Registration Dossier

Diss Factsheets

Toxicological information

Genetic toxicity: in vivo

Currently viewing:

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Cross-reference
Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
other information
Justification for type of information:
Justification is provided in the separate statement.
Reason / purpose for cross-reference:
assessment report
Conclusions:
The in-vivo genotoxicity of the registration substance sodium N-lauroyl glutamate is derived based on the read-across to Sodium N-cocoyl glycinate. Sodium N-cocoyl glycinate was found to be not clastogenic in micronucleus study in bone marrow in mice. No significant in-vivo clastogenicity can be derived for the registration substance sodium N-lauroyl glutamte.
Executive summary:

The in-vivo genotoxicity of the registration substance, sodium N-lauroyl glutamate, is derived based on the read-across to sodium N-cocoyl glycinate.

The registration substance and the read-across sources are amides of fatty acids and amino acids and can be characterized as "N-fatty acyl amino acids", of which endogeous occurence and metabolism are known. Based on the comparable chemical structure, comparable phys-chem data and expected comparable metabolism, these compound are likely exhibit comparable toxicity profiles.

 

The in-vivo clastogenicity of sodium N-cocoyl glycinate was investigated in micronucleus study in bone marrow in mice. Male mice were treated intraperitoneally at concentrations of 400, 200, 100 and 50 mg/kg bw, twice with a 24 hours interval. One death was observed in the 200 mg/kg body weight group (1/6 cases), and four deaths were observed in the 400 mg/kg body weight group (4/6 cases). The surviving animals were killed at 24 hours after the final treatment and the bone-marrow smears were prepared. The proportion of polychromatic erythrocytes (PCE) to total erythrocytes was lower in the 100 and 200 mg/kg bw groups, indicating toxic effect in the bone marrow tissue. The percentage of micronucleated polychromatic ethythrocytes (MNPCE) in the treated group was not significantly higher than that in the negative control group.

Sodium N-cocoyl glycinate is not clastogenic in in-vivo test system.

 

Likewise, the registration substance, sodium N-lauroyl glutamate is considered as of no significant clstogenic activity.

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
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
micronucleus assay

Test material

Constituent 1
Reference substance name:
Glycine, N-coco acyl derivs., sodium salts
EC Number:
291-350-5
EC Name:
Glycine, N-coco acyl derivs., sodium salts
Cas Number:
90387-74-9
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 or test system 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
Dose / conc.:
400 mg/kg bw/day
Dose / conc.:
200 mg/kg bw/day
Dose / conc.:
100 mg/kg bw/day
Dose / conc.:
50 mg/kg bw/day
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

Any other information on results incl. tables

Results of micronucleus test in male CD-1 mice after introperitoneal administration of sodium N-cocoyl glycinate

Concentrations (mg/mL)

No. of animals survived / 

No, of animals treated

Frequency of MNPCE (%)

PCE/RBC

Solvent control

6/6

0.07 ± 0.08

58.8 ± 2.68

50 x 2

6/6

0.18 ± 0.10

59.5 ± 7.45

100 x 2

6/6

0.07 ± 0.10

** 48.8 ± 5.83

200 x 2

5/6

0.08 ± 0.11

** 36.8 ± 4.61

400 x 2

2/6

0.10 

 * 50.6 ± 2.69

Positive control (MMC)

6/6

4.77 ± 1.02

* 50.6 ± 2.69

PCE: polychromatic erythrocytes

RBC: total erythrocytes

MNPCE: micronucleated PCE

MMC: mitomycin C

* significantly different from solvent control (P< 0.05)

** significantly different from solvent control (P < 0.01)

Applicant's summary and conclusion

Conclusions:
The in-vivo clastogenicity of sodium N-cocoyl glycinate was investigated in micronucleus study in bone marrow in mice. No significant clastogenicity was found.
Executive summary:

The in-vivo clastogenicity of sodium N-cocoyl glycinate was investigated in micronucleus study in bone marrow in mice. Male mice were treated intraperitoneally at concentrations of 400, 200, 100 and 50 mg/kg bw, twice with a 24 hours interval. One death was observed in the 200 mg/kg body weight group (1/6 cases), and four deaths were observed in the 400 mg/kg body weight group (4/6 cases). The surviving animals were killed at 24 hours after the final treatment and the bone-marrow smears were prepared. The proportion of polychromatic erythrocytes (PCE) to total erythrocytes was lower in the 100 and 200 mg/kg bw groups, indicating toxic effect in the bone marrow tissue. The percentage of micronucleated polychromatic ethythrocytes (MNPCE) in the treated group was not significantly higher than that in the negative control group.

Sodium N-cocoyl glycinate is not clastogenic in in-vivo test system.