Doses in rodent cancer studies: Sorting fact from fiction

The belief that rodent cancer bioassays predict for human cancers is a fund amental public health precept based on sound biological principles. Nonethe less, it is appropriate to periodically debate this point as scientific und erstanding of cancer causation advances. This presentation addresses one of the many factors that determines the predictive value of rodent tumor bioa ssay results for human health: This is the issue of dose. Examination of se veral recent National Toxicology Program (NTP) studies demonstrates that th e applied dose often far overestimates the actual effective dose, or maximu m blood concentration attained in a rodent, when compared with similar rela tionships in humans. Further examination of the NTP database on rodent toxi city and carcinogenicity studies revealed summary information on factors th at were pivotal in prechronic studies for selecting doses for chronic studi es. Contrary to popular belief, target organ toxicity was a determining fac tor in only about,half of the studies. The typically minimal nature of the lesions which limit doses for chronic studies is described for several comm on target sites. Taken together, these facts paint a far different picture than the common public perception of the ''massive'' doses used in chronic rodent studies and suggest that, in some cases, dose limitations are actual ly so severe as to limit the sensitivity of a chronic bioassay to detect a carcinogenic effect.