Table 5.
List of toxicological studies with the NF
| Reference | Type of study | Test system | Treatment/Dose | |
|---|---|---|---|---|
| Shibata et al. (1991a) | Genotoxicity | Bacterial reverse mutation test | Escherichia coli WP2 urvA, Salmonella Typhimurium SD100 and TM677 | Up to 5,000 µg/plate (absence and presence of S9 mix) |
| Chromosomal aberration test | Chinese hamster lung cells (CHL) |
6 h + 18 h recovery +/− S9 24 h and 48 h – S9 Range from 1 × 10–3–3.3 × 10−6 mol/L |
||
|
In vivo mammalian erythrocyte micronucleus test |
ddY male mice | 100–200 and 400 mg/kg | ||
|
Study number T‐G584 |
In vitro micronucleus test | Human lymphoblast TK6 cells |
4 h + 20 h recovery absence and presence of S9 24 h in absence of S9 Range from 0 to.50 ug/L |
|
| Matsuda et al. (1991a) | Acute toxicity | Acute single‐dose toxicity study | ICR mice and Sprague‐Dawley rats |
566–2,500 mg/kg in mice 4,823–10,000 mg/kg in rats |
| Matsuda et al. (1991b) | Subchronic toxicity | 90‐day repeated dose oral study | Crj:CD(SD) rats | 0, 37.5, 75, 150, 300, 600 and 1,200 mg/kg bw per day |
| 52‐week repeat‐dose toxicity | Crj:CD(SD) rats | 0, 18.75, 37.5, 75 and 150 mg/kg bw per day | ||
| Matsuda et al. (1995) | 13‐week repeated‐dose toxicity | Beagle dogs | 0, 50, 120 and 300 mg/kg bw per day | |
| 13‐week repeated‐dose toxicity | Beagle dogs | 0, 8 and 20 mg/kg bw per day | ||
| 52‐week repeated‐dose toxicity | Beagle dogs | 0, 20 and 50 mg/kg bw per day | ||
|
Yamaguchi et al. (1996) These studies are the same as Matsuda 1991b and 1995 where zinc, iron and copper contents in tissues are measured |
90‐day repeated‐dose oral study | Crj:CD(SD) rats | 0, 150, 300, 600 and 1,200 mg/kg bw per day | |
| 52‐week repeat‐dose toxicity | Crj:CD(SD) rats | 0, 75 and 150 mg/kg bw per day | ||
| 13‐week repeated‐dose toxicity | Beagle dogs | 0, 50, 120 and 300 mg/kg bw per day | ||
| 52‐week repeated‐dose toxicity | Beagle dogs | 0, 20 and 50 mg/kg bw per day | ||
| Matsuda et al. (1991c) |
Reproductive and evelopmental toxicity |
Males: 9 weeks prior and during mating Females: 2 weeks prior to mating through day 7 of gestation |
Crj:CD(SD) rats | 0, 300, 600 and 1,200 mg/kg bw per day |
| Females: days 7–17 of gestation | Crj:CD(SD) rats | 0, 150, 300 and 600 mg/kg bw per day | ||
| Females: from days 17 of gestation through day 20 post‐partum | Crj:CD(SD) rats | 0, 100, 250 and 600 mg/kg bw per day |