Relative Ranking of Potencies

Animal studies performed with carcinogenic substances have shown that there can even be extremely wide differences in the exposure levels of various substances necessary to induce mmors in the animals, i.e., the potency in terms of inducing carcinogenicity can vary widely from substance to substance. There are no reasons to beheve that humans should be different from experimental animals in this respect. 

In order to express the carcinogenic response or potency, a dose descriptor is used, for example the Tumorigenic Dose (TD). The TD is often set at a defined incidence, for example 5%, the TD5, defined as the dose (or concentration) associated with a 5% incidence of mmors. The dose descriptor can serve as the basis for development of an Exposure/Potency Index (EPl), which is the estimated daily human exposure divided by the TD. A calculated EPl of 10 for the TD5 represents a one million-fold difference between the human exposure and that at the lower end of the dose-response curve, on which the estimate of potency is based. 

The Carcinogenic Potency Database (CPDB) is a unique and widely used international database containing results from 6153 chronic, long-term animal cancer smdies on 1485 chemicals (CPDB 2007), see also Section 4.9.8. 

According to WHO/IPCS (1999), any model that fits the empirical data well is likely to provide a reasonable estimation of the TD5. Choice of the model may not be critical since estimation is within the observed dose range, thereby avoiding the numerous uncertainties associated with low-dose extrapolation. 

The US-EPA has in its 1996 Proposed Guidelines for Carcinogen Risk Assessment (US-EPA 1996) adopted the dose descriptor LEDio (the 95% lower confidence limit on a dose associated with a 10% extra tumor risk) whereas in its 2005 Guidelines for Carcinogen Risk Assessment (US-EPA 2005), no defined incidence has been recommended (see Section 6.3.2). Within the EU chemical s regulation, the dose descriptor T25 has been proposed (see Section 6.3.3). In the newly proposed MOE approach, the JECFA and the EFSA have recommended the dose descriptor BMDLio (see Section 6.4). 

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