Hrubec, Terry C.Seguin, Ryan P.Xu, L.Cortopassi, G. A.Datta, S.Hanlon, Alexandra L.Lozano, A. J.McDonald, V. A.Healy, C. A.Anderson, T. C.Musse, N. A.Williams, R. T.2021-08-262021-08-262021-01-012214-7500PMC8041661S2214-7500(21)00047-0 (PII)http://hdl.handle.net/10919/104713Humans are frequently exposed to Quaternary Ammonium Compounds (QACs). QACs are ubiquitously used in medical settings, restaurants, and homes as cleaners and disinfectants. Despite their prevalence, nothing is known about the health effects associated with chronic low-level exposure. Chronic QAC toxicity, only recently identified in mice, resulted in developmental, reproductive, and immune dysfunction. Cell based studies indicate increased inflammation, decreased mitochondrial function, and disruption of cholesterol synthesis. If these findings translate to human toxicity, multiple physiological processes could be affected. This study tested whether QAC concentrations could be detected in the blood of 43 human volunteers, and whether QAC concentrations influenced markers of inflammation, mitochondrial function, and cholesterol synthesis. QAC concentrations were detected in 80 % of study participants. Blood QACs were associated with increase in inflammatory cytokines, decreased mitochondrial function, and disruption of cholesterol homeostasis in a dose dependent manner. This is the first study to measure QACs in human blood, and also the first to demonstrate statistically significant relationships between blood QAC and meaningful health related biomarkers. Additionally, the results are timely in light of the increased QAC disinfectant exposure occurring due to the SARS-CoV-2 pandemic. Main Findings: This study found that 80 % of study participants contained QACs in their blood; and that markers of inflammation, mitochondrial function, and sterol homeostasis varied with blood QAC concentration.Pages 646-656application/pdfenCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 International7-DHC, 7-Dehydrocholesterol7-DHD, 7-Dehydrodesmosterol8-DHC, 8-DehydrocholesterolADBAC, alkyldimethylbenzyl ammonium chlorideANOVA, analysis of varianceBAC, benzalkonium chlorideCRP, C-reactive proteinDDAC, didecyldimethyl ammonium chlorideEnvironmental toxicologyFCCP, trifluoromethoxy carbonylcyanide phenylhydrazoneIL-10, interleukin 10IL-12, interleukin 12IL-6, interleukin 6IRB, Institutional Review BoardInflammationLC, liquid chromatographyLOD, level of detectionLOQ, level of quantificationLPS, lipopolysaccharideLipid metabolismMitochondrial functionNF-κB, nuclear factor kappa betaNOEL, no effect levelOCR, oxygen consumption rateOEL, occupational exposure limitQAC, quaternary ammonium compoundsQuaternary ammonium compoundsTNFα, tumor necrosis factor alpha0304 Medicinal and Biomolecular Chemistry0399 Other Chemical Sciences1103 Clinical SciencesArticle - Refereed2021-08-26https://doi.org/10.1016/j.toxrep.2021.03.0068Hanlon, Alexandra [0000-0002-9612-2197]338689512214-7500