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Diss Factsheets

Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

short-term repeated dose toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guideline
according to guideline
OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
not specified
GLP compliance:
Limit test:

Test material

Constituent 1
Reference substance name:
Diiron trioxide
EC Number:
EC Name:
Diiron trioxide
Cas Number:
Constituent 2
Reference substance name:

Test animals


Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
other: unchanged (no vehicle)
Remarks on MMAD:
MMAD / GSD: MMAD = 1.3 - 1.5 µm; GSD = 1.9 - 2.2
Analytical verification of doses or concentrations:
Duration of treatment / exposure:
2 weeks
Frequency of treatment:
6 hours/day, 5 days/week
No. of animals per sex per dose:

Results and discussion

Results of examinations

Clinical signs:
no effects observed
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:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed

Effect levels

Dose descriptor:
Remarks on result:
not determinable
no NOAEC identified

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

In summary, histopathological evaluation of rat lungs exposed to iron oxides revealed findings consistent with a 'poorly suluble particle' effect after the 2 -week exposure period, including the 3 -month postexposure period. Conclusive evidence of bioavailable iron or iron particles that were translocated to extrapulmonary organs was not observed.

Applicant's summary and conclusion

Executive summary:

In a subacute inhalation toxicity study Fe3O4, FeOOH and Fe2O3 particles were administered to Wistar rats (48 male per group) by means of the dynamic directed-flow nose-only technique, with exposure at mean actual concentrations of 0, 185.2, 195.7 and 210.2 mg/m3 air for 6 hours per day, 5 days/week for a total of 2 weeks. As a positive control for lung damage DQ12 was used, administered at 200.4 mg/m3. During the course of a 3-month postexposure period subgroups of rats were sacrified and examined on days 15, 29, 59 and 107. The MMAD of the particles was 1.3 -1.5 µm with a GSD of 1.9 -2.2. The exposure was not associated with any specific clinical signs and consistent changes in body weights. No NOAEC was defined. Iron oxides related findings could not be detected in the extrapulmonary organs (kidneys, testes, liver) both at the end of exposure and after 2 weeks of

recovery. Solubilized Fe was detected within/around the alveolar macrophages, but not in the interstitium and hepatic tissue.

Histopathological evaluations of the lungs demonstrated an effect-pattern consistent with that of poorly soluble particles.

This subacute inhalation toxicity study in the Wistar rats is acceptable and satisfies the guidelines requirement for a subacute inhalation study OECD 412 in rodents.