McFarland V A, Clarke J U
Environmental Laboratory, U.S. Army Engineer Waterways Experiment Station, Vicksburg, MS 39180.
Environ Health Perspect. 1989 May;81:225-39. doi: 10.1289/ehp.8981225.
Polychlorinated biphenyls (PCBs) as environmental contaminants often cannot be adequately described by reference to Aroclors or to total PCBs. Although there are 209 possible PCB configurations (congeners), perhaps half that number account for nearly all of the environmental contamination attributable to PCBs. Still fewer congeners are both prevalent and either demonstrably or potentially toxic. If potential toxicity, environmental prevalence, and relative abundance in animal tissues are used as criteria, the number of environmentally threatening PCB congeners reduces to about thirty-six. Twenty-five of these account for 50 to 75% of total PCBs in tissue samples of fish, invertebrates, birds, and mammals. A few PCB congeners that are sterically similar to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) are directly toxic. Other PCB congeners, as well as those that are directly toxic, may also be involved in toxicity indirectly by stimulating the production of (inducing) bioactivating enzyme systems. The most consequential of these have the ability to induce aryl hydrocarbon metabolizing mixed-function oxidases (MFOs). A result can be an increased capacity for bioactivation of otherwise nontoxic foreign compounds such as certain polynuclear aromatic hydrocarbons (PAH) to cytotoxic or genotoxic metabolites. The effectiveness of specific PCB congeners as inducers of different types of cytochrome P-450-dependent MFO systems is determined by their stereochemistry. Although MFO induction is not a proximate cause, it is a strong correlate of certain kinds of toxicities. Structural patterns can thus be used to discriminate among PCB congeners on the basis of toxic potential, if not entirely on toxicity per se. Congeners that demonstrate 3-methylcholanthrene-type (3-MC-type) and mixed-type MFO induction have the greatest toxic potential. These congeners most closely resemble 2,3,7,8-TCDD in their structures and in their toxic effects. The larger group of phenobarbital-type (PB-type) inducers have considerably less potential for contributing to toxic effects. Weak inducers and noninducing congeners have the least potential for toxicity. Using the rationale described in this paper, we assigned the most evironmentally threatening PCB congeners to four groups. Congeners assigned to Group 1 are considered most likely to contribute to adverse biological effects attributable to PCBs in an environmental sample. Group 1A contains the three most potent (pure 3-MC-type inducer) congeners, IUPAC numbers 77, 126, and 169. Six congeners, numbers 105, 118, 128, 138, 156, and 170, are assigned to Group 1B. These congeners are mixed-type inducers that have been reported frequently in environmental samples.(ABSTRACT TRUNCATED AT 400 WORDS)
多氯联苯(PCBs)作为环境污染物,通常无法通过提及艾氏剂或总多氯联苯来充分描述。尽管有209种可能的多氯联苯构型(同系物),但其中约一半的同系物几乎占了多氯联苯造成的所有环境污染。既普遍存在又具有明显或潜在毒性的同系物则更少。如果将潜在毒性、环境普遍性和在动物组织中的相对丰度作为标准,那么对环境构成威胁的多氯联苯同系物数量会减少到约36种。其中25种占鱼类、无脊椎动物、鸟类和哺乳动物组织样本中多氯联苯总量的50%至75%。一些在空间结构上与2,3,7,8 - 四氯二苯并 - p - 二恶英(2,3,7,8 - TCDD)相似的多氯联苯同系物具有直接毒性。其他多氯联苯同系物以及那些具有直接毒性的同系物,也可能通过刺激生物活化酶系统的产生(诱导)而间接参与毒性作用。其中最具影响力的能够诱导芳烃代谢混合功能氧化酶(MFOs)。结果可能是原本无毒的外来化合物如某些多环芳烃(PAH)生物活化能力增强从而产生细胞毒性或基因毒性代谢物。特定多氯联苯同系物作为不同类型细胞色素P - 450依赖性MFO系统诱导剂的有效性取决于它们的立体化学结构。虽然MFO诱导不是直接原因,但它与某些类型的毒性密切相关。因此,如果不能完全依据毒性本身,那么结构模式可用于根据潜在毒性区分多氯联苯同系物。表现出3 - 甲基胆蒽型(3 - MC型)和混合型MFO诱导的同系物具有最大的潜在毒性。这些同系物在结构和毒性作用上与2,3,7,8 - TCDD最为相似。较大的苯巴比妥型(PB型)诱导剂组对毒性作用的贡献潜力要小得多。弱诱导剂和非诱导同系物的毒性潜力最小。根据本文所述的原理,我们将对环境威胁最大的多氯联苯同系物分为四组。归入第1组的同系物被认为最有可能导致环境样本中多氯联苯产生不良生物效应。1A组包含三种最具效力的(纯3 - MC型诱导剂)同系物,国际纯粹与应用化学联合会(IUPAC)编号为77、126和169。六种同系物,编号为105、118、128、138、156和170,被归入1B组。这些同系物是混合型诱导剂,在环境样本中经常被检测到。(摘要截取自400字)