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Administrative data

Description of key information

In a 28 d study performed in rat (OECD guideline 407), the substance did not cause mortalities, signs of toxicity or any other changes or abnormalities. The NO(A)EL is considered to be 1000 mg/kg bw/d.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat

Additional information

Procedure and observation

A 28d study in rats (OECD guideline 407) was performed to evaluate the toxicity of the test substance after repeated application.

The test article was administered daily by oral gavage to rats of both sexes at dose levels of 0, 100, 300 and 1000 mg/kg body weight/day for a period of 28 days. The study comprised 5 animals per group and sex which were sacrificed after 28 days of treatment. Additional 5 rats per sex and group were treated for 28 days and then allowed a 14-day treatment-free recovery period after which they were sacrificed. Clinical signs, food consumption and body weights were recorded periodically during the treatment and recovery periods. Ophthalmoscopic examinations were performed at the end of the treatment and recovery periods. Haematology, urinalysis as well as pathological and microscopic analysis were performed.

All animals survived the scheduled treatment period. There were no test article-related clinical signs in any group. Pink faeces characteristic of the test article were noted for all treated groups from day 2 of dosing and throughout the treatment period. The pink colouration was not observed from day 2 of the treatment-free phase. Body weight and food consumption were unaffected by the test substance. There were no treatment-related effects on hematology, clinical biochemistry and urinalysis, neither at termination of the treatment nor at the end of the treatment free recovery period. All gross and microscopic lesions recorded in this study were considered to be spontaneous in origin. The only treatment-related finding at the terminal kill was red ingesta in the gastrointestinal tract due to the presence of the test substance. Changes in organ weight were not observed.

Discussion

In this subacute toxicity study, the test substance was administrated to rats over a period of 28 consecutive days. Neither during treatment period nor during post-observation period of 14 days occurred mortalities or any signs of toxicity. The biochemical analyses did not reveal abnormalities. Also pathology, organ weighing and microscopic examination were without findings. Based on the results of this study, 1000 mg/kg of the test article was established as the no-observed-adverse-effeet-level (NOAEL) and as the no-observed- effect-level (NOEL).

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is notconsidered to be classified for repeated dose toxicity under Directive 67/548/EEC, as amended for the 30th time in Directive 2008/58/EC.

 

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for repeated dose toxicity under Regulation (EC) No. 1272/2008, as amended for the second time in Directive (EC 286/2011).