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					 Advances in Dental Research

                           D. Adams and M. Addy
                         Adv. Dent. Res. 1994; 8; 291
                    DOI: 10.1177/08959374940080022401

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                                                                                            outhwashes have been in use for centuries as breath
                                                                                            fresheners, medicaments, and antiseptics. One of the
                                                                                            oldest, which is still in use today, is the combination of
Department of Basic Dental Science                                                          essential oil and phenolic compounds, Listerine. This
Dental School                                                                     formulation, derived from Lister's original work with carbolic
Cardiff CF4 4XY                                                                   acid, has been used since the end of the last century. Only in
Wales, UK                                                                         more recent times, however, have mouthrinses been given
'Department of Prosthodontics                                                     much credence as preventive agents against dental disease.
 and Periodontology                                                                   The increasing awareness of plaque as a major contributing
Dental Hospital and School                                                        factor in the initiation of caries and periodontal disease changed
Lower Maudlin Street                                                              the perception of mouthwashes by the dental profession, and
Bristol BSI 21Y, UK                                                               caused an upsurge in the search for anti-plaque agents (Mandel,
Adv Dent Res 8(2):291-301, July, 1994                                                 The prevention or removal of plaque is logical, since, in the
                                                                                  absence of plaque, neither caries nor periodontal disease is
                                                                                  found. Mechanical removal of plaque requires manual dexterity
Abstract—Mouthrinses have been used for centuries for                             and time, but few people can consistently maintain a plaque-
medicinal and cosmetic purposes, but it is only in recent years                   free status by this means alone. Additionally, there is little
that the rationale behind the use of the ingredients has been                     scientific evidence to indicate that mechanical tooth cleaning
subject to scientific research and clinical trials. Although                      perse has any influence on caries (Frandsen, 1986). A chemical
Listerine held its position for many years in the vanguard of the                 agent either as an adjunct to or a replacement for mechanical
anti-plaque agents, the advent of mouthrinses containing                          cleansing has long been sought. Hence, the arrival of
chlorhexidine was a major breakthrough in the research for a                      chlorhexidine was greeted enthusiastically by the profession,
chemical means to prevent disease. Since that time, and                           and although it has lived up to the early promise, the major
especially in the past ten years, the number of formulations that                 disadvantages of staining and unpleasant taste have provided
claim to have anti-plaque, anti-calculus, and anti-caries activity                an incentive to continue the search to find equally efficient
has increased, and much emphasis has been placed on such                          agents which lack side-effects. So far, none has been found.
substances as an adjunct to, or indeed to replace, conventional                       Studies in vitro and in vivo on chemical plaque control
toothbrushing techniques.                                                         agents in mouthrinses—in particular, chlorhexidine—are legion,
This review covers the literature on mouthrinses over the past                    and reviews on the subject in recent years are numerous (for
five years, concentrating more on the anti-plaque, anti-gingivitis,               example, see: Hull, 1980;Kornman, 1986; Addy, 1986; Mandel,
and anti-calculus formulations. In the first section, the methods                  1988), and no attempt will be made to re-review this extensive
of conducting clinical trials of mouthrinses are discussed, and                   literature. This review will be confined to an update of the
a plea is made for a greater degree of standardization of                         information on mouthrinses since 1988.
methodology with agreed acceptable levels of clinical benefit.                        Before dealing with individual active ingredients in
Trials of established mouthrinses are considered, and the                         mouthrinses, it is worth clarifying the complex situation of a
advantages and disadvantages of several newer formulations                        plethora of models to study a variety of endpoints.
discussed.                                                                            Clinical trials of mouthrinses take several forms, depending
From the review, it appears that chlorhexidine has no equal in                    on the expected benefit of the active ingredients and, almost,
 its effects on reduction of plaque and gingivitis, but major                     the whim of the individual researchers. This makes comparisons
drawbacks lie in the taste and stain-producing problems. The                      among trials of different materials difficult if not impossible.
pre-brushing rinse, Plax, does not have unqualified success in                    Trials can be divided into those that effect plaque removal,
 all trials, though the more recent European formulation may                      those that prevent plaque formation, those that inhibit or reduce
have promise. Newer rinses which inhibit bacterial adhesion to                     gingivitis, and those that reduce calculus formation.
 tooth surfaces also appear promising, and it is suggested that                    Additionally, there are studies on the effects on the microflora
 more work on combinations of active ingredients is necessary.                     of the mouth in vitro and in vivo.
This manuscript was presented at a Symposium entitled
"Mechanisms and Agents in Preventive Dentistry", held                                                           PLAQUE REMOVAL
October 28~November 1, 1992, in Chester, England, under                            These trials are mainly short-term, with plaque scored before
the auspices of the Council of Europe Research Group on                            and after a single rinse. They are easily controlled, since the
Surface and Colloid Phenomena.                                                     rinsing is supervised, and have been used more recently to

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292                                                                   ADAMS & ADDY                                                  ADV DEW RES JULY 1994

assess the plaque removal effects of several rinses, including a                     Another variant relates to the bias of the clinician or subject.
pre-brushing rinse (Binney et al., 1992).                                         Trials can be "single blind", where the clinician makes his
                                                                                  assessment of the subject without knowing which regime has
                    PLAQUE RE-GROWTH
                                                                                  been used by the subject, or "double blind", where neither the
In these trials, the subjects are given a thorough prophylaxis at                 subject nor the clinician is aware of the "treatment" until the
baseline, and plaque is allowed to accumulate over the short                      end of the trial.
term, varying from 16 hours to several days, without any other                       Finally, studies are designed to test the action of a specific
oral hygiene measures. The aim is to assess the plaque-                           ingredient or ingredients or designed to evaluate a complete
preventing ability of the agent, on its own.                                      formulation or product. Depending on the type of study,
                                                                                  controls usually will be quite different.
                  GINGIVITIS REDUCTION                                               In this review, the main thrust will be to examine both the
Studies on gingivitis reduction are usually of longer duration                    studies for each ingredient where it is used as a mouthrinse, and
than plaque removal or plaque re-growth studies, though in                        specific mouthrinse formulations available as oral hygiene
most cases the amount of plaque present is assessed together                      products to the public.
with the gingivitis. The American Dental Association (ADA)
guidelines on the use of trials to measure gingivitis reduction                                                    LISTERINE
insist on a period of at least 6 months. However, there have been                 The mouthrinse with the longest history of use is Listerine, a
studies of lesser duration, in spite of the guidelines, and known                 hydro-alcohol solution of thymol, menthol, eucalyptol, and
as "experimental gingivitis in man" studies. These may last                       methyl salicylate. Since Miller (1989) demonstrated that caries
from days to weeks. The reports are made up of those performed                    was due to micro-organisms, Listerine has been used as a
as "natural", i.e., where other oral hygiene measures are not                     mouthwash to try to prevent dental disease. Probably because
controlled and patients use their own particular techniques, in                   of its "disinfectant" smell and taste, it has gained much popular
addition to using the test rinses, and other trials where the oral                credence, and much of its popular appeal relates to its ability to
hygiene measures are strictly according to a set regime. Most                     dispel odors and create a "clean" sensation in the mouth.
long-term studies of the latter type rely to a large extent on the                    Anti-plaque activity has been demonstrated in several studies
compliance of the subjects.                                                       (reviewed by Ross et al, 1989), and Listerine is of sufficient
   The assessment of gingivitis is sometimes made by a gingival                   standing to have received the approval of the American Dental
index, with or without a "bleeding on probing" score (Hull,                       Association (1988a). The mode of action of the active ingredient
 1980).                                                                           or ingredients in the mouthrinse is not established, since there
                                                                                  are several antimicrobial agents in the hydro-alcohol base.
Trials on the reducing effect of an agent on calculus are of                                                   SHORT-TERM STUDIES
necessity long-term, i.e., for 6 months or longer. Calculus is                    Brecx et al. (1990) used a double-blind experimental gingivitis
measured by a calculus index, in particular the Volpe-Manhold                     model to compare anti-plaque, anti-gingivitis, and anti-
Index (Volpe et al,1967), which has gained almost universal                       microbial efficacies of Listerine, Meridol, and chlorhexidine.
acceptance. Trials have studied mostly effects on an agent on                     Meridol is a mixture of amine fluoride and stannous fluoride.
calculus only, but some have included assessments of plaque,                      After professional tooth cleaning, 36 subjects rinsed twice
gingivitis, and even stain.                                                       daily for 21 days with one of the three rinses or with a placebo
                                                                                  control as their only oral hygiene measure. At the end of 3
                           METHODS                                                weeks, plaque indices were lowest in the chlorhexidine group,
Clinical trials use two main methods. One is the parallel study,                  with the Listerine and Meridol groups having plaque indices
where control and test groups of subjects are matched as far as                   much higher than but not as high as that of the placebo. The
possible for age, sex, and periodontal disease status. Each                       reducing effects of Listerine and Meridol on plaque were
group uses only the test or the control regime. The other method                  significant only when the three-week results were compared.
is the cross-over study, which has the advantage of requiring                     Listerine and Meridol were not significantly better than the
fewer subjects without loss of power to detect statistically                      control at inhibiting gingivitis, whereas chlorhexidine reduced
significant differences. Each subject uses either the test or the                 gingivitis by 50% compared with the placebo. These authors
control rinse, is assessed at the end of the set period, and, after               used a vitality dye test on plaque bacteria to demonstrate that
a "wash-out period", will use the alternative formulation or                      chlorhexidine had the greatest effect on the proportion of
procedure to that used in the first procedure. Matching of                        viable organisms, followed by Meridol, with Listerine and the
subjects in groups is unnecessary, since every subject uses each                  placebo having no significant effect when compared with the
procedure and acts as his/her own control. Cross-over studies                     baseline.
typically use healthy volunteers and measure the inhibitory                          In a later study, Brecx et al (1992) reported the effects of
effects of agents on the development of plaque and gingivitis,
                                                                                  similar rinse formulations on plaque and gingivitis when used
alone or as adjuncts to tooth cleaning. Parallel studies may be
                                                                                  as adjuncts to normal tooth cleaning.
used similarly but also are used to study the action of agents in
                                                                                     In this study, two Meridol preparations—one containing
reducing plaque and gingivitis.
                                                                                  Aspartum and one containing Acesulfam—were compared

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VOL.   8(2)                                                            M0UTHR1NSES                                                               293

with Listerine, chlorhexidine, and a placebo. Plaque indices                      develop significantly more stain and supragingival calculus
were lowest with chlorhexidine, with one of the Meridol                           compared with baseline and control values. This work was
formulations and Listerine showing a significant reduction in                     submitted to the American Dental Association's Council on
plaque compared with the placebo rinse. The gingivitis scores                     Dental Therapeutics in 1988 prior to being published in full and
with the Listerine group were little better than those with                       was accepted as part of the evidence for the seal of approval by
placebo, and the authors concluded that there was little                          the ADA, together with two other reports showing long-term
advantage in combining Listerine and mechanical oral hygiene                      beneficial effects of Listerine on gingivitis and plaque.
measures, which had not been used in the earlier study (a                            In the report by Overholser et al (1990), it was suggested
finding contrary to that of Axelsson and Lindhe in 1987).                         that Listerine may play a role in the reduction of inflammation
    In another short-term experimental gingivitis study, Moran                    by some means other than its effects on salivary bacterial flora,
et al (1991) compared chlorhexidine and Listerine using a                         which did not change appreciably over 6 months. Kato et al
single-blind randomized triple cross-over design. A group of                      (1990) examined the effects of Listerine on the oral microflora
15 subjects used chlorhexidine, Listerine, or a placebo                           and found that the bactericidal effect is not as great as that of
mouthrinse for 19 days in the absence of normal tooth cleaning.                   chlorhexidine, which adds weight to the possibility that the
The wash-out periods were of 21 days' duration. Plaque areas                      reduction in gingivitis by Listerine in the long-term studies is
were measured, and these increased from baseline six-fold                         not wholly due to the reduction in the amount of plaque.
with saline rinsing and three-fold with Listerine when compared                      In a clinical trial, it was shown that Listerine delivered by an
with that in subjects using chlorhexidine. Although the increase                  oral irrigation device could result in significant reductions in
in gingivitis indices from baseline was lowest with chlorhexidine                 plaque, bacterial cell counts, and gingival bleeding. This study
and highest with saline, the differences were not significant.                    was of relatively short duration (6 weeks) and is interesting in
Listerine has not been reported previously as producing staining                  that both plaque removal and plaque re-growth were studied in
of the teeth, but Moran et al (1991) did find a significant                       the same mouths. This was accomplished by each subject
difference in severity of staining compared with placebo.                         having a half-mouth prophylaxis at the start of the trial (Ciancio
    From these short-term studies, it would seem that Listerine                   etal, 1989).
could reduce plaque compared with placebo, but its ability to                        Another interesting aspect of Listerine is in the effect on
reduce gingivitis is not marked.                                                  recurrent aphthous ulceration (Meiller et al, 1991). Listerine
                                                                                  was found to reduce the duration of the ulcers on average by
                    LONG-TERM STUDIES                                             two days and also the perception of severity by the patient,
Minah et al (1989) considered the effect of six months' usage                     compared with either a baseline period of observation or with
of Listerine on the plaque flora in 83 subjects using the                         a control 5% hydro-alcoholic mouthrinse. The numbers and
mouthwash twice daily. No significant increases in numbers of                     frequency of ulcers were reduced by both Listerine and control
presumptive oral pathogens, spirochetes, black-pigmented                          mouthrinses.
Bacteroides, Streptococcus mutans, or Candida albicans were                          Disadvantages of Listerine are few. The taste is unpleasant
found. The conclusion was that Listerine in the long term did                     with a burning sensation on the mucosa, although this does not
not induce any resistant strains in plaque, nor did it encourage                  appear to deter its use, and patients appear to adapt to it. It
undesirable oral pathogens.                                                       causes little if any staining and no enhancement of pathogenic
    The same group of workers also reported on a study of the                     organisms.
development of gingivitis over 6 months (De Paola et al,                             There is some evidence that Listerine could have deleterious
1989).                                                                            effects on dentin (Addy et al, 1991b). Thus, in a study of the
     In a double-blind trial, Listerine was used to supplement                    effects of mouthrinses on dentin, it has been shown that the
regular oral hygiene measures. Results showed that both                           smear layer produced by instrumentation of dentin can be
plaque and gingivitis were inhibited by 34% compared with the                     removed with soaking for 10 minutes with Listerine. Brushing
hydro-alcohol control. The results were highly statistically                      the dentin after exposure to Listerine enhanced the exposure of
significant. Overholser et al (1990), in a six-month study of                     dentinal tubules. Although the mouthrinse is not normally in
the development of gingivitis and plaque, compared the effects                    contact with the dentin for this length of time, the repeated use
of supervised rinsing twice daily with Listerine, Peridex (a                      of this agent, particularly as a pre-brushing rinse, is probably
chlorhexidine solution), and a hydro-alcohol control. The                         questionable at the present time. No doubt the acidity of
extent of staining and development of calculus over this period                   Listerine (pH 4.4) is related to its effect on dentin. However,
were also assessed and compared with the baseline scores,                         these studies were carried out in the absence of saliva, and may
which were measured immediately prior to a thorough                               not therefore be applicable to the in vivo situation.
prophylaxis at the start of the trial.
    The study showed that Listerine inhibited plaque and                                                       CHLORHEXIDINE
gingivitis development by 36% compared with results in the                         Chlorhexidine gluconate (CHX) is a cationic bis-biguanide,
group using the hydro-alcohol control. Interestingly, the subjects                 with a very broad antimicrobial spectrum. The first report of its
in the Listerine group did not develop significant levels of stain                 anti-plaque activity was by Loe and Schi0tt (1970). It is
or supragingival calculus compared with baseline or the control                    interesting now to read in this report at the meeting in Dundee
group. In contrast, subjects in the chlorhexidine group did                        in 1969 that "The primary objective of this experiment is not

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294                                                                   ADAMS & ADDY                                                  ADV DENT RES JULY 1994

to introduce chlorhexidine as a possible antimicrobial agent for                  These authors believed that Eludril, which was not simply a
the clinical prevention and control of plaque".                                   lower concentration of chlorhexidine gluconate than in the
    By 1974, there were already over 70 articles on the oral use                  0.2% mouthwash, contained substances which inactivated the
of chlorhexidine, and it has been proven many times over as the                   chlorhexidine, thus reducing its anti-plaque activity.
most effective agent, not only against plaque but also in long-                       An attempt to reduce the staining of chlorhexidine by using
term studies on gingivitis.                                                       peroxyborate after chlorhexidine rinsing showed promise (Addy
    It is now used as a positive control in many clinical trials of               et al, 1991a). Oxidizing mouthwashes markedly reduced
new mouthrinse formulations. The reduction in plaque indices                      staining after 2V2 days' "enforced" staining with tea after
is usually found to be on the order of 60%, while the gingival                    chlorhexidine, and the authors suggested that rinsing with
indices are reduced by about one-third (Grossman et al, 1986).                    peroxyborate may be useful after a course of therapy with
The American Dental Association (1988b) has approved its                          chlorhexidine.
use in Peridex, a 0.12% solution of chlorhexidine.                                    Chlorhexidine has been reported as having a toxic effect
    The major advantage of chlorhexidine over most other                          (Kenrad, 1990), and major changes in the oral mucosa were
compounds lies in its substantivity. It binds to soft and hard                    seen after extreme overdosage of mouthrinsing with
tissues in the mouth, enabling it to act over a long period after                 chlorhexidine gluconate. The changes included a thickening of
use of a formulation. Bacterial counts in saliva consistently                     the mucosa which resembled leukoplakia and disappeared
drop to between 10 and 20% of baseline after single rinses and                    when the dose was reduced.
remain at this level for at least 7 hours (Addy and Wright, 1978)                     Sensitivity to chlorhexidine was reported by Yusof and
and probably more than 12 hours (Schi0tt et al, 1970).                            Khoo (1988). Two cases were reported where the mucosa
    The main disadvantage of chlorhexidine is its taste, and a                    showed sensitivity to contact with chlorhexidine, but no allergies
barrier to continued used is its affinity for dietary compounds,                  to chlorhexidine have been reported from the Western countries.
some of which cause staining (Addy et al, 1985). In some                              In vitro growth of epithelial cells is inhibited to some extent
cases, staining of the teeth is severe, and removal requires a                    by 2 hours' exposure to a 250-fold dilution of 0.2% chlorhexidine
professional prophylaxis (Hoyos et al, 1977). Additionally,                       gluconate. Although in vitro results are not necessarily
tongue brushing may be required to remove the soft-tissue                         representative of what happens in the oral cavity, the results
discoloration. To overcome the problem of staining, lowered                       suggest that where the oral mucosa has been breached, healing
concentrations of CHX in rinses have been formulated as                           may be delayed if chlorhexidine is used (Shakespeare et al,
Peridex (0.12%) and Eludril (0.1 %). A comparison in vitro of                      1988). This must be balanced against the beneficial effects to
the 0.1% and 0.2% formulations (Addy etal, 1989b) showed                          healing of bacterial inhibition. Thus, healing of periodontal
that 0.1% CHX produced no staining of acrylic specimens                           surgical wounds is enhanced by CHX.
greater than that of controls, whereas the 0.2% formulation did                       Cline and Layman (1992) evaluated the effects of
cause heavy staining. Antimicrobial effects of the two products                   chlorhexidine on attachment and growth of human fibroblasts
were similar, but the overall profile for the 0.1% preparation                    and periodontal ligament cells. Treatment of root surfaces with
suggested that CHX in the 0.1 % rinse was partially or completely                 up to 0.12% had no effect on attachment. Morphology and
inactivated. The authors suggested that the detergent in the                      attachment were, however, affected by treatment with 0.2-2%
0.1% solutions inactivated the CHX and that the antimicrobial                     solutions of CHX. Direct exposure of cells to 0.01%
effect of the solution was derived more from the detergent than                   chlorhexidine caused a reduction of 90% in 3H-thymidine
CHX. They also suggested that the degree of staining in vitro                     uptake. This may be a factor to be considered in using
with CHX solutions could be used as an indication of possible                     chlorhexidine to irrigate subgingival areas.
antimicrobial activity in the mouth. It has also been reported                        In the report by Brecx et al (1992) referred to earlier,
that 0.1% chlorhexidine was more acceptable than 0.2%                             chlorhexidine over a three-week period reduced plaque and
 solutions to patients using the mouthwashes as post-operative                    gingivitis to the same extent, whether mechanical means of
prophylactics (Heps et al, 1988). No statistically significant                    oral hygiene were used or not. It was of interest to note that after
differences were found in the frequency of loss of taste,                         three weeks' use, the viability of bacteria in plaque was
burning sensation of the mucosa, and staining. Thirty patients                    beginning to rise and at 14 and 21 days was not significantly
were included in the study; four using the 0.2% solution                          different from baseline.
discontinued the mouthwash because of the side-effects.
   It was concluded that 0.1 % CHX is preferable to 0.2% CHX                                                    SANGUINARIA
as a prophylactic mouthwash after oral surgery (Heps et al,                        Sanguinaria is contained in the proprietary mouthwash Viadent
1988).                                                                             in the USA (Perioguard in the UK) and is an alkaloid from the
   Jenkins et al (1989), in a short-term single-blind cross-over                   plant Sanguinarina canadensis. It has been incorporated into
study, compared the effects of two commercially available                          dentifrices and mouthrinses, but there are conflicting reports
formulations containing 0.2% (Corsodyl) and 0.1% (Eludril)                         on its efficacy.
chlorhexidine on plaque reformation, gingivitis, and staining                          Wennstrom and Lindhe (1985) conducted a short-term
in a group of 14 volunteers. Gingivitis at 12 and 19 days was                      double-blind cross-over study of plaque re-growth and gingivitis
considerably less with 0.2% than with 0.1% formulations, but                       lasting two weeks for each experimental period, using a
staining was markedly reduced with the lower concentration.                        mouthrinse which was a 0.03 % solution of sanguinaria extract.

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VOL.   8(2)                                                             MOUTHRINSES                                                              295

They controlled the study with a placebo with similar taste and                   found, but there were reductions in numbers of the organisms
color. Plaque indices were 40% lower and gingivitis scored                        associated with gingivitis, which may have accounted for the
25% lower with the sanguinaria rinses compared with the                           reduction in gingivitis. Similar beneficial effects have been
controls. Normal toothbrushing was suspended during the trial                     found by Hannah et al. (1989) in a six-month trial of gingivitis
period, and with some of the subjects there was a slight                          prevention, in a group of orthodontic patients, using both
discoloration of the teeth and dorsum of the tongue.                              toothpaste and rinses containing sanguinaria extract and zinc
    There have been other encouraging studies with sanguinaria                    chloride, findings which were confirmed by Kopczyk et al
which are reviewed by Mandel (1988). Clinical trials with this                    (1991). It seems likely that if sanguinaria extract is to have any
material often have used a dentifrice and a mouthrinse, since                     benefit, it needs to be used in combination with zinc chloride,
the active ingredient can readily be incorporated into a toothpaste               and as both a toothpaste and mouthrinse. Such necessary
(Lobene et al, 1986b).                                                            combinations of products to attain efficacy must have cost-
    In a single-blind cross-over experimental gingivitis study,                   benefit implications.
Moran etal (1988) compared the effects of the sanguinarine-
zinc mouthwash Viadent, with 0.2% CHX, in the absence of all                                                    TRICLOSAN
other oral hygiene. The positive control, CHX, was significantly                  Saxton (1986) reported on the reduction of plaque and gingivitis
more effective than Viadent in inhibiting both plaque and                         by 2,4,4',trichloro-2-hydroxydiphenyl ether (triclosan) and
gingivitis. This study did not have a placebo control, but in a                   zinc citrate in a dentifrice, in 12 volunteers. The combination
later study (Moran et al, 1992a), this group used a four-day                      of triclosan and zinc citrate significantly improved the efficacy
plaque re-growth model to compare several rinses, including                       above a simple addition of effects of each alone.
sanguinarine with and without zinc chloride. In this study, a                         Nabi et al. (1989) showed that the copolymer
saline rinse was used as the placebo control. The use of                          polyvinylmethyl ether/maleic acid (PVM/MA) enhanced the
sanguinarine alone produced results which differed little from                    anti-bacterial activity of solutions of triclosan in vitro and
those of the group using saline. The combination of zinc                          enhanced the anti-caries activity of triclosan in rats.
chloride and sanguinarine produced a "modest" reduction in                            In a cross-over clinical trial, 20 subjects (Abello et al,
plaque growth, which could have been due to the zinc chloride                     1990) used triclosan/copolymer rinses for 7 days without
(Southards a/., 1987).Quirynenefa/. (1990) have shown that                        brushing, and the effects were compared with those when
zinc chloride on its own was almost as effective as sanguinarine                  subjects used rinses containing alcohol and water placebos and
and zinc chloride in a single-blind cross-over study of plaque                    a new pre-brushing rinse, Plax. Results showed that the triclosan/
re-growth. The experimental period lasted 18 days, and during                     copolymer reduced plaque by approximately one-half,
this period rinsing with either Viadent, Viadent without                          compared with the water placebo or the Plax rinse. Compared
sanguinarine, or CHX was the only oral hygiene procedure.                         with the alcohol placebo, the triclosan/copolymer rinse reduced
Plaque growth was assessed on 4 teeth in each of 12 subjects,                     plaque by 31%.
and hence numbers were perhaps not as high as one would                               A similar study (Singh et al, 1990) compared 0.03%
wish. However, the differences between the areas of the buccal                    triclosan and the copolymer, used as a pre-brushing rinse for
surfaces of the teeth covered by plaque were highly significant                   six days, with a flavored and colored-water placebo mouthrinse.
in a comparison of CHX and Viadent. Viadent was only                              Twice-daily rinses followed by brushing resulted in a 31%
slightly better than the control, and at only one period in the                   reduction in plaque compared with the placebo. Interestingly,
trial (3]h days) was there a statistically significant improvement                the reduction with water rinse alone in the previous study
in plaque inhibition with Viadent. The authors concluded that                     seemed greater than when followed by brushing, in this trial.
Viadent mouthrinse would have at most only a limited role as                          Using virtually the same protocol, 60 subjects rinsed with
a plaque inhibitor.                                                               water, Plax, or triclosan/copolymer (Rustogi et al, 1990).
    The possible beneficial effect of sanguinarine used as a                      Again, the triclosan/copolymer reduced plaque indices to 40%
mouthrinse over a long term is difficult to assess, since the                     of the placebo mouthrinse. Plax was not significantly different
majority of studies have used the rinse in combination with a                     from the water placebo.
sanguinarine dentifrice. For example, Harper et al. (1990a), in                       Plaque re-growth over a four-day period was used to compare
a six-month double-blind parallel study, assessed gingivitis                      the efficiencies of triclosan with and without copolymer,
and plaque in subjects using Viadent dentifrice together with                     stannous fluoride, stannous chloride/fluoride mixed, a stannous
a mouthrinse with sanguinaria extract and zinc chloride. The                      fluoride gel, and, as negative and positive controls, saline and
negative controls used the same products but without the                          0.12% chlorhexidine, respectively (Addy et al, 1990). The
sanguinaria extract or zinc chloride. Plaque and gingivitis                       saline rinse was significantly worse than all of the other rinses,
scores in the sanguinaria extract group were 21% and 25%                          but chlorhexidine was highly significantly better than the
lower than those in the control group at the end of 6 months.                     others, which could not be separated on the basis of their ability
"Bleeding on probing" assessments also showed a reduction in                      to reduce plaque formation. It was concluded that triclosan
the test group compared with controls. Harper et al. (1990b)                      added very little benefit.
also reported on the changes in microflora of the buccal                              This study raises the question of whether other ingredients
mucosa and of the supra- and subgingival plaque in this same                      in the triclosan/copolymer rinse exert plaque-inhibitory effects.
clinical trial. No opportunistic overgrowth of pathogens was                          The length of retention time for triclosan and zinc citrate in

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296                                                                   ADAMS & ADDY                                                ADV DENT RES JULY 1994

the mouth after use of toothpaste was studied by Cummins                          findings.
(1991). Saliva decay curves indicate a faster rate of clearance                      There have been several studies showing that Plax was no
from the mouth of triclosan compared with zinc. Triclosan was                     better than a placebo or water rinse (Kohut and Mankodi, 1989;
found in plaque for eight hours and in oral mucosa for at least                   Singh, 1990; Freitas etal, 1991; Chung etal, 1992; Binney et
three hours after brushing. The effects of zinc and triclosan                     al, 1993), and significantly, Lobene et al. (1990), in a six-
were concluded to be complementary and additive. However,                         month study conducted along the guidelines of the American
the relevance of retention studies may be questioned, since                       Dental Association, have shown, contrary to their earlier study
they indicate only the presence of a compound and not its                         (Lobene et al, 1986a), that Plax had no statistically significant
activity or availability.                                                         effect on plaque scores, gingivitis index, and microbiological
    It has been shown that 0.2% triclosan reduced salivary                        assays compared with water rinsing, confirming earlier short-
bacterial counts significantly up to three hours after rinsing                    term studies.
(Jenkins etal, 1991a). In this study, chlorhexidine and sodium                        Plax is now marketed in Europe by a different company
lauryl sulfate were included, both of which reduced bacterial                     with a revised formulation containing triclosan, and a recent
counts more than did triclosan. It was suggested that triclosan                   report provided encouraging findings for plaque and gingivitis.
did not offer any greater possibility of anti-plaque activity than
sodium lauryl sulfate alone. This was tested in a follow-up                                             SODIUM LAURYL SULFATE (SLS)
report by this group (Jenkins et al, 199 lb) when plaque scores                    This is an anionic detergent with a hydrophobic organic part,
and areas were recorded in a plaque re-growth study comparing                      which has a high affinity for protein molecules. It is widely
chlorhexidine, saline, triclosan, and sodium lauryl sulfate.                       used in dentifrices and mouthrinses, but recent work in the
Sodium lauryl sulfate produced complaints of burning in                            dental field has concentrated on its deleterious qualities rather
nearly all users, but the results confirmed that although triclosan                than on its benefits. As mentioned previously, it was used in
(0.2%) significantly reduced plaque, it was not as good as                         Plax as a detergent.
chlorhexidine and only slightly better than the detergent. Two                        In vitro work by Barkvoll et al (1988) has shown that SLS
other studies—by Deasy et al (1992) and by Lobene et al                            binds to hydroxyapatite and enamel through the hydration
(1992)—support the effectiveness of the triclosan/copolymer                        layer. This finding may be a factor in the inhibition of
combination. It seems clear from these studies that triclosan on                   monofluorophosphate protection against caries (Melsen and
its own has little place as an antiplaque rinse, but with zinc                     R0lla, 1983; Barkvoll, 1991) when SLS is incorporated into
chloride or copolymer its substantivity is increased and it has                    dentifrices with monofluorophosphate.
greater efficacy. This is supported by two long-term studies                          In his thesis on interactions of SLS and chlorhexidine,
where triclosan and the copolymer were incorporated into a                         Barkvoll (1991) drew attention to the neutralization of CHX
dentifrice. In these, a significant improvement in gingival                        even when these agents were applied separately and with time
health and plaque reduction, compared with placebo, was                            intervals between their separate applications. The interval
found (Garcia-Godoyeftf/., 1990; Cubells and Dalmau, 1991).                        between toothbrushing with a dentifrice containing SLS and
The combination of 0.2% triclosan with 0.5% zinc citrate was                       rinsing with CHX solutions should be "more than 30 minutes,
 also found to be beneficial in a six-month double-blind study                     probably nearer 2 hours".
 of gingivitis, calculus reduction, and plaque prevention.                            Barkvoll and R0lla (1989) studied the effect of SLS on the
                                                                                   oral mucosa in patients with allergic stomatitis. They suggested
                              PLAX                                                 that the denaturing effect of SLS on the oral mucin layer
The concept of a pre-brushing rinse was put forward by J.                          induced an increased exposure of the mucosa to various food
Lefoulon of Paris in about 1843. This was given renewed                            proteins, resulting in hypersensitivity.
impetus by the aggressive advertising of Plax, a pre-brushing                          Studies have demonstrated that 1% SLS in mouthwashes
rinse containing a number of ingredients including sodium                          exhibited plaque-inhibitory properties and substantivity, as
benzoate and sodium lauryl sulfate, which was claimed to                           measured by effects on salivary bacteria similar to those of a
reduce plaque by over 300% compared with brushing alone                            0.2% triclosan rinse (Jenkins et al, 1991a,b).
(Emling and Yankell, 1985). This was confirmed in a later
publication, when, with 20 subjects using Plax as a pre-                                                        HEXETIDINE
brushing rinse, there was significantly less plaque on buccal                      Hexetidine is the active ingredient in the product Oraldene.
and lingual surfaces than with a water rinse as placebo (Emling                    Since the study by Bergenholtz and Hanstrom (1974) showing
and Yankell, 1991). One other study, in 1989, compared Plax                        that Oraldene was less effective than a CHX rinse, there has
with Listerine. The ability of the rinse alone to reduce plaque                    been a dearth of data on this agent.
was assessed. The control in this case was water with flavor and                      A "preliminary" study of Oraldene (0.1% hexetidine) was
color, but no active ingredient. Plax was better than Listerine                    reported by Williams et al (1987). This was a plaque re-growth
or placebo, between which there was found to be no statistical                     study of seven days' duration, using the mouthrinse three times
difference (Bailey, 1989). A reduction in plaque scores was                        daily as the only oral hygiene procedure. A highly significant
also found in a three-month study with conditions as "normal"                      reduction of plaque accumulation was found, with the mean
as possible (O'Mahony and O'Mullane, 1991). However, the                           total plaque index of the Oraldene group being 40% lower than
design of the study calls into question the validity of the                        that of the placebo group.

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   There were several reversible side-effects with Oraldene,                       positive control and a placebo rinse. No mechanical oral
including soreness, slight ulceration, loss of taste, and numbness.                hygiene was allowed, and although the plaque scores with
   Recently, Grimm et al (1989) demonstrated an inhibition                         delmopinol rinsing were higher than those with CHX, the
of plaque development with a mouthrinse containing zinc,                           reduction from the scores with placebo rinsing was significant
fluoride, and hexetidine.                                                          and gave rise to optimism that delmopinol would be of benefit
   However, in an evaluation of its effects in the treatment of                    in reducing gingivitis. In a separate investigation in this report,
recurrent aphthous ulcers, Oraldene was found to provide no                        it was shown that delmopinol had very little effect on salivary
benefit to oral hygiene or gingival health (Chadwick et al,                        bacteria after one rinse, and the effect was lost in one hour.
1991). This clinical trial was a double-blind cross-over study                     Some subjects complained of the taste and a burning sensation
comparing Oraldene with placebo, with test periods of 6                            on the mucosa when they used this aqueous solution. The
weeks' duration. The incidental findings on plaque scores and                      conclusion is that delmopinol shows promise as an anti-plaque
"bleeding on probing" showed no significant differences                            agent and warrants further investigation.
between the groups at the end of the test periods.
                                                                                                                    ZINC SALTS
                         OCTENIDINE                                                Heavy metal salts have long been recognized as possessing
Beiswanger et al. (1990) conducted a three-month clinical trial                    antibacterial properties. Zinc ions have been found to reduce
of 0.1 % Octenidine mouthrinse in which 450 adults participated,                   the acidogenicity of plaque and inhibit its formation (Afseth
using their normal oral hygiene practices together with either                     and R0lla, 1980). While there are several studies of zinc in
a placebo or the test rinse twice a day. At 6 weeks and 3 months,                  dentifrices (reviewed by Gunbay etal, 1992), there have been,
soft tissue, gingivitis, and plaque accumulation were assessed,                    since 1988, practically no studies of zinc as the main active
and the degree of staining was measured at the end of the study.                   ingredient of mouthrinses. In the majority of cases, zinc salts
    Octenidine reduced plaque by one-third and gingivitis by                       have been used in combination with other agents.
one-half compared with the placebo, but left a high degree of                          Giertsen et al (1989) examined the dose-related effects of
staining, which was difficult to remove. It would appear that                      zinc chloride on plaque re-growth and acid production in
Octenidine offers no advantages over chlorhexidine, and is less                    plaque. The subjects in a four-day cross-over study rinsed
effective in its effect on plaque and gingivitis.                                  twice daily with 0, 5, 10, 20, or 100 mmol/L ZnCl2 for 4 days
                                                                                   in the absence of all other oral hygiene. This study is interesting
                         DELMOPINOL                                                in that the subjects chewed sucrose-containing chewing gum to
An alternative approach to antimicrobial attacks on dental                         enhance plaque formation, and the plaque re-growth results
plaque is to prevent the attachment or retention of bacteria on                    were analyzed as frequency distributions of the plaque index
the tooth by affecting its surface characteristics. Relatively                     scores 0, 1,2, and 3. A second panel of six subjects used
little work has been carried out in this aspect of prevention of                   placebo, 5 mmol/L or 100 mmol/L, in a cross-over study with
dental plaque, but recently Collaert et al. (1992a,b) have                         experimental periods of 3 days. It was found that plaque
revived interest with a surface-active agent, delmopinol                           formation was significantly reduced with 5,10, and 20 mmol/
hydrochloride. This agent is a substituted amino alcohol which                     L ZnCl2, but 100 mmol/L had little effect. The second panel
has little if any effect on salivary microflora. A significant                     was made up of six students who were heavy-plaque-formers,
dose-response effect was found in a group of volunteers when                       and on these the 100 mmol/L concentration significantly
plaque re-growth was assessed over two weeks, with rinsing as                      decreased plaque accumulation.
the only oral hygiene procedure. When gingival bleeding                                Zinc ions are considered to act by inhibition of glycolytic
indices were compared, there was no significant difference                         enzymes (Scheie et al, 1988), or by displacing magnesium
between rinsing with chlorhexidine and 0.2% delmopinol                             ions and hence inhibiting enzyme systems (Maryanski and
solution. Chlorhexidine and delmopinol were compared directly                      Wittenberger, 1975). There is evidence that zinc ions may
with 0.2% solutions as the only oral hygiene procedure over a                      inhibit both the adsorption of bacteria to the tooth surface and
period of 2 weeks. At the end of a preliminary two-week                            growth of existing plaque (Harrap etal, 1984; Saxton, 1986).
placebo period and at the end of rinsing with the active rinses,                       An assessment of the antimicrobial effects of zinc chloride
saliva samples were taken, gingival crevicular fluid flow was                      against oral streptococci was carried out by a seven-day
measured, gingivitis was scored by gingival index, plaque was                      mouthrinsing trial. The growth of plaque on Mylar foil was
measured planimetrically, and the plaque index scored. While                       analyzed for colony-forming units of Streptococcus mutans,
there were significant reductions in numbers of anaerobes,                         Streptococcus sanguis, and Streptococcus salivarius. There
aerobes and Streptococcus mutans in saliva of those rinsing                        was a significant decrease in total streptococcal colonies at
with CHX, no changes in these organisms were detected for                          seven days compared with placebo, and a selectively greater
subjects rinsing with delmopinol. However, there was no                            bactericidal effect on Streptococcus sanguis compared with
difference between delmopinol and chlorhexidine effects in                         Streptococcus salivarius (Dobl and Nossek, 1990; Nossek and
reducing crevicular fluid flow in gingivitis, though mean                          Dobl, 1990).
plaque extension was reduced more by chlorhexidine.
     Moran et al (1992b) studied plaque re-growth with                                                          COMBINATION RINSES
delmopinol in a four-day cross-over study using CHX as a                            As already noted, triclosan in combination with either zinc

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                                                                      ADAMS & ADDY                                                ADV DENT RES JULY 1994

citrate or a copolymer appears to achieve better results than                        Povidone iodine and hydrogen peroxide have been combined
when the agents are used alone. However, more comparative                         (Perimed) and compared with Listerine and Peridex (Maruniak
studies of these agents alone and their various possible                          et al, 1992) in a plaque and gingivitis trial lasting 14 days.
combinations are required.                                                        Seventy-one subjects used the rinses as their only oral hygiene
    Perdok et al (1988) used a double-blind cross-over study of                   procedures, and results were based on plaque index and papillary
plaque re-growth and gingivitis to test the efficacy of an amine                  bleeding scores. After 14 days, the average papillary bleeding
fluoride/stannous fluoride rinse. The rinse or a placebo was                      scores were better for Peridex and Perimed compared with
used as the only oral hygiene procedure for an experimental                       those for Listerine and water. The authors concluded that both
period of seven days. At the end of the period, the plaque index,                 Peridex and Perimed were effective in reducing plaque and
plaque area, gingival index, and microbial composition of the                     gingivitis, when used as a twice-daily mouthrinse by subjects
plaque were scored. The wash-out period between the cross-                        refraining from other oral hygiene measures. The combination
overs was eight weeks. Statistical analysis showed that the                       of Po vidone iodine and hydrogen peroxide appears to be better
active-component rinse produced scores of plaque growth and                       than povidone iodine alone.
gingivitis lower than those of the placebo group. No differences
in microbial composition of the plaque between the two groups                                                   ADVERSE EFFECTS
were found.                                                                        There has been, since 1988, an awareness that mouthrinses
    The combination of an amine fluoride and stannous fluoride                     may harm as well as aid oral hygiene measures. There have
has been studied for its effect on plaque growth in a trial lasting                been several reports of adverse effects, some of which have
5 months (Nemes et al, 1991). The amine fluoride/stannous                          been mentioned in the sections dealing with the individual
fluoride combination was formulated as both a toothpaste and                       agents. Other adverse effects are to be found in the following
a rinse, and compared in the trial with sodium fluoride toothpaste                 reports.
and rinse. The rinse was used after toothbrushing. The results                        Alcohol in mouthrinses, especially Listerine, was considered
showed that the plaque indices of the group using amine                            as a pre-disposing factor in cancer of the mouth, but this was
fluoride/stannous fluoride combination were reduced by 64%                         subsequently discounted fairly forcibly (Smigel, 1991).
and those using sodium fluoride by 40% relative to baseline                           Benzydamine oral rinse has been reported to cause a rash
figures. Counts of Streptococcus mutans and lactobacillus                          (Winn et al, 1991). Sodium retention in patients with
decreased in both groups, but no significant differences between                   hypertension, using Viadent, Plax, and Cepacol, was reported
the groups were found (Herczegh et al, 1991).                                      by Wagner et al (1989). Approximately 33% of the sodium
    Combinations of materials which might be considered                            contained in these mouthwashes was retained by the oral
beneficial can sometimes produce an inhibition of action.                          mucosa after rinsing. However, whether this is sufficient to
    Barkvoll et al (1989) have shown a deleterious effect of                       cause harm is not known.
SLS when combined with chlorhexidine. The SLS reduced the                             It was stressed by Fleszar (1989) that Listerine and Peridex
inhibition of chlorhexidine on the oral flora, and they suggested                  should be avoided in patients with untreated periodontitis. The
a two-hour gap between toothbrushing with paste including                          reduction in superficial inflammation may allow deeper
SLS and chlorhexidine mouthwashing. SLS remained in the                            infection to go untreated.
mouth for about 2 hours.                                                              SLS may cause damage to the oral mucosa (Barkvoll and
    In a test of the effects of toothpaste rinses on plaque re-                    R0lla, 1989).
growth, Addy et al. (1989a) found that toothpaste ingredients
reduced the efficiency of chlorhexidine, and it is probable that                                                   SUMMARY
the availability of chlorhexidine from the toothpaste was                          It would appear that chlorhexidine is still the best agent to
reduced. It may be that the SLS in the toothpaste material                         combat plaque and gingivitis, but its disadvantages remain to
inhibited the chlorhexidine. Monofluorophosphate is another                        be overcome. Listerine, though not as effective, can give good
common ingredient of toothpaste, and in a trial with a                             results. The reports on sanguinaria/zinc complexes, when used
combination of MFP and chlorhexidine, the action of                                in a mouthrinse alone, are not encouraging, but triclosan
chlorhexidine was reduced. There did appear to be a precipitation                  combined with copolymer or zinc seems effective as an anti-
when the solutions of the two compounds were mixed (Barkvoll                       plaque and anti-calculus agent.
et al, 1988). Triton X is often added to toothpastes as a                               Plax in its previous formulation has had mainly negative
detergent, but a combination with chlorhexidine is less effective                  reports, and the addition of triclosan in its new formulation
than chlorhexidine alone.                                                          shows promise.
    These are examples of the antagonism between cationic and                          Delmopinol warrants further investigation, and a
anionic components when combined in a formulation. All too                         combination of this agent with an antimicrobial might be an
often, active ingredients are included in formulations which                       interesting possibility.
have traditional ingredients, such as detergents, which interact                       There is a great need for more standardization of clinical
with the active ingredient with consequent reduction in efficacy.                  trials of mouthrinses and dentifrices. Although the ADA has
It is essential that clinical trials be carried out on any new                     established guidelines for trials of gingivitis-reducing agents,
formulations, even those containing "tried and tested" active                      it is necessary that minimum acceptable levels of reduction in
agents.                                                                            the various indices be defined.

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   If mouthrinses are to be used as adjuncts to normal tooth                        University of Oslo.
cleaning with toothbrushes and toothpaste, the ratio of cost to                  Barkvoll P, R0lla G (1989). Possible effects of sodium lauryl
gingival health benefits needs to be addressed. Moreover, it                        sulphate on the oral mucosa (abstract). J Dent Res 68(Spec
could be argued that proven benefits to periodontitis should be                     Iss):991.
the outcome measure of health benefit.                                           Barkvoll P, R0lla G, Bellagamba S (1988). Interaction between
                                                                                    chlorhexidine          digluconate         and       sodium
                        REFERENCES                                                  monofluorophosphate in vitro. Scand J Dent Res 96:30-33.
Abello R, Buitrago C, Prate CM, DeVizio W, Bakar SK                              Barkvoll P, R0lla G, Svendsen AK (1989). Interaction between
   (1990). Effect of mouthrinse containing triclosan and a co-                      chlorhexidine digluconate and sodium lauryl sulphate in
  polymer on plaque formation in the absence of oral hygiene.                       vitro and in vivo. J Clin Periodontol 16:593-595.
  Am J Dent 3:S57-S6L                                                            Beiswanger BB, Mallatt ME, Mau MS, Jackson RD, Hennon
Addy M (1986). Chlorhexidine compared with other locally                            DK (1990). The clinical effects of a mouthrinse containing
   delivered antimicrobials. A short review. J Clin Periodontol                     0.1% octenidine. J Dent Res 69:454-457.
   13:957-964.                                                                   Bergenholtz A, Hanstrom L (1974). The plaque inhibiting
Addy M, Wright R (1978). Comparison of the in vivo and in                           effect of Hexetidine (Oraldene) mouthwash compared to
   vitro antibacterial properties of povidone iodine and                            that of chlorhexidine. Community Dent Oral Epidemiol
  chlorhexidine gluconate mouthrinses. J Clin Periodontol                           2:70-74.
  5:198-205.                                                                     Binney A, Addy M, Newcombe R (1992). The effect of a
Addy M, Moran J, Griffiths A, Wills-Wood NJ (1985). Extrinsic                       number of commercial rinses compared to toothpaste on
  tooth discolouration by metals and chlorhexidine. 1: Surface                      plaque regrowth. J Periodontol 63:839-842.
   protein denaturation or dietary precipitation? Br Dent J                      Binney A, Addy M, Newcombe R (1993). The plaque removal
   159:331-334.                                                                     effects of single brushings and rinsings. J Clin Periodontol
Addy M, Jenkins S, Newcombe R (1989a). Studies on the                               4:181-185.
  effect of toothpaste rinses on plaque regrowth. 1. Influence                   Brecx M, Netuschil L, Reichert B, Schreil G (1990). Efficacy
   of surfactants on chlorhexidine efficacy. / Clin Periodontol                     of Listerine, Meridol and chlorhexidine mouthrinses on
   16:380-384.                                                                      plaque, gingivitis and plaque bacteria vitality. J Clin
Addy M, Wade WG, Jenkins S, Goodfield S (1989b).                                    Periodontol 17:292-297.
  Comparison of 2 commercially available chlorhexidine                           Brecx M, Brownstone E, MacDonald L, Gelskey S, Cheang M
   mouthrinses: 1. Staining and antimicrobial effects in vitro.                     (1992). Efficacy of Listerine, Meridol and chlorhexidine
   Clin Prev Dent 11(5): 10-14.                                                     mouthrinses as supplements to regular tooth cleaning
Addy M, Jenkins S, Newcombe R (1990). The effect of                                 measures. / Clin Periodontol 19:202-207.
   triclosan, stannous fluoride and chlorhexidine products on:                   Chadwick B, Addy M, Walker DM (1991). Hexetidine
   (1) Plaque regrowth over a 4 day period. J Clin Periodontol                      mouthrinse in the management of minor aphthous ulceration
   17:693-697.                                                                      and as an adjunct to oral hygiene. BrDentJ 171:83-87.
Addy M, Al-Arrayed F, Moran J (1991a). The use of an                             Chung L, Smith SR, Joyston-Bechal S (1992). The effect of
   oxidising mouthwash to reduce staining associated with                           using a prebrushing mouthrinse (Plax) on oral hygiene in
   chlorhexidine. Studies in vitro and in vivo. J Clin Periodontol                  man. J Clin Periodontol 19:670-681.
   18:267-271.                                                                   Ciancio SG, Mather ML, Zambon JJ, Reynolds HS (1989).
Addy M, Loyn T, Adams D (199 lb). Dentine hypersensitivity—                         Effect of a chemotherapeutic agent delivered by an oral
   effects of some proprietary mouthwashes on the dentine                           irrigation device on plaque, gingivitis and subgingival
   smear layer: a SEM study. J Dent 19:148-152.                                     microflora. J Periodontol 60:310-315.
Afseth J, R0lla G (1980). The in vivo effect of glucose solutions                Cline NV, Layman DL (1992). The effects of chlorhexidine on
   containing Cu++ and Zn++ on the acidogenicity of dental                          the attachment and growth of cultured human periodontal
   plaque. Acta Odontol Scand 38:229-233.                                           cells. J Periodontol 63:598-602.
American Dental Association (1988a). Council on Dental                           Collaert B, Attstrom R, de Bruyn H, Movert R (1992a). The
   Therapeutics accepts Listerine. J Am DentAssoc 117:515-                          effect of delmopinol rinsing on dental plaque formation and
   516.                                                                             gingivitis healing. J Clin Periodontol 19:274-280.
American Dental Association (1988b). Council on Dental                           Collaert B, Edwardsson S, Attstrom R, Hase JC, Astrom M,
   Therapeutics accepts Peridex. J Am Dent Assoc 117:516-                           Movert R (1992b). Rinsing with delmopinol 0.2% and
   517.                                                                             chlorhexidine 0.2%: short term effect on salivary
Axelsson P, Lindhe J (1987). Efficacy of mouthrinses in                             microbiology, plaque and gingivitis. J Periodontol 63:618-
   inhibiting dental plaque and gingivitis in man. J Clin                           625.
   Periodontol 14:205-212.                                                       Cubells AB, Dalmau LB (1991). The effect of triclosan/
Bailey L (1989). Direct plaque removal by a prebrushing                             copolymer/fluoride dentifrice on plaque formation and
   dental rinse. Clin Prev Dent 11:21-27.                                           gingivitis: A six month clinical study. J Clin Dent 2:63-69.
Barkvoll P (1991). Actions and interactions of sodium lauryl                     Cummins D (1991). Zinc citrate/triclosan: A new antiplaque
   sulfate and chlorhexidine in the oral cavity (thesis). Oslo:                     system for the control of plaque and the prevention of

                                                 Downloaded from by on April 28, 2010
300                                                                 ADAMS & ADDY                                               ADV DENT RES JULY 1994

   gingivitis: short term clinical and mode of action studies. J                   containing sanguinaria extract and zinc chloride upon the
   Clin Periodontol 18:455-461.                                                    microflora of the dental plaque and oral soft tissues. J
Deasy MJ, Battista G, Rustogi KN, Volpe AR (1992).                                 Periodontol 61:359-363.
   Antiplaque efficacy of a triclosan/co-polymer rinse: A                       Harrap GJ, Best JS, Saxton CA (1984). Human oral retention of
   plaque prevention clinical study. Am J Dent 5:91-94.                            zinc from mouthwashes containing zinc salts and its relevance
De Paola LG, Overholser CD, Meiller TF, Minah GE, Niehaus                          to dental plaque control. Arch Oral Biol 29:87-91.
   C (1989). Chemotherapeutic inhibition of supragingival                       Heps HU, Bjornland T, Skoglund LA (1988). Side-effects and
   dental plaque and gingivitis development. J Clin Periodontol                    patient acceptance of 0.2% versus 0.1 % chlorhexidine used
   16:311-315.                                                                     as post-operative prophylactic mouthwash. Int J Oral
Dobl P, Nossek H (1990). Einfluss von Zinkchloridmund-                             Maxillofac Surg 17:17-20.
   spulungen auf Kariesinduzierende Plaquestroptokokken.                        Herczegh A, Gombik A, Rost M, Wierzbicka M, Banoczy J
   2. Mitteilung: In vivo Untersuchungen zur antibakteriellen                      (1991). Amin fluorid es onfluorid tartalmu fogkrem es
   Wirkung von Zinkchlorid auf die Gesamtstreptokokkenflora                        szajoblito mikrobidogiai hatasossaganak vizsgalata. Forg
   der Zahnplaque. Zahn Mund Kieferheilkd 78:393-396.                              & 84:181-184.
Emling RC, Yankell SL (1985). First clinical studies of a new                   Hoyos DF, Murray JS, Shaw L (1977). The effect of
   prebrushing mouthrinse. Compend Contin Educ Dent 6:636-                         chlorhexidine gel on plaque and gingivitis in children. Br
   645.                                                                            Dent J 142:366-369.
Emling RC, Yankell SL (1991). An assessment of Plax                             Hull PS (1980). Chemical inhibition of plaque. J Clin
   prebrushing dental rinse used according to directions with                      Periodontol 7:431-442.
   supervised toothbrushing. J Clin Dent 2(4): 103-105.                         Jenkins S, Addy M, Newcombe R (1989). Comparison of 2
Fleszar TJ (1989). Effectiveness of mouthrinses. J Macomb                          commercially available chlorhexidine mouthrinses. II.
   Dent Soc 26(4)34-35.                                                            Effects on plaque reformation, gingivitis and toothstaining.
Frandsen A(1986). Mechanical oral hygiene practices. In: Loe                       Clin Prev Dent 11:12-16.
   H, Kleinman, DV, editors. Dental plaque control measures                     Jenkins S, Addy M, Newcombe R (1991a). Triclosan and
   and oral hygiene practices. Oxford: IRL Press, 93-116.                          sodium lauryl sulphate mouthrinses. I. Effects on salivary
Freitas LB, Collaert B, Attstrom R (1991). Effect of the pre-                      bacterial counts. J Clin Periodontol 18:140-144.
   brushing rinse, Plax, on dental plaque formation. / Clin                     Jenkins S, Addy M, Newcombe R (1991b). Triclosan and
   Periodontol 18:713-715.                                                          sodium lauryl sulphate mouthwashes. II. Effects on 4 day
Garcia-Godoy F, Garcia-Godoy F, Devizio W, Volpe AR,                               plaque regrowth. / Clin Periodontol 18:145-148.
   Ferlauto RJ, Miller JM (1990). Effect of triclosan/copolymer/                Kato T, Iijima H, Ishihara K, Kaneko T, Hirai K, Naito Y
   fluoride dentifrice on plaque formation and gingivitis. Am                       (1990). Antibacterial effects of Listerine on oral bacteria.
   J Dent 3:S15-S26.                                                               Bull Tokyo Dent Coll 31:301-307.
Giertsen E, Scheie AAa, R0lla G (1989). Dose related effects                    Kenrad B (1990). Toxin effects from chlorhexidine gluconate:
   of zinc chloride on dental plaque formation and plaque                          case report. Tandlaegebladet 94:489-491.
   acidogenicity in vivo. Caries Res 23:272-277.                                Kohut B, Mankodi S (1989). The effectiveness of a prebrushing
Grimm WD, Curth K, Koch M, Uhlmann S, Walther C (1989).                            mouthrinse in reducing supragingival plaque and gingivitis
   Klinisch-kontrollierte verbundstudie zur Plaquehemmung                          in single use and external use trials. Am J Dent 2:157-159.
   von Zincfluoridhexetidine. Stomatol ODR der DDR 39:16-                       Kopczyk R, Abrams H, Laster H (1991). Clinical and
   20.                                                                              microbiological effects of a sanguinaria-containing
Grossman E, Reiter GP, Sturzenberger OP, de la Rosa M,                              mouthrinse and dentifrice with and without fluoride during
   Dickinson TD, Ferreti GA (1986). Six month study of the                          6 months of use. J Dent Res 70:617-622.
   effects of a chlorhexidine mouthrinse on gingivitis in adults.               Kornman KS (1986). Antimicrobial agents. In: Loe H, Kleinman
   J Periodont Res 21:33-43.                                                       D V, editors. Dental plaque control measures and oral hygiene
Gunbay S, Bicakci N, Parlak H, Guneri T, Kirilmaz L (1992).                        practices. Oxford: IRL Press, 121-142.
   The effect of zinc chloride dentifrices on plaque growth and                 Lobene RR, Soparkar R, Emling RC, Yankell SL (1986a).
   oral zinc levels. Quint Int 23:619-624.                                          Plaque removal with a prebrushing mouthrinse (abstract). /
Hannah JJ, Johnson JD, Kuftinec NM (1989). Long term                               Dent Res 65(Spec Iss):771.
   clinical evaluation of toothpaste and oral rinse containing                  Lobene RR, Soparkar R, Newman MB (1986b). The effect of
   sanguinaria extract in controlling plaque, gingival                              a sanguinaria dentifrice on plaque and gingivitis. Compend
   inflammation and sulcular bleeding during orthodontic                            Contin Educ Dent 7:5185-5188.
   treatment. Am J Orthod Dentofac Orthop 96:199-207.                           Lobene RR, Pramod M, Soparkar PM, Newman MB (1990).
Harper DS, Mueller LF, Fine JB, Gordon J, Laster LL (1990a).                       Long term evaluation of a pre-brushing dental rinse for the
   Clinical efficacy of a dentifrice and oral rinse containing                      control of dental plaque and gingivitis. Clin Prev Dent
   sanguinaria extract and zinc chloride during six months of                       12(2):26-30.
   use. J Periodontol 61:352-358.                                               Lobene RR, Singh SM, Garcia L, Petrone ME, Volpe AR,
Harper DS, Mueller LF, Fine JB, Gordon J, Laster LL (1990b).                        Chaknis P (1992). Clinical efficacy of a triclosan/co-polymer
   Effect of 6 months use of a dentifrice and oral rinse                            pre-brush rinse. A plaque removal clinical study. J Clin

                                                Downloaded from by on April 28, 2010
VOL.   8(2)                                                          MOUTHRINSES                                                            301
  Dent 3:54-58.                                                                    effect of an amine fluoride-stannous fluoride containing
Loe H, Schi0tt CR (1970). The effects of suppression of the                        mouthrinse on enamel surface free energy and the
  oral microflora upon the development of dental plaque and                        development of plaque and gingivitis. Clin Prev Dent
  gingivitis. In: McHugh WD, editor. Dental plaque.                                10(5):3-9.
  Edinburgh: E. & S. Livingston, 247-255.                                       Quirynen M, Marechal M, van Steenberghe D (1990).
Mandel ID (1988). Chemotherapeutic agents for controlling                          Comparative antiplaque activity of sanguinarine and
  plaque and gingivitis. J Clin Periodontol 15:488-498.                            chlorhexidine in man. J Clin Periodontol 17:223-232.
Maruniak J, Clark WB, Walker CB, Magnusson I, Marks RG                          Ross NM, Charles CH, Dills SS (1989). Long term effects of
  (1992). The effect of three mouthrinses on plaque and                            Listerine antiseptic on dental plaque and gingivitis. J Clin
  gingivitis development. J Clin Periodontol 19:19-23.                             Dent 1:92-95.
Maryanski JH, Wittenberger CL (1975). Mannitol transport in                     Rustogi KN, Petrone DM, Singh SM, Volpe AR, Tavss E
  Streptococcus mutans. J Bacteriol 124:1475-1481.                                 (1990). Clinical study of a pre-brush rinse and a triclosan/
Meiller TF, Kutcher MJ, Overholser CD, Niehaus C, DePaola                          co-polymer mouthrinse: effect on plaque formation. Am J
  LG, Siegel MA (1991). Effect of an antimicrobial mouthrinse                      Dent 3:567-569.
  on recurrent aphthous ulcerations. Oral Surg Oral Med                         Saxton CA (1986). The effects of a dentifrice containing zinc
  Oral Pathol 72:425-429.                                                          citrate and 2,4,4'-trichloro-2'-hydroxydiphenyl ether. J
Melsen B, R0lla G (1983). Reduced clinical effect of                               Periodontol 57:555-561.
  monofluorophosphate in the presence of sodium lauryl                          Schi0tt CR, Loe H, Jensen SB, Kilian M, Davies RM, Glavind
  sulphate. Caries Res 17:549-553.                                                 K (1970). The effect of chlorhexidine mouthrinses on the
Miller WD (1889). Die Mikroorganismen der Mundhohle.                               human oral flora. J Periodont Res 5:84-89.
  Leipzig.                                                                      Scheie AAa, Assev S, R0lla G (1988). Combined effects of
Minah GE, DePaola LG, Overholser CD, Meiller TF, Niehaus                           xylitol, NaF and ZnCl2 on growth and metabolism of
  C, Lamm RA (1989). Effects of 6 months use of an antiseptic                      Streptococcus sobrinus OHZ176. APM1S 96:761-767.
  mouthrinse on supragingival dental plaque microflora. J                       Shakespeare V, Shakespeare PG, Evans BT (1988). Effects of
   Clin Periodontol 16:347-352.                                                    proprietary oral rinses containing chlorhexidine, hexetidine
Moran J, Addy M, Newcombe R (1988). A clinical trial to                            and benzydamine on the proliferation of human buccal
  assess the efficacy of sanguinarine-zinc mouthrinse                              epithelial cells in culture. Arch Oral Biol 33:881-885.
  (Viadent) compared with chlorhexidine mouthrinse                              Singh SM (1990). Efficacy of a prebrushing rinse in reducing
  (Corsodyl). J Clin Periodontol 15:612-616.                                       dental plaque. Am J Dent 3:15-16.
Moran J, Pal D, Newcombe R, Addy M (1991). Comparison of                        Singh SM, Rustogi KN, Volpe AR, Petrone DM, Robinson RS
  a phenolic and a 0.2% chlorhexidine mouthwash on the                             (1990). Effect of a mouthrinse containing triclosan and a
  development of plaque and gingivitis. Clin Prev Dent                             co-polymer on plaque formation in a normal oral hygiene
   13(4):31-35.                                                                    regimen. Am J Dent 3:563-565.
Moran J, Addy M, Roberts S (1992a). A comparison of natural                     Smigel K (1991). High alcohol mouthwashes are under scrutiny.
  product, triclosan and chlorhexidine mouthrinses on 4 day                        JNatl Cancer / ^ r 83:751.
  plaque regrowth. J Clin Periodontol 19:578-582.                               Southard GL, Parsons LG, Thomas LG, Boul ware RT, Woodall
Moran J, Addy M, Wade WG, Maynard JH, Roberts SE,                                  IR, Jones BJB (1987). The relationship of sanguinaria
   Astrom M (1992b). A comparison of delmopinol and                                extract concentration and zinc ion to plaque and gingivitis.
  chlorhexidine on plaque regrowth over a 4 day period and                         J Clin Periodontol 14:315-319.
   salivary bacterial counts. J Clin Periodontol 19:749-753.                    Volpe AR, Kapczak LJ, King WJ (1967). In vivo calculus
Nabi N, Mukherjee C, Gaffar A, Schmidt R (1989). In vitro and                      assessment. Part III. Periodontics 5:184-193.
   in vivo studies of triclosan/PM/MA co-polymer/NaF                            Wagner MJ, Tvrdy JL, Barnes GP, Lyon TC, Parker WA
   combination as an antiplaque agent. Am J Dent 2:197-206.                        (1989). Sodium retention from mouthwashes. Clin Prev
Nemes J, Banoczy J, Wierzbicka M, Rost M (1991). The effect                        Dent \\{4)'3-6.
   of mouthwashes containing amino-fluoride and stannous                        WennstromJ,LindheJ (1985). Some effects of a sanguinarine-
   fluoride on plaque formation and gingivitis in adults. Fogor                    containing mouthrinse on developing plaque and gingivitis.
   Sz 84:233-236.                                                                  J Clin Periodontol 12:867-872.
Nossek H, Dobl P (1990). Einfluss von Zinkchloridmund-                          Williams MJR, Adams D, Hillam DG, Ashley KC (1987). The
   spulungen auf kariesinduzierende Plaque streptokokken.                          effect of hexetidine 0.1% in the control of dental plaque. Br
   Zahn Mund Kieferheilkd 78:325-328.                                              Dent J 163:300-302.
O'Mahony G, O'Mullane DM (1991). Evaluation of a                                Winn DM, Blot WJ, McLaughlin JK, Austin DF, Greenberg
   prebrushing mouthrinse in controlling dental plaque. J Irish                    RS, Preston-Martin S (1991). Mouthwash use and oral
   Dent Assoc 31:44-41.                                                            conditions in the risk of oral pharyngeal cancer. Cancer Res
Overholser CD, Muller TF, De Paola LG, Minah GE, Niehaus                           51:3044-3047.
   C (1990). Comparative effects of 2 chemotherapeutic                          Yusof ZA (1988). Chlorhexidine mouthwash: a review of its
   mouthrinses on the development of supragingival dental                          pharmacological activity, clinical effects, uses and abuses.
   plaque. J Clin Periodontol 17:575-579.                                          Dent J Malaysia 10:9-16.
Perdok JF, Busscher HJ, Weerkamp AH, Arends J (1988). The                       Yusof WZ, Khoo SP (1988). Mucosal sensitivity to
                                                                                   chlorhexidine mouthwash. Singapore Dent J 13:39-40.
                                               Downloaded from by on April 28, 2010

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