Relevance of Rat a2u-Globulin Nephropathy and CPN to Humans

From the discussion above, it should be clear that the induction of tumors in a2u-g nephropathy is a male-rat-specific phenomenon, which does not occur in female rats or male or female mice, or in rats where the gene for hepatic s)mthesis of tt2u-g is absent. In addition, the chemicals that bind to a2u-g have been shown not to bind to human members of the lipocalin superfamily of proteins. Thus, it is now recognized that provided the chemical of interest meets the critEiia set by the various regulatory or authoritative bodies, such as the U.S. ERA and lARC, then chemicals producing a low incidence of RTT in male rats by this mode of action should be judged as having no relevance for hazard assessment in humans. 

In the few cases where a chemical may be judged as acting through modes of action involving both tt2u-g nephropathy and exacerbation of CPN, the judgment 

(1996). Alpha 2 mu-globulin nephropathy in white ravens. Environ Health Perspect 104, 1264-1267. 

Barter, 1. A., and Sherman, J. H. (1999). An evaluation of the carcinogenic hazard of 1,4-dichlorobenzene based on internationally recognized criteria. Regul Toxicol Pharmacol 29, 64—79. 

Barthold, S. W. (1979). Chronic progressive nephropathy in aging rats. Toxicol Pathol 7, 1-6. 

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