2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-3-pyridine carboxylate; imazapyr (ISO)

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The test substance was not mutagenic in several bacterial and mammalian test systems in vitro covering different genetic endpoints, e.g. point mutations, chromosome abberations, DNA damage and repair (BASF SE, 2012, 2013; American Cyanamid Company, 1982, 1983, 1984)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

AMES TEST

 

Key study (BASF SE, 40M0141/04M006, 2013)

In a primary reverse mutation assays in bacteria (Ames-test), the strains TA 1537, TA 100, TA 1535 and TA 98 of S. typhimurium and WP2 uvrA of E. coli were exposed to the test item in concentrations of 0, 33, 100, 333, 1000, 2600 and 5200 µg/plate. Standard plate tests and preincubation tests were both conducted in the presence and absence of mammalian metabolic activation (S9 mix). The positive controls induced the appropriate responses in the corresponding strains. The outcome of this GLP-study performed according to Guideline 471 was that the test item is not mutagenic.

 

Supporting study (BASF SE, 40M0141/04M005, 2012)

In a primary reverse mutation assay in bacteria (Ames-test), the strains TA 1537, TA 100, TA 1535 and TA 98 of S. typhimurium and WP2 uvrA of E. coli were exposed to the test item in concentrations of 0, 33, 100, 333, 1000, 2500 and 5000 µg/plate. Standard plate tests and preincubation tests were both conducted in the presence and absence of mammalian metabolic activation (S9 mix). The positive controls induced the appropriate responses in the corresponding strains. According to the certificate of analysis the test item expired before the conduction of the study. Therefore this study was only used as supporting study. Nevertheless, the outcome of this GLP-study performed according to Guideline 471 was that the test item is not mutagenic.

 

Supporting study (American Cyanamid Company, IZ-435 -001, 1983)

In a primary reverse mutation assay in bacteria (Ames-test), the strains TA 1537, TA 100, TA 1535, TA 1538 and TA 98 of S. typhimurium and WP2 uvrA of E. coli were exposed to the test item in concentrations of 0, 50, 500, 1581 and 5000 µg/plate. Standard plate tests and preincubation tests were both conducted in the presence and absence of mammalian metabolic activation (S9 mix). The positive controls induced the appropriate responses in the corresponding strains. The test was performed with three replicates per dose. In both tests, the outcome of this pre-guideline study was that the test item is not mutagenic.

 

IN VITRO CHO/HPRT MUTATION TEST

Key study (American Cyanamid Company, IS-435 -005, 1984)

In a primary HPRT study in CHO, concentrations of the test item of 0, 250, 500, 1000, 2500, 5000 µg/mL (with S9-activation) and 0, 125, 250, 500, 1000, 2500 µg/mL (without S9-activation)  were tested. All treatments using the test item produced mutation frequencies roughly equal to those produced by the solvent controls. In addition, appropriate statistical analysis of the data showed that mutation frequencies produced by treatments using the test item were not significantly different from the mutation frequencies produced by the solvent controls. The positive controls, however, did produce significantly different mutation frequencies.

 

 

Unscheduled DNA Synthesis TEST

Key study (American Cyanamid Company, IZ-435 -003, 1984)

In a primary unscheduled DNA synthesis study in rat hepatocyte cells, concentrations of the test item of 0, 50, 100, 500, 1000 and 5000 µg/mL were tested. The criteria established by this laboratory for a valid test have been satisfied. Based on these criteria, the test item did not produce a significant positive response at any level tested when compared to the solvent control. Therefore, under the conditions of this assay the test item is negative in the Rat Hepatocyte Unscheduled DNA Synthesis Assay.

 

Chromosomal Aberration Test

Key study (American Cyanamid Company, IZ-435 -06, 1984)

In a primary chromosomal aberration study in CHO cells, concentrations of the test item of 0, 50, 170, 500, 1700 and 5000 µg/mL were tested. No significant increases in percent aberrant cells or mean aberrations per cell either with or without metabolic activation were noted for the test item. Positive results with control chemicals in the presence and absence of metabolic (S-9) activation reflect the adequacy of the test procedure. Therefore, under the conditions of this study, the test item is not considered to be clastogenic at any of the levels tested.

 

CONCLUSION

In all genetic toxicity tests, the test item revealed no genetic toxicity or mutagenicity whereas the positive control induced the appropriate responses. This conclusion is corroborated by the negative outcome of an early rec-assay performed 1982 with the test item.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. The outcome of all genetic toxicity tests were negative for the test item. As a result the substance is not considered to be classified as mutagenic under Regulation (EC) No. 1272/2008, as amended for the ninth time in Regulation (EC) No 2016/1179.