5H-Cyclopenta[h]quinazoline, 6,6a,7,8,9,9a-hexahydro-7,7,8,9,9-pentamethyl-

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The substance is negative in the Ames test (OECD TG 471).

The substance is negative in the Chromosom Aberration test (OECD TG 473).

The substance is negative in the Mouse Lymphoma Assay (OECD TG 490).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The bacterial reverse mutation (Ames) study

The substance is tested in the Ames test (OECD TG 471), using Salmonella typhimurium strains TA100, TA1535, TA98 and TA1537 and E. coli strain WP2uvrA.

In the range finding test (plate incorporation), the substance was tested up to a concentration of 5000 µg/plate and caused a visible reduction in the growth of the Salmonella bacterial background lawns and/or substantial decreases in revertant colony frequency from 1500 µg/plate. No toxicity was noted to Escherichia coli strain WP2uvrA.

In the main test (pre-incubation method) the substance was tested up to a concentration of 5000 µg/plate in the first experiment and up to1500µg/plate (strain TA1535) or5000 µg/plate (all other strains) in the second experiment. The substance induced a slight toxic response with weakened bacterial background lawns initially noted from 50 µg/plate in the absence of S9‑mix and 500 µg/plate in the presence S9-mix.

In the Escherichia coli strain WP2uvrAweakened lawns were noted at 5000 µg/plate in the absence of S9-mix only. The sensitivity of the bacterial tester strains to the toxicity of the test substance varied slightly between strain type, exposures with or without S9‑mix and experimental methodology. 

No significant increases in the frequency of revertant colonies were recorded for any of the bacterial strains, with any dose of the test substance, either with or without metabolic activation or exposure method.

Based on this, the substance is not mutagenic in the Ames test.

Mouse lymphoma assay test:

The substance is tested in the Mouse Lymphoma Assay (OECD TG 490). Mouse lymphoma L5178Y cells cultured in vitro were exposed to the substance in duplicate, both with and without metabolic activation (2% S9 final concentration). The substance was tested in eight dose levels: 1.25 to 30 µg/mL for the 4-hour –S9 exposure, 1.75 to 48 µg/mL in the 4-hour +S9 exposure and 1.25 to 40 µg/mL for the 24-hour –S9 exposure. Vehicle and positive controls were included to confirm the validity of the study. The maximum dose level used was limited by test item induced toxicity. The test substance did not induce any toxicologically significant increases in the mutant frequency at any of the dose levels in the main test, in any of the three exposure groups.

Based on this, the substance is not mutagenic in the Mouse Lymphoma Assay.

In vitro cytogenicity:

The substance is tested in the Mammalian Chomosome Aberration test (OECD TG 473). The substance was evaluated for chromosome aberrations in two experiments under four treatment conditions (4 hour exposure, +2% S9 with cell harvest after 20 hours expression; 4 hour exposure, -S9 with cell harvest after 20 hours expression; 4 hour exposure, + 1% S9 with cell harvest after 20 hours expression; 24 hours exposure, -S9 without expression period). The substance was tested at concentrations 0 -120 μg/mL (+S9) and 0 -80 μg/mL (-S9) in the first experiment and 0 -80 μg/mL in the second experiment. Vehicle and positive control cultures were tested parallel to confirm the validity of the study. In both experiments, the substance did not induce any statistically significant increases in the frequency of cells with aberrations nor did it induce an increase in the numbers of polyploid cells, either in the absence or presence of metabolic activation. Based on this, the substance is not mutagenic in the Mammalian Chromosome Aberration test.

Justification for classification or non-classification

Based on the results of the gene mutations in bacterial cells (Ames test), cytogenicity information (Chromose Abberration test) and the gene mutations in mammalian cells (Mouse Lymphoma Assay), the substance is not genotoxic and therefore does not have to be classified for genotoxicity in accordance with EU CLP (EC no. 1272/2008 and its amendments).