苯并[C]屈 | 194-69-4

• 物质功能分类: 分析化学 - 标准品 - 挥发性有机化合物(VOCs)
• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 中文名称: 苯并[C]屈
• 英文名称: benzo[c]chrysene
• 英文别名: benzochrysene；Benzochrysen；benzchrysene；benzo(c)chrysene；benzo[c]chrysene；pentacyclo[12.8.0.02,11.03,8.015,20]docosa-1(14),2(11),3,5,7,9,12,15,17,19,21-undecaene
• CAS: 194-69-4
• 化学式: C₂₂H₁₄
• 分子量: 278.353
• InChiKey: YZWGEMSQAMDWEM-UHFFFAOYSA-N

物化性质

• 熔点：
  126.5°C
• 沸点：
  356.16°C (rough estimate)
• 密度：
  1.1489 (estimate)
• 颜色/状态：
  Needles from acetic acid
• 溶解度：
  In water, 3.26X10-3 mg/L at 25 °C (est)
• 蒸汽压力：
  9.03X10-10 mm Hg at 25 °C (est)
• 分解：
  When heated to decomposition it emits acrid smoke and irritating fumes.

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

ADMET

代谢

苯并[c]芘（BcC）是一种独特的多环芳烃环境污染物，在同一分子中同时具有湾区和峡湾区。我们之前已经证明，湾区和峡湾区的末端环都参与了BcC的体外代谢。在当前的研究中，我们准备了[14-(3)H]BcC并测试了假设，即BcC可以在雌性CD大鼠中激活为湾区和峡湾区的二醇环氧物。在6周大时，大鼠通过胃管给予单剂量的[14-(3)H]BcC（5毫克/只；比活性，6.7Ci/mmol）溶于0.5毫升的三辛酸甘油酯中。在前48小时内，20.3%的剂量通过粪便排出，2.8%通过尿液排出。1周后，累积分别排出了23.2%和3.5%。3-羟基苯并[c]芘、10-羟基苯并[c]芘和反式-7,8-二羟基-7,8-二氢苯并[c]芘是主要的粪便代谢物。在尿液中，检测到反式-1,2-二羟基-1,2-二氢苯并[c]芘、2-羟基苯并[c]芘、（+/-）-1,t-2,t-3,c-4-四羟基-1,2,3,4-四氢苯并[c]芘和（+/-）-9,t-10,t-11,c-12-四羟基-9,10,11,12-四氢苯并[c]芘，主要是作为葡萄糖醛酸和硫酸结合物。这两种四醇的鉴定清楚地表明，湾区和峡湾区的二醇环氧物作为BcC体内代谢的中间体形成。本研究的第二个目标是测试假设，即环氧基团的位置（峡湾区对湾区）决定了其致癌活性。因此，我们比较了湾区（+/-）-反式-1,2-二羟基-3,4-环氧-1,2,3,4-四氢苯并[c]芘和峡湾区（+/-）-反式-9,10-二羟基-11,12-环氧-9,10,11,12-四氢苯并[c]芘在大鼠乳腺中的致癌性。结果显示，峡湾区的二醇环氧物是一种强效的乳腺致癌物，而湾区的二醇环氧物在这种模型检测中缺乏活性。...

Benzo[c]chrysene (BcC), an environmental pollutant, is a unique polycyclic aromatic hydrocarbon that possesses both a bay region and a fjord region in the same molecule. We previously demonstrated that both bay region and fjord region terminal rings are involved in the in vitro metabolism of BcC. In the present investigation, we prepared [14-(3)H]BcC and tested the hypothesis that BcC can be activated to both bay region and fjord region diol epoxides in female CD rats. At 6 weeks of age, rats were gavaged with a single dose of [14-(3)H]BcC (5 mg/rat; specific activity, 6.7 Ci/mmol) in 0.5 mL of trioctanoin. During the first 48 h, 20.3% of the dose was eliminated in the feces and 2.8% was eliminated in the urine. After 1 week, cumulatively, 23.2 and 3.5%, respectively, were eliminated. 3-Hydroxybenzo[c]chrysene, 10-hydroxybenzo[c]chrysene, and trans-7,8-dihydroxy-7,8-dihydrobenzo[c]chrysene were the major fecal metabolites. In urine, trans-1,2-dihydroxy-1,2-dihydrobenzo[c]chrysene, 2-hydroxybenzo[c]chrysene, (+/-)-1,t-2,t-3,c-4-tetrahydroxy-1,2,3,4-tetrahydrobenzo[c]chrysene, and (+/-)-9,t-10,t-11,c-12-tetrahydroxy-9,10,11,12-tetrahydrobenzo[c]chrysene were detected, primarily as glucuronic acid and sulfate conjugates. The identification of the two tetraols clearly indicates that both bay region and fjord region diol epoxides are formed as intermediates in the metabolism of BcC in vivo. The second goal of this study was to test the hypothesis that the location of the epoxide moiety (fjord vs bay region) determines the carcinogenic activity. Thus, we compared the carcinogenicity of the bay region (+/-)-anti-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydrobenzo[c]chrysene and the fjord region (+/-)-anti-9,10-dihydroxy-11,12-epoxy-9,10,11,12-tetrahydrobenzo[c]chrysene in the rat mammary gland. The results clearly showed that the fjord region diol epoxide is a potent mammary carcinogen, while the bay region diol epoxide lacks activity in this model assay. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

研究了由Aroclor 1254处理的Sprague-Dawley大鼠微粒体激活的racemic苯并[c]芘-反-9,10-、苯并[g]芘-反-11,12-和二苯并[a,l]芘-反-11,12-二氢二醇到峡湾区顺-和反-二氢二醇环氧化的代谢活化。由于在实验条件下峡湾区二氢二醇环氧化的水解不稳定，因此通过在加入高氯酸后分析四醇作为其酸性水解产物来确定它们的酶促形成。通过HPLC分离形成的各种立体异构四醇，并通过与酸性水解合成的顺-和反-二氢二醇环氧化的真实四醇共相色谱进行鉴定，这些真实四醇通过NMR和UV光谱进行了表征。在标准化条件下，苯并[c]芘、苯并[g]芘和二苯并[a,l]芘的顺-二氢二醇环氧化的酸性水解形成两个四醇，其顺/反比分别为81:19、77:23和80:20，而反-二氢二醇环氧几乎完全进行反式水解。从微粒体培养中获得的立体异构四醇的比例表明，所有三种二氢二醇主要在相邻的烯丙基双键处被氧化为相应峡湾区二氢二醇环氧化的反-对映体，占乙酯可提取代谢物的4-35%。为了对代谢物进行定量评估，通过用硼三钠还原相应的邻-醌合成了(3)H标记的反-二氢二醇。在大鼠肝微粒体中，苯并[c]芘-反-9,10-和二苯并[a,l]芘-反-11,12-二氢二醇的代谢转化在最初的10分钟内相似地处于低范围（分别为6.2 +/- 1.2和3.4 +/- 1.0 nmol底物/nmol细胞色素P450/10分钟），而苯并[g]芘-反-11,12-二氢二醇的转化要高得多（20.6 +/- 2.2 nmol底物/nmol细胞色素P450/10分钟）。鉴于峡湾区二氢二醇环氧化的强烈内在诱变和致癌活性，我们的数据表明，即使在其形成相对较低水平时，它们也可能显著地贡献于母体烃的生物学活性。

Metabolic activation of the racemic benzo[c]chrysene-trans-9,10-, benzo[g]chrysene-trans-11,12- and dibenzo[a,l]pyrene-trans-11,12-dihydrodiols to fjord region syn- and anti-dihydrodiol epoxides by microsomes of Aroclor 1254-treated Sprague-Dawley rats has been examined. Since the fjord region dihydrodiol epoxides were hydrolytically unstable under the experimental conditions, their enzymatic formation was determined by analyzing the tetraols as their products of acidic hydrolysis upon addition of perchloric acid. The various stereoisomeric tetraols formed were separated by HPLC and identified by co-chromatography with authentic tetraols, which had been prepared by acidic hydrolysis of synthetically available syn- and anti-dihydrodiol epoxides and characterized by NMR and UV spectroscopy. Under standardized conditions the acidic hydrolysis of syn-dihydrodiol epoxides of benzo[c]chrysene, benzo[g]chrysene and dibenzo[a,l]pyrene resulted in the formation of two tetraols with cis/trans ratios of 81:19, 77:23 and 80:20, respectively, whereas the anti-dihydrodiol epoxides underwent almost exclusively trans hydrolysis. The proportion of the stereoisomeric tetraols obtained from microsomal incubations indicates that all three dihydrodiols are predominantly oxidized at the adjacent olefinic double bond to the anti-diastereomers of the corresponding fjord region dihydrodiol epoxides accounting for 4-35% of the ethyl acetate-extractable metabolites. To allow quantitative assessment of the metabolites (3)H-labeled trans-dihydrodiols were synthesized by reduction of the corresponding o-quinones with sodium borotritide. Metabolic conversion of benzo[c]chrysene-trans-9,10- and dibenzo[a,l]pyrene-trans-11,12-dihydrodiol by rat liver microsomes were in a similar low range during the first 10 min of incubation (6.2 +/- 1.2 and 3.4 +/- 1.0 nmol substrate/nmol cytochrome P450/10 min, respectively), whereas the conversion of benzo[g]chrysene-trans-11,12-dihydrodiol was much higher (20.6 +/- 2.2 nmol substrate/nmol cytochrome P450/10 min). Given the strong intrinsic mutagenic and carcinogenic activity of the fjord region dihydrodiol epoxides, our data indicate that their formation, even at a relatively low level, may contribute significantly to the biological activity of the parent hydrocarbons.

来源:Hazardous Substances Data Bank (HSDB)

代谢

多环芳烃在哺乳动物细胞中的代谢会导致生成被认为是终极致癌物的邻二醇环氧物，如果环氧环位于母体化合物的湾区或峡区。在当前研究中，chrysene、dibenz[a,h]anthracene和benzo[a]pyrene的湾区二醇环氧物的个体对映异构体以及benzo[c]phenanthrene、benzo[c]chrysene和benzo[g]-chrysene的峡区二醇环氧物已经与GSH一起在人类谷胱甘肽转移酶GSTM1-1（一个mu类酶）和GSTP1-1（一个pi类酶）的存在下进行了孵化。正如之前用GSTA1-1（一个alpha类酶）所展示的，M1-1和P1-1对本研究中的许多二醇环氧物表现出相当大的活性，尽管在催化效率和立体选择性方面观察到很大的变化。对于GSTM1-1，特别是湾区二醇环氧物的syn-对映异构体通常比峡区类似物更有效地与GSH结合。GSTM1-1对于在环氧环的苄基位置具有R-构型的对映异构体的结合显示出从无偏好（50%）到高度偏好（大于或等于90%）的立体选择性。对于GSTP1-1，该酶对湾区和峡区二醇环氧物都表现出了相当大的活性，并且在大多数情况下对anti-对映异构体有偏好。与GSTM1-1和之前对GSTA1-1的展示相反，GSTP1-1对于在苄基环氧碳上具有R-构型的对映异构体的结合显示出独有的偏好。对于GSTM1-1和GSTP1-1，化学上最活性的二醇环氧物，即反式-7,8-二羟基-9,10-环氧-7,8,9,-10-四氢苯并[a]芘的(+)-syn-对映异构体（BPDE），是最好的底物。与GSTA1-1一样，化合物的化学活性和亲脂性与其催化效率之间没有明显的相关性。在GSTP1-1和-A1-1的活性位点对二醇环氧物进行分子建模与基于功能研究的假设一致，即GSTA1-1的H位点可以容纳不同大小的立体异构体。此外，将anti-和syn-BPDE的对映异构体在GSTP1-1的活性位点进行建模为对在苄基环氧碳上具有R-构型的对映异构体的独有偏好提供了解释。这些异构体可以被紧密地适配在H位点，靠近GSH硫，而具有相反立体化学的异构体则不能。

Metabolism of polycyclic aromatic hydrocarbons in mammalian cells results in the formation of vicinal diol epoxides considered as ultimate carcinogens if the oxirane ring is located in a bay- or fjord-region of the parent compound. In the present study, individual stereoisomers of the bay-region diol epoxides of chrysene, dibenz[a,h]anthracene, and benzo[a]pyrene as well as of the fjord-region diol epoxides of benzo[c]phenanthrene, benzo[c]chrysene, and benzo[g]-chrysene have been incubated with GSH in the presence of human glutathione transferases GSTM1-1 (a mu-class enzyme) and GSTP1-1 (a pi-class enzyme). As previously shown with GSTA1-1 (an alpha-class enzyme) both M1-1 and P1-1 demonstrate considerable activity toward a number of the diol epoxides studied, although a great variation in catalytic efficiency and enantioselectivity was observed. With GSTM1-1, the bay-region diol epoxides, in particular the syn-diastereomers were in most cases more efficiently conjugated with GSH than the fjord-region analogues. GSTM1-1 demonstrated an enantioselectivity ranging from no preference (50%) to high preference (> or = 90%) for conjugation of the enantiomers with R-configuration at the benzylic position of the oxirane ring. With GSTP1-1, the enzyme demonstrated appreciable activity toward both bay- and fjord-region diol epoxides and, in most cases, a preference for the anti-diastereomers. In contrast to GSTM1-1 and as previously shown for GSTA1-1, GSTP1-1 showed an exclusive preference for conjugation of the enantiomers with R-configuration at the benzylic oxirane carbon. With both GSTM1-1 and GSTP1-1, the chemically most reactive diol epoxide, the (+)-syn-enantiomer of trans-7,8-dihydroxy-9,10-epoxy-7,8,9,-10-tetrahydrobenzo[a]pyrene (BPDE), was the best substrate. As for GSTA1-1, no obvious correlation between chemical reactivity or lipophilicity of the compounds and catalytic efficiencies was observed. Molecular modeling of diol epoxides in the active sites of GSTP1-1 and -A1-1 is in agreement with the assumption, based on functional studies, that the H-site of GSTA1-1 can accommodate stereoisomers of different sizes. Further, modeling of the enantiomers of anti- and syn-BPDE in the active site of GSTP1-1 provides an explanation for the exclusive preference for the enantiomers with R-configuration at the benzylic oxirane carbon. These isomers could be snuggly fitted in the H-site close to the GSH sulfur, whereas those with opposite stereochemistry could not.

来源:Hazardous Substances Data Bank (HSDB)

代谢

许多多环芳烃（PAHs）的致癌活性主要归因于它们各自的二醇环氧化合物，这些化合物可以根据环氧化合物功能的位置被分类为湾区或峡湾区。人类谷胱甘肽（GSH）转移酶Pi类（hGSTP1-1）在人类中具有多态性，表现在氨基酸残基在104位（异亮氨酸或缬氨酸）和/或113位（丙氨酸或缬氨酸）的不同，这对于PAH-二醇环氧化合物的解毒起着重要作用。在这里，我们报告了环氧化合物功能的位置决定了hGSTP1-1等位基因变异体对反式二醇环氧化合物异构体苯并[c]芘（B[c]C）的特异性。V104,A113（VA）和V104,V113（VV）变异体hGSTP1-1的催化效率（k(cat)/K(m)）分别比I104,A113（IA）异构体对湾区异构体（+/-）-反式-B[c]C-1,2-二醇-3,4-环氧化合物高出约2.3倍和1.7倍。另一方面，IA变异体在催化峡湾区异构体（+/-）-反式-B[c]C-9,10-二醇-11,12-环氧化合物的GSH结合方面，比VA和VV异构体分别高出约1.6倍和3.5倍。目前的研究结果清楚地表明，环氧化合物功能的位置决定了hGSTP1-1等位基因变异体在B[c]C激活的二醇环氧化合物异构体的GSH结合特异性。

Carcinogenic activity of many polycyclic aromatic hydrocarbons (PAHs) is mainly attributed to their respective diol epoxides, which can be classified as either bay or fjord region depending upon the location of the epoxide function. The Pi class human glutathione (GSH) transferase (hGSTP1-1), which is polymorphic in humans with respect to amino acid residues in positions 104 (isoleucine or valine) and/or 113 (alanine or valine), plays an important role in the detoxification of PAH-diol epoxides. Here, we report that the location of the epoxide function determines specificity of allelic variants of hGSTP1-1 toward racemic anti-diol epoxide isomers of benzo[c]chrysene (B[c]C). The catalytic efficiency (k(cat)/K(m)) of V104,A113 (VA) and V104,V113 (VV) variants of hGSTP1-1 was approximately 2.3- and 1.7-fold higher, respectively, than that of the I104,A113 (IA) isoform toward bay region isomer (+/-)-anti-B[c]C-1,2-diol-3,4-epoxide. On the other hand, the IA variant was approximately 1.6- and 3.5-fold more efficient than VA and VV isoforms, respectively, in catalyzing the GSH conjugation of fjord region isomer (+/-)-anti-B[c]C-9,10-diol-11,12-epoxide. The results of the present study clearly indicate that the location of the epoxide function determines specificity of the allelic variants of hGSTP1-1 in the GSH conjugation of activated diol epoxide isomers of B[c]C.

来源:Hazardous Substances Data Bank (HSDB)

代谢

哺乳动物对多环芳烃的代谢会导致形成邻二醇环氧化合物（存在两种对映异构体和两种非对映异构体），如果环氧环位于母体碳氢化合物的湾区或峡湾区域，则被认为是重要的终极致癌物。在当前研究中，湾区二醇环氧化合物的个别立体异构体，如屈曲苯、二苯并[a,h]蒽和苯并[a]芘，以及峡湾区域的苯并[c]菲、苯并[c]屈曲苯和苯并[g]屈曲苯，在存在或不存在人类谷胱甘肽S-转移酶同工酶GST A1-1的情况下与谷胱甘肽（GSH）进行孵化。通过高效液相色谱（HPLC）确定并量化了GSH结合物的形成。结果表明，GST A1-1同工酶催化了所有测试的二醇环氧化合物形成GSH结合物，尽管观察到催化效率有显著差异（超过20倍）。对于湾区和峡湾区域的反式二醇环氧化合物，在环氧环的苄基位置上，显著偏好结合具有R构型的对映异构体。在峡湾区域二醇环氧化合物的同式非对映异构体中也观察到了类似的底物对映选择性，即具有相应R配置的对映异构体被优先结合。相比之下，对于湾区同式二醇环氧化合物，这种底物选择性被反转，导致偏好具有S配置的对映异构体。化学上更具活性的同式非对映异构体通常是GST A1-1的更好底物，而不是相应的反式非对映异构体。然而，不同二醇环氧化合物非对映异构体之间的比较并未发现化合物化学活性和催化效率之间的明显相关性。此外，未观察到二醇环氧化合物亲脂性与催化效率之间的显著相关性。这表明立体化学因素，包括芳香环系统的尺寸和几何形状以及二醇环氧化合物的首选构象，是GST A1-1催化速率的主要决定因素。

Mammalian metabolism of polycyclic aromatic hydrocarbons results in the formation of vicinal diol epoxides (existing as enantiomeric pairs of two diastereomers) considered as important ultimate carcinogens if the oxirane ring is located in a bay or fjord region of the parent hydrocarbon. In the present study, individual stereoisomers of the bay region diol epoxides of chrysene, dibenz[a,h]anthracene and benzo[a]pyrene, as well as of the fjord region diol epoxides of benzo[c]phenanthrene, benzo[c]chrysene and benzo[g]chrysene, have been incubated with glutathione (GSH) in the presence or absence of human glutathione S-transferase isoenzyme GST A1-1, a class Alpha enzyme. The formation of GSH conjugates was determined and quantified by HPLC. The results demonstrate that the GST A1-1 isoenzyme catalyzes the formation of GSH conjugates of all diol epoxides tested, although a marked variation in catalytic efficiency (>20-fold) was observed. With both bay and fjord region anti-diol epoxides a significant preference for conjugation of the enantiomer with the R configuration at the benzylic position of the oxirane ring was noted. Among the syn diastereomers of the fjord region diol epoxides a similar substrate enantioselectivity was noted, i.e. the enantiomer with the corresponding R configuration was again preferentially conjugated. In contrast, for the bay region syn-diol epoxides this substrate selectivity was reversed, resulting in a preference for the enantiomer with the S configuration. The chemically more reactive syn diastereomers were in general better substrates for GST A1-1 than the corresponding anti diastereomers. However, a comparison between different diol epoxide diastereomers revealed no obvious correlation between chemical reactivity of the compounds and catalytic efficiencies. Furthermore, no significant correlation between diol epoxide lipophilicity and catalytic efficiency was observed. It is suggested that stereochemical factors, including the size and the geometry of the aromatic ring system and the preferred conformation of the diol epoxide, are involved as the major determinant for the rate of catalysis by GST A1-1.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

鉴定和使用：苯并(c)芘（B(c)C）是多核芳香烃（PAH）。它不是商业生产的，主要用于生物化学研究。PAH在有机物燃烧产物中普遍存在，包括香烟烟雾。人类暴露和毒性：没有数据可用。动物研究：它具有中等致癌活性。B(c)C是一种独特的多环芳香烃，同一分子中同时具有湾区和峡湾区。BcC的湾区和峡湾区端环都参与了体外代谢。B(c)C的代谢物形成DNA加合物。B[c]C在小鼠皮肤DNA中形成DNA加合物的程度低于其他中等致癌PAH。苯并[c]芘能够刺激环氧水解酶活性，但效果一般，并且是诱导大鼠肝脏CYP1A1活性的强诱导剂。

IDENTIFICATION AND USE: Benzo(c)chrysene (B(c)C) is polynuclear aromatic hydrocarbon (PAH). It is not produced commercially, and it used mostly in biochemical research. PAHs are ubiquitous in combustion products of organic matter, including cigarette smoke. HUMAN EXPOSURE AND TOXICITY: There are no data available. ANIMAL STUDIES: It has moderate carcinogenic activity. B(c)C is a unique polycyclic aromatic hydrocarbon that possesses both a bay region and a fjord region in the same molecule. Both bay region and fjord region terminal rings are involved in the in vitro metabolism of BcC. Metabolites of B(c)C form DNA adducts. The extent of DNA adduct formation by B[c]C in mouse skin DNA was lower than that of other moderately carcinogenic PAHs. Benzo[c]chrysene was capable of stimulating epoxide hydrolase activity, but the effect was modest, and it is a potent inducers of rat hepatic CYP1A1 activity.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需阀复苏器、袋阀面罩装置或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果发生呕吐，让患者前倾或置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗帮助。 /萘及其相关化合物/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Naphthalene and Related Compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有必要，协助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测休克，如有必要，进行治疗……。预见并治疗癫痫发作……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）连续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释。给予活性炭……。/萘及其相关化合物/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Naphthalene and Related Compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。开始静脉输注0.9%的生理盐水（NS）或乳酸钠林格氏液（LR）。必须保持充足的水分，以防止由于肌红蛋白尿导致的肾衰竭，除非出现脑水肿或肺水肿的迹象。对于伴有低容量血症征象的低血压，要谨慎输液。密切观察液体过载的迹象……如果病人在给予氧气后仍有严重低氧血症、发绀和心脏功能不全的症状，给予1%亚甲基蓝溶液……用安定（Diazepam）或劳拉西泮（Ativan）治疗癫痫……使用丙美卡因氢氯化物来协助眼部冲洗……/萘及其相关化合物/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious or is in severe respiratory distress. Start IV administration of 0.9% saline (NS) or lactated Ringer's (LR). Adequate hydration must be maintained to prevent renal failure secondary to myoglobinuria unless signs of cerebral or pulmonary edema are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Administer 1% solution methylene blue if patient is symptomatic with severe hypoxia, cyanosis, and cardiac compromise not responding to oxygen. ... Treat seizures with diazepam (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Naphthalene and Related Compounds/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

/其他毒性信息/ ... 在本次通信中，我们报告了在人类群体中最常见的hGSTP1-1的I104,A113等位基因，在对致癌抗二醇环氧化物的GSH结合反应中也最高效，这些抗二醇环氧化物包括苯并[g]荧蒽和苯并[c]菲（分别对应抗-BGCDE和抗-BCPDE）。hGSTP1-1(I104,A113)异构体对抗-BGCDE的催化效率为0.36 mM(-1) x s(-1)，比hGSTP1-1(V104,V113)高出约1.7倍（P < 0.05）。有趣的是，与密码子104异亮氨酸等位基因相比，某些癌症中密码子104缬氨酸等位基因的频率显著更高。与抗-BGCDE类似，hGSTP1-1(I104,A113)异构体对抗-BCPDE的催化效率也比其他hGSTP1-1变异体高出约1.4至2.2倍（P < 0.05）。这些观察结果很有趣，因为我们之前已经显示，与I104,A113异构体相比，V104,V113变异体在对苯并[a]芘的湾区抗二醇环氧化物（抗-BPDE）的GSH结合反应中最有效，与抗-BGCDE或抗-BCPDE不同，抗-BPDE是一个平面分子。总之，我们的结果表明，hGSTP1-1的多态性可能是人类对多环芳烃是病因因素的癌症易感性差异的一个重要因素，并且I104,A113变异体可能在解毒非平面、空间位阻较大的峡区二醇环氧化物（例如，抗-BGCDE）中发挥主要作用。

/OTHER TOXICITY INFORMATION/ ... In this communication, we report that the I104,A113 allele of hGSTP1-1, which is most frequent in human populations, is also most efficient in the GSH conjugation of carcinogenic anti-diol epoxides of benzo[g]chrysene and benzo[c]phenanthrene (anti-BGCDE and anti-BCPDE, respectively). The catalytic efficiency of hGSTP1-1(I104,A113) isoform toward anti-BGCDE, 0.36 mM(-1) x s(-1), was approximately 1.7-fold higher (P < 0.05) compared with hGSTP1-1(V104,V113). Interestingly, the frequency of codon 104-valine alleles is significantly higher in certain cancers compared with codon 104-isoleucine alleles. Like anti-BGCDE, the catalytic efficiency of hGSTP1-1(I104,A113) isoform toward anti-BCPDE was higher by about 1.4- to 2.2-fold (P < 0.05) than those of other hGSTP1-1 variants. These observations are interesting because we have shown previously that the V104,V113 variant, not the I104,A113 isoform, is most efficient in the GSH conjugation of bay-region anti-diol epoxide of benzo(a)pyrene (anti-BPDE), which, unlike anti-BGCDE or anti-BCPDE, is a planar molecule. In conclusion, our results suggest that hGSTP1-1 polymorphism may be an important factor in differential susceptibility of humans to cancers where polycyclic aromatic hydrocarbons are etiological factors and that I104,A113 variant may play a major role in the detoxification of nonplanar, sterically hindered fjord-region diol epoxides (e.g., anti-BGCDE).

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 海关编码：
  2902909090

制备方法与用途

类别：有毒物品

可燃性危险特性：

• 可燃
• 燃烧时会产生刺激烟雾

储运特性：

• 通风、低温、干燥

灭火剂：

• 干粉
• 泡沫
• 沙土
• 二氧化碳
• 雾状水

反应信息

• 作为产物：
  描述：

  1-溴菲 在 四(三苯基膦)钯 氢氧化钾 、 甲烷磺酸 、 cesium fluoride 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 乙腈 为溶剂， 反应 49.0h， 生成 苯并[C]屈
  参考文献：
  名称：

  具有峡湾区的 Cata- 和 Peri-Condensed 多环芳烃的简便通用合成

  摘要：

  Synthesis 2001, No. 6, 04 05 2001。文章标识符：1437-210X,E;2001,0,06,0841,0844,ftx,en;M03600SS.pdf。© Georg Thieme Verlag Stuttgart · 纽约 ISSN 0039-7881 摘要：Cata 和环缩合多环芳烃 (PAHs) 10a-d 和 11 已通过 Suzuki 交叉偶联反应方便地合成。在三到四个步骤中，这些具有峡湾区的 PAH 以 35-51% 的总产率从商业上或容易获得的芳基硼酸和芳基溴化物中获得。

  DOI：

  10.1055/s-2001-13401

文献信息

• Polycyclic Aromatic Hydrocarbons via Iron(III)-Catalyzed Carbonyl–Olefin Metathesis
  作者：Christopher C. McAtee、Paul S. Riehl、Corinna S. Schindler

  DOI：10.1021/jacs.7b01114

  日期：2017.3.1

  Polycyclic aromatic hydrocarbons are important structural motifs in organic chemistry, pharmaceutical chemistry, and materials science. The development of a new synthetic strategy toward these compounds is described based on the design principle of iron(III)-catalyzed carbonyl-olefin metathesis reactions. This approach is characterized by its operational simplicity, high functional group compatibility

  多环芳烃是有机化学、药物化学和材料科学中的重要结构基序。基于铁(III)催化的羰基-烯烃复分解反应的设计原理描述了这些化合物的新合成策略的开发。该方法的特点是操作简单、官能团兼容性高和区域选择性，同时依赖 FeCl3 作为环境友好、地球丰富的金属催化剂。已经获得了氧杂环丁烷作为催化羰基-烯烃闭环复分解反应中间体的实验证据。
• Methylarene-Based PAH Synthesis via Domino Cyclization of 1,1-Difluoro-1-alkenes
  作者：Kohei Fuchibe、Go Takao、Hiroki Takahashi、Shiori Ijima、Junji Ichikawa

  DOI：10.1246/bcsj.20190252

  日期：2019.12.15

  Polycyclic aromatic hydrocarbons (PAHs) containing 4–7 benzene rings were synthesized via a methylarene-based protocol. Trimethyl[2-(trifluoromethyl)allyl]silane was electrophilically benzylated wi...

  通过基于甲基芳烃的协议合成了含有 4-7 个苯环的多环芳烃 (PAH)。三甲基[2-(三氟甲基)烯丙基]硅烷经亲电苄化...
• Snatzke,G.; Kunde,K., Chemische Berichte, 1973, vol. 106, p. 1341 - 1362
  作者：Snatzke,G.、Kunde,K.

  DOI：——

  日期：——
• Weidlich, Chemische Berichte, 1938, vol. 71, p. 1203,1206
  作者：Weidlich

  DOI：——

  日期：——
• 241. Polycyclic aromatic hydrocarbons. Part XVIII. A general method for the synthesis of 3 : 4-benzphenanthrene derivatives
  作者：C. L. Hewett

  DOI：10.1039/jr9380001286

  日期：——