From medline search, 2/2/99
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.
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.
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.
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.
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.
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.
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.
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.
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)
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.
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.
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.
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.