Table 5.
Comparison of apical and transcriptional BMDs in furan-treated males
| Pathways | Transcriptional BMD(L)s | Apical BMD(L)s | ||||
|---|---|---|---|---|---|---|
| # of genes modeled (total # of genes in pathway) | BMD median (mg/kg bw) | BMDL median (mg/kg bw) | Apical endpoints | BMD (mg/kg bw) | BMDL (mg/kg bw) | |
| Cell damage and apoptosis | ||||||
| p38 MAPK signaling | 5 (108) | 0.08 | 0.05 | Kupffer cells pigmentation | 0.03 | 0.02 |
| ERK/MAPK signaling | 6 (176) | 0.17 | 0.04 | Hepatocytes apoptosis | 0.03 | 0.02 |
| NRF2-mediated oxidative stress response | 8 (169) | 0.62 | 0.47 | |||
| Inflammation | ||||||
| LPS/IL-1-mediated inhibition of RXR function | 15 (186) | 1.1 | 0.69 | ALP | 1.49 | 1.29 |
| Acute phase response signaling | 11 (157) | 1.22 | 0.83 | |||
| Biliary tract damage | ||||||
| Hepatic cholestasis | 5 (126) | 1.10 | 0.77 | Biliary tract hyperplasia | 1.45 | 0.54 |
| FXR/RXR Activation | 6 (79) | 1.38 | 0.91 | Biliary tract cholangiofibrosis | 1.84 | 1.02 |
| Bile acid biosynthesis, neutral pathway | 2 (10) | 1.43 | 0.94 | |||
“# of genes modeled” indicates the number of genes that were significant by ANOVA and could be modeled (i.e., filtered to include genes with BMDs less than the highest dose of 2 mg/kg bw and p value of fit ≥0.1)
“Total # of genes in pathway” indicates all of the genes that are involved in the entire pathway