Human health hazard assessment of quaternary ammonium compounds: Didecyl dimethyl ammonium chloride and alkyl (C12-C16) dimethyl benzyl ammonium chloride.

Quaternary ammonium compounds (Quats) are a large class of permanently charged cationic chemicals that are used in a variety of consumer and industrial products for their antimicrobial properties. Didecyl dimethyl ammonium chloride (DDAC) and alkyl (C12, C14, C16) dimethyl benzyl ammonium chloride (C12-C16 ADBAC) are frequently used as active ingredients in antimicrobials and are the focus of the current hazard assessment. Robust toxicology databases exist for both DDAC and C12-C16 ADBAC; however, the majority of available studies for DDAC and C12-C16 ADBAC are unpublished, but have been submitted to and reviewed by regulatory agencies (i.e., EPA and European Chemicals Agency) to support antimicrobial product registration. With the objective of contributing to public understanding of the robust and complete toxicology database available for DDAC and C12-C16 ADBAC, a comprehensive review was conducted using available peer-reviewed literature and unpublished data submitted to and summarized by regulatory agencies. A review of available literature indicates that DDAC and C12-C16 ADBAC have similar hazard profiles. Both DDAC and C12-C16 ADBAC are poorly absorbed via the oral and dermal exposure routes (≤10%), are not systemically distributed, and are primarily excreted in feces. DDAC and C12-C16 ADBAC are not dermal sensitizers, are not specific developmental or reproductive toxicants, are not carcinogenic or genotoxic, and do not cause systemic toxicity. DDAC and C12-C16 ADBAC are irritating/corrosive to skin at high concentrations, and are acutely toxic via the oral, dermal (C12-C16 ADBAC only), and inhalation exposure routes; however, both DDAC and C12-C16 ADBAC are considered non-volatile and are not readily aerosolized. Both DDAC and C12-C16 ADBAC can cause toxicity in repeated dose oral toxicity studies with no-observed-adverse-effect levels ranging from 10 to 93.1 mg/kg-day for DDAC and 3.7-188 mg/kg-day for C12-C16 ADBAC in subchronic and chronic studies conducted with beagles, mice, and rats. The toxicological effects associated with reported lowest-observed-adverse-effect levels for both DDAC and C12-C16 ADBAC are consistently characterized by reduced food consumption, reduced mean body weight, reduced body weight gain, and local irritation. These effects are consistent with the mode of action of an irritating/corrosive chemical. Based upon currently available data, the main concern associated with exposure to DDAC and C12-C16 ADBAC is local effects through irritation.