Trisodium trihydrogen 5,5',5''-(1,3,5-triazine-2,4,6-triyltriimino)tris[5-sulphonatosalicylate]

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

DURING THIS IN VITRO SALMONELLA/MAMMALIAN-MICROSOME ASSAY NO GENE MUTAGENIC ACTIVITY COULD BE DEMONSTRATED UNDER THE EXPERIMENTAL CONDITIONS REPORTED

In an IN VITRO ESCHERICHIA COLI REVERSE MUTATION ASSAY NO GENE MUTAGENIC ACTIVITY COULD BE DEMONSTRATED UNDER THE EXPERIMENTAL CONDITIONS REPORTED.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

well performed guideline like study with GLP but without confirmation of negative results in a second experiment

Qualifier:

according to guideline

Guideline:

other: Ames et al, Mutation Res. (1975) 31, 347-364

Deviations:

not specified

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain / cell type:

S. typhimurium TA 1538

Metabolic activation:

with and without

Metabolic activation system:

AROCLOR 1254 induced rat liver S-9 mix

Test concentrations with justification for top dose:

1.58 / 5 / 15.8 / 50 / 158 / 500 / 1580 and 5000 µg/plate

Vehicle / solvent:

DIMETHYLSULFOXIDE

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: methylmethanesulphonate, 9-aminoacridine, 2-nitrofluorene, N-ethyl-N-nitro-N-nitrosoguanidine without metabolic activation; 2-aminoanthracene, benzo(a)pyrene with metabolic activation.

Details on test system and experimental conditions:

METHOD OF APPLICATION: plate incorporation

NUMBER OF REPLICATIONS: each compound concentration including controls is tested in triplicate, without confirmation of negative results by further testing

Evaluation criteria:

SPECIAL ATTENTION WAS GIVEN TO A REPRODUCIBLE DOSE-EFFECT RELATIONSHIP.

A MUTAGENIC ACTIVITY WAS ASSUMED IF AT LEAST A TWO FOLD (FOR TA 100: ONE AND HALF FOLD) INCREASE OF THE NUMBER OF INDUCED REVERTANTS WAS OBTAINED IN COMPARISON WITH THE SPONTANEOUS REVERTANTS OF THE CORRESPONDING CONTROLS.

Key result

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Conclusions:

DURING THIS IN VITRO SALMONELLA/MAMMALIAN-MICROSOME ASSAY NO GENE MUTAGENIC ACTIVITY COULD BE DEMONSTRATED UNDER THE EXPERIMENTAL CONDITIONS REPORTED.

Executive summary:

THE TEST ITEM WAS TESTED FOR DETECTING ITS POTENTIAL GENE MUTAGENIC ACTIVITY ACCORDING TO THE PLATE INCORPORATION METHOD OF AMES ET AL. USING THE SALMONELLA THYPHIMURIUM STRAINS TA 98, TA 100, TA 1535, TA 1537 AND TA 1538.

THE TEST WAS PERFORMED WITH AND WITHOUT LIVER MICROSOMAL ACTIVATION. THE TEST MATERIAL WAS TESTED AT EIGHT CONCENTRATION: 1.58 / 5 / 15.8 / 50 / 158 / 500 / 1580 AND 5000 µg PER PLATE. EACH COMPOUND CONCENTRATION INCLUDING CONTROLS WAS TESTED IN TRIPLICATE.

A VERY SLIGHT PRECIPITATION OF THE TEST MATERIAL WAS OBSERVED AFTER POURING THE CONTENT OF THE TEST TUBE OVER THE SURFACE OF THE SELECTIVE AGAR PLATE AT THE CONCENTRATIONS OF 1580 AND 5000 µg PER PLATE. THE REVERTANTS WERE EASILY RECOGNIZABLE AND THE PLATES COULD BE EVALUATED.

UP TO THE HIGHEST TESTED DOSE, WITH AND WITHOUT MICROSOMAL ACTIVATION, NO RELEVANT INCREASE OF THE REVERTANT COLONY NUMBERS WAS OBTAINED IN ANY SALMONELLA THYPHIMURIUM STRAIN IN COMPARISON WITH THE CORRESPONDING CONTROLS.

NO TOXIC EFFECTS OF THE TEST MATERIAL WERE OBSERVED.

Reference 2

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

well performed guideline like study with GLP but without confirmation of negative results in a second experiment

Qualifier:

according to guideline

Guideline:

other: Green et al, Mutation Res. (1976) 38, 3 - 32

Deviations:

not specified

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

AROCLOR 1254 induced rat liver S-9 mix

Test concentrations with justification for top dose:

1.58 / 5 / 15.8 / 50 / 158 / 500 / 1580 and 5000 µg/plate

Vehicle / solvent:

dimethylsulfoxide

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: methylmethanesulphonate, N-ethyl-N-nitro-N-nitrosoguanidine (without metabolic activation); 2-aminoanthracene (with metabolic activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: plate incorporation

NUMBER OF REPLICATIONS: each compound concentration including controls is tested in triplicate, without confirmation of negative results by further testing

Evaluation criteria:

SPECIAL ATTENTION WAS GIVEN TO A REPRODUCIBLE DOSE-EFFECT RELATIONSHIP.
A MUTAGENIC ACTIVITY IS ASSUMED IF AT LEAST A TWO FOLD INCREASE OF THE NUMBER OF INDUCED REVERTANTS IS OBTAINED IN COMPARISON WITH THE SPONTANEOUS REVERTANTS OF THE CORRESPONDING CONTROL.

Key result

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Conclusions:

IN CONCLUSION IT CAN BE STATED THAT DURING THIS IN VITRO ESCHERICHIA COLI REVERSE MUTATION ASSAY NO GENE MUTAGENIC ACTIVITY COULD BE DEMONSTRATED UNDER THE EXPERIMENTAL CONDITIONS REPORTED.

Executive summary:

THE TEST ITEM WAS TESTED FOR DETECTING ITS POTENTIAL GENE MUTAGENIC ACTIYITY ACCORDING TO THE PLATE INCORPORATION METHOD OF GREEN ET AL, USING THE ESCHERICHIA COLI STRAIN WP2UVRA.

THE TEST WAS PERFORMED WITH AND WITHOUT LIVER MICROSOMAL ACTIYATION. THE TEST MATERIAL WAS TESTED AT EIGHT CONCENTRATIONS: 1.58 / 5 / 15.8 / 50 / 158 / 500 / 1580 AND 5000 µg PER PLATE. EACH COMPOUND CONCENTRATION INCLUDING CONTROLS WAS TESTED IN TRIPLICATE.

A VERY SLIGHT PRECIPITATION OF THE TEST MATERIAL WAS OBSERYED AFTER POURING THE CONTENT OF THE TEST TUBE OVER THE SURFACE OF THE SELECTIYE AGAR PLATE AT THE CONCENTRATIONS OF 1580 AND 5000 µg PER PLATE. THE REVERTANTS WERE EASILY RECOGNIZABLE AND THE PLATES COULD BE EYALUATED.

UP TO THE HIGHEST TESTED DOSE, WITH AND WITHOUT LIVER MICROSOMAL ACTIYATION, NO RELEVANT INCREASE OF THE REVERTANT COLONY NUMBERS WAS OBTAINED IN COMPARISON WITH THE CORRESPONDING CONTROLS.

NO TOXIC EFFECTS OF THE TEST MATERIAL WERE OBSERVED.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Mode of Action Analysis / Human Relevance Framework

No relevant findings observed

Additional information

Two Bacerial Reverse Mutation Assays were performed to investigate the potential of the test item to induce gene mutations using the following tester strains:

key_471 E. coli_1982_RCC_012385:

Escherichia colistrain WP2 uvrA, with and without metabolic activation.

key_471 S. typhimurium_1982_RCC_012385:

TA 1535, TA 1537, TA 98, TA 100, and 1538, with and without metabolic activation.

Although each of these tests is incomplete (regarding tester strains or confirmation of negative results) the set in its entirety fulfills all requirements of a fully valid study thus allowing the conclusion that the test item exerts no gene mutagenic activity in this test system.

Justification for selection of genetic toxicity endpoint
No single study was selected because in view of minor shortcomings in all available studies preference is given to the entirety of all available studies in order to get a fully valid data set.

Short description of key information:
AMES, key_471 E. coli_1982_RCC_012385: negative
AMES, key_471 S. typhimurium_1982_RCC_012385: negative

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Findings in the bacterial reverse mutation assays do not point to genotoxic properties of the test item.

Thus the substance subject to registration does not meet criteria for classification according to REGULATION (EC) No 1272/2008.