To evaluate the bleaching ability, the effect on enamel surface and cytotoxicity of novel toothwhitening formulations containing papain, ficin, or bromelain. Forty bovine dental discs (6 cm ×4 cm) were pigmentated and randomly allocated into the following groups (n = 10): Group 1, 20 wt% carbamide peroxide (control); group 2, 1% papain-based whitening; group 3, 1% ficin-based whitening; and group 4, 1% bromelain-based whitening. The whitening gels were prepared and applied on the enamel three times per day once a week, for 4 weeks. Color measurement was obtained by CIEDE2000. Enamel Knoop microhardness and roughness were evaluated. The WST-1 assay was used to evaluate the cell viability of mouse fibroblast cells (L929). Data were statistically analyzed by one-way analysis of variance (ANOVA) and Student Newman Keuls's post hoc test at α = 0.05 significance level. Bromelain, ficin-based, and carbamide peroxide bleaching gels showed a similar color change (p < 0.001). Higher enamel hardness decrease and higher enamel roughness were caused by the carbamide peroxide (p < 0.05). The experimental whitening gels did not affect cell viability. Tooth bleaching gels containing bromelain, papain, or ficin have substantial clinical potential to be used in the development of peroxidefree tooth whitening gels. Tooth whitening has become one of the most performed and demanded cosmetic dental procedures. It is a non-invasive treatment that improves the appearance of a patient smile, positively affecting the quality of life 1,2. The two whitening techniques traditionally used are the at-home and the in-office whitening techniques. Both techniques involve the use of different concentrations of carbamide or hydrogen peroxide as active agents 3. Concentrations of such active agents commonly used for in-office whitening therapy vary from 20%, 35% or even 38% 4. Despite that, the efficiency of whitening systems is consolidated in the literature and dental practice, incorrect application in excessive quantities of time can cause side effects 5. The most common drawback caused by the use of high hydrogen peroxide concentrations is tooth sensitivity 6. A study demonstrated that 85% of patients treated using an in-office bleaching technique report tooth sensitivity 7,8. It was hypothesized that tooth sensitivity after dental bleaching is related to the degradation of the hydrogen peroxide into reactive oxygen species (ROS) which can diffuse to the pulp chamber through the dentinal tubules, inducing the release of inflammatory mediators, like IL-1β and RANK-L 9,10. Although the use of analgesics, anti-inflammatories, antioxidants, corticosteroids, and opioid drugs are used as a way to minimize this side-effect, the use of oral medications is not able to reduce the risk of tooth sensitivity 11. An alternative to reduce or solve this problem is the use of natural compounds. Given their natural origin, these types of products have a certain guarantee on their non-toxic biological behavior, resulting in little or no
