Disodium (Z)-4-(9-octadecenylamino)-4-oxo-2(or 3)-sulphonatobutyrate

Endpoint summary

Description of key information

Assessment was based on read across with category members. A key study for acute oral toxicity with read across test substance  'Butanoic acid, 4-amino-4-oxo-2(or 3)-sulfo-, N-(C16-C18 (even numbered), C18 unsaturated alkyl), disodium salts’ containing 35% act. ingr. showed an LD50 value of 3640 mg act.ingr./kg for male and female rats;  clinical signs included activity reduction, incoordination, diarrhea and piloerection.  This was confirmed by a supporting study with other category member, therefore LD50>2000 mg/kg bw was accepted.. A key study for acute dermal toxicity with test item containing 25.5% act. ingr. in rats did not reveal relevant changes and resulted in an LD50 >2000 mg act.ingr./kg bw in male and female rats.  This was confirmed by a supporting study with other category member, therefore LD50>2000 mg act.ingr./kg bw was accepted.  Inhalation toxicity testing was waived based upon the fact that acute inhalation exposure as such is very unlikely for sulphosuccinates due to their substance properties.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

reliable (Klimisch 2)

Additional information

No data were available for registered substance, however data were available for read-across substances

- 'Butanoic acid, 4-amino-4-oxo-2(or 3)-sulfo-, N-(C16-C18 (even numbered), C18 unsaturated alkyl), disodium salts'

- 'Butanoic acid, 4-amino-4-oxosulfo-, N-tallow alkyl derivs., disodium salts' (CAS 68988-69-2).

Justification for read-across with subgroup members is provided in Section 13.

 

Acute oral toxicity

- In a key acute oral toxicity study with read-across substance 'Butanoic acid, 4-amino-4-oxo-2(or 3)-sulfo-, N-(C16-C18 (even numbered), C18 unsaturated alkyl), disodium salts', the test item as received (35% aqueous solution) was administered to 5 groups of SPF-Wistar rats (5 males and 5 females/group) at doses of 6.3, 7.94, 10.00, 12.60 and 15.90 mL/kg bw (Sterner and Stiglic, 1977). Mortalities occurred within 48h after application. The test substance evoked at the tested doses, an increasing degree of activity reduction, incoordination, diarrhea and piloerection. In the highest dose, animals also showed abnormalities in position and posture and decreased reflexive excitability. The symptoms occurred within 1 hour after application and held on for 24 hours . Thereafter, all surviving animals, showed normal behavior during the entire observation period. At the end of the 14 days observation period all surviving animals showed normal body weight gain rates. At necropsy , in the acute mortality group, strong reddened gastric and intestinal mucosa was found. At necropsy, in the group of animals killed at the end of testing, no pathological changes were found in skull, chest and abdominal cavity. The acute oral LD₅₀was 10.4 mL/kg bw, corresponding to 3640 mg act. ingr./kg bw.

- In a supporting acute oral toxicity study with CAS 68988-69-2 'Butanoic acid, 4-amino-4-oxosulfo-, N-tallow alkyl derivs., disodium salts', (Shaffer and Golz, 1956a) the test item (aqueous solution, 35% solids) was diluted further with water to a concentration of 20% solids, and administered to groups of young male albino rats in dosages ranging from 1250 mg/kg to 10000 mg active ingredient/kg bw. The acute oral LD₅₀calculated from the number of deaths occurring over a seven-day observation period following the dose is 2680 (1910-3760) mg act. ingr.kg bw. At the highest dosage level, all animals died within the first 24 hours; at lower dosages, some deaths were delayed for several days. In every case, depression and a profuse, watery diarrhea were the most conspicuous toxic signs observed prior to death. Post-mortem examination of animals that died did not disclose any remarkable pathology, although there was a slight evidence of gastrointestinal irritation. Similarly, at sacrifice and autopsy no pathology was found by gross inspection that was specifically attributable to the dose.

- In conclusion, it was clear from both studies that there is no hazard after acute oral dosing, therefore it can be accepted that LD₅₀>2000 mg act.ingr./kg in both studies

 

Acute dermal toxicity

- In a key dermal toxicity study with 'Butanoic acid, 4-amino-4-oxo-2(or 3)-sulfo-, N-(C16-C18 (even numbered), C18 unsaturated alkyl), disodium salts' , 5 male and 5 female CD rats were applied the registered test substance containing 25.5% active ingredient for 24 hours under occlusion at a dose level of 2000 mg act.ingr./kg bw and observed for 14 days (Haferkorn, 2013a). The rats revealed no signs of toxicity and no deaths. No skin reactions were observed at the application site. All animals gained the expected body weight throughout the whole experimental period. No signs or abnormalities were noted at necropsy. LD₅₀> 2000 mg/kg bw.

- In a supporting acute dermal toxicity study with CAS 68988 -69 -2 'Butanoic acid, 4-amino-4-oxosulfo-, N-tallow alkyl derivs., disodium salts' (Shaffer and Golz, 1956a) the test item was applied as a 35% aqueous dispersion, at a dosage of 10 g/kg of the dispersion (equivalent to 3 g/kg of contained solids) to the closely-clipped abdomen of each of 5 male albino rabbits. No appreciable irritation of the skin was present at the time of removal of the cuff. However, considerable difficulty was experienced in washing the residue of the dose from the skin, and a certain amount remained and hardened into a thin film. A mild to moderate degree of erythema developed in these areas in the course of several days following to application. No systemic toxic effects were observed as a result of the dose. All animals were sacrificed at the end of a 7-day observation period, and no significant gross pathology was found at autopsy. It is concluded the LD₅₀is >3000 mg/kg bw.

- In conclusion, it was clear from both studies that there is no hazard after acute dermal dosing, therefore it can be accepted that LD₅₀>2000 mg/kg in both studies

 

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

- There ws no hazard for acute oral and dermal toxicity, based on read across substances showing LD₅₀values >2000 mg/kg bw. Therefore no hazard for acute oral and dermal toxicity is expected for this structurally similar substance.

- 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 – dermal endpoint
Key study

Justification for classification or non-classification

The available acute toxicity studies demonstrate that substance is of low acute toxicity.Based on these results and according to the EC Directive (No.93/21/EEC) and CLP (No. 1272/2008 of 16 December 2008), classification is not obligatory for oral and dermal acute toxicity.