An evaluation of the utility of four in vitro short term tests for predicting the cytotoxicity of individual compounds derived from tobacco smoke
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An evaluation of results obtained earlier and now complemented to provide information on the activity of 305 compounds in four in vitro tests has been undertaken. Biological data based on the effects of these compounds on cell multiplication, oxidative metabolism, ciliary activity and membrane permeability are compared with a view to clarifying intersystem similarities and differences and, on the basis of a mean activity parameter, evaluating structure-activity and functionality-activity relationships.
High mean activity is observed for 59 compounds, of which 18 are phenols, 14 aldehydes, 8 N-heterocyclics, 7 alcohols and 5 hydrocarbons. The medium and low mean activity groups comprise 105 and 131 members, respectively, and both include representatives of all functionalities examined. Delineation of the 305 compounds using 45 descriptors, and computer-assisted matching of these and any combination of them against the mean activity showed the most toxic single descriptor group to be terpenoids followed by indoles and naphthalenes, and the most toxic two-descriptor group to be α, β-unsaturated carbonyls followed by n-alkyl alcohols, aldehydes and acids.
Examination of intersystem similarities and differences, using a high-medium-low scale, shows that all four systems give the same result for 35 percent of the compounds, three systems for 41 to 48 percent of the compounds, and two systems for 53 to 64 percent of the compounds. Of all compounds, 16 percent exhibit a high activity in one system and a low activity in the other three, or vice versa. Nearly, half od these discrepancies are caused by the membrane permeability system showing diverging results, while none of them are related to the brown fat cell system. The last test system is found to best represent the mean activity obtained from the four systems and the one of choice if reducing the number of tests from four to one.
Key WordsToxicity screening cytotoxic effects in vitro short term tests inhibition of cell growth inhibition of oxidative metabolism membrane damage ciliotoxicity compounds derived from tobacco smoke test system comparison
mean activity of four individual test system values (ACG, AOM, AMD, and ACA)
mean activity for N number of compounds
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