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1.
ALTEX ; 36(4): 623-633, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31210278

RESUMO

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.


Assuntos
Poluentes Atmosféricos/toxicidade , Transformação Celular Neoplásica/efeitos dos fármacos , Misturas Complexas/toxicidade , Gestão da Segurança/métodos , Animais , Relação Dose-Resposta a Droga , Camundongos , Camundongos Endogâmicos BALB C/embriologia , Material Particulado/toxicidade , Fenótipo , Estações do Ano
2.
Toxicol In Vitro ; 48: 78-85, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29305980

RESUMO

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.


Assuntos
Misturas Complexas/toxicidade , Oftalmopatias/induzido quimicamente , Irritantes/toxicidade , Testes de Toxicidade Aguda/métodos , Alternativas aos Testes com Animais , Animais , Linhagem Celular , Cosméticos/toxicidade , Epitélio Corneano/citologia , Epitélio Corneano/efeitos dos fármacos , Oftalmopatias/patologia , Humanos , Óleos , Valor Preditivo dos Testes , Coelhos , Reprodutibilidade dos Testes , Solubilidade , Água
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