Acute pulmonary toxicity and inflammation induced by combined exposure to didecyldimethylammonium chloride and ethylene glycol in rats

Abstract

Didecyldimethylammonium chloride (DDAC), an antimicrobial agent, has been reported to induce pulmonary toxicity in animal studies. DDAC is frequently used in spray-form household products in combination with ethylene glycol (EG). The purpose of this study was to evaluate the toxic interaction between DDAC and EG in the lung. DDAC at a sub-toxic dose (100 μg/kg body weight) was mixed with a non-toxic dose of EG (100 or 200 μg/kg body weight), and was administrated to rats via intratracheal instillation. Lactate dehydrogenase activity and total protein content in the bronchoalveolar lavage fluid (BALF) were not changed by singly treated DDAC or EG, but significantly enhanced at 1 d after treatment with the mixture, with the effect dependent on the dose of EG. Total cell count in BALF was largely increased and polymorphonuclear leukocytes were predominantly recruited to the lung in rats administrated with the mixture. Inflammatory cytokines, tumor necrosis factor-alpha and interleukin-6 also appeared to be increased by the mixture of DDAC and EG (200 μg/kg body weight) at 1 d post-exposure, which might be associated with the increase in inflammatory cells in lung. BALF protein content and inflammatory cell recruitment in the lung still remained elevated at 7 d after the administration of DDAC with the higher dose of EG. These results suggest that the combination of DDAC and EG can synergistically induce pulmonary cytotoxicity and inflammation, and EG appears to amplify the harmful effects of DDAC on the lung. Therefore pulmonary exposure to these two chemicals commonly found in commercial products can be a potential hazard to human health.

Prediction of the skin sensitization potential of didecyldimethylammonium chloride and 3,7-dimethyl-2,6-octadienal and mixtures of these compounds with the excipient ethylene glycol through the human Cell Line Activation Test and the Direct Peptide Reactivity Assay

“…This suggests that a non-sensitizing excipient such as EG could lessen the SS potency of an ingredient that actively sensitizes the skin. However, contrary to this result, other in vivo (Kwon et al, 2016) and in vitro (Kwon et al, 2015) studies showed that EG further potentiates the ability of DDAC to induce pulmonary toxicity. It is possible that this disparity reflects the different cell lines that were used, namely, the THP-1 human monocytic leukemia cell line versus the BEAS-2B normal human bronchial epithelial cell line.…”

Evaluation of pulmonary toxicity of benzalkonium chloride and triethylene glycol mixtures using in vitro and in vivo systems

“…DDAC‐induced cytotoxicity is potentiated in the presence of nontoxic doses of EG in human bronchial epithelial (BEAS‐2B) cells, and the effect is dependent on the concentration of EG . Moreover, rats intratracheally instilled with the mixture of DDAC and EG show significant pulmonary toxicity and inflammation, whereas the individual chemicals do not induce toxicity in respiratory organs . These findings appear to be quite similar to the results of the present study, with the same aspects of cytotoxicity induced by the combination of the QAC and organic solvent.…”

An analysis of a humidifier disinfectant case from a toxicological perspective

“…Besides the humidifier disinfectant, we need an exhaustive inspection on all biocide products that are distributed in Korea, especially spray products that easily expose biocide through air. Toxicological study using mice reports that ammonium chloride, which is used as a source material in deodorants, can cause pulmonary fibrosis, and a few studies confirm that didecyldimethylammonium chloride increases a number of inflammatory markers that cause pulmonary fibrosis [ 6 - 8 ]. Therefore, an exhaustive inspection is needed on all source materials used in products like disinfectants, sterilizers, preservatives, pest controls, and antifoulants distributed in Korea in order to understand the use of the products and figure out their potential risk.…”