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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:
02 Oct 2001 - 12 Feb 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
The initial body weights of 4 males were slightly over 45 g (45.8-47.8 g). The historical data used in this study is the summary of the data obtained in the years 1999 and 2000. These deviations, however, do not affect the validity of the study.
Qualifier:
according to
Guideline:
EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
Qualifier:
according to
Guideline:
EPA OPPTS 870.5395 (In Vivo Mammalian Cytogenetics Tests: Erythrocyte Micronucleus Assay)
Qualifier:
according to
Guideline:
JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
Version / remarks:
Kanpoan 287 (Japan EPA), Eisei 127 (MHW) and Heisei 09/10/31 Kikyoku No. 2 (MITI)
GLP compliance:
yes (incl. certificate)
Remarks:
Hessisches Ministerium für Umwelt, Landwirtschaft und Forsten, Wiesbaden
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
- Name of test material (as cited in study report): Protectol PE
- Physical state: colorless liquid
- Analytical purity: 99.9%
- Lot/batch No.: 664287
- Stability under test conditions: The stability of the test substance in water over a period of 96 hours has been verified analytically by the data owner.
- Storage condition of test material: Room temperature, under nitrogen

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: RCC Ltd., Biotechnology and Animal Breeding Division, Füllinsdorf, Switzerland
- Age at study initiation: 8 to 10 weeks at start of acclimatization
- Weight at study initiation: 40.7 ± 4.1 g at start of treatment. The initial body weights of 4 males were slightly over 45 g (45.8 - 47.8 g)
- Assigned to test groups randomly: yes
- Housing: single
- Diet (e.g. ad libitum): pelleted standard diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 4
- Humidity (%): 30 - 60
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: 0.5% CMC (carboxymethyl cellulose)
- Justification for choice of solvent/vehicle: The vehicle was chosen to its relative non-toxicity for the animals.
- Concentration of test material in vehicle: In accordance with the scheduled dose to be tested.
Duration of treatment / exposure:
not applicable
Frequency of treatment:
once
Post exposure period:
24 and 48 h after treatment
Doses / concentrationsopen allclose all
Dose / conc.:
125 mg/kg bw/day (nominal)
Remarks:
10 mL/kg body weight total volume applied
Dose / conc.:
250 mg/kg bw/day (nominal)
Remarks:
10 mL/kg body weight total volume applied
Dose / conc.:
500 mg/kg bw/day (nominal)
Remarks:
10 mL/kg body weight total volume applied
No. of animals per sex per dose:
6 males per dose
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide
- Route of administration: intraperitoneally, once
- Doses / concentrations: 40 mg/kg b.w.

Examinations

Tissues and cell types examined:
Tissue: Bone marrow
Cell type: erythrocytes in bone marrow
Evaluation criteria:
A test substance is classified as mutagenic if it induces either a dose-related increase in the number of micronucleated polychromatic erythrocytes, which clearly exceeds the negative control range or a relevant positive response for at least one of the test points.
A test substance producing neither a dose-related increase in the number of micronucleated polychromatic erythrocytes nor a positive response at any of the test points is considered non-mutagenic in this system.
Statistics:
The statistical significance of the findings at p<0.05 was assessed by means of the non-parametric Mann-Whitney test.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
yes
Remarks:
In the main experiment the males treated with the highest dose (500 mg/kg) showed clear signs of toxicity. For details refer to attached background material.

Any other information on results incl. tables

For tables of results refer to attached background material.

Applicant's summary and conclusion

Conclusions:
Interpretation of results: negative