5-(Acetyl-(3-(acetyl-(3,5-bis(2,3-dihydroxypropylcarbamoyl)-2,4,6-triiodophenyl)amino)-2- hydroxypropyl)amino)-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodobenzene-1,3-dicarboxamide; 5,5'-((2-Hydroxytrimethylene)bis(acetylimino))bis(N,N'-bis(2,3-dihydroxypropyl)-2,4,6- triiodoisophthalamide);

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12.08.1987-22.08.1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study meets the requirements of the OECD Principles of Good Laboratory Practice, Paris, 1992.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Reference

Name:

Unnamed

Type:

Constituent

Method

Species / strain

Species / strain 1

Species / strain / cell type:

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

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1538

Metabolic activation:

with and without

Test concentrations with justification for top dose:

Dose range finding test: 5000, 500, 50, 5 µgI/plate.Mutation tests: 5000, 1500, 500, 150, 50 µgI/plate.

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

water

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

Migrated to IUCLID6: without S-9 mix

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

water

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene

Remarks:

with S-9 mix

Results and discussion

Test results

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

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):negativeIt is concluded that no evidence of mutagenic potential of iodixanol was obtained in this bacterial test system at the dose levels used.

Executive summary:

Iodixanol was not toxic towards the tester strains. Therefore 5000 µgI/plate was chosen as the top dose level in the mutation tests.

No substantial increases in revertant colony numbers of any of the five tester strains were observed following treatment with iodixanol at any dose level, either in the presence or absence of metabolic activation (S-9 mix).

In the Ames test, five different strains of Salmonella typhimurium (TA 1535, 1537, 1538, 98 and 100) were tested for revertant colonies both in the presence and in the absence of a metabolising system (S9 mix) (10). Iodixanol was not toxic towards the tester strains, and therefore 5000 μgI/plate was chosen as the top concentration in the mutation tests. There were no substantial increases in revertant colonies in any of the tester strains following treatment with iodixanol at any concentration, either in the presence or in the absence of the S9 mix. The positive control substances in the test system (N-ethyl-N'-nitrosoguanidine, 9-aminoacridine, 2-nitrofluorene and 2-aminoanthracene) were highly mutagenic, thus confirming the sensitivity of the test system.

It was concluded that no evidence of mutagenic potential of iodixanol was obtained in this bacterial test system at the concentrations used.