Iron ores, agglomerates

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:

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 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

Details on test animals or test system 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.