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.

A Clearance Period After Soluble Lead Nanoparticle Inhalation did not Ameliorate the Negative Effects on Target Tissues Due to Decreased Immune Response

“…After 11 weeks, there was a decrease in the liver weight coefficient in the Pb/cl compared with the control group (p < 0.05). Some contribution to organ weight variability could be due to organ dissection; however, we observed similar alterations of organ weight coefficients after metal NP exposure, as was described previously in other studies [23,24].…”

A clearance period after soluble lead nanoparticle inhalation did not ameliorate the negative effects on target tissues due to decreased immune response

“…weeks, there was a decrease in the liver weight coe cient in the Pb/cl compared with the control group (p < 0.05). Some contribution to organ weight variability could be due to organ dissection; however, we observed similar alterations of organ weight coe cients after metal NP exposure, as was described previously in other studies [30,31].…”

Synthesis, Characterization, and Toxicity Assessment of Zinc Oxide-Doped Manganese Oxide Nanoparticles in a Macrophage Model

“…The toxicity of MnO x NPs has been previously reported by several studies [ 24 , 25 , 26 ]. For instance, an early study showed that 28-day oral repeated exposure to MnO 2 NPs in Wistar rats was associated with larger tissue distribution and increased toxicity (e.g., DNA damage, biochemical and histopathological alterations, etc.)…”

“…It is also recognized that a key attractive property of using MnO x NPs in cancer therapy stems from acting as a transition metal and hence participating in Fenton-like reactions to generate free radicals [ 21 , 22 , 23 ]. Previous reports demonstrated in vivo toxicity following exposure to MnO x NPs with increased toxicity outcomes in comparison to bulk materials [ 24 , 25 , 26 ]. An important toxicological aspect to consider is the biodegradability of ENMs [ 27 ].…”