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The mutagenicity of beta-alanine was examined in two Ames tests. One the study was conducted according to OECD TG 471 and 472 under GLP conditions. The mutagenicity of beta-alanine was examined using the plate incorporation method inS. typhimurium TA 100, TA 98, TA 1535, TA 1537 and E. coli WP2 uvr A, at concentrations up to 5000μg/plate with or without metabolic activation. In this study, the number of revertant colonies per plate with beta-alanine was less than twice that of the solvent control. These results are in agreement with another study of equal quality conducted according to Standards for Toxicity Investigations, and Procedures of Mutagenicity Test Using Microorganisms and Evaluation of Test Results (8 February 1999) and under GLP conditions. In this study the mutagenicity of beta-alanine was examined using the preincubation method in four S. typhimurium strains, TA98, TA100, TA1535, and TA1537, and in Escherichia coli strain, WP2 uvrA, with or without a metabolic activation system. In this study, the number of revertant colonies per plate with the test substance was less than twice that of the negative control.

A chromosome aberration study was conducted according to OECD TG 473 under GLP conditions. Chinese hamster fibroblasts (CHL/IU cells) were treated continuously (24 or 48 hours) in the absence of metabolic activation and shortly (6 hours) in the presence or absence of metabolic activation with beta-alanine at concentrations of 0.223, 0.446, and 0.891 mg/mL. The recovery time of the short-time treatment in the confirmation test was extended to 24 hours to examine whether beta-alanine shows delayed chromosome aberrations. No increase in clastogenicity (structural chromosome aberration) or polyploidy was observed in such conditions. Therefore, beta-alanine is judged to be non-mutagenic under the test conditions chosen.

No in vitro gene mutation study in mammalian cells conducted with beta-alanine is available. However, such study does not need to be conducted since beta-alanine is a naturally occurring and non-proteogenic beta-amino acid (i.e. is not used in the biosynthesis of any major proteins) endogenously produced by the liver. It is formed in vivo by the degradation of dihydrouracil and carnosine. It is a component of the naturally occurring peptides carnosine and anserine and also of pantothenic acid (vitamin B5) which itself is a component of coenzyme A. Once produced in the liver, beta-alanine is taken up by several tissues, including skeletal muscle. Under normal conditions, beta-alanine is metabolized into acetic acid. In addition, it s formed in vivo by the metabolism of spermine and L-aspartate, which is also a component of several RPMI mediums for cell cultures. Beta-alanine is found in living tissue, and does not pose a hazard to human health. Therefore, it can be expected that beta-alanine is not mutagenic in a gene mutation test in mammalian cells.

No in vivo genetic toxicity study on beta-alanine is available. However, there is no need for such studies to be conducted since already 2 Ames tests and 1 chromosome aberration test showed that beta-alanine is not mutagenic. Furthermore, beta-alanine is a naturally occurring and nonproteogenic beta-amino acid (i.e is not used in the biosynthesis of any major proteins) endogenously produced by the liver. Therefore, it can be expected that beta-alanine is not mutagenic in a gene mutation test in mammalian cells as well. Taken all these facts together, and for reasons of animal welfare, no in vivo test needs to be conducted.


Short description of key information:
-Gene Mutation (Ames test): negative in S. typhimurium strains TA 100, TA 98, TA 1535, TA 1537 and E. coli strain, WP2 uvrA at concentrations up to 5000 μg/plate with or without metabolic activation system (OECD TG 471 and 472, plate incorporation system, GLP conditions) .
-Gene Mutation (Ames test): negative in Salmonella typhimurium strains, TA98, TA100, TA1535, and TA1537, and in an Escherichia coli strain, WP2 uvrA, with or without a metabolic activation system according to Standards for Toxicity Investigations, and Procedures of Mutagenicity Test Using Microorganisms and Evaluation of Test Results (8 February 1999) and under GLP conditions.
-In-vitro cytogenetic study in mammalian cells: negative in Chinese hamster fibroblasts (CHL/IU cells) in presence and absence of metabolic activation (OECD TG 473 and GLP conditions).
- In-vitro gene mutation study: waiver.
- in-vivo genotoxic studies: waiver.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

On the basis of the above exposed, beta-alanine is not to be classified for genotoxicity according to DSD and CLP classification criteria.