Toxicokinetic testing strategies to demonstrate bone marrow exposure in in vivo micronucleus study for genotoxicity assessment of agrochemicals.
Regul Toxicol Pharmacol
; 110: 104552, 2020 Feb.
Article
en En
| MEDLINE
| ID: mdl-31836537
Following adoption of the new OECD test guideline (TG) 474 for the in vivo mammalian erythrocyte micronucleus (MN) test (29 July 2016), demonstration of exposure of target tissue (bone marrow) is required, if the test result is negative i.e. no cytogenetic damage. It implies that for many active ingredients, relevant metabolites or significant impurities with existing in vivo MN tests resulting in negative genotoxicity findings, evidence of target tissue exposure may be lacking and is considered a data gap in regulatory reviews. We present here toxicokinetic (TK) testing strategies for the design and conduct of studies that would demonstrate evidence of delivery of the test substance to the bone marrow. To illustrate this, three examples are presented with methods utilized under each scenario. We also propose a decision tree that may help design suitable TK studies to establish evidence of bone marrow exposure.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Médula Ósea
/
Árboles de Decisión
/
Pruebas de Micronúcleos
/
Agroquímicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Regul Toxicol Pharmacol
Año:
2020
Tipo del documento:
Article
Pais de publicación:
Países Bajos