1 São Paulo State University (UNESP), School of Sciences, Humanities and Languages, Assis, SP 19806-900, Brazil.
2 São Paulo State University (UNESP), School of Technology and Applied Sciences, Presidente Prudente, SP 19060-900, Brazil; São Paulo State University (UNESP), Institute of Geosciences and Exact Sciences, Rio Claro, SP 13506-900, Brazil.
3 Concordia University, Montreal, Quebec H3G 1M8, Canada.
4 São Paulo State University (UNESP), School of Sciences, Humanities and Languages, Assis, SP 19806-900, Brazil. Electronic address: sabrina.alessio@unesp.br.

Pesticides have boosted agricultural productivity but pose significant risks to environmental and human health. The intensification of agriculture has driven widespread pesticide use, with 66 % of global consumption allocated to sugarcane, soybean and corn. Sugarcane, a major monoculture in Brazil, India, and China, has driven a 700 % increase in pesticide use in Brazil over the past 40 years. Commonly used pesticides in Brazilian sugarcane farming include methyl parathion (PM), imazapic (IM), isoxaflutole (IS), and chlorantraniliprole (CL). Despite regulatory efforts by governmental agencies worldwide, the long-term toxicity of these substances on human health remains insufficiently studied. This study evaluates the cytotoxicity of PM, IM, IS, and CL at concentrations regulated by governmental agencies in human hepatocarcinoma (HepG2) cells. Given the liver's role in metabolizing xenobiotics, it is especially vulnerable to pesticide-toxicity. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and LDH (lactate dehydrogenase release) assays, alongside confocal microscopy, showed reduced cell viability and impaired membrane integrity, with progressive toxicity (from 24 to 96 h), primarily impacting mitochondrial activity. Surface pressure-area (p-A) isotherms, compressibility (C_S?¹), and atomic force microscopy (AFM) revealed distinct pesticide incorporation mechanisms into Langmuir monolayers of HepG2 lipid extracts, used as membrane models. The findings underscore the hepatotoxicity of PM, IM, IS, and CL, even at concentrations regulated by governmental agencies, emphasizing their potential human health hazards.