Vanden Heuvel J P, Clark G C, Tritscher A m, Lucier G W
Laboratory of Biochemical Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Fundam Appl Toxicol. 1994 Oct;23(3):465-9. doi: 10.1006/faat.1994.1128.
Polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls belong to a class of compounds, the polyhalogenated aromatic hydrocarbons (PHAHs), which are ubiquitous environmental contaminants. Due to the existence of a common mechanism of action, i.e., binding to the Ah receptor, the activity of members of this class of compounds is generally expressed relative to the prototypical 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as toxic equivalency factors (TEFs). In the present studies we examined the presence of liver of untreated PCDFs in standard laboratory feed and in the liver of untreated rats at three different ages (60, 140, and 200 days) in terms of concentration and in toxic equivalents (TEQs, TEF x concentration). Feed was shown to contain trace amounts of PCDDs and PCDFs and control rat liver was shown to contain several PCDD and PCDF congeners in terms of concentration of congener and concentration of TEQs contributed by that congener. The total concentration of TEQs increased with increasing age in rat liver, going from 20 ppt TEQ at 60 days to 78 ppt TEQ at 200 days of age. This accumulation in dioxin-like activity was due primarily to PCDFs. In particular the congener 2,3,4,7,8-pentachlorodibenzofuran accrued in untreated rat liver accounting for approximately 80% of the total TEQ at 200 days of age. These studies affirm the pervasive presence of PHAHs and suggest prudence in evaluating chronic rat studies in which interference from background levels of PCDDs and PCDFs may be a factor.
多氯二苯并对二噁英(PCDDs)、二苯并呋喃(PCDFs)和联苯属于多卤代芳烃(PHAHs)类化合物,它们是普遍存在的环境污染物。由于存在共同的作用机制,即与芳烃受体结合,这类化合物成员的活性通常相对于原型2,3,7,8-四氯二苯并对二噁英(TCDD)以毒性当量因子(TEFs)来表示。在本研究中,我们从浓度和毒性当量(TEQs,TEF×浓度)方面,检测了标准实验室饲料中未处理的PCDFs以及三种不同年龄(60、140和200天)未处理大鼠肝脏中的情况。结果显示饲料中含有痕量的PCDDs和PCDFs,对照大鼠肝脏中含有几种PCDD和PCDF同系物,包括同系物浓度以及该同系物贡献的TEQs浓度。大鼠肝脏中TEQs的总浓度随着年龄增长而增加,从60天时的20 ppt TEQ增加到200天时的78 ppt TEQ。二噁英类活性的这种积累主要归因于PCDFs。特别是2,3,4,7,8-五氯二苯并呋喃同系物在未处理大鼠肝脏中积累,在200天时占总TEQ的约80%。这些研究证实了PHAHs的普遍存在,并建议在评估慢性大鼠研究时要谨慎,因为PCDDs和PCDFs的背景水平干扰可能是一个因素。