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Additional information

In the key bacterial reverse mutation assay (equivalent toOECD guideline 471), isosorbide was tested in a GLP study at doses of 0, 50, 150, 500, 1500, 5000 µg/plate inSalmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 and E. Coli strins WP2 pKM101 and WP2 uvr A pKM 101. Water was used as the vehicle and positive controls were included in all incubations.

Cytotoxicity (defined as a moderately to extremely reduced background lawn) was not observed and no increase in the reverse mutation rate was noted at any isosorbide concentration either in the absence or presence of metabolic activation.

In the key mammalian chromosome aberration test (equivalent to OECD guideline 473), the test compound was studied at the maximum dose recommended by OECD guideline, 5000µg/ml and two lower doses chosen according to a ratio 2, i.e. 2500 and 1250 µg/ml which presented no cytotoxic effect.

Without and with metabolic activation a 4-hour treatment assay with one sampling at 20 hours after the start of treatment and without metabolic activation with a continuous treatment for 20 or 44 hours, no statistically variation of the number of breaks per cell or of the number of cells with aberration including or not the cells with only gaps. It is noted that in the second assay with metabolic activation, one cell of the culture treated by the high dose (5000µg/ml) presented one exchange and one complex arrangement, but this observation was isolated and was neither observed in the other culture nor in the other assay. Under these conditions this observation which did not induce a statistically significant number of breaks cannot be considered as biologically significant of a clastrogenic activity. In conclusion, the test item presented no significant clastogenic activity with and without metabolic activation in cultured human lymphocytes.

In the key mammalian gene mutation assay (equivalent toOECD guideline 476) the test compound was tested in a GLP study at doses of 625, 1250, 2500, 5000 µg/ml in mouse lymphoma L5178Y cells.

Water was used as the vehicle and methylmethanesulfonate and cyclophosphamide were used as the positive control compounds in the absence and presence of metabolic activation, respectively. No cytotoxicity and no increase in the mutant frequency were observed at any isosorbide concentration in the absence or presence of metabolic activation.

The test compound LAB 3085 induced no mutagenic activity being demonstrated at the TK Locus in L5178Y mouse lymphoma cell culture.


Short description of key information:
The genetic toxicity of isosorbide has been assessed in 3 in vitro studies: a bacterial reverse mutation assays, a mammalian chromosome aberration test and a mammalian gene mutation assay. Negative results were reported in all the studies.

Endpoint Conclusion: No adverse effect observed (negative)

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.