Alkyl dimethyl benzyl ammonium chloride (ADBAC) and didecyl dimethyl ammonium chloride (DDAC) are common quaternary ammonium compounds used as disinfectants in households, medical, and restaurant settings. They cause occupational skin and respiratory hazards in humans, and developmental and reproductive toxicity in mice. They also cause increased secretions of proinflammatory cytokines in cell lines and vaginal inflammation in porcine models; but have not been evaluated for developmental immunotoxicity. We assessed immunotoxicity in-vitro with J774A.1 murine macrophage cell line by analyzing cytokine production and phagocytosis; and evaluated developmental immunotoxicity in CD-1 mice by analyzing antibody production. Additionally, because of the associations between gut microbiome dysbiosis and immune disease, we monitored changes in the microbiome as a result of ADBAC+DDAC exposure. Production of cytokines TNF-alpha and IL-6 increased at low ADBAC+DDAC concentrations, and IL-10 decreased in the murine macrophages with ADBAC+DDAC exposure. The phagocytic function of macrophages was also severely decreased. ADBAC+DDAC altered the mouse microbiome by decreasing the relative abundance of Bacteroides and increases in Clostridia in F0 and F1 generations. IgG primary and secondary responses were altered in F1 male mice; and IgA and IgM production were decreased in secondary response in F2 male mice. Since ADBAC+DDAC show signs of immunotoxicity in mice, further studies are needed to reassess risk for human exposure as ADBAC+DDAC may be contributing to immune disease. / Master of Science / Disinfectants are used every day in households, hospitals, and restaurants. Two common ingredients in disinfectants are alkyl dimethyl benzyl ammonium chloride (ADBAC) and didecyl dimethyl ammonium chloride (DDAC). These chemicals can cause asthma and allergic dermatitis in humans. In animals, they cause reduced fertility, altered development, and tissue inflammation. Disinfectant exposure could potentially alter bacterial populations in the gut. Altered microbial populations are associated with many inflammatory diseases. This study evaluated ADBAC and DDAC for their ability to alter immune function and change bacterial populations in the gut. Exposure to ADBAC and DDAC caused inflammation and altered antibody production for two generations. ADBAC and DDAC exposure also significantly altered bacterial communities in the gut. Both changes in the immune function and changes in the gut bacteria could contribute to inflammatory disease. Humans are exposed frequently to ADBAC and DDAC. If these chemicals alter immune function in humans, they could be contributing significantly to human disease.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/79723 |
| Date | 19 October 2017 |
| Creators | McDonald, Valerie Alexandra |
| Contributors | Biological Sciences, Hrubec, Terry C., Sible, Jill C., Luo, Xin, Jones, Caroline N. |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Detected Language | English |
| Type | Thesis |
| Format | ETD, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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