Alpha2u-Globulin: Association with Chemically Induced Renal Toxicity andNeoplasia in the Male Rat

摘要

The report of a Technical Panel of the U.S. Environmental Protection Agency (EPA)Risk Assessment Forum describes conditions under which the Forum advises EPA risk assessors against using information on certain renal tubule tumors or nephrotoxicity to assess human risk. Risk assessment approaches generally assume that chemicals producing tumors in laboratory animals are a potential cancer hazard to humans. For most chemicals, including many rodent kidney carcinogens, this extrapolation remains appropriate. The scientific studies reviewed by the Technical Panel indicate, however, that some other chemicals induce accumulation of alpha(sub 2u)-globulin, a low-molecular-weight protein, in the male rat kidney. Female rats and other laboratory mammals administered the same chemicals do not accumulate low-molecular-weight protein in the kidney and they do not develop renal tubule tumors. Since humans appear to be more like other laboratory animals than like the male rat, in this special situation, the male rat is not a good model for assessing human risk.