Registration Dossier

Administrative data

Description of key information

Key studies were performed for oral acute toxicity according to OECD 401 method in male rats,  leading to a LD50 of >2830 mg act.ingr./kg bw, and for dermal acute toxicity according to OECD 402  method in male rabbits, demonstrating a LD50 of >4000 mg act.ingr./kg bw. Acute inhalation toxicity was waived based upon the fact that acute inhalation exposure as such is very unlikely for sulfosuccinates due to their substance properties

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:
1969
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The study was conducted non-GLP, with limited data on study design, however the study was conducted according to state of the art methods at that time period. The study is considered adequate, reliable and relevant.
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Not provided
- Age at study initiation: Not provided
- Weight at study initiation: mean weight 150-151 g
- Fasting period before study: 24 hours
- Housing: Not provided
- Diet (e.g. ad libitum): Not provided
- Water (e.g. ad libitum): Not provided
- Acclimation period: Not provided

ENVIRONMENTAL CONDITIONS
Not provided

IN-LIFE DATES: Not provided
Route of administration:
oral: unspecified
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20% w/v aqueous solution
- Justification for choice of vehicle: high solubility


MAXIMUM DOSE VOLUME APPLIED: 10.0 g/kg


Doses:
10.0, 5.0, 2.5 and 1.25 g test item/kg bw.
No. of animals per sex per dose:
5 males per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Frequency of observations=daily; Initial and
Terminal weighing
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Not provided
Sex:
male
Dose descriptor:
LD50
Effect level:
3 540 mg/kg bw
Based on:
dissolved
Remarks:
20% w/v aqueous dispersion of the product
Sex:
male
Dose descriptor:
LD50
Effect level:
2 830 mg/kg bw
Based on:
act. ingr.
Mortality:
5/5 animals in the 10.0 g/kg and 5.0 g/kg dose group died in the first 6 hours after dosing .
0/5 animals in the 2.5 g/kg and 1.25 g/kg dose group died during the 14 day observation period.
Clinical signs:
Diarrhea, lethargy, prostration, comatose
Body weight:
See Table 1
Gross pathology:
Survivors-normal
Other findings:
None

Table 1: Single oral dose Surfactant E-196 (80% active) in male albino rats.

              Animals fasted for 24 hours were dosed with 20% w/v aqueous dispersion of the product.

 

Dosage

Onset of (S) Signs, (D) Death, Hours and Days

DIED

Mean Wt.

Time of Recovery, Days

0-6

6-24

2

3

4

5

6

7

8-14

DOSED

I

T

1

2

3

4

5

6

7-14

10.0 g/kg

SD5

 

 

 

 

 

 

 

 

5/5

151

-

 

 

 

 

 

 

 

 5.0 g/kg

SD5

 

 

 

 

 

 

 

 

5/5

150

-

 

 

 

 

 

 

 

 2.5 g/kg

S

 

 

 

 

 

 

 

 

0/5

151

255

R

 

 

 

 

 

 

 1.25 g/kg

S

 

 

 

 

 

 

 

 

0/5

150

265

R

 

 

 

 

 

 

 

LD50= 3.54 g/kg with no range calculable (20% w/v dispersion)

Signs of intoxication: Diarrhea, lethargy, prostration, comatose.

Gross Autopsy: Survivors-normal.

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of Surfactant E-196 (80% active) dosed as an 20% w/v aqueous dispersion = 3.54 g/kg with no calculable range.
The product is considered to be slightly toxic by ingestion in single doses at very high doses (above limit dose) .
Executive summary:

Oral acute toxicity was tested in 5 male albino Wistar rats with a 20% w/v aqueous dispersion of Butanedioic acid, sulfo-, 1,4 -dicyclohexyl ester, sodium salt (80% purity) at 10000, 5000, 2500 and 1250 mg test item/kg bw. In the 10000 and 5000 mg/kg bw dose group all 5 animals died within 6 hours after dosing. In the 2500 and 1250 mg/kg bw dose group all animals survived the 14 days observation period. In all dose groups signs of intoxication were observed ( diarrhea, lethargy, prostration, comatose) and gross autopsy of the survivors was normal.The LD50 was calculated to be 3540 mg/kg; taking into account that the product contained 80% active ingredient LD 50 is corresponding to 2830 mg act.ingr./kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 830 mg/kg bw
Quality of whole database:
Reliable (Klimisch 2)

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
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:
1969
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The study was conducted non-GLP, with limited data on study design, however the study was conducted according to state of the art methods at that time period. The study is considered adequate, reliable and relevant.
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
other: albino
Sex:
male
Details on test animals and environmental conditions:
Not provided
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: Not provided
- % coverage: Not provided
- Type of wrap if used: an impervious cuff

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not provided
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5.0 g/kg (an aqueous paste of the product)
- Constant volume or concentration used: yes
- For solids, paste formed: yes


Duration of exposure:
24 hours
Doses:
5.0 g/kg aqueous paste of Surfactant E-196 (80% active)
No. of animals per sex per dose:
10 male rabbits
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: frequency of observations not provided; Initial and
Terminal weighing
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Not provided
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 4 000 mg/kg bw
Based on:
act. ingr.
Mortality:
1/10 animals died on the sixth day after dosing.
Clinical signs:
Hind leg weakness
Body weight:
Initial mean body weight was 2.84 kg. Terminal mean body weight was 2.75 kg.
Gross pathology:
Gross pathology of the survivors was normal.

Table1. Single dermal dose in male albino rabbits

             An aqueous paste of the product was held under an impervious cuff in continuous 24-hour

             contact with the shaved skin.

Dosage

Onset of (S) Signs, (D) Death, Hours and Days

DIED

Mean Wt.

Time of (R) Recovery, Days

DOSED

0-6

6-24

2

3

4

5

6

7

8-14

 

I

T

1

2

3

4

5

6

7-14

 5.0 g/kg

 

 

 

S

 

 

D1

 

 

1/10

2.84

2.75

 

 

 

 

 

 

R

  LD50 greater than 5.0 g/kg

Signs of intoxication: Hind leg weakness.

Skin irritation: Severe erythema and severe edema followed by eschar formation.

Gross autopsy: Survivors-normal

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
This test item is considered to be pratically non-toxic by single skin application.
Executive summary:

Acute dermal toxicity was tested in 10 male albino rabbits under covered application to the clipped skin of 5.0 g Butanedioic acid, sulfo-, 1,4 -dicyclohexyl ester, sodium salt (80% active ). There was one mortality at day 6 and weakness of the hind legs was seen in one animal. The survivors showed no gross pathology at autopsy.There was a severe erythema and severe edema followed by eschar formation. Dermal LD50 was >5000 mg/kg bw. Taking into account that the product contained 80% active ingredient, the LD50 corresponds with >4000 mg active ingredient/kg bw.

This test item is considered to be practically non-toxic by single skin application.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 000 mg/kg bw
Quality of whole database:
Reliable (Klimisch 2)

Additional information

Acute oral toxicity

A key oral acute toxicity study was performed with the registered substance in 5 male albino Wistar rats with a 20% w/v aqueous dispersion of the test item containing 80% active ingredient (American Cyanamid Company, 1969). Final doses were 10.0, 5.0 , 2.5 and 1.25 g act. ingr./kg bw. In the 10.0 and 5.0 g/kg bw dose group all 5 animals died within 6 hours after dosing. In the 2.5 and 1.25 g/kg bw dose group all animals survived the 14 days observation period. In all dose groups signs of intoxication were observed. The LD50 was calculated to be 3540 mg/kg on product basis or 2830 mg active ingredient/kg bw.

Acute dermal toxicity

A key study acute dermal toxicity study was performed with the registered substance in 10 male albino rabbits under covered application of 0.5 g test item containing 80% active ingredient (American Cyanamid Company, 1969). There was one mortality on day 6 and weakness of the hind legs was seen. The survivors showed no gross pathology at autopsy. There was a severe erythema and severe edema followed by eschar formation. This test item is considered to be practically non-toxic by single skin application. The LD50 was > 5000 mg/kg, corresponding to > 4000 mg active ingredient/kg bw.

Acute inhalation toxicity

Intoxication due to acute inhalation exposure of industrial workers or even the acute inhalation exposure as such is very unlikely for sulfosuccinates due to large particle size, low vapour pressure and high hydrophilic properties of the substance.  Based on these and other physicochemical properties, the inhalation and dermal route are not appropriate, and the default oral route of administration is most appropriate (ECHA R7a Guidance p 342). Additional inhalation testing would therefore neither lead to a better risk assessment, nor improve the safety of applications. On the basis of the argumentation summarized above an acute inhalation toxicity is waived.

 


Justification for selection of acute toxicity – oral endpoint
Key study

Justification for selection of acute toxicity – dermal endpoint
Key study

Justification for classification or non-classification

As LD50 values were above limit dose of 2000 mg/kg bw for oral and dermal application, the test item containing 80% active ingredient does not need to be classified and has no obligatory labelling requirement for acute oral and dermal toxicity according to the EC Directive (No.93/21/EEC) and CLP (No. 1272/2008 of 16 December 2008).