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Description of key information

Subactue oral toxicity was tested according to OECD 407 method in male rats at  0.25, 0.5 and 1 % in the diet for 32 days, corresponding with average doses of about 260,  510 and 1000 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.

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

Subacute oral toxicity

Feeding the test item (Shaffer and Golz, 1957) for 32 days at concentrations of 0.25%; 0.50% and 1 % in the diet of young male albino rats resulted in no significant signs of toxicity. These concentrations are equivalent to mean daily dosages of about 0.26, 0.51 and 1 g act. ingr./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 product. Although the study was conducted in male rats only, it was considered as a key study for subacute toxicity testing.

Subchronic and chronic oral toxicity

In a key subchronic oral repeated dose toxicity study (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 test items mixed into the diet. The various test items were category members of the Sulfosuccinates Diester Group, including the registered test substance. After 84 days hematological values, blood chemical values and 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 were 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) 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.

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 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.

Repeated dose inhalation or dermal toxicity

In accordance with column 2 of REACH legislation 2006R1907 Annex IX, these studies did not have to be conducted as repeated dose oral toxicity was investigated, which is an appropriate route of administration for systemic exposure.

Conclusion

- Based on the fact that no relevant target organ changes were seen up to the highest tested doses in the subacute studies (up to 1000 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 ca. 750 mg act. ingr./kg bw/day), classification is not warranted.