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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Justification for type of information:
see attachment "Iron oxide category read-across concept-HH " in IUCLID section 13.2.

Data source

Reference
Reference Type:
publication
Title:
Comparative toxicity of silicon dioxide, silver and iron oxide nanoparticles after repeated oral administration to rats.
Author:
Yun, J.W. et al.
Year:
2015
Bibliographic source:
Journal of Applied Toxicology 35: 681-693.

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
GLP compliance:
not specified
Remarks:
not specified in the publication

Test material

Constituent 1
Chemical structure
Reference substance name:
Diiron trioxide
EC Number:
215-168-2
EC Name:
Diiron trioxide
Cas Number:
1309-37-1
Molecular formula:
Fe2O3
IUPAC Name:
diiron trioxide
Test material form:
solid: nanoform
Details on test material:
Producer: NanoAmor Co, Ltd
Crystallinity: α form
Primary particle size: 60 nm
hydrodynamic size: 117.9 ± 78.0 nm
zeta potential: 13.6 mV

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Dose / conc.:
250 mg/kg bw/day (nominal)
Dose / conc.:
500 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
12 per group

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Description (incidence and severity):
The changes of serum biochemical parameters in the Fe2O3 nanoparticle groups were sporadic and were of a small magnitude, indicating that these differences were not considered dose-related adverse effects of the nanoparticle treatments.
Urinalysis findings:
no effects observed
Behaviour (functional findings):
no effects observed
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not examined

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
> 1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: no adverse effects observed

Target system / organ toxicity

Key result
Critical effects observed:
no

Applicant's summary and conclusion

Conclusions:
In the current repeated dose toxicity study, iron oxide red in water was administered via gavage to groups of 12 female Sprague-Dawley rats at dose levels of 250, 500, and 1000 mg/kg bw/day. The administration occurred daily for a 13-week period.

Fe2O3 nanoparticles had no significant effects on body weight, mean daily food and water consumption, when compared with control groups. There were no treatment-related changes in haematological, serum biochemical parameters or histopathological observations. Some changes in organ weights were observed: decreases in weight of pituitary gland and liver and increases in weight of adrenal gland and testis. According to the authors, ‘these changes were sporadic without dose-dependent trends, indicating that they were not considered toxicologically relevant’. In blood and all tissues tested, including liver, kidney, spleen, lung and brain, the concentration of Fe showed no dose-associated response in comparison to the control groups. Iron concentrations in the urine of Fe2O3 nanoparticle-treated rats showed no significant differences compared to those of control animals. Although not statistically significant, the concentrations of Fe in the faeces of treated animals were found to be higher than those of the control groups. The authors stated that the subchronic oral dosing with Fe2O3 nanoparticles showed no systemic toxicity to rats. The NOAEL was established to be greater than 1000 mg/kg bw/day, the highest dose tested in rats receiving Fe2O3 nanoparticles by gavage.