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非共平面的2,2',3,3',4,4',5,5',6,6'-十氯联苯(PCB 209)在原代培养的大鼠肝细胞中不会诱导细胞色素P450酶活性,没有遗传毒性,也不表现出内分泌调节活性。

Non-coplanar 2,2',3,3',4,4',5,5',6,6'-decachlorobiphenyl (PCB 209) did not induce cytochrome P450 enzyme activities in primary cultured rat hepatocytes, was not genotoxic, and did not exhibit endocrine-modulating activities.

作者信息

Han Xing, O'Connor John C, Donner E Maria, Nabb Diane L, Mingoia Robert T, Snajdr Suzanne I, Clarke Jane J, Kaplan A Michael

机构信息

DuPont Haskell Global Centers for Health & Environmental Sciences, Newark, DE 19714, USA.

出版信息

Toxicology. 2009 Jan 31;255(3):177-86. doi: 10.1016/j.tox.2008.10.013. Epub 2008 Oct 31.

DOI:10.1016/j.tox.2008.10.013
PMID:19022331
Abstract

2,2',3,3',4,4',5,5',6,6'-Decachlorobiphenyl (PCB 209) is a fully chlorinated, non-coplanar biphenyl. To demonstrate that PCB 209 is not likely to exhibit human health hazards common to coplanar PCBs it was tested for cytochrome P450 (P450) enzyme induction potentials, genetic toxicity, and endocrine-modulating activity. PCB 209 (dose from 0.005 to 5000 ng/mL) did not significantly induce P450 CYP1A, 2A, 2B, 3A, or 4A enzyme activities in primary cultured rat hepatocytes. In contrast, Aroclor 1260, a PCB mixture that contains approximately 60% chlorine by weight, showed significant induction of P450 CYP1A, 2A, 2B, and 3A within the same dose range. PCB 209 (dose from 100 to 5000 microg/plate) was negative in the bacterial mutagenicity (Ames) test in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 or in Eschericia coli strain WP2uvrA. PCB 209 (dose from 25 to 150 microg/mL) was also negative for forward mutations at the thymidine kinase (TK+/-) locus of L5178Y mouse lymphoma cells. The Ames and the mouse lymphoma assays were both conducted in the absence and presence of rat liver S9 fraction. PCB 209 (dose from 500 to 2000 mg/kg by single dose oral gavage) did not induce an increase in the frequency of micronuclei in polychromatic erythrocytes in mouse bone marrow in vivo. PCB 209 did not induce estrogenic effects when administered by gavage to ovariectomized adult female rats at 500 and 1000 mg/kg for 4 days, nor did it produce alterations consistent with endocrine-modulating activity in adult intact male rats when administered by gavage at 500 and 1000 mg/kg for 15 consecutive days.

摘要

2,2',3,3',4,4',5,5',6,6'-十氯联苯(PCB 209)是一种全氯代的非共面联苯。为证明PCB 209不太可能呈现共面多氯联苯常见的对人体健康的危害,对其进行了细胞色素P450(P450)酶诱导潜力、遗传毒性和内分泌调节活性测试。PCB 209(剂量为0.005至5000纳克/毫升)在原代培养的大鼠肝细胞中未显著诱导P450 CYP1A、2A、2B、3A或4A酶活性。相比之下,一种按重量计含约60%氯的多氯联苯混合物Aroclor 1260在相同剂量范围内显示出对P450 CYP1A、2A、2B和3A的显著诱导。PCB 209(剂量为100至5000微克/平板)在鼠伤寒沙门氏菌TA98、TA100、TA1535和TA1537菌株或大肠杆菌WP2uvrA菌株的细菌致突变性(艾姆斯)试验中呈阴性。PCB 209(剂量为25至150微克/毫升)在L5178Y小鼠淋巴瘤细胞胸苷激酶(TK+/-)位点的正向突变试验中也呈阴性。艾姆斯试验和小鼠淋巴瘤试验均在有无大鼠肝脏S9组分的情况下进行。PCB 209(单剂量经口灌胃剂量为500至2000毫克/千克)未在体内诱导小鼠骨髓多染红细胞微核频率增加。给卵巢切除的成年雌性大鼠按500和1000毫克/千克剂量经口灌胃4天,PCB 209未诱导雌激素效应,连续15天给成年完整雄性大鼠按500和1000毫克/千克剂量经口灌胃,它也未产生与内分泌调节活性一致的变化。

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