IMMUNOLOGICAL AND ENDOCRINE EFFECTS OF THE FLAME-RETARDANT PENTABROMODIPHENYL ETHER (DE-71) IN C57BL/6J MICE
IMMUNOLOGICAL AND ENDOCRINE EFFECTS OF THE FLAME-RETARDANT PENTABROMODIPHENYL ETHER (DE-71) IN C57BL/6J MICE
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DOI：
10.1016/0300-483x(94)90052-3
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发表时间：
1994-01-26
期刊：
影响因子：
4.5
通讯作者：
KERKVLIET, NI
中科院分区：
文献类型：
--
作者：
FOWLES, JR;FAIRBROTHER, A;KERKVLIET, NI
在欧洲和北美，多溴联苯醚是为用作商用塑料和纺织品的阻燃剂而生产的。这些研究调查了商用五溴二苯醚混合物DE-71对雌性C57 BL/6小鼠的急性和亚慢性免疫毒性和内分泌影响。在14天内，小鼠经口暴露于0、0.8、4.0、20、100或500 mg/kg DE-71急性单次给药，或暴露于总计0、250、500或1000 mg/kg的亚慢性日剂量。通过测量空斑形成细胞对绵羊红细胞（SRBC）的反应和自然杀伤细胞（NKC）对YAC-1靶细胞的活性（基础和聚I：C刺激）来评估免疫毒性。还测量了肝细胞色素P450含量和活性（乙氧基试卤灵-O-脱乙基酶（EROD）和戊氧基试卤灵-O-脱乙基酶（PROD））以及皮质酮（CS）和甲状腺素（T4）浓度。在急性或亚慢性暴露于剂量> 250 mg/kg的DE-71的小鼠中，PROD活性被诱导3-5倍。EROD活性和总微粒体细胞色素P450含量仅在DE-71亚慢性处理的小鼠中显著诱导; EROD的最大诱导为3.3倍。除100 mg/kg剂量外，所有剂量DE-71急性给药小鼠的总血清T4浓度均显著较低。亚慢性暴露后，DE-71处理小鼠的总T4和游离T4浓度呈剂量依赖性降低。亚慢性暴露于DE-71后，血浆CS水平升高。CS的升高与尸检时的捕获顺序相关，表明DE-71和应激的相互作用。关于免疫毒性，仅在亚慢性暴露于1000 mg DE-71/kg的小鼠中观察到抗SRBC反应的显著抑制，该暴露也导致胸腺重量降低。暴露于DE-71未改变NKC活性。
Polybrominated diphenyl ethers are manufactured for use as flame retardants in commercial plastics and textiles in Europe and North America. These studies investigated the acute and subchronic immunotoxicity and endocrine effects of a commercial pentabromodiphenyl ether mixture, DE-71, in female C57BL/6 mice. Mice were orally exposed to acute single doses of DE-71 of 0, 0.8, 4.0, 20, 100, or 500 mg/kg, or to subchronic daily doses totaling 0, 250, 500, or 1000 mg/kg over a 14 day period. Immunotoxicity was assessed by measuring the plaque-forming cell response to sheep erythrocytes (SRBC) and natural killer cell (NKC) activity (basal and poly I:C stimulated) to YAC-1 target cells. Liver cytochrome P450 content and activities (ethoxyresorufin-o-deethylase (EROD) and pentoxyresorufin-o-deethylase (PROD)) as well as corticosterone (CS) and thyroxine (T4) concentrations were also measured. PROD activity was induced 3-5-fold in mice exposed acutely or subchronically to DE-71 at doses > 250 mg/kg. EROD activity and total microsomal cytochrome P450 content were significantly induced only in mice treated subchronically with DE-71; maximum induction of EROD was 3.3-fold. Total serum T4 concentrations were significantly lower in mice treated acutely with DE-71 at all doses except the 100 mg/kg dose. Total and free T4 concentrations were dose-dependently decreased in DE-71-treated mice following subchronic exposure. Plasma CS levels were elevated following subchronic exposure to DE-71. The elevation of CS was correlated with order of capture at necropsy, suggesting an interactive effect of DE-71 and stress. In regard to immunotoxicity, significant suppression of the anti-SRBC response was seen only in mice exposed subchronically to 1000 mg DE-71/kg, an exposure that also resulted in decreased thymus weight. NKC activity was not altered by exposure to DE-71.