Table 2.
Reevaluation of liver histopathology as reported in US EPA (2021).
| DuPont OECD 408 9 | ||||||||
|---|---|---|---|---|---|---|---|---|
| 90-day gavage | Male Crl: CD1(ICR) | Female Crl: CD1(ICR) | ||||||
| Dose (mg/kg/day): | 0 | 0.1 | 0.5 | 5 | 0 | 0.1 | 0.5 | 5 |
| Mixed cell infiltrate | 6/10 | 6/10 | 4/10 | 6/10 | 5/10 | 3/10 | 3/10 | 7/10 |
| Hepatocellular single cell necrosis a | 0/10 | 1/10 | 0/10 | 9/10 | 0/10 | 0/10 | 0/10 | 3/10 |
| Cytoplasmic alteration | 0/10 | 0/10 | 10/10 | 10/10 | 0/10 | 0/10 | 0/10 | 10/10 |
| Focal necrosis | 0/10 | 0/10 | 0/10 | 1/10 | 1/10 | 0/10 | 2/10 | 4/10 |
| Cytoplasmic vacuolization | 0/10 | 0/10 | 0/10 | 0/10 | 0/10 | 0/10 | 0/10 | 0/10 |
| Extramedullary hematopoiesis | 0/10 | 0/10 | 0/10 | 1/10 | 0/10 | 0/10 | 0/10 | 0/10 |
| Increased pigment | 0/10 | 0/10 | 0/10 | 10/10 | 0/10 | 0/10 | 0/10 | 4/10 |
| Hepatocellular apoptosis b | 0/10 | 0/10 | 0/10 | 10/10 | 0/10 | 0/10 | 0/10 | 3/10 |
| Increased mitotic figures | 0/10 | 0/10 | 0/10 | 7/10 | 0/10 | 0/10 | 0/10 | 0/10 |
| Bile duct hyperplasia | 0/10 | 0/10 | 0/10 | 1/10 | 0/10 | 0/10 | 0/10 | 0/10 |
| DuPont OECD 421 8 | ||||||||
| ~60-88 days, gavage | Male Crl: CD1(ICR) | Female Crl: CD1(ICR) | ||||||
| Dose (mg/kg/day): | 0 | 0.1 | 0.5 | 5 | 0 | 0.1 | 0.5 | 5 |
| Mixed cell infiltrate | 6/25 | 3/25 | 11/25 | 8/25 | 12/25 | 7/25 | 17/25 | 15/25 |
| Hepatocellular single cell necrosis a | 1/25 | 1/25 | 2/25 | 24/25 | 0/25 | 2/25 | 3/25 | 19/25 |
| Cytoplasmic alteration | 0/25 | 0/25 | 10/25 | 25/25 | 0/25 | 1/25 | 16/25 | 25/25 |
| Focal necrosis | 0/25 | 0/25 | 4/25 | 3/25 | 2/25 | 2/25 | 4/25 | 5/25 |
| Cytoplasmic vacuolization | 0/25 | 0/25 | 3/25 | 0/25 | 0/25 | 0/25 | 0/25 | 1/25 |
| Extramedullary hematopoiesis | 0/25 | 0/25 | 1/25 | 2/25 | 0/25 | 0/25 | 0/25 | 1/25 |
| Increased pigment | 0/25 | 0/25 | 0/25 | 21/25 | 0/25 | 0/25 | 0/25 | 3/25 |
| Hepatocellular apoptosis b | 0/25 | 0/25 | 0/25 | 22/25 | 0/25 | 0/25 | 0/25 | 10/25 |
| Increased mitotic figures | 0/25 | 0/25 | 0/25 | 17/25 | 0/25 | 0/25 | 0/25 | 2/25 |
| Oval cell hyperplasia | 0/25 | 0/25 | 0/25 | 4/25 | 0/25 | 0/25 | 0/25 | 0/25 |
| Inflammation granulomatous | 0/25 | 0/25 | 0/25 | 0/25 | 0/25 | 0/25 | 1/25 | 0/25 |
| Polyarteritis nodosa | 0/25 | 0/25 | 0/25 | 0/25 | 0/25 | 0/25 | 0/25 | 1/25 |
Abbreviations: EPA, Environmental Protection Agency; OECD, Organization for Economic Cooperation and Development.
a
All lesions were considered minimal severity (1-10 cells in ten 20X fields; US EPA 3 pp. D-5)
b
All lesions were considered minimal to mild in severity (1-10 cells or 11-40 cells in ten 20X fields; US EPA 3 pp. D-6).