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1.
ALTEX ; 36(4): 623-633, 2019.
Article de Anglais | MEDLINE | ID: mdl-31210278

RÉSUMÉ

The use of in vitro alternative methods is a promising approach to characterize the hazardous properties of environmental chemical mixtures, including urban airborne particulate matter (PM). The aim of this study was to examine seasonal differences in the toxic and transforming potential of PM samples, by using the in vitro cell transformation assay in Bhas 42 cells for the prediction of potential carcinogenic effects. Bhas 42 cells are already initiated, and the v-Ha-ras transfection, together with genetic modification following the immortalization process, makes them a valuable model to study the late steps of cellular transformation leading to the acquisition of the malignant phenotype. Exposure to organic extracts of PM1 and PM2.5 induced dose-related effects. The transforming and cytotoxic properties are related to the amount of PM collected during the sampling campaign and associated with the concentrations of polycyclic aromatic hydrocarbons (PAHs) in the samples. All the samples induced cell transformation following prolonged exposure of 2 weeks. Our results support the utility of the in vitro top-down approach to characterise the toxicity of real mixtures, thereby supporting regulators in the decision-making process. The results also identify the need for appropriate assay selection within the in vitro testing strategy to address the complexity of the final adverse outcomes.


Sujet(s)
Polluants atmosphériques/toxicité , Transformation cellulaire néoplasique/effets des médicaments et des substances chimiques , Mélanges complexes/toxicité , Gestion de la sécurité/méthodes , Animaux , Relation dose-effet des médicaments , Souris , Souris de lignée BALB C/embryologie , Matière particulaire/toxicité , Phénotype , Saisons
2.
Toxicol In Vitro ; 48: 78-85, 2018 Apr.
Article de Anglais | MEDLINE | ID: mdl-29305980

RÉSUMÉ

The Short Time Exposure (STE) test method is an alternative method for assessing eye irritation potential using Statens Seruminstitut Rabbit Cornea cells and has been adopted as test guideline 491 by the Organisation for Economic Co-operation and Development. Its good predictive performance in identifying the Globally Harmonized System (GHS) No Category (NC) or Irritant Category has been demonstrated in evaluations of water-soluble substances, oil-soluble substances, and water-soluble mixtures. However, the predictive performance for oil-soluble mixtures was not evaluated. Twenty-four oil-soluble mixtures were evaluated using the STE test method. The GHS NC or Irritant Category of 22 oil-soluble mixtures were consistent with that of a Reconstructed human Cornea-like Epithelium (RhCE) test method. Inter-laboratory reproducibility was then confirmed using 20 water- and oil-soluble mixtures blind-coded. The concordance in GHS NC or Irritant Category among four laboratories was 90%-100%. In conclusion, the concordance in comparison with the results of RhCE test method using 24 oil-soluble mixtures and inter-laboratory reproducibility using 20 water- and oil-soluble mixtures blind-coded were good, indicating that the STE test method is a suitable alternative for predicting the eye irritation potential of both substances and mixtures.


Sujet(s)
Mélanges complexes/toxicité , Maladies de l'oeil/induit chimiquement , Irritants/toxicité , Tests de toxicité aigüe/méthodes , Alternatives à l'expérimentation animale , Animaux , Lignée cellulaire , Cosmétiques/toxicité , Épithélium antérieur de la cornée/cytologie , Épithélium antérieur de la cornée/effets des médicaments et des substances chimiques , Maladies de l'oeil/anatomopathologie , Humains , Huiles , Valeur prédictive des tests , Lapins , Reproductibilité des résultats , Solubilité , Eau
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