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Page 1: Benzene

Benzene 1

Benzene

Benzene

Identifiers

CAS number 71-43-2 [1] 

PubChem 241 [2]

ChemSpider 236 [3] 

UNII J64922108F [4] 

KEGG C01407 [5] 

ChEBI CHEBI:16716 [6] 

ChEMBL CHEMBL277500 [7] 

RTECS number CY1400000

Jmol-3D images Image 1 [8]

Properties

Molecular formula C6H6

Molar mass 78.11 g mol−1

Appearance Colorless liquid

Density 0.8765(20) g/cm3[9]

Melting point 5.5 °C, 278.7 K

Boiling point 80.1 °C, 353.3 K

Solubility in water 1.8 g/L (15 °C)[10][11][12]

λmax 255 nm

Viscosity 0.652 cP at 20 °C

Dipole moment 0 D

Hazards

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EU classification • Flammable (F)•• Carc. Cat. 1•• Muta. Cat. 2• Toxic (T)

R-phrases R45, R46, R11, R36/38,R48/23/24/25, R65

S-phrases S53, S45

NFPA 704

Flash point −11.63 °C, 262 K

Related compounds

Related compounds •• toluene•• borazine

  (verify) [13] (what is:  / ?)Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)

Infobox references

Benzene is an organic chemical compound with the molecular formula C6H6. Its molecule is composed of 6 carbonatoms joined in a ring, with 1 hydrogen atom attached to each carbon atom. Because its molecules contain onlycarbon and hydrogen atoms, benzene is classed as a hydrocarbon.Benzene is a natural constituent of crude oil, and is one of the most basic petrochemicals. Benzene is an aromatichydrocarbon and the second [n]-annulene ([6]-annulene), a cyclic hydrocarbon with a continuous pi bond. It issometimes abbreviated Ph–H. Benzene is a colorless and highly flammable liquid with a sweet smell. It is mainlyused as a precursor to heavy chemicals, such as ethylbenzene and cumene, which are produced on a billion kilogramscale. Because it has a high octane number, it is an important component of gasoline, composing a few percent of itsmass. Most non-industrial applications have been limited by benzene's carcinogenicity.

History

DiscoveryThe word "benzene" derives historically from "gum benzoin", sometimes called "benjamin" (i.e., benzoin resin), anaromatic resin known to European pharmacists and perfumers since the 15th century as a product of southeast Asia."Benzoin" is itself a corruption of the Arabic expression "luban jawi", or "frankincense of Java". An acidic materialwas derived from benzoin by sublimation, and named "flowers of benzoin", or benzoic acid. The hydrocarbonderived from benzoic acid thus acquired the name benzin, benzol, or benzene.[14]

Michael Faraday first isolated and identified benzene in 1825 from the oily residue derived from the production ofilluminating gas, giving it the name bicarburet of hydrogen.[15][16]

In 1833, Eilhard Mitscherlich produced it via the distillation of benzoic acid (from gum benzoin) and lime. He gavethe compound the name benzin.[17]

In 1836, the French chemist Auguste Laurent named the substance "phène";[18] this is the root of the word phenol,which is hydroxylated benzene, and phenyl, which is the radical formed by abstraction of a hydrogen atom (freeradical H•) from benzene.

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Historic benzene formulae as proposed by Kekulé.[19]

In 1845, Charles Mansfield, working underAugust Wilhelm von Hofmann, isolatedbenzene from coal tar.[20] Four years later,Mansfield began the first industrial-scaleproduction of benzene, based on the coal-tarmethod.[21][22] Gradually the sensedeveloped among chemists that substancesrelated to benzene represent a diversechemical family. In 1855 August Wilhelm

Hofmann used the word "aromatic" to designate this family relationship, after a characteristic property of many of itsmembers.[23]

Ring formulaThe empirical formula for benzene was long known, but its highly polyunsaturated structure, with just one hydrogenatom for each carbon atom, was challenging to determine. Archibald Scott Couper in 1858 and Joseph Loschmidt in1861[24] suggested possible structures that contained multiple double bonds or multiple rings, but too little evidencewas then available to help chemists decide on any particular structure.In 1865, the German chemist Friedrich August Kekulé published a paper in French (for he was then teaching inFrancophone Belgium) suggesting that the structure contained a six-membered ring of carbon atoms with alternatingsingle and double bonds. The next year he published a much longer paper in German on the same subject.[25][26]

Kekulé used evidence that had accumulated in the intervening years—namely, that there always appeared to be onlyone isomer of any monoderivative of benzene, and that there always appeared to be exactly three isomers of everydiderivative—now understood to correspond to the ortho, meta, and para patterns of arene substitution—to argue insupport of his proposed structure. Kekulé's symmetrical ring could explain these curious facts, as well as benzene's1:1 carbon-hydrogen ratio.[27]

Historic benzene formulae (from left to right) by Claus (1867),[28] Dewar (1867),[29]

Ladenburg (1869),[30] Armstrong (1887),[31] Thiele (1899)[32] and Kekulé (1865).Dewar benzene and prismane are different chemicals that have Dewar's and Ladenburg's

structures. Thiele and Kekulé's structures are used today.

The new understanding of benzene,and hence of all aromatic compounds,proved to be so important for both pureand applied chemistry that in 1890 theGerman Chemical Society organizedan elaborate appreciation in Kekulé'shonor, celebrating the twenty-fifthanniversary of his first benzene paper.

Here Kekulé spoke of the creation of the theory. He said that he had discovered the ring shape of the benzenemolecule after having a reverie or day-dream of a snake seizing its own tail (this is a common symbol in manyancient cultures known as the Ouroboros or Endless knot). This vision, he said, came to him after years of studyingthe nature of carbon-carbon bonds. This was 7 years after he had solved the problem of how carbon atoms couldbond to up to four other atoms at the same time. It is curious that a similar, humorous depiction of benzene hadappeared in 1886 in the Berichte der Durstigen Chemischen Gesellschaft (Journal of the Thirsty Chemical Society),a parody of the Berichte der Deutschen Chemischen Gesellschaft, only the parody had monkeys seizing each other ina circle, rather than snakes as in Kekulé's anecdote.[33] Some historians have suggested that the parody was alampoon of the snake anecdote, possibly already well known through oral transmission even if it had not yetappeared in print.[14] Others have speculated that Kekulé's story in 1890 was a re-parody of the monkey spoof, andwas a mere invention rather than a recollection of an event in his life. Kekulé's 1890 speech[34] in which theseanecdotes appeared has been translated into English.[35] If one takes the anecdote as the memory of a real event,circumstances mentioned in the story suggest that it must have happened early in 1862.[36]

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The cyclic nature of benzene was finally confirmed by the crystallographer Kathleen Lonsdale in 1929.[37][38]

Early applicationsIn the 19th and early-20th centuries, benzene was used as an after-shave lotion because of its pleasant smell. Prior tothe 1920s, benzene was frequently used as an industrial solvent, especially for degreasing metal. As its toxicitybecame obvious, benzene was supplanted by other solvents, especially toluene (methyl benzene), which has similarphysical properties but is not as carcinogenic.

Frozen benzene

In 1903, Ludwig Roselius popularized the use of benzene todecaffeinate coffee. This discovery led to the production of Sanka(Sanka = sans caféine = without caffeine). This process was laterdiscontinued. Benzene was historically used as a significant componentin many consumer products such as Liquid Wrench, several paintstrippers, rubber cements, spot removers and otherhydrocarbon-containing products. Some ceased manufacture of theirbenzene-containing formulations in about 1950, while others continuedto use benzene as a component or significant contaminant until the late1970s when leukemia deaths were found associated with Goodyear'sPliofilm production operations in Ohio. Until the late 1970s, manyhardware stores, paint stores, and other retail outlets sold benzene in small cans, such as quart size, forgeneral-purpose use. Many students were exposed to benzene in school and university courses while performinglaboratory experiments with little or no ventilation in many cases. This very dangerous practice has been almosttotally eliminated.

StructureBenzene represents a special problem in that, to account for all the bonds, there must be alternating double carbonbonds:[39]

The various representations of benzene

X-ray diffraction shows that all of six carbon-carbon bonds in benzeneare of the same length of 140 picometres (pm). The C–C bond lengthsare greater than a double bond (135 pm) but shorter than a single bond(147 pm). This intermediate distance is consistent with electrondelocalization: the electrons for C–C bonding are distributed equallybetween each of the six carbon atoms. Benzene has 8 hydrogen atomsfewer than the corresponding parent alkane, hexane. The molecule isplanar.[40] One representation is that the structure exists as asuperposition of so-called resonance structures, rather than either form

individually. The delocalization of electrons is one explanation for the thermodynamic stability of benzene andrelated aromatic compounds. It is likely that this stability contributes to the peculiar molecular and chemicalproperties known as aromaticity. To indicate the delocalized nature of the bonding, benzene is often depicted with acircle inside a hexagonal arrangement of carbon atoms.

The delocalized picture of benzene has been contested by Cooper, Gerratt and Raimondi in their article published in1986 in the journal Nature. They showed that the electrons in benzene are almost certainly localized, and thearomatic properties of benzene originate from spin coupling rather than electron delocalization.[41] This view hasbeen supported in the next-year Nature issue,[42][43][44] but it has been slow to permeate the general chemistrycommunity.

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As is common in organic chemistry, the carbon atoms in the diagram above have been left unlabeled. Realizing eachcarbon has 2p electrons, each carbon donates an electron into the delocalized ring above and below the benzene ring.It is the side-on overlap of p-orbitals that produces the pi clouds.Derivatives of benzene occur sufficiently often as a component of organic molecules that there is a Unicode symbolin the Miscellaneous Technical block with the code U+232C (⌬) to represent it with three double bonds,[45] andU+23E3 (⏣) for a delocalized version.[46]

Benzene derivativesMany important chemical compounds are derived from benzene by replacing one or more of its hydrogen atoms withanother functional group. Examples of simple benzene derivatives are phenol, toluene, and aniline, abbreviatedPhOH, PhMe, and PhNH2, respectively. Linking benzene rings gives biphenyl, C6H5–C6H5. Further loss ofhydrogen gives "fused" aromatic hydrocarbons, such as naphthalene and anthracene. The limit of the fusion processis the hydrogen-free allotrope of carbon, graphite.In heterocycles, carbon atoms in the benzene ring are replaced with other elements. The most important derivativesare the rings containing nitrogen. Replacing one CH with N gives the compound pyridine, C5H5N. Althoughbenzene and pyridine are structurally related, benzene cannot be converted into pyridine. Replacement of a secondCH bond with N gives, depending on the location of the second N, pyridazine, pyrimidine, and pyrazine.

ProductionFour chemical processes contribute to industrial benzene production: catalytic reforming, toluene hydrodealkylation,toluene disproportionation, and steam cracking. According to the ATSDR Toxicological Profile for benzene,between 1978 and 1981, catalytic reformats accounted for approximately 44–50% of the total U.S benzeneproduction.Until World War II, most benzene was produced as a by-product of coke production (or "coke-oven light oil") in thesteel industry. However, in the 1950s, increased demand for benzene, especially from the growing polymersindustry, necessitated the production of benzene from petroleum. Today, most benzene comes from thepetrochemical industry, with only a small fraction being produced from coal.

Catalytic reformingIn catalytic reforming, a mixture of hydrocarbons with boiling points between 60–200 °C is blended with hydrogengas and then exposed to a bifunctional platinum chloride or rhenium chloride catalyst at 500–525 °C and pressuresranging from 8–50 atm. Under these conditions, aliphatic hydrocarbons form rings and lose hydrogen to becomearomatic hydrocarbons. The aromatic products of the reaction are then separated from the reaction mixture (orreformate) by extraction with any one of a number of solvents, including diethylene glycol or sulfolane, and benzeneis then separated from the other aromatics by distillation. The extraction step of aromatics from the reformate isdesigned to produce aromatics with lowest non-aromatic components. Recovery of the aromatics, commonly referredto as BTX (benzene, toluene and xylene isomers), involves such extraction and distillation steps. There are a goodmany licensed processes available for extraction of the aromatics.In similar fashion to this catalytic reforming, UOP and BP commercialized a method from LPG (mainly propane andbutane) to aromatics.

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Toluene hydrodealkylationToluene hydrodealkylation converts toluene to benzene. In this hydrogen-intensive process, toluene is mixed withhydrogen, then passed over a chromium, molybdenum, or platinum oxide catalyst at 500–600 °C and 40–60 atmpressure. Sometimes, higher temperatures are used instead of a catalyst (at the similar reaction condition). Underthese conditions, toluene undergoes dealkylation to benzene and methane:

C6H5CH3 + H2 → C6H6 + CH4This irreversible reaction is accompanied by an equilibrium side reaction that produces biphenyl (aka diphenyl) athigher temperature:

2 C6H6 H2 + C6H5–C6H5If the raw material stream contains much non-aromatic components (paraffins or naphthenes), those are likelydecomposed to lower hydrocarbons such as methane, which increases the consumption of hydrogen.A typical reaction yield exceeds 95%. Sometimes, xylenes and heavier aromatics are used in place of toluene, withsimilar efficiency.This is often called "on-purpose" methodology to produce benzene, compared to conventional BTX(benzene-toluene-xylene) extraction processes.

Toluene disproportionationWhere a chemical complex has similar demands for both benzene and xylene, then toluene disproportionation (TDP)may be an attractive alternative to the toluene hydrodealkylation. In the broad sense, 2 toluene molecules are reactedand the methyl groups rearranged from one toluene molecule to the other, yielding one benzene molecule and onexylene molecule.Given that demand for para-xylene (p-xylene) substantially exceeds demand for other xylene isomers, a refinementof the TDP process called Selective TDP (STDP) may be used. In this process, the xylene stream exiting the TDPunit is approximately 90% paraxylene. In some current catalytic systems, even the benzene-to-xylenes ratio isdecreased (more xylenes) when the demand of xylenes is higher.

Steam crackingSteam cracking is the process for producing ethylene and other alkenes from aliphatic hydrocarbons. Depending onthe feedstock used to produce the olefins, steam cracking can produce a benzene-rich liquid by-product calledpyrolysis gasoline. Pyrolysis gasoline can be blended with other hydrocarbons as a gasoline additive, or routedthrough an extraction process to recover BTX aromatics (benzene, toluene and xylenes).

Other sourcesTrace amounts of benzene may result whenever carbon-rich materials undergo incomplete combustion. It isproduced in volcanoes and forest fires, and is also a component of cigarette smoke. Benzene is a principal productfrom the combustion of PVC (polyvinyl chloride).

UsesBenzene is used mainly as an intermediate to make other chemicals. About 80% of benzene is consumed in theproduction of three chemicals, ethylbenzene, cumene, and cyclohexane. Its most widely produced derivative isethylbenzene, precursor to styrene, which is used to make polymers and plastics. Cumene is converted phenol forresins and adhesives. Cyclohexane is used in the manufacture of Nylon. Smaller amounts of benzene are used tomake some types of rubbers, lubricants, dyes, detergents, drugs, explosives, and pesticides.

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In both the US and Europe, 50% of benzene is used in the production of ethylbenzene/styrene, 20% is used in theproduction of cumene, and about 15% of benzene is used in the production of cyclohexane (eventually to nylon).Currently, the production of and demand for benzene in the Middle East register the greatest increases worldwide. Itwill probably see its share of the global supply and demand expand by 3.7 and 3.3 percentage points, respectively,until 2018. However, the Asia-Pacific region will continue to dominate the market and account for almost half of theglobal demand.[47]

In laboratory research, toluene is now often used as a substitute for benzene. The solvent-properties of the two aresimilar, but toluene is less toxic and has a wider liquid range.

Major commodity chemicals and polymers derived from benzene. Clicking on the image loads the appropriate article

Component of gasolineAs a gasoline (petrol) additive, benzene increases the octane rating and reduces knocking. As a consequence,gasoline often contained several percent benzene before the 1950s, when tetraethyl lead replaced it as the mostwidely used antiknock additive. With the global phaseout of leaded gasoline, benzene has made a comeback as agasoline additive in some nations. In the United States, concern over its negative health effects and the possibility ofbenzene's entering the groundwater have led to stringent regulation of gasoline's benzene content, with limitstypically around 1%.[48] European petrol specifications now contain the same 1% limit on benzene content. TheUnited States Environmental Protection Agency introduced new regulations in 2011 that lowered the benzenecontent in gasoline to 0.62%.[49]

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ReactionsThe most common reactions of benzene involve substitution of a proton by other groups.[50] Electrophilic aromaticsubstitution is a general method of derivatizing benzene. Benzene is sufficiently nucleophilic that it undergoessubstitution by acylium ions and alkyl carbocations to give substituted derivatives.

Electrophilic aromatic substitution of benzene

The most widely practiced example of this reaction is the ethylation of benzene.

Approximately 24,700,000 tons were produced in 1999.[51] Highly instructive but of far less industrial significance isthe Friedel-Crafts alkylation of benzene (and many other aromatic rings) using an alkyl halide in the presence of astrong Lewis acid catalyst. Similarly, the Friedel-Crafts acylation is a related example of electrophilic aromaticsubstitution. The reaction involves the acylation of benzene (or many other aromatic rings) with an acyl chlorideusing a strong Lewis acid catalyst such as aluminium chloride or Iron(III) chloride.

Friedel-Crafts acylation of benzene by acetyl chloride

Sulfonation, chlorination, nitrationUsing electrophilic aromatic substitution, many functional groups are introduced onto the benzene framework.Sulfonation of benzene involves the use of oleum, a mixture of sulfuric acid with sulfur trioxide. Sulfonated benzenederivatives are useful detergents. In nitration, benzene reacts with nitronium ions (NO2

+), which is a strongelectrophile produced by combining sulfuric and nitric acids. Nitrobenzene is the precursor to aniline. Chlorinationin achieved with chlorine to give chlorobenzene.

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HydrogenationVia hydrogenation, benzene and its derivatives convert to cyclohexane and derivatives. This reaction is achieved bythe use of high pressures of hydrogen at high temperatures in the presence of a finely divided nickel, which serves asa catalyst. In the absence of the catalyst, benzene is impervious to hydrogen. This reaction is practiced on a verylarge scale industrially.

Metal complexesBenzene is an excellent ligand in the organometallic chemistry of low-valent metals. Important examples include thesandwich and half-sandwich complexes, respectively, Cr(C6H6)2 and [RuCl2(C6H6)]2.

Health effects

A bottle of benzene. The warnings show benzeneis a toxic and flammable liquid.

Benzene increases the risk of cancer and other illnesses. Benzene is anotorious cause of bone marrow failure. Substantial quantities ofepidemiologic, clinical, and laboratory data link benzene to aplasticanemia, acute leukemia, and bone marrow abnormalities.[52][53] Thespecific hematologic malignancies that benzene is associated withinclude: acute myeloid leukemia (AML), aplastic anemia,myleodysplastic syndrome (MDS), acute lymphoblastic leukemia(ALL), and chronic myeloid leukemia (CML).[54]

The American Petroleum Institute (API) stated in 1948 that "it isgenerally considered that the only absolutely safe concentration forbenzene is zero."[55] The US Department of Health and HumanServices (DHHS) classifies benzene as a human carcinogen. Long-termexposure to excessive levels of benzene in the air causes leukemia, apotentially fatal cancer of the blood-forming organs, in susceptibleindividuals. In particular, Acute myeloid leukemia or acutenon-lymphocytic leukaemia (AML & ANLL) is not disputed to becaused by benzene.[56] IARC rated benzene as "known to becarcinogenic to humans" (Group 1).

Human exposure to benzene is a global health problem. Benzene targets liver, kidney, lung, heart and the brain andcan cause DNA strand breaks, chromosomal damage, etc. Benzene causes cancer in both animals and humans.Benzene has been shown to cause cancer in both sexes of multiple species of laboratory animals exposed via variousroutes.[57][58]

Some women who inhaled high levels of benzene for many months had irregular menstrual periods and a decrease inthe size of their ovaries. Benzene exposure has been linked directly to the neural birth defects spina bifida andanencephaly.[59] Men exposed to high levels of benzene are more likely to have an abnormal amount ofchromosomes in their sperm, which impacts fertility and fetal development.[60]

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Exposure to benzene

Light refraction of benzene (above) and water(below)

Vapors from products that contain benzene, such as glues, paints,furniture wax, and detergents, can also be a source of exposure,although many of these have been modified or reformulated since thelate 1970s to eliminate or reduce the benzene content. Air aroundhazardous waste sites or gas stations may contain higher levels ofbenzene. Because petroleum hydrocarbon products are complexmixtures of chemicals, risk assessments for these products, in general,focus on specific toxic constituents. The petroleum constituents ofprimary interest to human health have been the aromatic hydrocarbons(i.e., benzene, ethylbenzene, toluene, and xylenes). In the U.S., OSHArequires that a mixture "shall be assumed to present a carcinogenichazard if it contains a component in concentrations of 0.1% or greater,which is considered to be a carcinogen.[61][62]

Outdoor air may contain low levels of benzene from automobileservice stations, wood smoke, tobacco smoke, the transfer of gasoline,exhaust from motor vehicles, and industrial emissions.[63] About 50%of the entire nationwide (United States) exposure to benzene resultsfrom smoking tobacco or from exposure to tobacco smoke.[64]

InhalationInhaled benzene is primarily expelled unchanged through exhalation. In a human study 16.4 to 41.6% of retainedbenzene was eliminated through the lungs within five to seven hours after a two- to three-hour exposure to 47 to 110ppm and only 0.07 to 0.2% of the remaining benzene was excreted unchanged in the urine. After exposure to 63 to405 mg/m3 of benzene for 1 to 5 hours, 51 to 87% was excreted in the urine as phenol over a period of 23 to 50hours. In another human study, 30% of absorbed dermally applied benzene, which is primarily metabolized in theliver, was excreted as phenol in the urine.[65]

Exposure through smokingExposure of the general population to benzene occurs mainly through breathing, the major sources of benzene beingtobacco smoke (about 50%) as well as automobile service stations, exhaust from motor vehicles and industrialemissions (about 20% altogether). The average smoker (32 cigarettes per day) takes in about 1.8 milligrams (mg) ofbenzene per day. This amount is about 10 times the average daily intake of benzene by nonsmokers.[66]

Exposure from soft drinksIn March 2006, the official Food Standards Agency in Britain conducted a survey of 150 brands of soft drinks. Itfound that four contained benzene levels above World Health Organization limits. The affected batches wereremoved from sale.[67] (See also benzene in soft drinks).

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Case examplesWater and soil contamination are important pathways of concern for transmission of benzene. In the US alone,approximately 100,000 sites have soil or groundwater contaminated with benzene.In 2005, the water supply to the city of Harbin in China with a population of almost nine million people, was cut offbecause of a major benzene exposure. Benzene leaked into the Songhua River, which supplies drinking water to thecity, after an explosion at a China National Petroleum Corporation (CNPC) factory in the city of Jilin on 13November.

Benzene exposure limitsThe United States Environmental Protection Agency has set a maximum contaminant level (MCL) for benzene indrinking water at 0.005 mg/L (5 ppb), as promulgated via the U.S. National Primary Drinking Water Regulations.[68]

This regulation is based on preventing benzene leukemogenesis. The maximum contaminant level goal (MCLG), anonenforceable health goal that would allow an adequate margin of safety for the prevention of adverse effects, iszero benzene concentration in drinking water. The EPA requires that spills or accidental releases into theenvironment of 10 pounds (4.5 kg) or more of benzene be reported.The U.S. Occupational Safety and Health Administration (OSHA) has set a permissible exposure limit of 1 part ofbenzene per million parts of air (1 ppm) in the workplace during an 8-hour workday, 40-hour workweek. The shortterm exposure limit for airborne benzene is 5 ppm for 15 minutes.[69] These legal limits were based on studiesdemonstrating compelling evidence of health risk to workers exposed to benzene. The risk from exposure to 1 ppmfor a working lifetime has been estimated as 5 excess leukemia deaths per 1,000 employees exposed. (This estimateassumes no threshold for benzene's carcinogenic effects.) OSHA has also established an action level of 0.5 ppm toencourage even lower exposures in the workplace.[70]

The U.S. National Institute for Occupational Safety and Health (NIOSH) revised the Immediately Dangerous to Lifeor Health (IDLH) concentration for benzene to 500 ppm. The current NIOSH definition for an IDLH condition, asgiven in the NIOSH Respirator Selection Logic, is one that poses a threat of exposure to airborne contaminants whenthat exposure is likely to cause death or immediate or delayed permanent adverse health effects or prevent escapefrom such an environment [NIOSH 2004]. The purpose of establishing an IDLH value is (1) to ensure that theworker can escape from a given contaminated environment in the event of failure of the respiratory protectionequipment and (2) is considered a maximum level above which only a highly reliable breathing apparatus providingmaximum worker protection is permitted [NIOSH 2004[71]].[72] In September 1995, NIOSH issued a new policy fordeveloping recommended exposure limits (RELs) for substances, including carcinogens. Because benzene can causecancer, NIOSH recommends that all workers wear special breathing equipment when they are likely to be exposed tobenzene at levels exceeding the REL (10-hour) of 0.1 ppm.[73] The NIOSH STEL (15 min) is 1 ppm.American Conference of Governmental Industrial Hygienists (ACGIH) adopted Threshold Limit Values (TLVs) forbenzene at 0.5 ppm TWA and 2.5 ppm STEL.

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Exposure monitoringAirborne exposure monitoring for benzene must be conducted in order to properly assess personal exposures andeffectiveness of engineering controls. Initial exposure monitoring should be conducted by an industrial hygienist orperson specifically trained and experienced in sampling techniques. Contact an AIHA Accredited Laboratory foradvice on sampling methods.[74]

Each employer with a place of employment where occupational exposures to benzene occur shall monitor each ofthese workplaces and work operations to determine accurately the airborne concentrations of benzene to whichemployees may be exposed.[75] Representative 8-hour TWA employee exposures need to be determined on the basisof one sample or samples representing the full shift exposure for each job classification in each work area. Unless airsamples are taken frequently, the employer does not know the concentration and would not know how much of aprotection factor is needed.[76]

In providing consultation on work safety during oil clean-up operations following the Deepwater Horizon accident,OSHA has worked with a number of other government agencies to protect Gulf cleanup workers. OSHA partneredwith the NIOSH to issue "Interim Guidance for Protecting Deepwater Horizon Response Workers and Volunteers"and recommend measures that should be taken to protect workers from a variety of different health hazards that theseworkers face.[77] OSHA conceded that it recognizes that most of its PELs are outdated and inadequate measures ofworker safety. In characterizing worker exposure, OSHA instead relies on more up-to-date recommended protectivelimits set by organizations such as NIOSH, the ACGIH, and the American Industrial Hygiene Association (AIHA),and not on the older, less protective PELS. Results of air monitoring are compared to the lowest known OccupationalExposure Limit for the listed contaminant for purposes of risk assessment and protective equipmentrecommendations.[78]

Biomarkers of exposureSeveral tests can determine exposure to benzene. Benzene itself can be measured in breath, blood or urine, but suchtesting is usually limited to the first 24 hours post-exposure due to the relatively rapid removal of the chemical byexhalation or biotransformation. Most persons in developed countries have measureable baseline levels of benzeneand other aromatic petroleum hydrocarbons in their blood. In the body, benzene is enzymatically converted to aseries of oxidation products including muconic acid, phenylmercapturic acid, phenol, catechol, hydroquinone and1,2,4-trihydroxybenzene. Most of these metabolites have some value as biomarkers of human exposure, since theyaccumulate in the urine in proportion to the extent and duration of exposure, and they may still be present for somedays after exposure has ceased. The current ACGIH biological exposure limits for occupational exposure are 500μg/g creatinine for muconic acid and 25 μg/g creatinine for phenylmercapturic acid in an end-of-shift urinespecimen.[79][80][81][82]

BiotransformationsEven if it is not a common substrate for the metabolism of organisms, benzene can be oxidized by both bacteria andeukaryotes. In bacteria, dioxygenase enzyme can add an oxygen molecule to the ring, and the unstable product isimmediately reduced (by NADH) to a cyclic diol with two double bonds, breaking the aromaticity. Next, the diol isnewly reduced by NADH to catechol. The catechol is then metabolized to acetyl CoA and succinyl CoA, used byorganisms mainly in the Krebs Cycle for energy production.The pathway for the metabolism of benzene is complex and begins in the liver. Several key enzymes are involved. These include cytochrome P450 2E1 (CYP2E1), quinine oxidoreductase (NQ01), GSH, and myeloperoxidase (MPO). CYP2E1 is involved at multiple steps: converting benzene to oxepin (benzene oxide), phenol to hydroquinone, and hydroquinone to both benzenetriol and catechol. Hydroquinone, benzenetriol and catechol are converted to polyphenols. In the bone marrow, MPO converts these polyphenols to benzoquinones. These intermediates and metabolites induce genotoxicity by multiple mechanisms including inhibition of topoisomerase II

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(which maintains chromosome structure), disruption of microtubules (which maintains cellular structure andorganization), generation of oxygen free radicals (unstable species) that may lead to point mutations, increasingoxidative stress, inducing DNA strand breaks, and altering DNA methylation (which can affect gene expression).NQ01 and GSH shift metabolism away from toxicity. NQ01 metabolizes benzoquinone toward polyphenols(counteracting the effect of MPO). GSH is involved with the formation of phenylmercapturic acid.[54][83]

Genetic polymorphisms in these enzymes may induce loss of function or gain of function. For example, mutations inCYP2E1 increase activity and result in increased generation of toxic metabolites. NQ01 mutations result in loss offunction and may result in decreased detoxification. Myeloperoxidase mutations result in loss of function and mayresult in decreased generation of toxic metabolites. GSH mutations or deletions result in loss of function and result indecreased detoxification. These genes may be targets for genetic screening for susceptibility to benzene toxicity.[84]

Molecular toxicologyThe paradigm of toxicological assessment of benzene is shifting towards the domain of molecular toxicology as itallows understanding of fundamental biological mechanisms in a better way. Glutathione seems to play an importantrole by protecting against benzene-induced DNA breaks and it is being identified as a new biomarker for exposureand effect.[85] Benzene causes chromosomal aberrations in the peripheral blood leukocytes and bone marrowexplaining the higher incidence of leukemia and multiple myeloma caused by chronic exposure. These aberrationscan be monitored using fluorescent in situ hybridization (FISH) with DNA probes to assess the effects of benzenealong with the hematological tests as markers of hematotoxicity.[86] Benzene metabolism involves enzymes codedfor by polymorphic genes. Studies have shown that genotype at these loci may influence susceptibility to the toxiceffects of benzene exposure. Individuals carrying variant of NAD(P)H:quinone oxidoreductase 1 (NQO1),microsomal epoxide hydrolase (EPHX) and deletion of the glutathione S-transferase T1 (GSTT1) showed a greaterfrequency of DNA single-stranded breaks.[87]

Biological oxidation and carcinogenic activityOne way of understanding the carcinogenic effects of benzene is by examining the products of biological oxidation.Pure benzene, for example, oxidizes in the body to produce an epoxide, benzene oxide, which is not excreted readilyand can interact with DNA to produce harmful mutations.

SummaryAccording to the Agency for Toxic Substances and Disease Registry (ATSDR) (2007), benzene is both ananthropogenically produced and naturally occurring chemical from processes that include: volcanic eruptions, wildfires, synthesis of chemicals such as phenol, production of synthetic fibers, and fabrication of rubbers, lubricants,pesticides, medications, and dyes. The major sources of benzene exposure are tobacco smoke, automobile servicestations, exhaust from motor vehicles, and industrial emissions; however, ingestion and dermal absorption ofbenzene can also occur through contact with contaminated water. Benzene is hepatically metabolized and excreted inthe urine. Measurement of air and water levels of benzene is accomplished through collection via activated charcoaltubes, which are then analyzed with a gas chromatograph. The measurement of benzene in humans can beaccomplished via urine, blood, and breath tests; however, all of these have their limitations because benzene israpidly metabolized in the human body into by-products called metabolites.[88]

OSHA regulates levels of benzene in the workplace.[89] The maximum allowable amount of benzene in workroomair during an 8-hour workday, 40-hour workweek is 1 ppm. Because benzene can cause cancer, NIOSH recommendsthat all workers wear special breathing equipment when they are likely to be exposed to benzene at levels exceedingthe recommended (8-hour) exposure limit of 0.1 ppm.[90]

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References[1] http:/ / www. commonchemistry. org/ ChemicalDetail. aspx?ref=71-43-2[2] http:/ / pubchem. ncbi. nlm. nih. gov/ summary/ summary. cgi?cid=241[3] http:/ / www. chemspider. com/ 236[4] http:/ / fdasis. nlm. nih. gov/ srs/ srsdirect. jsp?regno=J64922108F[5] http:/ / www. kegg. jp/ entry/ C01407[6] https:/ / www. ebi. ac. uk/ chebi/ searchId. do?chebiId=16716[7] https:/ / www. ebi. ac. uk/ chembldb/ index. php/ compound/ inspect/ CHEMBL277500[8] http:/ / chemapps. stolaf. edu/ jmol/ jmol. php?model=c1ccccc1[9] Lide, D. R., ed. (2005). CRC Handbook of Chemistry and Physics (86th ed.). Boca Raton (FL): CRC Press. ISBN 0-8493-0486-5.[10] Arnold, D.; Plank, C.; Erickson, E.; Pike, F. (1958). "Solubility of Benzene in Water". Industrial & Engineering Chemistry Chemical &

Engineering Data Series 3 (2): 253. doi:10.1021/i460004a016.[11] Breslow, R.; Guo, T. (1990). "Surface tension measurements show that chaotropic salting-in denaturants are not just water-structure

breakers". Proceedings of the National Academy of Sciences of the United States of America 87 (1): 167–9. Bibcode 1990PNAS...87..167B.doi:10.1073/pnas.87.1.167. PMC 53221. PMID 2153285.

[12] Coker, A. Kayode; Ludwig, Ernest E. (2007). Ludwig's Applied Process Design for Chemical And Petrochemical Plants (http:/ / books.google. com/ books?id=N8RcH8juG_YC& pg=PA114). 1. Elsevier. p. 114. ISBN 0-7506-7766-X. . Retrieved 2012-05-31.

[13] http:/ / en. wikipedia. org/ wiki/ Special%3Acomparepages?rev1=464365162& page2=%3ABenzene[14] Rocke, A. J. (1985). "Hypothesis and Experiment in the Early Development of Kekule's Benzene Theory". Annals of Science 42 (4):

355–81. doi:10.1080/00033798500200411.[15] Faraday, M. (1825). " On New Compounds of Carbon and Hydrogen, and on Certain Other Products Obtained during the Decomposition of

Oil by Heat (http:/ / gallica. bnf. fr/ ark:/ 12148/ bpt6k559209/ f473. image)". Philosophical Transactions of the Royal Society of London 115:440–466. doi:10.1098/rstl.1825.0022. JSTOR 107752.

[16] R. Kaiser (1968). "Bicarburet of Hydrogen. Reappraisal of the Discovery of Benzene in 1825 with the Analytical Methods of 1968".Angewandte Chemie International Edition in English 7 (5): 345–350. doi:10.1002/anie.196803451.

[17] Mitscherlich, E. (1834). " Über das Benzol und die Säuren der Oel- und Talgarten (http:/ / books. google. com/books?id=JEs9AAAAcAAJ& pg=PA39#v=onepage& q& f=false) (On benzol and oily and fatty types of acids)". Annalen der Pharmacie 9(1): 39–48. doi:10.1002/jlac.18340090103. In a footnote on page 43, Liebig, the journal's editor, suggested changing Mitscherlich's originalname for benzene (namely, "benzin") to "benzol", because the suffix "-in" suggested that it was an alkaloid (e.g., Chinin (quinine)), whichbenzene isn't, whereas the suffix "-ol" suggested that it was oily, which benzene is. Thus on page 44, Mitscherlich states: Da diese Flüssigkeitaus der Benzoësäure gewonnen wird, und wahrscheinlich mit den Benzoylverbindungen im Zusammenhang steht, so gibt man ihr am bestenden Namen Benzol, da der Name Benzoïn schon für die mit dem Bittermandelöl isomerische Verbindung von Liebig und Wöhler gewähltworden ist. (Since this liquid [benzene] is obtained from benzoic acid and probably is related to benzoyl compounds, the best name for it is"benzol", since the name "benzoïn" has already been chosen, by Liebig and Wöhler, for the compound that's isomeric with the oil of bitteralmonds [benzaldehyde].)

[18] Auguste Laurent (1836) "Sur la chlorophénise et les acides chlorophénisique et chlorophénèsique," Annales de Chemie et de Physique, vol.63, pp. 27–45, see p. 44 (http:/ / books. google. com/ books?id=Lx0AAAAAMAAJ& pg=PA44): Je donne le nom de phène au radicalfondamental des acides précédens (φαινω, j'éclaire), puisque la benzine se trouve dans le gaz de l'éclairage. (I give the name of "phène"(φαινω, I illuminate) to the fundamental radical of the preceding acid, because benzene is found in illuminating gas.)

[19] August Kekulé (1872). "Ueber einige Condensationsproducte des Aldehyds". Liebigs Ann. Chem. 162 (1): 77–124.doi:10.1002/jlac.18721620110.

[20] Hofmann, A. W. (1845) "Ueber eine sichere Reaction auf Benzol" (http:/ / books. google. com/ books?id=E-1AAAAAYAAJ& pg=PA200)(On a reliable test for benzene), Annalen der Chemie und Pharmacie, vol. 55, pp. 200–205; on pp. 204–205, Hofmann found benzene in coaltar oil.

[21] Mansfield, Charles Blachford (1849) "Untersuchung des Steinkohlentheers" (http:/ / books. google. com/ books?id=kD4aAQAAMAAJ&pg=PA162) (Investigation of coal tar), Annalen der Chemie und Pharmacie, vol. 69, pp. 162–180.

[22][22] Charles Mansfield filed for (November 11, 1847) and received (May 1848) a patent (no. 11,960) for the fractional distillation of coal tar.[23] Augustus W. Hoffman (1856) "On insolinic acid," (http:/ / rspl. royalsocietypublishing. org/ content/ 8/ 1. full. pdf+ html) Proceedings of

the Royal Society of London, vol. 8, pages 1–3. On page 3, Hoffmann states: "The existence and mode of formation of insolinic acid prove thatto the series of monobasic aromatic acids, Cn2Hn2-8O4, the lowest known term of which is benzoic acid, ...." [Note: The empirical formulas oforganic compounds that appear in Hoffmann's article are wrong because he uses the incorrect atomic masses of carbon (6 instead of 12) andoxygen (8 instead of 16).]

[24] J. Loschmidt, Chemische Studien (Vienna, Austria-Hungary: Carl Gerold's Sohn, 1861), pp. 30, 65 (http:/ / books. google. com/books?id=ksw5AAAAcAAJ& pg=PA30).

[25] Kekulé, F. A. (1865). "Sur la constitution des substances aromatiques" (http:/ / books. google. com/ books?id=bFsSAAAAYAAJ&pg=PA98). Bulletin de la Societe Chimique de Paris 3: 98–110. . On p. 100, Kekulé suggests that the carbon atoms of benzene could form a"chaîne fermée" (a closed chain, a loop).

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[26] Kekulé, F. A. (1866). "Untersuchungen über aromatische Verbindungen (http:/ / books. google. com/ books?id=pNryAAAAMAAJ&lpg=PA129) (Investigations of aromatic compounds)"]. Liebigs Annalen der Chemie und Pharmacie 137 (2): 129–36.doi:10.1002/jlac.18661370202. .

[27] Critics pointed out a problem with Kekulé's original (1865/1867) structure for benzene: Whenever benzene underwent substitution at theortho position, two distinguishable isomers should have resulted, depending on whether the double bond at the ortho position extendedclockwise or counterclockwise; however, no such isomers were observed. In 1872, Kekulé suggested that benzene had two complementarystructures and that these forms rapidly interconverted, so that if there were a double bond between any pair of carbon atoms at one instant, thatdouble bond would become a single bond at the next instant (and vice-versa). To provide a mechanism for the conversion process, Kekuléproposed that the valency of an atom is determined by the frequency with which it collided with its neighbors in a molecule. As the carbonatoms in the benzene ring collided with each other, each carbon atom would collide twice with one neighbor during a given interval and thentwice with its other neighbor during the next interval. Thus, a double bond would exist with one neighbor during the first interval and the otherneighbor during the next interval. See pages 86–89 (http:/ / de. wikipedia. org/ w/ index.php?title=Datei:Kekule_-_Ueber_einige_Condensationsproducte_des_Aldehyds. pdf& page=10) of Auguste Kekulé (1872) "Ueber einigeCondensationsprodukte des Aldehyds" (On some condensation products of aldehydes), Liebig's Annalen der Chemie und Pharmacie, 162:77–124, 309–320.

[28] Claus, Adolph K.L. Theoretische Betrachtungen und deren Anwendungen zur Systematik der organischen Chemie (Theoreticalconsiderations and their applications to the classification scheme of organic chemistry), Freiburg, Germany, 1867, p. 207

[29] Dewar, James (1867) "On the oxidation of phenyl alcohol, and a mechanical arrangement adapted to illustrate structure in the non-saturatedhydrocarbons," (http:/ / books. google. com/ books?id=PmlUAAAAIAAJ& pg=PA82) Proceedings of the Royal Society of Edinburgh 6:82–86.

[30] Ladenburg, Albert (1869) "Bemerkungen zur aromatischen Theorie" (http:/ / books. google. com/ books?id=Epg8AAAAIAAJ& pg=PA140)(Observations on the aromatic theory), Berichte der Deutschen Chemischen Gesellschaft 2: 140–142.

[31] Armstrong, Henry E. (1887) "An explanation of the laws which govern substitution in the case of benzenoid compounds," (http:/ / books.google. com/ books?id=4QbzAAAAMAAJ& pg=PA258) Journal of the Chemical Society, 51, 258–268; see p. 264.

[32] Thiele, Johannes (1899) "Zur Kenntnis der ungesättigten Verbindungen" (On our knowledge of unsaturated compounds), Justus Liebig’sAnnalen der Chemie,306: 87–266; see: "VIII. Die aromatischen Verbindungen. Das Benzol." (VIII. The aromatic compounds. Benzene.), pp.125–129. (http:/ / books. google. je/ books?id=NYw8AAAAIAAJ& pg=RA1-PA125) See further: Thiele (1901) "Zur Kenntnis derungesättigen Verbindungen," Justus Liebig’s Annalen der Chemie, 319: 129–143.

[33] English translation Wilcox, David H.; Greenbaum, Frederick R. (1965). "Kekule's benzene ring theory: A subject for lighthearted banter".Journal of Chemical Education 42 (5): 266–67. Bibcode 1965JChEd..42..266W. doi:10.1021/ed042p266.

[34] Kekulé, F. A. (1890). "Benzolfest: Rede" (http:/ / gallica. bnf. fr/ ark:/ 12148/ bpt6k90720c/ f1304. chemindefer). Berichte der DeutschenChemischen Gesellschaft 23: 1302–11. doi:10.1002/cber.189002301204. .

[35] Benfey O. T. (1958). "August Kekulé and the Birth of the Structural Theory of Organic Chemistry in 1858". Journal of Chemical Education35: 21–23. Bibcode 1958JChEd..35...21B. doi:10.1021/ed035p21.

[36] Gillis, Jean "Auguste Kekulé et son oeuvre, realisee a Gand de 1858 a 1867," Memoires de l'Academie Royale de Belgique, 37:1 (1866),1–40.

[37] K. Lonsdale (1929). "The Structure of the Benzene Ring in Hexamethylbenzene". Proceedings of the Royal Society 123A: 494.[38] K. Lonsdale (1931). "An X-Ray Analysis of the Structure of Hexachlorobenzene, Using the Fourier Method" (http:/ / gallica. bnf. fr/ ark:/

12148/ bpt6k56226p/ f558. table). Proceedings of the Royal Society 133A: 536–553. Bibcode 1931RSPSA.133..536L.doi:10.1098/rspa.1931.0166. .

[39] March, J. “Advanced Organic Chemistry” 4th Ed. J. Wiley and Sons, 1992: New York. ISBN 0-471-60180-2.[40] Moran, Damian; Simmonett, Andrew C.; Leach, Franklin E.; Allen, Wesley D.; Schleyer, Paul v. R.; Schaefer, Henry F. (2006). "Popular

Theoretical Methods Predict Benzene and Arenes To Be Nonplanar". Journal of the American Chemical Society 128 (29): 9342–3.doi:10.1021/ja0630285. PMID 16848464.

[41] Cooper, David L.; Gerratt, Joseph; Raimondi, Mario (1986). "The electronic structure of the benzene molecule". Nature 323 (6090): 699.Bibcode 1986Natur.323..699C. doi:10.1038/323699a0.

[42] Pauling, Linus (1987). "Electronic structure of the benzene molecule". Nature 325 (6103): 396. Bibcode 1987Natur.325..396P.doi:10.1038/325396d0.

[43] Messmer, Richard P.; Schultz, Peter A. (1987). "The electronic structure of the benzene molecule". Nature 329 (6139): 492.Bibcode 1987Natur.329..492M. doi:10.1038/329492a0.

[44] Harcourt, Richard D. (1987). "The electronic structure of the benzene molecule". Nature 329 (6139): 491. Bibcode 1987Natur.329..491H.doi:10.1038/329491b0.

[45] "Unicode Character 'BENZENE RING' (U+232C)" (http:/ / www. fileformat. info/ info/ unicode/ char/ 232c/ index. htm). . Retrieved2009-01-16.

[46] "Unicode Character 'BENZENE RING WITH CIRCLE' (U+23E3)" (http:/ / www. fileformat. info/ info/ unicode/ char/ 23e3/ index. htm). .Retrieved 2009-01-16.

[47] Market Study on Benzene by Ceresana Research (http:/ / www. ceresana. com/ en/ market-studies/ chemicals/ benzene).[48][48] Kolmetz, Gentry, Guidelines for BTX Revamps, AIChE 2007 Spring Conference

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[49] "Control of Hazardous Air Pollutants From Mobile Sources" (http:/ / www. epa. gov/ EPA-AIR/ 2006/ March/ Day-29/ a2315b. htm). U.S.Environmental Protection Agency. 2006-03-29. p. 15853. . Retrieved 2008-06-27.

[50] Stranks, D. R.; M. L. Heffernan, K. C. Lee Dow, P. T. McTigue, G. R. A. Withers (1970). Chemistry: A structural view. Carlton, Victoria:Melbourne University Press. p. 347. ISBN 0-522-83988-6.

[51] Vincent A.Welch, Kevin J. Fallon, Heinz-Peter Gelbke “Ethylbenzene” Ullmann’s Encyclopedia of Industrial Chemistry, Wiley-VCH,Weinheim, 2005. doi:10.1002/14356007.a10_035.pub2

[52][52] Harrison's Principles of Internal Medicine, 16th ed., p. 618.[53] Merck Manual, Home Edition, (http:/ / www. merckmanuals. com/ home/ print/ sec13/ ch159/ ch159a. html) "Overview of Leukemia".[54] Smith, Martyn T. (2010). "Advances in understanding benzene health effects and susceptibility". Ann Rev Pub Health 31: 133–48.

doi:10.1146/annurev.publhealth.012809.103646.[55] American Petroleum Institute, API Toxicological Review, Benzene, September 1948 (http:/ / web. archive. org/ web/ 20030310145140/

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[57] Huff J (2007). "Benzene-induced cancers: abridged history and occupational health impact". Int J Occup Environ Health 13 (2): 213–21.PMID 17718179.

[58] Rana SV; Verma Y (2005). "Biochemical toxicity of benzene". J Environ Biol 26 (2): 157–68. PMID 16161967.[59] Breathe carefully: air emissions of benzene may cause birth defects. — Environmental Health News (http:/ / www.

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[61] OSHA Hazard Communication Standard 1910.1200(d)(5)(ii), carcinogens under (d)(4) of this section (http:/ / www. osha. gov/ pls/oshaweb/ owadisp. show_document?p_table=STANDARDS& p_id=10099). Osha.gov. Retrieved on 2011-11-23.

[62] 10/16/2003 – OSHA-recognized chemicals as carcinogens or potential carcinogens for Hazard Communication purposes (http:/ / www.osha. gov/ pls/ oshaweb/ owadisp. show_document?p_table=INTERPRETATIONS& p_id=24730). Osha.gov (2003-10-16). Retrieved on2010-10-09.

[63] ToxFAQs for Benzene (http:/ / www. atsdr. cdc. gov/ tfacts3. html#bookmark04), Agency for Toxic Substances and Disease Registry,Department of Health and Human Services

[64] ToxGuide for Benzene (http:/ / www. atsdr. cdc. gov/ toxguides/ toxguide-3. pdf?id=39& tid=14), Agency for Toxic Substances and DiseaseRegistry, Department of Health and Human Services

[65] Benzene, CASRN: 71-43-2 (http:/ / toxnet. nlm. nih. gov/ cgi-bin/ sis/ search/ r?dbs+ hsdb:@term+ @rn+ 71-43-2). Hazardous SubstancesData Bank, U.S. National Library of Medicine. National Institutes of Health.

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[75] Benzene. – 1910.1028 (http:/ / www. osha. gov/ pls/ oshaweb/ owadisp. show_document?p_id=10042& p_table=STANDARDS). Osha.gov.Retrieved on 2010-10-09.

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[77] NIOSH/OSHA Interim Guidance for Protecting Deepwater Horizon Response Workers and Volunteers (http:/ / www. osha. gov/ oilspills/interimguidance. html), Osha.gov (2010-07-26)

[78] Hazards Associated with Oil Cleanup Operations (http:/ / www. osha. gov/ oilspills/ interim-guidance-qa. html). Osha.gov (2010-07-02).Retrieved on 2010-10-09.

[79] Ashley, DL; Bonin, MA; Cardinali, FL; McCraw, JM; Wooten, JV (1994). "Blood concentrations of volatile organic compounds in anonoccupationally exposed US population and in groups with suspected exposure" (http:/ / www. clinchem. org/ cgi/ reprint/ 40/ 7/ 1401. pdf).Clinical chemistry 40 (7 Pt 2): 1401–4. PMID 8013127. .

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[81] ACGIH. 2009 TLVs and BEIs. American Conference of Governmental Industrial Hygienists, Cincinnati, Ohio, 2009.[82] R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 144–148.[83] Snyder, R; Hedli, C.C. (1996). "An overview of benzene metabolism". Environ Health Perspect 104 (Suppl 6): 1165–1171. PMC 1469747.

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[86] Eastmond, D.A.; Rupa, DS; Hasegawa, LS (2000). "Detection of hyperdiploidy and chromosome breakage in interphase humanlymphocytes following exposure to the benzene metabolite hydroquinone using multicolor fluorescence in situ hybridization with DNAprobes". Mutat Res 322 (1): 9–20. PMID 7517507.

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[88] Agency for Toxic Substances and Disease Registry. (2007). Benzene: Patient information sheet. (http:/ / www. atsdr. cdc. gov/ mhmi/mmg3handout. pdf)

[89] Occupational Safety and Health Standards, Toxic and Hazardous Substances, 1910.1028 (http:/ / www. osha. gov/ pls/ oshaweb/ owadisp.show_document?p_id=10042& p_table=STANDARDS). Osha.gov. Retrieved on 2011-11-23.

[90] Public Health Statement for Benzene, Agency for Toxic Substances and Disease Registry. (August 2007). Benzene: Patient informationsheet (http:/ / www. atsdr. cdc. gov/ PHS/ PHS. asp?id=37& tid=14). Atsdr.cdc.gov (2011-03-03). Retrieved on 2011-11-23.

External links• Benzene (www.eco-usa.net) (http:/ / www. eco-usa. net/ toxics/ chemicals/ benzene. shtml)• International Chemical Safety Card 0015 (http:/ / www. inchem. org/ documents/ icsc/ icsc/ eics0015. htm)• USEPA Summary of Benzene Toxicity (http:/ / www. epa. gov/ iris/ subst/ 0276. htm)• NIOSH Pocket Guide to Chemical Hazards (http:/ / www. cdc. gov/ niosh/ npg/ npgd0049. html)• CID 241 (http:/ / pubchem. ncbi. nlm. nih. gov/ summary/ summary. cgi?cid=241) from PubChem• Dept. of Health and Human Services: TR-289: Toxicology and Carcinogenesis Studies of Benzene (http:/ / ntp.

niehs. nih. gov/ index. cfm?objectid=0707525C-0F07-05BF-A16CAC7B0ECC97B5)• Video Podcast (http:/ / www. ch. ic. ac. uk/ video/ faraday_l. m4v) of Sir John Cadogan giving a lecture on

Benzene since Faraday, in 1991• Substance profile (http:/ / ntp. niehs. nih. gov/ ntp/ roc/ eleventh/ profiles/ s019benz. pdf)• Benzene (http:/ / chem. sis. nlm. nih. gov/ chemidplus/ direct. jsp?regno=71-43-2) in the ChemIDplus database• NLM Hazardous Substances Databank – Benzene (http:/ / toxnet. nlm. nih. gov/ cgi-bin/ sis/ search/ a?dbs+

hsdb:@term+ @DOCNO+ 35)

Page 18: Benzene

Article Sources and Contributors 18

Article Sources and ContributorsBenzene  Source: http://en.wikipedia.org/w/index.php?oldid=509890205  Contributors: 08prl, 16@r, 7&6=thirteen, ABCD, AManWithNoPlan, AXRL, Acdx, Acewolf359, Aechman, Ajrocke,Akileapen, Al.Glitch, AlB1337, Alex723723, Alfio, Allens, American Eagle, Amyvel315, AndrewRA, Andux, Anlace, Annwhent2, Antandrus, Antije, ArnoGourdol, Artichoker, Arvindn,Atemperman, Aushulz, Aussie Alchemist, Ayeroxor, Aznlilbadboy, Bakilas, Balabalamm, Banus, Barticus88, Baseball 292992, Bazzargh, Beamertate, Beetstra, Benjah-bmm27, Bensaccount,Bichologo, Bkell, BlackRaspberry, Blahaccountblah, Bobblewik, Boing! said Zebedee, Bomac, Borb, BorzouBarzegar, Bowenpan, Brackenheim, Brane.Blokar, Brighterorange, Bryan Derksen,C6541, Cacycle, Camp3rstrik3r, CanadianLinuxUser, Canderson7, Cargoking, Casforty, Cassan, Cbacc, Charlesdrakew, Chase me ladies, I'm the Cavalry, Chem-awb, ChemNerd, Chempedia,Chenopodiaceous, Chimpman, Chiu frederick, Chris Capoccia, ChrisTek, Christian75, Chriswiki, Chuunen Baka, Ciaccona, Colonel Tom, Common Man, Contango, Conversion script,Courcelles, Craigy144, Crispyrolls93, Cwkmail, Cyberevil, Cyde, Cygfrydd Llewellyn, DD 8630, DFS454, DMacks, DO11.10, DVD R W, Daniel Case, Davidruben, Dbiel, DeadEyeArrow,Deblovi, Dekergnp, Deli nk, Dethomas, Deviator13, DocWatson42, DocteurCosmos, Dominus, Download, DrBob, DragonflySixtyseven, Dratman, Dravick, Drphilharmonic, Dtsang, Dysprosia,Dzordzm, ESkog, Ebaksa, EconoPhysicist, Ed Poor, EdH, Edgar181, Edivorce, Edsanville, Eeekster, Eequor, Egonw, ElBenevolente, Eleassar, Element16, ElliottEnterprise, Emijrp, Endimion17,Eoscariii, Epbr123, Epop fr, Ergzay, Esurnir, Euryalus, EvaK, Ewen, Exabyte, FTGHSmith, Fcueto, FelixP, Fornaeffe, Fred Bauder, Freywa, Fttguitarist, Gaius Cornelius, Gauravjuvekar, Gavinsidhu, Gazjo, Gcjdavid, Gentgeen, Giftlite, Gilliam, Gmaxwell, GraemeL, Graham87, GregorB, Ground Zero, GroupWizard, Grunt, Gruzd, Gundwane, H Padleckas, Hadal, Halmstad,HatedHero, Hayabusa future, Hazel77, HazyM, Hellbus, Heron, Hertz1888, Heteren, Hobartimus, Ian01, Ilesn, Imasleepviking, InfoCan, Iridium77, IslandHopper973, Isopropyl, Itub,Ivarmcdonald, J.Steinbock, JForget, JLaTondre, JSpung, Jachin, Jack B108, JamesBWatson, JamesChemFindIt, Jameswilson, Jamialv, Jamieicis, Jauerback, Jauhienij, Jbworks0917, Jeeves,Jeffq, JeramieHicks, Jessicap123, Joanjoc, Jojojlj, Jon Harald Søby, Jons63, Jrtayloriv, Julie8806, Jynto, Jü, Kandar, Karlhahn, Kattlguard, KenFehling, Kenyon, Kjkolb, Kkolmetz, Kku,Klawehtgod, Kozuch, Kpengboy, Ktsquare, Kupos, Kymacpherson, L Kensington, La goutte de pluie, Lainestl, Lamro, LarryMorseDCOhio, Lbb972, Lchiarav, Leszek Jańczuk, Leyo, Ling.Nut,Littlealien182, LizardWizard, Llort, Logical2u, Logophile, Louisajb, Luna Santin, M.mural.lee, MarcK, Marek69, Mark Arsten, Martinman11, MastCell, Materialscientist, Mato, Mav,Mbeychok, Mdhowe, Mervyn, Metalloid, Metamagician3000, MichaK, Michael Frind, Michall, Mike 7, Mikespedia, Mild Bill Hiccup, Mjmcb1, Montrealais, Moreau1, Morning277, Mph2010,Mr. Vernon, Mr3641, MrADHD, Muchie11791, NCFCQ, Nagy, Nao1958, NawlinWiki, Nbauman, Nenad Seguljev, Neparis, Nerguy, Nick, Nickeudaly, Nickptar, Nonagonal Spider, Northgrove,Nuberger13, Nufy8, Nuggetboy, Nunquam Dormio, Ochemstudent21, Onco p53, Only, Opelio, Ortonmc, Paaerduag, Parable1991, Paul Drye, Paul-L, Pcbene, Peak, Pelirojopajaro, Persian PoetGal, PeterSymonds, Phasechange, Phgao, Physchim62, Pinethicket, Pinto1978, Pisanidavid, Pit, Platonicmaria, Polonium, Prari, Prmacn, Pylori, Pádraic MacUidhir, Qocheedy daiin, Quidam65,Qxz, R. S. Shaw, R9tgokunks, RK, RMFan1, Rabid Lemur, RaseaC, Rbaselt, Renamed vandal 86, Retired username, Reyk, Rice.brendan, Rich Farmbrough, Rifleman 82, Rje, Rjwilmsi,Rocastelo, Root4(one), Rossheth, RuudVisser, Ryulong, Rzepa, S2000magician, Sabbut, Sandshinobi23, Sciencen3rd, Sciurinæ, SemperBlotto, Semperf, Seraphimblade, Shaddack, Shawcity,Sheepd, Shefgodeep, Shellreef, Shimmin, Shinjiman, Shyamal, Silverbutterflies, Simoes, SimonP, Sitek, Sleeping123, Smk99, Smokefoot, Snezzy, Snowolf, Solipse, Solipsist, Some jerk on theInternet, Spiffy sperry, SpikeTorontoRCP, Srnec, Ssomme, SteinAlive, Stemonitis, Stephenb, Steveholland87, Steviedpeele, Stone, Subsolar, Superfly2005, Sverdrup, Synergy, TSLIII, Tarquin,Taweetham, Taxman, Tetracube, The Thing That Should Not Be, Thekrazykool809, Thisisshorty, Timpo, Timwi, Tisdalepardi, Tom-, Townview science, Tpk5010, Traceymarr, TreyHarris,Unconcerned, Unitknow, Unyoyega, User A1, V8rik, Vladsinger, Vonfraginoff, Vuo, Vyacheslav Nasretdinov, W2raphael, Walkerma, Wavelength, Weiteck, Wervo, Whoop whoop pull up, Wik,Wiki alf, Wikislemur, WilfriedC, William Avery, Wimvandorst, Wk muriithi, Wkltan, Wmahan, WriterHound, XJamRastafire, Xchrisblackx, Xcomradex, Xeno, Xprofj, Yahia.barie,Yakobbokay, Zxmaster, ~K, 688 ,حسن علي البط anonymous edits

Image Sources, Licenses and ContributorsFile:Benzene-2D-full.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Benzene-2D-full.svg  License: Public Domain  Contributors: JyntoFile:Benzene-aromatic-3D-balls.png  Source: http://en.wikipedia.org/w/index.php?title=File:Benzene-aromatic-3D-balls.png  License: Public Domain  Contributors: Benjah-bmm27File:Benzene circle.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Benzene_circle.svg  License: Public Domain  Contributors: user:Vyacheslav NasretdinovFile:Benzene-3D-vdW.png  Source: http://en.wikipedia.org/w/index.php?title=File:Benzene-3D-vdW.png  License: Public Domain  Contributors: Benjah-bmm27File:Yes check.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Yes_check.svg  License: Public Domain  Contributors: AnomieFile:X mark.svg  Source: http://en.wikipedia.org/w/index.php?title=File:X_mark.svg  License: Public Domain  Contributors: User:GmaxwellFile:Historic Benzene Formulae Kekulé (original).png  Source: http://en.wikipedia.org/w/index.php?title=File:Historic_Benzene_Formulae_Kekulé_(original).png  License: Public Domain Contributors: Friedrich August Kekulé von Stradonitz (1829–1896)File:Historic Benzene Formulae V.3.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Historic_Benzene_Formulae_V.3.svg  License: Public Domain  Contributors: JüFile:Solid benzene.png  Source: http://en.wikipedia.org/w/index.php?title=File:Solid_benzene.png  License: Creative Commons Attribution-Sharealike 3.0  Contributors: User:Endimion17File:Benzene Representations.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Benzene_Representations.svg  License: Creative Commons Attribution-Sharealike 3.0  Contributors:VladsingerImage:Equilibrium.svg  Source: http://en.wikipedia.org/w/index.php?title=File:Equilibrium.svg  License: Public Domain  Contributors: L'AquatiqueFile:Benzene_uses.png  Source: http://en.wikipedia.org/w/index.php?title=File:Benzene_uses.png  License: Creative Commons Attribution-Sharealike 3.0  Contributors: ItubFile:OChem-Mech-ElectrophilicAromaticSubstitution-General.png  Source: http://en.wikipedia.org/w/index.php?title=File:OChem-Mech-ElectrophilicAromaticSubstitution-General.png License: Public domain  Contributors: Conscious, David Berardan, Leyo, ShizhaoFile:EtC6H5route.png  Source: http://en.wikipedia.org/w/index.php?title=File:EtC6H5route.png  License: Creative Commons Attribution-Sharealike 3.0  Contributors: User:SmokefootFile:Friedel-Crafts acylation of benzene by ethanol chloride.png  Source: http://en.wikipedia.org/w/index.php?title=File:Friedel-Crafts_acylation_of_benzene_by_ethanol_chloride.png License: GNU Free Documentation License  Contributors: User:DiberriFile:Benzol.JPG  Source: http://en.wikipedia.org/w/index.php?title=File:Benzol.JPG  License: GNU Free Documentation License  Contributors: de:benutzer:BDXX. Original uploader wasDFS454 at en.wikipediaFile:Lichtbrechung von Benzol.jpg  Source: http://en.wikipedia.org/w/index.php?title=File:Lichtbrechung_von_Benzol.jpg  License: Creative Commons Attribution-Sharealike 3.0 Contributors: Robin Müller

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