Registration Dossier

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:
key study
Study period:
1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study according to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
GLP compliance:
yes (incl. certificate)
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): Sodium cocoyl glycinate
- Physical state: liquid
- Analytical purity: 28% active
- Composition of test material, percentage of components: 28% active, sodium chloride, water
- Lot/batch No.: 970925
- Expiration date of the lot/batch: 1999
- Stability under test conditions: stable
- Storage condition of test material: refrigerated and shielded conditions

Test animals

Species:
mouse
Strain:
ICR
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Japan
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: 33.2 - 40.6 g
- Assigned to test groups randomly: yes
- Housing: aluminium box-type cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26°C
- Humidity (%): 40 - 70 %
- Air changes (per hr): 10 - 15 cycles per hour
- Photoperiod (hrs dark / hrs light): 12 hour light / dark cycle

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: physiological saline
- Justification for choice of solvent/vehicle: recommended vehicle
- Concentration of test material in vehicle: 0.5, 1, 2 and 4 % (w/v)

Duration of treatment / exposure:
24 hours
Frequency of treatment:
two intraperitoneal injections within a 24 hour interval
Post exposure period:
no post exposure period
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
50 mg/kg body weight
Basis:
other: intraperitoneally administered
Remarks:
Doses / Concentrations:
100 mg/kg body weight
Basis:
other: intraperitoneally administered
Remarks:
Doses / Concentrations:
200 mg/kg body weight
Basis:
other: intraperitoneally administered
Remarks:
Doses / Concentrations:
400 mg/kg body weight
Basis:
other: intraperitoneally administered
No. of animals per sex per dose:
6
Control animals:
yes, concurrent vehicle
Positive control(s):
Mitomycin C

Examinations

Tissues and cell types examined:
bone marrow from right femur
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION:
Doses were selected on the basis of a preliminary dose-range finder.

TREATMENT AND SAMPLING TIMES:
Treatment period was 24 hours. The test solutions were administered intraperitoneally, twice within this 24 hour time interval.

DETAILS OF SLIDE PREPARATION:


METHOD OF ANALYSIS:

OTHER:

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
RESULTS OF RANGE-FINDING STUDY
- Dose range: 250, 500, 1000, 2000 mg/kg body weight
- Solubility: yes
- Clinical signs of toxicity in test animals: yes


RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): no induction of micronuclei
- Appropriateness of dose levels and route: dose levels based on pre-test, intraperitoneal administration is a recommended route
- Statistical evaluation: yes

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Based on the study results, the test item sodium cocoyl glycinate was not mutagenic in the micronucleus test in mice.
Executive summary:

To investigate the potency of eliciting micronuclei in vivo of sodium cocoyl glycinate, a micronucleus study was conducted in male CD-l mice similar to OECD TG 474 in accordance with the principles of GLP. Tested was an aqueous solution of the registered UVCB substance in a typical concentration as put on the market. Based on a preliminary dose-range-finding staudy, sodium cocoyl glycinate was intraperitoneally administered to mice at 400, 200, 100 and 50 mg/kg body weight, twice with a 24-hour interval. The bone-marrow smears were prepared 24 hours following the final administration. One death was observed in the 200 mg/kg body weight group (116 cases), and four deaths were observed in the 400 mg/kg body weight group (4/6 cases). The percentage of MNPCE in each of sodium cocoyl glycinate group was not significantly higher than that in the negative control group. The bone-marrow smears in the negative control group were clearly negative, and the bone-marrow smears in the positive control group were clearly positive. The proportion of PCE to total erythrocytes was also examined, and the growth of erythroblasts was inhibited in the 100 mg/kg body weight or higher concentration groups. Base on the above results, sodium cocoyl glycinate was not clastogenic in this in vivo micronucleus test in mice. Cytotoxicity, most likeley due to the surfactant characteristics of sodium cocoyl glycinate, was observed as determined by the decrease of the number of immature erythroblasts, indicating that the notified chemical has reached the bone marrow.