Denatonium Benzoate

Huaping Xu, et al. PREPRINT (Version 1) available at Research Square, 2021.

Denatonium benzoate (DB) is one of the most bitter compounds known to man and may be added to a variety of cosmetics, causing asthma symptoms with DB exposure. To investigate the impact of denatonium benzoate (DB) on IgE-mediated mast cell activation and allergy susceptibility using in vitro and in vivo models.
Methods: 1) In Vitro: IgE-sensitized RBL-2H3 rat mast cells or KU812 human basophils were incubated with DB. The main parameters measured were β-hexosaminidase (β-hex) release, Ca2+ mobilization, and FcεRIα cell-surface expression. 2) In Vivo: BALB/c mice with ovalbumin (OVA)-induced allergy received DB. Assessed anaphylactic symptoms, jejunal mucus thickness, serum β-hex/histamine/OVA-specific IgE levels, and mast cell FcεRIα expression.
Key Findings:
· DB promoted IgE-mediated degranulation in mast cells/basophils, with increased β-hex release (RBL-2H3: +137%, KU812: +89%) and Ca2+ influx.
· DB induced FcεRIα expression on mast cells (protein: +2.1-fold; mRNA: +1.8-fold vs. controls).
· In OVA-allergic mice, DB aggravated anaphylaxis by exacerbating the severity of diarrhea and jejunal mucus thickness, and increasing serum β-hex (+68%), histamine (+52%), and OVA-specific IgE (+75%), as well as mast cell FcεRIα in intestinal mucosa.
Conclusion: DB potentiates IgE-mediated allergic responses by enhancing FcεRIα expression on mast cells, promoting degranulation and exacerbating anaphylaxis. This evidence supports DB as a potential risk factor for allergy susceptibility.

Xu, Mark, et al. Canadian Journal of Ophthalmology 53.6 (2018): 605-608.

The aim of this double-blind randomized pilot study was to assess the feasibility of denatonium benzoate (100 ppm) as a noninvasive nasolacrimal duct patency diagnostic.
Methods: Participants with presumed normal lacrimal systems aged 18-35 years (n = 28) were randomized to either the intervention group (100 parts per million denatonium benzoate in sterile water; n = 14) or the control group (sterile water only; n = 14). After instilling topical tetracaine in the right conjunctival cul-de-sac, three drops of the study solution were administered at 1-minute intervals to the right conjunctival cul-de-sac. The primary outcome was presence of strong, persistent, bitter taste, and the secondary outcome was time-to-taste. Lacrimal irrigation was performed in all participants.
Key Results: Bitter solution was detected by all (100%) intervention participants and none (0%) of the controls (p < 0.001). In the intervention group, 71% (n = 10) had experienced the taste ≤ 15 minutes, 79% (n = 11) ≤ 30 minutes, and 100% (n = 14) ≤ 2 hours, with duration of bitterness perception usually lasting for 1-2 hours. The lacrimal system was normal on irrigation in all participants, and no adverse events were reported.
Conclusion: Detection of nasolacrimal duct patency by perception of a strong bitter taste in healthy participants could be performed using denatonium benzoate reliably. It could have a role as a simple, noninvasive diagnostic test.