Effectiveness of a new non-hydrogen peroxide bleaching agent after single use - a double-blind placebo-controlled short-term study

Abstract Tooth whitening represents perhaps the most common aesthetic procedure in dentistry worldwide. The efficacy of bleaching depends on three aspects: bleaching agent, bleaching method, and tooth color. Objective: This in vivo study aimed to examine whitening effects on frontal teeth of the upper and lower jaws using an over-the-counter (OTC) non-hydrogen peroxide bleaching agent in comparison to a placebo after one single use. Material and methods: Forty subjects (25 female; 15 male) participated in this double-blind randomized placebo-controlled trial. The subjects were randomly allocated to two groups (n=20). The test group received the OTC product (iWhite Instant) and the placebo group received an identically composed product except for the active agents. Each subject was treated with a prefilled tray containing iWhite Instant or the placebo for 20 minutes. The tooth shade of the front teeth (upper and lower jaws) was assessed before (E_0), immediately after (E_1) and 24 h after treatment (E_2), using a shade guide (VITA classical). Statistical testing was accomplished using the Mann-Whitney U test (p<0.001). The dropout rate was 0%. Results: There were no significant differences at E_0 between placebo and test groups regarding the tooth color. Differences in tooth color changes immediately after (ΔE1_0) and 24 h after treatment (ΔE2_0) were calculated for both groups. The mean values (standard deviations) of tooth color changes for ΔE1_0 were 2.26 (0.92) in the test group and 0.01 (0.21) in the placebo group. The color changes for ΔE2_0 showed mean values of 2.15 (1.10) in the test group and 0.07 (0.35) in the placebo group. For ΔE1_0 and ΔE2_0 significant differences were found between the groups. Conclusion: In this short-term study, the results showed that a non-hydrogen peroxide bleaching agent has significant whitening effects immediately and 24 h after a single-use treatment.


Introduction
According to representative data from the United Kingdom and from a study with Chinese urban population, the prevalence of tooth discoloration in 13-tooth whitening is perhaps the most frequently applied aesthetic procedure in dentistry.
The etiology of tooth discolorations is multi-causal and can result from individual behavior, diseases, injury and other exposures along with various physiological processes 1 . Professional cleaning of discolored teeth is a common procedure to remove the majority of extrinsic strains. Various bleaching techniques and products are used to remove intrinsic and over-the-counter bleaching products.
Most bleaching products use hydrogen peroxide as active agent. However, bleaching treatments with peroxide may cause local adverse effects such as oral mucosa irritation, pulpal sensitivity, pulpitis or alteration of the enamel surface 14 . On the other hand, bleaching is a relatively safe procedure that predominantly causes severe adverse effects only at high hydrogen peroxide concentrations on hard tissue, soft tissue and restorative materials 15 . The (SCCP) 4 reported that the use of tooth whitening products containing >0.1 to 6.0% hydrogen peroxide or equivalent hydrogen peroxide-releasing substances is safe after consultation with a dentist.
However, this concentration is too low to have any noticeable effect on the color of teeth.
Legally, products that contain more than 0.1% hydrogen peroxide can only be sold to a dentist 24 . In January 2008, the SCCP recommended 6% hydrogen peroxide as a safe limit to use for home bleaching if supervised by a dentist 24 . Tooth bleaching based on non-peroxide systems are available as over-thecounter products in the form of gels, rinses, gums, 10,15,24 . Auschill, et al. 5 side effects of three different bleaching treatments: Whitestrips (OTC product, 5.3% hydrogen peroxide), Opalescence PF 10% (home bleaching, 10% carbamide peroxide) and Opalescence Xtra Boost (in-office bleaching, 38% hydrogen peroxide). The side effects were reversible and the test products had no harmful effect on the tooth surfaces. Additionally, the treatments were effective in removing intrinsic stains 4 , but given the actual legislation, such products are no longer allowed to be sold as OTC products without supervision of a dentist. Various studies investigated the effectiveness, safety and possible rebound effect of at-home and OTC agents. The most common side effects after bleaching were dental hypersensitivity and gingival irritation 18 containing hydrogen peroxide is generally based on cumulative and repeated treatments; no instant clinical studies were found for non-peroxide bleaching products. Only one study examined a non-peroxide at-home bleaching product based on sodium chloride in vitro and observed deteriorating effects on dental enamel 20 .
A novel OTC bleaching agent based on nonperoxide gel was investigated in this study. It contains phthalimido peroxy caproic acid (PAP) and calcium lactate gluconate as active ingredients and has a high potential of oxidation with release of active oxygen.
The gel should be placed on a ready-to-use tray. The calcium-lactate-gluconate is an implemented complex to remineralize and conserve dental hard tissue. A combination of bleaching and remineralization agents 8,23 .
Thus, the purpose of this randomized, double-blind, and placebo-controlled short-term study was to OTC non-peroxide bleaching agent after a single-use application.
In this double-blind study, the primary goal was to test the hypothesis that there are significant differences in tooth color units (1-16 units) between a novel OTC non-peroxide bleaching and placebo immediately after a single-use application regarding the effectiveness of bleaching. The secondary goal was to determine the color change as well as the side effects between baseline and after 24 h plus between immediately and after 24 h bleaching.
Effectiveness of a new non-hydrogen peroxide bleaching agent after single use -a double-blind placebo-controlled short-term study The ingredients of the products used in this study are listed in Figure 1. The products had the same packaging.

Material and Methods
The key list that documented to which group the       The examiner observed two subjects (immediately after treatment) and three (24 h after treatment) with gingival irritation on soft tissue during the study in the test group. None of the subjects had dental hypersensitivity. Three subjects in the placebo group were diagnosed with hypersensitivity and three with gingival irritation (immediately after treatment) ( Table   2).
Two subjects in the test group reported gingival irritation, one subject gingival edema immediately after treatment and one subject reported tooth hypersensitivity immediately after treatment. These adverse events had disappeared after 24 h ( Table   2). In the placebo group, three subjects reported "no comment" instead of "no gingival irritation" or "gingival irritation".

Discussion
Bleaching is an oxidative process that alters the The bleaching treatment is intended to be part of a complete dental procedure. The dentist's examination is necessary to ensure the correct indications for bleaching, and he/she monitors the treatment to 19 . A double-blind placebocontrolled clinical study was conducted to evaluate initial color improvement after a single-use application of the newly marketed non-peroxide bleaching system.
The results of our study demonstrated that the nonperoxide bleaching system is effective.
Gerlach and Zhou 13 (2001) showed that the more yellow the teeth at the baseline the better the outcome of the tooth bleaching 13 . Therefore, the bleaching groups were balanced for baseline tooth color and age. The test bleaching products may potentially cause irreversible damage if used on a long-term basis; so we decided to perform a single-use application under the supervision of a dentist.
The tooth color alterations were assessed using  shown to be effective for weak tooth discolorations 16 .
In this study, 59% of all examined teeth between baseline and immediately after bleaching showed an improved color shade in the test group ( Figure   5). Nevertheless, not all teeth were homogenously bleached depending on the position and individual characteristics like discoloration pattern or anatomic structure. The ready-to-use tray may also be a reason for irregular bleaching results and gingival irritation. Effectiveness of a new non-hydrogen peroxide bleaching agent after single use -a double-blind placebo-controlled short-term study The color stability after bleaching has been largely 2,6,28 . The bleaching effect is well known and depends not only on the bleaching method but also on subjects' food and lifestyle habits 21 . We investigated the shortterm effect of the novel OTC non-peroxide bleaching was observed within 24 h after bleaching. Further studies about the effectiveness after 14 days of the application and a long-term color stability after months are needed for the non-hydrogen peroxide bleaching agent.
The single use and the short-term observation for the effect of color stability were the limitations of this study, which, on the other hand, were necessary to assess the initial effectiveness of the new bleaching agent. The single application of the novel product for hydrogen peroxide products.

Conclusions
Within the limitations of this study, the results showed that single-use bleaching containing a phthalimido peroxy caproic acid (PAP) agent yielded placebo. These results remained stable in time, e.g.
24 h after application.