Risk assessment of the chiral pesticide fenamiphos in a human model: Cytochrome P450 phenotyping and inhibition studies

Autor(es)

Perez de Albuquerque, Nayara Cristina ^[1] ; Carrao, Daniel Blascke ^[1] ; Habenschus, Maisa Daniela ^[1] ; Fonseca, Franciele Saraiva ^[1] ; da Silva, Rodrigo Moreira ^[2] ; Lopes, Norberto Peporine ^[2] ; Rocha, Bruno Alves ^[3] ; Barbosa, Jr., Fernando ^[4] ; Moraes de Oliveira, Anderson Rodrigo ^{[1, 5]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Fis & Quim, BR-14090903 Ribeirao Preto, SP - Brazil

^[3] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Quim, Campus Diadema, BR-09972270 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, BR-14040903 Ribeirao Preto, SP - Brazil

^[5] UNESP, Inst Chem, Natl Inst Alternat Technol Detect Toxicol Evaluat, POB 355, BR-14800900 Araraquara, SP - Brazil

• Tipo de documento: Artigo de Revisão
• Fonte: Food and Chemical Toxicology; v. 146, DEC 2020.
• Citações Web of Science: 0

Resumo

Fenamiphos (FS) is a chiral organophosphate pesticide that is used to control nematodes in several crops. Enantioselective differences may be observed in FS activity, bioaccumulation, metabolism, and toxicity. Humans may be exposed to FS through occupational and chronic (food, water, and environmental) exposure. FS may cause undesirable CYP450 pesticide-drug interactions, which may impact human health. Here, the CYP450 isoforms involved in enantioselective FS metabolism were identified, and CYP450 inhibition by rac-FS, (+)-FS, and (-)-FS was evaluated to obtain reliable information on enantioselective FS risk assessment in humans. CYP3A4 and CYP2E1 metabolized FS enantiomers, and CYP2B6 may participate in rac-FS metabolism. In addition, rac-FS, (+)-FS, and (-)-FS were reversible competitive CYP1A2, CYP2C19, and CYP3A4/5 inhibitors. High stereoselective inhibition potential was verified; rac-FS and (-)-FS strongly inhibited and (+)-FS moderately inhibited CYP1A2. Stereoselective differences were also detected for CYP2C19 and CYP3A4/5, which were strongly inhibited by rac-FS, (+)-FS, and (-)-FS. Our results indicated a high potential for CYP450 drug-pesticide interactions, which may affect human health. The lack of stereoselective research on the effect of chiral pesticides on the activity of CYP450 isoforms highlights the importance of assessing the risks of such pesticides in humans. (AU)

• Processo FAPESP: 14/50945-4 - INCT 2014: Instituto Nacional de Tecnologias Alternativas para Detecção, Avaliação Toxicológica e Remoção de Micropoluentes e Radioativos
• Beneficiário: Maria Valnice Boldrin
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/15680-5 - Estudos enantiosseletivos in vitro de metabolismo, inibição enzimática e toxicidade do praguicida fipronil
• Beneficiário: Daniel Blascke Carrão
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/02533-1 - Estudos enantiosseletivos de metabolismo, citotoxicidade e genotoxicidade in vitro do nematicida Fenamifós
• Beneficiário: Nayara Cristina Perez de Albuquerque
• Modalidade de apoio: Bolsas no Brasil - Doutorado