Pre-validation of an alternative test method for prediction of developmental neurotoxicity.
Food Chem Toxicol
; 164: 113070, 2022 Jun.
Article
em En
| MEDLINE
| ID: mdl-35483486
ABSTRACT
Exposure to neurodevelopmental toxicants can cause permanent brain injury. Hance, determining the neurotoxicity of unknown substances is essential for the safety of substance. As an alternative method to animal studies, developmental neurotoxicity test (DNT) and the first discriminant function (DF) were established in previous study. This study aimed to increase the predictability of the DNT method and perform a mobility test. Two endpoints of 29 newly investigated substances were used to establish a second-generation DF (2nd GDF). As two endpoints, the half-inhibitory concentration of the cell viability (IC50) was determined using a cell counting kit-8 assay. The half-inhibitory concentration of differentiation (ID50) was determined by measuring the green fluorescent protein (GFP) intensity in 46C cells. The substances were treated dose-dependently to measure IC50 and ID50. The 2nd GDF classified 29 chemicals accurately as toxic and non-toxic. Four participants of three independent laboratories were enrolled to test the mobility. The results of the test set were highly accurate in reproducibility (100% of accuracy, sensitivity, and specificity) and mobility (accuracy 93.33%, sensitivity 90.91%, and specificity 100%). In conclusion, the protocol is transferable, reproducible, and accurate. Therefore, this could be a standardizing method for determining a neurotoxicant as an alternative for animal experiments.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Testes de Toxicidade
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Síndromes Neurotóxicas
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Food Chem Toxicol
Ano de publicação:
2022
Tipo de documento:
Article
País de publicação:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM