Gust_2024_Environ.Toxicol.Pharmacol__104615

Neurotoxicity investigations of inhaled organophosphorus pesticide (OP), ethyl-parathion (EP), were conducted in Sprague Dawley rats comparing exposures to EP volatilized at 0, 1, 10, and 20mg/m(3) versus EP incorporated into soil dust (5mg/m(3)) at 0, 0.0095, 0.09, and 0.185mg/mg(3). All exposures were sublethal, caused no respiratory effects, and no effects on balance and coordination behavior. Both volatilized and dust-incorporated EP exposures significantly decreased acetylcholinesterase (AChE) activity in plasma and hippocampus tissue. Correspondingly, plasma and hippocampal dopamine levels spiked in these exposures suggesting compensatory cholinergic / dopaminergic signal balancing. The EP exposures significantly increased expression of pro-inflammatory genes, including MAPK-14, IL6, IL1beta, and TNF-alpha, while global RNA-seq results identified significant enrichment of inflammation, oxidative stress, and apoptosis pathways. Remarkably, dust-incorporated EP impacted similar molecular endpoints as volatilized EP but at concentrations two orders of magnitude lower highlighting potentially increased potency of EP incorporated into soil dust.