Urinary tract calculi and thresholds in carcinogenesis.
Numerous chemicals administered to rodents at relatively high doses produce urinary tract calculi, resulting in erosions or ulcerations of the urothelium, consequent regenerative hyperplasia, and ultimately tumors. This is a high-dose (threshold) phenomenon, which appears to occur more readily in rodents than in primates, including humans. Several anatomic and urinary physiologic differences between rodents and humans affect the quantitative extrapolation from results in rodent bioassays to human risk assessment. For most chemicals producing tumors by this mode of action, human exposures are significantly lower than would be expected to be required for production of calculi, and therefore pose no carcinogenic hazard to humans.
Cohen
S M
SM
Department of Pathology and Microbiology, University of Nebraska Medical Center, 983135 Nebraska Medical Center, Omaha, NE 68198-3135, USA. scohen@unmc.edu
Johansson
S L
SL
Arnold
L L
LL
Lawson
T A
TA
D000818:Animals; D006801:Humans; D051379:Mice; D051381:Rats; D018570:Risk Assessment; D014545:Urinary Calculi / Q000150:complications* / Q000473:pathology; D014571:Urologic Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology