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Description of key information

The oral LD50 study on Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6 has reliability rating 2 and the procedure used meets the requirements of the limit test for acute oral toxicity described by the OECD Guideline 401. The results of this GLP compliant study indicate that the test material has little toxic effect when administered as a single oral dose to the rat at a dose level of 5000 mg/kg bw. The test material used consists of 40% active ingredient and 60% water. As the oral LD50 of the product is > 5000 mg/kg bw, the LD50 of the active ingredient is considered to be > 2000 mg/kg bw.

The dermal LD50 study (OECD Guideline 402) on Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6 is performed according to GLP and has reliability rating 1. It is therefore considered acceptable for classification and labelling purposes. The LD50 of the active ingredient is considered to be > 2000 mg/kg bw, and it does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity.

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:
February 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No data on batch no and composition is included in the study report. Internal data on composition is available. Study according to guideline/standards.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
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: Charles River (UK) Ltd., Margate, Kent, UK
- Age at study initiation: no info except for young adult
- Weight at study initiation: 91 ± 6 g (males), 90 ± 3 g (females)
- Fasting period before study: overnight prior to dosing
- Housing: five per sex in polypropylene cages
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Humidity (%): 49-61
- Air changes (per hr): no info
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 6 To: 20 February 1987
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: not indicated
- Amount of vehicle (if gavage): 20 mL/kg
- Justification for choice of vehicle: no info

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg

DOSAGE PREPARATION (if unusual): the test material was neutralised to a pH of 7.0 using 1.0 M citric acid and then diluted with
distilled water to give a dose volume of 20 mL/kg at a dose level of 5000 mg/kg

Doses:
5000 mg/kg bw
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:frequently after dosing and then daily; BW weekly
- Necropsy of survivors performed: yes
- Other examinations performed: no
Statistics:
Not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
other: no mortality
Mortality:
None
Clinical signs:
One female and five male animals exhibited piloerection within one hour of dosing, one male animal also exhibiting perinasal staining.The animals had fully recovered by Day 2 (Day 1 is day of dosing).
Body weight:
No treatment-related effects
Gross pathology:
No abnormalities noted
Other findings:
No
Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The test material used consists of 40% active ingredient and 60% water. As the oral LD50 of the product is > 5000 mg/kg bw, the LD50 of the active ingredient is considered to be > 2000 mg/kg bw. Therefore the active ingredient is classified as Category V, according to OECD-GHS criteria.
Executive summary:

The toxicity of the test material was assessed following its oral administration to a group of five male and five female rats. The procedure used meets the requirements of the limit test for acute oral toxicity described by the OECD (Organisation for Economic Co-operation and Development). Following overnight fasting rats were administered the test material, by peroral injection, at a dose level of 5000 mg/kg bw. All animals were observed for a fourteen day period for any signs of toxicity or other effects of treatment. One female and five male animals exhibited piloerection within one hour of dosing, one male animal also exhibiting perinasal staining. The animals had fully recovered by Day 2 (Day 1 is day of dosing). No other effects to treatment were observed throughout the duration of the study and no abnormalities were detected at necropsy. The results of this study indicate that the test material, Ampholak YJH, has little toxic effect when administered as a single oral dose to the rat at a dose level of 5000 mg/kg bw. The test material used consists of 40% active ingredient and 60% water. As the oral LD50 of the product is > 5000 mg/kg bw, the LD50 of the active ingredient is considered to be > 2000 mg/kg bw. Therefore it is classified as Category V, according to OECD-GHS criteria.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
02 - 16 May 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.
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
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No 8147, April 2011; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes
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:
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 10 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean (males: 271 grams; females: 186 grams).
- Housing: Individual housing in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle.

IN-LIFE DATES: From: 02 - 16 May 2012
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

The test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D)*, successively covered with aluminum foil and Coban elastic bandage*. A piece of Micropore tape* was additionally used for fixation of the bandages in females only. *. Manufacturers: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul, Minnesota, U.S.A. (Coban & Micropore).

Frequency: Single dosage, on Day 1.

Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.
Duration of exposure:
24 hours.
Doses:
2000 mg/kg (4.63 mL/kg) body weight. Dose levels were corrected for a purity of 40%.

No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Dose volume: 4.63 mL/kg

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: none.
Statistics:
None.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture and/or chromodacryrrhoea were noted in all animals on Day 1 and/or 2. In addition, one female and one male showed piloerection on Day 1. No skin effects were noted on the treated skin during the observation period.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
One female showed smaller spleen compared to normal. No further abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
none
Conclusions:
The dermal LD50 value of Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-ß-alaninate in Wistar rats was established to exceed 2000 mg/kg body weight. Based on these results, Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-ß-alaninate does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Two acute studies are available onSodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6, one on acute oral toxicity and one on acute dermal toxicity.

 

The oral LD50 study on Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6 has reliability rating 2 and the procedure used meets the requirements of the limit test for acute oral toxicity described by the OECD Guideline 401. The reliability rating of 2 is based on the fact that there is no information on batch number or composition of the substance within the report. Internal data on composition is available, and the result from this study is considered to give a true evaluation of the acute oral toxicity potential of the substance. The results of this GLP compliant study indicate that the test material has little toxic effect when administered as a single oral dose to the rat at a dose level of 5000 mg/kg bw. The test material used consists of 40% active ingredient and 60% water. As the oral LD50 of the product is > 5000 mg/kg bw, the LD50 of the active ingredient is considered to be > 2000 mg/kg bw.

The dermal LD50 study (OECD Guideline 402) on Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6 is performed in 2012 according to GLP and has reliability rating 1. It is therefore considered reliable to use for classification and labelling purposes. The LD50 of the active ingredient is considered to be > 2000 mg/kg bw, and it does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity

 

Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate), CAS 94441-92-6 it is a paste with a low vapour pressure of 1.5 mPa at 20°C and therefore inhalation exposure is unlikely. Data on acute inhalation is lacking, but the low potential for inhalation exposure means this is not required.

Justification for selection of acute toxicity – oral endpoint

The available study on Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6, is acceptable for classification and labelling purposes being of Klimisch 2 validity. The LD50 of the active ingredient is considered to be > 2000 mg/kg bw, and it is classified as Category V, according to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011).

Justification for selection of acute toxicity – inhalation endpoint

No inhalation LC50 data is available for Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate), CAS 94441-92-6,  however it is a paste with a low vapour pressure of 1.5 mPa at 20°C, significant exposure to vapours would not be expected at ambient temperatures so the lack of an inhalation LD50 is not considered significant as inhalation is not an expected route of exposure.

Justification for selection of acute toxicity – dermal endpoint

The available study on Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate, CAS No 94441-92-6, is acceptable for classification and labelling purposes being of Klimisch 1 validity. The LD50 of the active ingredient is considered to be > 2000 mg/kg bw, and it does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011), nor the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.

Justification for classification or non-classification

Although the acute oral study has a reliability of 2, it is considered to be correct and based upon the classification criteria according to the Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008, Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate), CAS 94441-92-6 does not have to be classified and labeled with respect to acute oral toxicity in the rat.

 

Based upon the classification criteria according to the Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008, Sodium N-(2-carboxyethyl)-N-(2-ethylhexyl)-β-alaninate), CAS 94441-92-6 does not have to be classified and labeled with respect to acute dermal toxicity in the rat.