Sodium 1,4-bis(1,3-dimethylbutyl) sulphonatosuccinate

Endpoint summary

Description of key information

Oral acute toxicity was tested according to OECD 401 method in male rats,  leading to a LD50 of 1750 mg act.ingr./kg bw. Dermal acute toxicity was tested 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:

1957

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: 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 for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

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:

Not provided

Route of administration:

oral: gavage

Vehicle:

water

Doses:

Aerosol MA-80% was diluted with water to a solution of 5% solids.
The doses were 0.31 g/kg, 0.63 g/kg, 1.25 g/kg and 2.50 g/kg in terms of solids (active ingredient).

No. of animals per sex per dose:

5 males

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, body weight

Statistics:

method of moving averages

Sex:

male

Dose descriptor:

LD50

Effect level:

1 750 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: no range calculable

Mortality:

All animals died within 24 hours following 2.5 g act. ingr./kg bw, but all survived at the lower dosages.

Clinical signs:

other: Following lethal doses the animals exhibited profound depression and severe diarrhea prior to death. At the lower dosages the animals were depressed to greater or lesser degree for 24 to 48 hours, but thereafter regained normal appearance and behavi

Gross pathology:

Moderate to severe irritation with hemorrhage of the gastrointestinal tract was found at post-mortem examination in the high dose group.
At autopsy there was a greater than usual distension of the intestines in some instances, but otherwise no significant gross findings in the other dose groups.

Table 1: Dosage & Results

Animal Number	Body weight in Grams	Weight Change in 7 Days	Dosage in g act.ingr./kg bw	Dose in Grams	Dose in ml of Solution	Days to Death
R 9973	103	-	2.50	0.26	5.2	<1
R 9974	109	-	2.50	0.28	5.5	<1
R 9977	106	-	2.50	0.27	5.3	<1
R 9979	94	-	2.50	0.24	4.7	<1
R 9980	94	-	2.50	0.24	4.7	<1
R 9982	101	10	1.25	0.13	2.5	S
R 9983	90	25	1.25	0.12	2.3	S
R 9985	90	24	1.25	0.12	2.3	S
R 9988	101	24	1.25	0.13	2.5	S
R 9989	116	40	1.25	0.15	2.9	S
R 9990	91	22	0.63	0.06	1.14	S
R 9993	99	6	0.63	0.06	1.24	S
R 9995	96	6	0.63	0.06	1.20	S
R 9996	101	14	0.63	0.06	1.26	S
R 9997	108	19	0.63	0.07	1.35	S
R 9998	96	12	0.31	0.03	0.61	S
R 9999	98	12	0.31	0.03	0.62	S
R 10000	100	37	0.31	0.03	0.63	S
R 10001	90	19	0.31	0.03	0.57	S
R 10002	97	13	0.31	0.03	0.61	S

S= Survived

LD₅₀=1.75 g/kg (No Range Calculable)

NOTE: For purposes of calculation of an LD₅₀by the method of moving averages, a mortality of 5/5 at

5g/kg is assumed.

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 of Butanediodic acid, sulfo-, 1,4-bis(1,3-dimethylbutyl) ester, sodium salt is 1.75 g/kg in terms of solids content (active ingredient), and the test item is considered, therefore, to be a slightly toxic by ingestion at single dose. NOTE: For purposes of calculation of an LD50 by the method of moving averages, a mortality of 5/5 at 5g/kg bw is assumed.

Executive summary:

The test item as received (80% solids) was diluted with water to a solution of 5% solids content (act. ingr.), and administered in single doses by gavage to groups of young, male albino rats at dosages ranging from 310, 630, 1250 and 2500 mg act. ingr./kg. All animals died within 24 hours following 2500 mg/kg, but all survived at the lower dosages. The acute oral LD₅₀ was calculated to be 1750 mg active ingredient/kg with no confidence limits determinable. Following lethal doses the animals exhibited profound depression and severe diarrhea prior to death. Moderate to severe irritation with haemorrhage of the gastrointestinal tract was found at post-mortem examination. At the lower dosages the animals were depressed to greater or lesser degree for 24 to 48 hours, but thereafter regained normal appearance and behaviour. They were observed for a total of seven days following the dose, and then sacrificed. At autopsy there was a greater than usual distension of the intestines in some instances, but otherwise no significant gross findings.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 750 mg/kg bw

Quality of whole database:

Reliable (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:

1957

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: 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 for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

other: albino

Sex:

male

Details on test animals or test system and environmental conditions:

Not provided

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the cuff and any excess of the dose were removed
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.5 mL/kg; 5 mL/kg; 10 mL/kg
- Concentration (if solution): solution containing 80 % solids ( 80 % active ingredient)
- Constant concentration used: yes; different volumes

VEHICLE
Not applicable

Duration of exposure:

24 hours

Doses:

2.5 mL/kg, 5.0 mL/kg and 10.0 mL/kg

No. of animals per sex per dose:

4

Control animals:

no

Details on study design:

TEST SITE
- Area of exposure: trunk
- % coverage: Not provided
- Type of wrap if used: a cuff of polyethylene film

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the cuff and any excess of the dose were removed
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.5 mL/kg, 5.0 mL/kg and 10.0 mL/kg
- Concentration (if solution): 80%
- Constant concentration used: different volumes

Statistics:

the method of moving averages

Sex:

male

Dose descriptor:

LD50

Effect level:

5 mL/kg bw

Based on:

test mat.

95% CL:

> 2.6 - < 9.6

Remarks on result:

other: test material is 80% solution

Sex:

male

Dose descriptor:

LD50

Effect level:

4 000 mg/kg bw

Based on:

act. ingr.

95% CL:

> 2 100 - < 7 700

Mortality:

At a dosage of 10 mL/kg there was severe erythema, edema and necrosis of the skin, and all animals died within one to three days following the removal of the dose . At the two lower dosages, there was one death each.

Clinical signs:

other: At a dosage of 10 mL/kg there was severe erythema, edema and necrosis of the skin, and all animals died within one to three days following the removal of the dose having exhibited extreme depression over this interval. Erythema and edema were initially q

Gross pathology:

Post-mortem examination in the high dose group gave additional evidence of severe injury to the skin and abdominal wall.
Survivors were observed for a total of 7 days after application of the dose, and then sacrificed. At autopsy there was no gross pathology that could be related to administration of the product.

Table 1. Dosage & Results

Animal Number	Body weight in Grams	Weight Change in 7 Days	Dosage in mL/kg	Dose in mL	Days to Death
H 815	3372	-	10.0	33.7	3
H 817	3562	-	10.0	35.6	2
H 818	3900	-	10.0	39.0	2
H 819	3580	-	10.0	35.8	<1
H 821	2720	-	10.0	27.2	<1
H 823	3680	-160	5.0	18.4	S
H 824	3142	-	5.0	15.7	4
H 825	4098	-987	5.0	20.5	S
H 826	3091	-182	5.0	15.5	S
H 832	3729	-161	2.5	9.3	S
H 833	3557	-237	2.5	8.9	S
H 835	3805	-	2.5	9.5	4
H 836	4120	-408	2.5	10.3	S

S= Survived

LD₅₀ =5.0 (2.6-9.6) mL/kg as 80% solution

LD₅₀ =4.0 (2.1-7.7) g/kg as contained solids

 

NOTE: For purposes of calculation of anLD₅₀ by the method of moving averages, a mortality of 4/4 at

20 mL/kg is assumed.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the test item for male albino rabbits by single skin application under these circumstances is 5.0 (2.6-9.6) mL/kg, corresponding with 4.0 g/kg bw of the active ingredient.
For purposes of calculation of an LD50 by the method of moving averages a mortality of 4/4 at 20 mL/kg is assumed.

Executive summary:

The test item as received (solution containing 80% solids) was supplied to the closely-clipped skin of male albino rabbits in single doses that remained in contact with the skin for a period of 24 hours. Four animals were used at each of three dosage levels; namely, 2.5 mL/kg, 5 mL/kg and 10 mL/kg respectively. The dose was retained by means of a cuff of polyethylene film which encircled the trunk of the animal. At the end of the period of exposure, the cuff and any excess of the dose were removed, and the skin examined for primary irritation.

At a dosage of 10 mL/kg there was severe erythema, edema and necrosis of the skin, and all animals died within one to three days following the removal of the dose having exhibited extreme depression over this interval. Post-mortem examination gave additional evidence of severe injury to the skin and abdominal wall. At the two lower dosages, there was one death each, and the LD₅₀ was calculated to be 5.0 (2.6-9.6) mL/kg, or 4.0 g/kg bw of the active ingredient.

Erythema and edema were initially quite severe at the lower dosages, but the edema subsided within 24 to 48 hours. Erythema, however, persisted for 4 to 5 days. Survivors were observed for a total of 7 days after application of the dose, and then sacrificed. At autopsy there was no gross pathology that could be related to administration of the product.

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 acute oral toxicity study (Shaffer, 1957) was conducted with the registered substance containing 78-80% active ingredient, diluted with water to a solution of 5% solids content (act. ingr.), and administered in single doses by gavage to groups of young, male albino rats at dosages of 310, 630, 1250 and 2500 mg act. ingr./kg. All animals died within 24 hours following 2500 mg/kg, but all survived at the lower dosages. The acute oral LD₅₀ was calculated to be 1750 mg/kg with no confidence limits determinable. Following lethal doses the animals exhibited profound depression and severe diarrhea prior to death. Moderate to severe irritation with haemorrhage of the gastrointestinal tract was found at post-mortem examination. At the lower dosages the animals were depressed to greater or lesser degree for 24 to 48 hours, but thereafter regained normal appearance and behaviour. They were observed for a total of seven days following the dose, and then sacrificed. At autopsy there was a greater than usual distension of the intestines in some instances, but otherwise no significant gross findings.

Acute dermal toxicity

A key acute dermal toxicity study (Shaffer, 1957) was conducted with the registered substance containing 78-80% active ingredient. The product as received was supplied to the closely-clipped skin of male albino rabbits in single doses that remained in contact with the skin for a period of 24 hours. Four animals were used at each of three dosage levels, namely 2.5, 5 and 10 mL/kg respectively. The dose was retained by means of a cuff of polyethylene film which encircled the trunk of the animal. At the end of the period of exposure, the cuff and any excess of the dose were removed, and the skin examined for primary irritation. At a dosage of 10 mL/kg there was severe erythema, edema and necrosis of the skin, and all animals died within one to three days following the removal of the dose having exhibited extreme depression over this interval. Post-mortem examination gave additional evidence of severe injury to the skin and abdominal wall. At the two lower dosages, there was one death each, and the LD₅₀ was calculated to be 5.0 (2.6-9.6) mL/kg or 4.0 (2.1-7.7) g/kg as contained solids. Erythema and edema were initially quite severe at the lower dosages, but the edema subsided within 24 to 48 hours. Erythema, however, persisted for 4 to 5 days. Survivors were observed for a total of 7 days after application of the dose, and then sacrificed. At autopsy there was no gross pathology that could be related to administration of the product.

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

The test substance is classified according to CLP regulation (No. 1272/2008 of 16 December 2008) as Category 4 for acute oral toxicity with signal word 'Warning'. and Hazard statement H302: Harmfull if swallowed. Based on these results and according to the CLP (No. 1272/2008 of 16 December 2008), the test substance does not need to be classified and has no obligatory labelling requirement for dermal toxicity.