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In 2-year studies, the nongenotoxic pyrethroid insecticide permethrin produced hepatocellular tumors in CD-1 mice but not in Wistar rats. Recently, we demonstrated that the mode of action (MOA) for mouse liver tumor formation by permethrin involves activation of the peroxisome proliferator-activated receptor alpha (PPARα), resulting in a mitogenic effect. In the present study, the effects of permethrin and 2 major permethrin metabolites, namely 3-phenoxybenzoic acid and trans-dichlorochrysanthemic acid, on cytochrome P450 mRNA levels and cell proliferation (determined as replicative DNA synthesis) were evaluated in cultured CD-1 mouse, Wistar rat, and human hepatocytes. Permethrin and 3-phenoxybenzoic acid induced CYP4A mRNA levels in both mouse and human hepatocytes, with trans-dichlorochrysanthemic acid also increasing CYP4A mRNA levels in mouse hepatocytes. 3-Phenoxybenzoic acid induced CYP4A mRNA levels in rat hepatocytes, with trans-dichlorochrysanthemic acid increasing both CYP4A mRNA levels and replicative DNA synthesis. Permethrin, 3-phenoxybenzoic acid, and trans-dichlorochrysanthemic acid stimulated replicative DNA synthesis in mouse hepatocytes but not in human hepatocytes, demonstrating that human hepatocytes are refractory to the mitogenic effects of permethrin and these 2 metabolites. Thus, although some of the key (eg, PPARα activation) and associative (eg, CYP4A induction) events in the established MOA for permethrin-induced mouse liver tumor formation could occur in human hepatocytes at high doses of permethrin, 3-phenoxybenzoic acid, and/or trans-dichlorochrysanthemic acid, increased cell proliferation (an essential step in carcinogenesis by nongenotoxic PPARα activators) was not observed. These results provide additional evidence that the established MOA for permethrin-induced mouse liver tumor formation is not plausible for humans.
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http://dx.doi.org/10.1093/toxsci/kfaa017 | DOI Listing |
Environ Res
December 2024
Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA. Electronic address:
We investigated the effect of exposure to pesticide mixtures during pregnancy on the placental transcriptome, to link these exposures and placental functions. The Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE) enrolled pregnant farmworkers from Thailand (n = 248), who were primarily exposed to organophosphate (OP) and pyrethroid pesticides. We measured maternal urinary levels of six non-specific OP metabolites expressed as three summary measures (dimethylalkylphosphates (DMAP), diethylalkylphosphates (DEAP), and dialkylphosphates (DAP) and three pyrethroid metabolites (3-phenoxybenzoic acid (3-PBA), cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA, trans-DCCA) during early, middle, and late pregnancy, and adjusted for urine dilution using creatinine.
View Article and Find Full Text PDFInt J Hyg Environ Health
November 2024
Cell Toxicology Team, National Food Institute, Technical University of Denmark, 2800, Kgs. Lyngby, Denmark.
Pyrethroids constitute a large group of insecticides widely used in agriculture, indoor environments, and in vector control. Structurally, pyrethroids resemble thyroid hormones, and have been suggested to be thyroid hormone disruptors based on experimental studies. During pregnancy, even minor disturbances in maternal levels can affect fetal brain development.
View Article and Find Full Text PDFJ Agric Food Chem
November 2024
School of Food and Bioengineering, Xihua University, Chengdu 610039, Sichuan, China.
Pyrethroid pesticide residues have detrimental effects on soil ecology and crop growth during insecticidal operations in agriculture. In this study, a novel strain VF-2 was isolated from long-term pesticide-treated cropland and had a maximum degradation efficiency of 81.66% for synthetic pyrethroid β-cypermethrin (β-CY) under optimized conditions.
View Article and Find Full Text PDFJ Hazard Mater
October 2023
College of Food Science, Sichuan Agricultural University, Ya'an, Sichuan 625014, People's Republic of China. Electronic address:
Prolonged and widespread use of pyrethroid pesticides a significant concern for human health. The initial step in pyrethroid bioremediation involves the hydrolysis of ester-bond. In the present study, the esterase genes est10 and est13, derived from Bacillus subtilis, were successfully cloned and expressed in Escherichia coli.
View Article and Find Full Text PDFSci Total Environ
December 2024
Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University, Chongqing 400715, China; Academy of Agricultural Sciences, Southwest University, Chongqing 400715, China. Electronic address:
This study comprehensively investigated the comparative acute toxicities, degradation, transcriptome, and oxidative stress induction of fenpropathrin (FEN) and its main metabolite 3-phenoxybenzoic acid (3-PBA)in soil-earthworm microcosms. FEN degradation half-life ranged from 19.09 to 28.
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