Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In accordance with Regulation (EU) No. 1907/2006, Annex VI and VII, following in vitro tests were performed and are reported here:

- reverse mutation assay in vitro in bacteria,

- forward mutation assay in vitro in mammalian cells,

- Micro Nucleus assay in vitro in mammalian cells,

All tests were performed according to international Guidelines and validity criteria are fulfilled.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (positive)

Genetic toxicity in vivo

Description of key information

In accordance with Regulation (EU) No. 1907/2006, Annex VI and VII, IX and with regard to positive results in available in vitro tests following in vivo tests were performed and are reported here:

- Comet Assay in Stomach and Liver of the Rat,

- Micronucleus test in Bone Marrow Cells

All tests were performed according to international Guidelines and validity criteria are fulfilled.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Mode of Action Analysis / Human Relevance Framework

From the available in-vitro studies, no clear mode of action is determinable:

in bacteria gene mutation occurs without metabolic activation,

in mammalian cells, gen mutations occurs only in the presence of metabolic activation.

For both assays, genotoxicity is observed only in high doses.

The micro nucelus test in mammalian cells showed effects also at lower doses with and without metabolic activation.

These results show that 2,2'-Azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride has the ability to damage the DNA

of bacteria as well as specific mammalian cells when the cells are directly exposed.

The available in vivo tests did not show any signs of genotoxicity.

The bioavailability of the substance was demonstrated in these tests by cytotoxic effects.

Additional information

Justification for classification or non-classification

The available in vitro tests show positive results for the genotoxicity endpoint, however the available in vivo tests do not confirm this.

Two in vivo genotoxicity tests were performed testing the Endpoints gene mutation and chromosome aberration. No Genotoxic effects were observed in these tests.

The substance Azobis(Isobutyronitrile) which exhibits the general structural elements of 2,2'-Azobis[2 -(2 -imidazolin-2 -yl)propane] dihydrochloride is not classified as Mutagen (cat. 1 or 2).

Therefore, laying down the considerations in Regulation (EC) No. 1272/2008 Annex I, table 3.5.1., the data is conclusive but not sufficient for classification.