Interpretation of male rat renal tubule tumors.
Based on an analysis of recent scientific studies, a Technical Panel of the U.S. Environmental Protection Agency's (EPA) Risk Assessment Forum recently advised EPA risk assessors against using information on certain male rat renal tubule tumors to assess human risk under conditions specified in a new Forum report. Risk assessment approaches generally assume that chemicals producing tumors in laboratory animals are a potential cancer hazard to humans. For most chemicals, including classical rodent kidney carcinogens such as N-ethyl-N-hydroxyethylnitrosamine, this extrapolation remains appropriate. Some chemicals, however, induce accumulation of alpha 2u-globulin (alpha 2u-g), a low molecular weight protein, in the male rat kidney. The alpha 2u-g accumulation initiates a sequence of events that appears to lead to renal tubule tumor formation. 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. Because 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. The Forum report stresses the need for full scrutiny of a substantial set of data to determine when it is reasonable to presume that renal tumors in male rats are linked to a process involving alpha 2u-g accumulation and to select appropriate procedures for estimating human risks under such circumstances.
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U.S. Environmental Protection Agency, Washington, DC 20460.
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D000510:Alpha-Globulins / Q000378:metabolism; D000818:Animals; D003627:Data Interpretation, Statistical; D004195:Disease Models, Animal; D006801:Humans; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D007684:Kidney Tubules; D008297:Male; D051381:Rats; D012307:Risk Factors; D014481:United States; D014484:United States Environmental Protection Agency
D000510:Alpha-Globulins; C013803:alpha 2u globulin