N-methylisopropylamine

Endpoint summary

Additional information

N-Methylisopropylamine (MIPA) was tested for its mutagenic potential in Salmonella typhimurium and Escherichia coli (BASFSE40M0834/074117, 2008). A standard plate test (SPT) and a preincubation test (PIT) were conducted according to the OECD TG 471 (1997). The tester strains were: TA1535, TA100, TA1537, TA98 and E. coli WP2 uvrA. Testing was done in absence and presence of S9 mix. Negative and positive controls were included. The test concentrations were as follows: 1st Experiment (all strains, standard plate test with and without S-9 mix, 3 plates/dose): 0; 20; 100; 500; 2500 and 5000 µg/plate; 2nd Experiment (all strains, preincubation test with and without S-9 mix, 3 plates/dose): 0; 200; 400; 800; 1600 and 3200 µg/plate; 3rd Experiment (all strains, preincubation test without S-9 mix, 3 plates/dose): 0; 10; 50; 250; 1250; 2500 µg/plate; 3rd Experiment (all strains, preincubation test with S-9 mix, 3 plates/dose): 0; 20; 100; 500; 2500 and 5000 µg/plate .

When tested in all strains mentioned above under SPT and PIT conditions, with and without S9 mix, the test item did not induce an increase in his+ or trp+ revertant colonies at concentrations up to 5000 µg/plate. A cytototoxic effect was observed in the SPT depending on the strain and test conditions from 2 500 μg/plate onward; in the PIT, cytotoxicity was observed from 1250 µg/plate onward. No test item precipitation was observed within the concentration range tested, with and without S9-mix. Referring to controls,the results of the negative as well as the positive controls performed in parallel corroborated the validity of this study, since the values fulfilled the acceptance criteria of this study. Thus, under the experimental conditions chosen, N-methylisopropylamine is not mutagenic in the bacterial reverse mutation assay in the absence and presence of metabolic activation.

MIPA was further assessed for its potential to induce structural chromosomal aberrations (clastogenic activity) and/or changes in the number of chromosomes (aneugenic activity) in V79 cells in vitro (BASFSE40M0834/074117, 2008). Testing was done both in the presence and in the absence of a metabolizing system (S9 mix), according to the OECD TG 473 (1997). Two experiments were conducted, with concentrations between 46.9 and 750 µg/mL. Negative and positive controls were included.

N-Methylisopropylamine did not cause any biologically relevant increase in the number of structurally aberrant metaphases incl. and excl. gaps at both sampling times either with or without S9 mix in the two experiments performed independently of each other. No relevant increase in the frequency of cells containing numerical chromosome aberrations was demonstrated either. The negative controls (vehicle controls) gave frequencies of aberrations within the range expected for the V79 cell line. Both of the positive control chemicals (and CCP), led to the expected increase in the number of cells with structural chromosomal aberrations.

Thus, under the experimental conditions described, N-Methylisopropylamine has no chromosome-damaging (clastogenic) effect in V79 cells in the absence and the presence of metabolic activation.

 

Referring to in vivo mutagenicity, since no study on MIPA, showed to be corrosive, is available, the micronucleus test (MNT) conducted with the systemically available form N-Methylisopropylamine-HCl (MIPA-HCl) according to the OECD TG 474 (1997) was considered for read-across (BASFSE26M0413/084306, 2009).

N-Methylisopropylamine-hydrochloride was tested in the Micronucleus test according to the OECD TG 474 with male NMRI mice. The animals were treated once by gavage with 2000, 1000 and 500 mg/kg bw of the test item; purified water served for vehicle and thus, for vehicle control. The positive control substance for clastogenicity was cyclophosphamid; the positive control substance for

aneugenicity was vincristine sulfate. Bone marrow samples were prepared 24 and 48 h after treatment. 2000 polychromatic erythrocytes (PCEs) from each animal of every test group was evaluated and investigated for micronuclei (MN). The normochromatic erythrocytes (NCEs) which occur are also scored.

The single oral administration of the vehicle purified water at a volume of 10 mL/kg bw led to 0.8‰ polychromatic erythrocytes containing micronuclei after the 24-hour sacrifice interval or to 1.6‰ after the 48-hour sacrifice interval, respectively. After the single administration of the highest dose of 2000 mg/kg bw, 1.0‰ polychromatic erythrocytes containing micronuclei were found at both sacrifice intervals (24 hours and 48 hours). In the two lower dose groups, 1000 and 500 mg/kg bw, rates of micronuclei of about 1.4‰ each were detected after a sacrifice interval of 24 hours. The ratio of polychromatic to normochromatic erythrocytes was always close to the range of the vehicle control values in all dose groups. Referring to the positive controls, cyclophosphamide led to a statistically significant increase (18.9‰) in the number of polychromatic erythrocytes containing mainly small micronuclei, as expected. Vincristine sulfate produced a statistically significant increase (66.6‰) in the number of polychromatic erythrocytes containing micronuclei. A significant portion increase, 16.3‰ was attributable to large micronuclei. Thus, under the experimental conditions chosen here, the test item N-Methylisopropylamine-hydrochloride showed no chromosome-damaging (clastogenic) effect, and there were no indications of any impairment of chromosome distribution in the course of mitosis (aneugenic activity) in bone marrow cells in vivo.

Short description of key information:
N-Methylisopropylamine (MIPA) was tested for its mutagenic potential in Salmonella typhimurium and Escherichia coli, in the standard plate test (SPT) and the preincubation test (PIT), according to the OECD TG 471 (BASFSE40M0834/074117, 2008). Under the experimental conditions chosen, N-methylisopropylamine is not mutagenic in the bacterial reverse mutation assay in the absence and presence of metabolic activation.
MIPA was further assessed for chromosome aberration in V79 cells in vitro both in the presence and in the absence of a metabolizing system (S9 mix), according to the OECD TG 473 (BASFSE40M0834/074117, 2008)
Referring to in vivo mutagenicity, since no study on MIPA, showed to be corrosive, is available, the micronucleus test (MNT) conducted with N-Methylisopropylamine-hydrochloride (MIPA-HCl) according to the OECD TG 474 was considered for read-across (BASFSE26M0413/084306, 2009). Under the experimental conditions chosen here, MIPA-HCl showed no chromosome-damaging (clastogenic) effect, and there were no indications of any impairment of chromosome distribution in the course of mitosis (aneugenic activity) in bone marrow cells in vivo.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the negative results of all available data, there is no need for classification of MIPA for mutagenicity either according to the EU Directive 67/548/EC or the the CLP Regulation 1272/2008 .