ABSTRACT

Polychlorinated biphenyls (PCBs) have been assessed for immunotoxicity; however, humans and wildlife are exposed to multiple PCBs environmentally. Therefore, the aim of this study was to examine the effects of a complex 37 PCB congener mixture identified in blubber specific to dolphins residing in the estuarine waters of Charleston, South Carolina. Immunotoxicity was determined in adult female B₆C₃F₁ mice by assessing lymphocyte proliferation, splenic and thymic immunophenotypes, and IgM production. Mice were exposed via oral gavage to the PCB-mixture (0, 1.8, 3.6, 7.1, or 14.3 mg/kg/day) for 28 days to yield a targeted total administered dose (TAD) 0, 50, 100, 200, or 400 mg/kg. Significant increased liver weight occurred at the highest treatment. IgM production was suppressed compared to control for all treatments. Numbers of thymic CD4+/CD8+, CD4-/CD8-, and CD4+/CD8- cells were not altered, but numbers of thymic CD4-/CD8+ cells were significantly increased in the highest treatment. Lymphocyte proliferation was not markedly affected by any treatment. The numbers of splenic CD4/CD8 T-cells or MHCII+ cells were not significantly changed. Humoral immunity using the plaque-forming cell assay for determining the specific IgM antibody-forming cell response appeared to be the most sensitive endpoint affected. As the lowest concentration tested resulted in decreased IgM production and total and free thyroxine (T₄) serum levels a NOAEL was not identified. The calculated ED₅₀ for suppression of IgM production was 2.4 mg/kg/day.

摘要

已评估多氯联苯 (PCB) 的免疫毒性；然而，人类和野生动物在环境中会接触到多种多氯联苯。因此，本研究的目的是检查在鲸脂中鉴定出的复杂的 37 PCB 同系物混合物对居住在南卡罗来纳州查尔斯顿河口水域的海豚的影响。在成年女性中测定免疫毒性 B ₆ C ₃ F ₁通过评估淋巴细胞增殖、脾脏和胸腺免疫表型以及 IgM 产生来检测小鼠。小鼠通过口服强饲法暴露于 PCB 混合物（0、1.8、3.6、7.1 或 14.3 mg/kg/天）28 天，以产生目标总给药剂量 (TAD) 0、50、100、200 或400 毫克/公斤。在最高治疗时出现显着增加的肝脏重量。与所有处理的对照相比，IgM 产生受到抑制。胸腺 CD4+/CD8+、CD4-/CD8- 和 CD4+/CD8- 细胞的数量没有改变，但在最高处理中胸腺 CD4-/CD8+ 细胞的数量显着增加。淋巴细胞增殖不受任何治疗的显着影响。脾脏 CD4/CD8 T 细胞或 MHCII+ 细胞的数量没有显着变化。使用斑块形成细胞测定法确定特异性 IgM 抗体形成细胞反应的体液免疫似乎是受影响的最敏感终点。由于测试的最低浓度导致 IgM 产量和总甲状腺素和游离甲状腺素 (T₄ ) 未鉴定出 NOAEL 的血清水平。用于抑制 IgM 产生的计算 ED ₅₀为 2.4 mg/kg/天。