A Toxicological Evaluation of Methylliberine (Dynamine®)
Table 3
Results of the in vitro mammalian chromosomal aberration test.
Experiment A
Groups
S9-mix
Treatment time
Sampling time
Cytotoxicity
Mean number of aberrant cells /150 cells
% of aberrant cells
Mean number of aberrations/150 cells
Mean aberrations
Chromosome
Chromatid
Others
Gap+
Gap−
Gap-
Gap+
Gap−
Gap
Del
Exchange
Gap
Del
Exchange
Test item
250 µg/mL
−
3 h
20 h
5
7
4
2.333
7
4
0
0
0
4
4
0
—
500 µg/mL
−
3 h
20 h
16
7
4
2.667
7
4
2
1
1
1
2
1
—
1000 µg/mL
−
3 h
20 h
27
9
5
3.000
9
5
1
1
1
4
3
0
—
2000 µg/mL
−
3 h
20 h
32
8
3
2.000
8
3
3
0
1
3
2
0
—
Vehicle control
−
3 h
20 h
0
8
4
2.667
8
4
1
0
2
3
2
0
—
Positive control
−
3 h
20 h
50
39
33
22.000
57
38
7
8
6
12
13
12
—
Test item
250 µg/mL
+
3 h
20 h
6
8
5
3.000
9
6
2
1
2
2
1
3
—
500 µg/mL
+
3 h
20 h
17
10
4
2.667
10
4
3
1
1
4
2
1
—
1000 µg/mL
+
3 h
20 h
20
9
5
3.000
9
5
1
1
1
4
1
2
—
2000 µg/mL
+
3 h
20 h
32
8
4
2.667
8
4
1
1
1
4
3
0
—
Vehicle control
+
3 h
20 h
0
8
6
3.667
9
6
1
1
3
3
2
1
—
Positive control
+
3 h
20 h
52
44
38
25.333
88
59
10
8
7
19
11
34
—
Experiment B
Test item
125 µg/mL
−
20 h
20 h
6
7
4
2.333
8
4
1
1
1
3
2
1
—
250 µg/mL
−
20 h
20 h
20
9
4
2.667
9
4
1
1
1
4
2
1
—
500 µg/mL
−
20 h
20 h
56
8
3
2.000
8
3
2
1
1
3
1
0
—
Vehicle control
−
20 h
20 h
0
6
3
2.000
6
3
1
0
1
2
2
0
—
Positive control
−
20 h
20 h
52
41
34
22.667
67
46
8
7
7
13
13
20
—
Test item
125 µg/mL
−
20 h
28 h
6
6
3
2.000
6
3
1
0
2
2
2
0
—
250 µg/mL
−
20 h
28 h
22
7
3
2.667
8
3
2
1
0
3
2
1
—
500 µg/mL
−
20 h
28 h
56
8
4
2.667
9
4
1
0
2
4
3
0
—
Vehicle control
−
20 h
28 h
0
7
4
2.333
7
4
1
0
2
3
2
1
—
Positive control
−
20 h
28 h
49
46
41
27.000
73
48
7
7
7
18
16
20
—
Test item
250 µg/mL
+
3 h
28 h
4
7
3
2.000
7
3
0
1
1
4
2
0
—
500 µg/mL
+
3 h
28 h
23
8
4
2.333
8
4
2
0
1
3
2
1
—
1000 µg/mL
+
3 h
28 h
26
8
3
2.000
8
3
2
0
1
4
2
1
—
2000 µg/mL
+
3 h
28 h
33
9
4
2.333
10
4
2
1
2
4
1
0
—
Vehicle control
+
3 h
28 h
0
7
3
2.000
7
3
1
0
2
4
2
0
—
Positive control
+
3 h
28 h
53
45
42
27.667
89
62
8
9
9
20
17
28
—
Abbreviations: −, without S9-mix; +, with S9=mix; del deletion; gap−, excluding gaps; gap+, including gaps. Vehicle control, DME medium; positive control with S9-mix, cyclophasphamide (5.0 µg/mL); positive control without S9-mix (experiment A), EMS (1.0 µg/mL); positive control without S9-mix (experiment B), EMS (0,4 µg/mL). Cytotoxicity=100-RICC (relative increase in cell counts). ∗∗p < 0.01.
