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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

In a 28 d study performed in rat (OECD guideline 407, GLP conform), the substance did not cause mortalities or signs of toxicity. Increased liver weights and higher numbers of blood platelets of the high dose group were observed. All effects were reversible within the recovery period. The NOEL is considered to be 241 mg/kg bw/d for female and 245 mg/kg bw/d for male animals, the NOAEL is considered to be 1060 for femals and 1110 mg/kg bw/ day for male animals.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1 060 mg/kg bw/day
Study duration:
subacute
Species:
rat

Additional information

Procedure and observations

A 28d study in rats (OECD guideline 407, GLP conform) was performed to evaluate the toxicity of the test substance after repeated application (Ciba 1991f). The test article was administered daily in diet to SPF-bred RAI rats of both sexes at dose levels of 0, 120, 600, 3000 and 12000 ppm for a period of 28 days. The study comprised 10 animals per group and sex which were sacrificed after 28 days of treatment. Additional 10 rats per sex and group were used at 0 and 12000 ppm. These animals 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. 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. Body weight gain was unaffected by the test substance and pathology as well as microscopic examination were without findings. Differences to the controls were restricted to the high dose group: slightly increased food consumption during the treatment period, reversible effects of minimally higher number of blood platelets and slightly increased absolute and relative liver weights (females) were noted.

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 hematological analyses revealed higher numbers of blood platelets in males (17% to control, in historical range) and females (28% to control, out of historical range) of the high dose group. This effect was reversible within the recovery period and is considered as treatment releated, non-adverse effect. The increased liver weight of the females (28% absolute, 19.7% liver/brain ratio) of the high dose group was also reversible within post-observation period. Respective histopathological liver examination was without findings and a dose-effect-relationship was not obvious. However, the increase in liver weight indicates uptake of the substance to a certain degree, transport and subsequent metabolism in liver cells. Based on the results of this study, 3000 ppm or 241 mg/kg (female) and 245 mg/kg bw (male) of the test article were established as the no-observable- effect-level (NOEL) and 12.000 ppm or 1060 (female) and 1110 (male) mg/kg bw/day were established as No-Adverse-Effect-Level (NOAEL).

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 not considered to be classified 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 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).