Registration Dossier

Administrative data

Description of key information

Several studies for oral and dermal acute toxicity were performed on related substances, demonstrating LD50 >2000 mg/kg bw for both routes. Inhalation toxicity testing was waived based upon the fact that acute inhalation exposure as such is very unlikely due to the physchem properties of the substance and the handling during production and use

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to GLP and valid methods, therefore the study is considered relevant, adequate and reliable for classification.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
other: CD/Crl:CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: At start of administration: approx. 8 weeks
- Weight at study initiation: At start of administration: 169 - 184 g
- Fasting period before study: Approx. 16 hours before administration (only tap water was then available ad libitum)
- Housing: During the 14-day observation period the animals were kept in groups of 3 animals in MAKROLON cages ( type III plus) . Granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany)
- Diet (e.g. ad libitum): Commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (e.g. ad libitum): Drinking water in bottles was offered ad libitum.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C (maximum range)
- Humidity (%): 55% ± 15% (maximum range)
- Air changes (per hr): 12 to 18-fold air change per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: July 18, 2012 To: August 7, 2012
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 4.22 mL/kg bw

DOSAGE PREPARATION (if unusual):
Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1- oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts was used as supplied. The administration volume was 4.22 mL/kg bw for a dose of 2000 mg/kg bw as the density of the test item was 1.14 g/mL and a correction factor of 2.41 was employed in order to correct for a content of the solid material of 41.5% only.
The pH value of the supplied test item was 6.4.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The dose used is selected from a series of defined dose levels. Due to the small number of animals used with this method, there is no need to perform a range finding test.

Doses:
1 dose group (Limit test): 2000 mg/kg bw (dose level refers to the solids ingredients of the test item)
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. All surviving animals were observed for a period of 14 days. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study. Changes in weight were calculated and recorded.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity as well as behaviour pattern; tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma), body weight, gross pathology
Statistics:
No statistical analysis could be performed (the method used is not intended to allow a calculation of a precise LD50 value).
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: actual ingested (gavage)
Mortality:
No death was recorded within the test period.
Clinical signs:
Under the present test conditions, a single oral administration of 2000 mg Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1- oxo(C12-C18(even numbered) and C18unsaturated)¬alkyl))¬amino]ethyl]esters, disodium salts/kg bw did not reveal any signs of toxicity.
Body weight:
All animals gained the expected weight throughout the whole study period.
Gross pathology:
No pathological changes were observed at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the EC-Commission directive 67/548/EEC and its subsequent amendments on the approximation of the laws, regulations and administrative provision relating to the classification, packaging and labelling of dangerous substances and the results obtained under the present test conditions,Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1- oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts requires no classification (as LD50 > 2000 mg/kg).
Also, according to the EC Regulation 1272/2008 and subsequent regulations, the test material is not classified for acute oral toxicity.
Executive summary:

In this experiment Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1- oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts was examined for acute toxicity after a single oral administration to 6 femaleCD/Crl:CD(SD)rats. The test substance dosed by oral gavage at 2000 mg active ingredient/kg bw did not reveal any signs of toxicity. No death was recorded within the 14 days observation period. All animals gained the expected weight throughout the whole study period. No pathological changes were observed at necropsy.The LD50value was ranked exceeding 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Reliability 2 for all studies

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:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to GLP and valid methods, therefore the study is considered relevant, adequate and reliable for classification.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
other: CD/Crl:CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: At dosing: Males: approx. 8 weeks; Females: Approx. 9 weeks
- Weight at study initiation: At dosing: Males: 215 - 237 g; Females: 217 – 239 g
- Fasting period before study: Approx. 16 hours before administration (only tap water was then available ad libitum)
- Housing: During the 14-day observation period the animals were kept in groups of 3 animals in MAKROLON cages ( type III plus) . Granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany)
- Diet (e.g. ad libitum): Commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (e.g. ad libitum): Drinking water in bottles was offered ad libitum.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C (maximum range)
- Humidity (%): 55% ± 15% (maximum range)
- Air changes (per hr): Not provided
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: July 18, 2012 To: August 6, 2012
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: The shaved intact dorsal skin, between the fore and hind extremities
- % coverage: 5 cm x 6 cm, approx. 1/10 of body surface
- Type of wrap if used: The test item was held in contact with the skin with 8 layers of gauze. The gauze was covered with a plastic sheet and secured with adhesive plaster strips (Omniplast (P. HARTMANN AG, 89522 Heidenheim, Germany) on the application site for 24 hours

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

TEST MATERIAL
- Amount(s) applied (volume or weight with unit) 4.22 mL/kg bw
- Constant volume or concentration used: yes



Duration of exposure:
24 hours
Doses:
1 dose group (Limit test): 2000 mg/kg bw (dose level refers to the solids ingredients of the test item)
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. All animals were observed for a period of 14 days. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study. Changes in weight were calculated and recorded.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity as well as behaviour pattern; tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma), body weight, gross pathology
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
None of the animals died prematurely.
Clinical signs:
Under the present test conditions, a single dermal administration of 2000 mg Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1- oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts/kg bw to rats revealed no signs of toxicity.
Body weight:
All animals gained the expected body weight throughout the whole experimental period.
Gross pathology:
No macroscopic findings were observed at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the EC-Commission directive 67/548/EEC and its subsequent amendments on the approximation of the laws, regulations and administrative provision relating to the classification, packaging and labelling of dangerous substances and the results obtained under the present test conditions,Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1- oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts requires no labeling (as LD50 > 2000 mg/kg).
Also, according to the EC Regulation 1272/2008 and subsequent regulations, the test material is not classified for acute dermal toxicity.
Executive summary:

In this experiment, Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1- oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts was examined for acute toxicity after a single dermal application to rats. One dose level of 2000 mg/kg bw was administered on the shaved intact dorsal skin, between the fore and hind extremities of 5 male and 5 female CD/Crl:CD(SD) rats. The test item was held in contact with the skin with 8 layers of gauze. The gauze was covered with a plastic sheet and secured with adhesive plaster strips on the application site for 24 hours. All animals were observed for a period of 14 days. Under the present test conditions, a single dermal administration of 2000 mg active ingredient/kg bw to rats revealed no signs of toxicity and no deaths. All animals gained the expected body weight throughout the whole experimental period. No macroscopic findings were observed at necropsy.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Reliability 2 for all studies

Additional information

No test data were available for current substance, however read across data were available from:

a) Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1-oxo(C12-C18 (even numbered) and C18 unsaturated)alkyl))amino]ethyl]esters, disodium salts

b) Reaction product of (R)-12-hydroxy-N-(2-hydroxyethyl)oleamide and maleic anhydride and sodium hydrogensulfite.

c) Lanoline alcohol sulphosuccinated sodium salt.

d) Alkenes hydroformylated, sulfosuccinates, sodium salt

All results are consistent and the results can be applied also to the registered substance


Justification for selection of acute toxicity – oral endpoint
All studies are perfomed on similar substances, all composed by the same sulphosuccinic part and differrent chainlenghts: chainlenght can vary from very high molecular weight (like in hydroformilation products and lanoline) to relatively low like in the dioctyl drivative. They contribute and agree to the same result. The substance is not toxic for acute oral exposure

Justification for selection of acute toxicity – dermal endpoint
All studies are perfomed on similar substances, all composed by the same sulphosuccinic part and differrent chainlenghts: chainlenght can vary from very high molecular weight (like in hydroformilation products and lanoline) to relatively low like in the dioctyl drivative. They contribute and agree to the same result. The substance is not toxic for acute dermal exposure

Justification for classification or non-classification

Oral acute toxicity

The substance is not classified for oral toxicity because it doesn't meet the classification criteria of the CLP regulation n. 1272/2008:

Oral (mg/kg bodyweight)

Category 1: ATE ≤ 5

Category 2: 5 < ATE≤ 50

Category 3: 50 < ATE≤ 300

Category 4: 300 < ATE≤ 2 000

Different Sufosuccinates were tested, showing acute oral toxicity values >= 2.000 mg/Kg (range 2.000 - 3540 mg/Kg)

Inhalation acute toxicity

According to the Annex VIII of the REACH Regulation n. 1907/2006, inhalation route is not considered appropriate, based also on vapour pressure and the test can be waived.

Dermal acute toxicity

The substance is not classified for dermal toxicity because it doesn't meet the classification criteria of the CLP regulation n. 1272/2008:

Dermal (mg/kg bodyweight)

Category 1: ATE ≤ 50

Category 2: 50 < ATE≤ 200

Category 3: 200 < ATE≤ 1000

Category 4: 1000 < ATE≤ 2000

The value selected is > 2.000 mg/Kg.