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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
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)

Data source

Reference
Reference Type:
publication
Title:
Importance of DNA - adduct formation and gene expression profiling of disease candidate genes in rats exposed to bitumen fumes
Author:
Halter R, Hansen T, Seidel A, Ziemann C, Borlak J
Year:
2007
Bibliographic source:
Journal of Occupational and Environmental Hygiene, 4 (S1), p 44-64

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Principles of method if other than guideline:
Micronucleus formation in peripheral blood and bone marrow
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: low viscosity hydrocarbon liquid
Details on test material:
test material was a paving grade bitumen comprising 70% air-rectified bitumen and 30% vacuum residue

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no information provided
- Age at study initiation: ~ 5 weeks
- Weight at study initiation: no information provided
- Assigned to test groups randomly: yes, by weight
- Fasting period before study: no information provided
- Housing: two / cage
- Diet (e.g. ad libitum): Altomin 1324N ad-lib
- Water (e.g. ad libitum): tap water ad-lib
- Acclimation period: no information provided

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2C
- Humidity (%): 40-70%
- Air changes (per hr): 12-15
- Photoperiod (hrs dark / hrs light): 12:12

IN-LIFE DATES: From: To: no information provided

Administration / exposure

Route of administration:
inhalation
Vehicle:
dilution air
Details on exposure:
Animals were exposed by nose only inhalation to a mixture of aerosol and vapour, generated using an evaportion condensation generator. Exposures were for 4hrs/day, 5 days/week for up to 2 years.
Periheral blood samples were take after 5 days, 1 month and 12 months for micronucleus assessment in erythrocytes
Bone marrow samples were taken after 12 months exposure for micronucleus assessment.
Duration of treatment / exposure:
Up to 104 weeks.
Frequency of treatment:
4hrs/day, 5 days/week
Post exposure period:
none specifed
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 4, 20, 100 mg/m3
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
0, 4.1, 20.7, 103.9 mg/m3
Basis:
analytical conc.
BIA method
Remarks:
Doses / Concentrations:
0, 6.8, 344, 172.5 mg/m3
Basis:
other: converted absolute concentration
Control animals:
yes, sham-exposed
Positive control(s):
none specified

Examinations

Tissues and cell types examined:
Peripheral blood - polychromatic erythtrocytes
Bone marrow - polychromatic erythtrocytes
Details of tissue and slide preparation:
Lithium-heparin treated blood samples were smeared on glass slides and stained with Grunald and Geisma solution for microscopic analysis.
Bome marrow cells were harvested to produce a cell suspension that was smeared on glass slides and stained with Grunwald and Geisma solution for microscopic analysis.
Evaluation criteria:
Comparison of control and bitumen treated animals
Statistics:
No information provided

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Remarks:
Bone marrow micronucleus and peripheral blood
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 Periheral blood erythrocyte micronucleus and bone marrow micronucleus
There was no evidence of increased micronucleu formation in rat bone marrow and peripheral blood cells following up to 12 months exposure to bitumen fumes.
Executive summary:

Male and female rats were exposed by inhalation to a mixture of aerosol and vapour derived from a bitumen fume condensate, collected from a heated storage tank. Following periods of exposure of up to 12 months, there was no evidence of increased micronucleus formation in bone marrow and peripheral blood cells.

Systemic exposure to bitumen fumes was confirmed by presence of PAH metabolites in urine, increased metabolising activity in lung, DNA adducts in respirtatory tissue and repression of RBCcount in bone marrow.

Exposure to bitumen fumes was not genotoxic in an in-vivo micronucleus assay.