Table 4.
Histopathological findings—expanded single dose intravenous toxicity study of 211At-NaAt in mice –
| Inspection time | 5 days after administration | ||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sex | Male | ||||||||||||||||||||||||||||||||
| Group | Control | 5 MBq/kg | 20 MBq/kg | 50 MBq/kg | |||||||||||||||||||||||||||||
| No. of animals | 10 | 10 | 10 | 10 | |||||||||||||||||||||||||||||
| Grade of lesion | N | ± | + | ++ | + + + | N | ± | + | + + | + + + | N | ± | + | + + | + + + | N | ± | + | + + | + + + | |||||||||||||
| Organ | Histopathological findings | ||||||||||||||||||||||||||||||||
| Thyroid | : Decreased colloid | 9 | 0 | 1 | 0 | 0 | 6 | 0 | 3 | 0 | 1 | 0 | 0 | 5 | 4 | 1 | 1 | 0 | 1 | 1 | 7 | ||||||||||||
| : Degenration/necrosis, follicular cell | 9 | 0 | 1 | 0 | 0 | 7 | 0 | 2 | 0 | 1 | 0 | 0 | 9 | 0 | 1 | 1 | 0 | 1 | 3 | 5 | |||||||||||||
| : Infiltrate, inflammatory cell, diffuse | 10 | 0 | 0 | 0 | 0 | 8 | 1 | 0 | 1 | 0 | 0 | 6 | 3 | 1 | 0 | 1 | 1 | 2 | 6 | 0 | |||||||||||||
| Stomach | : Cyst, glandular, squamous metaplasia | 10 | 0 | 0 | 0 | 0 | 9 | 0 | 1 | 0 | 0 | 9 | 0 | 1 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | ||||||||||||
| : Dilatation, gland | 9 | 0 | 1 | 0 | 0 | 8 | 0 | 2 | 0 | 0 | 7 | 0 | 3 | 0 | 0 | 8 | 0 | 2 | 0 | 0 | |||||||||||||
| : Infiltrate, inflammatory cell, focal | 10 | 0 | 0 | 0 | 0 | 9 | 0 | 1 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | |||||||||||||
| Kidney | : Cast, hyaline | 9 | 0 | 1 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | ||||||||||||
| : Regenaration, tubule | 8 | 0 | 1 | 1 | 0 | 10 | 0 | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | |||||||||||||
| Testis | : Hypoplasia | 10 | 0 | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | 9 | 0 | 0 | 1 | 0 | ||||||||||||
| : Sperm stasis, focal | 10 | 0 | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | 9 | 0 | 1 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | |||||||||||||
| Epididymis*1 | : Degeneration/necrosis, epithelial, focal | Not examined | 0 | 0 | 1 | 0 | 0 | Not examined | Not examined | ||||||||||||||||||||||||
| : Fibrosis, focal | 0 | 0 | 1 | 0 | 0 | ||||||||||||||||||||||||||||
| : Infiltrate, inflammatory cell, focal | 0 | 1 | 0 | 0 | 0 | ||||||||||||||||||||||||||||
| Intraperitoneal nodule*1 | : Congestion | Not examined | 0 | 0 | 1 | 0 | 0 | Not examined | Not examined | ||||||||||||||||||||||||
| : Fibrous capsule | 0 | 0 | 1 | 0 | 0 | ||||||||||||||||||||||||||||
| : Necrotic liver mass | 0 | 0 | 1 | 0 | 0 | ||||||||||||||||||||||||||||
| Inspection time | 5 days after administration | ||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sex | Female | ||||||||||||||||||||||||||||||||||||
| Group | Control | 5 MBq/kg | 20 MBq/kg | 50 MBq/kg | |||||||||||||||||||||||||||||||||
| No. of animals | 10 | 10 | 10 | 10 | |||||||||||||||||||||||||||||||||
| Grade of lesion | N | ± | + | ++ | +++ | N | ± | + | ++ | +++ | N | ± | + | ++ | +++ | N | ± | + | ++ | +++ | |||||||||||||||||
| Organ | Histopathological findings | ||||||||||||||||||||||||||||||||||||
| Thyroid | : Decreased colloid | 10 | 0 | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | 0 | 0 | 8 | 2 | 0 | 0 | 0 | 0 | 6 | 4 | ||||||||||||||||
| : Degenration/necrosis, follicular cell | 10 | 0 | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | 0 | 0 | 9 | 1 | 0 | 0 | 0 | 1 | 5 | 4 | |||||||||||||||||
| : Infiltrate, inflammatory cell, diffuse | 10 | 0 | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | 0 | 5 | 5 | 0 | 0 | 0 | 0 | 6 | 4 | 0 | |||||||||||||||||
| Stomach | : Cyst, glandular, squamous metaplasia | 10 | 0 | 0 | 0 | 0 | 9 | 0 | 1 | 0 | 0 | 9 | 0 | 1 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | ||||||||||||||||
| : Dilatation, gland | 9 | 0 | 1 | 0 | 0 | 6 | 0 | 4 | 0 | 0 | 9 | 0 | 1 | 0 | 0 | 6 | 0 | 4 | 0 | 0 | |||||||||||||||||
| : Infiltrate, inflammatory cell, focal | 10 | 0 | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | 9 | 0 | 1 | 0 | 0 | |||||||||||||||||
| Kidney | : Vacuolation, tubule, outer medulla | 10 | 0 | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | 10 | 0 | 0 | 0 | 0 | 7 | 0 | 3 | 0 | 0 | ||||||||||||||||
| Adrenal | : Accessory adrenocortical tissue | 10 | 0 | 0 | 0 | 0 | Not examined | Not examined | 9 | 0 | 1 | 0 | 0 | ||||||||||||||||||||||||
| Intraperitoneal nodule*1 | : Congestion | Not examined | 0 | 0 | 1 | 0 | 0 | Not examined | Not examined | ||||||||||||||||||||||||||||
| : Fibrous capsule | 0 | 0 | 1 | 0 | 0 | ||||||||||||||||||||||||||||||||
| : Necrotic liver mass | 0 | 0 | 1 | 0 | 0 | ||||||||||||||||||||||||||||||||
| Inspection time | 14 days after administration | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sex | Male | Female | |||||||||||||||||||
| Group | Control | 50 MBq/kg | Control | 50 MBq/kg | |||||||||||||||||
| No. of animals | 5 | 5 | 5 | 5 | |||||||||||||||||
| Grade of lesion | N | ± | + | ++ | +++ | N | ± | + | ++ | +++ | N | ± | + | ++ | +++ | N | ± | + | ++ | +++ | |
| Organ | Histopathological findings | ||||||||||||||||||||
| Thyroid | : Decreased colloid | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 |
| : Fibrosis | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | |
| : Infiltrate, inflammatory cell, diffuse | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 1 | 0 | |
| Stomach | : Cyst, glandular, squamous metaplasia | 5 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 0 | 3 | 0 | 2 | 0 | 0 | 4 | 0 | 1 | 0 | 0 |
| : Dilatation, gland | 2 | 0 | 3 | 0 | 0 | 1 | 0 | 4 | 0 | 0 | 5 | 0 | 0 | 0 | 0 | 3 | 0 | 2 | 0 | 0 | |
| Kidney | : Vacuolation, tubule, outer medulla | 5 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 0 | 4 | 0 | 1 | 0 | 0 |
| Adrenal | : Degenration/necrosis, focal, cortex and medulla | 5 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 1 | 0 | 5 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 0 |
| : Fibrosis, cortex | 5 | 0 | 0 | 0 | 0 | 4 | 0 | 1 | 0 | 0 | 5 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 0 | |
| : Mineralization, focal, cortex and medulla | 5 | 0 | 0 | 0 | 0 | 4 | 0 | 1 | 0 | 0 | 5 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 0 | |
| : Pigmentation, yellowish brown, cortex | 5 | 0 | 0 | 0 | 0 | 4 | 0 | 1 | 0 | 0 | 5 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 0 | |
| Testis | : Multinucleated giant cell | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | ||||||||||
No remarkable changes were seen in the brain, parathyroid, trachea, esophagus, salivary gland (submandibular gland), salivary gland (sublingual gland), sublingual gland, thymus, heart, lung, bronchia, liver, gall bladder, pancreas, duodenum, jejunum, colon, mesenteric lymph node, spleen, adrenal, urinary bladder, femur, bone marrow and eye
Grade of lesion : N Normal, ± Minimal or abnormality, + Slight, ++ Moderate, +++ Severe
*1 N=1 (5 MBq/kg)