Tryphonas H, Bondy G, Hodgen M, Coady L, Parenteau M, Armstrong C, Hayward S, Liston V
Toxicology Research Division, Food Directorate, Health Products and Foods Branch, Health Canada, Tunneys' Pasture, Ross Ave., Ottawa, Ontario, Canada K1A 0L2.
Food Chem Toxicol. 2003 Jan;41(1):107-18. doi: 10.1016/s0278-6915(02)00184-9.
The immunotoxicity of cis- and trans-nonachlor and chlordane were investigated in adult male and female Sprague-Dawley rats following a 28-day oral (gavage) treatment. Rats were randomly assigned to six experimental groups: cis-nonachlor, females; trans-nonachlor, females; technical chlordane females; cis-nonachlor, males; trans-nonachlor, males; technical chlordane, males. The immunologic endpoints included: quantification of the total serum immunoglobulin (Ig) levels and subclasses and flow cytometric analysis of peripheral blood leukocytes and T-lymphocyte subsets, evaluation of the lymphoproliferative activity of splenocytes in response to concanavalin A (Con A) and Salmonella typhimurium (STM) mitogens, and natural killer (NK) cell activity of splenocytes. Satellite experiments to examine the delayed-type hypersensitivity (DTH) response to oxazolone, and resistance to Listeria monocytogenes were set up for female rats treated with cis- or trans-nonachlor. Statistically significant (P<0.05) effects included: increased serum immunoglobulin M (IgM) levels in the chlordane-treated females at the 25 mg/kg dose (pairwise comparison); increased serum IgG(1) and IgG(2c) in the cis-nonachlor-treated males at the 2.5 and 25 mg/kg doses and increased serum IgG(2a) levels at all doses; increased serum IgG(2b) at the 25 mg/kg dose and decreased (dose-related) serum IgM levels in the cis-nonachlor-treated male rats; increased (linear trend) IgG(1) and IgG(2a) in the cis-nonachlor-treated females with effects on IgG(2a) significant at the 25 mg/kg dose compared with control; increased serum IgG(2a) in the trans-nonachlor-treated male and female rats at the 2.5 mg/kg dose; increased absolute numbers (linear trend) of peripheral white blood cells, B lymphocytes, natural killer (NK) cells, T-suppressor/cytotoxic lymphocytes, and the double positive (T-helper/inducer, T-suppressor/cytotoxic) cells in the trans-nonachlor-treated females; increased (non-linear trend) lymphoproliferative activity in the Con A-stimulated splenocytes and decreased (linear trend) activity in the S. typhimurium mitogen-stimulated splenocytes of the cis-nonachlor-treated females; reduced resistance to L. monocytogenes in the cis-nonachlor (day 3, P=0.034)- and trans-nonachlor (day 2, P=0.0001)-treated females, and reduced (linear trend) NK cell activity in the cis-nonachlor-treated males. The present data indicated that the chlordane compounds tested in this study had significant effects on a number of immunologic endpoints. In comparison to technical chlordane, cis- and trans-nonachlors were more immunotoxic. Therefore, an evaluation of the risk these chlorinated compounds may pose to human health should consider the potential effects different chlordane compounds may have on the immune system.
在成年雄性和雌性Sprague-Dawley大鼠经28天口服（灌胃）给药后，研究了顺式和反式九氯以及氯丹的免疫毒性。大鼠被随机分为六个实验组：顺式九氯，雌性；反式九氯，雌性；工业氯丹，雌性；顺式九氯，雄性；反式九氯，雄性；工业氯丹，雄性。免疫指标包括：血清总免疫球蛋白（Ig）水平及其亚类的定量分析，外周血白细胞和T淋巴细胞亚群的流式细胞术分析，脾细胞对刀豆蛋白A（Con A）和鼠伤寒沙门氏菌（STM）促有丝分裂原的淋巴细胞增殖活性评估，以及脾细胞的自然杀伤（NK）细胞活性。针对用顺式或反式九氯处理的雌性大鼠，开展了卫星实验以检测对恶唑酮的迟发型超敏反应（DTH）以及对单核细胞增生李斯特菌的抵抗力。具有统计学意义（P<0.05）的效应包括：在25 mg/kg剂量下，氯丹处理的雌性大鼠血清免疫球蛋白M（IgM）水平升高（两两比较）；在2.5和25 mg/kg剂量下，顺式九氯处理的雄性大鼠血清IgG(1)和IgG(2c)升高，且所有剂量下血清IgG(2a)水平均升高；在25 mg/kg剂量下，顺式九氯处理的雄性大鼠血清IgG(2b)升高，血清IgM水平降低（与剂量相关）；在顺式九氯处理的雌性大鼠中，IgG(1)和IgG(2a)升高（呈线性趋势），与对照组相比，在25 mg/kg剂量下对IgG(2a)的影响具有显著性；在2.5 mg/kg剂量下，反式九氯处理的雄性和雌性大鼠血清IgG(2a)升高；在反式九氯处理的雌性大鼠中，外周白细胞、B淋巴细胞、自然杀伤（NK）细胞、T抑制/细胞毒性淋巴细胞以及双阳性（T辅助/诱导、T抑制/细胞毒性）细胞的绝对数量增加（呈线性趋势）；在顺式九氯处理的雌性大鼠中，Con A刺激的脾细胞的淋巴细胞增殖活性增加（呈非线性趋势），鼠伤寒沙门氏菌促有丝分裂原刺激的脾细胞的活性降低（呈线性趋势）；在顺式九氯（第3天，P = 0.034）和反式九氯（第2天，P = 0.0001）处理的雌性大鼠中，对单核细胞增生李斯特菌的抵抗力降低，在顺式九氯处理的雄性大鼠中，NK细胞活性降低（呈线性趋势）。本研究数据表明，本研究中测试的氯丹化合物对多个免疫指标有显著影响。与工业氯丹相比，顺式和反式九氯的免疫毒性更强。因此，对这些氯代化合物可能对人类健康构成的风险进行评估时，应考虑不同氯丹化合物对免疫系统可能产生的潜在影响。
