Butanedioic acid, sulfo-, C-C16-18-alkyl esters, disodium salt

Endpoint summary

Description of key information

No repeated dose toxicity study is available for the target substance C16 -18 sulfosuccinate. The repeated dose toxicity was assessed based on information of a read-across substance.

A combined repeated dose and reproductive/developmental screening study which was performed with a close homolog C12 -18 sulfosuccinate according to OECD guideline 422 showed NOAEL-levels of 60 mg/kg bw for paternal/maternal toxicity, 120 mg/kg bw for reproductive toxicity and 120 mg/kg bw for developmental toxicity.

For risk assessment, the lowest NOAEL of 60 mg/kg bw with the read-across substance C12 -18 sulfosuccinate tested in the OECD 422 study was selected.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

60 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Klimisch 1

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

- A key study for subacute toxicity was performed by means of an oral combined repeated dose and reproduction/development screening study according to OECD guideline 422 (Hansen, 2013a) with a read-across substance (C12 -18 sulfosuccinate). The test item was a solid formulation (containing >93% active ingredient) which was administered as a watery solution orally by gavage to rats at dose levels of 60, 120 and 300 mg act. ingr./kg bw/day for at least 28 days in male rats up to 54 days in female rats. One of 10 male and one of 10 female animals at 300 mg/kg bw/day died prematurely on test day 33 or on gestation day 9. Slight to moderate salivation was noted in a few male and female animals at 120 mg/kg bw/day; at 300 mg/kg bw/day, piloerection and a slight to extreme salivation was noted for several to all male and female animals on several days.Reduced body weight was noted for the male animals at 120 mg/kg bw/day and for both sexes at 300 mg/kg bw/day. Increases in ALAT, aP and ASAT and decreases in globulin, cholesterol, chloride and potassium concentrations were noted for the male and/or female animals of the intermediate and/or the high dose group (120 and/or 300 mg/kg bw/day). Several organ weights were seen in males and females dosed at 120 and 300 mg/kg bw/day, most remarkably for the thymus and liver weights of the animals of the high dose group. Macroscopic inspection revealed changes in the stomach of male animals dosed at 300 mg/kg bw/day and female animals dosed at 120 and 300 mg/kg bw/day. Histopathological examination revealed changes in the liver (hepatocellular hypertrophy and macrovesicular vacuolation) and the non-glandular stomach (squamous cell hyperplasia) of male and female animals dosed at 300 mg/kg bw/day. These latter changes are considered to be related to a local activity of the test item. As humans lack a forestomach, the relevance of these changes for humans is questionable.

NOAEL-level were as follows: 60 mg/kg bw for paternal/maternal toxicity and 120 mg/kg bw for reproductive and developmental toxicity (see Section 7.8.1 and 7.8.2).

In conclusion, NOAEL-levels of 60 mg/kg bw for paternal/maternal toxicity, 120 mg/kg bw for reproductive toxicity and 120 mg/kg bw for developmental toxicity were obtained in a combined repeated dose and reproductive/developmental screening study which was performed with the read-across substance according to OECD guideline 422. Therefore, no classification is needed.

Conclusion

- For risk characterisation, the paternal/maternal NOAEL of 60 mg/kg bw in the OECD 422 study with the read-across substance was selected as most conservative value.

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver; digestive: stomach; urogenital: kidneys

Justification for classification or non-classification

As there were no relevant findings below classification threshold of 100 mg/kg bw, classification for repeated dose toxicity is not warranted according to the EC Directive (No.93/21/EEC) and CLP (No. 1272/2008 of 16 December 2008).