss Contact Dermatitis Research Group.

AUTHORS: Perrenoud D; Bircher A; Hunziker T; Suter H; Bruckner-Tuderman L; Stager J; Thurlimann W; Schmid P; Suard A; Hunziker N

AUTHOR AFFILIATION: Service de Dermatologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

SOURCE: Contact Dermatitis 1994 May;30(5):276-9

CITATION IDS: PMID: 8088140 UI: 94374149

ABSTRACT: From February 1989 to January 1990, the Swiss Contact Dermatitis Research Group conducted a 1-year study to examine the frequency of sensitization to a series of 13 common preservatives. A group of 2295 consecutive outpatients with suspected allergic contact dermatitis (age range 7-90 years, with a mean age of 42; 911 males, 1384 females) was tested. The %s of positive reactions to the preservatives studied are as follows, in descending order: formaldehyde 5.7%, benzalkonium chloride 5.5%, Kathon CG 5.5%, thimerosal 4.2%, chlorhexidine digluconate 2.0%, DMDM hydantoin 1.7%, paraben mix 1.7%, chloroacetamide 1.5%, Bronopol 1.2%, imidazolidinyl urea 1.0%, quaternium 15 1.0%, triclosan 0.8%, 2,4-dichlorobenzyl alcohol 0.4%. These relatively high values suggest a heavy exposure of the Swiss population to topical preservatives. Compared to previous studies, the sensitization rate to Kathon CG has stabilized in Switzerland over the last 2 years. Sensitization to formaldehyde portrayed impressive geographical variation, with sensitization rates up to 9% in western and only 3% in eastern Switzerland. The low sensitization rate to parabens argues for their inclusion in a medicament or preservative series, rather than in the standard series.

TITLE: Gingival absorption of triclosan following topical mouthrinse application.

AUTHORS: Lin YJ; Fung KK; Kong BM; DeSalva SJ

SOURCE: Am J Dent 1994 Feb;7(1):13-6

CITATION IDS: PMID: 9115672 UI: 97260285

ABSTRACT: This study assessed the gingival uptake and urinary excretion of triclosan in dogs following topical applications of a mouthrinse containing 0.03% of triclosan. Five different phases were conducted to define the time course of plasma concentration. The effect of plaque on gingival absorption was also measured. Phase I: Animals' teeth were cleaned of plaque via scraping. Blood sampling time was 0-2 hours. Phase II: Plaque was not removed from the animals' teeth. Blood sampling time was 0-2 hours. Phase III: Plaque was not removed from the animals' teeth. Blood sampling time was 0-6 hours. Phase IV: Plaque was not removed from the animals' teeth. Blood sampling time was 0-12 hours. Phase V: Animals' teeth were cleaned of plaque via scraping. Blood sampling time was 0-12 hours. The test substance was administered to 1 male and 1 female dog in Phases I, II, IV and V, and to 1 male dog in Phase III. The same animals were used in each phase. On the first day of each phase, the animals were treated with distilled water for a 15-minute period. The animals were exposed daily to the test material for a 15-minute period during the remaining 7 days of each phase. The test material was administered using custom-made acrylic applicator trays to enclose the maxillar premolars and molars and gingiva of one- half of the upper jaw. A leak-proof seal along the mucogingival junction and palatal mucosa was established and maintained during the exposure period.(ABSTRACT TRUNCATED AT 250 WORDS)

TITLE: Acute toxicity, percutaneous absorption and effects on hepatic mixed function oxidase activities of 2,4,4'-trichloro-2'-hydroxydiphenyl ether (Irgasan DP300) and its chlorinated derivatives.

AUTHORS: Kanetoshi A; Katsura E; Ogawa H; Ohyama T; Kaneshima H; Miura T

AUTHOR AFFILIATION: Hokkaido Institute of Public Health, Japan.

SOURCE: Arch Environ Contam Toxicol 1992 Jul;23(1):91-8

CITATION IDS: PMID: 1637203 UI: 92344442

ABSTRACT: Acute toxicity of 2,4,4'-trichloro-2'-hydroxydiphenyl ether (Irgasan DP300) (I) and its three chlorinated derivatives, 2',3,4,4'-tetrachloro- 2-hydroxydiphenyl ether (II), 2',4,4',5-tetrachloro-2-hydroxydiphenyl ether (III) and 2',3,4,4',5-pentachloro-2-hydroxydiphenyl ether (IV), in mice were examined by intraperitoneal injection. The LD50 values of Irgasan DP300, II, III and IV were 1,090, 710, 650 and 430 mg/kg, respectively. The percutaneous absorptions of these tritiated compounds were also examined by the application on the backs of mice. The radioactivities in most tissues reached to the maximal levels at 12 h or 18 h after dosing, which corresponded to 11-76% of the maximal levels given by the oral administration (Kanetoshi et al. 1988a). These results show the high percutaneous absorbability of Irgasan DP300 and its chlorinated derivatives. The intraperitoneal administrations of III and IV to rats induced hepatic microsomal aminopyrine N-demethylase and aniline 4-hydroxylase activities similarly to phenobarbital. These chlorinated derivatives also increased cytochrome P-450 content, and the activities of aminopyrine N-demethylase and N-methylaniline N- demethylase in hepatic microsomes from mice. The extents of the increases were similar to those by phenobarbital and 3- methylcholanthrene.

TITLE: Triclosan: a safety profile.

AUTHORS: DeSalva SJ; Kong BM; Lin YJ

SOURCE: Am J Dent 1989 Sep;2 Spec No:185-96

CITATION IDS: PMID: 2638179 UI: 90290654

ABSTRACT: Triclosan (2, 4, 4'-trichloro-2'-hydroxydiphenyl ether), an antimicrobial agent, has been used extensively for 20 years in consumer products, principally in deodorants, soaps and other dermatological preparations. Recently, the use of triclosan has been extended to oral health care products such as dentifrices. This paper reviews safety information, both pre-clinical and clinical studies, from the literature, data submitted to the Antimicrobial I OTC Review Panel and unpublished work from the Pharmacology and Toxicology Department of the Colgate-Palmolive Company. The data spans acute, subacute, subchronic and chronic toxicity; mutagenicity, carcinogenicity, reproduction/teratology and pharmacokinetics. Results of these studies show that triclosan is well tolerated by a variety of species including man. In clinical studies with triclosan in solutions and dentifrices, a steady state was reached by day 7 with blood levels in the parts per billion (ppb) range and urine as the main route of excretion. Based on these studies, triclosan can be considered safe for use in dentifrice and mouthrinse products.

TITLE: The acute toxicity of penta-, hexa-, and heptachlorohydroxydiphenyl ethers in mice.

AUTHORS: Miller TL; Lorusso DJ; Walsh ML; Deinzer ML

SOURCE: J Toxicol Environ Health 1983 Aug-Sep;12(2-3):245-53

CITATION IDS: PMID: 6655733 UI: 84090302

ABSTRACT: The acute intraperitoneal LD50 values of various hydroxychlorodiphenyl ethers (HO-ClX-DPEs; X = 5-7) in mice have been determined. The acute toxicities observed were on the order of, or slightly less than, that observed previously for 2-hydroxy-2',4,4'-trichlorodiphenyl ether (2-HO- Cl3-DPE; Irgasan DP-300; Triclosan), a commonly used bactericide. However, the acute toxicities determined for these compounds were substantially less than have been observed for HO-Cl9-DPEs and pentachlorophenol. The HO-ClX-DPEs had a marked hypothermic effect, similar to that produced by 2-HO-Cl3-DPE. Symptomatology following exposure to the HO-ClX-DPEs (X = 5-7) suggested a nonspecific depressant effect on the central nervous system.

TITLE: The acute toxicity of nonachloropredioxin and 3- and 4- hydroxynonachlorodiphenyl ether in mice.

AUTHORS: Miller TL; Lorusso DJ; Deinzer ML

SOURCE: J Toxicol Environ Health 1982 Oct-Nov;10(4-5):699-707

CITATION IDS: PMID: 7161822 UI: 83138865

ABSTRACT: The acute intraperitoneal LD50 values of hydroxynonachlorodiphenyl ethers (HO-Cl9-DPEs) in mice have been determined. The acute toxicity of each of these compounds is compared with that of pentachlorophenol (PCP) and 2-hydroxy-2',4,4'-trichlorodiphenyl ether (2-HO-Cl3-DPE; Irgasan DP-300; Triclosan), a commonly used bactericide. The order of acute toxicity observed was: 2-HO-Cl9-DPE greater than technical PCP approximately equal to pure PCP greater than 3-HO-Cl9-DPE greater than 4-HO-Cl9-DPE greater than 2-HO-Cl3-DPE. Symptomatology following exposure to the HO-Cl9-DPEs was similar to that observed for PCP, a known uncoupler of oxidative phosphorylation. 2-HO-Cl3-DPE, however, produced clinical signs suggestive of a suppressive effect on the central nervous system. Data on time response following a lethal dose of each of these compounds was also obtained.

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