Humans 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.
RESULTS: 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.

Mithramycin (MTR) is a clinically approved DNA-binding antitumor antibiotic currently in Phase 2 clinical trials at National Institutes of Health for treatment of osteosarcoma. In view of the resurgence in the studies of this generic antibiotic as a human medicine, we have examined the binding properties of MTR with the integral component of chromatin - histone proteins - as a part of our broad objective to classify DNA-binding molecules in terms of their ability to bind chromosomal DNA alone (single binding mode) or both histones and chromosomal DNA (dual binding mode). The present report shows that besides DNA, MTR also binds to core histones present in chromatin and thus possesses the property of dual binding in the chromatin context. In contrast to the MTR-DNA interaction, association of MTR with histones does not require obligatory presence of bivalent metal ion like Mg(2+). As a consequence of its ability to interact with core histones, MTR inhibits histone H3 acetylation at lysine 18, an important signature of active chromatin, in vitro and ex vivo. Reanalysis of microarray data of Ewing sarcoma cell lines shows that upon MTR treatment there is a significant down regulation of genes, possibly implicating a repression of H3K18Ac-enriched genes apart from DNA-binding transcription factors. Association of MTR with core histones and its ability to alter post-translational modification of histone H3 clearly indicates an additional mode of action of this anticancer drug that could be implicated in novel therapeutic strategies.