Mill scale (ferrous metal)

Genetic toxicity: in vivo

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

Test material information

Constituent 1

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.