Feldspar minerals, magnetite and quartz, calcination products of copper mining residues.

Neurotoxicity

Administrative data

Endpoint:

neurotoxicity

Remarks:

other: in vivo and in vitro studies

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: special investigation

Data source

Reference

Reference Type:

publication

Title:

Neurotoxic potential of iron oxide nanoparticles in the rat brain striatum and hippocampus

Author:

Wu J, Ding T, Sun J

Year:

2013

Bibliographic source:

NeuroToxicology 34 (2013) 243–253

Materials and methods

Principles of method if other than guideline:

The study focuses on the effects of Fe3O4-NPs on the striatum and hippocampus, including oxidative injury and the accumulation and retention of Fe3O4-NPs. The study also explores the molecular mechanism of oxidative damage in dopaminergic neurons.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

Test material form:

solid: nanoform

Details on test material:

The Fe3O4-NPs employed in this study were measured by TEM to be 30 nm in size (Fig. 2A) and remained spherical after being labelled with 125I. The hydrodynamic diameters of the Fe3O4-NPs and 125I-Fe3O4-NPs in physiological saline were 496+/- 86 nm and 462+/-75 nm, respectively. Zeta potential determination revealed that the Fe3O4-NPs and 125I-Fe3O4-NPs were 9.1+/- 2.2 mV and 8.4+/- 2.1 mV in physiological saline, respectively. Statistical comparisons showed no significant increases in size or zeta potential in the labelled particles (p > 0.05).

Test animals

Species:

rat

Strain:

other: SD

Sex:

male

Administration / exposure

Route of administration:

other: intranasal

Vehicle:

physiological saline

Duration of treatment / exposure:

The rats in our studies were divided into four groups:
(1) intranasally instilled with 125I-Fe3O4-NPs for 1 day (In1d, euthanised at 1 d);
(2) intranasally instilled with 125IFe3O4-NPs for 7 days (In7d, euthanised at 8 d);
(3) 7 days postinstillation (post in 7d, euthanised at 14 d);
(4) 14 days postinstillation (post in 14d, euthanised at 21 d)

Frequency of treatment:

The rats in our studies were divided into four groups:
(1) intranasally instilled with 125I-Fe3O4-NPs for 1 day (In1d, euthanised at 1 d);
(2) intranasally instilled with 125IFe3O4-NPs for 7 days (In7d, euthanised at 8 d);
(3) 7 days postinstillation (post in 7d, euthanised at 14 d);
(4) 14 days postinstillation (post in 14d, euthanised at 21 d)

No. of animals per sex per dose:

Six animals were euthanised at each time point (2 d, 8 d, 14 d, and 21 d)

Results and discussion

Any other information on results incl. tables

A regional distribution of Fe3O4-NPs was observed in rat brains after the particles were intranasally instilled for seven days. The particles were found to be deposited at particularly high concentrations in the rat striata and hippocampi. Over half of the Fe3O4-NPs were retained in the striata for a minimum of 14 days, and may have induced oxidative damage to the region. However, no injuries were observed in the hippocampi. These in vitro studies demonstrate that Fe3O4-NPs may decrease neuron viability, trigger oxidative stress, and activate JNK- and p53-mediated pathways to regulate the cell cycle and apoptosis. These results also suggest that environmental exposure to Fe3O4-NPs may play a role in the development of neurodegenerative diseases.

Applicant's summary and conclusion

Executive summary:

This study focuses on the effects of Fe3O4-NPs on the striatum and hippocampus, including oxidative injury and the accumulation and retention of Fe3O4-NPs. This study also explores the molecular mechanism of oxidative damage in dopaminergic neurons.

A regional distribution of Fe3O4-NPs was observed in rat brains after the particles were intranasally instilled for seven days. The particles were found to be deposited at particularly high concentrations in the rat striata and hippocampi. Over half of the Fe3O4-NPs were retained in the striata for a minimum of 14 days, and may have induced oxidative damage to the region. However, no injuries were observed in the hippocampi. These in vitro studies demonstrate that Fe3O4-NPs may decrease neuron viability, trigger oxidative stress, and activate JNK- and p53-mediated pathways to regulate the cell cycle and apoptosis. These results also suggest that environmental exposure to Fe3O4-NPs may play a role in the development of neurodegenerative diseases.