L-Threonine, N-coco acyl derivs., monosodium salts

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

other: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1997

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

An experimental study on the acute oral toxicity of the test item itself is not available.
According to REACH Regulation Annex XI, 1.5, obligatory endpoints recommended for REACH registration according to REACH Annexes VII – X can be covered by the concept of „Grouping of substances and read-across approach“, in case the respective substances, selected for read-across, exhibit similar physicochemical, toxicological and ecotoxicological properties.
The test item Acylthreoninate TH-CS-11-T and the read-across substance Acylglycinate GCS-11-T are structurally closely related substances, which differ predominantly in the in the amino acid anion (Alaninate vs. Glycinate). According to available experimental studies, both substances exhibit results on major relevant endpoints (physico-chemical properties, environmental fate and behavior, ecotocicity, human toxicity) that are in a comparable range. Moreover, the kind of natural amino acid anion is not expected to have any significant adverse effect contributing to overall substance toxicity of either of the compounds.
Therefore, it can be assumed that the results obtained with these structurally related substances are appropriate according to criteria of REACH Annex XI, 1.5, to serve for read-across for uncovered obligatory endpoints of the test item Acylthreoninate TH-CS-11-T recommended for REACH registration according to REACH Annexes VII and VIII.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

GLP compliance:

not specified

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

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

Molecular formula:

Molecular formula for this UVCB is not available.

IUPAC Name:

Glycine, N-coco acyl derivs., sodium salts

Specific details on test material used for the study:

Name: Sodium cocoyl glycinate
Lot No.: 970925
Description: Clear liquid
Composition: 31.5% solution
Storage: Cool, dark place
Supplier: Fine Chemicals Development Laboratory, Central Research Laboratories, Ajinomoto Co., Inc.

Test animals

Species:

mouse

Strain:

ICR

Sex:

male/female

Details on test animals or test system and environmental conditions:

4-week-old male and female ICR mice were purchased from Charles River Japan. After the 7-day quarantine and acclimatization period, 15 male and 15 female mice that did not have any abnormality in their general condition or growth and whose body weights were similar to the mean body weight were selected for use in the study. The animals were stratified based on body weight, and then randomly allocated to groups (5 mice of each sex per group). The age of the animals at the time of administration was 5 weeks old, and the body weight of the males was 22.8 to 24.8 g, and the body weight of the females was 19.7 g to 23.8 g. This type of animal was chosen because it is most commonly used in acute toxicity studies and there are much background data.
The animals were kept in a polycarbonate cage in an animal-keeping room. The temperature was set at 23 ± 3°C, humidity was set at 55 ± 15%, ventilation was set at 12 cycles per hour (all-fresh-air method) and the lighting period was 12 hours. Three to five mice were kept in one cage during the acclimatization period, and five mice were kept in one cage during the study period. White flakes were laid on the bottom of the cage and were replaced with new flakes once a week. Food was withheld for the period beginning on the afternoon of the day before administration and until 2 hours following administration. At all other times the animals had free access to solid food for laboratory animals CRF-1 and tap water, both during the acclimatization and study periods.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Distilled water for injection was added to 1.6 g or 3.2 g of the test item and mixed. Distilled water for injection was further added to the mixture to prepare 20 mL of 2.5% or 5% (w/v) test item solutions. The solutions were stored in a refrigerator until required for use.
In accordance with Guidelines for Safety Studies in Guidelines for Safety Evaluation of New Cosmetics, two doses were established in this study, i.e. 2000 or 1000 mg/kg bw. The test solution was orally administered forcedly to mice using a flexible Teflon tube. Food was withheld for 18 hours prior to administration. 0.4 mL per 10 g of body weight was administered once during the morning of the day of administration. The mice in the negative control group received distilled water for injection in the same manner as mice in the test article group.

Doses:

2000 or 1000 mg/kg bw

No. of animals per sex per dose:

5 / dose / sex

Control animals:

yes

Details on study design:

Acute toxicity symptoms were observed for two hours immediately following administration. General condition was observed during the afternoon of the day of administration (six hours following administration), and each morning until 14 days following administration (once a day).
All animals were weighed at the time of administration, 1, 7 and 14 days following administration.
All animals were sacrificed humanely by bleeding under ether anesthesia 14 days following administration. Organs were macroscopically observed.

Statistics:

Bartlett’s test for homogeneity was conducted for body weight distribution. If the distribution in both groups was equivalent, one-way analysis of variance (ANOVA) was carried out. If ANOVA revealed a significant difference between the groups, Dunnett’s multiple comparison test (a paired comparison of the mean values of the control and the test article groups) was performed. If the distribution was not equivalent, a Kruskal-Wallis rank-test was performed. If the rank-test revealed a significant difference between the groups, Dunnett’s multiple comparison test (a paired comparison of the mean values of the control and the test article groups) was performed

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality was observed during the study in any group.

Clinical signs:

other: Loss of vigor was observed in one case in the male 2.0 g/kg group, wet hair around the anus was observed in one case in each of the male 1.0 g/kg, male 2.0 g/kg and female 2.0 g/kg groups during the observation period for acute toxicity symptoms. No abnor

Gross pathology:

A cyst in the left kidney in one case and edema in the uterus in one case were observed in the female 1.0 g/kg group. Edema in the left ovary was observed in one case in the female 2.0 g/kg group.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

From this study an oral LD50 value of > 2000 mg/kg bw can be derived.

Executive summary:

In this study no male or female mouse died following single oral administration of the test item at dose levels of 1000 or 2000 mg/kg bw. Loss of vigor was observed in one case in the male 2.0 g/kg group, wet hair around the anus was observed in one case in each of the male 1.0 g/kg, male 2.0 g/kg and female 2.0 g/kg groups during the observation period for acute toxicity symptoms. No abnormality was observed six hours following administration and onwards. Therefore it is considered that these symptoms are temporary and mild. Body weight increase was inhibited one day following administration in the male 1.0 g/kg group. This was not observed in the male 2.0 g/kg group. In autopsies, a cyst in the left kidney in one case and edema in the uterus in one case were observed in the female 1.0 g/kg group. Edema in the left ovary was observed in one case in the female 2.0 g/kg group. However, these conditions develop spontaneously in this type of mouse, and it is considered irrelevant to the administration of the test article. Therefore, from this study an oral LD50 value of > 2000 mg/kg bw can be derived.