Table 1. Levels relevant to toxicological evaluation of dichlobentiazox.
| 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, 300, 900, 3 000 ppm | M: 22 F: 74 |
M: 65 F: 263 |
M: Hyaline droplet accumulation in renal
tubule cortex and others F: Epithelial villus hypertrophy/hyperplasia of duodenum |
| M: 0, 22, 65, 236 F: 0, 25, 74, 263 | |||||
| Two-year combined chronic
toxicity /carcinogenicity study |
0, 120, 550, 2 500 ppm | M: 5.03 F: 7.01 |
M: 23.5 F: 31.9 |
FM: Epithelial villus
hypertrophy/hyperplasia of duodenum and others (Not carcinogenic) |
|
| M: 0, 5.03, 23.5, 108 F: 0, 7.01, 31.9, 144 | |||||
| Two-generation reproductive toxicity study | 0, 62.5, 250, 1 000 | Parent M: 62.5 F: 1 000 Offspring FM: 1000 |
Parent M: 250 F: - Offspring FM: - |
Parent M: Suppressed body weight F: No toxicity Offspring FM: No toxicity (No effect on reproduction) |
|
| Developmental toxicity | 0, 62.5, 250, 1 000 | Maternal: 250 Embryo/fetus: 250 |
Maternal: 1 000 Embryo/fetus: 1 000 |
Maternal: Suppressed body weight and decreased feed
consumption Embryo/fetus: Delayed ossification (absent ossification of fifth and sixth sternebrae) (Not teratogenic) |
|
| Mouse | 90-day subacute toxicity study | 0, 100, 450, 2 000 ppm | M: 65 F: 80 |
M: 315 F: 381 |
FM: Epithelial villus hypertrophy/hyperplasia of duodenum and others |
| M: 0, 14, 65, 315 F: 0, 19, 80, 381 | |||||
| 78-week carcinogenicity study | 0, 50, 325, 2 000 ppm | M: 247 F: 258 |
M: - F: - |
FM: No toxicity (Not carcinogenic) |
|
| M: 0, 5.8, 38, 247 F: 0, 6.6, 42, 258 | |||||
| Rabbit | Developmental toxicity study | 0, 15, 50, 150 | Maternal: 50 Embryo/fetus: 150 |
Maternal: 150 Embryo/fetus: - |
Maternal: Decreased/suppressed body weight, decreased
feed consumption and others Embryo/fetus: Not toxic (Not teratogenic) |
| Dog | 90-day subacute toxicity study | 0, 10, 70, 500 | FM: 10 | FM: 70 | FM: Bile duct hyperplasia in liver |
| One-year chronic toxicity study | 0, 5, 50, 500/200 | FM: 50 | FM: 500/200 | M: Bile duct hypertrophy in liver and others F: Decreased RBC, Ht or Hb and others |
|
| ADI | NOAEL: 5.03 SF: 100 ADI: 0.05 |
||||
| The critical study for setting the ADI | Two-year combined chronic toxicity/carcinogenicity study in rats | ||||
ADI, Acceptable daily Intake; NOAEL, No-observed-adverse-effect level; SF, Safety Factor
Lowest-observed-adverse-effect level (LOAEL) was not derived.
1) The adverse effect observed at LOAEL