FISH IN IMMUNOTOXICITY RISK ASSESSMENT

最近的研究表明，鱼类的免疫系统代表了一个高度 免疫毒素暴露的敏感靶点。此外，鱼类似乎 哺乳动物在受到这种免疫毒素攻击后的反应类似。这些 报告表明，鱼类可能是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。的 拟议的研究将确定免疫筛选的能力， 证明了对免疫毒性（免疫抑制）的高预测值 在啮齿类动物中检测罗非鱼中的免疫毒素 尼罗罗非鱼9种化学药剂与阳性啮齿动物 免疫毒性分类及5种致鼠阴性药物 将使用8种免疫测定法评价免疫毒性分类 在罗非鱼身上。在鱼类中评估的免疫筛选（以及估计的 啮齿类动物中每种免疫抑制试验的个体预测值 将包括：1）脾抗体空斑形成细胞（PFC）试验 [78%]; 2）自然杀伤（NK）细胞毒性[69%]; 3）T细胞 淋巴组织增生反应[67%]; 4）脾脏/体重比[61%]; 5)脾细胞构成[56%]; 6）混合淋巴细胞反应[56]%; 7）B 细胞淋巴增殖反应（50%）; 8例外周血白细胞 计数[43%]。个体和成对一致性（例如，总和 特异性和灵敏度，其中灵敏度是 用免疫测定预测免疫毒性， 真正的免疫毒素，特异性是指 使用免疫分析正确识别非免疫毒性化学品） 这些免疫测试中的每一个的值来预测免疫毒性化合物， 然后计算罗非鱼。本项目的同化数据 将首次确定免疫筛选的能力， 在实验室啮齿动物中准确识别化学品的预测值 鱼类中的免疫毒素特别是，该项目将确定 利用鱼类（罗非鱼）替代哺乳动物的潜力 用于免疫毒性筛查，以及 所选择的免疫筛选的免疫毒性对于所选择的一组 鱼类中的免疫毒素

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.