Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

N-(3-Aminopropyl)-imidazol showed no genotoxic effects in various in vitro tests (Ames test, HPRT test, chromosomal aberration test).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

N-(3-Aminopropyl)-imidazol showed no genotoxic effects in the in vivo MNT test.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Mode of Action Analysis / Human Relevance Framework

not specified

Additional information

In vitro study: Bacterial system

N-(3-Aminopropyl)-imidazol was tested in the bacterial reverse mutation assay with S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2 uvrA in concentrations between 20 -5000 µg/plate (OECD471; 1999; RL1). An increase in the number of his+ or trp+ revertants was not observed in the standard plate test or in the preincubation test either with or without S-9 mix. A weak bacteriotoxic effect (slight decrease in the number of revertans, slight reduction in the titer) was occasionally observed in the standard plate test depending on the strain and the conditions from about 2500 µg/plate onward. In the preincubation assay bacteriotoxicity (reduced background growth, decrease in the number of revertants, reduction in the titer) was observed depending on the strain and the test conditions from about 500 µg - 2500 µg/plate onward. In conclusion, the test substance N-(3-Aminopropyl)-imidazol is not mutagenic in the Salmonella typhimurium/Escherichia coli reverse mutation assay under the experimental conditions chosen here.

In vitro study: Mammalian cell gene mutation test

N-(3-Aminopropyl)-imidazol was tested in a HPRT test with chinese hamster ovary (CHO) cells in a concentration between 0.16 -1250 µg/ml (OECD476; 2012; RL1). The vehicle controls gave mutant frequencies within the range expected for the CHO cell line. Both positive control substances, EMS and MCA, led to the expected increase in the frequencies of forward mutations. In this study, in the experimental parts after 4 hours exposure in the absence and the presence of metabolic activation no cytotoxicity was observed up to the highest required concentration tested for gene mutations. Besides, in the 2nd Experiment in the absence of metabolic activation after 24 hours exposure the highest concentrations evaluated for gene mutations were clearly cytotoxic. The 2nd Experiment in the presence of S9 mix was discontinued due to a technical error. On the basis from the results of the present study, the test substance did not cause any relevant increase in the mutant frequencies either without S9 mix or after adding a metabolizing system in three experiments performed independently of each other. The test substance N-(3-Aminopropyl)-imidazol is not mutagenic in the HPRT locus assay under in vitro conditions in CHO cells in the absence and the presence of metabolic activation.

In vitro study: Chromosomal aberration test

N-(3-Aminopropyl)-imidazol was tested in a chromosomal aberration assay in chinese hamster lung fibroblasts (V79) in concentrations up to 1300 µg/ml (OECD473; 1999; RL1). In both experiments, in the absence and presence of S9 mix, no biologically relevant increase in the number of cells carrying structural chromosome aberrations was observed. In the absence and in the presence of S9 mix, the aberration rates of the cells after treatment with the test article were within the range of the solvent control and within the range of our historical control data: 0.0 % -4.0 %. The observed apparent dose related increases in experiment II after 18 h treatment in the absence of S9 mix were regarded as being irrelevant, since they were within our historical control data range and caused by a statistical arrangement of the values. In both experiments, no biologically relevant increase in the rate of polyploid metaphases was found after treatment with the test article as compared to the rates of the solvent controls. In both experiments, EMS (600 and 1200 µg/ml, respectively) and CPA (0.71 µg/ml) were used as positive controls and showed distinct increases in cells with structural chromosome aberrations. In conclusion, the test article N-(3-Aminopropyl)-imidazol did not induce structural chromosome aberrations in V79 cells (Chinese hamster cell line).

In vivo study:

N-(3-Aminopropyl)-imidazol was tested in a MNT in mice in concentrations between 375, 750 and 1500 mg/kg (OECD474; 2011; RL1). After treatment with the test item the number of PCEs was not decreased as compared to the mean value of PCEs of the vehicle control thus indicating that N-(3-Aminopropyl)-imidazol did not exert any cytotoxic effects in the bone marrow. In comparison to the corresponding vehicle controls there was no statistically significant or biologically relevant enhancement in the frequency of the detected micronuclei at any preparation interval and dose level after administration of the test item. The mean values of micronuclei observed after treatment with N-(3-Aminopropyl)-imidazol were near or below to the value of the vehicle control group. Cyclophosphamide administered orally [40 mg/kg b.w.; 10 mL/kg b.w.; once] was used as positive control which showed a substantial and biologically relevant increase of induced micronucleus frequency. The test item did not induce micronuclei as determined by the micronucleus test in the bone marrow cells of the mouse.

Justification for classification or non-classification

Based on the negative in vitro and in vivo results a GHS classification according to Annex I of the Regulation EC/1272/2008 is not required