Renal tumors, chemicals increasing incidence

Additional supporting evidence includes demonstration of (a) reversible binding of the chemical or a metabolite to tt2o-g, (b) a sustained increase in cell proliferation in the proximal tubules (P2 segment), and (c) a dose-response relationship between hyaline droplet severity and renal tumor incidence (lARC 1999). 

CHEMICALS INCREASING THE INCIDENCE OF RENAL TUMORS THROUGH EXACERBATION OF SPONTANEOUS CHRONIC PROGRESSIVE NEPHROPATHY (CPN)... 

Conventional rodent toxicity studies characterize adverse effects of a chemical primarily on apical endpoints such as clinical signs or pathological states. Evidence of organ toxicity in the form of an apical endpoint does not always provide mechanistic understanding of the toxicity involved (see Chapter 13). The exposure of rodents in a cancer bioassay model can result in species-specific responses that are not relevant to humans (e.g., alpha2u-globulin-induced rat renal tumors) (see Chapter 18) (EPA 1991). Rodents may also have increased sensitivity to a particular toxicity pathway relative to humans (e.g., disruption of thyroid homeostasis and thyroid follicular tumors in rodents) (EPA 1998 I ARC 2001). There are rodent responses to chemical treatment in tissues where there is a high spontaneous incidence to develop... 

CHEMICALS THAT INCREASE THE INCIDENCE OF RENAL TUBULE TUMORS 483... 

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