ze, evaluate, and interpret data contained in NTP carcinogenicity databases. One recent evaluation involved analyzing and interpreting data from a study to determine if small fish could provide carcinogenicity information similar to the traditional rodent bioassays. In this set of studies, two species of fish were exposed to three chemicals known to be rodent carcinogens. Following a similar protocol as for rodents, fish were exposed to these chemicals for up to 16 months and necropsied at an interim or final time point. Several problems inherent to fish suggest that they will not be a good substitute for rodents in the bioassay. Fish that died early were consumed by other fish and not available for necropsy. One of the chemicals encouraged algae growth, and attempts to reduce the algae led to some fish deaths. Because of their similar appearances, males and females could not be separated, so reproduction during the study was possible, but could not be tracked. Nearly all of the tumors occurred in the liver and occasionally in the gallbladder, limiting the richness of the carcinogenicity information. Thus, until these logistical problems can be solved, the NTP bioassay will not benefit from using fish rather than rodents. An ongoing evaluation involves comparison of several dioxin-related compounds and their mixtures. Because these compounds are present together in the environment, humans are exposed to mixtures of these compounds, but the activity of these mixtures has been rarely investigated. The goal of our studies is to evaluate the World Health Organization?s (WHO) Toxic Equivalency Factor (TEF) values that estimate the relative toxicity of these compounds as compared with TCDD. We are completing studies in which rodents were exposed to various doses of TCDD, PCBs, PCDDs, PCDFs or mixtures of these compounds. Each study is being separately reported in the NTP Technical Report series, but in addition, the WHO TEFs will be incorporated into mathematical models to compare carcinogenic responses among compounds. In this way, we will be able to determine, for specific endpoints, whether the WHO TEF values are accurate, or whether adjustments in the relative potencies of these compounds need to be made. We will also be able to evaluate whether compounds have additive effects, synergistic effects, or antagonistic effects when present in mixtures. In another project, we are evaluating the possibilities of using the nematode, C. elegans, as a screening tool for assessing toxicological potential of chemicals. In this set of studies, we are using a high throughput system (flow cytometry) to measure growth, reproduction, and movement of the nematodes following exposure to varying doses of a wide range of chemicals. Because of the pilot study nature of this work, we are currently involved with developing experimental designs, resolving measurement issues, and evaluating methods for statistical analyses.
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