Interactions between cadmium and decabrominated diphenyl ether on blood cells count in rats-Multiple factorial regression analysis

Toxicology. 2017 Feb 1:376:120-125. doi: 10.1016/j.tox.2016.05.011. Epub 2016 May 12.

Abstract

The objective of this study was to assess toxicity of Cd and BDE-209 mixture on haematological parameters in subacutely exposed rats and to determine the presence and type of interactions between these two chemicals using multiple factorial regression analysis. Furthermore, for the assessment of interaction type, an isobologram based methodology was applied and compared with multiple factorial regression analysis. Chemicals were given by oral gavage to the male Wistar rats weighing 200-240g for 28days. Animals were divided in 16 groups (8/group): control vehiculum group, three groups of rats were treated with 2.5, 7.5 or 15mg Cd/kg/day. These doses were chosen on the bases of literature data and reflect relatively high Cd environmental exposure, three groups of rats were treated with 1000, 2000 or 4000mg BDE-209/kg/bw/day, doses proved to induce toxic effects in rats. Furthermore, nine groups of animals were treated with different mixtures of Cd and BDE-209 containing doses of Cd and BDE-209 stated above. Blood samples were taken at the end of experiment and red blood cells, white blood cells and platelets counts were determined. For interaction assessment multiple factorial regression analysis and fitted isobologram approach were used. In this study, we focused on multiple factorial regression analysis as a method for interaction assessment. We also investigated the interactions between Cd and BDE-209 by the derived model for the description of the obtained fitted isobologram curves. Current study indicated that co-exposure to Cd and BDE-209 can result in significant decrease in RBC count, increase in WBC count and decrease in PLT count, when compared with controls. Multiple factorial regression analysis used for the assessment of interactions type between Cd and BDE-209 indicated synergism for the effect on RBC count and no interactions i.e. additivity for the effects on WBC and PLT counts. On the other hand, isobologram based approach showed slight antagonism for the effects on RBC and WBC while no interactions were proved for the joint effect on PLT count. These results confirm that the assessment of interactions between chemicals in the mixture greatly depends on the concept or method used for this evaluation.

Keywords: Cadmium; Decabrominated diphenyl ether; Interactions; Multiple factorial regression.

MeSH terms

  • Animals
  • Blood Cell Count / methods
  • Blood Cells / drug effects*
  • Blood Cells / physiology
  • Cadmium / blood*
  • Cadmium / toxicity*
  • Drug Interactions / physiology
  • Halogenated Diphenyl Ethers / blood*
  • Halogenated Diphenyl Ethers / toxicity*
  • Male
  • Rats
  • Rats, Wistar
  • Regression Analysis

Substances

  • Halogenated Diphenyl Ethers
  • Cadmium
  • decabromobiphenyl ether