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Diss Factsheets

Administrative data

Endpoint:
in vivo mammalian cell study: DNA damage and/or repair
Remarks:
Type of genotoxicity: DNA damage and/or repair
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Mill scale is mainly and primarily composed of high-purity iron oxides (on average above 65%, i.e. FeO, Fe2O3, Fe3O4). Besides, other metal oxides and spinels, elements, and trace compounds such as oil residues <1% for all the uses except for batteries and Melting charge for which <3% can be found in the mill scale. More information on the justification of read across can be found in the attached document in the endpoint summarie of section 7.
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Hematite (Fe2O3) enhances benzo[alpha]pyrene genotoxicity in endotracheally treated rat, as determined by Comet Assay.
Author:
Garry S, Nesslany F, Aliouat EM, Haguenoer JM, and Marzin D.
Year:
2003
Bibliographic source:
Mutation Research, 538: 19-29

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The alkaline single-cell gel electrophoresis (SCGE; Comet Assay) was used to measure DNA single-strand breaks in four cell types (alveolar macrophages, lung cells, peripheral lymphocytes and hepatocytes) of rats after endotracheal administration of a single dose of an iron oxide (hematite; Fe2O3).
GLP compliance:
not specified
Remarks:
It is not customary to refer to GLP compliance in publications
Type of assay:
mammalian comet assay

Test material

Constituent 1
Chemical structure
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
Constituent 2
Reference substance name:
iron(III) oxide
IUPAC Name:
iron(III) oxide
Details on test material:
- Name of test material (as cited in study report): hematite (purchased from Merck, Nogent-sur-Marne, France)
- Molecular formula (if other than submission substance): Fe2O3
- Physical state: solid; particle size of 1 µm
- Analytical purity: >98%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male

Administration / exposure

Route of administration:
other: endotracheal administration
Duration of treatment / exposure:
non relevant;endotracheal instillation, once performed
Frequency of treatment:
single dose
Post exposure period:
24h
Doses / concentrations
Remarks:
Doses / Concentrations:
0.75 mg (about 3.75 mg/kg bw) suspended in 0.15 ml saline; only one dose tested
Basis:
other: dose administered endotracheally
No. of animals per sex per dose:
3
Control animals:
yes, concurrent vehicle

Examinations

Tissues and cell types examined:
alveolar macrophages, lung cells, peripheral lymphocytes (venous blood) and hepatocytes

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Remarks:
for all cell types
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
not examined

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Induction of DNA breaks by the iron oxide after endotracheal administration to rats, was not observed in any of the four cell types tested.
Executive summary:

The alkaline single-cell gel electrophoresis (SCGE; Comet Assay) was used to measure DNA single-strand breaks in four cell types (alveolar macrophages, lung cells, peripheral lymphocytes and hepatocytes) of OFA Sprague–Dawley rats 24 h after endotracheal administration of a single dose of an iron oxide (hematite; Fe2O3) (0.75 mg/animal; about 3.75 mg/kg bw). No statistically significant damage was observed in alveolar macrophages, lung cells, peripheral lymphocytes and hepatocytes from endotracheally treated rats, compared to the controls.

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