Multixenobiotic resistance (MXR) inhibition and interactive toxic effects of the cationic surfactant, benzalkonium chloride, in embryonic medaka (Oryzias latipes)
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Contaminated environments represent a challenge to resident species. Organisms must possess underlying mechanisms of resistance to protect against a broad range of environmental insults. One mechanism likely conferring resistance is expression of low substrate specificity membrane efflux transporters termed multixenobiotic resistance (MXR). MXR transporters confer resistance by preventing toxics from entering into cells and also by expelling potentially cyto- and genotoxic metabolites. Chemicals known as chemosensitizers, which can inhibit MXR function thus represent a threat to aquatic organisms. This study used embryos of medaka (Oryzias latipes) to measure MXR activity and inhibition through a dye exclusion assay. This assay was used to investigate the chemosensitizing potential of the emerging contaminant, benzalkonium chloride (BAC), representative of a class of quaternary ammonium compounds, which are high production volume cationic surfactants. BAC was found to be a potent inhibitor of MXR at high concentrations in early life stage medaka. BAC was also determined to be developmental toxicant as evidenced by the occurrence of morphological deficits in medaka fry in a long term developmental toxicity test. Most interestingly, there was a greater than additive toxic effect when embryos were co-exposed to BAC and the common organic contaminant, benzo[a]pyrene. As an environmentally relevant source of BAC and other contaminants, chlorinated effluent was also assessed and found to both inhibit MXR and be embryotoxic. These results highlight the need to further investigate the mechanisms of BAC induced toxicity. This study is among the first to demonstrate sub-lethal effects of this important group of widely used chemicals which may have significant ecological consequence to aquatic organisms by enhancing the toxicity of co-occurring contaminants.