Registration Dossier

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:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment
Cross-reference
Reason / purpose:
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

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: IFFA CREDO (L'Arbresle, France)
- Weight at study initiation: 180-210 g
- Housing: solid plastic sides and stainless steel grid tops
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±2
- Humidity (%): 55±15
- Photoperiod (hrs dark / hrs light):12

Administration / exposure

Route of administration:
other: endotracheal administration
Vehicle:
sterile physiological saline (0.15 ml)
Details on exposure:
Endotracheal instillation after anesthetization of the animals
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
Positive control(s):
no data

Examinations

Tissues and cell types examined:
alveolar macrophages, lung cells, peripheral lymphocytes (venous blood) and hepatocytes
Details of tissue and slide preparation:
see below 'any other information on materials and methods'.
Evaluation criteria:
see below 'any other information on materials and methods'.
Statistics:
non-parametric Kruskall-Wallis test and Mann-Whitney U-test

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
Additional information on results:
No statistically significant increase of singe strand breaks was observed in alveolar macrophages, lung cells, peripheral lymphocytes and hepatocytes from endotracheally treated rats, compared to the controls. The mean of the OTM median values for hematite treatment (±S.E.) can be seen in Fig. 1 (see attachment below).

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.