Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information
Short description of key information:
Reproduction toxicity studies were performed in the rat using LAB 3822 the maximum administered dose was 0.81 g/kg isosorbide equivalent, this dose is weakly lower than the maximum recommended dose in the OECD guideline (1 g/kg/day). However, this study was considered as acceptable because the dose maximum dose tested is close to this maximum recommended dose, Isosorbide is highly bioavailable and high level of the systemic exposure was clearly demonstrated, because isosorbide is not metabolized and this fact explained the high level of systemic exposure and the study was not limited to this limit dose but 3 dose levels were tested and finally at this dose level the results demonstrated clearly the absence of toxicity for the dam and for the foetus. On the other hand data from literature, although limited, confirmed the absence of this type of toxic effects. In the absence of reproductive toxicity potential, there is no need for a classification of Isosorbide. Due to the use of Isosorbide from several years as a drug, human data are available and demonstrated the good tolerance for long duration of treatment at high doses. Under these considerations, the available data are sufficient to conclude that Isosorbide presents a very weak toxicity level that no complementary studies are needed for risk assessment and that isosorbide need no classification.

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.