On the rodent bioassays currently being conducted on 44 chemicals: a RASH analysis to predict test results from the National Toxicology Program.
We use a method of relative potency comparisons to rank the potential strength of 44 compounds being tested in rodent carcinogenicity bioassays. All of our previous hazard evaluations have been for human conditions where great numbers of simultaneous and serial exposures may act in combination to produce a neoplasm comprised of 2(20) to 2(30) cells commonly expected to derive from a single precancerous cell. For human exposures, we have always assumed an initiated target tissue containing at least one transformed but subcarcinogenic cell per organ. Thus, for man we have focused on empirical correspondences that may help to index the monoclonal growth of a particular cell lineage during cancer expansion. In contrast to humans, initiation of target tissues in animals subjected to National Toxicity Program (NTP) bioassays may not be a given condition, because of extensive precautions taken to minimize exposures to contaminates in food, water and cage environments. For this evaluation, we used categorical assignments of 'unlikely', 'possible' and 'probable' carcinogens adapted from NTP tests. Our rank ordering, of compounds according to maximum doses tested in male mice and male rats, is coded accordingly to the three outcomes taken from the NTP tests, but the magnitude of potency depend completely upon our particular method of comparing toxicological data. We have attempted to demonstrate that a relative potency based analysis of a diversity of toxicological data may be useful for rank ordering potentially hazardous compounds to be tested by the NTP and for range-finding of their effective test doses to be administered during chronic test protocols.
Jones
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Health and Safety Research Division, Oak Ridge National Laboratory, TN 37831-6101.
Easterly
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D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D005260:Female; D008297:Male; D051379:Mice; D051381:Rats; D011916:Rats, Inbred F344; D012306:Risk; D014116:Toxicology / Q000379:methods
D002273:Carcinogens