Renal tumors, chemicals increasing

Cancer. No studies have been conducted in human populations to determine whether mirex or chlordecone causes cancer. However, studies in mice and rats have demonstrated the ability of mirex to cause liver tumors (Innes et al. 1969 NTP 1990 Ulland et al. 1977a), pheochromocytomas (NTP 1990), and rare renal tumors (NTP 1990). A study in mice and rats also showed the ability of chlordecone to increase liver tumors (NC11976). As indicated above, available data on the genotoxicity of mirex and chlordecone indicate that these chemicals do not cause cancer by a mutagenic mechanism but rather by tumor promotion. Both mirex and chlordecone are considered by the DHHS to be substances that may reasonably be anticipated to be carcinogens and by IARC to be possible human carcinogens. EPA has not classified mirex or chlordecone as to their carcinogenicity. 

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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