FISH IN IMMUNOTOXICITY RISK ASSESSMENT

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Recent research indicates the fish immune system represents a highly sensitive target of immunotoxicant exposure. Further, fish appear to respond similarly to mammals following such immunotoxicant assault. These reports indicate that fish may represent a viable alternate species to mammals which can be employed for chemical immunotoxicity screening. The proposed studies will determine the ability of immune screens with demonstrated high predictive value for immunotoxicity (immunosuppression) in rodents to detect immunotoxicants in the tilapian fish species Oreochromis niloticus. Nine chemical agents with positive rodent immunotoxicity classification and five agents with negative rodent immunotoxicity classification will be evaluated using eight immune assays in tilapia. The immune screens to be evaluated in fish (and the estimated individual predictive value of each test for immunosuppression in rodents will include the: 1) spleen antibody plaque forming cell (PFC) assay [78%]; 2) natural killer (NK) cell cytotoxicity [69%]; 3) T cell lymphoproliferative responses [67%]; 4) spleen to body-weight ratio [61%]; 5) splenic cellularity [56%]; 6) mixed lymphocyte response [56]%; 7) B cell lymphoproliferative responses (50%]; and 8) peripheral leukocyte counts [43%]. The individual and pairwise concordance (e.g., sum of specificity and sensitivity, where sensitivity is the probability to predict an immunotoxicant with the immune assay given the compound is truly an immunotoxicant, and where specificity is the probability of correctly identifying non-immunotoxic chemicals using the immune assays) values of each of these immune tests to predict immunotoxic compounds in tilapia will then be calculated. The assimilated data from this project will determine for the first time the ability of immune screens with high predictive value in laboratory rodents to accurately identify chemical immunotoxicants in fish. In particular, the project will determine the potential for use of a fish species (tilapia) as an alternate to mammals for immunotoxicity screening, as well as the predictive value for immunotoxicity of the selected immune screens for a selected set of immunotoxicants in fish.