title: Interactions between cadmium and decabrominated diphenyl ether on blood cells count in rats-Multiple factorial regression analysis.
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.
authors.affiliation: University of Belgrade-Faculty of Pharmacy, Department of Toxicology "Akademik Danilo Soldatović", Vojvode Stepe 450, 11221 Belgrade, Serbia. Electronic address: makitox@pharmacy.bg.ac.rs.
authors.forename: Marijana
authors.initials: M
authors.lastname: Curcic
authors.affiliation: University of Belgrade-Faculty of Pharmacy, Department of Toxicology "Akademik Danilo Soldatović", Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Buha
authors.affiliation: Clinical centre of Serbia, Laboratory of Medical Biochemistry, Pasterova 2, 11000 Belgrade, Serbia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Stankovic
authors.affiliation: Ministry of Agriculture and environmental protection, Ruze Jovanovica 27, 11070 Belgrade, Serbia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Milovanovic
authors.affiliation: University of Belgrade-Faculty of Pharmacy, Department of Toxicology "Akademik Danilo Soldatović", Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Zorica
authors.initials: Z
authors.lastname: Bulat
authors.affiliation: University of Belgrade-Faculty of Pharmacy, Department of Toxicology "Akademik Danilo Soldatović", Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Danijela
authors.initials: D
authors.lastname: Đukić-Ćosić
authors.affiliation: University of Belgrade-Faculty of Pharmacy, Department of Toxicology "Akademik Danilo Soldatović", Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Evica
authors.initials: E
authors.lastname: Antonijević
authors.affiliation: National Poison Control Centre, Crnotravska 17, 11000 Belgrade, Serbia.
authors.forename: Slavica
authors.initials: S
authors.lastname: Vučinić
authors.affiliation: University of Belgrade-Faculty of Pharmacy, Department of Toxicology "Akademik Danilo Soldatović", Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Matović
authors.affiliation: University of Belgrade-Faculty of Pharmacy, Department of Toxicology "Akademik Danilo Soldatović", Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Biljana
authors.initials: B
authors.lastname: Antonijevic
mesh_terms: D000818:Animals; D001772:Blood Cell Count / Q000379:methods; D001773:Blood Cells / Q000187:drug effects* / Q000502:physiology; D002104:Cadmium / Q000097:blood* / Q000633:toxicity*; D004347:Drug Interactions / Q000502:physiology; D055768:Halogenated Diphenyl Ethers / Q000097:blood* / Q000633:toxicity*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis
chemical_list: D055768:Halogenated Diphenyl Ethers; D002104:Cadmium; C010902:decabromobiphenyl ether
keywords: Cadmium; Decabrominated diphenyl ether; Interactions; Multiple factorial regression