Registration Dossier

Administrative data

Description of key information

Subactue oral toxicity was tested according to OECD 407 method in male rats at 0.125, 0.25 and 0.5% in the diet for 32 days, corresponding with average doses of 130, 250 and 510 mg/kg bw. Subchronic oral toxicity was further tested equivalent to OECD 408  method in male and female rats at 1% in the diet for 90 days,corresponding with ca. 750 mg act. ingr./kg bw on average basis.  These studies did not reveal toxicity, therefore 1% in the diet, corresponding with >= 750 mg act.ingr./kg bw can be accepted as NOAEL. Repeated dose toxicity was tested in various species, including rats, dogs, rabbits and monkeys. The NOAEL of 750 mg/kg bw/day obtained in the key study in rats was confirmed to be consistent with data from docusate sodium and category members in supporting studies in rats; other data from other species were of limited reliability and relevance and therefore not taken into account.

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
750 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
reliable (Klimisch 2)
Organ:
colon

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

Feeding the registered substance (78 -80% purity) in the diet for 32 days at concentrations of 0.125%, 0.25% and 0.5% in the diet of young male albino rats resulted in no significant signs of toxicity (Shaffer, 1957). These concentrations were equivalent to mean daily dosages of about 130, 250 and 510 mg active ingredient/kg bw, respectively. Appearance and behaviour of the animals were normal and at sacrifice and autopsy at the conclusion of the period of feeding, there was no gross pathology that could be attributed to ingestion of the test item. Administration of test item up to 0.5% in the diet (equivalent to 510 mg act.ingr./kg bw/day) for 32 days in rats did not result in any relevant changes in the subacute toxicity study.

Subchronic and chronic toxicity

A key 90-day oral repeated dose toxicity study in rats was also available for the registered substance (Plank et al., 1969). Six groups of 40 albino rats (20 male, 20 female Charles River Strain) plus 1 control group (20 male, 20 female) were fed with 1% of various sulfosuccinate category member mixed into the diet. After 84 days hematological values, blood chemical values, urinalysis values were measured for all animals. Tissues were examined pathologically at the conclusion of the 90-days test period. Organ to body weight and organ to brain weight ratios were calculated. No significant differences in clinical blood chemistry studies and absolute organ weights have been detected. Body weights organ to body weight ratios, hematologic studies and urinalysis were not different between test and control animals. No deaths or abnormal behavioral reactions occurred; no gross pathological findings were noted. Administration of category members at 1% in the diet (10000 ppm equivalent to ca.750 mg/kg body weight/day on average basis) for 90 days in rats did not result in any relevant changes in the subchronic toxicity study. The NOAEL was therefore considered worst case to be 750 mg act.ingr./kg bw/day.

The validity of the study was supported by additional audits on the raw data and histopathological evaluation. Although deficiencies were detected compared to current standards, the study was concluded to be valid and reliable.

In a supporting study, groups of 10 (5 male & 5 female) Wistar rats were treated for 6 months at concentrations of 0.25, 0.5, 0.75, 1.0 and 1.25 g/kg diet, corresponding to doses of 190, 370, 550, 750 and 870 mg/kg bw/day. Occasional spells of diarrhea occurred in some animals, particularly at the higher doses. Neither the total red cell, total white cell, nor the differential counts of rats was affected by the continued administration . The dose level of 750 mg/kg was confirmed as NOAEL (Literature, Benaglia et al. 1943).

Other studies were also available from literature in various species (Literature, Benaglia et al. 1943 and Case et al., 1977) in dogs, rabbits and Rhesus monkeys. The other species were considered to be less appropriate due to the gastrointestinal tensioactive local irritation by which systemic effects could not be fully evaluated.

 

General assessment and conclusion

- The fact that no relevant target organ changes were seen up to highest concentration of 1% in diet for 90 days, allows to conclude that corresponding intake of 750 mg/kg bw is NOAEL.

Further information supporting the safety of the test substance is provided in the read across justification for the Diester category, showing that all substances in the group had a NOAEL of at least 750 mg/kg bw (justification with data matrix separately attached in Section 13).


A new 90 -day repeated dose toxicity study in rats was requested based on ECHA Communication number CCH-D-2114330559-45-01/F. The results will be provided as soon as possible with an update of the dossier.Docusate sodium was used as read across substance for the registration of potassium 1,2-bis(2-ethylhexyloxycarbonyl)ethanesulphonate (CAS 7491-09-0). Based on information gaps in the old 90 -day study, ECHA requested a new subchronic toxicity (90 -day) study in rats by oral route. The new study with docusate sodium will be conducted for both the registrations of both potassium 1,2-bis(2-ethylhexyloxycarbonyl)ethanesulphonate and docusate sodium, but also for the other diester sulfosuccinates.

Justification for classification or non-classification

As there were no changes observed in the repeated dose toxicity studies up to 1% in the diet, corresponding with ca. 750 mg active ingredient/kg bw, classification according to EC Directive (No.93/21/EEC) and CLP (No. 1272/2008 of 16 December 2008) is not needed.