Identification of Metabolism and Excretion Differences of Procymidone between Rats and Humans Using Chimeric Mice: Implications for Differential Developmental Toxicity.
J Agric Food Chem
; 66(8): 1955-1963, 2018 Feb 28.
Article
em En
| MEDLINE
| ID: mdl-29313347
ABSTRACT
A metabolite of procymidone, hydroxylated-PCM, causes rat-specific developmental toxicity due to higher exposure to it in rats than in rabbits or monkeys. When procymidone was administered to chimeric mice with rat or human hepatocytes, the plasma level of hydroxylated-PCM was higher than that of procymidone in rat chimeric mice, and the metabolic profile of procymidone in intact rats was well reproduced in rat chimeric mice. In human chimeric mice, the plasma level of hydroxylated-PCM was less, resulting in a much lower exposure. The main excretion route of hydroxylated-PCM-glucuronide was bile (the point that hydroxylated-PCM enters the enterohepatic circulation) in rat chimeric mice, and urine in human chimeric mice. These data suggest that humans, in contrast to rats, extensively form the glucuronide and excrete it in urine, as do rabbits and monkeys. Overall, procymidone's potential for causing teratogenicity in humans must be low compared to that in rats.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Compostos Bicíclicos com Pontes
/
Quimera
/
Fungicidas Industriais
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article