Adverse Outcome Pathway for Antimicrobial Quaternary Ammonium Compounds

ABSTRACT

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.

KEYWORDS:

• Adverse Outcome Pathway
• Data Derived Extrapolation Factors (DDEFs)
• quaternary ammonium compounds (QACs)
• risk assessment

Disclosure statement

This work was funded by the Quat Residue Group (QRG), under the auspices of Ignite Solutions (associated with the Household and Commercial Products Association). The two authors do occasional paid scientific analysis for the QRG.

Data Availability Statement

The authors state that there is no data set associated with the paper.Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Notes

1. For conciseness these chemicals are referred to as ADBAC and DDAC, but, as mentioned above, each of these are groups of chemicals which have similar, but not identical, structures.

2. Heme oxygenase-1, also referred to as HO-1 or heat shock protein 90, is implicated in cytotoxic events and the inflammatory signaling response in alveolar epithelial cells (Rock and Kono 2008; Singal 2010).

3. Rodents do not have an emetic reflex, so emesis would not be expected in these species.

Additional information

Funding

This work was supported by the Quat Residue Group (QRG) under the auspices of Ignite Solutions (associated with the Household and Commercial Products Association) [grant number not applicable].