fatty acid chloride, C12, reaction product with sodium glutamate and sodium hydroxide

Genetic toxicity: in vivo

Administrative data

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:

key study

Justification for type of information:

Justification for read-across is provided in chapter 13 as separate statement

Cross-reference

Reason / purpose for cross-reference:

assessment report

Reference

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

Reason / purpose for cross-reference:

read-across source

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

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

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

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

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:

Key result

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

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)

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.

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

fatty acid chloride, C12, reaction product with sodium glutamate and sodium hydroxide

EC Number:

947-842-3

IUPAC Name:

fatty acid chloride, C12, reaction product with sodium glutamate and sodium hydroxide

Test material form:

solid: particulate/powder

Results and discussion

Test results

Key result

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

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.