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Description of key information

A 28 day oral gavage study resulted in a NOAEL of 1000 mg/kg bw.
A 5 day inhalation study resulted in a NOAEL of 10000 ppm.

Key value for chemical safety assessment

Additional information

Groups of 10 animals (five male and five female) were dosed by oral gavage at doses of 0, 40, 200 and 1000 mg/kg bw. No treatment related effects were seen in the 40 or 200 mg/kg bw groups. In the liver, centrilobular acidophilic change of the hepatocytes was found in both sexes of the 1000 mg/kg group in the histological examination. This change is known to be seen in the case of hypertrophy of the hepatocytes caused by induction of the drug metabolizing enzymes. Furthermore, hypertrophy of the hepatocytes is generally considered to be a result of the adaptive change. There is a possibility that acidophilic change of the hepatocytes observed in this study was also a result of the adaptive change as well as the case of hypertrophy of the hepatocytes. However, there was no change in the liver weight in this study. Good reversibility of this change was suggested, since it was not observed at the end of the recovery period.

 

In the 5 day inhalation study, animals were dosed at 10000 ppm, 6 hours per day for 5 days. No mortality was observed and body weight gains in the treated animals were similar to those in the control group. Liver weight gain was observed in the treated animals and a reduction in cholesterol was also seen. These effects are similar to those noted in the 28 day oral study and are considered to be adaptive responses. Since only one dose was tested, this was determined to be the NOAEL for this study.

Justification for classification or non-classification