Registration Dossier

Administrative data

Description of key information

The acute toxicity of the registration substance, sodium N-lauroyl glutamate, is derived based on the read-across to sodium N-cocoyl glutamate and 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.

Sodium N-cocoyl glutamate was investigated for its acute oral toxicity according to the OECD 401. Five male and five female rats were treated per gavage at dose 2000 mg/kg bw. No effect was found. LD50 > 2000 mg/kg bw was obtained.

Sodium N-cocoyl glycinate was investigated for its acute oral toxicity according to the OECD 423. Six female rats were treated per gavage at dose 2000 mg/kg bw. No effect was found. LD50 > 2000 mg/kg bw was obtained.

Sodium N-cocoyl glycinate was investigated for its acute dermal toxicity according to the OECD 402. Five male and five female rats were treated semioccusively with 2000 mg/kg bw with the test item. After 24hours the patch was removed and the animals were observed for 14 days, sacrificed and examined macroscopically. No significant effect was found. The LD50 > 2000 mg/kg bw was obtained.

Likewise the registration substance, sodium N-lauroyl glutamate is considered as of low acute toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
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
Reason / purpose for cross-reference:
assessment report
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral toxicity of the registration substance Sodium N-lauroyl glutamate is derived based on the read-across to Sodium N-cocoyl glutamate and Sodium N-cocoyl glycinate. The LD50 > 2000 mg/kg bw can be reliably derived.
Executive summary:

The acute oral toxicity of the registration substance, sodium N-lauroyl glutamate, is derived based on the read-across to sodium N-cocoyl glutamate and sodium N-cocoyl glycinate.

Sodium N-cocoyl glutamate was investigated for its acute oral toxicity according to the OECD 401. Five male and five female rats were treated per gavage at dose 2000 mg/kg bw. No effect was found. LD50 > 2000 mg/kg bw was obtained.

Sodium N-cocoyl glycinate was investigated for its acute oral toxicity according to the OECD 423. Six female rats were treated per gavage at dose 2000 mg/kg bw. No effect was found. LD50 > 2000 mg/kg bw was obtained.

Likewise the LD50 > 2000 mg/kg bw can be reliably derived for the registration substance, sodium N-lauroyl glutamate.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Observation period of 14 days
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
no mortality was found
Clinical signs:
no clinical signs were found
Body weight:
the development of body weight within the observation period of 14 days were normal
Gross pathology:
no effect found
Interpretation of results:
GHS criteria not met
Conclusions:
Sodium N-cocoyl glutamate was investigated for its acute oral toxicity according to the OECD 401. The LD50 > 2000 mg/kg bw was obtained.
Executive summary:

Sodium N-cocoyl glutamate was investigated for its acute oral toxicity according to the OECD 401. Five male and five female rats were treated per gavage with 2000 mg/kg bw with the test item. No effect was found. The LD50 > 2000 mg/kg bw was obtained.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories
- Age at study initiation: 11 weeks
- Weight at study initiation: 178 - 200 g
- Fasting period before study: none, except overnight fasting period before dosing
- Housing: in groups of three in Makrolon type-4 cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 10 - 15 per hour
- Photoperiod (hrs dark / hrs light): light / dark cycle of 12 hours
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Limit dose
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
6 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs and mortality daily, body weighs on test days 1, 8 and 15
- Necropsy of survivors performed: yes
Statistics:
No
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occured during the study
Clinical signs:
No clinical signs observed during the study
Body weight:
not influenced
Gross pathology:
No macroscopic findings were recorded at necropsy
Other findings:
none
Interpretation of results:
GHS criteria not met
Conclusions:
Sodium N-cocoyl glycinate was investigated for its acute oral toxicity according to the OECD 423. The LD50 > 2000 mg/kg bw was obtained.
Executive summary:

Sodium N-cocoyl glutamate was investigated for its acute oral toxicity according to the OECD 423. Six female rats were treated per gavage with 2000 mg/kg bw with the test item. No effect was found. The LD50 > 2000 mg/kg bw was obtained.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Two valid studies on the read-across substances, in which consistent results were obtained.

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
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
Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal toxicity of the registration substance Sodium N-lauroyl glutamate is derived based on the read-across to Sodium N-cocoyl glycinate. The LD50 > 2000 mg/kg bw can be reliably derived.
Executive summary:

The acute dermal toxicity 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 investigated for its acute dermal toxicity according to the OECD 402. Five male and five female rats were treated semioccusively with 2000 mg/kg bw with the test item. After 24hours the patch was removed and the animals were observed for 14 days, sacrificed and examined macroscopically. No significant effect was found. The LD50 > 2000 mg/kg bw was obtained.

Likewise, the acute dermal toxicity of sodium N-lauroyl glutamate is expected to be of no concern.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2010-08-24 to 2010-11-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Test Animals:
Animals: Rat, RccHan: WIST(SPF)
Rationale: Recognized by international guidelines as a recommended test system.
Breeder: Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM / The Netherlands
Number of Animals per Group: 5 males and 5 females
Total Number of Animals: 5 males and 5 females
Age (when treated): Males: 9 weeks, Females: 11 weeks
Body Weight Range (when treated): 228 g – 253 g (males), 189 g – 207 g (females)
Identification: Unique cage number and corresponding color-coded spots on the tail. The animals were marked during acclimatization.
Randomization: Selected by hand at time of delivery. No computer generated randomization program.
Acclimatization: Eight days under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

Environmental Conditions:
Conditions: Standard Laboratory Conditions. Air-conditioned with 10-15 air changes per hour, and continuously monitored environment with ranges for room temperature 22 ± 3 °C and for relative humidity between 30-70%, automatically controlled light cycle of 12 hours light and 12 hours dark, music during the daytime light period.
Accommodation: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding (‘Lignocel’ J. Rettenmaier&Söhne GmbH&CoKG, 73494 Rosenberg / Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) during treatment and observation. Paper enrichment, Reference no. 207057, batch no. 67, (Enviro-dri from Lillico, Biotechnology, Surrey / UK) was included.
Diet: Pelleted standard Teklad Rat-Mouse Diet 2914C, irradiated, batch no. 30/10 (Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) ad libitum. Results of analyses for contaminants are archived at Harlan Laboratories Ltd.
Water: Community tap water from Füllinsdorf ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at Harlan Laboratories Ltd.
Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Details on dermal exposure:
Preparation of Dose Formulations:
Dose levels are in terms of the test item as supplied by the Sponsor. The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume). The formulation was prepared shortly before the application using a magnetic stirrer, a spatula and an Ultra-Turrax as homogenizers. Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

Test Item Administration:
One day before treatment, the backs of the animals were clipped with an electric clipper, exposing an area of approximately 10% of the total body surface. Only those animals without injury or irritation on the skin were used in the test. On test day 1, the test item was applied evenly on the intact skin with a syringe and covered with a surgical gauze pad (ca. 5 x 5 cm) held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and an elastic adhesive restrainer bandage wrapped around the abdomen.
The application volume was 6 mL/kg.
Twenty-four hours after the application the dressing was removed and the skin was flushed with lukewarm tap water and drapped off with disposable paper towels. Thereafter, the reaction sites were assessed. All animals were re-shaved on test day 8 to facilitate the reading of the local reactions.
Rationale: Dermal administration was used as this is one possible route of human exposure during manufacture, handling and use of the test item.
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not required
Details on study design:
Purpose:
The purpose of this study was to assess the acute dermal toxicity of Sodium N-cocoylglycinate when administered to rats by single semi-occlusive dermal application, followed by an observation period of 14 days. This study should provide a rational basis for risk assessment.

Vehicle:
The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date. Therefore, solubility testing was excluded from the statement of compliance. According to the Sponsor, the test item is soluble in water up to a concentration of 25%. Therefore, polyethylene glycol 300 (PEG 300) was used as vehicle and the test item could be dispersed at the technically highest concentration of 33 % (w/w). This was achieved with an Ultra Turrax and resulted in a white liquid, which was considered dermally applicable.
The following information was provided by Harlan Laboratories Ltd.:
Identification: Polyethylene glycol 300 (PEG 300)
Description: Colorless viscous liquid
Lot Number: STBB 3451
Source: Sigma-Aldrich Chemie GmbH, Riedstr. 2, D-89555 / Germany
Stability of the Vehicle: Stable under storage conditions
Expiry Date: 30-Apr-2012
Storage Conditions: At room temperature (range of 20 ± 5 °C), light protected.
Safety Precautions: Routine hygienic procedures were used to ensure the health and safety of the personnel.

Observations:
Viability / Mortality: Daily during the acclimatization period. Once before treatment, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
Clinical Signs: Daily during the acclimatization period. Once before treatment, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. All abnormalities will be recorded.
Local Dermal Signs: Once daily during days 2 (following dressing removal) through day 15 using the numerical scoring system described in Appendix I.
Body Weights: On test days 1 (prior to administration), 8 and 15.

Pathology:
Necropsy: All animals were sacrificed at the end of the observation period by carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. An external examination and opening of the abdominal and thoracic cavities for examinations of major organs was performed. The appearance of any macroscopic abnormalities was recorded. No organs or tissues were retained.

Data Compilation:
Viability/mortality was recorded on data sheets.
Body weights were recorded on-line with the ToxControl Computer System.
Clinical signs, local dermal signs, mortality data and macroscopic findings were compiled into the ToxControl Computer System during recording.
The ToxControl Computer System has been licenced for Harlan Laboratories Ltd. and validated with respect to data collection, storage and retrievability.
Statistics:
No statistical analysis was used.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
No intercurrent deaths occurred during the course of the study.
Clinical signs:
No clinical signs were recorded throughout the entire observation period.
Body weight:
One animal (No. 8) lost body weight (-1.0%) during the first week after test item administration. However, the animal regained weight until the end of the observation period. Otherwise, the body weight of the animals was within the range commonly recorded for animals of this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.

Local dermal signs:

Very slight to slight erythema was observed on test day 2 (1 male) or from test day 2 to test day 4 (1 female) or test day 6 (1 male). Very slight to slight oedema and slightly maculated crusts were observed in one female (No. 10) from test day 2 to 3 or from test day 7 to 15, the end of the observation period. Slight desquamation was noted in one male and three females during test day 3 to test day 7 or 11 and in one male from test day 8 to test day 12. Slight to moderate desquamation was noted in one female from test day 3 to test day 14. The test item caused white to yellow discoloration of the treated skin in two males and one female on test day 2.

Interpretation of results:
GHS criteria not met
Conclusions:
Sodium N-cocoyl glycinate was investigated for its acute dermal toxicity according to the OECD 402. The LD50 > 2000 mg/kg bw was obtained.
Executive summary:

Sodium N-cocoyl glycinate was investigated for its acute dermal toxicity according to the OECD 402. Five male and five female rats were treated semioccusively with 2000 mg/kg bw with the test item. After 24hours the patch was removed and the animals were observed for 14 days, sacrificed and examined macroscopically. No significant effect was found. The LD50 > 2000 mg/kg bw was obtained.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
One valid study on the read-across substance.

Additional information

Justification for classification or non-classification

The acute toxicity of the registration substance sodium N-lauroyl glutamate is derived based on the read-across to Sodium N-cocoyl glutamate and Sodium N-cocoyl glycinate. No concern can be reliably derived for the registration substance for oral and dermal routes and therefore no classification is assigned.

No data is available for inhalation route.