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Description of key information

The repeated dosel toxicity of the registration substance is derived based on the read-across approach. 
The supporting substance CAS 71786 -60 -2 was tested for its repeated dose toxicity according to OECD 422 Test Guideline and the NOAEL of 30 mg/kg/day was obtained. The major effect found at 30 and 125 mg/kg/day was changes in forestomach and in stomach, indicating the local irritation as the mode of action.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
30 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Reliable and robust read-across based on the category formation. Consistent results obtained in the two available studies.

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

The repeated dose toxicity of the registration substance is derived based on the read-across approach.

- The supporting substance CAS 71786 -60 -2 was tested for its repeated dose toxicity according to OECD 422 Test Guideline. The major effect found at 30 and 125 mg/kg/day was changes in forestomach and in stomach, indicating the local irritation as the mode of action. Further, the effect on the hematopoietic system was found based on the minimal changes in hematology parameters and the slightly increased spleen weights in males. Also the liver weight was minimally increased for males, which was considered as adaptive responce. Based on the histopathological changes observed in the stomach the NOAEL of 30 mg/kg bw was derived for the systemic toxicity. At dose of 125 mg/kg bw lower litter size was evident. The NOAEL of 30 mg/kg bw was derived for the reproductive toxicity.

- The supporting substance CAS 72786 -60 -2 was investigated for its repeated dose toxicity by oral application to rats for up to 14 days at doses of 0, 75, 150 and 250 mg/kg bw. The study was performed for the purpose of dose-range finding for the main study (OECD 422). The investigation parameters were limited to clinical signs, body weight development, food consumption and gross pathology. Severe toxicity such as mortality and emaciation occurred at the dose of 250 mg/kg bw/day. Tissue damages in the gastro-intestinal tract were evident in dose-dependent manner. Further, liver enlargement was found at dose of 150 mg/kg bw and 75 mg/kg bw. Taking account that the registration substance as well as the introduced supporting substance CAS 71786 -60 -2 are classified for its corrosivity for eyes and skin and the the most critical effects in the available repeated dose toxicity studies were the irritation in the gastro-intestinal tract, it is reasonable to derive the local irritation effect ("portal of entry" effect) and the related inflammatory responce as the mode of action. The NOAEL of 30 mg/kg bw obtained in the OECD 422 study is proposed to be used for the DNEL derivation.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The study provided ufficient evidences to identify the target organ, mode of action, and effects on the reproduction performance. A reliable NOAEL could be obtained for the repeated dose toxicity.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
Local effects would be expected to be irritation/corrosion which are local concentration rather than dose dependent. The classification as corrosive will ensure dermal exposure is well controlled.

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

Justification for classification or non-classification

No classification is warranted for the registration substance with respect to the endpoint repeated dose toxicity.

In the studies available for the assessment of the repeated dose toxicity (one OECD 422 study and one 14 -day repeated dose toxicity study; oral application for both studies), the tissue damage on the direct contact site in the gatric tract was found to be the most critical effect. Taking into account that the registration substance is classified as corrosive to skin and eye, these effects are to be described as "portal of entry effect" and should be considered as of limited relevance for the chronic toxicity assessment. No apparent systemic toxicity was found up to dose level of 125 mg/kg/day in the OECD 422 study, in which the animals were treated up to forty-five days. No classification is justified.