Table 1.
Summary of liver histopathology in HFPO-DA repeat-dose studies in mice.
| Dupont OECD 407 12 | ||||||||
|---|---|---|---|---|---|---|---|---|
| 28-day gavage | Male Crl: CD1(ICR) | Female Crl: CD1(ICR) | ||||||
| Dose (mg/kg/day): | 0 | 0.1 | 3 | 30 | 0 | 0.1 | 3 | 30 |
| Hepatocellular hypertrophy | 0/10 | 0/10 | 10/10 | 10/10 | 0/10 | 0/10 | 10/10 | 10/10 |
| Necrosis, single cell | 0/10 | 0/10 | 4/10 | 10/10 | 0/10 | 0/10 | 0/10 | 4/10 |
| Mitotic figures | 0/10 | 0/10 | 0/10 | 9/10 | 0/10 | 0/10 | 0/10 | 5/10 |
| 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 |
| Hepatocellular hypertrophy | 0/10 | 0/10 | 8/10 | 10/10 | 0/10 | 0/10 | 0/10 | 10/10 |
| Hepatocellular single cell Necrosis | 0/10 | 0/10 | 0/10 | 10/10 | 0/10 | 0/10 | 0/10 | 1/10 |
| Mitotic figures | 0/10 | 0/10 | 0/10 | 9/10 | 0/10 | 0/10 | 0/10 | 0/10 |
| Increased pigment Kupffer cells | 0/10 | 0/10 | 0/10 | 10/10 | 0/10 | 0/10 | 0/10 | 1/10 |
| 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 |
| Hepatocellular hypertrophy | 0/25 | 0/24 | 12/24 | 24/24 | 0/24 | 0/22 | 14/24 | 24/24 |
| Necrosis, single cell | 1/25 | 1/24 | 5/24 | 24/24 | 1/24 | 3/22 | 2/24 | 21/24 |
| Mitotic figures | 0/25 | 0/24 | 0/24 | 18/24 | 0/24 | 0/22 | 0/24 | 5/24 |
| Increased pigment Kupffer cells | 0/25 | 0/24 | 0/24 | 21/24 | 0/24 | 0/22 | 0/24 | 5/24 |
| Focal necrosis | 0/25 | 0/24 | 1/24 | 1/24 | 1/24 | 0/22 | 3/24 | 5/24 |
| Blake et al 15 | ||||||||
| Embryonic days 1.15-E17.5, gavage | Maternal CD-1, ED11.5 | |||||||
| Dose (mg/kg/day): | 0 | 2 | 10 | |||||
| Cytoplasmic alteration | 0/5 | 5/5 | 5/5 | |||||
| Cell death (apoptosis and necrosis) | 0/5 | 4/5 | 3/5 | |||||
| Increased mitotic figures | 0/5 | 3/5 | 4/5 | |||||
| Vacuolation | 0/5 | 0/5 | 5/5 | |||||
| Focal regions of classic necrosis | 1/5 | 0/5 | 1/5 | |||||
| Maternal CD-1, ED17.5 | ||||||||
| Dose (mg/kg/day): | 0 | 2 | 10 | |||||
| Cytoplasmic alteration | 0/5 | 5/5 | 5/5 | |||||
| Cell death (apoptosis and necrosis) | 0/5 | 0/5 | 5/5 | |||||
| Increased mitotic figures a | 5/5 | 0/5 | 0/5 | |||||
| Vacuolation | 0/5 | 0/5 | 5/5 | |||||
| Focal regions of classic necrosis | 0/5 | 1/5 | 1/5 | |||||
| Wang et al 7 | ||||||||
| 28-day gavage | Male ICR (incidence not reported) | |||||||
| Dose (mg/kg/day): | 0 | 1 | ||||||
| Swollen hepatocytes | X | |||||||
| Swollen nucleus | X | |||||||
| Necrosis | X | |||||||
| Mild steatosis | X | |||||||
| Inclusion bodies | X | |||||||
| Karyolysis | X | |||||||
| Guo et al 13 | ||||||||
| 28-day gavage | Male Balb/c (incidence not reported) | |||||||
| Dose (mg/kg/day): | 0 | 0.4 | 2 | 10 | ||||
| Steatosis | X | |||||||
| Xu et al 16 | ||||||||
| GD0-parturition, gavage | Maternal Balb/c (incidence not reported) | |||||||
| Dose (mg/kg/day): | 0 | 2 | ||||||
| Hepatocyte hypertrophy | X | |||||||
| Disarrangement | X | |||||||
| Cytoplasmic loss | X | |||||||
| Nuclear migration | X | |||||||
| Acidophil bodies | X | |||||||
| Inflammatory cell infiltration | X | |||||||
Abbreviations: GD, gestational day; HFPO-DA, ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate; OECD, Organization for Economic Cooperation and Development.
a
May be a reporting error in Supplemental Table S7 of Blake et al.