Abstract
Didecyldimethylammonium bromide (DDAB) is a fourth generation dialkyl-quaternary ammonium compound (QAC) that is used in numerous products for its antimicrobial properties. While many QACs have been associated with allergic disease, the toxicity and sensitization of DDAB have not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of DDAB following dermal application in a murine model. DDAB induced significant irritancy (0.0625–2%), 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% to 2%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.057%. Immune cell phenotyping along with local and systemic IgE levels were evaluated following 4 and 14 days of dermal application. 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 (DLNs) following 4 and 14 days of dermal exposure with significant increases in the number of activated B-cells and dendritic cells. However, increased activation of CD4+ T-cell and CD8+ T-cells was only observed following four days of DDAB exposure. Exposure to DDAB also induced increased production of IgE as evaluated by phenotypic analysis of DLN B-cells (IgE+ B-cells) and measurement of total serum IgE levels following 14 days but not four days of dermal application. Significant increases in gene expression were observed in the DLN (Il-4, Il-10, and ox40l) and ear (tslp) following 4 and 14 days of DDAB exposure. These results demonstrate the potential for development of irritation and hypersensitivity responses to DDAB following dermal exposure and raise concerns about the effects of exposure duration on hypersensitivity responses.
Highlights
Quaternary ammonium compounds (QAC) have been used for over 50 years as water-based surface disinfectants due to their low volatility and broad antimicrobial capabilities (Zhang et al 2015)
Cleaning products that contain QAC and other disinfectants are commonly used to prevent the spread of serious infectious disease and their use is encouraged in clinical and other health care settings to prevent the transmission of pathogens
Working concentrations of QAC in disinfectants and cleaning products typically range from 0.01% to 1%, but can be as high as 5% which is a similar range to the concentrations tested in the present study (Bank, Hazardous Substances Data 2010)
Summary
Quaternary ammonium compounds (QAC) have been used for over 50 years as water-based surface disinfectants due to their low volatility and broad antimicrobial capabilities (Zhang et al 2015). There are many different QAC that are increasingly being used in hospitals, hotels, and in consumer products They are primarily used as cleaners and disinfectants for non-critical surfaces, algaecides, fabric softeners, antistatic agents, and wood preservatives (Rajkowska et al 2016). The fourth generation of QAC is twin chain compounds or dialkyl QAC that allow for a wide spectrum of activity These new synthetic polymeric QAC contain multiple positively charged amine centers that confer antimicrobial, anti-static, and surfactant properties in solution. They have stronger antimicrobial ability compared to their single chain predecessors which include improved tolerance to anionic surfactants, protein soil and water hardness salts. In an effort to reduce the incidence of pathogen induced illnesses, newer generations of QAC are continually being developed
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