N-chlorotaurine, a novel endogenous antimicrobial agent - Tolerability testing in a mouse model

Objective: To investigate the tolerability of N-chlorotaurine, a new antimi crobial agent, by application to the middle ear in a mouse model. Methods: Five BALB/c mice were each injected through the tympanic membrane with 5 muL of 0.1%, 1.0%, and 10% N-chlorotaurine and compared with animals in which 0.9% isotonic sodium chloride solution, 0.2% gentamicin sul fate, and 0.25% trimethyltin chloride were instilled. Auditory brainstem respons es to clicks were evaluated repeatedly between 4 and 75 days after injectio n, and histologic investigations of the inner ear were performed subsequent ly. Three additional groups of mice were injected with isotonic sodium chlo ride solution, 1.0% N-chlorotaurine, and 0.25% trimethyltin, and brainstem re sponses to tone bursts of 8, 16, and 32 kHz were tested. In addition, th e middle ear was examined histologically. Results: Mice treated with isotonic sodium chloride solution, 0.1% N-chloro taurine, and 0.2% gentamicin sulfate did not show changes in response thres hold. Treat ment with 1.0% and 10% N-chlorotaurine caused a reversible incr ease in auditory brainstem response thresh old by 20 dB 4 days after applic ation because of local irritation around the perforation of the tympanic me mbrane. In contrast, 0.25% trimethyltin showed a permanent elevation of aud itory brainstem response threshold of 10 to 15 dB and a scattered loss of o uter hair cells predominantly in the apical turn. No alterations of the inn er ear were observed in the other treatment groups. The mucous membrane of the middle ear remained unaffected in all test groups. Conclusion: Application of N-chlorotaurine to the middle ear is well tolera ted without adverse effects and may be a useful new endogenous antimicrobia l agent for local treatment of otologic infections.