title: Some patterns of metallic nanoparticles' combined subchronic toxicity as exemplified by a combination of nickel and manganese oxide nanoparticles.
abstract: Stable suspensions of NiO and/or Mn3O4 nanoparticles with a mean diameter of 16.7 ± 8.2 nm and 18.4 ± 5.4 nm, respectively, prepared by laser ablation of 99.99% pure metals in de-ionized water were repeatedly injected IP to rats at a dose of 0.50 mg or 0.25 mg 3 times a week up to 18 injections, either separately or in different combinations. Many functional indices as well as histological features of the liver, spleen, kidneys and brain were evaluated for signs of toxicity. The accumulation of Ni and Mn in these organs was measured with the help of AES and EPR methods. Both metallic nanoparticles proved adversely bio-active, but those of Mn3O4 were found to be more noxious in most of the non-specific toxicity manifestations. Moreover, they induced a more marked damaging effect in the neurons of the caudate nucleus and hippocampus which may be considered an experimental correlate of manganese-induced parkinsonism. Mathematical analysis based on the Response Surface Methodology (RSM) revealed a diversity of combined toxicity types depending not only on particular effects these types are assessed for but on their level as well. The prognostic power of the RSM model proved satisfactory.
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, 620014, Russia. Electronic address: bkaznelson@etel.ru.
authors.forename: Boris A
authors.initials: BA
authors.lastname: Katsnelson
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, 620014, Russia.
authors.forename: Ilzira A
authors.initials: IA
authors.lastname: Minigaliyeva
authors.affiliation: Institute of Industrial Ecology, The Urals Branch of the Russian Academy of Sciences, Ekaterinburg, Russia.
authors.forename: Vladimir G
authors.initials: VG
authors.lastname: Panov
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, 620014, Russia.
authors.forename: Larisa I
authors.initials: LI
authors.lastname: Privalova
authors.affiliation: Institute of Industrial Ecology, The Urals Branch of the Russian Academy of Sciences, Ekaterinburg, Russia.
authors.forename: Anatoly N
authors.initials: AN
authors.lastname: Varaksin
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, 620014, Russia.
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Gurvich
authors.affiliation: The Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Ekaterinburg, 620014, Russia.
authors.forename: Marina P
authors.initials: MP
authors.lastname: Sutunkova
authors.affiliation: The Institute of Natural Sciences, The Ural Federal University, Ekaterinburg, Russia.
authors.forename: Vladimir Ya
authors.initials: VY
authors.lastname: Shur
authors.affiliation: The Institute of Natural Sciences, The Ural Federal University, Ekaterinburg, Russia.
authors.forename: Ekaterina V
authors.initials: EV
authors.lastname: Shishkina
authors.affiliation: The Central Research Laboratory of the Ural Medical University, Ekaterinburg, Russia.
authors.forename: Irene E
authors.initials: IE
authors.lastname: Valamina
authors.affiliation: The Central Research Laboratory of the Ural Medical University, Ekaterinburg, Russia.
authors.forename: Oleg H
authors.initials: OH
authors.lastname: Makeyev
mesh_terms: D000818:Animals; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D017895:Manganese Compounds / Q000008:administration & dosage / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D008954:Models, Biological; D009532:Nickel / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D010087:Oxides / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D051381:Rats
chemical_list: D017895:Manganese Compounds; D010087:Oxides; C027424:manganese oxide; D009532:Nickel; C028007:nickel monoxide
keywords: Manganese (II,III) oxide; Mathematical analysis of combined action; Nanoparticles; Nickel (II) oxide; Subchronic toxicity