TLV-TWA 50 ppm (～212 mg/m3) (ACGIH
and NIOSH), 100 ppm (～425 mg/m3)
(OSHA and MSHA); ceiling 200 ppm, peak
600 ppm/5 min/3 h (OSHA); STEL 100 ppm
（～425 mg/m3) (ACGIH).
LogP：
2.96 at 25℃
物理描述：
Styrene monomer, stabilized appears as a clear colorless to dark liquid with an aromatic odor. Vapors heavier than air and irritating to the eyes and mucous membranes. Subject to polymerization. If the polymerization takes place inside a closed container, the container may rupture violently. Less dense than water and insoluble in water. Used to make plastics, paints, and synthetic rubber.
颜色/状态：
Colorless to yellowish, oily liquid
气味：
Characteristic, sweet, balsamic, almost floral odor that is extremely penetrating
蒸汽密度：
3.6 (Air = 1)
蒸汽压力：
6.40 mm Hg at 25 °C
亨利常数：
Henry's Law constant = 0.00275 atm cu m/mole at 25 °C
最近通过LC-ESI-MS在小鼠尿液中识别出了苯乙烯的新代谢物，三种异构的烯基苯基硫酸（2-、3-和4-VPMA）。在这项研究中，4-VPMA以及2-和3-VPMA的微量也在接触苯乙烯蒸汽浓度为23至244 mg/立方米的手工层压工人尿液中被发现。这些轮班结束时的样本中4-VPMA的浓度为4.59±3.64 ng/mL（平均值±标准差；n=10），而工作轮班后次日早晨发现的浓度为2.14±2.07 ng/mL（平均值±标准差；n=10）。在次日早晨的样本中，4-VPMA与苯基乙二酸浓度之间发现了强烈的相关性（R=0.959），而在轮班结束和次日早晨样本中4-VPMA与扁桃酸之间的相关性要弱得多。4-VPMA的排泄仅占吸收的苯乙烯剂量的约3.5 x 10(-4)%。尽管代谢产率非常低，但VPMAs的形成清楚地表明了苯乙烯环氧化反应的发生和程度，这一反应被认为是具有毒理学相关性的代谢途径。
New metabolites of styrene, three isomeric vinylphenylmercapturic acids (2-, 3-, and 4-VPMA), were recently identified by LC-ESI-MS in the urine of mice. In this study, 4-VPMA together with traces of 2- and 3-VPMA were found also in the urine of hand-lamination workers, which were exposed to styrene vapors at concentrations ranging from 23 to 244 mg/cu m. Concentrations of 4-VPMA in these end-of-shift samples were 4.59+/-3.64 ng/mL (mean+/-S.D.; n=10), those found next morning after the work-shift were 2.14+/-2.07 ng/mL (mean+/-S.D.; n=10). Strong correlation (R=0.959) was found in the next-morning samples between concentrations of 4-VPMA and phenylglyoxylic acid, whereas correlations found between 4-VPMA and mandelic acid in both end-of-shift and next-morning samples were much weaker. The excretion of 4-VPMA accounted for only about 3.5 x 10(-4)% of the absorbed dose of styrene. Despite very low metabolic yield, formation of VPMAs clearly indicates occurrence and extent of styrene ring oxidation considered to be a toxicologically relevant metabolic pathway.
Human P450 2A13 is the most efficient enzyme for catalyzing the metabolism of nicotine and metabolic activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). It is conceivable that P450 2A13 also metabolizes chemicals in air pollutants because this enzyme is highly expressed in the respiratory tract. In this study, /the authors/ investigated the possibility that P450 2A13 can metabolize naphthalene, styrene, and toluene, which are included in air pollutants as well as tobacco smoke, although they were known to be metabolized by P450 1A2 or 2E1. /They/ found that P450 2A13 catalyzed 1- and 2-naphthol formations from naphthalene with higher intrinsic clearances (kcat/ Km) (3.1- and 2.2-fold, respectively) than P450 1A2 and also more efficiently catalyzed the styrene 7,8-oxide formation from styrene and the benzylalcohol formation from toluene than P450 2E1. The overlapping substrate specificity of P450 2A13 with P450 2E1 was supported by the finding that P450 2A13 catalyzed chlorzoxazone 6-hydroxylation (8-fold higher value of kcat/ Km) and p-nitrophenol 2-hydroxylation (19-fold higher value of kcat/ Km), which are marker activities of P450 2E1. Thus, /the authors/ found that P450 2A13 metabolizes diverse environmental chemicals and has overlapping substrate specificities of P450 1A2 and 2E1, suggesting that P450 2A13 plays important roles in the local metabolism of environmental chemicals in the respiratory tract related to toxicity or carcinogenicity.
The current study was aimed at examining the role of cytochrome P450 (CYP450) activation and the electrophile-sensitive transient receptor potential ankyrin 1 receptor (TRPA1) in mediating the sensory irritation response to styrene and naphthalene. Toward this end, the sensory irritation to these vapors was measured in female C57Bl/6J mice during 15-min exposure via plethysmographic measurement of the duration of braking at the onset of each expiration. The sensory irritation response to 75 ppm styrene and 7 ppm naphthalene was diminished threefold or more in animals pretreated with the CYP450 inhibitor metyrapone, providing evidence of the role of metabolic activation in the response to these vapors. The sensory irritation response to styrene (75 ppm) and naphthalene (7.6 ppm) was virtually absent in TRPA1-/- knockout mice, indicating the critical role of this receptor in mediating the response. Thus, these results support the hypothesis that styrene and naphthalene vapors initiate the sensory irritation response through TRPA1 detection of their CYP450 metabolites.
The CYP2E1 has been identified as the main cytochrome P450 isoform involved in human styrene metabolism. CYP2E1 presents polymorphism in humans and the different genotypes may, at least partly, be related to the different levels of individual expression of enzyme activity. /Investigators/ studied whether the genetic polymorphisms and phenotype of CYP2E1 modulate the level of urinary styrene metabolites and if they can be used for assessing risks of occupational exposure to styrene. A population of 49 male workers exposed to styrene (average level 362.7 mg/cu m) and a control group were selected. Samples of urine, blood and buccal swab were taken to determine the urinary biological indicators (phenylglyoxylic acid and mandelic acid), to quantify mRNA of CYP2E1 in blood using RT-PCR and to analyze different polymorphisms of enzyme CYP2E1 from buccal swab. /Investigators/ found decreased expression of mRNA of the enzyme, as well as decreased excretion of the styrene metabolites in individuals carrying the CYP2E1*5B heterozygote allele (cl/c2) with respect to the wild-type homozygote (c1/c1), which indicates a reduction in the inducibility of the enzyme in the presence of this polymorphism. The results show that the combined effect of both the CYP2E1 phenotype, measured by the expression of the specific mRNA in blood samples, and the CYP2E1*5B allele genotype, may explain the variability of urinary excretion of the styrene metabolites.
来源:Hazardous Substances Data Bank (HSDB)
代谢
苯乙烯已知的人类代谢物包括苯乙烯7,8-氧化物。
Styrene has known human metabolites that include Styrene 7,8-oxide.
IDENTIFICATION AND USE: Styrene is a colorless to yellowish, oily liquid. It is used in the manufacture of plastics, synthetic rubber, and resins, and as an insulator. It is also used as a flavoring agent for ice cream and candy. HUMAN STUDIES: Humans acutely exposed to styrene by inhalation to 800 ppm (3.4 mg/L) for 3 hr experience immediate eye and throat irritation, increased nasal mucous secretion, metallic taste, drowsiness, and vertigo. After test termination, slight muscular weakness, accompanied by inertia and depression were noted. Long-term contact with styrene results in blistering of the skin and development of dermatitis, which is thought to result from defatting of the skin. Effects on the liver (e.g., increased serum bile acid and enhanced activity of plasma enzymes) and reproductive system (e.g., decreased frequency of births and increased frequency of spontaneous abortions in female workers) have been reported. Epidemiologic studies found styrene workers had increased mortality or incidences of lymphohematopoietic cancers (leukaemia or lymphoma or all), with suggestive evidence for pancreatic and esophageal tumors. No adequate human studies are available for styrene-7,8-oxide although this is the primary and active epoxide metabolite of styrene. Both are genotoxic and form DNA adducts in humans. Products having high irritancy to the human eye are formed when styrene is photo-oxidized with ozone and nitrogen dioxide as in formation of smog. Also, a potent lacrimator has been formed when styrene wastes became mixed with bromine or chlorine wastes and reacted under the influence of sunlight. ANIMAL STUDIES: Acute exposure of animals to styrene causes irritation of the skin and respiratory tract, and central nervous system effects. Liquid styrene is a skin irritant which, on direct contact, causes erythema. Styrene in the rabbit eye caused moderate conjunctival irritation and slight, transient corneal injury. Nystagmus was demonstrated in rabbits, and during styrene exposure the directions of the rotatory nystagmus reversed. Rats and guinea pigs that inhaled 10,000 ppm styrene became comatose within minutes and died after 30 to 60 minutes of exposure. Animals exposed at 2500 ppm showed weakness and stupor, followed by incoordination, tremor, and coma; death followed within 8 hours. A 50% reduction in respiratory rate occurred in mice that inhaled 160 ppm for 3 minutes; mice that inhaled 250 ppm for two 6-hr periods or 500 ppm for a single 6-hr period developed severe centrilobular hepatic necrosis. Mice inhaling 125 ppm styrene, 6 hrs/day for 4 days developed increased liver weight. When rats were given 0, 125, or 250 ppm commercial grade styrene in their drinking water for three generations, no treatment-related changes in reproduction could be detected. Long-term chemical carcinogenesis bioassays showed that styrene caused lung cancers in several strains of mice and mammary cancers in rats and styrene-7,8-oxide caused tumors of the forestomach in rats and mice and of the liver in mice. Styrene induced reverse mutations in Salmonella typhimurium TA1535 and TA100 in presence of metabolic activation. It was not mutagenic to TA1537, TA1538 or TA98. Styrene was not mutagenic in spot test with various strains of Salmonella typhimurium without metabolic activation. It did not induce forward mutations in Schizosaccharomyces pombe, even with metabolic activation. In host-mediated assay using male mice, 1000 mg/kg styrene increased gene conversion frequency in Saccharomyces cerevisiae strain D4. The endocrine disruptor activity of styrene in humans and other vertebrates appears to be negligible. ECOTOXICITY STUDIES: Offspring numbers were reduced in Ceriodaphnia dubia bred in polystyrene cups. The swimming activity of the amphipod, Pontoporeia affinis, was stimulated by styrene at concentrations between 2.3 and 23 mg/L. Higher styrene levels (35 and 46 mg/L) caused amphipods to cease swimming for several days, then resume greater than normal activity.
Styrene 7,8-oxide, a metabolite of styrene, can form DNA adducts by binding to deoxyguanosine. It is also mutagenic and causes increased frequency of sister chromatid exchange, chromosomal aberrations, micronucleated cells, and DNA strand breaks. (L1831)
Styrene is reasonably anticipated to be a human carcinogen based on limited evidence of carcinogenicity from studies in humans, sufficient evidence of carcinogenicity from studies in experimental animals, and supporting data on mechanisms of carcinogenesis.
Evaluation: There is limited evidence in humans for the carcinogenicity of styrene. There is limited evidence in experimental animals for the carcinogenicity of styrene. Styrene is possibly carcinogenic to humans (Group 2B).
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A4；不能分类为人类致癌物。/苯乙烯，单体/
A4; Not classifiable as a human carcinogen. /Styrene, monomer/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
人体吸收苯乙烯可以通过所有途径进行，但主要通过呼吸道。
The absorption of styrene in humans proceeds by all routes, but mainly through the respiratory tract.
Styrene vapors are absorbed through lung; percutaneous absorption of styrene during exposure to concentrations up to 2.5 g/cu M (600 ppm) in air is insignificant (about 2%) as compared with the respective pulmonary absorption. The percutaneous absorption of liquid styrene through skin of hand is 9-15 mg/sq cm/hr and that of aqueous solution (66-269 mg/L) is 40-180 ug/sq cm/hr. Styrene is soluble in blood and has been found in fat tissue. It was found in SC fat samples from 13/17 workers for as long as 3 days after most recent occupational exposure to more than 4.2 mg/cu M (1 ppm) styrene in air. It is rapidly depleted in breath following exposure to 420 mg/cu M (100 ppm) in air.
The tissue distribution and excretion of an oral dose of 20 mg/kg of (14)C-labeled styrene was studied in both male and female rats at various time intervals after admin. Organ with highest concn was kidney, followed by liver and pancreas. Principal route of excretion was by way of the kidneys, with 90% of dose appearing in urine within 24 hr. Less than 2% of the dose was recovered from the feces.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
已观察到，苯乙烯会穿过胎盘。
Styrene, it has been observed, crosses the placenta.
1.周国泰，化学危险品安全技术全书，化学工业出版社，1997 2.国家环保局有毒化学品管理办公室、北京化工研究院合编，化学品毒性法规环境数据手册，中国环境科学出版社.1992 3.Canadian Centre for Occupational Health and Safety,CHEMINFO Database.1998 4.Canadian Centre for Occupational Health and Safety, RTECS Database, 1989
An enantioselective alkoxycarbonylation-amination cascade process of terminalallenes with CO, methanol, and arylamines has been developed. It proceeds under mild conditions (room temperature, ambient pressure CO) via oxidative Pd(II) catalysis using an aromatic spiroketal-based diphosphine (SKP) as a chiral ligand and a Cu(II) salt as an oxidant and affords a wide range of α-methylene-β-arylamino
2‐Pyridyl Sulfoxide: A Versatile and Removable Directing Group for the Pd
<sup>II</sup>
‐Catalyzed Direct CH Olefination of Arenes
作者：Alfonso García‐Rubia、M. Ángeles Fernández‐Ibáñez、Ramón Gómez Arrayás、Juan Carlos Carretero
DOI：10.1002/chem.201003633
日期：2011.3.21
Removable and versatile: The 2‐pyridylsulfinyl group has proved to be an efficient directinggroup in the PdII‐catalyzed aryl ortho CH olefination. This catalyst system enables the sequential double olefination to give asymmetrically di‐ortho‐functionalized arenes. The sulfinyl directinggroup can be easily cleaved, providing access to 1,3‐disubstituted arenes, or transformed into a thiol group.
Alternate Heme Ligation Steers Activity and Selectivity in Engineered Cytochrome P450-Catalyzed Carbene-Transfer Reactions
作者：Kai Chen、Shuo-Qing Zhang、Oliver F. Brandenberg、Xin Hong、Frances H. Arnold
DOI：10.1021/jacs.8b09613
日期：2018.12.5
platform of engineered cytochrome P450 enzymes to carry out carbene-transfer reactions using a lactone-based carbene precursor. By simply altering the heme-ligating residue, we obtained two enzymes that catalyzeolefincyclopropanation (Ser) or S-H bond insertion (Cys). Both enzymes exhibit high catalytic efficiency and stereoselectivity, thus enabling facile access to structurally diverse spiro[2.4]lactones
我们报告了工程细胞色素 P450 酶的生物催化平台，以使用基于内酯的卡宾前体进行卡宾转移反应。通过简单地改变血红素连接残基，我们获得了两种催化烯烃环丙烷化 (Ser) 或 SH 键插入 (Cys) 的酶。这两种酶都表现出高催化效率和立体选择性，因此可以轻松获得结构多样化的螺[2.4]内酯和α-硫代-γ-内酯。计算研究揭示了卡宾 SH 插入的机制，并解释了轴向配体如何控制反应性和选择性。这项工作扩展了血红素蛋白的催化库，并提供了有关如何调整这些酶以适应新化学反应的见解。
Electrochemical sulfonylation of thiols with sulfonyl hydrazides: a metal- and oxidant-free protocol for the synthesis of thiosulfonates
作者：Zu-Yu Mo、Toreshettahally R. Swaroop、Wei Tong、Yu-Zhen Zhang、Hai-Tao Tang、Ying-Ming Pan、Hong-Bin Sun、Zhen-Feng Chen
DOI：10.1039/c8gc02143k
日期：——
We have developed a new metal- and oxidant-free method for the synthesis of anticancer thiosulfonates via sulfonylation of thiols.
我们已经开发出一种新的无金属和氧化剂的方法，通过对硫醇进行磺化合成抗癌硫代磺酸酯。
Direct Dearomatization of Pyridines via an Energy-Transfer-Catalyzed Intramolecular [4+2] Cycloaddition
The catalytic dearomatization of pyridines, accessing medicinally relevant N-heterocycles, is of high interest. Currently direct, dearomative strategies rely generally on reduction or nucleophilic addition, thus limiting the architecture of the dearomatized products to a six-membered ring. We herein introduce a catalytic, dearomative cycloaddition reaction with pyridines using photoinduced energy transfer
