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The mutagenic potential of the test article (Clear colorless liquid, Batch 41260127919/Lot 2) was evaluated in the Bacterial Reverse Mutation Assay with S. typhimurium strains TA98, TA100, TA1535, and TA1537 and E. coli strain WP2 uvrA in the presence and absence of a metabolic activation system (S9-mix rat liver induced by Phenobarbital and B-napthoflavone). The study was performed in compliance with OECD GLP (1997). The test method was based on OECD No. 471 (1997) and EC No. 440/2008 Part B (2008). The test article was dissolved in dimethyl sulfoxide (DMS). A dose range-finding test was performed with concentration up to 5000 ug/plate in the absence and presence of metabolic activation in strains TA100 and WP2uvrA. Based on the results of the dose range finding test, the test article was tested at concentrations of 33 to 5000 ug/plate in the TA1535, TA1537 and TA98 strains in the presence and absence of 5% S9 mix. A second assay was performed in all strains with doses of 100 to 5000 ug/plate in the presence and absence of 10% S9 mix. Strain specific positive controls and vehicle controls were tested in parallel. All treatments were performed in triplicate. No increase in revertant colonies was observed in either the presence or absence of metabolic activation in any strain tested. All criteria for a valid test were met as described in the protocol. Moderate cytotoxicity was observed in strains TA98 and TA100 at 1000 and 5000 ug/plate and extreme cytotoxicity was observed in WP2uvrA at 5000 ug/plate.  Based on the results of the study, the test article was not mutagenic in the Bacterial Reverse Mutation Assay in either the presence or absence of metabolic activation.

 

The potential of the test article (Clear colorless liquid, Purity 98.6%, Batch 41260127919/Lot 2) to induce chromosome aberrations was evaluated in human blood peripheral lymphocytes in the presence and absence of metabolic activation (S9 phenobarbitol and beta-naphthoflavone induced rat livers). The study was performed under GLP (OECD, 1997) conditions. The test method was based on OECD Guideline no. 473 (1997), and EC No. 440/2008, Part B (2008). The test material was dissolved in dimethyl sulfoxide (DMSO). The final concentration of the solvent in the culture medium was 1.0% (v/v). A negative control (DMSO) and positive controls were also prepared (without metabolic activation: Mitomycin C, with metabolic activation: Cyclophosphamide) and tested in parallel with the test article. A dose range finding test was conducted in the presence and absence of metabolic activation beyond the limit of solubility to obtain adequate toxicity data. In the first cytogenetic assay the test article was tested up to 300 µg/ml with and without metabolic activation for a 3 hour exposure (24 hour fixation time). In the second cytogenetic assay the test article was tested up to a concentration of 300 µg/ml without metabolic activation for a 24 hour exposure (24 hour fixation time) and a 48 hour exposure(48 hour fixation time), and with metabolic activation for a 3 hour exposure (24 hour fixation time). Precipitation of the test article occurred at the 1000 µg/ml dose levels. In the absence of S9-mix (24 hour exposure time) no appropriate dose levels could be selected for scoring of chromosome aberrations since at the concentration of 200 ug/mL not enough cytotoxicity was observed, whereas at 250 ug/mL too much toxicity was observed. As a result, dose levels of 200, 220, and 240 ug/mL were retested in that range. No significant increase in cells with chromosomal aberrations, polyploidy, or endoreduplication was observed relative to the controls in the absence or presence of S9-mix. Based on the results of the study, the test article is not clastogenic in human lymphocytes in the presence or absence of metabolic activation.


Short description of key information:
In vitro genetic toxicity studies have been conducted on IOFH. The results of the studies are:

Bacterial Reverse Mutation Assay: Not mutagenic when tested according to OECD 471.

Chromosome Aberration Assay: Not clastogenic when tested according to OECD 473.

Endpoint Conclusion:

Justification for classification or non-classification

Criteria for classifying the test article as genotoxic or mutagenic were not met.