Carcinogenic Potencies Across Species

29 May

Although the parameter of carcinogenic potency is not of major concern to regulatory agencies, there have been a number of attempts at relating this parameter to carcinogenesis in the human. In 1989 Crump attempted to relate the potency of carcinogens in mice and humans, using a po- tency calculation somewhat similar to the T25 (Dybing et al., 1997), but did not find a great deal of concordance. Their results are seen in Figure 13.14, with the key for the chemical symbols in the figure legend. These authors suggest several reasons for lack of concordance,  a major one being that confirmed human carcinogens have not been adequately studied in many animal mod- els. However,  they concluded,  on the basis of the data seen in Figure 13.14, that animal and

Figure 13.13 Range of carcinogenic  potency as determined  by the TD50  potency relationship  of Peto et al. (1984). (Adapted from Gold et al., 1998, with permission of the authors and publisher.)

human potencies as measured by them were strongly correlated. Somewhat earlier than the data presented in Figure 13.14 was the study of Gold et al. (1987), who applied the TD50  potency index from animal studies to a number of chemicals having chronic occupational exposure for U.S. workers. They proposed the use of the TD50 to develop an index termed the permitted expo- sure/rodent potency (PERP), which does not estimate absolute risks directly, but rather is indica- tive of relative hazards for the substances to exposed workers. In a more recent study, Dedrick and Morrison (1992) related the carcinogenicity of several alkylating agents in causing leukemia in patients treated for cancer compared with the potency of these agents to induce neoplasms in

Figure 13.14 Human TD25  estimates versus animal TD25  estimates obtained from a log-log plot with data from any experiment,  re- gardless of route of exposure. The best estimate of the animal TD25  is plotted for each chemical, with the vertical lines extending from that point representing  the upper and lower bounds for the human TD25  and the horizontal lines representing  the corresponding  bounds for the animal TD25. The chemicals that were studied are listed as follows, with the abbreviations seen in the figure:

rats and mice. In general, a good correlation among species was observed when the carcinogenic potency was based on the total lifetime exposure.

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