(2) treatment/fixation time = 48/48 hours; positive control: 0.1 µg/mL MMC; with metabolic activation, 1, 3 and 10 µg/mL; treatment/fixation time: 3/48 hours, positive control: 15 µg/mL cyclophosphamide; OECD TG 473 Test method: Tests were carried out in duplicate in two independent Comment: experiments. Experiment 1: The test substance did not induce a statistically significant increase in chromosomal aberrations, both in the absence and presence of metabolic activation, compared with negative controls. Experiment2: In the 48 hour treatment/fixation experiment, there was a statistically significant increase in chromosomal aberrations, particularly at the highest test concentration of 10 µg/mL where there was also evidence of precipitation. In the 24 hour treatment/fixation experiment, no evidence of increased chromosomal aberrations was seen. In the 3 hour treatment/48 fixation experiment, there was an elevated incidence of double minutes1 at 3 µg/mL test concentration. Since this occurred only at the intermediate dose level, and in only one of the duplicate cultures, it was considered to have little biological relevance. The lack of any chromosomal aberrations in the solvent control makes interpretation of the data difficult. The testing facility quotes a historical control range of 0 to 5, with a mean of 0.9. It is considered that the mean, 0.9, is more representative of a true historical control value than the range. A higher weighting is therefore placed on the finding of significant chromosome aberrations at the highest concentration of 10µg/L and accordingly the test substance is considered to be a weak clastogen. in vitro Double minutes two, usually circular, of a chromatid lacking a centromere. – 1
(2) treatment/fixation time = 48/48 hours; positive control: 0.1 µg/mL MMC; with metabolic activation, 1, 3 and 10 µg/mL; treatment/fixation time: 3/48 hours, positive control: 15 µg/mL cyclophosphamide; Test method: OECD TG 473 Comment: Tests were carried out in duplicate in two independent experiments. Experiment 1: The test substance did not induce a statistically significant increase in chromosomal aberrations, both in the absence and presence of metabolic activation, compared with negative controls. Experiment2: In the 48 hour treatment/fixation experiment, there was a statistically significant increase in chromosomal aberrations, particularly at the highest test concentration of 10 µg/mL where there was also evidence of precipitation. In the 24 hour treatment/fixation experiment, no evidence of increased chromosomal aberrations was seen. In the 3 hour treatment/48 fixation experiment, there was an elevated incidence of double minutes1 at 3 µg/mL test concentration. Since this occurred only at the intermediate dose level, and in only one of the duplicate cultures, it was considered to have little biological relevance. The lack of any chromosomal aberrations in the solvent control makes interpretation of the data difficult. The testing facility quotes a historical control range of 0 to 5, with a mean of 0.9. It is considered that the mean, 0.9, is more representative of a true historical control value than the range. A higher weighting is therefore placed on the finding of significant chromosome aberrations at the highest concentration of 10µg/L and accordingly the test substance is considered to be a weak in vitro clastogen. 1 Double minutes – two, usually circular, of a chromatid lacking a centromere.