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多氯联苯(PCBs)安全性评估综述,特别提及生殖毒性。

Review of the safety assessment of polychlorinated biphenyls (PCBs) with particular reference to reproductive toxicity.

作者信息

Battershill J M

机构信息

Department of Health, Health Environment and Food Division (M), Skipton House, London, UK.

出版信息

Hum Exp Toxicol. 1994 Sep;13(9):581-97. doi: 10.1177/096032719401300901.

DOI:10.1177/096032719401300901
PMID:7986570
Abstract
  1. The methods used to evaluate the toxicological effects of PCBs in animals have been reviewed. 2. The data show that Toxic Equivalency Factors (TEFs) could be developed to assess the potential toxicity of PCB mixtures for certain specific target organ effects (such as the liver and immune system) but would be inappropriate for other effects (e.g. thyroid function and neurochemical effects). More data on a wider range of individual PCB congeners and a method for systematically balancing toxicodynamic and toxicokinetic data are required before the TEF approach can be fully evaluated. 3. With the exception of the teratogenic effects seen in mice and the anti-oestrogenic effects reported in in vitro studies, there are insufficient data on individual PCB congeners to evaluate the structure-activity relationships for the effects of PCBs on reproduction. The data also show that individual PCBs may have opposing effects on a particular aspect of reproduction (for example individual PCB congeners may have either oestrogenic or anti-oestrogenic effects). Studies with individual PCB congeners have shown both enhancement and antagonism of the teratogenic effects of 2, 3, 7, 8-tetrachloro dibenzo-p-dioxin (TCDD) in the mouse. It is not possible to use TEFs to evaluate the reproductive effects of PCBs. 4. The mechanism(s) responsible for the effects of PCBs on postnatal neurobehavioural development in rodents and monkeys have not been elucidated. At least two groups of PCBs which might be responsible for the observed effects have been identified in this review, one affecting the dopaminergic system and the other group affecting thyroid hormone levels. Considerably more research would be required before the TEF approach could be applied to the effects of PCBs on postnatal neurobehavioural development. This would include research on an appropriate animal model to determine whether the critical toxicological mechanism is mediated through the Ah receptor. 5. The reproductive toxicity of complex PCB mixtures such as those found in foods will depend on the identifies and relative proportions of individual PCB congeners in the mixture. It is not possible to give an accurate estimate of a NOAEL or LOAEL from the reproduction studies using commercial PCB mixtures which could be readily applied to the safety assessment of PCBs present as contaminants in food. 6. It is concluded that the data presented in this paper support the hypothesis that there is no satisfactory method derived from the available studies in laboratory animals for evaluating the potential risk of adverse effects on reproduction posed by contamination of foods with PCBs.
摘要
  1. 已对用于评估多氯联苯在动物体内毒理学效应的方法进行了综述。2. 数据表明,可以制定毒性当量因子(TEF)来评估多氯联苯混合物对某些特定靶器官效应(如肝脏和免疫系统)的潜在毒性,但不适用于其他效应(如甲状腺功能和神经化学效应)。在能够全面评估TEF方法之前,需要更多关于更广泛范围的单个多氯联苯同系物的数据以及一种系统平衡毒效动力学和毒代动力学数据的方法。3. 除了在小鼠中观察到的致畸效应以及体外研究中报道的抗雌激素效应外,关于单个多氯联苯同系物的数据不足以评估多氯联苯对生殖影响的构效关系。数据还表明,单个多氯联苯可能对生殖的某个特定方面具有相反的影响(例如,单个多氯联苯同系物可能具有雌激素或抗雌激素效应)。对单个多氯联苯同系物的研究表明,2,3,7,8 - 四氯二苯并 - p - 二恶英(TCDD)在小鼠中的致畸效应既有增强作用也有拮抗作用。无法使用TEF来评估多氯联苯对生殖的影响。4. 多氯联苯对啮齿动物和猴子出生后神经行为发育影响的机制尚未阐明。在本综述中已确定至少两组可能导致观察到的效应的多氯联苯,一组影响多巴胺能系统,另一组影响甲状腺激素水平。在能够将TEF方法应用于多氯联苯对出生后神经行为发育的影响之前,需要进行更多的研究。这将包括对合适动物模型的研究,以确定关键的毒理学机制是否通过芳烃受体介导。5. 复杂多氯联苯混合物(如食品中发现的那些)的生殖毒性将取决于混合物中单个多氯联苯同系物的种类和相对比例。从使用商业多氯联苯混合物的生殖研究中无法准确估计无观察到有害作用水平(NOAEL)或最低观察到有害作用水平(LOAEL),而这些估计不能轻易应用于食品中作为污染物存在的多氯联苯的安全性评估。6. 得出的结论是,本文所呈现的数据支持这样一种假设,即从实验室动物的现有研究中没有令人满意的方法来评估食品中多氯联苯污染对生殖造成不良影响的潜在风险。

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