Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purity 99.8 %
AZ 04803 of September 5th, 1990, Analytisches Laboratorium Hoechst AG

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: HOECHST AG, Kastengrund, SPFbreeding colony
- Strain: Hoe: NMRKf (SPF71)
- Age at study initiation: 7 weeks
- Weight at study initiation: males: 28 g - 37 g (average 32.4 g); females: 22 g - 28 g (average 25.2 g)
- Housing: 5 animals per makrolon cage
- Diet: Altromin 1324 rat/mice diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 10%
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
Sesame oil
Concentration of test material in vehicle: 15 mg/mL
Amount of vehicle: 10 mL/kg bw
Post exposure period:
24, 48 72 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
1500 mg/kg bw.
Basis:
nominal conc.
No. of animals per sex per dose:
5
Positive control(s):
Endoxan R (cyclophosphamide)
- Route of administration: oral
- Doses / concentrations: 50 mg/kg bw

Examinations

Tissues and cell types examined:
Polychromatic erythrocytes gained from femoral bone marrow.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Negative controls validity:
valid
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
The test results indicate that, under the conditions of the present study, o-chlorobenzal chloride is not mutagenic in the micronucleus test.
Executive summary:

o-Chlorobenzal chloride was tested in the micronucleus test.The test compound was administered orally by gavage to male and female mice. The following doses were tested: 0 and 1500 mg o-chlorobenzal chloride per kg bodyweight.

The 1500 mg o-chlorobenzal chloride dose level was chosen since a preliminary study had shown it to be the maximum tolerated dose level.

The animals were treated once with the test compound and according to the test procedure the animals were killed 24, 48 or 72 hours after administration of the test compound.

EndoxanR was used as positive control substance and was administered orally at a dose of 50 mg per kg bodyweight.

The number of polychromatic and normochromatic erythrocytes containing micronuclei was not increased. The ratio of polychromatic/normochromatic erythrocytes in both male and female remained unaffected by the treatment with o-chlorobenzal chloride and was statistically not different from the control values.

EndoxanR induced in both males and females a marked statistically significant increase in the number of polychromatic cells with micronuclei, indicating the sensitivity of the system. The ratio of polychromatic erythrocytes to normocytes was not changed to a significant extent.

The results indicate that, under the conditions of the present study, o-chlorobenzal chloride is not mutagenic in the micronucleus test.