FISH IN IMMUNOTOXICITY RISK ASSESSMENT

最近的研究表明，鱼的免疫系统代表着高度的 免疫毒物暴露的敏感目标。此外，鱼似乎 对这种免疫毒素攻击后的哺乳动物也有类似的反应。这些 报告表明，鱼可能代表着一种可行的替代物种 可用于化学免疫毒性筛选的哺乳动物。这个 拟议的研究将确定免疫筛查的能力 对免疫毒性(免疫抑制)有很高的预测价值 在啮齿动物身上检测罗非鱼物种中的免疫毒物 尼罗罗非鱼。9种化学药剂对啮齿动物呈阳性反应 免疫毒性分类及5种阴性啮齿动物制剂 免疫毒性分类将使用八种免疫检测方法进行评估 在罗非鱼身上。待评估的鱼类免疫筛查(和估计的 各试验对啮齿动物免疫抑制的个体预测价值 将包括：1)脾抗体空斑形成细胞(PFC)检测 [78%]；2)自然杀伤细胞杀伤[69%]；3)T细胞 淋巴增殖性反应[67%]；4)脾/体重比[61%]； 5)脾细胞密度[56%]；6)混合淋巴细胞反应[56%]；7)B 细胞淋巴增殖性反应(50%)；8)外周血白细胞 计入[43%]。个体和成对和谐(例如，和 特异性和敏感度，其中敏感度是指 用免疫分析预测免疫毒物，给定化合物是 真正的免疫毒剂，其中特异性是 使用免疫分析正确识别非免疫毒性化学物质) 每种免疫试验在预测免疫毒性化合物方面的价值 然后罗非鱼将被计算出来。来自该项目的同化数据 将第一次确定免疫筛查的能力与高 在实验室啮齿动物中准确识别化学物质的预测价值 鱼中的免疫毒素。特别是，该项目将确定 一种鱼类(罗非鱼)作为哺乳动物替代品的潜力 用于免疫毒性筛查，以及对 所选免疫屏幕对所选一组 鱼中的免疫毒素。

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.