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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
short-term repeated dose 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:
OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
aerosol dispenser: not specified
Remarks:
migrated information: aerosol

Test animals

Species:
rat
Strain:
Wistar
Sex:
male

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
nose only
Vehicle:
air
Remarks on MMAD:
MMAD / GSD: MMAD = 1.5 µm; GSD ~2
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
6 hours/day 5 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
10.1, 19.7, 45.6, 95.8 mg/m³
Basis:
analytical conc.
No. of animals per sex per dose:
30
Control animals:
yes
Details on study design:
Post-exposure period: 6 month

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
10.1 mg/m³ air
Sex:
male

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

RS-Freetext:
The evaluation of the lungs of rats exposed to four different concentrations of magnetite revealed
findings clearly consistent with a poor soluble particle effect after 4-weeks exposure period followed by a 6-month postexposure period. Conclusive evidence of bioavailable iron particles that were translocated to extrapulmonary organs to any appreciable extent was not observed. Extrapulmonary effects causally linked to the exposure of magnetite were not found at any exposure concentration and time point. At the end of the 6-month postexposure period, the findings causally linked to the exposure to iron oxide (e.g. broncho-alveolar hypercellularity, septal thickening) showed a decrease in incidence and/or severity and occured essentially only at 95.8 mg/m³, a concentration shown to be high enough to cause a self-sustained type of inflammation due to a substantially delayed clearance of particles (t1/2 = 165 days) as a result of lung overload. Thus, the results of this study support the view that the NOAEL of magnetite is 10.1 mg/m³ with borderline effects at 19.7 mg/m³, a concentration considered to be at the transition of lung overloading.

Applicant's summary and conclusion

Conclusions:
NOAEL (no-observed adverse effect level) of Magnetite is 10.1 mg/m³ with borderline effects at 19.7 mg/m³.
Executive summary:
The evaluation of the lungs of rats exposed to four different concentrations of magnetite revealed findings clearly consistent with a poor soluble particle effect after 4-weeks exposure period followed by a 6-month postexposure period. Conclusive evidence of bioavailable iron particles that were translocated to extrapulmonary organs to any appreciable extent was not observed. Extrapulmonary effects causally linked to the exposure of magnetite were not found at any exposure concentration and time point. Thus, the results of this study support the view that the NOAEL of magnetite is 10.1 mg/m³ with borderline effects at 19.7 mg/m³, a concentration considered to be at the transition of lung overloading.