Table 1. Levels relevant to toxicological evaluation of isofetamid.
| Species | Study | Dose (mg/kg bw/day) |
NOAEL (mg/kg bw/day) |
LOAEL (mg/kg bw/day) |
Critical endpoints1) |
|---|---|---|---|---|---|
| Rat | 90-day subacute toxicity study |
0, 100, 1,000, 10,000 ppm M: 0, 6.65, 68.9, 637 F: 0, 7.83, 78.0, 741 |
M: 6.65 F: 7.83 |
M: 68.9 F: 78.0 |
F/M: Diffuse Hepatocellular hypertrophy, etc |
| 90-day subacute neurotoxicity study |
0, 500, 3,000, 15,000 ppm M: 0, 34, 207, 1,050 F: 0, 40, 245, 1,210 |
M: 207 F: 1,210 |
M: 1,050 F: - |
M: Depressed body weight F: No toxicological effects (Not neurotoxic) |
|
| One-year chronic toxicity study |
0, 30, 100, 500, 5,000 ppm M: 0, 1.39, 4.68, 22.7, 237 F: 0, 1.82, 5.92, 30.0, 311 |
M: 22.7 F: 30.0 |
M: 237 F: 311 |
F/M: Increased absolute/relative liver weights, Diffuse hepatocellular hypertrophy, etc |
|
| Two-year carcinogenicity study |
0, 30, 100, 500, 5,000 ppm M: 0, 1.21, 4.07, 20.3, 210 F: 0, 1.55, 5.02, 26.1, 263 |
M: 20.3 F: 26.1 |
M: 210 F: 263 |
F/M: Hypertrophy of thyroid follicular epithelial cell, etc (Not carcinogenic) |
|
| Two-generation reproductive toxicity study |
0, 100, 1,000, 10,000 ppm PM: 0, 5.76, 57.1, 594 PF: 0, 8.85, 90.5, 908 F1M: 0, 6.02, 60.1, 643 F1F: 0, 8.69, 89.1, 906 |
Parent PM: 57.1 PF: 8.85 F1M: 60.1 F1F: 8.69 |
Parent PM: 594 PF: 90.5 F1M: 643 F1F: 89.1 |
Parent F/M: Increased absolute/ relative liver weights, etc. |
|
| Offspring PM: 57.1 PF: 90.5 F1M: 60.1 F1F: 89.1 |
Offspring PM: 594 PF: 908 F1M: 643 F1F: 906 |
Offspring F/M: Depressed body weight, etc. (No effect on reproduction) |
|||
| Developmental toxicity study |
0, 100, 300, 1,000 | Maternal:
300 Embryo/fetus: 1,000 |
Maternal: 1,000 Embryo/fetus: - |
Maternal: Trend in increased absolute liver weights and increased relative liver weights Embryo/fetus: No toxicologi- cal effects (Not teratogenic) |
|
| Mouse | 90-day subacute toxicity study | 0, 100, 1,000, 8,000 ppm M: 0, 13, 129, 1,070 F: 0, 16, 161, 1,310 |
M: 129 F: 161 |
M: 1,070 F: 1,310 |
F/M: Increased absolute/ relative liver weights, etc |
| 78-week carcinogenicity study |
0, 100, 800, 3,000(F),
4,000(M) ppm M: 0, 12, 92, 502 F: 0, 14, 118, 431 |
M: 12 F: 118 |
M: 92 F: 431 |
F/M: Depressed body weight, etc (Not carcinogenic) |
|
| Rabbit | Developmental toxicity study |
0, 100, 300, 1,000 | Maternal: 300 Embryo/fetus: 1,000 |
Maternal: 1,000 Embryo/fetus: - |
Maternal: Depressed body weight, etc Embryo/fetus: No toxicologi- cal effects (Not teratogenic) |
| Dog | 90-day subacute toxicity study | 0, 100, 1,000, 10,000 ppm M: 0, 2.95, 29.3, 301 F: 0, 3.07, 32.7, 314 |
M: 2.95 F: 3.07 |
M: 29.3 F: 32.7 |
F/M: Increase in ALP, etc |
| One-year chronic toxicity study | 0, 60, 200, 6,000 ppm M: 0, 1.61, 5.34, 166 F: 0, 1.57, 5.58, 178 |
M: 5.34 F: 5.58 |
M: 166 F: 178 |
F/M: Increased absolute/ relative liver weight, Centrilobular hypertrophy of hepatocytes, etc |
|
| ADI | NOAEL: 5.34 SF: 100 ADI: 0.053 |
||||
| The critical study for setting ADI | One-year chronic toxicity study in dogs | ||||
M, Male; F, Female; F/M, both sexes; PM, Male in P (Parent) generation; PF, Female in P generation; F1M, Male in F1 generation; F1F, Female in F1 generation; -, LOAEL was not derived; 1), The adverse effect observed at LOAEL; ADI, Acceptable daily intake; SF, Safety factor