Parameter
|
Sex
|
Dose (mg/kg)
|
---|
0 mg/kg
|
1000 mg/kg
|
2500 mg/kg
|
5000 mg/kg
|
---|
13 wk
|
26 wk
|
Recovery
|
13 wk
|
26 wk
|
Recovery
|
13 wk
|
26 wk
|
Recovery
|
13wk
|
26 wk
|
Recovery
|
---|
Body weight
|
Male
|
486.2 ± 16.4
|
604.4 ± 70.0
|
641.3 ± 95.7
|
516.3 ± 101.3
|
634.6 ± 60.1
|
670.7 ± 65.7
|
482.3 ± 44.4
|
628.1 ± 67.7
|
660.4 ± 39.7
|
481.8 ± 39.5
|
637.8 ± 82.5
|
691.7 ± 63.8
|
Female
|
291.3 ± 16.8
|
331.8 ± 27.2
|
338.9 ± 35.6
|
280.9 ± 17.0
|
333.4 ± 32.2
|
329.7 ± 34.7
|
266.0 ± 9.3
|
308.3 ± 25.7
|
318.4 ± 15.2
|
269.0 ± 36.4
|
322.2 ± 31.9
|
336.6 ± 29.5
|
Brain
|
Male
|
2.096 ± 0.064
|
2.240 ± 0.124
|
2.163 ± 0.103
|
2.214 ± 0.115
|
2.221 ± 0.095
|
2.191 ± 0.090
|
2.080 ± 0.117
|
2.281 ± 0.079
|
2.224 ± 0.092
|
2.092 ± 0.183
|
2.238 ± 0.089
|
2.261 ± 0.049
|
Female
|
1.996 ± 0.066
|
2.021 ± 0.064
|
2.088 ± 0.096
|
1.947 ± 0.040
|
2.011 ± 0.064
|
2.028 ± 0.043
|
2.006 ± 0.046
|
2.008 ± 0.105
|
2.003 ± 0.063
|
1.985 ± 0.029
|
2.040 ± 0.060
|
2.029 ± 0.039
|
% to body weight
|
Male
|
0.431 ± .016
|
0.376 ± 0.054
|
0.344 ± 0.055
|
0.439 ± 0.067
|
0.352 ± 0.033
|
0.329 ± 0.034
|
0.434 ± 0.039
|
0.366 ± 0.036
|
0.338 ± 0.027
|
0.436 ± 0.043
|
0.356 ± 0.046
|
0.329 ± 0.030
|
Female
|
0.687 ± 0.041
|
0.612 ± 0.041
|
0.621 ± 0.066
|
0.695 ± 0.045
|
0.608 ± 0.060
|
0.620 ± 0.065
|
0.754 ± 0.023*
|
0.655 ± 0.057
|
0.630 ± 0.019
|
0.747 ± 0.082
|
0.638 ± 0.065
|
0.606 ± 0.051
|
Thymus
|
Male
|
0.297 ± 0.097
|
0.270 ± 0.069
|
0.262 ± 0.063
|
0.351 ± 0.170
|
0.219 ± 0.106
|
0.250 ± 0.092
|
0.313 ± 0.043
|
0.223 ± 0.084
|
0.200 ± 0.038
|
0.270 ± 0.048
|
0.262 ± 0.056
|
0.224 ± 0.059
|
Female
|
0.367 ± 0.057
|
0.245 ± 0.073
|
0.187 ± 0.057
|
0.325 ± 0.041
|
0.232 ± 0.038
|
0.225 ± 0.045
|
0.283 ± 0.053
|
0.226 ± 0.061
|
0.214 ± 0.071
|
0.304 ± 0.091
|
0.231 ± 0.063
|
0.218 ± 0.023
|
% to body weight
|
Male
|
0.061 ± 0.018
|
0.044 ± 0.009
|
0.041 ± 0.008
|
0.065 ± 0.019
|
0.034 ± 0.013*
|
0.037 ± 0.013
|
0.065 ± 0.011
|
0.035 ± 0.012
|
0.030 ± 0.005*
|
0.056 ± 0.008
|
0.041 ± 0.008
|
0.032 ± 0.006
|
Female
|
0.126 ± 0.017
|
0.074 ± 0.023
|
0.055 ± 0.014
|
0.116 ± 0.015
|
0.070 ± 0.010
|
0.069 ± 0.015
|
0.106 ± 0.018
|
0.073 ± 0.017
|
0.067 ± 0.021
|
0.112 ± 0.026
|
0.071 ± 0.014
|
0.065 ± 0.009
|
Heart
|
Male
|
1.381 ± 0.111
|
1.625 ± 0.204
|
1.653 ± 0.259
|
1.494 ± 0.193
|
1.710 ± 0.229
|
1.613 ± 0.225
|
1.408 ± 0.156
|
1.702 ± 0.169
|
1.749 ± 0.138
|
1.467 ± 0.093
|
1.699 ± 0.182
|
1.912 ± 0.182
|
Female
|
0.832 ± 0.042
|
1.100 ± 0.101
|
1.046 ± 0.138
|
0.917 ± 0.094
|
1.089 ± 0.109
|
1.013 ± 0.091
|
0.905 ± 0.066
|
1.024 ± 0.091
|
0.986 ± 0.069
|
0.969 ± 0.102
|
1.098 ± 0.136
|
1.014 ± 0.068
|
% to body weight
|
Male
|
0.284 ± 0.014
|
0.270 ± 0.029
|
0.258 ± 0.004
|
0.294 ± 0.037
|
0.271 ± 0.039
|
0.240 ± 0.015*
|
0.292 ± 0.021
|
0.272 ± 0.021
|
0.265 ± 0.020
|
0.306 ± 0.028
|
0.268 ± 0.016
|
0.277 ± 0.016
|
Female
|
0.286 ± 0.012
|
0.333 ± 0.034
|
0.308 ± 0.010
|
0.326 ± 0.023*
|
0.328 ± 0.027
|
0.308 ± 0.016
|
0.341 ± 0.036*
|
0.334 ± 0.044
|
0.310 ± 0.016
|
0.362 ± 0.025**
|
0.341 ± 0.032
|
0.302 ± 0.018
|
Lung
|
Male
|
1.782 ± 0.201
|
1.831 ± 0.271
|
1.845 ± 0.237
|
1.862 ± 0.779
|
1.876 ± 0.246
|
1.910 ± 0.094
|
1.528 ± 0.103*
|
1.930 ± 0.088
|
1.916 ± 0.052
|
1.516 ± 0.066*
|
1.898 ± 0.127
|
2.099 ± 0.322
|
Female
|
1.210 ± 0.061
|
1.434 ± 0.110
|
1.409 ± 0.098
|
1.506 ± 0.538
|
1.449 ± 0.168
|
1.28 ± 0.062*
|
1.210 ± 0.072
|
1.438 ± 0.166
|
1.419 ± 0.048
|
1.204 ± 0.192
|
1.443 ± 0.138
|
1.503 ± 0.152
|
% to body weight
|
Male
|
0.366 ± 0.038
|
0.304 ± 0.041
|
0.289 ± 0.025
|
0.354 ± 0.087
|
0.296 ± 0.034
|
0.287 ± 0.033
|
0.318 ± 0.021*
|
0.310 ± 0.029
|
0.291 ± 0.016
|
0.316 ± 0.026
|
0.300 ± 0.028
|
0.303 ± 0.035
|
Female
|
0.416 ± 0.024
|
0.434 ± 0.036
|
0.418 ± 0.043
|
0.537 ± 0.189
|
0.438 ± 0.064
|
0.394 ± 0.041
|
0.456 ± 0.037
|
0.466 ± 0.036
|
0.446 ± 0.025
|
0.447 ± 0.021
|
0.450 ± 0.048
|
0.448 ± 0.041
|
Liver
|
Male
|
11.492 ± 1.894
|
12.852 ± 1.753
|
14.019 ± 2.841
|
12.564 ± 3.570
|
13.450 ± 1.903
|
14.001 ± 1.859
|
11.882 ± 1.267
|
14.860 ± 2.256*
|
15.212 ± 1.286
|
11.380 ± 0.892
|
16.043 ± 3.106*
|
16.306 ± 1.798
|
Female
|
6.885 ± 0.495
|
8.213 ± 1.184
|
7.582 ± 0.862
|
7.057 ± 0.719
|
8.522 ± 0.984
|
7.761 ± 1.048
|
6.920 ± 0.305
|
8.136 ± 0.742
|
7.659 ± 0.794
|
7.356 ± 1.218
|
8.733 ± 0.742
|
7.594 ± 0.724
|
% to body weight
|
Male
|
2.356 ± 0.312
|
2.125 ± 0.125
|
2.180 ± 0.190
|
2.407 ± 0.256
|
2.117 ± 0.187
|
2.084 ± 0.143
|
2.461 ± 0.062
|
2.363 ± 0.209**
|
2.301 ± 0.061
|
2.366 ± 0.123
|
2.498 ± 0.193**
|
2.357 ± 0.164
|
Female
|
2.369 ± 0.223
|
2.481 ± 0.355
|
2.239 ± 0.151
|
2.510 ± 0.189
|
2.561 ± 0.237
|
2.351 ± 0.132
|
2.605 ± 0.169
|
2.644 ± 0.205
|
2.402 ± 0.171
|
2.728 ± 0.105*
|
2.728 ± 0.300
|
2.258 ± 0.159
|
Spleen
|
Male
|
0.614 ± 0.042
|
0.799 ± 0.116
|
0.833 ± 0.115
|
0.639 ± 0.105
|
0.849 ± 0.110
|
0.795 ± 0.096
|
0.708 ± 0.166
|
0.810 ± 0.115
|
0.868 ± 0.133
|
0.673 ± 0.073
|
0.916 ± 0.101*
|
0.859 ± 0.104
|
Female
|
0.431 ± 0.023
|
0.618 ± 0.149
|
0.582 ± 0.108
|
0.460 ± 0.054
|
0.544 ± 0.074
|
0.553 ± 0.060
|
0.478 ± 0.035
|
0.574 ± 0.115
|
0.545 ± 0.035
|
0.446 ± 0.081
|
0.518 ± 0.080
|
0.543 ± 0.057
|
% to body weight
|
Male
|
0.126 ± 0.006
|
0.133 ± 0.022
|
0.130 ± 0.009
|
0.126 ± 0.021
|
0.134 ± 0.009
|
0.118 ± 0.007
|
0.147 ± 0.030
|
0.129 ± 0.009
|
0.131 ± 0.018
|
0.140 ± 0.015
|
0.145 ± 0.015
|
0.124 ± 0.009
|
Female
|
0.148 ± 0.009
|
0.187 ± 0.046
|
0.172 ± 0.026
|
0.164 ± 0.020
|
0.164 ± 0.021
|
0.168 ± 0.013
|
0.180 ± 0.016**
|
0.186 ± 0.033
|
0.171 ± 0.006
|
0.167 ± 0.028
|
0.162 ± 0.026
|
0.162 ± 0.018
|
Kidney
|
Male
|
2.832 ± 0.228
|
3.343 ± 0.322
|
3.406 ± 0.309
|
2.943 ± 0.433
|
3.421 ± 0.481
|
3.449 ± 0.451
|
2.766 ± 0.141
|
3.519 ± 0.316
|
3.856 ± 0.456
|
3.013 ± 0.428
|
3.622 ± 0.410
|
4.178 ± 0.503*
|
Female
|
1.655 ± 0.139
|
1.896 ± 0.164
|
1.868 ± 0.199
|
1.568 ± 0.152
|
1.932 ± 0.175
|
1.914 ± 0.255
|
1.605 ± 0.045
|
1.978 ± 0.175
|
1.892 ± 0.111
|
1.626 ± 0.192
|
2.025 ± 0.164
|
1.857 ± 0.167
|
% to body weight
|
Male
|
0.582 ± 0.031
|
0.557 ± 0.056
|
0.537 ± 0.060
|
0.577 ± 0.070
|
0.540 ± 0.072
|
0.513 ± 0.029
|
0.577 ± 0.058
|
0.563 ± 0.048
|
0.584 ± 0.062
|
0.624 ± 0.059
|
0.572 ± 0.059
|
0.603 ± 0.026
|
Female
|
0.569 ± 0.052
|
0.574 ± 0.058
|
0.552 ± 0.031
|
0.558 ± 0.048
|
0.582 ± 0.054
|
0.581 ± 0.049
|
0.604 ± 0.027
|
0.643 ± 0.049**
|
0.594 ± 0.024*
|
0.606 ± 0.029*
|
0.632 ± 0.056
|
0.552 ± 0.034
|
Adrenal grand
|
Male
|
0.068 ± 0.012
|
0.050 ± 0.006
|
0.062 ± 0.009
|
0.059 ± 0.013
|
0.056 ± 0.007
|
0.051 ± 0.005*
|
0.062 ± 0.012
|
0.055 ± 0.009
|
0.057 ± 0.005
|
0.053 ± 0.009*
|
0.056 ± 0.008
|
0.065 ± 0.010
|
Female
|
0.066 ± 0.007
|
0.063 ± 0.009
|
0.067 ± 0.009
|
0.061 ± 0.009
|
0.063 ± 0.008
|
0.055 ± 0.006*
|
0.066 ± 0.006
|
0.065 ± 0.012
|
0.064 ± 0.011
|
0.061 ± 0.008
|
0.069 ± 0.009
|
0.057 ± 0.010
|
% to body weight
|
Male
|
0.014 ± 0.002
|
0.008 ± 0.002
|
0.010 ± 0.001
|
0.012 ± 0.004
|
0.009 ± 0.001
|
0.008 ± 0.001*
|
0.013 ± 0.003
|
0.009 ± 0.002
|
0.009 ± 0.001
|
0.011 ± 0.002
|
0.009 ± 0.002
|
0.009 ± 0.001
|
Female
|
0.023 ± 0.002
|
0.019 ± 0.003
|
0.020 ± 0.002
|
0.022 ± 0.003
|
0.019 ± 0.003
|
0.017 ± 0.001*
|
0.025 ± 0.003
|
0.021 ± 0.004
|
0.020 ± 0.004
|
0.023 ± 0.004
|
0.022 ± 0.003
|
0.017 ± 0.003
|
Testis(Rt.)/ Ovary (Lt.)
|
Male
|
3.391 ± 0.243
|
3.669 ± 0.398
|
3.767 ± 0.306
|
3.607 ± 0.142
|
3.606 ± 0.788
|
3.666 ± 0.315
|
3.324 ± 0.689
|
3.831 ± 0.472
|
3.822 ± 0.331
|
3.594 ± 0.362
|
3.632 ± 0.851
|
4.047 ± 0.343
|
Female
|
3.594 ± 0.362
|
0.146 ± 0.030
|
0.164 ± 0.049
|
0.145 ± 0.017
|
0.157 ± 0.038
|
0.157 ± 0.047
|
0.149 ± 0.017
|
0.156 ± 0.022
|
0.152 ± 0.016
|
0.148 ± 0.018
|
0.166 ± 0.036
|
0.164 ± 0.017
|
% to body weight
|
Male
|
0.698 ± 0.052
|
0.610 ± 0.054
|
0.593 ± 0.050
|
0.716 ± 0.109
|
0.567 ± 0.109
|
0.548 ± 0.033
|
0.684 ± 0.095
|
0.613 ± 0.079
|
0.579 ± 0.032
|
0.751 ± 0.114
|
0.571 ± 0.128
|
0.587 ± 0.046
|
Female
|
0.046 ± 0.007
|
0.044 ± 0.010
|
0.048 ± 0.014
|
0.051 ± 0.005*
|
0.048 ± 0.013
|
0.049 ± 0.015
|
0.056 ± 0.007*
|
0.051 ± 0.006
|
0.048 ± 0.006
|
0.055 ± 0.002
|
0.052 ± 0.010
|
0.049 ± 0.006
|
Epididymis (Lt.)/Uterus
|
Male
|
1.264 ± 0.099
|
1.542 ± 0.205
|
1.555 ± 0.142
|
1.440 ± 0.207
|
1.547 ± 0.329
|
1.562 ± 0.403
|
1.322 ± 0.170
|
1.550 ± 0.306
|
1.575 ± 0.170
|
1.431 ± 0.080*
|
1.511 ± 0.271
|
1.669 ± 0.262
|
Female
|
0.649 ± 0.173
|
0.803 ± 0.289
|
0.883 ± 0.114
|
0.879 ± 0.283
|
0.991 ± 0.340
|
0.970 ± 0.274
|
0.715 ± 0.195
|
0.907 ± 0.213
|
0.691 ± 0.152
|
0.752 ± 0.338
|
0.770 ± 0.264
|
0.893 ± 0.365
|
% to body weight
|
Male
|
0.260 ± 0.021
|
0.260 ± 0.054
|
0.245 ± 0.026
|
0.285 ± 0.050
|
0.244 ± 0.047
|
0.231 ± 0.043
|
0.273 ± 0.015
|
0.248 ± 0.050
|
0.239 ± 0.032
|
0.299 ± 0.035
|
0.240 ± 0.053
|
0.241 ± 0.029
|
|
Female
|
0.225 ± 0.070
|
0.245 ± 0.092
|
0.264 ± 0.048
|
0.315 ± 0.108
|
0.299 ± 0.102
|
0.296 ± 0.084
|
0.269 ± 0.074
|
0.298 ± 0.082
|
0.217 ± 0.044
|
0.272 ± 0.084
|
0.240 ± 0.082
|
0.271 ± 0.125
|
- Note: Data represents body weights right before necropsy, after fasting; Values are mean ± S.D. (n = 5 (4 weeks or recovery), 10 (26 weeks), recovery (30 weeks)/sex/dose). * P < 0.05 & ** P < 0.01 compared with normal group.