Table 1.
Criteria to establish the role of α2u-globulin nephropathy in renal carcinogenesis.
| US EPA (1991)a |
| Increased number and size of hyaline droplets in renal proximal tubule cells of treated male rats |
| Protein in the hyaline droplets is α2u-globulin Additional pathological sequence of lesions |
| IARC (1999)b |
| Essential Evidence |
| Tumors occur only in male rats |
| Acute exposure exacerbates hyaline droplet formation |
| α2u-Globulin accumulates in hyaline droplets |
| Subchronic lesions include granular casts and linear papillary mineralization |
| Absence of hyaline droplets and other histopathological changes in female rats and mice |
| Negative for genotoxicity |
| Additional Supporting Evidence |
| Reversible binding of chemical to α2u-globulin |
| Increased sustained cell proliferation in proximal tubule (P2 segment) |
| Dose-response relationship between hyaline droplet severity and renal tumor incidence |