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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No genetic toxicity study with calcium dibenzoate is available, thus the genetic toxicity will be addressed with existing data on the individual moieties calcium and benzoate.

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

Genetic toxicity in vivo

Description of key information

No genetic toxicity study with calcium dibenzoate is available, thus the genetic toxicity will be addressed with existing data on the individual moieties calcium and benzoate.

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

Additional information

Calcium

Considering the overall weight of evidence, such as in vitro data and the crucial role of calcium in cellular processes such as DNA-polymerase and cell cycle functioning as well as its role in approved in vitro genotoxicity experiments show that calcium does not exert any genotoxic or mutagenic effects to mammalian cells. Based on the above existing information on the genotoxicity of calcium substances and the weight of evidence information, calcium is considered as not genotoxic.

 

Benzoic acid

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.

 

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.

 

Calcium dibenzoate

Calcium dibenzoate is not expected to be genotoxic, since the moiety benzoic acid respectively benzoate has neither shown a gene mutation potential in bacteria or mammalian cells nor a clastogenic potential in in vitro and in vivo cytogenicity studies.

The use of calcium substances as essential supplements in cell culture media used for genotoxicity tests demonstrates the absence of an mutagenic potential of the moiety calcium in vitro. Taking further into consideration the biochemical role of calcium in the human body and the normal daily dietary requirements, an in vivo genotoxic effect of calcium is also considered highly unlikely. Further testing is not required. For further information on the toxicity of the individual moieties, please refer to the relevant sections in the IUCLID and CSR.

Justification for classification or non-classification

As the two moieties of calcium dibenzoate do not have a genotoxic activity, calcium dibenzoate in all probability has also no potential to induce genotoxic effects.

According to the criteria of REGULATION (EC) No 1272/2008 and its subsequent adaptions, calcium dibenzoate does not have to be classified and has no obligatory labelling requirement for germ cell mutagenicity.