Registration Dossier

Administrative data

Description of key information

Sprague Dawley rats were administered ad libitum with isosorbide by dietary admixture at concentrations of 12500, 25000 and 50000 ppm (corresponding to daily dose-levels of 784, 1577 or 3347 mg/kg/day for the males and 937, 2060 or 3970 mg/kg/day for the females) for 13 weeks.  This GLP study was equivalent to OECD Test Guideline 408.  
The No Observed Effect Level (NOEL) was established at 12500 ppm (corresponding to 748 mg/kg/day in males and 937 mg/kg/day in females) and the No Observed Adverse Effect Level (NOAEL) was set at 50000 ppm (corresponding to 3347 mg/kg/day in males and 3970 mg/kg/day in females).
No supporting oral studies were located and no inhalation or dermal repeat-dose toxicity studies have been conducted.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
3 347 mg/kg bw/day
Study duration:
chronic
Species:
rat

Additional information

The test item was clinically well tolerated at all dose-levels. No mortality or clinical signs were observed. In addition, no relevant differences related to the test item were noted in the body weight gain or food consumption of treated groups. Treatment with the test item at 25000 or 50000 ppm caused transient increase of water consumption.

No treatment-related hematological, blood biochemistry and urinary parameter changes were recorded.

No histopathological findings were noted at necropsy.

Consequently, following administration of ISOSORBIDE to rats for 13 weeks by dietary admixture, the No Observed Effect Level (NOEL) was established at 12500 ppm (corresponding to 748 mg a.i./kg/day in males and 937 mg a.i./kg/day in females) and the No Observed Adverse Effect Level (NOAEL) was set at 50000 ppm (corresponding to 3347 mg a.i./kg/day in males and 3970 mg a.i./kg/day in females).

Justification for classification or non-classification

The substance does not meet the criteria for classification and labelling for this endpoint, as set out in Regulation (EC) NO. 1272/2008.