title: Size-Dependent Toxicity Differences of Intratracheally Instilled Manganese Oxide Nanoparticles: Conclusions of a Subacute Animal Experiment.
abstract: Incomplete information on toxicological differences of micro- and nanometer-sized particles raised concerns about the effects of the latter on health and environment. Besides chemical composition, size and surface-to-volume ratio of nanoparticles (NPs) can affect toxicity. To investigate size-dependent toxicity differences, we used particles made of dioxide of the neurotoxic heavy metal manganese (Mn), typically found in inhaled metal fumes, in three size ranges (size A, 9.14 ± 1.98 nm; size B, 42.36 ± 8.06 nm; size C, 118.31 ± 25.37 nm). For modeling the most frequent route of exposure to Mn, NPs were given to rats for 6 weeks by intratracheal instillation. Of each NP size, 3 or 6 mg/kg body weight was given while control animals were vehicle treated. Neurotoxicity was assessed by measuring spontaneous locomotor activity in an open field and by recording spontaneous and evoked electrical activity from the somatosensory cortical area. Mn content of brain, lung, and blood, measured by ICP-MS, were correlated to the observed functional alterations to see the relationship between Mn load and toxic effects. Body weight gain and organ weights were measured as general toxicological indices. The toxicity of size A and size B NPs proved to be stronger compared to size C NPs, seen most clearly in decreased body weight gain and altered spontaneous cortical activity, which were also well correlated to the internal Mn dose. Our results showed strong effect of size on NP toxicity, thus, beyond inappropriateness of toxicity data of micrometer-sized particles in evaluation of NP exposure, differentiation within the nano range may be necessary.
authors.affiliation: Department of Public Health, University of Szeged Faculty of Medicine, 6720, Szeged, Dóm tér 10., Hungary. mate.zsuzsanna@med.u-szeged.hu.
authors.forename: Zsuzsanna
authors.identifier: http://orcid.org/0000-0003-0446-5422
authors.initials: Z
authors.lastname: Máté
authors.affiliation: Department of Public Health, University of Szeged Faculty of Medicine, 6720, Szeged, Dóm tér 10., Hungary.
authors.forename: Edina
authors.initials: E
authors.lastname: Horváth
authors.affiliation: Department of Applied and Environmental Chemistry, University of Szeged Faculty of Science and Informatics, Szeged, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Kozma
authors.affiliation: Department of Applied and Environmental Chemistry, University of Szeged Faculty of Science and Informatics, Szeged, Hungary.
authors.forename: Tímea
authors.initials: T
authors.lastname: Simon
authors.affiliation: Department of Applied and Environmental Chemistry, University of Szeged Faculty of Science and Informatics, Szeged, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kónya
authors.affiliation: Department of Public Health, University of Szeged Faculty of Medicine, 6720, Szeged, Dóm tér 10., Hungary.
authors.forename: Edit
authors.initials: E
authors.lastname: Paulik
authors.affiliation: Department of Public Health, University of Szeged Faculty of Medicine, 6720, Szeged, Dóm tér 10., Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Papp
authors.affiliation: Department of Public Health, University of Szeged Faculty of Medicine, 6720, Szeged, Dóm tér 10., Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Szabó
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000069555:Injection, Intratympanic; D008297:Male; D017895:Manganese Compounds / Q000008:administration & dosage; D053758:Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010087:Oxides / Q000008:administration & dosage / Q000633:toxicity*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D018675:Toxicity Tests
chemical_list: D017895:Manganese Compounds; D010087:Oxides; C027424:manganese oxide
keywords: Intratracheal; Manganese; Neurotoxicity; Rat; Toxicity