Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

In order to avoid unnecessary animal testing one of the three genetic toxicity tests (which are required by Annex VII and VIII of REACH regulation) was read acrossed from Benzoguanamine. It was decided to support the negative AMES test by the performance of a test according to OECD Guideline 476 (In vitro Mammalian Cell Gene Mutation Test) and to propose a Read-Across approach for the endpoint "8.4.2. In vitro cytogenicity study in mammalian cells or in vitro micronucleus study".

Justification for Read-Across:

Irrespective of metabolic activation Acetoguanamine was not able to induce reverse mutations in Salmonella typhimurium just as Benzoguanamine did not in the Ames test. The molecule structure of Acetoguanamine supports the negative effect. It is completely integrated in the structure of Benzoguanamine. There are no additional functional groups which could be relevant regarding structural alerts for mutagenicity. Since Benzoguanamine showed no obvious potential to impact genomic integrity it can be assumed that Acetoguanamine will show the same properties.  

According to OECD TG 473 and GLP two tests were performed with Benzoguanamine. In the first test Benzoguanamine was tested for chromosomal aberation with human lymphocytes cells in concentrations up to 2500 µg/mL with and without metabolic activation system. There was no evidence for cytotoxicity with metabolic activation system within and above the solubility limit. Cytotoxicity was detected without metabolic activation system within and above the solubility limit (Pateman 1993). In the second test Benzoguanamine was tested for chromosomal abberation in Chinese Hamster Lung (CHL) cells with and without metabolic activation system. Cytotoxicity was observed without metabolic activation system. Findings for cytoxicity with metabolic activation system was ambiguous (Nakajima 1999). The cytogenetic effect observed in in vitro assays however, could not be reproduced in the micronucleus tests in vivo (Honarvar 2000).


Short description of key information:
Acetoguanamine revealed no mutagenic activity in the Ames Test (OECD 471) and in the Mouse Lymphoma Test (OECD 476).
Furthermore endpoint data from Benzoguanamine was read-acrossed to Acetoguanamine to fulfill the requirements of Annex VIII of REACH regulation.
Cytogenic effects for Benzoguanamine were observed when tested according to OECD TG 476 and 473. The cytogenetic effects, observed in in-vitro assays, could not be reproduced in the in vivo micronucleus tests. Based on these results, it could be concluded that Benzoguanamine, as well as Acetogunanamine, is not genotoxic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

In accordance to Directive 67/548/EEC, respectively Regulation (EC) No 1272/2008, Acetoguanamine does not need to be classified for genotoxicity.