Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

AMES:

An AMES test was performed according to OECD guideline and GLP principles. All bacterial strains showed negative responses up to 5000 ug/plate, i.e. no significant dose-related increase in the number of revertants with or without metabolic activation was seen. No cytotoxicity and/or precipitation of the test substance was observed. The negative and strain-specific positive control values were within the laboratory historical control data ranges indicating that the test conditions were adequate and that the metabolic activation system functioned properly. Based on the results of this study it is concluded that guanidinium phosphate (1:1) is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay with or without metabolic activation.

 

MLA:

A mouse lymphoma assay was conducted according to OECD 476 guideline and GLP principles. The spontaneous mutation frequencies in the solvent-treated control cultures were between the minimum and maximum value of the historical control data range Positive control chemicals, methyl methane sulfonate and cyclophosphamide induced appropriate responses. In the absence of S9-mix, guanidinium phosphate (1:1) did not induce a significant increase in the mutation frequency in the first experiment. This result was confirmed in an independent repeat experiment with modifications in the duration of treatment time. In the presence of 8% v/v S9-mix, guanidinium phosphate (1:1) did not induce a significant increase in the mutation frequency in the first experiment. This result was confirmed in an independent repeat experiment with 12% v/v S9 for metabolic activation. It is concluded that guanidinium phosphate (1:1) is not mutagenic in the mouse lymphoma L5178Y test system under the experimental conditions described in this report.

 

CA:

In a chromosome aberration study, Chinese hamster fibroblasts were exposed to different concentrations of guanidine in the absence of S9 -mix. The substance was tested up to cytotoxic concentrations in one experiment. Guanidine did not induce chromosome aberrations under the test conditions used. Although the study was undertaken before OECD and GLP guidelines were in place and the publication lacks basic data on substance (purity, Lot/batch number). Several substances were tested in parallel with expected outcome of the positive and negative controls, demonstrating reliability of the experiment.

In the Chromosome aberration assay, the test substance was only tested without metabolic activation. The reason not to perform additional testing is twofold: Both the AMES test and the Mouse Lymphoma assay showed negative results with metabolic activation. Moreover, the chemical structure of the compound does not indicate potential metabolic activation.

Therefore the data presented here are considered sufficient for final conclusion on the genotoxicity of guanidinium phosphate (1:1).


Justification for selection of genetic toxicity endpoint
No study was selected, since all three in vitro studies were negative.

Short description of key information:
Three in vitro tests were performed (AMES test, chromosome aberration test and MLA assay). Guanidinium phosphate (1:1) was shown to be negative without metabolic activation in all three tests. Mutagenicity testing with metabolic activation was only tested in the AMES test and the MLA assay, both with a negative result.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available data, guanidinium phosphate (1:1) is not classified for genotoxicity according to CLP Regulation (EC) No. 1272/2008.