The available toxicity data of benzalkonium chloride (BKC) clearly shows that it is toxic; however, the weight of evidence favors the view that at doses encountered in nasally and orally inhaled pharmaceutical preparations it is well tolerated. The adverse toxicological data predominantly come from in vitro and animal studies in which doses and exposure periods employed were excessive in relation to the clinical doses and their posology and, therefore, not directly applicable to the clinic. The conflict between the in vitro and animal data and the clinical experience can be reconciled by understanding some of the physicochemical properties of BKC, the nasal and respiratory tract microenvironments, the doses used, and the posology.
Keywords: benzalkonium chloride; dose; lung; micelle formation; nasal cavity; protein binding; respiratory tract; toxicity.