Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

In vitro: One key study and two supporting studies indicated that 1 -nitropropane did not induce reverse mutations in the Salmonella Typhimurium (Ames) test with or without metabolic activation.  Similarly, it was negative in a chromosomal aberration test using Chinese hamster lung cells with or without metabolic activation.  1 -Nitropropane was negative in DNA repair tests using rat hepatic or rat, mouse, hamster or human extrahepatic cell lines.  Conversely, onein vitrotest indicated that 1-NP enhanced the formation of micronuclei in Chinese Hamster lung cells V79. Another in vitro mammalian cell gene mutation test (HPRT) did show an increase in the number of 6-thioguanine resistant mutations.  However, both of these positive results should be interpreted in light of conflicting in vitro testing and the higher tiered in vivo testing, specifically, where the bone marrow micronucleus test and the in vivo rat UDS test were negative.

In vivo: The micronucleus test in the rat did not show an increase in polychromatic erythrocytes in the bone marrow. In the same experiment, liver did have a higher level of micronucleated hepatocytes than control.  However, the increase in the frequency of micronuclei in the hepatocyte may be due to increased cell proliferation.  Results in the rat confirm earlier findings that 1-nitropropane was negative in the mouse micronucleus test.  1 -Nitropropane did not induce an increase in DNA repair in an in vivo rat UDS study at doses as high as 80 mg/kg.  The lack of genotoxic potential is supported by two negative carcinogenicity studies in rats.  


Short description of key information:
Eight in vitro studies were identified to evaluate 1-nitropropane for its genotoxicity, these include one key study for the Salmonella typhimurium reverse mutation assay and two supporting studies, a key study for the in vitro mammalian cell chromosomal aberration test, and two in vitro DNA repair tests. Two studies, an in vitro micronucleus assay and an HGPRT are compared with the higher tiered in vivo test to determine the overall classification of 1-ntiropropane. Of the eight studies, three were GLP (DNA repair tests gave no indication that they were or were not GLP) and all were conducted under guideline or comparable to a guideline study.

Three in vivo studies were identified to evaluate 1-nitropropane for its genotoxicity. Two were in vivo rat and mouse micronucleus tests and the other in vivo rat hepatocyte UDS study. All were negative.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Majority of thein vitro and the higher tiered in vivo genotoxicity studies with 1 -nitropropane were negative, therefore no classification for genotoxicity is required.