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Monte Carlo Simulation of Rodent Carcinogenicity Bioassays
Author(s) -
Shlyakhter Alexander,
Goodman Gay,
Wilson Richard
Publication year - 1992
Publication title -
risk analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.972
H-Index - 130
eISSN - 1539-6924
pISSN - 0272-4332
DOI - 10.1111/j.1539-6924.1992.tb01309.x
Subject(s) - bioassay , monte carlo method , statistics , standard deviation , toxicology , linear regression , correlation , mathematics , biology , genetics , geometry
In this paper we describe a simulation, by Monte Carlo methods, of the results of rodent carcinogenicity bioassays. Our aim is to study how the observed correlation between carcinogenic potency (β or ln2/TD 50 ) and maximum tolerated dose (MTD) arises, and whether the existence of this correlation leads to an artificial correlation between carcinogenic potencies in rats and mice. The validity of the bioassay results depends upon, among other things, certain biases in the experimental design of the bioassays. These include selection of chemicals for bioassay and details of the experimental protocol, including dose levels. We use as variables in our simulation the following factors: (1) dose group size, (2) number of dose groups, (3) tumor rate in the control (zero‐dose) group, (4) distribution of the MTD values of the group of chemicals as specified by the mean and standard deviation, (5) the degree of correlation between β and the MTD, as given by the standard deviation of the random error term in the linear regression of log β on log (1/MTD), and (6) an upper limit on the number of animals with tumors. Monte Carlo simulation can show whether the information present in the existing rodent bioassay database is sufficient to reject the validity of the proposed interspecies correlations at a given level of stringency. We hope that such analysis will be useful for future bioassay design, and more importantly, for discussion of the whole NCI/ NTP program.