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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment

Data source

Reference
Reference Type:
publication
Title:
ANTIMUTAGENIC EFFECT OF PHENOLIC ACIDS
Author:
Birosova L., Mikulasova M., Vaverkova S.
Year:
2005
Bibliographic source:
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2005, 149(2):489–91.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In the present study, the plate-incorporation test of the Salmonella mutagenicity assay was used to examine the effect of selected phenolic acids against 5NFAA and sodium azide mutagenicity.
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
3,4,5-trihydroxybenzoic acid
EC Number:
205-749-9
EC Name:
3,4,5-trihydroxybenzoic acid
Cas Number:
149-91-7
Molecular formula:
C7H6O5
IUPAC Name:
3,4,5-trihydroxybenzoic acid
Test material form:
solid
Details on test material:
Name: gallic acid

Method

Species / strain
Species / strain / cell type:
S. typhimurium TA 100
Test concentrations with justification for top dose:
30, 60, 120, 250, 500 µg/plate
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
no
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
other: 3-(5-nitro-2-furyl)acrylic acid (5NFAA)
Details on test system and experimental conditions:
The inhibitory effect of phenolic acids on mutation induction by several positive mutagens was investigated with Salmonella typhimurium TA100 using pre-incubation method. 0.1 ml of the positive mutagen, 0.1ml of phenolic acid and 0.1 ml of bacterial culture (cultivation for 16 h at 37 °C, approximate cell density 2–5 × 108 cells/ml) were mixed and preincubated at 37 °C for 30 min. Soft agar (2 ml) was added and the mixture was poured onto minimal agar plates. After 48 h of incubation at 37 °C the number of revertants was counted. The results from the antimutagenicity studies represent the mean of three separate experiments, each run in triplicate, and they were statistically evaluated using the Student’s t-test. Antimutagenicity was expressed as percentage of mutagenicity inhibition following the formula: % mutagenicity = 100–[(X1/X2) × 100] where X1 = number of revertants per plate in the presence of mutagen and antimutagen, X2 = number of revertants per plate in the absence of antimutagen.
Statistics:
Results were statistically evaluated using the Student’s t-test.

Results and discussion

Test results
Species / strain:
S. typhimurium TA 100
Metabolic activation:
not specified
Genotoxicity:
other: Inhibition of the mutagenicity
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Additional information on results:
The positive control of mutagen in each case was considered as 100 % mutagenicity. Gallic acid was the only phenolic acid successful in inhibiting the mutagenicity of 5NFAA by more then 50 % at the concentration of 500 μg/plate. All tested compounds (with the exception of cichoric acid) decreased the number of revertants induced by sodium azide by about 20–35 %. Similarly as in the case of 5NFAA, the effect of sodium azide was significantly reduced by gallic acid and within the concentration tested a marked dose-dependence was found. At the highest used concentration this phenolic acid inhibits mutagenic activity of sodium azide by 82 %.

Applicant's summary and conclusion

Conclusions:
In the present study, the Salmonella typhimurium tester strain TA 100 was used in the plate-incorporation test to examine the antimutagenic potential of caffeic, ferulic and cichoric acids extracted from plant species of genera Echinacea (L) Moench, as well as of another phenolic acids, on 3-(5-nitro-2-furyl)acrylic acid (5NFAA) and sodium azide mutagenicity. All tested compounds possess antimutagenic activity. In the case of 5NFAA, the antimutagenic potency of tested compounds was in the order of gallic acid > ferulic acid > caffeic acid > syringic acid > vanillic acid.
The mutagenic effect of sodium azide was inhibited by tested phenolic acids by about 20–35 %. The most effective compound, gallic acid inhibits this effect by 82 % in the concentration of 500 μg/plate. The only exception from favourable properties of tested phenolic acids is cichoric acid, which in the contrary significantly increased the mutagenic effect of 5NFAA.
Executive summary:

In the present study, the Salmonella typhimurium tester strain TA 100 was used in the plate-incorporation test to examine the antimutagenic potential of caffeic, ferulic and cichoric acids extracted from plant species of genera Echinacea (L) Moench, as well as of another phenolic acids, on 3-(5-nitro-2-furyl)acrylic acid (5NFAA) and sodium azide mutagenicity. All tested compounds possess antimutagenic activity. In the case of 5NFAA, the antimutagenic potency of tested compounds was in the order of gallic acid > ferulic acid > caffeic acid > syringic acid > vanillic acid.

The mutagenic effect of sodium azide was inhibited by tested phenolic acids by about 20–35 %. The most effective compound, gallic acid inhibits this effect by 82 % in the concentration of 500 ?g/plate. The only exception from favourable properties of tested phenolic acids is cichoric acid, which in the contrary significantly increased the mutagenic effect of 5NFAA.

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