Registration Dossier

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

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:
weight of evidence
Study period:
November 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: acceptable well-documented study report which meets basic scientific principles

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
no guideline followed
Guideline:
EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
Version / remarks:
Study conducted prior to guideline publication
Deviations:
yes
Principles of method if other than guideline:
Inhalation exposure of two groups of rats to atmospheres containing 0 or 100 ppm ß-chloroprene, for six hours per day on 5 consecutive days.
Bone marrow prepartion made following termination after the last day of dosing. Slides were examined or poly- and normochromatic erythrocytes and the number of micronuclei per 2000 erythrocytes examined (400 erythrocytes examined per animal)
GLP compliance:
no
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): ß-chloroprene
- Lot/batch No.: No data
- Expiration date of the lot/batch: No data
- Stability under test conditions: No data
- Storage condition of test material: No data
No further details included in the report.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Central Institute for the Breeding of Laboratory Animals
- Age at study initiation: The animals were about 5 weeks old at the start of treatment.
- Weight at study initiation:
- Assigned to test groups randomly: [no/yes, under following basis: ]
- Fasting period before study:
- Housing:All animals were housed in screen-bottomed cages, in air-conditioned rooms
- Diet (e.g. ad libitum): Stock diet ad libitum except during exposure
- Water (e.g. ad libitum): ad libitum except during exposure
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 °C ± 1°C
- Humidity (%):
- Air changes (per hr): Not stated
- Photoperiod (hrs dark / hrs light): 12h/ 12h

IN-LIFE DATES: Not stated in report

Administration / exposure

Route of administration:
inhalation
Vehicle:
Air
Details on exposure:
Details of the expsoure method not included in this report. Animals were exposed to atmospheres containing 0 or 100 ppm Beta-chloroprene in air.
Duration of treatment / exposure:
6 hours/day for 5 consecutive days
During the exposures the animals were housed without food or water in a stainless steel/glass inhalation chamber in wire screen cages, five animals to a cage.
Temperature and humidity inside the chamber was 22 ± 1°C and 60 ± 5% respectively.
After each exposure the animals were returned to their living cages and provided with stock diet and tap water ad libitum.
Body weights were recorded at days 1 and 5 of the exposure period. Immediately after the last exposure the animals were killed by decapitation.
The bone marrow of the femora was flushed with centrifuge tubes containing foetal calf serum and centrifuged. The excess serum was removed.
The cells were then resuspended by mixing gently with a Pasteur pipette.
A drop was placed on a slide cleaned with methanol overnight and spread with a haemocytometer cover glass.
Five slides were prepared from each animal. The smears were air dried, fixed in methanol and stained according to May-Grunwald Giemsa.
A total of 400 erythrocytes on each slide were examined microscopically and the number of micronucleated erythrocytes and the ratio of poly- and normochromatic erythrocytes recorded.
Frequency of treatment:
once daily for 5 days
Post exposure period:
Not applicable
No. of animals per sex per dose:
5 males and 5 females

Examinations

Tissues and cell types examined:
Bone marrow smears prepared from femora.
Poly and normochromatic cell ratios determined and the number of micronucleated cells per 2000 erythrocytes determined.
Details of tissue and slide preparation:
Immediately after the last exposure the animals were killed by decapitation. The bone marrow of the femora was flushed with centrifuge tubes containing foetal calf serum and centrifuged. The excess serum was removed. The cells were then resuspended by mixing gently with a Pasteur pipette. A drop was placed on a slide cleaned with methanol overnight and spread with a haemocytometer cover glass. Five slides were prepared from each animal. The smears were air dried, fixed in methanol and stained according to May-Grunwald Giemsa. A total of 400 erythrocytes on each slide were examined microscopically and the number of micronucleated erythrocytes and the ratio of poly- and normochromatic erythrocytes recorded.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative

Any other information on results incl. tables

GENERAL REACTIONS

No mortality or abnormalities of condition or behaviour, attributable to treatment were observed in any of the animals during the exposure period.

BODY WEIGHT CHANGE

Body weight gain in males as well as in female test animals was less than in the controls. One male of the control group (looking unwell at the start of treatment) weighed considerably less than the rest of the group and was therefore excluded from the calculations of mean body weights.

MICRONUCLEUS TEST

The incidence of micronucleated erythrocytes and the % of polychromatic erythrocytes in the control group and the Beta-chloroprene treated group were comparable.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Based on the results of the study, Beta-chloroprene did not show any evidence of mutagenic activity in the micronucleus test
Executive summary:

Based on the results of the study, Beta-chloroprene did not show any evidence of mutagenic activity in the micronucleus test