Mill scale (ferrous metal)

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

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

Test material information

Constituent 1

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 / concentrations

Doses / concentrations 1

Dose / conc.:

250 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

500 mg/kg bw/day (nominal)

Doses / concentrations 3

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.