Comparison of 17 methods of predicting the carcinogenicity of 30 chemicals.

Bristol et al. (1) recently introduced and summarized 17 sets of predictions of the carcino-genicity of 30 chemicals currently undergoing long-term rodent cancer bioassay in the National Toxicology Program (NTP). These predictions will eventually be compared with the bioassay outcomes. To aid that process, a summary table was provided by Bristol et al. (1). In the legend to that summary table, Bristol et al. (1) noted that reference should be made to the original papers for a completely reliable representation of the individual predictions made. The summary table is rather complex in construction and, in some aspects, it is unclear. For example, the code "NP" can mean two distinct things, and the separate terms "undecided," "equivocal," "no prediction made," and "abstained" are not always distinct in meaning. Given that this table will eventually be used to check the validity of the predictive methods used, it should be clear and reliable. Toward this end, the table has been simplified below (Table 1). Designations of genotoxic and nongenotoxic have been removed and three terms-"not possible," "uncertain,"and "equivocal"-have been combined into a question mark (?; not equivalent to a prediction of equivocal carcinogenicity). It will be necessary to review and correct the entries in the table so that an accurate compilation of the predictions is available for future reference. For example, it is difficult to reconcile the entries under COMPACT with the data presented by Lewis et al. in their table 3 (2). Further, the reason for having identical entries under SHE and under Kerckaert et al. [the source of the single set of SHE data (3)] is unclear. It is important to have these and other uncertainties clarified to prevent confusion later, a task that can only be done by those who hold the predictions originally submitted (i.e., Bristol et al.). Several general points are evident from Table 1, each ofwhich may require refinement when a revised summary table is produced, but each of which should essentially survive that process. First, all of the chemicals are credited with at least one positive prediction-no uniformly positive or negative predictions have been made. The least number of positive predictions was for compound 27, where only the CASE system predicted activity. At the other extreme, 14 positive predictions were made for compound 3. Second, there is a wide range of predictions made by these several methods for the 30 chemicals. Thus, according to Table 1, …