title: Risk assessment of mixtures: possibility of prediction of interaction between chemicals.
abstract: OBJECTIVE
  Potentiation, inhibition, antagonism, synergism or other interactions of chemicals in an organism may significantly affect the toxicity of chemical mixtures. Therefore, a suitable physicochemical parameter is sought as a predictor of these effects.
  
  
  METHODS
  Acute toxicity EC50 (mol/l) was used as an index of toxic hazard. The EC50 was defined here as the concentration inhibiting movement of 50% of Tubifex tubifex worms in a standardised short-term test. The EC50 for the mixture benzene/ethanol was measured over the whole range of molar fractions between 0 and 1. The determined EC50 values were compared with those calculated by the effect-addition and concentration-addition models. The distribution of benzene and ethanol between the aqueous and gaseous phases was determined by gas chromatography.
  
  
  RESULTS
  The determined EC50 of the benzene/ethanol mixtures exhibited deviations from the values predicted using the EC50 of the single compounds. The magnitude of this deviation depended on the composition of the mixture, and could be as high as 80% if the effect-addition model is used or 20% if the concentration-addition model is applied. The air/water distribution coefficients of benzene and ethanol measured in aqueous solutions of their mixtures exhibit unobservable to slight deviations from those obtained by simple summation.
  
  
  CONCLUSIONS
  The determined values of the EC50 of benzene/ethanol mixtures calculated by either the concentration-addition or effect-addition model differ from the true values due to interactions among chemicals. The deviations depend on a quantitative composition of a mixture. The air/water distribution coefficient of chemicals in a mixture is not the most suitable predictor of the interactions.
authors.affiliation: National Institute of Public Health, Srobárova 48, 10042 Prague 10, Czech Republic. miltic@yahoo.com
authors.forename: Milon
authors.initials: M
authors.lastname: Tichý
authors.forename: Václav
authors.initials: V
authors.lastname: Borek-Dohalský
authors.forename: Marián
authors.initials: M
authors.lastname: Rucki
authors.forename: Josef
authors.initials: J
authors.lastname: Reitmajer
authors.forename: Ladislav
authors.initials: L
authors.lastname: Feltl
mesh_terms: D000388:Air; D000818:Animals; D001554:Benzene / Q000633:toxicity; D002492:Central Nervous System Depressants / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000633:toxicity; D005544:Forecasting; D007928:Lethal Dose 50; D008956:Models, Chemical; D009835:Oligochaeta; D018570:Risk Assessment; D014867:Water; D015262:Xenobiotics / Q000737:chemistry / Q000633:toxicity*
chemical_list: D002492:Central Nervous System Depressants; D015262:Xenobiotics; D014867:Water; D000431:Ethanol; D001554:Benzene