Acute and subacute effects of drugs in embryos of Danio rerio. QSAR grouping and modelling

Ecotoxicol Environ Saf. 2019 May 15:172:232-239. doi: 10.1016/j.ecoenv.2019.01.081. Epub 2019 Jan 31.

Abstract

The final fate of many drugs is release into the natural aquatic environment. It is necessary to assess the toxicity caused by this situation and the associated concerns for human beings. Zebrafish (Danio rerio) is a common biomodel used to assess toxicity in aquatic environments. The zebrafish embryo toxicity test was selected to evaluate the acute toxicity of several drugs (diphenhydramine, gentamicin, tobramycin, enalapril and lidocaine) due to the lack of such information. Lethal and sublethal effects were detected, and the LC50 values of the drugs ranged from 11.0 mg/L to 422·102 mg/L. For all of the drugs tested, these values were higher than the concentrations found in the natural environment. Therefore, there was a low environmental toxicological risk. Nevertheless, teratogenic effects were also recorded when embryos of zebrafish were exposed to caffeine (control drug), diphenhydramine and lidocaine at lower concentrations than the respective LC50 values. Quantitative structure-activity relationship analysis was also performed to analyse these drugs and other chemicals with pharmaceutical uses as well as previous toxicological data in this vertebrate after 48 h of exposure. It is estimated that the partition coefficient, log P, is the main physicochemical property related to the ecotoxicological data and can be used for the development of a mathematical model.

Keywords: Acute toxicity; Drugs; Fish embryo test; Lethal effects; QSAR; Sublethal effects; Zebrafish.

MeSH terms

  • 1-Octanol / chemistry
  • Animals
  • Drug-Related Side Effects and Adverse Reactions
  • Embryo, Nonmammalian / drug effects*
  • Models, Theoretical*
  • Pharmaceutical Preparations / chemistry
  • Quantitative Structure-Activity Relationship
  • Toxicity Tests
  • Water / chemistry
  • Water Pollutants, Chemical / chemistry*
  • Water Pollutants, Chemical / toxicity*
  • Zebrafish / embryology*

Substances

  • Pharmaceutical Preparations
  • Water Pollutants, Chemical
  • Water
  • 1-Octanol