pentasodium 3,7,11-tris(carboxylatomethyl)-15-(C12-18)-alkyl-3,7,11,15-tetraazaheptadecane-1,17-dioate

Endpoint summary

Description of key information

For all of the four substances within the amphoteric glycinate substance group there are available acute oral toxicity data. The endpoint data covers the smallest (shortest alky, lowest number amine and carboxymethylated groups, CAS no 2098351-38-1) as well as the biggest structure (longest alkyl-unsaturated, highest number amine and carboxymethylated groups, CAS no 2060541-49-1) within the group. The studies have been performed under GLP and according to current OECD 401 guideline. In all of the studies the maximum dose tested was 5000 mg/kg bw on the technical products. As the technical products consists of approximately 40 % active ingredient, it is estimated that doses corresponding to 2000 mg a.i./kg bw were tested. The LD50 values are therefore considered to be > 2000 mg a.i./kg bw and no classification for acute oral toxicity is therefore required according to CLP.  

No toxic effects were seen within this dose range for any of the tested substances. This is also in line with the QSAR predictions available on this group of structures. ACD ToxSuite indicates LD50 values > 2000 mg/kg bw for all of the four substances. Within a category of structures the acute toxicity is decreased for longer chain lengths, but increased for alkyl chains with higher unsaturation. This is also predicted by the QSAR models.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 August 1993 - 8 September 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Page 3 with GLP compliance statement is missing.

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: from Harlan Olac Ltd., Bicester, Oxon, England.
- Age at study initiation: 4-7 weeks
- Weight at study initiation: 88-103g
- Fasting period before study: Access to food only was prevented overnight prior to and approximately 4 hours after dosing.
- Housing: housed in groups of up to five rats of the same sex in metal cages with wire mesh floors.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 60
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: 25 August 1993 - 8 September 1993

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 4.34 ml/kg

Doses:

5g/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality
Cages of rats were checked at least twice daily for any mortalities.
Bodyweight
The bodyweight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes were calculated.
- Necropsy of survivors performed: yes
- Other examinations performed:
Clinical signs
Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 (a period of seven hours). On subsequent days animals were observed once in the morning and again at the end of the experimental day. This latter observation was at approximately 16.30 hours on week
days or 11.30 hours on Saturdays, Sundays and public holidays. The nature and severity of the clinical signs and time were recorded at each observation. All animals were observed for 14 days after dosing.

Statistics:

not applicable

Preliminary study:

Not performed

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Remarks on result:

other: None of the animals died.

Mortality:

There were no deaths following a single oral dose of Ampholak 7CX at 5.0 g/kg bodyweight.

Clinical signs:

other: Piloerection was observed in all rats within five minutes of dosing. This sign persisted and was accompanied at later intervals on Day 1 by abnormal body carriage (hunched posture) and pallor of the extremities. Recovery of all rats, as judged by external

Gross pathology:

No macroscopic abnormalities were observed for animals killed on Day 15.

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The results of this study indicate that the test material has no toxic effect when administered as a single oral dose to the rat at a dose level of 5000mg/kg body weight. The composition of the test material is estimated to be 40% active ingredient (incl NaCl) and 60 % water. Therefore, based on active ingredient, the tested dose level is considered to be 2000mg/kg body weight based on Amines, N-(3-aminopropyl)-N’-C12-18-alkyltrimethylenedi-, N-(carboxymethyl)derivs., sodium salts (CAS no 2060541-51-5). Under the conditions of this study the LD50 > 2000 mg/kg bw.

Executive summary:

A study was performed to assess the acute oral toxicity of the test material to the rat. The method followed was that described in EEC Methods for the determination of toxicity, Annex to Directive 92169lEEC (OJ No. L383A, 29.12.92), Part B, Method B. 1. Acute toxicity (oral). A group of ten fasted rats (five males and five females) was given a single dose by gavage of the test substance, as supplied, at a dose level of 5.0 g/kg bodyweight. All animals were killed and examined macroscopically on Day 15, the end of the observation period.

There were no deaths. Clinical signs of reaction to treatment consisted of piloerection, abnormal body carriage and pallor of the extremities, recovery was complete by Day 2. All rats achieved anticipated bodyweight gains throughout the study. No abnormalities were recorded at the macroscopic examination on Day 15. Based on the active ingredient of the test material, the LD50 > 2000 mg a.i./kg bw for the Amines, N-(3-aminopropyl)-N’-C12-18-alkyltrimethylenedi-, N-(carboxymethyl)derivs., sodium salts (CAS no 2060541-51-5).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The available study on Amines, N-(3-aminopropyl)-N’-C12-18-alkyltrimethylenedi-, N-(carboxymethyl)derivs., sodium salts (CAS no 2060541-51-5), is performed according the available guidelines, under GLP and is considered acceptable for classification and labelling purposes being of reliability rating 2. Certificate of analysis is not included in the report, but composition of the product is considered to be well known. Also the data on the other three substances within the same group indicates the same lack of toxicity and this is also in line with the QSAR predictions available on this group of structures.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute dermal toxicity

Based on molecular profiling, dermal absorption is expected to be (much) lower than oral. Taking together the low acute oral toxicity profile within the amphoteric, glycinate group of substances, and the expected low dermal absorption, it is not considered justified from an animal well-fare perspective to perform any additional acute dose toxicity studies. 

 

Acute inhalation toxicity

The measured vapour pressure data on the freeze-dried triamine based amphoteric, glycinate with the shortest alkyl chain(Amines, N-(3-aminopropyl)-N’-C12-18-alkyltrimethylenedi-, N-(carboxymethyl)derivs., sodium salts with CAS number 2060541-51-5)is available and used for the entire group. This value is low and also considered to be a worst case compared to the vapour pressure for the aqueous solutions of the substances which are manufactured, used and put on the marked. Taking together the low acute oral toxicity profile within this group of substances and the low vapour pressure of the aqueous technical product in combination with the low potential for aerosol formation, it is not considered justified from an animal well-fare perspective to perform any additional acute dose toxicity studies. 

Justification for classification or non-classification

The conclusion from the available studies within the group of substances, is thatSodium cocoamphopolycarboxyglycinate (Amines, N-(3-aminopropyl)-N’-C12-18-alkyltrimethylenedi-, N-(carboxymethyl)derivs., sodium salts with CAS no 2060541-51-5) and the other three substances within the amphoteric, glycinate substane group, are not to be classified for acute toxicity according to Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008.