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Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

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

Additional information

Procedure and observations

 

Based upon the data of the acute oral toxicity study and a 5d-range-finder study, 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 Wistar rats of both sexes at dose levels of 0, 10, 50 and 300 mg/kg body weight/day for a period of 28 days. The study comprised 10 animals per group and sex which were sacrificed after 28 days of treatment. 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. Reduced food consumption leading to decreased body weight was observed in the high dose group. Also changes in haematology and an increase in liver weight (hepatocellular hypertrophy) were recorded in this group. All effects resolved within post observation period

                                           

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 signs of toxicity. Changes in haematology and liver weight at the high dose group were fully reversible and therefore not considered as adverse effects. The mean body weight of the 300 mg/kg group was also after the recovery period slightly decreased. But a tendency to approach the values of the control group was observable during the second week of the post observation period.

Based on the results of this study, 50 mg/kg of the test article was established as the no-observed-effect-level (NOEL).

 

Repeated dose studies via dermal or inhalative route were not performed. The results of other dermal tests to acute toxicity, irritation and sensitization show that the substance does not cause any reaction to skin. Therefore, toxic effects after repeated dermal application are not expected. The substance has a particle size of 153 µm and is therefore not inhalable.


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

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC):

The available study is considered reliable and suitable for classification purposes under 67/548/EEC. As a result the test item is not considered to be classified for its potential for repeated dose toxicity under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/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 test item is not considered to be classified for its potential for repeated dose toxitity under Regulation (EC) No. 1272/2008.