Prediction of acute toxicity of chemicals in mixtures: worms Tubifex tubifex and gas/liquid distribution.
The aim of this contribution is to support our proposal of the procedure for predicting acute toxicity of binary mixtures by QSAR analysis techniques. The changes of a mixture composition are described by molar ratio R and visualized in the R-plot (QCAR--quantitative composition-activity relationships). The approach was inspired by Rault and Dalton's laws, their positive and negative deviations in the behavior of a mixture of real gases, by Loewe and Muischnek isoboles and by the Finney test of additivity. Acute toxicity was determined by the laboratory test with woms Tubifex tubifex. The additivity of the acute toxicity in the binary mixture benzene + nitrobenzene was confirmed and a new interaction is described: "mixed interaction" with the binary mixture aniline + ethanol. The "mixed interaction" means that depending on mixture composition, both potentiation and inhibition can occur. As the first physicochemical descriptor of the changes caused by the changing composition of binary mixtures, the gas/liquid equilibrium was studied and a composition of the gaseous phase was determined by a gas chromatographic method. The method for determination of concentrations in the gaseous phase was described. The gaseous phase composition of benzene + nitrobenzene. benzene + ethanol, benzene + aniline and ethanol + aniline mixtures was analyzed. It was found that if the concentrations of the mixture's components in the gaseous phase behave nonideally (they are not additive), the acute toxicity of the same mixture is not additive as well. Another descriptor to distinguish between potentiation and inhibition will be, however, necessary. The properties, both gaseous phase composition and the acute toxicity, of the benzene + nitrobenzene mixture are additive. In mixtures with the mixed interaction, the R-plot of the composition of the gaseous phase is complex with a large variation of results.
Tichý
M
M
National Institute of Public Health, Praha, Czech Republic. miltic@yahoo.com
Borek-Dohalský
V
V
Matousová
D
D
Rucki
M
M
Feltl
L
L
Roth
Z
Z
D000814:Aniline Compounds / Q000633:toxicity; D000818:Animals; D001554:Benzene / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D002492:Central Nervous System Depressants / Q000633:toxicity; D004347:Drug Interactions; D004785:Environmental Pollutants / Q000633:toxicity*; D000431:Ethanol / Q000633:toxicity; D005544:Forecasting; D005740:Gases; D007928:Lethal Dose 50; D009578:Nitrobenzenes / Q000633:toxicity; D009835:Oligochaeta; D013329:Structure-Activity Relationship
D000814:Aniline Compounds; D002273:Carcinogens; D002492:Central Nervous System Depressants; D004785:Environmental Pollutants; D005740:Gases; D009578:Nitrobenzenes; D000431:Ethanol; C036077:nitrobenzene; D001554:Benzene; C023650:aniline