A recent study... identified glucuronide and sulfate conjugates of 4-hydroxy-2,3,7,8-tetraCDF and 3-hydroxy-2,7,8-triCDF as the major biliary metabolites in rats dosed intravenously with 2,3,7,8-tetraCDF.
Thirteen chlorinated compounds were detected in bile collected for 48 hr from female Sprague Dawley rats given a single oral dose of 678 ug TCDF (79.4% pure)/kg bw. The four major metabolites considered to originate from TCDF were trichloromethoxy-dibenzofuran, two trichlorodimethoxy-dibenzofurans, and tetrachloromethoxydibenzofuran. The remaining nine metabolites, detected in minute amounts, originated most likely from contaminating PCDFs (1% triCDF, 8.4% tetraCDFs, 11.2% pentaCDFs).
Limited data suggest that autoinduction of metabolism and biliary excretion does occur for PCDFs, in contrast to PCDDs. Pretreatment of rats with 2,3,7,8-TCDF (1.0 umol/kg, 3 days earlier) significantly increased the biliary excretion of a subsequent dose of (14C)2,3,7,8-TCDF. The naive rats excreted 5.7 + or - 2.4% of the dose over the initial 8 hr, while the pretreated rats excreted 13.2 + or - 3.2% of the (14C)2,3,7,8-TCDF. Similarly, pretreatment of rats with 2,3,4,7,8-pentaCDF (500 ug/kg, /orally/, 3 days earlier) resulted in a two-fold increase in the biliary elimination of a subsequent dose of (14C)2,3,4,7,8-pentaCDF. These results suggest that pretreatment with 2,3,7,8-TCDF and 2,3,4,7,8-pentaCDF induces the metabolism of these congeners.
...Isolated hepatocytes and liver slices in suspension culture and hepatic microsomes were used as in vitro models to assess the hepatic uptake and metabolism of [3H]- and [14C]TCDD and [3H]TCDF (0.01-1.0 uM) in control and induced (5 ug TCDD/kg, 3 days earlier) male Sprague-Dawley rats. TCDD pretreatment, with an increase in cytochromes P450 1A1 and 1A2 (CYP1A1, CYP1A2), produced an increase in the hepatic uptake of TCDD, while no increase in the hepatic uptake of TCDF was observed. ...The rates of metabolism of TCDD and TCDF were directly proportional to their concentrations. ...Very limited metabolism of TCDD and TCDF was observed in control rat liver (0.45 and 3.2 pmol/hr/g hepatocyte wet wt at 0.1 uM, respectively). TCDD induced its own rate of metabolism about two- to fivefold at 1.0 uM but no induction was observed at 0.01 and 0.1 uM. In contrast, TCDD markedly induced the rate of TCDF metabolism at all substrate concentrations.
...Metabolism of all three compounds appears to be the rate-limiting step for excretion, which is primarily via the bile into the feces. Therefore, the biliary elimination of TCDF, TCDD, and TCB was examined as an indirect measure of metabolism. Male F344 rats were anesthetized with pentobarbital, the bile duct was cannulated, and 0.1 mumol [3H]TCDD, [14C]TCDF, or [14C]TCB/kg bw was administered iv. Bile was collected for 0-8 hr while the animals were kept under anesthesia. To determine if TCDF was able to induce its own metabolism in vivo, a single dose of 1.0 mumol TCDF/kg was administered to rats by oral gavage 3 days prior to iv injection of 0.1 or 0.3 mumol [14C]TCDF/kg. Biliary excretion and hepatic concentrations of [14C]TCDF were significantly increased in the pretreated animals. These results suggest an autoinduction of TCDF metabolism. Essentially all biliary [14C]TCDF radioactivity was attributable to metabolites. High-pressure liquid chromatography profiles of biliary radioactivity from 0-4 hr were qualitatively different between naive and pretreated rats. To determine if pretreatment with TCDD altered the metabolism of TCDF and vice versa, a single dose of 1.0 mumol TCDF/kg or 0.1 mumol TCDD/kg was administered by oral gavage 3 days prior to iv injection of 0.1 mumol [3H]TCDD or [14C]TCDF/kg, respectively.
Halogenated dibenzofurans (PCDFs and PBDFs) bind the aryl hydrocarbon receptor (AhR), which increases its ability to activate transcription in the XRE (xenobiotic resoponse element) promoter region. Specifically AhR binds to the PCDF, translocates it to the nucleus and together with hydrocarbon nuclear translocator (ARNT) and xenobiotic responsive element (XRE) increases the expression of CYP1A1 and aryl hydrocarbon hydroxylase (CYP1B1). AhR signaling also increseases conversion of arachidonic acid to prostanoids via cyclooxygenase-2, alters Wnt/beta-catenin signaling downregulating Sox9 and alters signaling by receptors for inflammatory cytokines. AhR signalling also alters proteasomal degradation of steroid hormone receptors, alters cellular UVB stress response and changes the differentiation of certain T-cell subsets. The resulting AhR mediated activation and alteration leads to body weight loss, cancer and thymic atrophy (characteristic of immune and endocrine disruption) which are common toxic responses to PCDFs and related toxic halogenated aryl hydrocarbons.
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌物分类
3, 无法归类其对人类致癌性的类别。(L135)
3, not classifiable as to its carcinogenicity to humans. (L135)
CDFs cause vomiting and diarrhea, anemia, more frequent lung infections, numbness and other effects on the nervous system, and mild changes in the liver. However, there were no permanent liver changes or definite liver damage found in people who ingested CDFs. (L952)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
暴露途径
吸入（L952）；皮肤（L952）；口服（L952）
Inhalation (L952) ; dermal (L952) ; oral (L952)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
症状
皮肤和眼部刺激，尤其是严重的痤疮、肤色变黑以及带有分泌物的肿胀眼睑是CDF中毒最明显的健康影响。
Skin and eye irritations, especially severe acne, darkened skin color, and swollen eyelids with discharge are the most obvious health effects of the CDF poisoning. (L952)
Labeled tetrachlorodibenzofuran was admin orally and iv to male Fischer 344 rats at 0.1 and 1.0 mumole/kg. TCDF was completely absorbed. Within 3 days, <5% remained in liver or fat and <2% remained in skin, with no other tissues exhibiting significant amount of radioactivity. The liver was the main site of accumulation, with lesser amounts being present in adipose tissues and skin. It was excreted primarily by fecal route. More than 50% of the dose was excreted in feces within 48 hr and over 90% within 5 days. Approx 3% was eliminated in urine within 5 days. 5% of the radioactivity administered was excreted in bile within 4 hr as 1 or more metabolites of TCDF.
Tissue distribution of receptor protein for tetrachlorodibenzo-p-dioxin (TCDD) in male Sprague-Dawley rats was determined by isoelectric focusing in polyacrylamide gel of cytosol labeled With (3)H-TCDD. In order for the TCDD receptor to focus as a single sharp peak at pi (isoelectric point) of 5.2, partial proteolysis of the receptor was carried out. Radioactivity bound to this peak was completely displaced when labeling of cytosol was carried out in the presence of 100 fold unlabeled 2,3,7,8-tetrachlorodibenzofuran.
High absorption (90%) was... reported for 2,3,7,8-tetraCDF in male Fischer-344 rats administered a single gavage dose of the /chlorodibenzofuran/ in Emulphor/ethanol.
Estimation of dioxin emission from fires in chemicals
摘要：
The formation of the 17 toxic 2,3,7,8-substituted PCDDs and PCDFs during combustion of selected chemicals were measured by high-resolution GC/MS. The 16 chemicals studied were commonly used chlorinated pesticides, industrial chemicals, and PVC. In a series of experiments carried out in a DIN 53,436 furnace, 2.5 g of these compounds were burned at 500 degrees C and 900 degrees C, respectively. The resultant yields ranged from 740 ng ITEQ/g for pentachlorophenol, to below 0.01 ng ITEQ/g for PVC and dichlobenil. The results show that some chemicals generate PCDD/F in very high possibly dangerous - amounts during burning, whereas others generate insignificant amounts. The influence of scale were studied for chlorobenzene and 4-chloro-3-nitro-benzoic acid in additional experiments, carried out in a cone calorimeter burning 20 g substance, and in ISO 9705 room test burning about 50 kg. A good agreement between the results for large and small scale indicated that formation of PCCD/F during a fire may be estimated from laboratory experiments. This suggest laboratory test may be used to screen for chemicals posing a hazard for release of PCDD/F during fires. (C) 1999 Elsevier Science Ltd. All rights reserved.
作者：Mariusz K. Cieplik、Jose Pastor Carbonell、Christina Muñoz、Sarah Baker、Sophie Krüger、Per Liljelind、Stellan Marklund、Robert Louw
DOI：10.1021/es026292g
日期：2003.8.1
sintering facility could satisfactorily imitate the large-scale process, in part or as a whole. Results obtained with realistic feed mixtures point at dioxin formation in the sinter bed at levels significant enough to explain a major part of the outputs observed in the real-life process. With approximately 8 ppm (wt) of chloride added as NaCl, the PCDD/F output doubled, but with the same proportion of
