Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vivo

Description of key information
Several Ames tests are available which gave negative results with and without metabolic activation (Haworth 1979, Ishidate 1983, Zeiger 1984).Tests on effects on chromosomes were in general negative without metabolic activation, though one study (Ishidate, 1983) gave an ambiguous result without metabolic activation. The key study an in vitro micronucleus assay with and without metabolic activation gave negative results (Nesslany, 1999).A battery of in vivo data on sodium benzoate are available which are clearly negative and considered as reliable for the test substance based upon a toxicokinetic evaluation.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vivo:

All available tests for gene mutations in bacteria did not show any effects of the test substance with or without metabolic activation. A

poorly reported test in yeast (no metabolic activation) was positive, but the validity of this result could not be checked (Piper, 1999). No effects were reported after exposure of prophage containing E.coli strains (Rossmann, 1991) or in an SOS/umu test in S. typhimurium (Nakumara 1987). For cytogenetic effects, a chromosome aberration test was ambiguous without metabolic activation (Ishidate, 1983). Several other limited reported tests on sister chromatid exchange (without metabolic activation) were negative. The test substance was positive in a Comet assay (Esref, 2009), but it was clearly negative in an in vitro micronucleus test (with and without metabolic activation) (Nesslany, 1999).

Additional studies were identified, but were not available for review. The available results confirm that the test substance does not induce gene mutations and is not likely to induce effects on the chromosomal level.

A battery of in vivo tests were conducted with the structurally related sodium benzoate and these all clearly indicated no cytogenetic effects. These studies are considered to fully address and over-ride the ambiguous results found in the in-vitro data set. The toxicokinetic evaluation on sodium benzoate concluded that the substance will not be taken up as the salt, but rather as the test substance entity (NOTOX 2010). Therefore it can be concluded that the results for the test substance will not differ from those found in in vivo tests with sodium benzoate.

Based on the clear negative in-vivo results, it is concluded that the test substance does not induce genetic toxicity.


Justification for selection of genetic toxicity endpoint
In-vivo data selected as the higher level study

Justification for classification or non-classification

A range of in-vitro tests were negative with one ambiguous result. These tests are confirmed as negative by no effects in a battery of in vivo studies with the structural analogue sodium benzoate.