P24-17 Organophosphorus pesticides and neurotoxicity: Evaluation of human and animal cell model

Organophosphorus (OP) pesticides are among the most widely used agrochemicals globally, playing a crucial role in insect control and food production. Their application raises serious concerns about the impact on human health and environmental safety. OP pesticides, e.g. meth-amidophos, fenamiphos, ethoprophos, and phosalone interfere with the cholinergic system. At concentrations from 4 µM to 90 µM, they inhibit acetylcholinesterase (AChE), a key enzyme in neurotransmission. However, beyond their inhibitory effect, their neurotoxic potential could also be additionally triggered by secondary cellular effects, including oxidative stress and mitochondrial dysfunction. To evaluate these effects, we examined both animal and human-derived neural cell models, comparing their responses to pesticide exposure over 24 hours at varying concentrations. Cytotoxicity was observed in both models, though differences in sensitivity and cellular response were noted for fenamiphos and ethoprophos (IC 50 as low as 250 µM). Some pesticides demonstrated pronounced neurotoxic effects, potentially due to alterations in cellular processes that disrupt homeostasis and contribute to unregulated cell death. Increased production of reactive oxygen species following pesticide exposure, as for ethoprophos in less than 1 hour, was linked to oxidative damage and cell death. Comparing animal and human-derived cell models, this study aims to determine the extent to which their responses are comparable by providing insights into pesticide-induced cytotoxicity. Understanding the cellular effects of pesticide exposure is critical for assessing their broader toxicological impact and evaluating the relevance of different toxicity testing models. Acknowledgments: This research was supported by the Croatian Science Foundation (IP-2022-10-6685), European Regional Development Fund (KK.01.1.1.02.0007), and the European Union – Next Generation EU (Class: 643-02/23-01/00016, Reg. no. 533-03-23-0006).