Evaluation of the irritancy and hypersensitivity potential following topical application of didecyldimethylammonium chloride

Abstract

Didecyldimethylammonium chloride (DDAC) is a dialkyl-quaternary ammonium compound that is used in numerous products for its bactericidal, virucidal and fungicidal properties. There have been clinical reports of immediate and delayed hypersensitivity reactions in exposed individuals; however, the sensitization potential of DDAC has not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of DDAC following dermal exposure in a murine model. DDAC induced significant irritancy (0.5 and 1%), evaluated by ear swelling in female Balb/c mice. Initial evaluation of the sensitization potential was conducted using the local lymph node assay (LLNA) at concentrations ranging from 0.0625–1%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.17%. Dermal exposure to DDAC did not induce increased production of IgE as evaluated by phenotypic analysis of draining lymph node B-cells (IgE+B220+) and measurement of total serum IgE levels. Additional phenotypic analyses revealed significant and dose-responsive increases in the absolute number of B-cells, CD4+ T-cells, CD8+ T-cells and dendritic cells in the draining lymph nodes, along with significant increases in the percentage of B-cells (0.25% and 1% DDAC) at Day 10 following 4 days of dermal exposure. There was also a significant and dose-responsive increase in the number of activated CD44 + CD4 + and CD8+ T-cells and CD86+ B-cells and dendritic cells following exposure to all concentrations of DDAC. These results demonstrate the potential for development of irritation and hypersensitivity responses to DDAC following dermal exposure and raise concerns about the use of this chemical and other quaternary ammonium compounds that may elicit similar effects.

Formation of lamellar body-like structure may be an initiator of didecyldimethylammonium chloride-induced toxic response

“…9 D). Meanwhile, contrary to our expectation ( Anderson et al, 2016 ), the level of IL-4 and IFN-γ showed the decreasing trend in the lung of both sexes of mice treated with DDAC compared to control, and the levels of most of cytokines (or chemokines) were not significantly different between groups ( Supplementary Fig. 5 ).…”

Topical Application of the Quaternary Ammonium Compound Didecyldimethylammonium Chloride Activates Type 2 Innate Lymphoid Cells and Initiates a Mixed-Type Allergic Response

“…both ACD and asthma) (De Vooght et al ., 2010; Matheson et al ., 2005). The quaternary ammonium compound (QAC), didecyldimethylammonium chloride (DDAC) was identified by our lab to be a T-cell mediated/Th1 sensitizer (Anderson et al ., 2016) using standard classifications schemes. However, clinical evidence suggests this LMW chemical can induce multiple types of hypersensitivity reactions (Geier et al ., 2013; Houtappel et al ., 2008; Vandenplas et al ., 2013).…”

Divergent hypersensitivity responses following topical application of the quaternary ammonium compound, didecyldimethylammonium bromide

“…This laboratory has published data on numerous chemicals, generally classified as T H 2-mediated or IgE-mediated chemical sensitizers, including o -phthalaldehyde (OPA), glutaraldehyde, and toluene diisocyanate (TDI), that have induced elevations in IgE (local and total) at 10 days following four days of chemical treatment (Azadi et al 2004; Anderson et al 2010, 2016). In the present study, antibody levels were also examined following 14 days of continuous chemical application.…”

“…Evaluation of DDAC showed similar trends for sensitization potential, IgE and immunophenotyping (surface markers and activation status) as DDAB; however, only the four-day exposure period was examined in the study and higher concentrations of DDAC (0.25–1%) were used compared to DDAB (Anderson et al 2016). These findings suggest that the hypersensitivity responses induced by DDAB might have different mechanisms and mediators based on exposure duration; while not analyzed in this study, it is possible that DDAC and other QAC may have similar exposure/duration mediated divergent mechanisms.…”

“…While a role for QAC in allergic disease has been suggested, the exact mechanism of sensitization to these compounds remains to be investigated. Previously, the irritancy and sensitization potential of didecyl-dimethylammonium chloride (DDAC), one of the newer fourth generation QAC that has been described as a sensitizer in epidemiology studies, were evaluated (Anderson et al 2016). DDAC induced significant irritancy (0.5 and 1%), evaluated by ear swelling in female BALB/c mice and was identified as a sensitizer with a calculated EC3 value of 0.17% (local lymph node assay (LLNA)).…”