Toxicological insights and health risks of Didecyldimethylammonium Chloride (DDAC): an integrative review.

Didecyldimethylammonium chloride (DDAC) is a broad-spectrum quaternary ammonium compound (QAC) extensively utilized as a disinfectant and biocide. Widespread use of DDAC, significantly amplified during COVID-19 pandemic, increased human and environmental exposures, indicating need for updated, quantitative risk assessments. To comprehensively evaluate toxicological profile, exposure pathways, and risk characterization of DDAC, this integrative review synthesized regulatory databases (EPA, ECHA), peer-reviewed literature, and large-scale European Food Safety Authority (EFSA) monitoring data (>200,000 samples). Data demonstrated that DDAC exhibited low systemic absorption (<10%) and rapid fecal excretion, with no apparent evidence of carcinogenic, genotoxic or reproductive toxicity. Reported no observed adverse effect level (NOAEL) varied depending upon species, study design, exposure route, and toxicological endpoint, with regulatory studies reporting values ranging from approximately 10 to 93.1 mg/kg/day. Quantitative margin of exposure (MOE) analyses confirm both (1)dietary intake, despite sporadic high residues in specific animal products, and (2) routine occupational dermal exposures maintained large safety margins. Conversely, aerosol-generating applications, such as fogging and humidifier use, present narrower margins, emphasizing critical role of ventilation parameters. Overall, DDAC exhibited low systemic toxicity under typical exposure conditions due to limited absorption and rapid elimination. However, accumulating mechanistic evidence indicates that DDAC might initiate portal-of-entry toxicity, including dermal, ocular, and respiratory irritation related to membrane disruption, mitochondrial dysfunction, oxidative stress, and inflammatory responses. Integrating regulatory evaluations with recent mechanistic findings provides a more comprehensive understanding of DDAC-induced toxicity, identifies important uncertainties regarding chronic aerosol exposure and environmental persistence, supporting continued refinement of human health and environmental risk assessments.