Benzene - Wikipedia, The Free Encyclopedia

7/30/2019 Benzene - Wikipedia, The Free Encyclopedia

1/18

Benzene

benzene

cyclohexa-1,3,5-triene

1,3,5-cyclohexatriene

benzol

phene

Identifiers

CAS number 71-43-2

PubChem 241

ChemSpider 236

UNII J64922108F

KEGG C01407

ChEBI CHEBI:16716

ChEMBL CHEMBL277500

RTECS number CY1400000

Jmol-3D images Image 1

(http://chemapps.stolaf.edu

/jmol/jmol.php?model=c1ccccc1)

Properties

Molecular formula C6H

6

Molar mass 78.11 g mol1

BenzeneFrom Wikipedia, the free encyclopedia

See also: Benzole

Benzene is an organic chemical compound with themolecular formula C

6H

6. Its molecule is composed of 6

carbon atoms joined in a ring, with 1 hydrogen atomattached to each carbon atom. Because its moleculescontain only carbon and hydrogen atoms, benzene isclassed as a hydrocarbon.

Benzene is a natural constituent of crude oil, and is oneof 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 PhH. Benzene is a colorless andhighly flammable liquid with a sweet smell. It is mainlyused as a precursor to heavy chemicals, such asethylbenzene and cumene, which are produced on a

billion kilogram scale. Because it has a high octanenumber, it is an important component of gasoline,composing a few percent of its mass. Mostnon-industrial applications have been limited by

benzene's carcinogenicity.

Contents1 History

1.1 Discovery1.2 Ring formula1.3 Early applications

2 Structure3 Benzene derivatives4 Production

4.1 Catalytic reforming

4.2 Toluene hydrodealkylation4.3 Toluene disproportionation4.4 Steam cracking4.5 Other sources

5 Uses5.1 Component of gasoline

6 Reactions6.1 Sulfonation, chlorination, nitration6.2 Hydrogenation6.3 Metal complexes

7 Health effects8 Exposure to benzene

8.1 Inhalation8.2 Exposure through smoking

IUPAC name

Systematic name

Other names

SMILES

InChI

zene - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Benzene

18 01/11/2012 11:33


2/18

Appearance Colorless liquid

Density 0.8765(20) g/cm3[1]

Melting point5.5 C, 278.7 K

Boiling point80.1 C, 353.3 K

Solubility in water 1.8 g/L (15 C)[2][3][4]

max

255 nm

Viscosity 0.652 cP at 20 C

Dipole moment 0 D

Hazards

MSDS External MSDS

EU classification Flammable (F)

Carc. Cat. 1

Muta. Cat. 2Toxic (T)

R-phrases R45, R46, R11, R16,

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

Supplementary data page

Structure and

properties

n, r, etc.

Thermodynamic

data

Phase behaviour

Solid, liquid, gas

Spectral data UV, IR, NMR, MS

(verify) (what is: / ?)

Except where noted otherwise, data are given for

materials in their standard state (at 25 C, 100 kPa)

Infobox references

8.3 Exposure from soft drinks8.4 Case examples8.5 Benzene exposure limits8.6 Exposure monitoring8.7 Biomarkers of exposure8.8 Biotransformations8.9 Molecular toxicology8.10 Biological oxidation andcarcinogenic activity8.11 Summary

9 See also10 References11 External links

History

Discovery

The word "benzene" derives historically from "gumbenzoin", sometimes called "benjamin" (i.e., benzoinresin), an aromatic resin known to European pharmacistsand perfumers since the 15th century as a product ofsoutheast Asia. "Benzoin" is itself a corruption of theArabic expression "luban jawi", or "frankincense ofJava". An acidic material was derived from benzoin by

sublimation, and named "flowers of benzoin", or benzoicacid. The hydrocarbon derived from benzoic acid thus

acquired the name benzin, benzol, or benzene.[5]

Michael Faraday first isolated and identified benzene in1825 from the oily residue derived from the productionof illuminating gas, giving it the name bicarburet of

hydrogen.[6][7]

In 1833, Eilhard Mitscherlich produced it via the

distillation of benzoic acid (from gum benzoin) and lime.He gave the compound the name benzin.[8]

In 1836, the French chemist Auguste Laurent named the

substance "phne";[9] this is the root of the word phenol,which is hydroxylated benzene, and phenyl, which is theradical formed by abstraction of a hydrogen atom (freeradical H) from benzene.

In 1845, Charles Mansfield, working under AugustWilhelm von Hofmann, isolated benzene from coal

tar.[11] Four years later, Mansfield began the firstindustrial-scale production of benzene, based on the

coal-tar method.[12][13] Gradually the sense developedamong chemists that substances related to benzene


18 01/11/2012 11:33


3/18

Historic benzene formulae as proposed by

Kekul.[10]

Historic benzene formulae (from left to right) by Claus (1867),[19] Dewar (1867),[20] Ladenburg

(1869),[21]

Armstrong (1887),[22]

Thiele (1899)[23]

and Kekul (1865). Dewar benzene and prismane aredifferent chemicals that have Dewar's and Ladenburg's structures. Thiele and Kekul's structures are used

today.

represent a diverse chemical family. In 1855 AugustWilhelm Hofmann used the word "aromatic" todesignate this family relationship, after a characteristic

property of many of its members.[14]

Ring formula

The empirical formula for benzene was long known, but its highly polyunsaturated structure, with just onehydrogen atom for each carbon atom, was challenging to determine. Archibald Scott Couper in 1858 and

Joseph Loschmidt in 1861[15] suggested possible structures that contained multiple double bonds or multiplerings, but too little evidence was then available to help chemists decide on any particular structure.

In 1865, the German chemist Friedrich August Kekul published a paper in French (for he was then teachingin Francophone Belgium) suggesting that the structure contained a six-membered ring of carbon atoms withalternating single and double bonds. The next year he published a much longer paper in German on the same

subject.[16][17] Kekul used evidence that had accumulated in the intervening yearsnamely, that therealways appeared to be only one isomer of any monoderivative of benzene, and that there always appeared to

be exactly three isomers of every diderivativenow understood to correspond to the ortho, meta, and parapatterns of arene substitutionto argue in support of his proposed structure. Kekul's symmetrical ring

could explain these curious facts, as well as benzene's 1:1 carbon-hydrogen ratio.[18]

The new

understanding of benzene, and hence of all aromatic compounds, proved to be so important for both pureand applied chemistry that in 1890 the German Chemical Society organized an elaborate appreciation inKekul's honor, celebrating the twenty-fifth anniversary of his first benzene paper. Here Kekul spoke of thecreation of the theory. He said that he had discovered the ring shape of the benzene molecule after having areverie or day-dream of a snake seizing its own tail (this is a common symbol in many ancient culturesknown as the Ouroboros or Endless knot). This vision, he said, came to him after years of studying thenature of carbon-carbon bonds. This was 7 years after he had solved the problem of how carbon atoms could

bond to up to four other atoms at the same time. It is curious that a similar, humorous depiction of benzenehad appeared in 1886 in theBerichte der Durstigen Chemischen Gesellschaft(Journal of the ThirstyChemical Society), a parody of theBerichte der Deutschen Chemischen Gesellschaft, only the parody had

monkeys seizing each other in a circle, rather than snakes as in Kekul's anecdote.[24] Some historians havesuggested that the parody was a lampoon of the snake anecdote, possibly already well known through oral

transmission even if it had not yet appeared in print.[5] Others have speculated that Kekul's story in 1890was a re-parody of the monkey spoof, and was a mere invention rather than a recollection of an event in his

life. Kekul's 1890 speech[25] in which these anecdotes appeared has been translated into English.[26] If onetakes the anecdote as the memory of a real event, circumstances mentioned in the story suggest that it must

have happened early in 1862.[27]

The cyclic nature of benzene was finally confirmed by the crystallographer Kathleen Lonsdale in

1929.[28][29]


18 01/11/2012 11:33


4/18

Frozen benzene

The various representations of

benzene

Early applications

In the 19th and early-20th centuries, benzene was used as an after-shave lotion because of its pleasant smell.Prior to the 1920s, benzene was frequently used as an industrial solvent, especially for degreasing metal. Asits toxicity became obvious, benzene was supplanted by other solvents, especially toluene (methyl benzene),which has similar physical properties but is not as carcinogenic.

In 1903, Ludwig Roselius popularized the use of benzene todecaffeinate coffee. This discovery led to the production of Sanka(Sanka = sans cafine = without caffeine). This process was laterdiscontinued. Benzene was historically used as a significantcomponent in many consumer products such as Liquid Wrench,several paint strippers, rubber cements, spot removers and otherhydrocarbon-containing products. Some ceased manufacture of their

benzene-containing formulations in about 1950, while otherscontinued to use benzene as a component or significant contaminantuntil the late 1970s when leukemia deaths were found associatedwith Goodyear's Pliofilm production operations in Ohio. Until thelate 1970s, many hardware stores, paint stores, and other retailoutlets sold benzene in small cans, such as quart size, for general-purpose use. Many students were exposedto benzene in school and university courses while performing laboratory experiments with little or noventilation in many cases. This very dangerous practice has been almost totally eliminated.

Structure

Main article: Aromaticity

Benzene represents a special problem in that, to account for all the bonds, there must be alternating doublecarbon bonds:[30]

X-ray diffraction shows that all of six carbon-carbon bonds inbenzene are of the same length of 140 picometres (pm). The CCbond lengths are greater than a double bond (135 pm) but shorterthan a single bond (147 pm). This intermediate distance is consistentwith electron delocalization: the electrons for CC bonding aredistributed equally between each of the six carbon atoms. Benzenehas 8 hydrogen atoms fewer than the corresponding parent alkane,

hexane. The molecule is planar.[31] One representation is that thestructure exists as a superposition of so-called resonance structures,rather than either form individually. The delocalization of electrons isone explanation for the thermodynamic stability of benzene and

related 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 depictedwith a circle inside a hexagonal arrangement of carbon atoms.

The delocalized picture of benzene has been contested by Cooper, Gerratt and Raimondi in their articlepublished in 1986 in the journal Nature. They showed that the electrons in benzene are almost certainlylocalized, and the aromatic properties of benzene originate from spin coupling rather than electron

delocalization.[32] This view has been supported in the next-year Nature issue,[33][34][35] but it has beenslow to permeate the general chemistry community.

As is common in organic chemistry, the carbon atoms in the diagram above have been left unlabeled.Realizing each carbon has 2p electrons, each carbon donates an electron into the delocalized ring above and


18 01/11/2012 11:33


5/18

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 Unicodesymbol in the Miscellaneous Technical block with the code U+232C () to represent it with three double

bonds,[36] and U+23E3 ( ) for a delocalized version.[37]

Benzene derivatives

Main article: Aromatic hydrocarbons

Many important chemical compounds are derived from benzene by replacing one or more of its hydrogenatoms with another functional group. Examples of simple benzene derivatives are phenol, toluene, andaniline, abbreviated PhOH, PhMe, and PhNH2, respectively. Linking benzene rings gives biphenyl,

C6H5C6H5. Further loss of hydrogen gives "fused" aromatic hydrocarbons, such as naphthalene and

anthracene. The limit of the fusion process is the hydrogen-free allotrope of carbon, graphite.

In heterocycles, carbon atoms in the benzene ring are replaced with other elements. The most important

derivatives are the rings containing nitrogen. Replacing one CH with N gives the compound pyridine,C

5H

5N. Although benzene and pyridine are structurally related, benzene cannot be converted into pyridine.

Replacement of a second CH bond with N gives, depending on the location of the second N, pyridazine,pyrimidine, and pyrazine.

Production

Four chemical processes contribute to industrial benzene production: catalytic reforming, toluenehydrodealkylation, toluene disproportionation, and steam cracking. According to the ATSDR Toxicological

Profile for benzene, between 1978 and 1981, catalytic reformats accounted for approximately 4450% of thetotal U.S benzene production.

Until World War II, most benzene was produced as a by-product of coke production (or "coke-oven lightoil") in the steel industry. However, in the 1950s, increased demand for benzene, especially from thegrowing polymers industry, necessitated the production of benzene from petroleum. Today, most benzenecomes from the petrochemical industry, with only a small fraction being produced from coal.

Catalytic reforming

In catalytic reforming, a mixture of hydrocarbons with boiling points between 60200 C is blended withhydrogen gas and then exposed to a bifunctional platinum chloride or rhenium chloride catalyst at 500525C and pressures ranging from 850 atm. Under these conditions, aliphatic hydrocarbons form rings and losehydrogen to become aromatic hydrocarbons. The aromatic products of the reaction are then separated fromthe reaction mixture (or reformate) by extraction with any one of a number of solvents, including diethyleneglycol or sulfolane, and benzene is then separated from the other aromatics by distillation. The extractionstep of aromatics from the reformate is designed to produce aromatics with lowest non-aromaticcomponents. Recovery of the aromatics, commonly referred to as BTX (benzene, toluene and xyleneisomers), involves such extraction and distillation steps. There are a good many licensed processes availablefor extraction of the aromatics.

In similar fashion to this catalytic reforming, UOP and BP commercialized a method from LPG (mainlypropane and butane) to aromatics.

Toluene hydrodealkylation


18 01/11/2012 11:33


6/18

Toluene hydrodealkylation converts toluene to benzene. In this hydrogen-intensive process, toluene is mixedwith hydrogen, then passed over a chromium, molybdenum, or platinum oxide catalyst at 500600 C and4060 atm pressure. Sometimes, higher temperatures are used instead of a catalyst (at the similar reactioncondition). Under these conditions, toluene undergoes dealkylation to benzene and methane:

C6H5CH3 + H2 C6H6 + CH4

This irreversible reaction is accompanied by an equilibrium side reaction that produces biphenyl (akadiphenyl) at higher temperature:

2 C6H6 H2 + C6H5C6H5

If the raw material stream contains much non-aromatic components (paraffins or naphthenes), those arelikely decomposed 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 oftoluene, with similar efficiency.

This is often called "on-purpose" methodology to produce benzene, compared to conventional BTX(benzene-toluene-xylene) extraction processes.

Toluene disproportionation

Where a chemical complex has similar demands for both benzene and xylene, then toluenedisproportionation (TDP) may be an attractive alternative to the toluene hydrodealkylation. In the broadsense, 2 toluene molecules are reacted and the methyl groups rearranged from one toluene molecule to theother, yielding one benzene molecule and one xylene molecule.

Given that demand forpara-xylene (p-xylene) substantially exceeds demand for other xylene isomers, arefinement of the TDP process called Selective TDP (STDP) may be used. In this process, the xylene streamexiting the TDP unit is approximately 90% paraxylene. In some current catalytic systems, even the benzene-to-xylenes ratio is decreased (more xylenes) when the demand of xylenes is higher.

Steam cracking

Steam cracking is the process for producing ethylene and other alkenes from aliphatic hydrocarbons.Depending on the 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 agasoline additive, or routed through an extraction process to recover BTX aromatics (benzene, toluene andxylenes).

Other sources

Trace 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 principalproduct from the combustion of PVC (polyvinyl chloride).

Uses

Benzene is used mainly as an intermediate to make other chemicals. About 80% of benzene is consumed inthe production of three chemicals, ethylbenzene, cumene, and cyclohexane. Its most widely producedderivative is ethylbenzene, precursor to styrene, which is used to make polymers and plastics. Cumene isconverted phenol for resins and adhesives. Cyclohexane is used in the manufacture of Nylon. Smaller


18 01/11/2012 11:33


7/18

amounts of benzene are used to make some types of rubbers, lubricants, dyes, detergents, drugs, explosives,and pesticides.

In both the US and Europe, 50% of benzene is used in the production of ethylbenzene/styrene, 20% is usedin the production of cumene, and about 15% of benzene is used in the production of cyclohexane (eventually

to nylon).[citation needed]

Currently, the production of and demand for benzene in the Middle East register the greatest increasesworldwide. It will 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 the global demand.[38]

In laboratory research, toluene is now often used as a substitute for benzene. The solvent-properties of thetwo are similar, 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 gasoline

As 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 themost widely used antiknock additive. With the global phaseout of leaded gasoline, benzene has made acomeback as a gasoline additive in some nations. In the United States, concern over its negative healtheffects and the possibility of benzene's entering the groundwater have led to stringent regulation of

gasoline's benzene content, with limits typically around 1%.[39] European petrol specifications now containthe same 1% limit on benzene content. The United States Environmental Protection Agency introduced new

regulations in 2011 that lowered the benzene content in gasoline to 0.62%.[40]

Reactions

The most common reactions of benzene involve substitution of a proton by other groups.[41] Electrophilic


18 01/11/2012 11:33


8/18

aromatic substitution is a general method of derivatizing benzene. Benzene is sufficiently nucleophilic that itundergoes substitution 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.[42] Highly instructive but of far less industrialsignificance is the Friedel-Crafts alkylation of benzene (and many other aromatic rings) using an alkyl

halide in the presence of a strong Lewis acid catalyst. Similarly, the Friedel-Crafts acylation is a relatedexample of electrophilic aromatic substitution. The reaction involves the acylation of benzene (or manyother aromatic rings) with an acyl chloride using a strong Lewis acid catalyst such as aluminium chloride orIron(III) chloride.

Friedel-Crafts acylation of benzene by acetyl

chloride

Sulfonation, chlorination, nitration

Using electrophilic aromatic substitution, many functional groups are introduced onto the benzeneframework. Sulfonation of benzene involves the use of oleum, a mixture of sulfuric acid with sulfur trioxide.Sulfonated benzene derivatives are useful detergents. In nitration, benzene reacts with nitronium ions

(NO2+), which is a strong electrophile produced by combining sulfuric and nitric acids. Nitrobenzene is the

precursor to aniline. Chlorination in achieved with chlorine to give chlorobenzene.

Hydrogenation

Via hydrogenation, benzene and its derivatives convert to cyclohexane and derivatives. This reaction isachieved by the use of high pressures of hydrogen at high temperatures in the presence of a finely dividednickel, which serves as a catalyst. In the absence of the catalyst, benzene is impervious to hydrogen. Thisreaction is practiced on a very large scale industrially.


18 01/11/2012 11:33


9/18

A bottle of benzene. The warnings

show benzene is a toxic and

flammable liquid.

Metal complexes

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

Health effects

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 aplastic

anemia, acute leukemia, and bone marrow abnormalities.[43][44] 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).[45]

The American Petroleum Institute (API) stated in 1948 that "it isgenerally considered that the only absolutely safe concentration for

benzene is zero."[46] The US Department of Health and HumanServices (DHHS) classifies benzene as a human carcinogen.Long-term exposure to excessive levels of benzene in the air causesleukemia, a potentially fatal cancer of the blood-forming organs, insusceptible individuals. In particular, Acute myeloid leukemia oracute non-lymphocytic leukaemia (AML & ANLL) is not disputed to

be caused by benzene.[47] 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 thebrain and can cause DNA strand breaks, chromosomal damage, etc. Benzene causes cancer in both animalsand humans. Benzene has been shown to cause cancer in both sexes of multiple species of laboratory

animals exposed via various routes.[48][49]

Some women who inhaled high levels of benzene for many months had irregular menstrual periods and adecrease in the size of their ovaries. Benzene exposure has been linked directly to the neural birth defects

spina bifida and anencephaly.[50] Men exposed to high levels of benzene are more likely to have an

abnormal amount of chromosomes in their sperm, which impacts fertility and fetal development.[51]

Exposure to benzene

Vapors from products that contain benzene, such as glues, paints, furniture wax, and detergents, can also bea source of exposure, although many of these have been modified or reformulated since the late 1970s toeliminate or reduce the benzene content. Air around hazardous waste sites or gas stations may contain higherlevels of benzene. Because petroleum hydrocarbon products are complex mixtures of chemicals, riskassessments for these products, in general, focus on specific toxic constituents. The petroleum constituentsof primary interest to human health have been the aromatic hydrocarbons (i.e., benzene, ethylbenzene,toluene, and xylenes). In the U.S., OSHA requires that a mixture "shall be assumed to present a carcinogenic

hazard if it contains a component in concentrations of 0.1% or greater, which is considered to be acarcinogen.[52][53]

Outdoor air may contain low levels of benzene from automobile service stations, wood smoke, tobacco

smoke, the transfer of gasoline, exhaust from motor vehicles, and industrial emissions.[54] About 50% of the


18 01/11/2012 11:33


10/18

Light refraction of benzene (above)

and water (below)

entire nationwide (United States) exposure to benzene results from

smoking tobacco or from exposure to tobacco smoke.[55]

Inhalation

Inhaled benzene is primarily expelled unchanged through exhalation.In a human study 16.4 to 41.6% of retained benzene was eliminated

through the lungs within five to seven hours after a two- tothree-hour exposure to 47 to 110 ppm and only 0.07 to 0.2% of theremaining benzene was excreted unchanged in the urine. Afterexposure to 63 to 405 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 50 hours.In another human study, 30% of absorbed dermally applied benzene,which is primarily metabolized in the liver, was excreted as phenol in

the urine.[56]

Exposure through smoking

Exposure of the general population to benzene occurs mainly throughbreathing, the major sources of benzene being tobacco smoke (about50%) as well as automobile service stations, exhaust from motorvehicles and industrial emissions (about 20% altogether). Accordingto the CDC, "The mean number of cigarettes per day (cpd) among daily smokers in 1993 was 19.6 (21.3 cpdfor men and 17.8 cpd for women) and in 2004 was 16.8 (18.1 cpd for men and 15.3 cpd for women)."http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5444a2.htm According to the August 2007 PublicHealth Statement, the average smoker smokes 32 cpd, which in turn the average smoker would take in about1.8 milligrams (mg) of benzene per day. This amount is about 10 times the average daily intake of benzene

by nonsmokers.[57]

Exposure from soft drinks

In March 2006, the official Food Standards Agency in Britain conducted a survey of 150 brands of softdrinks. It found that four contained benzene levels above World Health Organization limits. The affected

batches were removed from sale.[58] (See also benzene in soft drinks).

Case examples

Water and soil contamination are important pathways of concern for transmission of benzene. In the USalone, approximately 100,000 sites have soil or groundwater contaminated with benzene.[citation needed]

In 2005, the water supply to the city of Harbin in China with a population of almost nine million people, wascut off because of a major benzene exposure. Benzene leaked into the Songhua River, which suppliesdrinking water to the city, after an explosion at a China National Petroleum Corporation (CNPC) factory in

the city of Jilin on 13 November.[citation needed]

Benzene exposure limits

The United States Environmental Protection Agency has set a maximum contaminant level (MCL) forbenzene in drinking water at 0.005 mg/L (5 ppb), as promulgated via the U.S. National Primary Drinking

Water Regulations.[59] This regulation is based on preventing benzene leukemogenesis. The maximumcontaminant level goal (MCLG), a nonenforceable health goal that would allow an adequate margin of


f 18 01/11/2012 11:33


11/18

safety for the prevention of adverse effects, is zero benzene concentration in drinking water. The EPArequires that spills or accidental releases into the environment of 10 pounds (4.5 kg) or more of benzene bereported.

The U.S. Occupational Safety and Health Administration (OSHA) has set a permissible exposure limit of 1part of benzene per million parts of air (1 ppm) in the workplace during an 8-hour workday, 40-hour

workweek. The short term exposure limit for airborne benzene is 5 ppm for 15 minutes.[60] These legal

limits were based on studies demonstrating compelling evidence of health risk to workers exposed tobenzene. The risk from exposure to 1 ppm for a working lifetime has been estimated as 5 excess leukemiadeaths per 1,000 employees exposed. (This estimate assumes no threshold for benzene's carcinogeniceffects.) OSHA has also established an action level of 0.5 ppm to encourage even lower exposures in the

workplace.[61]

The U.S. National Institute for Occupational Safety and Health (NIOSH) revised the ImmediatelyDangerous to Life or Health (IDLH) concentration for benzene to 500 ppm. The current NIOSH definitionfor an IDLH condition, as given in the NIOSH Respirator Selection Logic, is one that poses a threat ofexposure to airborne contaminants when that exposure is likely to cause death or immediate or delayed

permanent adverse health effects or prevent escape from such an environment [NIOSH 2004]. The purposeof establishing an IDLH value is (1) to ensure that the worker can escape from a given contaminatedenvironment in the event of failure of the respiratory protection equipment and (2) is considered a maximumlevel above which only a highly reliable breathing apparatus providing maximum worker protection is

permitted [NIOSH 2004[62]].[63] In September 1995, NIOSH issued a new policy for developingrecommended 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 to benzene at levels exceeding the REL (10-hour) of 0.1 ppm.[64] The NIOSH STEL (15 min) is 1ppm.

American Conference of Governmental Industrial Hygienists (ACGIH) adopted Threshold Limit Values

(TLVs) for benzene at 0.5 ppm TWA and 2.5 ppm STEL.

Exposure monitoring

Airborne exposure monitoring for benzene must be conducted in order to properly assess personal exposuresand effectiveness of engineering controls. Initial exposure monitoring should be conducted by an industrialhygienist or person specifically trained and experienced in sampling techniques. Contact an AIHA

Accredited Laboratory for advice on sampling methods.[65]

Each employer with a place of employment where occupational exposures to benzene occur shall monitoreach of these workplaces and work operations to determine accurately the airborne concentrations of

benzene to which employees may be exposed.[66] Representative 8-hour TWA employee exposures need tobe determined on the basis of one sample or samples representing the full shift exposure for each jobclassification in each work area. Unless air samples are taken frequently, the employer does not know the

concentration and would not know how much of a protection factor is needed.[67]

In providing consultation on work safety during oil clean-up operations following the Deepwater Horizonaccident, OSHA has worked with a number of other government agencies to protect Gulf cleanup workers.

OSHA partnered with the NIOSH to issue "Interim Guidance for Protecting Deepwater Horizon ResponseWorkers and Volunteers" and recommend measures that should be taken to protect workers from a variety of

different health hazards that these workers face.[68] OSHA conceded that it recognizes that most of its PELsare outdated and inadequate measures of worker safety. In characterizing worker exposure, OSHA insteadrelies on more up-to-date recommended protective limits set by organizations such as NIOSH, the ACGIH,


f 18 01/11/2012 11:33


12/18

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 Occupational Exposure Limit for the listed

contaminant for purposes of risk assessment and protective equipment recommendations.[69]

Biomarkers of exposure

Several tests can determine exposure to benzene. Benzene itself can be measured in breath, blood or urine,

but such testing is usually limited to the first 24 hours post-exposure due to the relatively rapid removal ofthe chemical by exhalation or biotransformation. Most persons in developed countries have measureable

baseline levels of benzene and other aromatic petroleum hydrocarbons in their blood. In the body, benzene isenzymatically converted to a series of oxidation products including muconic acid, phenylmercapturic acid,

phenol, catechol, hydroquinone and 1,2,4-trihydroxybenzene. Most of these metabolites have some value asbiomarkers of human exposure, since they accumulate in the urine in proportion to the extent and durationof exposure, and they may still be present for some days after exposure has ceased. The current ACGIH

biological exposure limits for occupational exposure are 500 g/g creatinine for muconic acid and 25 g/g

creatinine for phenylmercapturic acid in an end-of-shift urine specimen.[70][71][72][73]

Biotransformations

Even if it is not a common substrate for the metabolism of organisms, benzene can be oxidized by bothbacteria and eukaryotes. In bacteria, dioxygenase enzyme can add an oxygen molecule to the ring, and theunstable product is immediately reduced (by NADH) to a cyclic diol with two double bonds, breaking thearomaticity. Next, the diol is newly reduced by NADH to catechol. The catechol is then metabolized toacetyl CoA and succinyl CoA, used by organisms 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 areinvolved. These include cytochrome P450 2E1 (CYP2E1), quinine oxidoreductase (NQ01), GSH, and

myeloperoxidase (MPO). CYP2E1 is involved at multiple steps: converting benzene to oxepin (benzeneoxide), phenol to hydroquinone, and hydroquinone to both benzenetriol and catechol. Hydroquinone,benzenetriol and catechol are converted to polyphenols. In the bone marrow, MPO converts thesepolyphenols to benzoquinones. These intermediates and metabolites induce genotoxicity by multiplemechanisms including inhibition of topoisomerase II (which maintains chromosome structure), disruption ofmicrotubules (which maintains cellular structure and organization), generation of oxygen free radicals(unstable species) that may lead to point mutations, increasing oxidative stress, inducing DNA strand breaks,and altering DNA methylation (which can affect gene expression). NQ01 and GSH shift metabolism awayfrom toxicity. NQ01 metabolizes benzoquinone toward polyphenols (counteracting the effect of MPO). GSH

is involved with the formation of phenylmercapturic acid.[45][74]

Genetic polymorphisms in these enzymes may induce loss of function or gain of function. For example,mutations in CYP2E1 increase activity and result in increased generation of toxic metabolites. NQ01mutations result in loss of function and may result in decreased detoxification. Myeloperoxidase mutationsresult in loss of function and may result in decreased generation of toxic metabolites. GSH mutations ordeletions result in loss of function and result in decreased detoxification. These genes may be targets for

genetic screening for susceptibility to benzene toxicity.[75]

Molecular toxicology

The paradigm of toxicological assessment of benzene is shifting towards the domain of molecular

toxicology as it allows understanding of fundamental biological mechanisms in a better way. Glutathioneseems to play an important role by protecting against benzene-induced DNA breaks and it is being identified

as a new biomarker for exposure and effect.[76] Benzene causes chromosomal aberrations in the peripheralblood leukocytes and bone marrow explaining the higher incidence of leukemia and multiple myeloma


f 18 01/11/2012 11:33


13/18

caused by chronic exposure. These aberrations can be monitored using fluorescent in situ hybridization(FISH) with DNA probes to assess the effects of benzene along with the hematological tests as markers of

hematotoxicity.[77] Benzene metabolism involves enzymes coded for by polymorphic genes. Studies haveshown that genotype at these loci may influence susceptibility to the toxic effects 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 greater frequency of DNA

single-stranded breaks.[78]

Biological oxidation and carcinogenic activity

One way of understanding the carcinogenic effects of benzene is by examining the products of biologicaloxidation. Pure benzene, for example, oxidizes in the body to produce an epoxide, benzene oxide, which isnot excreted readily and can interact with DNA to produce harmful mutations.

Summary

According to the Agency for Toxic Substances and Disease Registry (ATSDR) (2007), benzene is both an

anthropogenically produced and naturally occurring chemical from processes that include: volcaniceruptions, wild fires, synthesis of chemicals such as phenol, production of synthetic fibers, and fabrication ofrubbers, lubricants, pesticides, medications, and dyes. The major sources of benzene exposure are tobaccosmoke, automobile service stations, exhaust from motor vehicles, and industrial emissions; however,ingestion and dermal absorption of benzene can also occur through contact with contaminated water.Benzene is hepatically metabolized and excreted in the urine. Measurement of air and water levels of

benzene is accomplished through collection via activated charcoal tubes, which are then analyzed with a gaschromatograph. The measurement of benzene in humans can be accomplished via urine, blood, and breathtests; however, all of these have their limitations because benzene is rapidly metabolized in the human body

into by-products called metabolites.[79]

OSHA regulates levels of benzene in the workplace.[80] The maximum allowable amount of benzene inworkroom air during an 8-hour workday, 40-hour workweek is 1 ppm. Because benzene can cause cancer,

NIOSH recommends that all workers wear special breathing equipment when they are likely to be exposed

to benzene at levels exceeding the recommended (8-hour) exposure limit of 0.1 ppm.[81]

See also

6-membered aromatic rings with one carbon replaced by another group: borabenzene, benzene,silabenzene, germabenzene, stannabenzene, pyridine, phosphorine, arsabenzene, pyrylium saltIndustrial Union Department v. American Petroleum InstituteBenzene in soft drinksBTEX

References

^ Lide, D. R., ed. (2005). CRC Handbook of Chemistry and Physics (86th ed.). Boca Raton (FL): CRC Press.ISBN 0-8493-0486-5.

1.

^ Arnold, D.; Plank, C.; Erickson, E.; Pike, F. (1958). "Solubility of Benzene in Water".Industrial & EngineeringChemistry Chemical & Engineering Data Series3 (2): 253. doi:10.1021/i460004a016 (http://dx.doi.org/10.1021%2Fi460004a016) .

2.

^ Breslow, R.; Guo, T. (1990). "Surface tension measurements show that chaotropic salting-in denaturants are notjust water-structure breakers" (//www.ncbi.nlm.nih.gov/pmc/articles/PMC53221/) . Proceedings of the NationalAcademy of Sciences of the United States of America87 (1): 1679. Bibcode 1990PNAS...87..167B(http://adsabs.harvard.edu/abs/1990PNAS...87..167B) . doi:10.1073/pnas.87.1.167 (http://dx.doi.org

3.


f 18 01/11/2012 11:33


14/18

/10.1073%2Fpnas.87.1.167) . PMC 53221 (//www.ncbi.nlm.nih.gov/pmc/articles/PMC53221) . PMID 2153285(//www.ncbi.nlm.nih.gov/pubmed/2153285) . //www.ncbi.nlm.nih.gov/pmc/articles/PMC53221/.^ Coker, A. Kayode; Ludwig, Ernest E. (2007).Ludwig's Applied Process Design for Chemical AndPetrochemical Plants (http://books.google.com/books?id=N8RcH8juG_YC&pg=PA114) . 1. Elsevier. p. 114.ISBN 0-7506-7766-X. http://books.google.com/books?id=N8RcH8juG_YC&pg=PA114. Retrieved 2012-05-31.

4.

^ ab Rocke, A. J. (1985). "Hypothesis and Experiment in the Early Development of Kekule's Benzene Theory".Annals of Science42 (4): 35581. doi:10.1080/00033798500200411 (http://dx.doi.org/10.1080%2F00033798500200411) .

5.

^ Faraday, M. (1825). "On New Compounds of Carbon and Hydrogen, and on Certain Other Products Obtainedduring the Decomposition of Oil by Heat (http://gallica.bnf.fr/ark:/12148/bpt6k559209/f473.image) ".Philosophical Transactions of the Royal Society of London115: 440466. doi:10.1098/rstl.1825.0022(http://dx.doi.org/10.1098%2Frstl.1825.0022) . JSTOR 107752 (http://www.jstor.org/stable/107752) .

6.

^ R. Kaiser (1968). "Bicarburet of Hydrogen. Reappraisal of the Discovery of Benzene in 1825 with theAnalytical Methods of 1968".Angewandte Chemie International Edition in English7 (5): 345350.doi:10.1002/anie.196803451 (http://dx.doi.org/10.1002%2Fanie.196803451) .

7.

^ Mitscherlich, E. (1834). "ber das Benzol und die Suren 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 Pharmacie9 (1): 3948. doi:10.1002/jlac.18340090103 (http://dx.doi.org/10.1002%2Fjlac.18340090103) . In a footnote on page 43, Liebig, the journal's editor, suggested changing

Mitscherlich's original name for benzene (namely, "benzin") to "benzol", because the suffix "-in" suggested that itwas an alkaloid (e.g., Chinin (quinine)), which benzene isn't, whereas the suffix "-ol" suggested that it was oily,which benzene is. Thus on page 44, Mitscherlich states: Da diese Flssigkeit aus der Benzosure gewonnenwird, und wahrscheinlich mit den Benzoylverbindungen im Zusammenhang steht, so gibt man ihr am besten den

Namen Benzol, da der Name Benzon schon fr die mit dem Bittermandell isomerische Verbindung von Liebigund Whler gewhlt worden ist. (Since this liquid [benzene] is obtained from benzoic acid and probably is relatedto benzoyl compounds, the best name for it is "benzol", since the name "benzon" has already been chosen, byLiebig and Whler, for the compound that's isomeric with the oil of bitter almonds [benzaldehyde].)

8.

^ Auguste Laurent (1836) "Sur la chlorophnise et les acides chlorophnisique et chlorophnsique,"Annales deChemie et de Physique, vol. 63, pp. 2745, see p. 44 (http://books.google.com/books?id=Lx0AAAAAMAAJ&

pg=PA44) : Je donne le nom de phne au radical fondamental des acides prcdens (, j'claire), puisque labenzine se trouve dans le gaz de l'clairage. (I give the name of "phne" (, I illuminate) to the fundamental

radical of the preceding acid, because benzene is found in illuminating gas.)

9.

^ August Kekul (1872). "Ueber einige Condensationsproducte des Aldehyds".Liebigs Ann. Chem.162 (1):77124. doi:10.1002/jlac.18721620110 (http://dx.doi.org/10.1002%2Fjlac.18721620110) .

10.

^ 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.200205; on pp. 204205, Hofmann found benzene in coal tar oil.

11.

^ 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. 162180.

12.

^ Charles Mansfield filed for (November 11, 1847) and received (May 1848) a patent (no. 11,960) for thefractional distillation of coal tar.

13.

^ 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 13. On page 3, Hoffmann states:"The existence and mode of formation of insolinic acid prove that to the series of monobasic aromatic acids,C

n2H

n2-8O

4, the lowest known term of which is benzoic acid, ...." [Note: The empirical formulas of organic

compounds that appear in Hoffmann's article are wrong because he uses the incorrect atomic masses of carbon (6instead of 12) and oxygen (8 instead of 16).]

14.

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

15.

^ Kekul, F. A. (1865). "Sur la constitution des substances aromatiques" (http://books.google.com/books?id=bFsSAAAAYAAJ&pg=PA98) .Bulletin de la Societe Chimique de Paris3: 98110.http://books.google.com/books?id=bFsSAAAAYAAJ&pg=PA98. On p. 100, Kekul suggests that the carbon

atoms of benzene could form a "chane ferme" (a closed chain, a loop).

16.

^ Kekul, F. A. (1866). "Untersuchungen ber aromatische Verbindungen (http://books.google.com/books?id=pNryAAAAMAAJ&lpg=PA129) (Investigations of aromatic compounds)"].Liebigs Annalen derChemie und Pharmacie137 (2): 12936. doi:10.1002/jlac.18661370202 (http://dx.doi.org/10.1002%2Fjlac.18661370202) . http://books.google.com/books?id=pNryAAAAMAAJ&lpg=PA129.

17.


f 18 01/11/2012 11:33


15/18

^ Critics pointed out a problem with Kekul's original (1865/1867) structure for benzene: Whenever benzeneunderwent substitution at the ortho position, two distinguishable isomers should have resulted, depending onwhether the double bond at the ortho position extended clockwise or counterclockwise; however, no such isomerswere observed. In 1872, Kekul suggested that benzene had two complementary structures and that these formsrapidly 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 theconversion process, Kekul proposed that the valency of an atom is determined by the frequency with which itcollided with its neighbors in a molecule. As the carbon atoms in the benzene ring collided with each other, each

carbon atom would collide twice with one neighbor during a given interval and then twice with its other neighborduring 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 8689 (http://de.wikipedia.org/w/index.php?title=Datei:Kekule_-

_Ueber_einige_Condensationsproducte_des_Aldehyds.pdf&page=10) of Auguste Kekul (1872) "Ueber einigeCondensationsprodukte des Aldehyds" (On some condensation products of aldehydes),Liebig's Annalen derChemie und Pharmacie, 162: 77124, 309320.

18.

^ Claus, Adolph K.L. Theoretische Betrachtungen und deren Anwendungen zur Systematik der organischenChemie (Theoretical considerations and their applications to the classification scheme of organic chemistry),Freiburg, Germany, 1867, p. 207

19.

^ Dewar, James (1867) "On the oxidation of phenyl alcohol, and a mechanical arrangement adapted to illustratestructure in the non-saturated hydrocarbons," (http://books.google.com/books?id=PmlUAAAAIAAJ&pg=PA82)Proceedings of the Royal Society of Edinburgh6: 8286.

20.

^ Ladenburg, Albert (1869) "Bemerkungen zur aromatischen Theorie" (http://books.google.com/books?id=Epg8AAAAIAAJ&pg=PA140) (Observations on the aromatic theory),Berichte der DeutschenChemischen Gesellschaft2: 140142.

21.

^ Armstrong, Henry E. (1887) "An explanation of the laws which govern substitution in the case of benzenoidcompounds," (http://books.google.com/books?id=4QbzAAAAMAAJ&pg=PA258)Journal of the ChemicalSociety, 51, 258268; see p. 264.

22.

^ Thiele, Johannes (1899) "Zur Kenntnis der ungesttigten Verbindungen" (On our knowledge of unsaturatedcompounds),Justus Liebigs Annalen der Chemie,306: 87266; see: "VIII. Die aromatischen Verbindungen. DasBenzol." (VIII. The aromatic compounds. Benzene.), pp. 125129. (http://books.google.je/books?id=NYw8AAAAIAAJ&pg=RA1-PA125) See further: Thiele (1901) "Zur Kenntnis der ungesttigenVerbindungen,"Justus Liebigs Annalen der Chemie, 319: 129143.

23.

^ English translation Wilcox, David H.; Greenbaum, Frederick R. (1965). "Kekule's benzene ring theory: Asubject for lighthearted banter".Journal of Chemical Education42 (5): 26667. Bibcode 1965JChEd..42..266W(http://adsabs.harvard.edu/abs/1965JChEd..42..266W) . doi:10.1021/ed042p266 (http://dx.doi.org/10.1021%2Fed042p266) .

24.

^ Kekul, F. A. (1890). "Benzolfest: Rede" (http://gallica.bnf.fr/ark:/12148/bpt6k90720c/f1304.chemindefer) .Berichte der Deutschen Chemischen Gesellschaft23: 130211. doi:10.1002/cber.189002301204 (http://dx.doi.org/10.1002%2Fcber.189002301204) . http://gallica.bnf.fr/ark:/12148/bpt6k90720c/f1304.chemindefer.

25.

^ Benfey O. T. (1958). "August Kekul and the Birth of the Structural Theory of Organic Chemistry in 1858".Journal of Chemical Education35: 2123. Bibcode 1958JChEd..35...21B (http://adsabs.harvard.edu/abs/1958JChEd..35...21B) . doi:10.1021/ed035p21 (http://dx.doi.org/10.1021%2Fed035p21) .

26.

^ Gillis, Jean "Auguste Kekul et son oeuvre, realisee a Gand de 1858 a 1867,"Memoires de l'Academie Royale

de Belgique, 37:1 (1866), 140.

27.

^ K. Lonsdale (1929). "The Structure of the Benzene Ring in Hexamethylbenzene". Proceedings of the RoyalSociety123A: 494.

28.

^ 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 Society133A: 536553.Bibcode 1931RSPSA.133..536L (http://adsabs.harvard.edu/abs/1931RSPSA.133..536L) .doi:10.1098/rspa.1931.0166 (http://dx.doi.org/10.1098%2Frspa.1931.0166) . http://gallica.bnf.fr/ark:/12148/bpt6k56226p/f558.table.

29.

^ March, J. Advanced Organic Chemistry 4th Ed. J. Wiley and Sons, 1992: New York. ISBN 0-471-60180-2.30.^ 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 Society128 (29): 93423. doi:10.1021/ja0630285 (http://dx.doi.org/10.1021%2Fja0630285) .

PMID 16848464 (//www.ncbi.nlm.nih.gov/pubmed/16848464) .

31.

^ Cooper, David L.; Gerratt, Joseph; Raimondi, Mario (1986). "The electronic structure of the benzenemolecule".Nature323 (6090): 699. Bibcode 1986Natur.323..699C (http://adsabs.harvard.edu/abs/1986Natur.323..699C) . doi:10.1038/323699a0 (http://dx.doi.org/10.1038%2F323699a0) .

32.

^ Pauling, Linus (1987). "Electronic structure of the benzene molecule".Nature325 (6103): 396. Bibcode33.


f 18 01/11/2012 11:33


16/18

1987Natur.325..396P (http://adsabs.harvard.edu/abs/1987Natur.325..396P) . doi:10.1038/325396d0(http://dx.doi.org/10.1038%2F325396d0) .^ Messmer, Richard P.; Schultz, Peter A. (1987). "The electronic structure of the benzene molecule".Nature329(6139): 492. Bibcode 1987Natur.329..492M (http://adsabs.harvard.edu/abs/1987Natur.329..492M) .doi:10.1038/329492a0 (http://dx.doi.org/10.1038%2F329492a0) .

34.

^ Harcourt, Richard D. (1987). "The electronic structure of the benzene molecule".Nature329 (6139): 491.Bibcode 1987Natur.329..491H (http://adsabs.harvard.edu/abs/1987Natur.329..491H) . doi:10.1038/329491b0(http://dx.doi.org/10.1038%2F329491b0) .

35.

^ "Unicode Character 'BENZENE RING' (U+232C)" (http://www.fileformat.info/info/unicode/char/232c/index.htm) . http://www.fileformat.info/info/unicode/char/232c/index.htm. Retrieved 2009-01-16.36.

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

37.

^ Market Study on Benzene by Ceresana Research (http://www.ceresana.com/en/market-studies/chemicals/benzene) .

38.

^ Kolmetz, Gentry, Guidelines for BTX Revamps, AIChE 2007 Spring Conference39.^ "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. http://www.epa.gov/EPA-AIR/2006/March/Day-29/a2315b.htm. Retrieved 2008-06-27.

40.

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

41.

^ Vincent A.Welch, Kevin J. Fallon, Heinz-Peter Gelbke Ethylbenzene Ullmanns Encyclopedia of IndustrialChemistry, Wiley-VCH, Weinheim, 2005. doi:10.1002/14356007.a10_035.pub2 (http://dx.doi.org/10.1002%2F14356007.a10_035.pub2)

42.

^ Harrison's Principles of Internal Medicine, 16th ed., p. 618.43.^ Merck Manual, Home Edition, (http://www.merckmanuals.com/home/print/sec13/ch159/ch159a.html)"Overview of Leukemia".

44.

^ ab Smith, Martyn T. (2010). "Advances in understanding benzene health effects and susceptibility".Ann RevPub Health31: 13348. doi:10.1146/annurev.publhealth.012809.103646 (http://dx.doi.org/10.1146%2Fannurev.publhealth.012809.103646) .

45.

^ American Petroleum Institute, API Toxicological Review, Benzene, September 1948 (http://web.archive.org/web/20030310145140/http://hobsonlaw.com/benzene_pages/pdffile.pdf) , Agency for Toxic Substances and

Disease Registry, Department of Health and Human Services

46.

^ WHO. INTERNATIONAL AGENCY FOR RESEARCH ON CANCER, IARC Monographs on the Evaluationof Carcinogenic Risks to Humans, Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs(http://monographs.iarc.fr/ENG/Monographs/suppl7/suppl7.pdf) , Volumes 1 to 42, Supplement 7

47.

^ Huff J (2007). "Benzene-induced cancers: abridged history and occupational health impact".Int J OccupEnviron Health13 (2): 21321. PMID 17718179 (//www.ncbi.nlm.nih.gov/pubmed/17718179) .

48.

^ Rana SV; Verma Y (2005). "Biochemical toxicity of benzene".J Environ Biol26 (2): 15768. PMID 16161967(//www.ncbi.nlm.nih.gov/pubmed/16161967) .

49.

^ Breathe carefully: air emissions of benzene may cause birth defects. Environmental Health News(http://www.environmentalhealthnews.org/ehs/newscience/benzene-linked-to-neural-tube-birth-defects/) .Environmentalhealthnews.org (2010-10-26). Retrieved on 2011-04-17.

50.

^ Benzene exposure linked to sperm abnormalities that cause birth defects. Environmental Health News(http://www.environmentalhealthnews.org/ehs/newscience/benzene-linked-to-sperm-abnormalities) .Environmentalhealthnews.org (2010-02-16). Retrieved on 2011-04-17.

51.

^ 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.

52.

^ 10/16/2003 OSHA-recognized chemicals as carcinogens or potential carcinogens for Hazard Communicationpurposes (http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=INTERPRETATIONS&p_id=24730) . Osha.gov (2003-10-16). Retrieved on 2010-10-09.

53.

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

54.

^ ToxGuide for Benzene (http://www.atsdr.cdc.gov/toxguides/toxguide-3.pdf?id=39&tid=14) , Agency for ToxicSubstances and Disease Registry, Department of Health and Human Services

55.

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

56.

^ Public Health Statement. Benzene (http://www.atsdr.cdc.gov/ToxProfiles/tp3-c1-b.pdf) , Division of Toxicologyand Environmental Medicine, August 2007

57.


f 18 01/11/2012 11:33


17/18

^ "FDA: Too Much Benzene In Some Drinks" (http://www.cbsnews.com/stories/2006/05/19/health/main1638170.shtml) , CBS News, May 19, 2006. Retrieved July 11, 2006.

58.

^ Drinking Water Contaminants|Drinking Water Contaminants|US EPA (http://water.epa.gov/drink/contaminants/index.cfm#Organic) . Water.epa.gov. Retrieved on 2010-10-09.

59.

^ Chemical Sampling Information Benzene (http://www.osha.gov/dts/chemicalsampling/data/CH_220100.html) .Osha.gov. Retrieved on 2011-11-23.

60.

^ Benzene Toxicity: Standards and Regulations|ATSDR Environmental Medicine & Environmental HealthEducation CSEM (http://web.archive.org/web/20100610004540/http://www.atsdr.cdc.gov/csem/benzene

/standards_regulations.html) . Atsdr.cdc.gov (2000-06-30). Retrieved on 2010-10-09.

61.

^ NIOSH respirator selection logic. Cincinnati, OH: U.S. Department of Health and Human Services, PublicHealth Service, Centers for Disease Control, National Institute for Occupational Safety and Health, DHHS(NIOSH). Publication No. 2005-100.

62.

^ Documentation for Immediately Dangerous to Life or Health Concentrations (IDLH): Introduction(http://www.cdc.gov/niosh/idlh/idlhintr.html#CNU) . Cdc.gov. Retrieved on 2011-11-23.

63.

^ "Public Health Statement for Benzene" U.S. Department of Health and Human Services, Public Health Service,Centers for Disease Control, National Institute for Occupational Safety and Health (http://www.atsdr.cdc.gov/PHS/PHS.asp?id=37&tid=14) . Atsdr.cdc.gov (2011-03-03). Retrieved on 2011-11-23.

64.

^ Benzene. Product and Technical Information (http://www.sunocochem.com/HES/BenzeneBookFINAL.pdf) .(PDF) . Retrieved on 2011-11-23.

65.

^ 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.

66.

^ 01/10/1990 Use of Air-Purifying Respirators In Dangerous Concentrations of Gases Or Vapors(http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=INTERPRETATIONS&p_id=19907) .Osha.gov. Retrieved on 2010-10-09.

67.

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

68.

^ 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.

69.

^ Ashley, DL; Bonin, MA; Cardinali, FL; McCraw, JM; Wooten, JV (1994). "Blood concentrations of volatileorganic compounds in a nonoccupationally exposed US population and in groups with suspected exposure"(http://www.clinchem.org/cgi/reprint/40/7/1401.pdf) . Clinical chemistry40 (7 Pt 2): 14014. PMID 8013127

(//www.ncbi.nlm.nih.gov/pubmed/8013127) . http://www.clinchem.org/cgi/reprint/40/7/1401.pdf.

70.

^ Fustinoni, S; Buratti, M; Campo, L; Colombi, A; Consonni, D; Pesatori, AC; Bonzini, M; Farmer, P et al.(2005). "Urinary t,t-muconic acid, S-phenylmercapturic acid and benzene as biomarkers of low benzeneexposure". Chemico-biological interactions153154: 2536. doi:10.1016/j.cbi.2005.03.031 (http://dx.doi.org/10.1016%2Fj.cbi.2005.03.031) . PMID 15935823 (//www.ncbi.nlm.nih.gov/pubmed/15935823) .

71.

^ ACGIH. 2009 TLVs and BEIs. American Conference of Governmental Industrial Hygienists, Cincinnati, Ohio,2009.

72.

^ R. Baselt,Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City,CA, 2008, pp. 144148.

73.

^ Snyder, R; Hedli, C.C. (1996). "An overview of benzene metabolism" (//www.ncbi.nlm.nih.gov/pmc/articles/PMC1469747/) .Environ Health Perspect104 (Suppl 6): 11651171. PMC 1469747 (//www.ncbi.nlm.nih.gov

/pmc/articles/PMC1469747) . PMID 9118888 (//www.ncbi.nlm.nih.gov/pubmed/9118888) .//www.ncbi.nlm.nih.gov/pmc/articles/PMC1469747/.

74.

^ Dougherty, D; Garte, S; Barchowsky, A; Zmuda, J; Taioli, E (2008). "NQO1, MPO, CYP2E1, GSTT1 andSTM1 polymorphisms and biological effects of benzene exposurea literature review". Toxicology Letters182(13): 717. doi:10.1016/j.toxlet.2008.09.008 (http://dx.doi.org/10.1016%2Fj.toxlet.2008.09.008) .PMID 18848868 (//www.ncbi.nlm.nih.gov/pubmed/18848868) .

75.

^ Fracasso, M.E.; Doria, D; Bartolucci, GB; Carrieri, M; Lovreglio, P; Ballini, A; Soleo, L; Tranfo, G et al.(2009). "Low air levels of benzene: Correlation between biomarkers of exposure and genotoxic effects". Toxicol

Lett192 (1): 228. doi:10.1016/j.toxlet.2009.04.028 (http://dx.doi.org/10.1016%2Fj.toxlet.2009.04.028) .PMID 19427373 (//www.ncbi.nlm.nih.gov/pubmed/19427373) .

76.

^ Eastmond, D.A.; Rupa, DS; Hasegawa, LS (2000). "Detection of hyperdiploidy and chromosome breakage ininterphase human lymphocytes following exposure to the benzene metabolite hydroquinone using multicolor

fluorescence in situ hybridization with DNA probes".Mutat Res322 (1): 920. PMID 7517507(//www.ncbi.nlm.nih.gov/pubmed/7517507) .

77.

^ Garte, S; Taioli, E; Popov, T; Bolognesi, C; Farmer, P; Merlo, F (2000). "Genetic susceptibility to benzenetoxicity in humans".J Toxicol Environ Health A71 (22): 14821489. doi:10.1080/15287390802349974(http://dx.doi.org/10.1080%2F15287390802349974) . PMID 18836923 (//www.ncbi.nlm.nih.gov/pubmed

78.


f 18 01/11/2012 11:33


18/18

/18836923) .^ Agency for Toxic Substances and Disease Registry. (2007). Benzene: Patient information sheet.(http://www.atsdr.cdc.gov/mhmi/mmg3handout.pdf)

79.

^ 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 on2011-11-23.

80.

^ Public Health Statement for Benzene, Agency for Toxic Substances and Disease Registry. (August 2007).Benzene: Patient information sheet (http://www.atsdr.cdc.gov/PHS/PHS.asp?id=37&tid=14) . Atsdr.cdc.gov

(2011-03-03). Retrieved on 2011-11-23.

81.

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 PubChemDept. 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 onBenzene since Faraday, in 1991Substance 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 ChemIDplusdatabase

NLM Hazardous Substances Databank Benzene (http://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+35)

Retrieved from "http://en.wikipedia.org/w/index.php?title=Benzene&oldid=519290497"

Categories: Annulenes Simple aromatic rings IARC Group 1 carcinogens Soil contaminationHydrocarbon solvents Hazardous air pollutants Immunotoxins Mutagens TeratogensOccupational safety and health

This page was last modified on 22 October 2012 at 23:14.Text is available under the Creative Commons Attribution-ShareAlike License; additional terms mayapply. See Terms of Use for details.Wikipedia is a registered trademark of the Wikimedia Foundation, Inc., a non-profit organization.


Benzene - Wikipedia, The Free Encyclopedia

Documents