Adverse Outcome Pathway for Antimicrobial Quaternary Ammonium Compounds.

Quaternary ammonium compounds (QACs) or quats are a large class of antimicrobial chemicals used in households and institutions as sanitizers and disinfectants. These chemicals are utilized as food processing sanitizers, algicides, in the process of water treatment, and preservatives in cosmetics. The aim of this study was to determine an Adverse Outcome Pathway (AOP) whereby two widely used QACs, alkyl dimethyl benzyl ammonium chloride (ADBAC) and didecyl dimethyl ammonium chloride (DDAC), may result in respiratory tract and gastrointestinal tract effects. When inhaled or ingested, these QACs are incorporated into the epithelial cell membrane at the point of contact. With sufficient dosage, the epithelial membrane is disrupted, reducing its fluidity, and releasing cellular contents. Further, ADBAC and DDAC might disrupt mitochondrial functions leading to decreased ATP production. Both events might lead to cell death, either attributed to direct lysis, necrosis, or apoptosis. Pro-inflammatory mediators are recruited to the tissue, inducing inflammation, edema, and excess mucus production. The primary tissue-level adverse outcome is epithelial degeneration and dysplasia. Most important, no apparent metabolism or distribution is involved in QAC action. Based upon this knowledge, it is suggested to replace default Uncertainty Factors for risk assessments with a set of Data Derived Extrapolation Factors.