Butanedioic acid, sulfo-, 4-C12-14 (even numbered)-alkyl esters, disodium salts

Endpoint summary

Description of key information

Acute oral toxicity with read across substance CAS No. 90268-36-3 (Butanedioic acid, sulfo-, 1-C12-18-

alkyl esters, disodium salts) containing >= 90% active ingredient showed an LD50 between 580 and

1400 mg/kg for male and female rats in the key study; the registered substance was therefore considered

harmful if swallowed. Acute dermal toxicity testing in rats with 2 read across substances did not reveal

relevant changes and resulted in an LD50 > 2000 mg/kg bw. Inhalation toxicity testing was waived based

upon the fact that acute inhalation exposure as such is very unlikely for sulfosuccinates due to their

substance properties and the risk management measures that are already implemented.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1986-1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to GLP and valid testing guidance, however limited data on test substance identification were provided. Nevertheless, the study is reliable, relevant and adequate for classification.

Justification for type of information:

See attached read-across justification

Reason / purpose for cross-reference:

read-across source

Sex:

male

Dose descriptor:

LD50

Effect level:

> 580 - < 1 400 mg/kg bw

Based on:

test mat.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 580 - < 1 400 mg/kg bw

Based on:

test mat.

Mortality:

Dose 2000 mg/kg: 2/2 male and 2/2 female animals died 24 hours after application.
Dose 1400 mg/kg: 4/5 male animals died 24 hours after application and 5/5 female animals died 6-24 hours after application.
Dose 580 mg/kg: 0/5 male animals died 14 days after application and 1/5 female died 24hours-14 days after application.

Clinical signs:

other: Dose 2000 mg/kg: Piloerection and decreased activity was seen in all male and female animals (4/4) after ca. 1 h. Piloerection, decreased activity and diarrhea was seen in 2/2 males after ca. 2 h and in 2/2 females after ca. 2-5 h. Piloerection, decreased

Gross pathology:

Dose 2000 mg/kg:
2/2 male animals had a gastro-intestinal tract high-grade filled with liquid, mucosa partially reddish discolored and low-grade emphysema. 2/2 female animals had a bloodily nose and muzzle, otherwise the same symptoms as the males.
Dose 1400 mg/kg:
4/5 males showed strongly reddish discolored medulla, emphysema of the lungs, accumulation of liquid in the thick and small intestine, 1/5 showed no pathological signs. 5/5 female animals showed showed strongly reddish discolored medulla, emphysema of the lungs, accumulation of liquid in the thick and small intestine, and in addition 1/5 female showed low-grade bleedings in the fundus area.
Dose 580 mg/kg:
The male animals had no special findings. 3/5 females had no special findings. 1/5 female had moderate hydrometra, 1/5 female showed a strongly reddish discolored medulla, emphysema of the lungs and accumulation of liquid in the thick and small intestine.

Table 1. Mean body weights and body weight gain

	Males: mean body weights (g)			Females: mean body weights (g)
Dose (mg/kg)	2000	1400	580	2000	1400	580
-1d	212	207	209	178	179	181
Start experiment	201	196	197	165	169	171
2 d	-	186*	212	-	-	175
7 d	-	217*	237	-	-	178
14 d	-	250*	267	-	-	186
Body weight gain	-	43	58	-	-	5

d = days after application

* = value of one survivor

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The oral LD50 of the read-across test item containing ≥ 90% active ingredient was <1400 mg/kg >580 mg/kg for male rats and <1400 mg/kg >580 mg/kg for female rats.

Executive summary:

The acute oral toxicity of the read-across test item containing ≥90% act. ingr. was tested by oral gavage in young Wistar rats at dose levels of 580, 1400 and 2000 mg/kg bw. The read-across test compound was administered by single gavage in aqua dest. as solvent and an application volume of 20 mL/kg bw to fasted animals. Two (low and mid dose) or five rats (high dose) were used per sex and dose. Clinical observations and gross macroscopic observations were observed at all dose levels . The LD₅₀was <1400 mg/kg and >580 mg/kg for male rats and <1400 mg/kg and >580 mg/kg for female rats. According to “Off. J. Europ. Commun., L 257, 1983, p. 18”, the test item can be classified as acute harmful.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

580 mg/kg bw

Quality of whole database:

High quality (Klimish 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:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

See attached read-across justification

Reason / purpose for cross-reference:

read-across source

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:

other: A very slight erythema (barely perceptible) on the application site was observed in all 5 of 5 male and 5 of 5 female animals on test days 2 and 3.

Gross pathology:

No macroscopic findings were observed at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The read-across test item (>95% purity) requires no labelling (as LD50 > 2000 mg/kg bw).
Also, according to the EC Regulation 1272/2008 and subsequent regulations, the read-across test material is not classified for acute dermal toxicity.

Executive summary:

In this experiment, the read-across test item (>95% purity) was examined for acute toxicity after a single dermal application to rats at one dose level of 2000 mg act. ingr./kg bw. The read-across test item was applied once for 24 hours on the shaved intact dorsal skin of rats (5 cm x 6 cm, approx. 1/10 of body surface). This treatment was followed by an observation period of 2 weeks. Under the present test conditions, a single dermal administration of 2000 mg/kg bw to rats revealed no signs of toxicity and no deaths. A very slight erythema (barely perceptible) on the application site was observed in all 5 of 5 male and 5 of 5 female animals on test days 2 and 3. 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

Value:

2 000 mg/kg bw

Quality of whole database:

High quality (Klimisch 1)

Additional information

Acute oral toxicity

No data were available for the registered substance, but read across data were available from subgroup

members (see separate read across justification document for the mono-ester sulfosuccinates in

Section 13):

- A key study for acute oral toxicity was available with test item CAS No. 90268-36-3 ( Butanedioic acid,

sulfo-, 1-C12-18-alkyl esters, disodium salts) containing >= 90% active ingredient dosed by gavage in

Wistar rats at 480, 1400 and 2000 mg/kg bw (Potokar, 1987). Five (for low and mid dose) and two rats

(for high dose) were used per sex. Clinical observations and gross macroscopic observations were

observed at all dose levels. The LD50 was between 580 and 1400 mg/kg for male and female rats,

and therefore the test item was considered harmfull.

- A supporting study with read across substance CAS No. 37294-49-8 ( Disodium C-isodecyl

sulphonatosuccinate) in 5 male albino Wistar rats dosed with 50% active ingredient (Chemical Hygiene

Fellowship Carnegie-Mellon Institute of Research, 1975a) at 10.0; 5.0 and 2.5 mL/kg bw (5000; 2500 and

1250 mg act.ingr./kg bw). All 5 animals died within 6-24 hours after dosing at the highest dose group.

In the 5.0 mL (2500 mg act.ingr.)/kg bw dose group 3 of 5 animals died within 6-24 hours after dosing.

The 2 survivors recovered after 3 days. In the 2.5 mL (1250 mg act.ingr.)/kg bw dose group all animals

survived and recovered after 2 days. At 30 minutes they were sluggish at all dose levels. Gross autopsy

showed slight changes in the lungs, livers, spleens, stomach, intestines and kidneys. The LD50 was

4.67 mL (2340 mg act.ingr.)/kg bw.

- In conclusion, the test item is considered of low toxic potential based on the most detrimental study,

indicating an LD50 between 580 and 1400 mg/kg bw. For the LD50 value, 580 mg/kg was used as

worst case value.

 

Acute dermal toxicity

No data were available for the registered substance, but read across data were available from category

members (see separate read across justification document for the mono-ester sulfosuccinates in

Section 13):

- A key study for acute oral toxicity was available with test item CAS No. 90268-36-3 ( Butanedioic acid,

sulfo-, 1-C12-18-alkyl esters, disodium salts) containing >95% active ingredient (Haferkorn, 2013).

One dose level of 2000 mg/kg bw was employed. The test item was applied once for 24 hours on the

shaved intact dorsal skin of rats (5 cm x 6 cm, approx. 1/10 of body surface). This treatment was followed

by an observation period of 2 weeks. There were no signs of toxicity and no deaths. A very slight erythema

(barely perceptible) on the application site was observed in all 5 of 5 male and 5 of 5 female animals on

test days 2 and 3. All animals gained the expected body weight throughout the whole experimental period.

No macroscopic findings were observed at necropsy.

- In a supporting study with test item CAS No. 37294-49-8 ( Disodium C-isodecyl sulphonatosuccinate)

containing 37% active ingredient (Carpenter, 1971a) at 10.0 and 5.0 mL/kg bw (3700 and 1850 mg

act.ingr./kg bw), all 5 animals of the high dose group died within 6-24 hours after dosing, whereas the

5.0 mL/kg bw dose group all animals survived and recovered after 3 days. At 15 minutes animals were

sluggish at both doses, at 1 hour there was diarrhea at 10 mL/kg. Gross autopsy showed changes in

the lungs, livers, stomach, intestines, kidneys and adrenals. The LD50 was 7.07 mL (2620 mg act.ingr.)/

kg bw.

- In conclusion, there is no hazard for acute dermal toxicity, based on read across substances showing

LD50 values >2000 mg/kg bw.

 

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 is considered of low toxic potential based on the most detrimental study, indicating an
LD50 between 580 and 1400 mg/kg bw. For the LD50 value, 580 mg/kg was used as worst case value.

- There is no hazard for acute dermal toxicity, based on read across substances showing LD50 values >2000 mg/kg bw.

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

Justification for classification or non-classification

Base upon read across data, the test substance is classified according to CLP regulation (No.
1272/2008 of 16 December 2008), Category 4 for acute oral toxicity with signal word 'WARNING'.

Based on the read across data and according 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.