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EC number: - | CAS number: -
Toxicological information
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 23 February 1998
- Reliability:
- 1 (reliable without restriction)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 998
- Report date:
- 1998
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- Adopted July 1997
- Deviations:
- not specified
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- quality assurance statement included
- Type of assay:
- other: Micronucleus assay in rats
Test material
- Reference substance name:
- Chondroitin disaccharide deltadi-4S sodium salt
- Cas Number:
- 136144-56-4
- Molecular formula:
- C14H19NO14S•2Na
- IUPAC Name:
- Chondroitin disaccharide deltadi-4S sodium salt
- Reference substance name:
- α-deltaUA-[1→3]-GalNAc-6S = α-[4-deoxy-L-threo-hex-4-enopyranosyluronic acid] sodium salt-[1→3]-N-acetyl-D-galactosamine-6-sulphate
- Cas Number:
- 136132-72-4
- Molecular formula:
- C14H19NO14S•2Na
- IUPAC Name:
- α-deltaUA-[1→3]-GalNAc-6S = α-[4-deoxy-L-threo-hex-4-enopyranosyluronic acid] sodium salt-[1→3]-N-acetyl-D-galactosamine-6-sulphate
- Reference substance name:
- unknown metal constituents
- IUPAC Name:
- unknown metal constituents
- Reference substance name:
- Chloride
- Cas Number:
- 16887-00-6
- Molecular formula:
- Cl
- IUPAC Name:
- Chloride
- Reference substance name:
- Ethanol
- EC Number:
- 200-578-6
- EC Name:
- Ethanol
- Cas Number:
- 64-17-5
- Molecular formula:
- C2H6O
- IUPAC Name:
- Ethanol
- Reference substance name:
- unknown constituent
- Molecular formula:
- unknown
- IUPAC Name:
- unknown constituent
- Reference substance name:
- Glucuronic acid
- EC Number:
- 229-486-4
- EC Name:
- Glucuronic acid
- Cas Number:
- 6556-12-3
- Molecular formula:
- C6H10O7
- IUPAC Name:
- (2S,3S,4S,5R,6R)-3,4,5,6-Tetrahydroxyoxane-2-carboxylic acid / (2S,3S,4S,5R,6R)-3,4,5,6- Tetrahydroxyoxane-2-carboxylic acid
- Reference substance name:
- (2R,3S,5R)-3-amino-6-(hydroxyméthyl)oxane-2,4,5-triol
- Cas Number:
- 7535-00-4
- Molecular formula:
- C6H13NO5
- IUPAC Name:
- (2R,3S,5R)-3-amino-6-(hydroxyméthyl)oxane-2,4,5-triol
- Reference substance name:
- group of unknown constituents
- Molecular formula:
- unknown
- IUPAC Name:
- group of unknown constituents
- Test material form:
- solid
Constituent 1
Constituent 2
Constituent 3
Constituent 4
Constituent 5
Constituent 6
Constituent 7
Constituent 8
Constituent 9
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- 162 g to 190 g (males) 137 g to 164 g (females), 5 to 6 weeks old
Environmental conditions: period of acclimatization of mini 5 days; ventilated rooms; temperature of 22°C and humidity of 55%; lighting 12 hours a day.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- 1% Carboxymethylcellulose in distilled water
- Details on exposure:
- oral intubation
- Frequency of treatment:
- 3 daily treatments
- Post exposure period:
- 24h
Doses / concentrations
- Dose / conc.:
- 2 000 mg/kg bw/day
- Remarks:
- dose administered three times
- No. of animals per sex per dose:
- 2 males and 2 females, exposed to 3 consecutive doses in a preliminary assay, 5 males and 5 females, exposed to 3 consecutive doses of the test substance in a confirmatory assay,
- Control animals:
- yes
- Positive control(s):
- Exposed to cyclophosphamide, a clastogenic agent, at dose of 25 mg/kg (intraperitoneal route)
Examinations
- Tissues and cell types examined:
- Erythrocytes
- Details of tissue and slide preparation:
- The bone marrow is extracted from the rats femurs with foetal calf serum. The cell suspensions are centrifuged for 5 min at 1000 rpm. The supernatant is eliminated and the centrifugate is spread on slides. The smears are stained using a technique derived from the May Grunwald Giemsa technique which makes it possible to distinguish between polychromatic and normochromatic erythrocytes.
- Evaluation criteria:
- Ratio between normochromatic and polychromatic erythrocytes, determined by analysis of 1000 erythrocytes/animal min.
- Statistics:
- Statistical analysis is performed for micronucleus numbers using the Mann Whitney U rank test (non parametric test used because the distribution of the numbers of micronuclei does not correspond to a Gaussian distribution but to a Poisson-type distribution).
The statistical comparison for the polychromatic/normochromatic erythrocyte ratio and for the weight homogeneity within the sex of each group is performed using the Student's test.
Results and discussion
Test results
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Remarks:
- mortality endpoint only
- Vehicle controls validity:
- valid
- Negative controls validity:
- not specified
- Positive controls validity:
- valid
- Additional information on results:
- The validity criteria were fulfilled.
The minimum lethal dose of the test compound was higher than 2000 mg/kg/d (x3) by the oral route in rat. Under these conditions this dose was retained as the limit dose for the micronucleus test according to the OECD guideline recommendation.
There was no statistically significant difference between the weights of trated and control rats.
Applicant's summary and conclusion
- Conclusions:
- In an OECD 474 micronucleus test in male and female rats, no mortality nor clastogenic activity can be demonstrated after 3 administrations of the test substance by oral route at 2000 mg/kg/d.
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