Methodological approaches to the study of the combined effect of atmospheric pollutants as illustrated by chlorinated hydrocarbons

Abstract

The combined effect of substances with a unidirectional toxic action was studied with the use of several chlorinated hydrocarbons, including 1,2-dichloropropane, 1,2,3-trichloropropane, and perchlorethylene at various concentrations. The results of the study can be used as the basis for the development of methodological approaches to the study of the combined action of toxic substances administered by inhalation. The research plan also incorporated the problem of explaining the nature of the action of the mixture of the test compounds in acute, subacute, and chronic animal experiments. All of the studies were conducted with each compound alone and then in various combinations by using the concentration--time relationship, since a correct evaluation of the combined action of compounds can be obtained by comparing these with the effects observed for the action of each component alone. A graphic representation was obtained of the onset time for a given effect (loss of righting reflex for 50% of the animals) as a function of the active concentrations for the short-term effect of high concentrations of 1,2-dichloropropane, 1,2,3-trichloropropane, and perchloroethylene based on the concentration--time relationship. The nature of the combined action of various combinations (two and three substances) with respect to concentration was studied by using these graphs. At high concentrations, the action of various combinations of the studied substances is additive. An inverse relationship was discovered in subacute experiments between the inactive concentrations and the onset time for changes in the vital activity indices of an organism: the lower the concentration, the later the changes. Additional data were obtained as the result of morphofunctional studies on the toxic properties of the studied compounds, on damage reactions and on adaptational changes. This is of interest from the point of view of explaining the mechanism of action at various concentrations.