Background: Foodborne infections affect approximately 600 million people annually. Simultaneously, many plants contain substances like organic acids, which have antimicrobial activity. The aim of this study was to examine the effects of 21 organic acids, naturally occurring in plants, on four foodborne bacteria (Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Salmonella enterica Typhimurium) and two fungi (Geotrichum candidum and Penicillium candidum). Methods: The minimal inhibitory concentrations (MIC) of the organic acids against foodborne bacteria and in silico toxicity prediction of acids were investigated. Results: Benzoic and salicylic acids exhibit the best activity against foodborne bacteria (mean MIC < 1 mg/mL). Acetic, chlorogenic, formic, malic, nicotinic, and rosmarinic acids demonstrate slightly weaker activity (mean MICs 1–2 mg/mL). Other acids have moderate or poor activity. The effectiveness of organic acids against foodborne fungi is weaker than against bacteria. Most acids require high concentrations (from 10 to >100 mg/mL) to inhibit fungal growth effectively. The predicted LD50 of organic acids ranges from 48 to 5000 mg/kg. Those potentially safe as food preservatives (MIC < LD50) include ascorbic, chlorogenic, malic, nicotinic, rosmarinic, salicylic, succinic, tannic, and tartaric acids. The studied organic acids are not carcinogenic but many can cause adverse effects such as skin sensitization, eye irritation, and potential nephrotoxicity, hepatotoxicity, or neurotoxicity. Conclusions: Most of the investigated plant-derived organic acids exhibit good antibacterial activity and moderate or poor antifungal effects. Among 21 acids, only 9 appear to be safe as food preservatives (MIC < LD50). The relationship between MIC and LD50 is crucial in determining the suitability of organic acids as food preservatives, ensuring that they are effective against bacteria or fungi at concentrations that are not harmful to humans.
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