Sodium 1,2-diisobutoxycarbonylethanesulphonate

Endpoint summary

Description of key information

Oral acute toxicity testing equivalent to OECD 401 test method was performed in male rats, leading to an LD50 of 2772 mg act.ingr./kg bw. Dermal acute toxicity testing equivalent to OECD 402 test method was performed in male rabbits, demonstrating an LD50 > 2250 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:

other: see 'Remark'

Remarks:

The study is performed in male animals only, with a +-45% active ingredient formulation, and not under GLP compliance. The study is conducted similar to OECD standard and shows consistent results, therefore the study is considered to be adequate, reliable and relevant.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

No. animals

Principles of method if other than guideline:

Only male rats were used.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

Not provided

Route of administration:

oral: unspecified

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20% w/v

Doses:

10.0g/kg, 5.0 g/kg and 2.5 g/kg

No. of animals per sex per dose:

5 male rats per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Necropsy of survivors performed: yes
- Body weight: initial & terminal

Sex:

male

Dose descriptor:

LD50

Effect level:

6 160 mg/kg bw

Based on:

test mat.

95% CL:

4 660 - 8 120

Sex:

male

Dose descriptor:

LD50

Effect level:

2 772 mg/kg bw

Based on:

act. ingr.

95% CL:

2 097 - 3 654

Mortality:

5/5 in the 10.0 g/kg group
1/5 in the 5.0 g/kg group
0/5 in the 2.5 g/kg group

Clinical signs:

other: Motor ataxia, dyspnea, comatose, and death within 1 hour at 10 g/kg

Gross pathology:

Decedents: mucosa of stomach and intestines extremely hyperemic
Survivors: normal

Table 1. Body weights & clinical signs

Dosage	Onset of (S) Signs, (D) Death, Hours and Days									Died/Dosed	MEAN WT		Time of (R) Recovery, Days
	0-6	6-24	2	3	4	5	6	7	8-14		I	T	1	2	3	4	5	6	7-14
10.0 g/kg	SD5									5/5	103	-
5.0 g/kg					D1					1/5	106	221
2.5 g/kg										0/5	105	219

 I: initial; T: terminal

 

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

A mortality of 5/5 at a dosage of 20g/kg was assumed for calculation of the rat oral LD50.
The rat oral LD50 is calculated to be 6160mg/kg, corresponding to 2772 mg act.ingr./kg.

Executive summary:

Oral acute toxicity was tested in 5 male albino Wistar rats/group with a test item containing 44 -46% active ingredient at 10, 5 and 2.5 g/kg bw (4500; 2250 and 1125 mg act.ingr./kg bw). In the high dose group all 5 animals died within 6 hours after dosing. In the mid dose group 1 of 5 animals died on day 4; in the low dose group all animals survived. Clinical neurological signs were observed at the highest dose only and gross autopsy showed extremely hyperemic mucosa of stomach and intestines in the decedents, whereas survivors were normal. The LD₅₀ was calculated to be 6160 mg/kg, corresponding to 2772 mg act.ingr./kg

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 772 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:

1969

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study is performed in male animals only, with a +-45% active ingredient formulation, and not under GLP compliance. The study is conducted similar to OECD standard and shows consistent results, therefore the study is considered to be adequate, reliable and relevant.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

male animals only

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

other: albino

Sex:

male

Details on test animals or test system and environmental conditions:

Not provided

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE data: Not provided

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5 g/kg
- Concentration (if solution): Not provided
- Constant volume or concentration used: yes
- For solids, paste formed: yes

VEHICLE: Not applicable

Duration of exposure:

24 hours

Doses:

5.0 g/kg

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations:daily
- Necropsy of survivors performed: yes
- Other examinations performed: body weight initial & terminal

Sex:

male

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 250 mg/kg bw

Based on:

act. ingr.

Mortality:

0/10

Clinical signs:

other: Signs of intoxication: None observed Skin irritation: Well-defined erythema and slight edema followed by desiccation of skin Gross autopsy: Normal

Gross pathology:

Normal

Table1. Body weights and clinical observations

Dosage	Onset of (S) Signs, (D) Death, Hours and Days									Died/ Dosed	MEAN WT		Time of (R) Recovery, Days
	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										0/10	2.91	3.10

I: initial; T: terminal

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No signs of intoxication and normal gross autopsy were observed at the dosage of 5g/kg of the test item in a 24-hour occlusive contact with shaved skin of male albino rabbits. There was a well-defined erythema and slight edema by desiccation of the skin.

Executive summary:

Acute dermal toxiciy study was tested in 10 male albino rabbits under covered application to the clipped skin of 5 g test item containing 44 -46% active ingredient (2250 mg act.ingr./kg bw). There were no mortalities, no signs of intoxication and no gross autopsy. There was a well-defined erythema and slight edema by desiccation of the skin. The LD₅₀ was >5 g/kg bw (corresponding with >2250 mg act.ingr./kg bw).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 250 mg/kg bw

Quality of whole database:

High quality (Klimisch 2)

Additional information

Acute oral toxicity

A key oral acute toxicity study in 5 male albino Wistar rats/group was conducted with the registered substance containing 44-46% active ingredient at 10, 5 and 2.5 g formulation/kg bw (4500; 2250 and 1125 mg act.ingr./kg bw) (American Cyanamid Company, 1969). In the high dose group all 5 animals died within 6 hours after dosing. In the mid dose group 1 of 5 animals died on day 4; in the low dose group all animals survived. Clinical neurological signs were observed at the highest dose only and gross autopsy showed extremely hyperemic mucosa of stomach and intestines in the decedents, whereas survivors were normal.The LD₅₀ was calculated to be 6160 mg/kg, corresponding to 2772 mg act.ingr./kg.

In conclusion, there was no hazard for acute oral toxicity.

Acute dermal toxicity

A key dermal acute toxicity study was performed with the registered substance in 10 male albino rabbits under covered application to the clipped skin of 5 g test item containing 44 -46% active ingredient (2250 mg act.ingr./kg bw) (American Cyanamid Company, 1969). There were no mortalities, no signs of intoxication and no gross autopsy. There was a well-defined erythema and slight edema by desiccation of the skin. The LD₅₀ was >5 g/kg bw (corresponding with >2250 mg act.ingr./kg bw).

In conclusion, there was 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

- The substance did not show acute hzard as LD₅₀values of registered substance for both oral and dermal toxicity exceeded 2000 mg/kg bw.

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

Justification for selection of acute toxicity – oral endpoint
Key study

Justification for selection of acute toxicity – inhalation 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 substance does not need to be classified and has no obligatory labelling requirement for acute oral and dermal toxicity according to CLP (No. 1272/2008 of 16 December 2008).