Evaluation of the enantioselective in vitro metabolism of the chiral pesticide fipronil employing a human model: Risk assessment through in vitro-in vivo correlation and prediction of toxicokinetic parameters.
Food Chem Toxicol
; 123: 225-232, 2019 Jan.
Article
em En
| MEDLINE
| ID: mdl-30385190
ABSTRACT
The chiral pesticide fipronil is employed as a racemic mixture to control pests. Although there are no enantioselective differences in the fipronil enantiomer activities toward target organisms, fipronil enantiomers may exhibit enantioselective differences in their bioaccumulation, toxicity, and metabolism toward non-target organisms, including humans. The present work aims to provide significant reliable enantioselective information concerning fipronil risk assessment in humans. For that, the in vitro metabolism of rac-fipronil, S-fipronil, and R-fipronil by human liver microsomes was evaluated, the in vivo enantioselective toxicokinetic parameters were predicted and the main CYP450 isoforms involved in the enantioselective metabolism were determined. The obtained results demonstrated that fipronil may undergo a clearance by the liver and it is exclusively metabolized by the CYP3A4 isoform. Although no significative stereoselective differences were observed, the results provide reliable information on fipronil risk assessment for humans.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Praguicidas
/
Pirazóis
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article