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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline study - very well documented. Iron(II)Oxide belongs to the iron oxides family and presents comparable physico chemical properties, leading to similar behaviour for the all members of the iron oxide substances. In particular, based on affinity of the chemical structure, Iron Oxide (Fe3O4) and Iron(III)Oxide (Fe2O3) are selected to support read across for the Iron(II)Oxide dossier. Full justification paper is provided in the current Summary Section.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report date:
2006

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Triiron tetraoxide
EC Number:
215-277-5
EC Name:
Triiron tetraoxide
Cas Number:
1317-61-9
Molecular formula:
Fe3O4
IUPAC Name:
Magnetite
Details on test material:
other TS: Fe3O4 (iron content: 69.5%)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Remarks on MMAD:
MMAD / GSD: MMAD was 1.3 µm, GDS ~2
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
6 hours/day 5 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
4.7, 16.6, 52.1 mg/m³
Basis:
analytical conc.
No. of animals per sex per dose:
20
Control animals:
yes

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:
no effects observed
Water consumption and compound intake (if drinking water study):
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Details on results:
The lung and LALN (lung associated lymph nodes) weights were increased at 52.1 mg/m³ in males and at 16.6 mg/m³ in females

Effect levels

Dose descriptor:
NOAEL
Effect level:
4.7 mg/m³ air
Sex:
male/female
Basis for effect level:
other: see any other information on results incl. tables

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

. Rats exposed subchronically to three different concentrations of Fe3O4 revealed findings clearly consistent with and typical for a poorly soluble particle. Congruent with previous studies addressing the retention kinetics of inhaled Fe3O4 particles, neither analytical nor toxicological evidence existed that free, biosoluble iron was liberated from the inhaled dust to any appreciable extend. Also in this study no evidence of extrapulmonary toxicity existed. With regard to indices considered to be adverse, viz. increased counts of cells and especially PMNs in BAL, elevated LDH as marker of cytotoxicity, and ß-NAG as marker of increased lysosomal activities 4.7 mg/m³ constitute an exposure level without evidence of adversity. These findings match those observed by histopathology

Applicant's summary and conclusion

Executive summary:
Rats exposed subchronically to three different concentrations of Fe3O4 revealed findings clearly consistent with and typical for a poorly soluble particle. The retention kinetics of inhaled Fe3O4 particles revealed neither analytical nor toxicological evidence that free, biosoluble iron was liberated from the inhaled dust to any appreciable extend. Also in this study no evidence of extrapulmonary toxicity existed. The results of this study support the view, that the NOAEL of Fe3O4 is 4.7 mg/m³.