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Diss Factsheets

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (only 1000 bone marrow cells scored, limited evaluated parameters, evaluation criteria not clearly specified, TS purity not specified, no GLP).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
only 1000 bone marrow cells scored [instead of 2000 immature erythrocytes per animal], limited evaluated parameters, evaluation criteria not clearly specified
GLP compliance:
no
Type of assay:
micronucleus assay

Test material

Constituent 1
Reference substance name:
Copper, [29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]-, [[3-(1-methylethoxy)propyl]amino]sulfonyl derivs.
EC Number:
279-767-0
EC Name:
Copper, [29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]-, [[3-(1-methylethoxy)propyl]amino]sulfonyl derivs.
Cas Number:
81457-65-0
IUPAC Name:
81457-65-0
Details on test material:
- Lot/batch No.: EN 80104
No additional details provided

Test animals

Species:
hamster, Chinese
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Ciba-Geigy Ltd. Tierfarm, 4334 Sisseln, Switzerland
- Weight at study initiation: 20-28 g for females, 21-33 g for males
- Fasting period before study: overnight prior to dosing
- Housing: individually
- Diet (e.g. ad libitum): Hamster food, NAFAG No. 924, Nafag AG, Gossau, SG; ad libitum
- Water (e.g. ad libitum): drinking water; ad libitum
- Acclimation period: no data (not applicable)

ENVIRONMENTAL CONDITIONS (the animal room was air conditioned)
- Temperature (°C): 21-23°C
- Humidity (%): 56-60%
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: peanut oil (arachid oil)
- Concentration of test material in vehicle: 5.65, 11.7 and 23.4 mg/ml
- Amount of vehicle (if gavage or dermal): a total of 20 ml/kg bw was administered
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
The test substance was administered in arachid oil
Duration of treatment / exposure:
2 days
Frequency of treatment:
once a day
Post exposure period:
24 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
116, 234 and 468 mg/kg bw
Basis:
actual ingested
No. of animals per sex per dose:
6
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide
- Route of administration: orally
- Doses / concentrations: 128 mg/kg bw in 20 ml/kg arachid oil

Examinations

Tissues and cell types examined:
bone marrow cells
Details of tissue and slide preparation:
DETAILS OF SLIDE PREPARATION:
Bone marrow was harvested from both femurs and drawn up in siliconized pipette filled with approx. 0.5 µl rat serum. A homogeneous suspension was obtained by aspirating the content of pipette gently about three times. Small drops of the mixture were then transferred on to a slide, spread out by pulling it behind a polished cover glass and the preparations were air-dried. 3 hours later, the slides were successively stained in undiluted May-Gruenwald solution, in May-Gruenwald solution/water (1/1) and then in Giemsa's. After being rinsed in methanol (55%) and washed off twice in water, they were immersed in water, rinsed with distilled water and air-dried. The slides were then cleared in Xylol and mounted in Eukitt.

METHOD OF ANALYSIS:
The slides of 3 female and 3 male animals each of the negative control group, the positive control group and of the groups treated with various doses of the test substance were examined. 1000 bone marrow cells each were scored per animal and the following anomalies were registered: (a) single Jolly bodies; (b) fragments of nuclei in erythrocytes; (c) micronuclei in erythroblasts, (d) micronuclei in leucopoietic cells; (e) polyploid cells.
Evaluation criteria:
not specified
Statistics:
The significance of difference was assessed by X2-test.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Remarks:
In all dosage groups the percentage of cells displaying anomalies of nuclei did not differ significantly from the negative control.
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid

Any other information on results incl. tables

The positive control yielded a marked increase of the percentage of cells with anomalies.Here the mean percentage of anomalies was 5.6, whereas the negative control yielded a percentage of 0.17. The difference is highly significant (p<0.05).

Table 1: Total percent cells with anomalies of nuclei

Treatment

Dose level (mg/kg bw)

Total percent cells with anomalies of nuclei

Peanut oil

0

0.17 ± 0.05

Cyclophosphamid

128

5.63 ± 1.29

 

Test substance

117

0.17 ± 0.10

234

0.12 ± 0.08

468

0.08 ± 0.08

 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative

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