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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
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

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

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
no
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Specific details on test material used for the study:
Information from study report:
- Name of test material: Hostapur SAS 60
- Appearance/Further information: aqueous slurry (approx. 60 % w/w active ingredient); Hostapur SAS 60 is equal to 60 % Hostapur SAS 93 in water
- Batch number: no information
- Purity (of Hostapur SAS 93): 91-95 % active ingredient
- Solubility and stability of the test substance in the solvent/vehicle: The substance is known to be stable in water (the substance is also marketed in water)

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Hoe:NMRKf (SPF71)
- Source: Hoechst AG
- Age at study initiation: 4-9 weeks
- Weight at study initiation (mean): males 23.6 - 28.9 g, females 21.2 - 26.8 g
- Housing: in groups of 5 animals in plastic cages
- Diet and water: ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
Aqua bidestillata
Details on exposure:
Application volume 20 ml/kg bw

The substance was freshly dissolved in the vehicle immediately before each application
Duration of treatment / exposure:
The test substance was administered twice, administrations separated by 24 hours.
Frequency of treatment:
The test substance was administered twice.
Post exposure period:
6 hours after 2nd administration the animals were sacrificed.
Doses / concentrationsopen allclose all
Dose / conc.:
360 mg/kg bw/day (actual dose received)
Remarks:
(corresponding to 600 mg/kg test material with 60 % act. ingr.)
Dose / conc.:
720 mg/kg bw/day (actual dose received)
Remarks:
(corresponding to 1200 mg/kg test material with 60 % act. ingr.)
Dose / conc.:
1 440 mg/kg bw/day (actual dose received)
Remarks:
(corresponding to 2400 mg/kg test material with 60 % act. ingr.)
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
none

Examinations

Tissues and cell types examined:
Bone marrow smears examined
Details of tissue and slide preparation:
DETAILS OF SLIDE PREPARATION: Bone marrow smears were prepared from one femur of each animal. The smears were stained according to Wright (Journal of Medical Research 7: 138, 1902).

METHOD OF ANALYSIS: 2000 polychromatic erythrocytes were evaluated per animal, the number of normochromatic erythrocytes showing micronuclei was determined, the ratio of polychromatic to normochromatic erythrocytes was calculated.
Statistics:
Wilcoxon's test for the ratio of normochromatic to polychromatic erythrocytes and for the number of normochromatic and polychromatic erythrocytes with micronuclei.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Additional information on results:
No effect on behaviour or general condition was observed in dose groups 600 and 1200 mg/kg bw (act. ingr. 360 and 720 mg/kg bw). Within dose group 2400 mg/kg bw (act. ingr. 1440 mg/kg bw) all animals died (two - 1 male, 1 female - within 2 hours after the first administration, the remaining animals 1 to 2.5 hours after the second administration). A repeat of the testing at the same dosage also induced 100 % mortality.

The number of polychromatic erythrocytes with micronuclei were in dose groups 600 and 1200 mg/kg within historical controls-values. The number of normochromatic erythrocytes with micronuclei were in the same range than the polychromatic erythrocytes.

The evaluation of the bone marrow smears revealed no indications for a test substance-related depression of erythropoesis, but the values of normochromatic erythrocytes scattered in a broad range for treated and control groups.

Overall, no indication for a mutagenic potential was seen in this study.

Applicant's summary and conclusion

Executive summary:

A mouse bone marrow micronucleus test was conducted similar to OECD TG 474 but at a time before the guideline was available. In this study 5 male and 5 female mice per dose group, received two oral (gavage) administrations, separated by 24 hours, at doses of 360, 720, and 1440 mg/kg bw (act. ingr.; corresponding to 600, 1200 or 2400 mg/kg bw test material).

In dose groups 360 and 720 mg/kg bw no effect on behaviour or general conditions was observed after test substance administration. 100 % mortality occurred in the highest dose group, therefore only bone marrow smears of the medium and low dose were assessed for genotoxicity. As result the numbers of polychromatic erythrocytes with micronuclei was unaffected by the treatment. The evaluation of the bone marrow smears revealed no indications for a test substance-related depression of erythropoesis, but the values of normochromatic erythrocytes scattered in a broad range for treated and control groups. Overall, no indication for a mutagenic potential was seen in this study.