Comparative study of acetaminophen and 4-methoxyphenol toxicity

Abstrakt

Acetaminophen (APAP, paracetamol) is one of the most widely used human drugs, and simultaneously, one of the most frequently detected pharmaceutical micropollutants in environmental matrices. The major metabolites of acetaminophen are generally considered to be glucuronide and sulfate conjugates, p-aminophenol, hydroquinone, and NAPQI, while 4-MP may occur as one of the transformation products under specific environmental degradation pathways. Determining and comparing the toxicity of these compounds is crucial for environmental and public health. In this study, the toxicity of APAP and 4-MP was assessed using two model microorganisms, Escherichia coli ATCC-25922 and Candida albicans ATCC-1023, based on growth inhibition. The susceptibility of microorganisms belonging to the human microbiome (E. coli, E. hormaechei, S. epidermidis, L. rhamnosus, and C. albicans) to both compounds was determined by calculating the minimum inhibitory concentrations (MICs). Genotoxicity was estimated using the genotoxin-sensitive recA promoter in E. coli RFM443 recA::luxCDABE. Reactive oxygen species (ROS) production was measured in E. coli exposed to both compounds at concentrations of 0.1, 1, 10, 100, and 1000 mg·L⁻¹ as an oxidative stress indicator. Comparative analysis revealed similar sensitivity of E. coli and C. albicans to both compounds at 100 mg·L⁻¹, though at 10 mg·L⁻¹, 4-MP exerted a stronger inhibitory effect on both strains than APAP. MIC assays showed that E. coli and E. hormaechei were more sensitive to 4-MP than to APAP, while no significant differences were observed for the remaining strains. APAP demonstrated a stronger genotoxic effect than 4-MP in E. coli cells. ROS data indicate that oxidative stress is the primary molecular mechanism underlying the toxicity and genotoxicity of both compounds. Future studies should investigate the toxicity of APAP and 4-MP mixtures under environmentally relevant exposure conditions.