Residues (petroleum), hydrodesulfurized vacuum

Genetic toxicity: in vivo

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

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

Test material information

Constituent 1

Reference substance name:

Aerosol of fume condensate from a commercial paving grade bitumen

IUPAC Name:

Aerosol of fume condensate from a commercial paving grade bitumen

Constituent 2

Reference substance name:

70% air-rectified asphalt – CAS 64742-93-4 and 30% vacuum residue – CAS 64741-56-6

IUPAC Name:

70% air-rectified asphalt – CAS 64742-93-4 and 30% vacuum residue – CAS 64741-56-6

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 or test system 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 / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 4, 20, 100 mg/m3
Basis:
nominal conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
0, 4.1, 20.7, 103.9 mg/m3
Basis:
analytical conc.
BIA method

Doses / concentrations 3

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.