5-amino-2,4,6-triiodo-1,3-benzenedicarbonyldichloride

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Results of available in vitro studies:

-Bacterial reverse mutation assay (OECD 471): positive

-Chromosome aberration assay (OECD 473): positive

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (positive)

Genetic toxicity in vivo

Description of key information

Results of available in vivo studies:

- In vivo rat liver DNA repair test: negative

-Mammalian erythrocytes micronucleus assay :negative

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Mode of Action Analysis / Human Relevance Framework

Ames test

The mutagenic effect of the test item was assessed according to OECD 471 and EU Method B14 guideline.

The test substance was tested in the Ames Salmonella/microsome plate test with four histidine-requi ring strains of Salmonella typhimurium (TA1535, TA1537, TA100 and TA98) in the absence and presence of metabolic activation. The test substance was found to be mutagenic in this assay.

Due to the positive response in the bacterial mutation assay, an available chromosomal aberration test is available. The test susbtance was assessed for potential to induce structural chromosome aberrations in cultured peripheral human lymphocytes in the presence and absence of a metabolic activation system accroding to OECD 473 and EU Method B10. It was concluded that the test substance is clastogenic in human lymphocytes under the experimental conditions.

 

The test substance was assessed for induction of DNA repair in hepatocytes following acute oral administration to Specific Pathogen Free outbred albino Hsd/Ola Sprague-Dawley male rats at dosages of 200, 1000 and 2000 mg/kg bodyweight

The test substance did not cause any substantial increases in either the gross nuclear grain count or the net nuclear grain count (ie the gross nuclear grain count minus the cytoplasmic grain count) at any dose level at either sampling time.

Positive control group animals showed a large and highly significant increase (P < 0.001) in the net nuclear grain count which was accompanied by a large increase in the gross nuclear grain count.

It is concluded that the test substance did not cause unscheduled DNA synthesis in the rat liver in this in vivo test system.

 

To complete the assessment the test substance was evaluated for the potential to induce micronuclei in polychromatic erythrocytes in th ebone marrow of the mouse, according to EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test).

It was concluded that the test substance is not mutagenic in the micronucleus test under the experimental conditions.

Justification for classification or non-classification

The overall evaluation of the potential of the test substance to induce genetic toxicity was based on: positive responses in a bacterial reverse mutation assay and in vitro chromosomal aberration assay; negative responses in an in vivo micronucleus assay and in vivo rat liver DNA repair test.

According to ECHA Guidance R.7a, positive in vitro outcomes need to be further investigated in representative in vivo assays. As the in vivo micronucleus and in vivo rat liver DNA repair test outcomes were negative, thus the test substance is not classified for genetic toxicity within the CLP Regulation (EC 1272/2008).