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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Genetic toxicity: in vivo

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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: Comparable to guideline study with acceptable restrictions (limited documentation)

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 486 (Unscheduled DNA Synthesis (UDS) Test with Mammalian Liver Cells in vivo)
Deviations:
yes
Remarks:
only one sampling time (12 h) and only 50 cells/animal evaluated
GLP compliance:
not specified
Type of assay:
unscheduled DNA synthesis

Test material

Constituent 1
Chemical structure
Reference substance name:
Nitrobenzene
EC Number:
202-716-0
EC Name:
Nitrobenzene
Cas Number:
98-95-3
Molecular formula:
C6H5NO2
IUPAC Name:
nitrobenzene
Details on test material:
- Name of test material (as cited in study report): nitrobenzene; Eastman Kodak
- Analytical purity: no data

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Labs, Kingston, NY
- Weight at study initiation: 175 - 275 g
- Diet (e.g. ad libitum): NIH-07 feed (Ziegler Brothers, Gardner, PA), ad libitum
- Water (e.g. ad libitum): untreated tap water, ad libitum

Sera from the animals were tested and did not contain antibodies against pneumonia virus of mice, revirus 3, GD VII, Kilham rat virus, H-1, Sendai, mouse adenovirus, mouse hepatitis virus, lymphocytic chorioimeningitis virus or rat corona virus.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: corn oil
- Amount of vehicle (if gavage or dermal): 0.1 - 0.4 mL/100g body weight
Details on exposure:
The highest dose was generally selected to be at or near the LD50 when such information is available.
Duration of treatment / exposure:
single dose
Post exposure period:
Hepatocytes were isolated 12 h after treatment.
Doses / concentrations
Remarks:
Doses / Concentrations:
200 and 500 mg/kg in corn oil
Basis:
actual ingested
No. of animals per sex per dose:
3
Control animals:
yes, concurrent vehicle
Positive control(s):
2-acetylaminofluorene; methylmethanesulfonate, benzidine (genotoxic hepatocarcinogens)
- Route of administration: oral, gavage
- Doses / concentrations: 2-AAF: 50 mg/kg; MMS: 100 mg/kg; benzidine: 200 mg/kg

Examinations

Tissues and cell types examined:
freshly isolated hepatocytes
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: The highest dose was generally selected to be at or near the LD50 when such information is available.


DETAILS OF SLIDE PREPARATION: Cultures were washed twice with Williams Medium E (WE), fixed followed by six washes with deionized water. When dry, coverslips were mounted with permount and dipped in Kodak NTB-2 emulsion diluted 1.1 with water. Slides were exposed for 12 - 14 days at -20°C and developed for quantitative autoradiography.


METHOD OF ANALYSIS: An area of the slide was randomly selected and 50 morphologically unaltered cells were counted (ARKTEK Model 880 colony counter interfaced to a microscope). All counts were made on the "OBJ AREA" mode. The highest of three nuclear-sized areas over the cytoplasm and adjacent to the nucleus was subtracted from the nuclear count to give net grains/nucleus. The percentage of cells in repair, which is a useful indicator of the extent of damage throughout the liver, is defined as those exhibiting five or more net grains.


OTHER: Cells were incubated in WE medium containing 10% fetal calf serum for ca. 90 min at 37 °C to allow attachment of the cells to the coverslips. Cultures were washed and incubated in WE containing 10 µCi/mL 3H-thymidine for 4 hours. Cultures were again washed and incubated overnight (14 - 16 h) in 0.25 mM thymidine.
Evaluation criteria:
Five or more net grains/nucleus was considered positive.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid

Any other information on results incl. tables

Chemical

Dose [mg/kg]

Time [h]

Net grains ± SE

Cells in repair [%] ± SE

Corn oil

2

-5.1 ± 0.5

1 ± 0

12

-4.4 ± 0.5

3 ± 1

Nitrobenzene

200

12

-4.4 ± 1.2

5 ± 2

500

12

-5.6 ± 1.3

6 ± 3

2-AAF

50

2

13.2 ± 2.7

71 ± 7

12

45.0 ± 11.3

96 ± 3

Applicant's summary and conclusion