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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study - very well documented, study was performed with Fe3O4 as a representative for the iron oxide group - see Category approach for Fe2O3, Fe3O4, FeOOH, ZnFe2O4 and (Fe,Mn)2O3

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:
Iron oxide
Test material form:
aerosol dispenser: not specified
Remarks:
migrated information: aerosol
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:
air
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

Effect levels

Dose descriptor:
NOAEL
Effect level:
4.7 mg/m³ air
Sex:
male/female
Basis for effect level:
other: see "Remarks"

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.