| 摘要 |
The invention provides methods for analyzing and predicting the in vivo respiratory toxicity of a compound (e.g., pharmaceutical, biological, cosmetic, or chemical compounds) or composition comprising a combination of an in vitro mammalian cell model with multiple endpoint analysis, and time and concentration response curves. The methods allow the determination of a predicted in vivo respiratory toxicity value of a compound without the use of animals, with a high degree of accuracy. The methods comprise detecting any combination of cell viability markers and expression levels of genes implicated in respiratory toxicity and/or sensitization, such as pro-inflammatory response genes, combining the viability and gene expression level data with concentration response and time response data, conducting a computational analysis, and comparing test compound data to a database of known respiratory toxicants/sensitizers to predict and/or analyze the respiratory toxicity. An indication of organ specificity is provided by a toxicity index, which is determined by comparing mean 1050 values in lung cells to mean 1050 values in liver cells. |
