Enantioselective inhibition of human CYP2C19 by the chiral pesticide ethofumesate: Prediction of pesticide-drug interactions in humans

Perovani, Icaro Salgado; Bucci, Jade Lorena Mariano; Carrão, Daniel Blascke; Barbetta, Maike Felipe Santos; Silva, Rodrigo Moreira da; Lopes, Norberto Peporine; Oliveira, Anderson Rodrigo Moraes de

doi:10.1016/j.cbi.2021.109552

Cited by 6 publications

(4 citation statements)

References 40 publications

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“…Our pesticide mix also contained carbofuran, 3-keto-carbofuran, and 3OH-carbofuran, but we did not detect any of these related compounds above their LODs of 0.73, 1.23, and 0.53 μg/kg, respectively. Ancymidol is a synthetic plant growth retardant that is commonly used for ornamental horticulture. , Fumesate is a primary metabolite of ethofumesate, a chiral herbicide used to control grasses and broad-leaf weeds . Metazachlor is an herbicide used to control weeds by inhibiting plant enzymes, and in soil its half-life ranges from 19 to 82 days .…”

Section: Resultsmentioning

confidence: 99%

“…61,62 Fumesate is a primary metabolite of ethofumesate, a chiral herbicide used to control grasses and broad-leaf weeds. 63 Metazachlor is an herbicide used to control weeds by inhibiting plant enzymes, and in soil its half-life ranges from 19 to 82 days. 64 Previous work shows that very low levels (0.005 mg/kg) of metazachlor are taken up by rapeseed after applying metazachlor at the recommended dose.…”

Section: Environmentalmentioning

confidence: 99%

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(Non)targeted Chemical Analysis and Risk Assessment of Organic Contaminants in Darkibor Kale Grown at Rural and Urban Farms

Brueck,

Xin,

Lupolt

et al. 2024

Environ. Sci. Technol.

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This study investigated the presence and human hazards associated with pesticides and other anthropogenic chemicals identified in kale grown in urban and rural environments. Pesticides and related compounds (i.e., surfactants and metabolites) in kale samples were evaluated using a nontargeted data acquisition for targeted analysis method which utilized a pesticide mixture containing >1,000 compounds for suspect screening and quantification. We modeled population-level exposures and assessed noncancer hazards to DEET, piperonyl butoxide, prometon, secbumeton, terbumeton, and spinosyn A using nationally representative estimates of kale consumption across life stages in the US. Our findings indicate even sensitive populations (e.g., pregnant women and children) are not likely to experience hazards from these select compounds were they to consume kale from this study. However, a strictly nontargeted chemical analytical approach identified a total of 1,822 features across all samples, and principal component analysis revealed that the kale chemical composition may have been impacted by agricultural growing practices and environmental factors. Confidence level 2 compounds that were ≥5 times more abundant in the urban samples than in rural samples (p < 0.05) included chemicals categorized as "flavoring and nutrients" and "surfactants" in the EPA's Chemicals and Products Database. Using the US-EPA's Cheminformatics Hazard Module, we identified that many of the nontarget compounds have predicted toxicity scores of "very high" for several end points related to human health. These aspects would have been overlooked using traditional targeted analysis methods, although more information is needed to ascertain whether the compounds identified through nontargeted analysis are of environmental or human health concern. As such, our approach enabled the identification of potentially hazardous compounds that, based on their hazard assessment score, merit follow-up investigations.

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Section: Resultsmentioning

confidence: 99%

Section: Environmentalmentioning

confidence: 99%

(Non)targeted Chemical Analysis and Risk Assessment of Organic Contaminants in Darkibor Kale Grown at Rural and Urban Farms

Brueck,

Xin,

Lupolt

et al. 2024

Environ. Sci. Technol.

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“…OCPs have antiandrogenic effects and can suppress androgen-mediated gene activation [ 78 ]. Thus, xenobiotic detoxification genes play a key role in assessing the risks associated with chronic pesticide exposure [ 79 ].…”

Section: Discussionmentioning

confidence: 99%

“…The key enzymes in antioxidant systems are superoxide dismutase 1 (SOD1) and glutamate cysteine ligase (GCLM and GCLC subunits). Polymorphisms of genes encoding antioxidant enzymes can be associated with susceptibility to the development of multifactorial diseases, such as cardio-vascular diseases, amyotrophic lateral sclerosis [ 79 ], Parkinson’s disease, and hemolytic anemia [ 82 ]. The transcription factor NFE2L3, which binds antioxidant response elements in target genes, is involved in various cellular processes, including carcinogenesis, stress response, differentiation, and inflammation [ 48 , 49 , 50 , 83 ].…”

Section: Discussionmentioning

confidence: 99%

Individual Risk Assessment for Population Living on the Territories Long-Term Polluted by Organochlorine Pesticides

Garshin,

Altynova,

Djangalina

et al. 2023

Toxics

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The long-term storage of unutilized pesticides raised new problems of long-term environmental contamination. The study presents the results of surveying 151 individuals in 7 villages living close to pesticide-contaminated localities. All individuals have been surveyed concerning their consumption habits and lifestyle characteristics. An assessment of the general exposure risks of the local population was carried out using the analysis of pollutants in food products and the average levels of their consumption in the region. The cohort risk evaluation revealed that the greatest risk was associated with the regular consumption of cucumbers, pears, bell peppers, meat, and milk. The new model to estimate individual risks of long-term pesticide pollution was proposed as a calculation of the combined action of 9 risk factors, including individual genotypes, age, lifestyle, and personal pesticide consumption rates. The analysis of the predictive ability of this model showed that the final score for individual health risks corresponded to the development of chronic diseases. A high level of chromosomal aberrations was evidenced for individual genetic risk manifestations. The combined influence of all risk factors revealed contributions of 24.7% for health status and 14.2% for genetic status, while other impacts go to all unaccounted factors.

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Chiral fungicide penconazole: Absolute configuration, bioactivity, toxicity, and stereoselective degradation in apples

Nie

Zhang

et al. 2022

Science of The Total Environment

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Enantioselective inhibition of human CYP2C19 by the chiral pesticide ethofumesate: Prediction of pesticide-drug interactions in humans

Cited by 6 publications

References 40 publications

(Non)targeted Chemical Analysis and Risk Assessment of Organic Contaminants in Darkibor Kale Grown at Rural and Urban Farms

(Non)targeted Chemical Analysis and Risk Assessment of Organic Contaminants in Darkibor Kale Grown at Rural and Urban Farms

Individual Risk Assessment for Population Living on the Territories Long-Term Polluted by Organochlorine Pesticides

Chiral fungicide penconazole: Absolute configuration, bioactivity, toxicity, and stereoselective degradation in apples

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