3-isopropoxypropylamine

Endpoint summary

Additional information

Gene mutation assay

 

The genotoxic activity of 3-isopropoxypropylamine was evaluated in the Ames test on Salmonella typhimurium according to the OECD 471 guideline (Haddouk, 1998). Doses from 156.25 to 5000µg/plate were tested on five strains (TA 98, TA 100, TA 1535, TA 1537 and TA 102) in presence or absence of metabolic activation. Two methods were used: direct plate incorporation (1st experiment and 2nd experiment for TA 1535 only) and preincubation 60 min at 37°C (2^ndexperiment for all strains except TA 1535) and the number of revertants colonies is evaluated 48 to 72 hours later. The number of revertants of the vehicle and positive controls was as specified in the acceptance criteria. Without metabolic activation, the test substance did not induce any significant increase in the number of revertants, in any of the 5 strains. With metabolic activation, an increase of the number of revertant colonies was observed at the dose level of 2500 µg/plate for the TA1535 strain (2.66-6.16 fold higher than control values). In conclusion, 3-isopropoxypropylamine showed mutagenic activity in the Ames test on Salmonella typhimurium TA 1535 strain in the absence metabolic activation.

 

Chromosomal aberration assay

 

The potential of 3-isopropoxypropylamine to induce structural or numerical damage was evaluated in bone marrow cells of mice. The study was performed according to the international guidelines (OECD 474 and Commission Directive No. B12) and in compliance with the principles of Good Laboratory Practice (Sarlang, 2010). A preliminary toxicity test was performed to define the dose-levels to be used for the cytogenetic study. In the main study, three groups of five male and five female Swiss Ico: OF1 (IOPS Caw) mice were given oral administrations of 3-isopropoxypropylamine at dose-levels of 125, 250 and 500 mg/kg/day, over a 2-day period. One group of five males and five females received the vehicle (water for injections) under the same experimental conditions, and acted as control group. One group of five males and five females received the positive control test item (cyclophosphamide) once by oral route at the dose-level of 50 mg/kg/day. The animals of the treated and vehicle control groups were killed 24 hours after the last treatment and the animals of the positive control group were killed 24 hours after the single treatment. Bone marrow smears were then prepared. For each animal, the number of the micronucleated polychromatic erythrocytes (MPE) was counted in 2000 polychromatic erythrocytes. The polychromatic (PE) and normochromatic (NE) erythrocyte ratio was established by scoring a total of 1000 erythrocytes (PE + NE). In the two vehicle control groups, the frequency of MPE as well as the PE/NE ratio were consistent with our historical data. Cyclophosphamide induced a significant increase (p < 0.01) in the frequency of MPE, indicating the sensitivity of the test system under our experimental conditions. The study was therefore considered as valid.  In all groups treated with 3-isopropoxypropylamine, the frequencies of MPE were similar to those of their respective vehicle control groups, and no statistically significant differences were observed. The PE/NE ratios were not statistically significantly different from that of the respective vehicle control groups. 3-isopropoxypropylamine did not induce damage to the chromosomes or the mitotic apparatus of mice bone marrow cells after two oral administrations, at a 24-hour interval, at the dose-levels of 125, 250 and 500 mg/kg/day.

Short description of key information:
3-isopropoxypropylamine showed mutagenic activity in the Ames test on Salmonella typhimurium TA 1535 strain in the absence metabolic activation. 3-isopropoxypropylamine did not induce damage to the chromosomes or the mitotic apparatus of mice bone marrow cells after two oral administrations, at a 24-hour interval, at the dose-levels of 125, 250 and 500 mg/kg/day.

Endpoint Conclusion: