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 vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August-September 1987

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study was conducted scientifically and in accordance with Good Laboratory Practices.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes

Type of assay:

micronucleus assay

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male/female

Administration / exposure

Route of administration:

intravenous

Doses / concentrations

Remarks:

Doses / Concentrations:3.2 grI/kg bwBasis:

No. of animals per sex per dose:

40 male and 40 female

Control animals:

yes

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negativeIt was concluded from the results obtained that iodixanol showed no evidence of mutagenic potential or bone marrow toxicity when administered by intravenous in the in vivo mouse micronucleus test

Executive summary:

Thirty mice were given 3.2 gI/kg of iodixanol as a single injection via the lateral caudal vein, while a negative control group received a similar volume of saline. The positive control group (10 mice) were dosed orally by gavage with 20 ml/kg of 0.6 mg/kg Mitomycin C. There were no mortalities, but some of the animals dosed with iodixanol showed such clinical signs as hunched posture, waddling, decreased respiratory rate, and in three animals, ptosis. The clinical signs were evident from dosing and lasted up to 4 hours. Five males and five females from the negative control and the test compound groups were sacrificed 24, 48 and 72 hours after dosing, while the positive control group was sacrificed 24 hours after dosing. Samples of bone marrow erythrocytes were obtained from femur, and smears prepared and inspected for micronuclei. At least 1000 erythrocytes from each animal were assessed.

Iodixanol did not induce any statistically significant increase in the number of micronucleated polychromatic or normochromatic erythrocytes at any sampling time. Also the ratio of polychromatic to normochromatic erythrocytes was unaffected by the iodixanol treatment.

Oral treatment with Mitomycin C had no clinical effects, but significantly increased the frequency of micronucleated polychromatic erythrocytes and also decreased the ratio of polychromatic to normochromatic erythrocytes. It was concluded from the results obtained

that iodixanol showed no evidence of mutagenic potential or bone marrow toxicity when administered by intravenous injection in the in vivo mouse micronucleus test.