The environmentally widespread polycyclic aromatic hydrocarbon (PAH) benzo[k]fluoranthene is a potent AHH inducer. This has been proven by recording the benz[a]anthracene metabolite profile in the rat liver by means of gas chromatography/mass spectrometry (GC/MS) technique. Even a total dose of 3 times 50 micrograms/kg body wt increases the metabolism of benz[a]anthracene by a factor of 2. The formation of the 8,9- as well as the 5,6-dihydrodiol is stimulated to about the same extent, whereas the formation of the 10,11-dihydrodiol is suppressed. After comparatively low doses of the inducer, a metabolite is formed which corresponds in all parameters with the postulated ultimate carcinogen 3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenz[a]anthracene. This metabolite and a number of other primary and secondary oxidation products could be identified after incubation with induced but not with normal microsomes. Therefore, it should be emphasised that metabolite profiles have to be recorded instead of measuring brutto conversions of PAH substrates to evaluate inducing effects.
来源:Hazardous Substances Data Bank (HSDB)
代谢
环境因素苯并(j)-荧蒽和苯并(k)荧蒽的代谢被研究了，使用的是Aroclor 1254预处理的大鼠肝脏上清液，这些上清液能有效激活苯并(j)荧蒽和苯并(k)荧蒽，转化为对鼠伤寒沙门氏菌TA 100具有诱变性的代谢物。通过高压液相色谱分离出苯并(j)荧蒽的六种代谢物带，并测试了每个带有激活作用的代谢物对S. typhimurium TA 100的诱变性。主要的诱变带包含两种二氢二醇，其中一种通过与其合成参照标准比较被鉴定为9,10-二氢-9,10-二羟基苯并(j)荧蒽。9,10-二氢-9,10-二羟基苯并(j)荧蒽在激活后对S. typhimurium TA 100具有诱变性，可能是由于转化为了相应的二氢二醇环氧化合物。苯并(k)荧蒽的主要二氢二醇代谢物通过与合成标准比较被鉴定为8,9-二氢-8,9-二羟基苯并(k)荧蒽。这种二氢二醇也可以转化为二氢二醇环氧化合物，对S. typhimurium TA 100具有激活后的诱变性。这项研究的结果表明，代谢成二氢二醇是苯并(j)荧蒽和苯并(k)荧蒽激活为S. typhimurium TA 100最终诱变剂的一条途径。
The metabolism of the environmental agents benzo(j)-fluoranthene and benzo(k)fluoranthene was investigated using supernatants from the livers of Aroclor 1254-pretreated rats, which are effective in activating benzo(j)fluoranthene and benzo(k)fluoranthene to metabolites mutagenic toward Salmonella typhimurium TA 100. Six bands of metabolites of benzo(j)fluoranthene were separated by high-pressure liquid chromatography, and each band was tested for mutagenicity toward S. typhimurium TA 100 with activation. The major mutagenic band contained two dihydrodiols, one of which was identified as 9,10-dihydro-9, 10-dihydroxybenzo(j)fluoranthene by comparison to a synthetic reference standard. 9,10-Dihydro-9,10-dihydroxybenzo(j)fluoranthene was mutagenic toward S. typhimurium TA 100 with activation, presumably as a result of conversion to the corresponding dihydrodiol-epoxide. The major dihydrodiol metabolite of benzo(k)fluoranthene was identified, by comparison to a synthetic standard, as 8,9-dihydro-8,9-dihydroxybenzo(k)fluoranthene. This dihydrodiol, which could also be converted to a dihydrodiol-epoxide, was mutagenic toward S. typhimurium TA 100 with activation. The results of this study indicate that metabolism to dihydrodiols is one pathway in the activation of benzo(j)fluoranthene and benzo(k)fluoranthene to ultimate mutagens for S. typhimurium TA 100.
The metabolism of 3-, 8- and 9-fluorobenzo[k]fluoranthene (B[k]F) relative to B[k]F was investigated. The major metabolites of B[k]F formed in vitro using rat liver S-9 metabolism systems were 8,9-dihydro-8,9-dihydroxyB[k]F, the 2,3-quinone of B[k]F and 3-, 8- and 9-hydroxyB[k]F. Fluorine substitution within the structure of B[k]F substantially altered the types of metabolites formed in vitro. The most pronounced effect was observed with 9-fluoroB[k]F. In contrast to B[k]F, the 8,9-dihydro-8,9-dihydroxy-, 9-hydroxy- and 10,11-dihydro-10,11-dihydroxy derivatives were not detected as metabolites of 9-fluoroB[k]F. However, either the 2,3- or 4,5-dihydrodiol of 9-fluoroB[k]F was detected. In the case of 8-fluoroB[k]F, neither the 8- nor 11-hydroxy- derivatives were detected. The principle dihydrodiols formed from 8-fluoroB[k]F were the 10,11-dihydrodiol and either the 2,3-or 4,5-dihydrodiol. The pattern of metabolites formed with 3-fluoroB[k]F was similar to that observed with B[k]F with the exception that neither the 3- nor 4-hydroxy derivatives were formed. Mass spectral data indicated that fluoro substitution is not lost to any appreciable extent during the metabolism of 3-, 8- and 9-fluoroB[k]F. The mutagenic activity of these B[k]F fluoro derivatives along with B[k]F, 2,3-dihydro-2,3-dihydroxyB[k]F, the 2,3-quinone of B[k]F and 8,9-dihydro-8,9-dihydroxyB[k]F were evaluated in Salmonella typhimurium TA100 in the presence of rat liver S-9 metabolism systems. 3-FluoroB[k]F was more mutagenic than B[k]F, while both 8- and 9-fluoroB[k]F were less active. While the 2,3-dihydrodiol and 2,3-quinone were weakly active, the 8,9-dihydrodiol had similar mutagenic potency to B[k]F.
来源:Hazardous Substances Data Bank (HSDB)
代谢
8,9-二氢二醇已被检测为苯并(k)荧蒽的代谢物。
The 8,9-dihydrodiol has been detected as a metabolite of benzo(k)fluoranthene.
PAH metabolism occurs in all tissues, usually by cytochrome P-450 and its associated enzymes. PAHs are metabolized into reactive intermediates, which include epoxide intermediates, dihydrodiols, phenols, quinones, and their various combinations. The phenols, quinones, and dihydrodiols can all be conjugated to glucuronides and sulfate esters; the quinones also form glutathione conjugates. (L10)
IDENTIFICATION AND USE: Benzo(k)fluoranthene (B(k)F) is a solid. There is no commercial production or known use of this compound. Benzo(k)fluoranthene occurs ubiquitously as a product of incomplete combustion. It also occurs in fossil fuels. Polycyclic aromatic hydrocarbons are a group of chemicals that are formed during the incomplete burning of coal, oil, gas, wood, garbage, or other organic substances, such as tobacco and charbroiled meat. HUMAN EXPOSURE AND TOXICITY: It is reasonably anticipated to be a human carcinogen. In human breast cancer cells, exposure to 0.1 to 1 uM B(k)F induced CYP1A1/1B1-catalyzed 17 beta-estradiol (E(2)) metabolism, whereas B(k)F levels greater than 1 uM inhibited E(2) metabolism. ANIMAL STUDIES: Intraperitoneal injection of 2.1 umol benzo[k]fluoranthene into newborn mice induced lung adenomas in 6.3% and 16.7% of males and females, respectively, and liver hepatomas and adenomas in 18.8% of males. Benzo(k)fluoranthene produced tumors after lung implantation in mice and when administered with a promoting agent in skin painting bioassays. Intrapulmonary injection of benzo[k]fluoranthene caused lung cancer (squamous-cell carcinoma) in female rats, and subcutaneous injection of benzo[k]fluoranthene caused cancer at the injection site (sarcoma) in mice of both sexes. Benzo(k)fluoranthene was reported to induce mutations in Salmonella typhimurium strain TA100 (his-/his+) at a concentration of 10 ug/plate and in strain TA98 at a concentration of 5 ug/plate in the presence of an exogenous metabolic system. ECOTOXICITY STUDIES: Benzo(k)fluoranthene was not phototoxic and presented no toxicity for the three organisms tested up to 300 mg/kg, concentration rarely found in the environment (tested in Daphnia magna, Hyalella azteca, and Chironomus riparius).
The ability of PAH's to bind to blood proteins such as albumin allows them to be transported throughout the body. Many PAH's induce the expression of cytochrome P450 enzymes, especially CYP1A1, CYP1A2, and CYP1B1, by binding to the aryl hydrocarbon receptor or glycine N-methyltransferase protein. These enzymes metabolize PAH's into their toxic intermediates. The reactive metabolites of PAHs (epoxide intermediates, dihydrodiols, phenols, quinones, and their various combinations) covalently bind to DNA and other cellular macromolecules, initiating mutagenesis and carcinogenesis. (L10, L23, A27, A32)
CLASSIFICATION: B2; probable human carcinogen. BASIS FOR CLASSIFICATION: Based on no human data and sufficient data from animal bioassays. Benzo[k]fluoranthene produced tumors after lung implantation in mice and when administered with a promoting agent in skin-painting studies. Equivocal results have been found in a lung adenoma assay in mice. Benzo[k]fluoranthene is mutagenic in bacteria. HUMAN CARCINOGENICITY DATA: None. ANIMAL CARCINOGENICITY DATA: Sufficient.
No data are available in humans. Sufficient evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 2B: The agent is possibly carcinogenic to humans.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
芘（k）:有充分理由预期对人类是一种致癌物。/多环芳烃/
Benzo(k)fluoranthene: reasonably anticipated to be a human carcinogen. /Polycyclic Aromatic Hydrocarbons/
Benzo(k)fluoranthene was detected in skin oil of 9 roofers at median concentration of 0.2 ng/mg (range: 0.02-2.2); total ng in sample from 36 sq cm area of forehead, 0.8 median (range: 0.5 to 4.3).
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
芘（k）被胃肠道和肺部迅速吸收。一般来说，多环芳烃类化合物具有很高的脂溶性，能够通过上皮膜。
Benzo(k)fluoranthene is absorbed readily from the gastrointestinal tract and lung. In general, polycyclic aromatic hydrocarbons are highly lipid soluble and can pass across epithelial membranes.
Ruthenium-Catalyzed Peri- and Ortho-Alkynylation with Bromoalkynes via Insertion and Elimination
摘要：
The alkynylation of naphthols takes place with total regiocontrol at the peri position of the hydroxyl group in the presence of [RuCl2(p-cymene)](2) as the catalyst. This reaction features high functional group tolerance. The related ortho-alkynylation of benzoic acids proceeds under similar conditions and also shows wide functional group tolerance. Both reactions proceed through metalation, insertion of the alkyne, and bromide elimination.
Scholl Cyclizations of Aryl Naphthalenes: Rearrangement Precedes Cyclization
作者：Sarah L. Skraba-Joiner、Erin C. McLaughlin、Aida Ajaz、Rajesh Thamatam、Richard P. Johnson
DOI：10.1021/acs.joc.5b01559
日期：2015.10.2
We provide evidence that this classic organic name reaction proceeds through sequential and reversible formation of 1,2′- and 2,2′-binaphthyl isomers. Acid-catalyzed isomerization of 1,1′-binaphthyl to 2,2′-binaphthyl has been noted previously. The superacid trifluoromethanesulfonic acid (TfOH), 1 M in dichloroethane, catalyzes these rearrangements, with slower cyclization to perylene. Minor cyclization
在1910年，Scholl，Seer和Weitzenbock报告了AlCl 3催化的1，1'-联萘基环化为per。我们提供的证据表明，这种经典的有机名称反应是通过顺序地和可逆地形成1,2'-和2,2'-联萘异构体而进行的。先前已经注意到酸催化的1，1′-联萘基异构化为2，2′-联萘基。在二氯乙烷中1 M的超强酸三氟甲磺酸（TfOH）催化这些重排，但环化成to的速度较慢。次要环化产物为苯并[ k ]荧蒽和苯并[ j]荧蒽。在环境温度下，观察到的1,1'-联萘，1,2'-联萘和2,2'-联萘的平衡比<1：3：97。DFT计算与包含溶剂化的支持，其中一个机械方案本位-arenium离子是负责重排; 但是，对于环化步骤，我们无法区分芳族离子机理和自由基阳离子机理。在相似的反应条件下，1-苯基萘与2-苯基萘相互转化，后者以平衡状态（5:95的比例）受青睐，并且也缓慢转化为荧蒽。计算再次支持用于重排的芳烃离子机制。
Emission Factors and Importance of PCDD/Fs, PCBs, PCNs, PAHs and PM<sub>10</sub> from the Domestic Burning of Coal and Wood in the U.K.
作者：Robert G. M. Lee、Peter Coleman、Joanne L. Jones、Kevin C. Jones、Rainer Lohmann
DOI：10.1021/es048745i
日期：2005.3.1
fuels. However, their combined emissions from the domestic burning of coal and wood would contribute only a few percent to annual U.K.emission estimates. Emissions of PAHs and PM10 were major contributors to U.K. national emission inventories. Major emissions were found from the domestic burning for Cl1,2,3DFs, while the contribution of PCDD/F-sigmaTEQ to total U.K.emissions was minor.
本文介绍了当煤和木材经过受控燃烧实验时针对一系列持久性有机污染物（POPs）得出的排放因子（EFs），旨在模拟空间供暖的家庭燃烧。排放了各种各样的持久性有机污染物，煤炭的排放量高于木材的排放量。对于颗粒物，PM10（大约10 g / kg燃料）和多环芳烃（对于sigmaPAHs大约100 mg / kg燃料）获得了最高的EF。对于氯化物，多氯联苯（PCB）的EF最高，而多氯萘（PCN），二苯并-对-二恶英（PCDD）和二苯并呋喃（PCDF）的丰度较低。对于sigmaPCB，EF大约为1000 ng / kg燃料，对于sigmaPCNs大约为100s ng / kg燃料，对于sigmaPCDD / Fs大约为100 ng / kg燃料。该研究证实，一氯化至三氯化二苯并呋喃Cl1,2,3DFs是低温燃烧过程（如煤炭和木材的国内燃烧）的有力指标。结论是，在固体燃料燃烧期间通常形成许多PCB和PC
Three-Step Synthesis of Fluoranthenes through Pd-Catalyzed Inter- and Intramolecular C–H Arylation
the preparation of fluoranthenes, involving Miura’s intermolecular C–Harylation, nonaflation, and intramolecularC–Harylation, has been developed. Various 1-naphthols and haloarenes were successfully used as substrates. Reaction conditions that afford high site selectivity have been developed for the intramolecularC–Harylation step.
Fluoranthene and benzo[k]fluoranthene (3) are nonalternant polyaromatic hydrocarbons. Their derivatives, 3-acetyl, 8-acetyl, 3-nitro, and 3-aminofluoranthenes (4, 5, 7, and 8) were reacted in FSO3H...
α-oxoketene dithioacetal 2 has been subjected to various [3 + 3] aromatic and heteroaromatic annulation and other heterocyclization reactions previously developed in our laboratory, providing short and efficientroutes to a diverse range of known and unknown acenaphtho-annulated linear and angular PAHs, heteroaromatics and five-membered heterocycles in good yields. Thus, benzo- and naphthoannulation of 2 with
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