Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

GLP OECD 471 assay: negative

Chromosomal aberration and SCE: negative

Taurine's lack of genotoxic potential is corroborated by its long history of use, endogenous nature, natural occurrence in the human diet, and lack of structural alerts for genotoxicity. In addition, the SCF (1999, 2003) concluded that based on the available toxicology studies, taurine does not exhibit any potential for genotoxicity or carcinogenicity.

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09.05.1994 - 23.08.1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay
Specific details on test material used for the study:
A 3 kg sample of MTC Taurine A (lot no. 302-3), fine opaque/white crystals and a 3 kg sample of MTC Taurine B (lot no. OISRM), a fine white aggregated crystalline powder, both contained in clear plastic jars, were received from Mitsui Toatsu Chemicals Incorporated on 13 April 1994. They were stored cool in the dark until required. The ident'ity, strength, purity and stability of the test materials were the responsibility of the Sponsor.
Target gene:
HIS Operon, TRP operon
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Metabolic activation system:
Arocror 1254 induced rat liver S9 mix
Test concentrations with justification for top dose:
from 50 to 5000 ug per plate (toop dose according to guideline)
Vehicle / solvent:
water
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
N-ethyl-N-nitro-N-nitrosoguanidine
benzo(a)pyrene
methylmethanesulfonate
other: 2 -Aminoanthracene
Details on test system and experimental conditions:
According to guideline
Rationale for test conditions:
According to guideline
Evaluation criteria:
According to guideline
Statistics:
According to guideline
Key result
Species / strain:
other: all strains tested
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Conclusions:
It was concluded that MTC Taurine A and MTC Taurine B were devoid of mutagenic activity under the conditions of the test.
Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosomal Aberration Test)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 479 (Genetic Toxicology: In Vitro Sister Chromatid Exchange Assay in Mammalian Cells)
GLP compliance:
not specified
Type of assay:
in vitro mammalian chromosome aberration test
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source of test material: Sigma Chemical Co.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: dissolved in phosphate-buffered saline (PBS) lacking Cat+ and Mg++, and dispensed to the cultures at the final concentration of 10e-3 M.
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Metabolic activation:
without
Test concentrations with justification for top dose:
10e-3 M
Untreated negative controls:
yes
Positive controls:
yes
Positive control substance:
mitomycin C
Details on test system and experimental conditions:
CHO cells are routinely cultured in our laboratory in Ham F-10 medium (Flow) supplemented with 15% fetal calf serum (FCS), 1% Lglutamine, 2% penicillin (5,000 IU/ml), and streptomycin (5,000 ig/ ml).
Under these conditions, the average cell cycle lasts 12 hr. In all experiments, cells were seeded at a density of 1 X 10e6 per 5-ml flask; after 4 hr, cells were treated according to the various protocols.
For SCE and chromosomal aberrations (ChAb) analysis, cultures were treated with the appropriate concentrations of taurine. After 15 min in combined treatment cultures, MMC was added for 2 hr.
Treatment with H2O2 was performed in NaCl (0.9%) for 0.5 hr at 37°C. The cultures were then washed twice in nonsupplemented medium, and incubated in fresh complete medium containing BrdUrd at a final concentration of 5 x 10e-6 M.
The cells were fixed after 26 hr for SCE analysis, and after 16 and 22 hr for ChAb analysis. Colchicine (5 x 10e-7 M) was always added 2 hr before the cells were fixed.
The normal Giemsa-Hoechst techniquewith slight modifications, was used for the differential staining of sister chromatids.
For SCE analysis and ChAb analysis, 40 second mitoses (M2) and 100 first mitoses (M1) were scored from coded slides for each point in each experiment. All experiments were repeated three times. For each experimental point, 1,000 cells were scored for the mitotic index (M.I.), and 100 metaphases were analyzed for first (M1), second (M2), and third and successive (M3) mitosis determination (proliferation index).
For cytofluorimetric analysis, cells were seeded for 15 min in PBS lacking Ca++ and Mg”, and containing 2’,7’-dichlorofluorescin diacetate (DCFH-DA) (5 µM), as well as sodium azide (5 mM), which was added to inhibit cellular catalase. The medium was then removed and the cells seeded in PBS containing taurine; after 15 min the mutagens were added in the same conditions as for the cytogenetic experiments. In the case of the MMC assay, 0.5 hr treatment was also perfomed to avoid fluorescence decrease due to a long period of incubation.
After trypsinization, the cells were analyzed in a FACSTAR cytometer (Becton Dickinson) equipped with a 5-watt argon laser (Coherent) (488 nm emission).
Statistics:
For the SCE analysis, means and standard errors were determined. Control and treated cultures were compared by Student’s t-test.
For cytofluorimetric data, the Kolmogorov-Smimov test [Young, 19771 was applied to compare the distribution of fluorescence for each type of treatment.
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Taurine was not able to induce SCEs and ChAb under this experimental conditions at the tested doses. Furthermore, neither agent affected mitotic and proliferation (M1-M3) indices.
H202 induced a significant increase in ChAb (36% abnormal cells) and a slight increase in SCEs, which accords with literature data [Oya et al., 1986; Larramendy et al., 1987; Tachon, 1990; Rueff et al., 19931].
H202 induced a substantial proportion of heavily damaged cells. Conversely, MMC is a good inducer of SCEs (51.1 +/- 1.89 and 44 f+/- 1.27) and ChAb (24-36% aberrant metaphases).
When taurine was used for combined treatment with H202, a slight decrease of SCEs was obtained (17% reduction), while the decrease in ChAb is more evident (from 52 total aberrations to 29). As H202 treatment induces a slight decrease in the mitotic index, taurine is able to restore the mitotic index to control level. The effect on the proliferation index is more evident. Conversely, taurine is unable to reduce MMC-induced SCEs and ChAb.
Conclusions:
These data are in accordance with the possibility that taurine partially scavenges oxygen species, consequently reducing SCEs and ChAb induced by H202.
On the other hand, as expected, there is no effect on MMC-induced SCEs and ChAb.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the available information, no classification is warranted.