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Administrative data

Description of key information

Key data for subacute toxicity were available from an oral (gavage) OECD 422 study in rats with read-across substance 'Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1-oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts', at dose levels given by oral gavage of 100, 300 and 1000 mg/kg bw/day. No relevant effects were observed at 100 and 300 mg/kg bw. At the dose of 1000 mg/kg bw, decreased body weight, increased serum ALAT and decreased serum albumin were observed as systemic changes, whereas macroscopic and microscopic stomach changes were observed as local changes, the latter without relevance to humans. NOAEL for paternal/maternal toxicity was 300 mg/kg bw/day

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
High quality (Klmisch 1)
System:
gastrointestinal tract
Organ:
liver
stomach

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Subacute toxicity

Studies were available for read-across substance Butanedioic acid, 2(or 3)-sulfo-, 4-[2-[(1-oxo(C12-C18(even numbered) and C18unsaturated)alkyl))amino]ethyl]esters, disodium salts (CAS 68784-08-7).

- A key study for repeated dose toxicity was performed by means of an oral combined repeated dose and reproduction/development screening study according to OECD guideline 422 (Hansen, 2013a). The test item was administered orally by gavage to rats with a liquid formulation containing 41.5% active ingredient at dose levels of 100, 300 and 1000 mg/kg bw/day for at least 28 days in male rats and at least 39 days in females. No test item-related premature death was noted in any treatment group. No signs of clinical toxicity were noted for the male and female rats of the low and intermediate dose groups (100 and 300 mg/kg bw/day), whereas slightly increased salivation was noted in one male rat at 1000 mg/kg bw/day. No observational and functional neurological findings were seen up to the highest dose group. A slight reduction in body weight was noted for the male and female rats dosed at 1000 mg/kg bw/day. The laboratory examinations revealed an increased serum ALAT activity for the male and female rats dosed at 1000 mg/kg bw/day, and a decreased serum albumin concentration for the male rats of the high dose group. No test item-related changes were noted during the macroscopic inspection at autopsy with the exception of changes in the stomach from 2 male animals from the high dose group. Microscopic examination revealed the occurrence of squamous cell hyperplasia in the non-glandular mucosa of the forestomach and acute inflammation in the male and female rats of the high dose group. These changes are considered to be local, and not relevant for humans as humans lack a forestomach. NOAEL for paternal/maternal toxicity was 300 mg/kg bw/day.

- In a supporting 14-day dose-range-finding study (Hansen, 2013b) the dose levels were selected for a combined repeated dose and reproduction/developmental toxicity screening test. 5 Male and 5 female rats were treated once daily with a liquid formulation containing 41.5% active ingredient at dose levels of 100, 300 and 1000 mg act.ingr./kg bw/day by oral gavage administration. None of the animals died prematurely. Salivation was noted for 2 of 5 male animals treated with 1000 mg/kg bw/day starting on day 9 and increased faeces was noted for 3 of 5 male and 2 of 5 female high dosed animals starting on test day 5. The food consumption of the male and female animals treated with 1000 mg/kg bw/day was slightly increased by 9% for the males and by 10% for the females in test week 2. None of the male and female rats treated orally with 100, 300 or 1000 mg/kg bw/day revealed any test item-related changes in body weight, body weight gain as well as relative and absolute organ weights or at macroscopic inspection at necropsy. Maximum tolerated dose was 1000 mg/kg bw.

 

 

Conclusion

- The NOAEL of 300 mg/kg bw in the OECD 422 study with registered substance was considered as the most conservative value, therefore this was selected as the descriptor for DNEL calculations.

- Further information supporting the safety of the test substance is provided in the read across justification for the N2 and N3 subgroups, showing that all substances in these sulfosuccinates subgroups had similar NOAELs (justification with data matrix separately attached in Section 13).

Justification for classification or non-classification

Based on these results and according to the CLP Guidance (No. 1272/2008 of 16 December 2008), the test substance does not have to be classified and has no obligatory labelling requirement for repeated dose toxicity.