Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Key studies for acute oral and dermal toxicity testing in rats and rabbits, respectively, were available for test item containing 35.8% active ingredient. LD50 values were 6500 and 3500 mg act.ingr./kg bw, respectively, therefore there is no acute toxicity hazard.  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:
1955
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented study report which meets basic scientific principles. For some data limited details were available, however the study is relevant, adequate and reliable for classification.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
7 days observation instead of 14 days
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: albino
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Not provided
- Age at study initiation: Not provided
- Weight at study initiation: Not provided
- Fasting period before study: Not provided
- Housing: By groups
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Not provided

ENVIRONMENTAL CONDITIONS: Not provided


Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
10.0, 14.7, 21.5 and 31.6 mL/kg bw . The material as received was reported to contain 35% active ingredient.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration:7 days
- Frequency of observations and weighing: Not provided
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs
Statistics:
Thompson moving average method
Sex:
male
Dose descriptor:
LD50
Effect level:
18.7 mL/kg bw
Based on:
test mat.
Remarks on result:
other: confidence limits from 13.7 to 25.6 mL/kg bw
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 6.6 mL/kg bw
Based on:
act. ingr.
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 6 500 mg/kg bw
Based on:
other: solids content
Remarks on result:
other: confidence limits from 4.8-9.0 g/kg bw
Mortality:
In the 1.0 mL/kg bw dose group 1/5 animals died, in the 14.7 mL/kg dose group 1/5 animals died, in the 21.5 mL/kg dose group 3/5 animals died and in the 31.6 mL/kg dose group 5/5 animals died.
Clinical signs:
Following oral administration of [Trade name], the rats at all dosage levels appeared depressed and exhibited labored respiration and a watery diarrhea. The surviving animals continued to exhibit these signs for 24 or 48 hours following oral administration. Thereafter, the survivors at the two lower dosage levels appeared normal, while those at the 21.5 mL/kg level appeared slightly depressed through the fifth day following dosage.
Body weight:
Not provided
Gross pathology:
Gross autopsies performed upon the animals that died showed the following significant gross pathology: hyperemic lungs, irritation of the gastrointestinal tract, and congested kidneys and adrenals. Gross autopsies performed upon the surviving animals at the end of the observation period showed no significant pathology.
Other findings:
Not provided

Table 1. Acute toxicity of [Trade name] following oral administration of the undiluted material to male albino rats. Values are number of animals dead/number of animals tested, cumulative.

 

Dose (mL/kg)

Time of death (days)

1

2

3

4

5

6

7

10.0

0/5

1/5

1/5

1/5

1/5

1/5

1/5

14.7

0/5

0/5

0/5

1/5

1/5

1/5

1/5

21.5

3/5

3/5

3/5

3/5

3/5

3/5

3/5

31.6

3/5

4/5

4/5

5/5

 

 

 

LD50 (mL/kg) = 18.7

Confidence limits (mL/kg) = 13.7-25.6

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item is considered to be a practically non-toxic material by ingestion in single doses. The acute LD50 of undiluted test item for male albino rats, calculated by the Thompson moving average method, is 18.7 mL/kg of body weight, with confidence limits from 13.7 to 25.6 mL/kg. Based on a concentration of 35% active ingredient, the acute oral LD50 would be approximately 6.6 mL/kg, corresponding to ca. 6500 mg act.ingr./kg bw.
Executive summary:

Groups of five male albino rats each were administered orally by stomach tube the undiluted test item containing 35.8% active ingredient at dosage levels of 10.0, 14.7, 21.5, or 31.6 mL/kg of body weight. Rats at all dosage levels appeared depressed and exhibited labored respiration and a watery diarrhea. The surviving animals continued to exhibit these signs for 24 or 48 hours following oral administration. Thereafter, the survivors at the two lower dosage levels appeared normal, while those at the 21.5 m L/kg level appeared slightly depressed through the fifth day following dosage.
Gross autopsies performed upon the animals that died showed hyperemic lungs, irritation of the gastrointestinal tract, and congested kidneys and adrenals. Surviving animals at the end of the observation period showed no significant pathology.
The acute LD50 of undiluted test item for male albino rats was ca. 6500 mg act.ingr./kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
6 500 mg/kg bw
Quality of whole database:
High quality (Klimisch 2)

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:
1955
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study is performed with a 35,8% active ingredient formulation, and not under GLP compliance. However, the study is conducted according to state of the art methods at that period. Therefore the study is considered to be adequate, reliable and relevant.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Observation period of 7 days instead of 14 days
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
other: albino
Sex:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Not provided
- Age at study initiation: Not provided
- Weight at study initiation: Not provided
- Fasting period before study: Not provided
- Housing: Individually
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Not provided

ENVIRONMENTAL CONDITIONS
Not provided


Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: abdomen
- % coverage: Not provided
- Type of wrap if used: The material was applied to the closely clipped abdominal skin under rubber damming. The trunks of the animals were wrapped securely with a gauze and adhesive tape binder.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours

TEST MATERIAL
- Concentration (if solution): 35.8%
- Constant volume or concentration used: no


Duration of exposure:
24 hours
Doses:
1.00 mL/kg, 2.15 mL/kg, 4.64 mL/kg and 10 mL/kg
No. of animals per sex per dose:
4
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Not provided
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 10 mL/kg bw
Based on:
test mat.
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 3.5 other: g/kg bw
Based on:
act. ingr.
Remarks:
35%
Mortality:
There were no mortalities at any dosage level tested.
Clinical signs:
Throughout the observation period the animals exhibited normal behavior and appearance. A single dermal application produced a mild degree of dermal irritation.
Body weight:
At the time of sacrifice, the majority of the animals exhibited an increase over their initial body weights.
Gross pathology:
At gross autopsy the organs of all animals appeared to be within normal limits.
Other findings:
Not provided
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 of undiluted test item for albino rabbits is > 10 mL/kg bw, corresponding to > 3500 mg act.ingr./kg bw.
Executive summary:

Groups of four albino rabbits were used to study the dermal toxicity and irritative properties of the test item containing 35.8% act. ingr. following a single application of the undiluted material at dosage levels of 1.00, 2.15, 4.64, or 10 mL/kg of body weight. The material was applied to the closely clipped abdominal skin under rubber damming. The trunks of the animals were wrapped securely with a gauze and adhesive tape binder. After an exposure of 24 hours the binders were removed and the abdomens were sponged with water in order to remove any unabsorbed material. The animals were observed for gross signs of dermal irritation and systemic toxicity for a period of seven days, after which they were sacrificed and gross autopsies performed. There were no mortalities at any dosage level tested. A single dermal application produced a mild degree of dermal irritation. The acute dermal LD50 of undiluted test item for albino rabbits is > 10 mL/kg bw, corresponding to > 3500 mg act.ingr./kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 500 mg/kg bw
Quality of whole database:
High quality (Klimisch 2)

Additional information

Acute oral toxicity

In a key acute oral toxicity study, groups of five male albino rats each were administered orally by stomach tube test item containing 35.8% active ingredient at 10.0, 14.7, 21.5, or 31.6mL/kg of body weight (Tusing, 1955). Rats at all dosage levels appeared depressed and exhibited labored respiration and a watery diarrhea. The surviving animals continued to exhibit these signs for 24 or 48 hours following oral administration. Thereafter, the survivors at the two lower dosage levels appeared normal, while those at the 21.5 mL/kg level appeared slightly depressed through the fifth day following dosage. Gross autopsies performed upon the animals that died showed hyperemic lungs, irritation of the gastrointestinal tract, and congested kidneys and adrenals. Surviving animals at the end of the observation period showed no significant pathology. The acute LD50 was ca. 6500 mg act.ingr./kg bw. In conclusion, there is no hazard for acute oral toxicity.

Acute dermal toxicity

In a key acute dermal toxicity, groups of four albino rabbits received a single application of test item containing 35.8% active ingredient at 1.00, 2.15, 4.64, or 10 mL/kg of body weight (Tusing, 1955). The material was applied to the closely clipped abdominal skin under rubber damming. The trunks of the animals were wrapped securely with a gauze and adhesive tape binder. After an exposure of 24 hours the binders were removed and the abdomens were sponged with water in order to remove any unabsorbed material. The animals were observed for gross signs of dermal irritation and systemic toxicity for a period of seven days, after which they were sacrificed and gross autopsies performed. There were no mortalities at any dosage level. The acute dermal LD50 was >10 mL/kg bw, corresponding to >3500 mg act.ingr./kg bw. In conclusion, there is no hazard for acute dermal toxicity.

Acute inhalation toxicity

Inhalation is very unlikely due to large particle size, low vapour pressure and high hydrophilic properties of the substance. Based on these and other physicochemical properties, the inhalation route is not appropriate; the oral and dermal route of administration are therefore applied as first and second relevant routes (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 study is waived.

 

Conclusion

- Based on read across substances showing LD50values >2000 mg/kg bw, there is no hazard for acute oral and dermal toxicity

- Inhalation toxicity testing was waived based upon the fact that acute inhalation exposure as such is very unlikely.


Justification for classification or non-classification

Based on these results and according to the EC Directive (No.93/21/EEC) and CLP (No. 1272/2008 of 16 December 2008), the test substance does not have to be classified and has no obligatory labelling requirement for dermal toxicity.