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Administrative data

Description of key information

No test data were available for current substance, however read across data were available  from read-across substances CAS No. 23386-52-9 and CAS No. 848588-96-5. Subacute oral toxicity testing for 32 days up to 1% in the diet  in male rats did not lead to toxicity and showed a NOAEL of 768 mg act.ingr./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.  These studies did not reveal toxicity, therefore 1% in the diet, corresponding with ca. 750 mg act.ingr./kg bw can be accepted as NOAEL.

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:
Klimisch 2

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

No test data were available for registered substance, however read across data were available from CAS No. 23386-52-9 (Sodium dicyclohexyl sulfosuccinate) and CAS No. 55184-72-0 (Butanedioic acid, sulfo-, 1,4-diisotridecyl ester, sodium salt). Justification for read across within the category of sulfosuccinates Di-esters is documented in a separate document attached in Section 13.

 

Subacute toxicity

Data on subacute toxicity were available from following source chemicals:

- CAS No. 23386-52-9 (Sodium dicyclohexyl sulfosuccinate): Feeding of test substance containing 80% active ingredient for 32 days at concentrations of 0.25, 0.5 and 1 % in the diet of young male albino rats resulted in no significant signs of toxicity (Key study; American Cyanamid Company, 1969c). These concentrations corresponded with mean test item intake of about 240, 470 and 960 mgL/kg bw, respectively. Appearance and behaviour of the animals were normal, and at sacrifice and autopsy at the conclusion of the feeding period, there was no gross pathology that could be attributed to ingestion of the test item. Administration of test item up to 1% in the diet for 32 days in rats did not result in any relevant changes in the subacute toxicity study. Taking into account that the test item contained 80% active ingredient, the highest dose level corresponded with a NOAEL of 768 mg act.ingr./kg bw.

- CAS No. 55184-72-0 (Butanedioic acid, sulfo-, 1,4-diisotridecyl ester, sodium salt): Feeding of a test substance containing 97-98% active ingredient for 28 days at concentration of 100, 1000 and 10000 ppm in the diet in male rats (corresponding with 7.47, 74.7 and 812 mg act.ingr./kg bw/day on average) resulted in doubtful findings (Tusing, 1953). Animals dosed at 1000 and 10000 ppm levels showed a slightly greater retardation in growth than rats at 100 ppm. Food consumption for all groups was comparable to the controls during the 28-day period. One control animal died after 4 days of feeding. Gross autopsy revealed some incidence of intestinal irritation at all levels. Various other findings were observed at necropsy, however a respiratory infection was present, therefore the interpretation of the study is difficult. Therefore the study was considered to be supporting.

In conclusion, a NOAEL-level of 1000 ppm in the diet corresponding with 768 mg/kg bw was obtained with read across substance CAS No. 23386 -52 -9 in a subacute toxicity study in rats. No relevant target organ changes were observed up to highest dose. Based on structural similarity, the substance is considered to be safe and no classification is needed.

 

Subchronic and chronic toxicity

Data on subchronic toxicity were also available for both source chemicals in the same study. In a key subchronic oral repeated dose toxicity study, six groups of 40 albino rats (20 males, 20 females) plus 1 control group (20 males, 20 females) were fed with 1% of various test items mixed into the diet (Plank et al., 1969a,b). After 84 days hematological values, blood chemical values, urinalysis values were measured for all animals, and 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 were detected for CAS No. 23386-52-9 (Sodium dicyclohexyl sulfosuccinate). A slight increase in SGPT (serum glutamic pyruvic transaminase) and SAP (serum alkaline phosphatase) were the only findings for CAS No. 55184-72-0 (Butanedioic acid, sulfo-, 1,4-diisotridecyl ester, sodium salt). 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 act. ingr./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 to be worst case 750 mg/kg bw/day.

In conclusion a NOAEL of 1% in the diet, corresponding with 750 mg/kg bw, was obtained in a 90 -day study wiht read across substances CAS No. 23386-52-9 and 55184-72 -0 and other category members. No relevant target organ changes were observed up to highest dose. Based on structural similarity, the substance is considered to be safe and no classification is needed.

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 supporting studies with category member Docusate sodium, 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 870mg/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.

Conclusion

- Based on the fact that no relevant target organ changes were seen up to the highest tested doses in the subacute studies (approximating 768 and 812 mg act.ingr./kg bw) and that no relevant changes were seen at the dose of 750 mg act. ingr./kg bw in the 90-day toxicity study , it can be concluded that the substance is safe and that 750 mg act.ingr./kg bw is NOAEL.

- Further information supporting the safety of the test substance is provided in the read across justification for the Di-ester 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).


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Key study

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 to >750 mg act. ingr./kg bw/day), classification is not warranted according to the EC Directive (No.93/21/EEC) and CLP (No. 1272/2008 of 16 December 2008).