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Administrative data

Description of key information

The potential of the test material to cause repeated dose toxicity was investigated in the rat in a study conducted using methodology similar to that outlined in the standardised guideline OECD 452. Animals were fed diet containing the test material for up to 24 months. Haematological and serum biochemical examinations were conducted for all dose groups and at terminal sacrifice, the animals were subjected to histopathologic examination and assessed for neoplasms. No neoplastic response following test material administration was noted.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
50 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
The study was awarded a reliability score of 2. The quality of the database is therefore considered to be good.

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The potential of the test material to cause repeated dose toxicity was investigated in a study conducted using methodology similar to that outlined in the standardised guideline OECD 452. The study was assigned a reliability score of 2 in accordance with the criteria of Klimisch et al. (1997).  

Groups of 40 Slc:Wistar rats of both sexes were fed diet containing 0, 30, 100, 300 and 1000 ppm of the test material for up to 24 months, with interim examinations at 6, 12 and 18 months.

The general condition of the animals was observed and body weights were recorded throughout the study. At 6, 12, 18 and 24 months after the start of test material administration, haematological and serum biochemical examinations were conducted for all dose groups. Haemoglobin concentration, mean corpuscular volume, platelet count, blood urea nitrogen, phospholipids, total cholesterol, glutamate oxaloacetate transaminase and γ-glutamyl transpeptidase were all analysed. Also following 6, 12, 18 and 24 months of test material administration, histopathological examinations were performed for all groups.

Mortality in treated rats was comparable to that of controls. No remarkable general findings were observed in the control and treated groups throughout the experimental period. Significant reduction of body weight gain was found in the female 1000 ppm group from 12 months onward. No remarkable changes in food consumption were observed in the control and treated groups throughout the experimental period.

The haematological, biochemical and histopathological examinations revealed slight microcytic anaemia, changes in some biochemical parameters relating to liver function and focal necrosis of liver cells following test material administration. The changes observed in females were more severe than those in males. No neoplastic response following test material administration was noted.

It was concluded that the test material causes liver injury characterised by focal necrosis with microcytic anaemia and elevations of serum phospholipids and cholesterol levels presumably occurring as secondary effects following the liver injury.

Under the conditions of this study, the no observed adverse effect level (NOAEL) for carcinogenicity was 1000 ppm, the highest dose tested. The NOAEL for toxicity was determined to be 30 ppm. The lowest observed adverse effect level (LOAEL) for toxicity was determined to be 100 ppm.


Justification for selection of carcinogenicity via oral route endpoint:
Only one study available.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance does not require classification with respect to carcinogenicity.