Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 200-745-3 | CAS number: 71-00-1
Effect of amino acids on spontaneous mutagenesis in E. coli
Values are the means of relative mutants per total cells data (mutant frequency on test plates divided by mutant frequency on control plates) from triplicate plate-assay experiments for LacZ53 strains.
Amino acid tested
Relative Lac+mutagenesis in the presence of 2 mM
Values did not indicate a significant effect on mutagenesis by either of two criteria.
In this study, 19 amino acids were tested to see if their catabolism was mutagenic, using uvrB cells. More specifically, the goal was to find a type of mutagenesis that is regulated by DNA repair genes. The study was not GLP and no OECD guideline was followed. A plate assay for mutagenesis was performed in which E. coli strains were incubated with the test substance for 3 days at 37°C with or without glucose present. Hereafter, Lac+ mutants were scored and the ratio test/control was determined, taking into account the growth-normalization factors.
L-histidine did not show a significant effect on Lac reversion in the uvrB strain, and thus, was found not to be mutagenic.
The chromosome aberration assay of Zhang (1992) investigated the effect ot L-histidine on sister-chromatid exchange (SEC) frequency in human peripheral blood lymphocytes. The chromosome preparations were made according to the Giemsa method. No guideline was followed to conduct this study, however, it is similar to the OECD 479. The concentrations tested were 10, 50 and 100 µg/mL.
An increase in the number of SCE was seen at the three tested concentrations, when compared to control cells. A statistical significant dose-related increase in the mean number of the SCEs was not investigated. Nevertheless, it was concluded that L-histidine can induce SCE in human peripheral blood lymphocytes at any concentration.
However, as L-histidine is an essential substance for the growth of the peripheral blood lymphocytes it is very unexpected that it can induce SCE. The current hypothesis is that the exogenous addition of amino acids to the cells can result in an imbalance of the amino acids in the medium, causing metabolic disturbances in the cells. And after influencing the activity of various enzymes this might induce SCE.
In the gene mutation assay of Sargentini and Smith (1986) 19 amino acids, including L-histidine, were tested to see if their catabolism was mutagenic, using uvrB cells. More specifically, the goal was to find a type of mutagenesis that is regulated by DNA repair genes. The study was not GLP and no OECD guideline was followed, however, the study was well conducted and documented. A plate assay for mutagenesis was performed in which E. coli strains were incubated with the test substance for 3 days at 37°C with or without the presence of glucose. Hereafter, Lac+ mutants were scored and the ratio test/control was determined, taking into account the growth-normalization factors.
L-histidine did not show a significant effect on Lac reversion in the uvrB strain, and thus, L-histidine was found not to be mutagenic.
The criteria used for the classification of genotoxicity are Table 3.5.1 and section 220.127.116.11. of the CLP regulation No 1272/2008. According to these criteria L-histidine does not require classification for germ cell mutagenicity. Moreover, the genotoxic/mutagenic potential of L-histidine can be excluded for various reasons. L-histidine is a naturally occuring essential amino acid and a normal constituent in living cells. It is ingested daily in significant amounts and a basic metabolite and building block of all living organisms. Aditionally, L-histidine was shown not be a carcinogen (Ikezaki, 1996).
In conclusion, we can state that L-histidine does not require to be classified according to the criteria of the CLP regulation for this endpoint.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Close Do not show this message again