Benzene is an organic chemical compound with the molecular formula C6H6.

Its molecule is
composed of 6 carbon atoms joined in a ring, with 1 hydrogen atom attached to each carbon
atom. Because its molecules contain only carbon and hydrogen atoms, benzene is classed as
a hydrocarbon.
Benzene is a natural constituent of crude oil, and is one of the most
elementary petrochemicals. Benzene is an aromatic hydrocarbon and the second n!"
annulene #6!"annulene$, a cyclic hydrocarbon with a continuouspi bond. It is sometimes
abbre%iated &h'H. Benzene is a colorless and highly(ammable li)uid with a sweet smell. It is
mainly used as a precursor to hea%y chemicals, such as ethylbenzene and cumene, which are
produced on a billion *ilogram scale. Because it has a high octane number, it is an important
component of gasoline, comprising a few percent of its mass. +ost non"industrial applications
ha%e been limited by benzene,s carcinogenicity.
Contents
hide!
1 History
1.1 -isco%ery
1.. /ing formula
1.0 1arly applications
. 2tructure
0 Benzene deri%ati%es
3 &roduction
3.1 Catalytic reforming
3.. 4oluene hydrodeal*ylation
3.0 4oluene disproportionation
3.3 2team crac*ing
3.5 6ther sources
5 7ses
5.1 Component of gasoline
6 /eactions
6.1 2ulfonation, chlorination, nitration
6.. Hydrogenation
6.0 +etal comple8es
9 Health e:ects
; 18posure to benzene
;.1 Inhalation
;.. 18posure through smo*ing
;.0 18posure from soft drin*s
;.3 Case e8amples
;.5 Benzene e8posure limits
;.6 18posure monitoring
;.9 Biomar*ers of e8posure
;.; Biotransformations
;.< +olecular to8icology
;.1= Biological o8idation and carcinogenic acti%ity
;.11 2ummary
< 2ee also
1= /eferences
11 18ternal lin*s
History[edit]
Discovery[edit]
4he word >benzene> deri%es historically from >gum benzoin>, sometimes called >benjamin>
#i.e., benzoin resin$, an aromatic resin *nown to 1uropean pharmacists and perfumers since
the 15th century as a product of southeast ?sia.<! ?n acidic material was deri%ed from
benzoin by sublimation, and named >(owers of benzoin>, or benzoic acid. 4he hydrocarbon
deri%ed from benzoic acid thus ac)uired the name benzin, benzol, or benzene.1=!
+ichael @araday Arst isolated and identiAed benzene in 1;.5 from the oily residue deri%ed
from the production of illuminating gas, gi%ing it the namebicarburet of hydrogen.[11] [12]
In 1;00, 1ilhard +itscherlich produced it %ia the distillation of benzoic acid#from gum benzoin$
and lime. He ga%e the compound the name benzin.10!
In 1;06, the @rench chemist ?uguste Baurent named the substance >phCne>D13! this is the
root of the word phenol, which is hydro8ylatedbenzene, and phenyl, which is the radical
formed by abstraction of a hydrogen atom #free radical HE$ from benzene.
Historic benzene formulae as proposed by Fe*ulG.15!
In 1;35, Charles +ansAeld, wor*ing under?ugust Hilhelm %on Hofmann, isolated benzene
from coal tar.16! @our years later, +ansAeld began the Arst industrial"scale production of
benzene, based on the coal"tar method.[17] [18] Iradually the sense de%eloped among
chemists that substances related to benzene represent a di%erse chemical family. In
1;55 ?ugust Hilhelm Hofmann used the word >aromatic> to designate this family relationship,
after a characteristic property of many of its members.1<!
In 1<<9, benzene was detected in deep space..=!
Ring formula[edit]
4he empirical formula for benzene was long *nown, but its highlypolyunsaturated structure,
with just one hydrogen atom for each carbonatom, was challenging to determine. ?rchibald
2cott Couper in 1;5; andJoseph Boschmidt in 1;61.1! suggested possible structures that
contained multiple double bonds or multiple rings, but too little e%idence was then a%ailable
to help chemists decide on any particular structure.
In 1;65, the Ierman chemist @riedrich ?ugust Fe*ulG published a paper in @rench #for he was
then teaching in @rancophone Belgium$ suggesting that the structure contained a si8"
membered ring of carbon atoms with alternating single and double bonds. 4he ne8t year he
published a much longer paper in Ierman on the same subject.[22] [23] Fe*ulG used e%idence
that had accumulated in the inter%ening yearsKnamely, that there always appeared to be
only one isomer of any monoderi%ati%e of benzene, and that there always appeared to be
e8actly three isomers of e%ery disubstituted deri%ati%eKnow understood to correspond to the
ortho, meta, and para patterns ofarene substitutionKto argue in support of his proposed
structure..3!Fe*ulG,s symmetrical ring could e8plain these curious facts, as well as benzene,s
1L1 carbon"hydrogen ratio..5!
Historic benzene formulae #from left to right$ by Claus #1;69$,.6! -ewar #1;69$,.9! Badenburg #1;6<$,
.;! ?rmstrong #1;;9$,.<! 4hiele #1;<<$0=! and Fe*ulG #1;65$. -ewar benzene and prismane are di:erent
chemicals that ha%e -ewar,s and Badenburg,s structures. 4hiele and Fe*ulG,s structures are used today.
4he new understanding of benzene, and hence of all aromatic compounds, pro%ed to be so
important for both pure and applied chemistry that in 1;<= the Ierman Chemical 2ociety
organized an elaborate appreciation in Fe*ulG,s honor, celebrating the twenty"Afth
anni%ersary of his Arst benzene paper. Here Fe*ulG spo*e of the creation of the theory. He
said that he had disco%ered the ring shape of the benzene molecule after ha%ing a re%erie or
day"dream of a sna*e seizing its own tail #this is a common symbol in many ancient cultures
*nown as the 6uroboros or 1ndless *not$.01! 4his %ision, he said, came to him after years of
studying the nature of carbon"carbon bonds. 4his was 9 years after he had sol%ed the
problem of how carbon atoms could bond to up to four other atoms at the same time. It is
curious that a similar, humorous depiction of benzene had appeared in 1;;6 in the Berichte
der Durstigen Chemischen Gesellschaft #Journal of the 4hirsty Chemical 2ociety$, a parody of
the Berichte der Deutschen Chemischen Gesellschaft, only the parody had mon*eys seizing
each other in a circle, rather than sna*es as in Fe*ulG,s anecdote.0.! 2ome historians ha%e
suggested that the parody was a lampoon of the sna*e anecdote, possibly already well *nown
through oral transmission e%en if it had not yet appeared in print.1=! #2ome others ha%e
speculated that Fe*ulG,s story in 1;<= was a re"parody of the mon*ey spoof, and was a mere
in%ention rather than a recollection of an e%ent in his life.citation needed!$ Fe*ulG,s 1;<=
speech00! in which these anecdotes appeared has been translated into 1nglish.03! If the
anecdote is the memory of a real e%ent, circumstances mentioned in the story suggest that it
must ha%e happened early in 1;6..05!
4he cyclic nature of benzene was Anally conArmed by the crystallographer Fathleen
Bonsdale in 1<.<.[36] [37]
Early applications[edit]
In the 1<th and early".=th centuries, benzene was used as an after"sha%e lotion because of its
pleasant smell. &rior to the 1<.=s, benzene was fre)uently used as an industrial sol%ent,
especially for degreasing metal. ?s its to8icity became ob%ious, benzene was supplanted by
other sol%ents, especially toluene #methyl benzene$, which has similar physical properties but
is not as carcinogenic.
In 1<=0, Budwig /oselius popularized the use of benzene to deca:einate co:ee. 4his
disco%ery led to the production of2an*a. 4his process was later discontinued. Benzene was
historically used as a signiAcant component in many consumer products such as Bi)uid
Hrench, se%eral paint strippers, rubber cements, spot remo%ers and other hydrocarbon"
containing products. 2ome ceased manufacture of their benzene"containing formulations in
about 1<5=, while others continued to use benzene as a component or signiAcant
contaminant until the late 1<9=s when leu*emia deaths were found associated with
Ioodyear,s &lioAlm production operations in 6hio. 7ntil the late 1<9=s, many hardware stores,
paint stores, and other retail outlets sold benzene in small cans, such as )uart size, for
general"purpose use. +any students were e8posed to benzene in school and uni%ersity
courses while performing laboratory e8periments with little or no %entilation in many cases.
4his %ery dangerous practice has been almost totally eliminated.
Structure[edit]
Main article: Aromaticity
Benzene represents a special problem in that, to account for the bond lengths )uantitati%ely,
there must either be electron delocalization #molecular orbital theory$ or a spin coupling of
the p"orbitals #%alence bond theory$L0;!
4he %arious representations of benzene
M"ray di:raction shows that all si8 carbon"carbon bonds in benzene are of the same length, at
13= picometres#pm$. 4he C'C bond lengths are greater than a double bond, #105 pm$, but
shorter than a single bond, #139 pm$. 4his intermediate distance is consistent with
electron delocalizationL the electrons for C'C bonding are distributed e)ually between each of
the si8 carbon atoms. Benzene has ; hydrogen atoms fewer than the corresponding parent
al*ane, he8ane. 4he molecule is planar.0<! 4he +6 description in%ol%es the formation of three
delocalized N orbitals spanning all si8 carbon atoms, while in OB theory the aromatic
properties of benzene originate from spin coupling of all si8 N orbitals.[40] [41] [42] [43] It is
li*ely that this stability contributes to the peculiar molecular and chemical properties *nown
asaromaticity. 4o indicate the delocalized nature of the bonding, benzene is often depicted
with a circle inside a he8agonal arrangement of carbon atoms.
?s is common in organic chemistry, the carbon atoms in the diagram abo%e ha%e been left
unlabeled. /ealizing each carbon has .p electrons, each carbon donates an electron into the
delocalized ring abo%e and below the benzene ring. It is the side"on o%erlap of p"orbitals that
produces the pi clouds.
-eri%ati%es of benzene occur suPciently often as a component of organic molecules that
there is a 7nicode symbol in the+iscellaneous 4echnical bloc* with the code 7Q.0.C #R$ to
represent it with three double bonds,33! and 7Q.010 #S$ for a delocalized %ersion.35!
Benzene derivatives[edit]
Main articles: Aromatic hydrocarbons and Alkylbenzenes
+any important chemical compounds are deri%ed from benzene by replacing one or more of
its hydrogen atoms with anotherfunctional group. 18amples of simple benzene deri%ati%es
are phenol, toluene, and aniline, abbre%iated &h6H, &h+e, and &hTH., respecti%ely. Bin*ing
benzene rings gi%es biphenyl, C6H5'C6H5. @urther loss of hydrogen gi%es >fused> aromatic
hydrocarbons, such as naphthalene and anthracene. 4he 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. 4he most
important deri%ati%es are the rings containing nitrogen. /eplacing one CH with T gi%es the
compound pyridine, C5H5T. ?lthough benzene and pyridine arestructurally related, benzene
cannot be con%erted into pyridine. /eplacement of a second CH bond with T gi%es, depending
on the location of the second T, pyridazine, pyrimidine, and pyrazine.
Production[edit]
@our chemical processes contribute to industrial benzene productionL catalytic
reforming, toluene hydrodeal*ylation, toluene disproportionation, and steam crac*ing.
?ccording to the ?42-/ 4o8icological &roAle for benzene, between 1<9; and 1<;1, catalytic
reformats accounted for appro8imately 33'5=U of the total 7.2 benzene production.
7ntil Horld Har II, most benzene was produced as a by"product of co*e production #or >co*e"
o%en light oil>$ in the steelindustry. Howe%er, in the 1<5=s, increased demand for benzene,
especially from the growing polymers industry, necessitated the production of benzene from
petroleum. 4oday, most benzene comes from the petrochemical industry, with only a small
fraction being produced from coal.
Catalytic reforming[edit]
In catalytic reforming, a mi8ture of hydrocarbons with boiling points between 6='.== VC is
blended with hydrogen gas and then e8posed to a bifunctional platinum chloride
or rhenium chloride catalyst at 5=='5.5 VC and pressures ranging from ;'5= atm. 7nder
these conditions, aliphatic hydrocarbons form rings and lose hydrogen to become aromatic
hydrocarbons. 4he aromatic products of the reaction are then separated from the reaction
mi8ture #or reformate$ by e8traction with any one of a number of sol%ents,
including diethylene glycol or sulfolane, and benzene is then separated from the other
aromatics by distillation. 4he e8traction step of aromatics from the reformate is designed to
produce aromatics with lowest non"aromatic components. /eco%ery of the aromatics,
commonly referred to as B4M #benzene, toluene and 8ylene isomers$, in%ol%es such e8traction
and distillation steps. 4here are a good many licensed processes a%ailable for e8traction of
the aromatics.
In similar fashion to this catalytic reforming, 76& and B& commercialized a method from B&I
#mainly propane and butane$ to aromatics.
Toluene hydrodealkylation[edit]
4oluene hydrodeal*ylation con%erts toluene to benzene. In this hydrogen"intensi%e process,
toluene is mi8ed with hydrogen, then passed o%er a chromium, molybdenum,
or platinum o8ide catalyst at 5=='6== VC and 3='6= atm pressure. 2ometimes, higher
temperatures are used instead of a catalyst #at the similar reaction condition$. 7nder these
conditions, toluene undergoes deal*ylation to benzene and methaneL
C6H5CH0 Q H. W C6H6 Q CH3
4his irre%ersible reaction is accompanied by an e)uilibrium side reaction that
produces biphenyl #a*a diphenyl$ at higher temperatureL
. C
6H
6 H
. Q C
6H
5'C
6H
5
If the raw material stream contains much non"aromatic components #paraPns or
naphthenes$, those are li*ely decomposed to lower hydrocarbons such as methane, which
increases the consumption of hydrogen.
? typical reaction yield e8ceeds <5U. 2ometimes, 8ylenes and hea%ier aromatics are used in
place of toluene, with similar ePciency.
4his is often called >on"purpose> methodology to produce benzene, compared to con%entional
B4M #benzene"toluene"8ylene$ e8traction processes.
Toluene disproportionation[edit]
Hhere a chemical comple8 has similar demands for both benzene and 8ylene, then
toluene disproportionation #TDP$ may be an attracti%e alternati%e to the toluene
hydrodeal*ylation. In the broad sense, . toluene molecules are reacted and the methyl groups
rearranged from one toluene molecule to the other, yielding one benzene molecule and one
8ylene molecule.
Ii%en that demand for para"8ylene #p"8ylene$ substantially e8ceeds demand for other 8ylene
isomers, a reAnement of the 4-& process called elective TDP #24-&$ may be used. In this
process, the 8ylene stream e8iting the 4-& unit is appro8imately <=U para8ylene. In some
current catalytic systems, e%en the benzene"to"8ylenes ratio is decreased #more 8ylenes$
when the demand of 8ylenes is higher.
team cracking[edit]
2team crac*ing is the process for producing ethylene and other al*enes from aliphatic
hydrocarbons. -epending on the feedstoc* used to produce the oleAns, steam crac*ing can
produce a benzene"rich li)uid by"product called pyrolysis gasoline. &yrolysis gasoline can be
blended with other hydrocarbons as a gasoline additi%e, or routed through an e8traction
process to reco%er B4M aromatics #benzene, toluene and 8ylenes$.
!ther sources[edit]
4race amounts of benzene may result whene%er carbon"rich materials undergo
incomplete combustion. It is produced in%olcanoes and forest Ares, and is also a component
of cigarette smo*e. Benzene is a principal product from the combustion of &OC #poly%inyl
chloride$.
Uses[edit]
Benzene is used mainly as an intermediate to ma*e other chemicals. ?bout ;=U of benzene is
consumed in the production of three chemicals, ethylbenzene, cumene, and cyclohe8ane. Its
most widely produced deri%ati%e is ethylbenzene, precursor to styrene, which is used to ma*e
polymers and plastics. Cumene is con%erted phenol for resins and adhesi%es.Cyclohe8ane is
used in the manufacture of Tylon. 2maller amounts of benzene are used to ma*e some types
of rubbers,lubricants, dyes, detergents, drugs, e8plosi%es, and pesticides.
In both the 72 and 1urope, 5=U of benzene is used in the production of ethylbenzeneXstyrene,
.=U is used in the production of cumene, and about 15U of benzene is used in the production
of cyclohe8ane #e%entually tonylon$.citation needed!
Currently, the production of and demand for benzene in the +iddle 1ast register the greatest
increases worldwide.
In laboratory research, toluene is now often used as a substitute for benzene. 4he sol%ent"
properties of the two are similar, but toluene is less to8ic and has a wider li)uid range.
+ajor commodity chemicals and polymers deri%ed from benzene. Clic*ing on the image loads the
appropriate article
Component of gasoline[edit]
?s a gasoline #petrol$ additi%e, benzene increases the octane rating and reduces *noc*ing. ?s
a conse)uence, gasoline often contained se%eral percent benzene before the 1<5=s,
when tetraethyl lead replaced it as the most widely used anti*noc* additi%e. Hith the global
phaseout of leaded gasoline, benzene has made a comebac* as a gasoline additi%e in some
nations. In the 7nited 2tates, concern o%er its negati%e health e:ects and the possibility of
benzene,s entering thegroundwater ha%e led to stringent regulation of gasoline,s benzene
content, with limits typically around 1U.36! 1uropean petrol speciAcations now contain the
same 1U limit on benzene content. 4he 7nited 2tates 1n%ironmental &rotection
?gencyintroduced new regulations in .=11 that lowered the benzene content in gasoline to
=.6.U.39!
Reactions[edit]
4he most common reactions of benzene in%ol%e substitution of a proton by other groups.
3;! 1lectrophilic aromatic substitution is a general method of deri%atizing benzene. Benzene
is suPciently nucleophilic that it undergoes substitution byacylium ions and
al*yl carbocations to gi%e substituted deri%ati%es.
1lectrophilic aromatic substitution of benzene
4he most widely practiced e8ample of this reaction is the ethylation of benzene.
?ppro8imately .3,9==,=== tons were produced in 1<<<.3<! Highly instructi%e but of far less
industrial signiAcance is the@riedel"Crafts al*ylation of benzene #and many other aromatic
rings$ using an al*yl halide in the presence of a strong Bewis acid catalyst. 2imilarly,
the @riedel"Crafts acylation is a related e8ample of electrophilic aromatic substitution. 4he
reaction in%ol%es the acylation of benzene #or many other aromatic rings$ with an acyl
chloride using a strong Bewis acid catalystsuch as aluminium chloride or Iron#III$ chloride.
@riedel"Crafts acylation of benzene by acetyl chloride
ulfonation" chlorination" nitration[edit]
7sing electrophilic aromatic substitution, many functional groups are introduced onto the
benzene framewor*. 2ulfonation of benzene in%ol%es the use of oleum, a mi8ture of sulfuric
acid with sulfur trio8ide. 2ulfonated benzene deri%ati%es are usefuldetergents. In nitration,
benzene reacts with nitronium ions #T6.Q$, which is a strong electrophile produced by
combining sulfuric and nitric acids. Titrobenzene is the precursor to aniline. Chlorination in
achie%ed with chlorine to gi%echlorobenzene in the presence of a catalyst such as aluminium
trichloride.
#ydrogenation[edit]
Oia hydrogenation, benzene and its deri%ati%es con%ert to cyclohe8ane and deri%ati%es. 4his
reaction is achie%ed by the use of high pressures of hydrogen at high temperatures in the
presence of a Anely di%ided nic*el, which ser%es as a catalyst. In the absence of the catalyst,
benzene is imper%ious to hydrogen. 4his reaction is practiced on a %ery large scale
industrially.
$etal comple%es[edit]
Benzene is an e8cellent ligand in the organometallic chemistry of low"%alent metals.
Important e8amples include the sandwich and half"sandwich comple8es,
respecti%ely, Cr#C6H6$. and /uCl.#C6H6$!..
Health efects[edit]
? bottle of benzene. 4he warnings show benzene is a to8ic and (ammable li)uid.
Benzene increases the ris* of cancer and other illnesses. Benzene is a notorious cause of
bone marrow failure. 2ubstantial )uantities of epidemiologic, clinical, and laboratory data lin*
benzene to aplastic anemia, acute leu*emia, and bone marrow abnormalities.[50] [51] 4he
speciAc hematologic malignancies that benzene is associated with includeL acute myeloid
leu*emia #?+B$, aplastic anemia, myelodysplastic syndrome #+-2$, acute lymphoblastic
leu*emia #?BB$, and chronic myeloid leu*emia #C+B$.5.!
4he ?merican &etroleum Institute #?&I$ stated in 1<3; that >it is generally considered that the
only absolutely safe concentration for benzene is zero.>50! 4he 72 -epartment of Health and
Human 2er%ices #-HH2$ classiAes benzene as a humancarcinogen. Bong"term e8posure to
e8cessi%e le%els of benzene in the air causesleu*emia, a potentially fatal cancer of the blood"
forming organs, in susceptible indi%iduals. In particular, ?cute myeloid leu*emia or acute
nonlymphocytic leu*emia#?+B Y ?TBB$ is not disputed to be caused by benzene.53! I?/C
rated benzene as >*nown to be carcinogenic to humans> #Iroup 1$.
Human e8posure to benzene is a global health problem.vague! Benzene targets li%er, *idney,
lung, heart and the brain and can cause -T? strand brea*s, chromosomaldamage, etc.
Benzene causes cancer in animals including humans. Benzene has been shown to cause
cancer in both se8es of multiple species of laboratory animals e8posed %ia %arious routes.[55]
[56]
2ome women who inhaled high le%els of benzene for many months had
irregular menstrual periods and a decrease in the size of their o%aries. Benzene e8posure has
been lin*ed directly to the neural birth defects spina biAda and anencephaly.59!+en e8posed
to high le%els of benzene are more li*ely to ha%e an abnormal amount of chromosomes in
their sperm, which impacts fertility and fetal de%elopment.5;!
Exposure to benzene[edit]
Bight refraction of benzene #abo%e$ and water #below$
See also : Benzene in soft drinks!nvironmental e"posure to benzene
Oapors from products that contain benzene, such as glues, paints, furniture wa8, and
detergents, can also be a source of e8posure, although many of these ha%e been modiAed or
reformulated since the late 1<9=s to eliminate or reduce the benzene content. ?ir around
hazardous waste sites or gas stations may contain higher le%els of benzene. Because
petroleum hydrocarbon products are comple8 mi8tures of chemicals, ris* assessments for
these products, in general, focus on speciAc to8ic constituents. 4he petroleum constituents of
primary interest to human health ha%e been the aromatic hydrocarbons #i.e., benzene,
ethylbenzene, toluene, and 8ylenes$. In the 7.2., 62H? re)uires that a mi8ture >shall be
assumed to present a carcinogenic hazard if it contains a component in concentrations of
=.1U or greater, which is considered to be a carcinogen.[59] [60]
6utdoor air may contain low le%els of benzene from automobile ser%ice stations, wood smo*e,
tobacco smo*e, the transfer of gasoline, e8haust from motor %ehicles, and industrial
emissions.61! ?bout 5=U of the entire nationwide #7nited 2tates$ e8posure to benzene results
from smo*ing tobacco or from e8posure to tobacco smo*e.6.!
&nhalation[edit]
Inhaled benzene is primarily e8pelled unchanged through e8halation. In a human study 16.3
to 31.6U of retained benzene was eliminated through the lungs within A%e to se%en hours
after a two" to three"hour e8posure to 39 to 11= ppm and only =.=9 to =..U of the remaining
benzene was e8creted unchanged in the urine. ?fter e8posure to 60 to 3=5 mgXm0 of benzene
for 1 to 5 hours, 51 to ;9U was e8creted in the urine as phenol o%er a period of .0 to 5=
hours. In another human study, 0=U of absorbed dermally applied benzene, which is primarily
metabolized in the li%er, was e8creted as phenol in the urine.60!
E%posure through smoking[edit]
18posure of the general population to benzene occurs mainly through breathing, the major
sources of benzene being tobacco smo*e #about 5=U$ as well as automobile ser%ice stations,
e8haust from motor %ehicles and industrial emissions #about .=U altogether$. ?ccording to
the C-C, >4he mean number of cigarettes per day #cpd$ among daily smo*ers in 1<<0 was
1<.6 #.1.0 cpd for men and 19.; cpd for women$ and in .==3 was 16.; #1;.1 cpd for men and
15.0 cpd for women$.>63!?ccording to the ?ugust .==9 &ublic Health 2tatement, the a%erage
smo*er smo*es 0. cpd, which in turn the a%erage smo*er would ta*e in about 1.; milligrams
#mg$ of benzene per day. 4his amount is about 1= times the a%erage daily inta*e of benzene
by nonsmo*ers.65!
E%posure from soft drinks[edit]
This section requires expansion.(April 2013)
In +arch .==6, the oPcial @ood 2tandards ?gency in Britain conducted a sur%ey of 15=
brands of soft drin*s. It found that four contained benzene le%els abo%e Horld Health
6rganization limits. 4he a:ected batches were remo%ed from sale.66!#2ee also benzene in
soft drin*s$.
Case e%amples[edit]
Hater and soil contamination are important pathways of concern for transmission of benzene.
In the 72 alone, appro8imately 1==,=== sites ha%e soil or groundwater contaminated with
benzene.citation needed!
In .==5, the water supply to the city of Harbin in China with a population of almost nine
million people, was cut o: because of a major benzene e8posure. Benzene lea*ed into
the 2onghua /i%er, which supplies drin*ing water to the city, after an e8plosion at a China
Tational &etroleum Corporation #CT&C$ factory in the city of Jilin on 10 To%ember.citation
needed!
Benzene e%posure limits[edit]
4he 7nited 2tates 1n%ironmental &rotection ?gency has set a ma8imum contaminant
le%el #+CB$ for benzene in drin*ing water at =.==5 mgXB #5 ppb$, as promulgated %ia the 7.2.
Tational &rimary -rin*ing Hater /egulations.69! 4his regulation is based on pre%enting
benzene leu*emogenesis. 4he ma8imum contaminant le%el goal #+CBI$, a nonenforceable
health goal that would allow an ade)uate margin of safety for the pre%ention of ad%erse
e:ects, is zero benzene concentration in drin*ing water. 4he 1&? re)uires that spills or
accidental releases into the en%ironment of 1= pounds #3.5 *g$ or more of benzene be
reported.
4he 7.2. 6ccupational 2afety and Health ?dministration #62H?$ has set a permissible
e8posure limit of 1 part of benzene per million parts of air #1 ppm$ in the wor*place during an
;"hour wor*day, 3="hour wor*wee*. 4he short term e8posure limit for airborne benzene is 5
ppm for 15 minutes.6;! 4hese legal limits were based on studies demonstrating compelling
e%idence of health ris* to wor*ers e8posed to benzene. 4he ris* from e8posure to 1 ppm for a
wor*ing lifetime has been estimated as 5 e8cess leu*emia deaths per 1,=== employees
e8posed. #4his estimate assumes no threshold for benzene,s carcinogenic e:ects.$ 62H? has
also established an action le%el of =.5 ppm to encourage e%en lower e8posures in the
wor*place.6<!
4he 7.2. Tational Institute for 6ccupational 2afety and Health #TI62H$ re%ised
the Immediately -angerous to Bife and Health #I-BH$ concentration for benzene to 5== ppm.
4he current TI62H deAnition for an I-BH condition, as gi%en in the TI62H /espirator 2election
Bogic, is one that poses a threat of e8posure to airborne contaminants when that e8posure is
li*ely to cause death or immediate or delayed permanent ad%erse health e:ects or pre%ent
escape from such an en%ironment TI62H .==3!. 4he purpose of establishing an I-BH %alue is
#1$ to ensure that the wor*er can escape from a gi%en contaminated en%ironment in the e%ent
of failure of the respiratory protection e)uipment and #.$ is considered a ma8imum le%el
abo%e which only a highly reliable breathing apparatus pro%iding ma8imum wor*er protection
is permitted TI62H .==39=!!.91! In 2eptember 1<<5, TI62H issued a new policy for
de%eloping recommended e8posure limit #/1Bs$ for substances, including carcinogens.
Because benzene can cause cancer, TI62H recommends that all wor*ers wear special
breathing e)uipment when they are li*ely to be e8posed to benzene at le%els e8ceeding the
/1B #1="hour$ of =.1 ppm.9.!4he TI62H 241B #15 min$ is 1 ppm.
?merican Conference of Io%ernmental Industrial Hygienists #?CIIH$ adopted 4hreshold Bimit
Oalues #4BOs$ for benzene at =.5 ppm 4H? and ..5 ppm 241B.
E%posure monitoring[edit]
?irborne e8posure monitoring for benzene must be conducted in order to properly assess
personal e8posures and e:ecti%eness of engineering controls. Initial e8posure monitoring
should be conducted by an industrial hygienist or person speciAcally trained and e8perienced
in sampling techni)ues. Contact an ?IH? ?ccredited Baboratory for ad%ice on sampling
methods.90!
1ach employer with a place of employment where occupational e8posures to benzene occur
shall monitor each of these wor*places and wor* operations to determine accurately the
airborne concentrations of benzene to which employees may be e8posed.93! /epresentati%e
;"hour 4H? employee e8posures need to be determined on the basis of one sample or
samples representing the full shift e8posure for each job classiAcation in each wor* area.
7nless air samples are ta*en fre)uently, the employer does not *now the concentration and
would not *now how much of a protection factor is needed.95!
In pro%iding consultation on wor* safety during oil clean"up operations following the
-eepwater Horizon accident, 62H? has wor*ed with a number of other go%ernment agencies
to protect Iulf cleanup wor*ers. 62H? partnered with the TI62H to issue >Interim Iuidance
for &rotecting -eepwater Horizon /esponse Hor*ers and Oolunteers> and recommend
measures that should be ta*en to protect wor*ers from a %ariety of di:erent health hazards
that these wor*ers face.96! 62H? conceded that it recognizes that most of its &1Bs are
outdated and inade)uate measures of wor*er safety. In characterizing wor*er e8posure, 62H?
instead relies on more up"to"date recommended protecti%e limits set by organizations such as
TI62H, the ?CIIH, and the ?merican Industrial Hygiene ?ssociation #?IH?$, and not on the
older, less protecti%e &1B2. /esults of air monitoring are compared to the lowest *nown
6ccupational 18posure Bimit for the listed contaminant for purposes of ris* assessment and
protecti%e e)uipment recommendations.99!
Biomarkers of e%posure[edit]
2e%eral tests can determine e8posure to benzene. Benzene itself can be measured in breath,
blood or urine, but such testing is usually limited to the Arst .3 hours post"e8posure due to
the relati%ely rapid remo%al of the chemical by e8halation or biotransformation. +ost persons
in de%eloped countries ha%e measureable baseline le%els of benzene and other aromatic
petroleum hydrocarbons in their blood. In the body, benzene is enzymatically con%erted to a
series of o8idation products including muconic acid, phenylmercapturic
acid, phenol, catechol, hydro)uinone and 1,.,3"trihydro8ybenzene. +ost of these metabolites
ha%e some %alue as biomar*ers of human e8posure, since they accumulate in the urine in
proportion to the e8tent and duration of e8posure, and they may still be present for some
days after e8posure has ceased. 4he current ?CIIH biological e8posure limits for occupational
e8posure are 5== ZgXg creatinine for muconic acid and .5 ZgXg creatinine for
phenylmercapturic acid in an end"of"shift urine specimen.[78] [79] [80] [81]
Biotransformations[edit]
1%en if it is not a common substrate for the metabolism of organisms, benzene can be
o8idized by both bacteria andeu*aryotes. In bacteria, dio8ygenase enzyme can add
an o8ygen molecule to the ring, and the unstable product is immediately reduced #by T?-H$
to a cyclic diol with two double bonds, brea*ing the aromaticity. Te8t, the diol is newly
reduced by T?-H to catechol. 4he catechol is then metabolized to acetyl Co? and succinyl
Co?, used by organisms mainly in the Frebs Cycle for energy production.
4he pathway for the metabolism of benzene is comple8 and begins in the li%er. 2e%eral *ey
enzymes are in%ol%ed. 4hese include cytochrome &35= .11 #C[&.11$, )uinine o8idoreductase
#T\=1$, I2H, and myelopero8idase #+&6$. C[&.11 is in%ol%ed at multiple stepsL con%erting
benzene to o8epin #benzene o8ide$, phenol to hydro)uinone, and hydro)uinone to both
benzenetriol and catechol. Hydro)uinone, benzenetriol and catechol are con%erted to
polyphenols. In the bone marrow, +&6 con%erts these polyphenols to benzo)uinones. 4hese
intermediates and metabolites induce genoto8icity by multiple mechanisms including
inhibition of topoisomerase II #which maintains chromosome structure$, disruption of
microtubules #which maintains cellular structure and organization$, generation of o8ygen free
radicals #unstable species$ that may lead to point mutations, increasing o8idati%e stress,
inducing -T? strand brea*s, and altering -T? methylation #which can a:ect gene
e8pression$. T\=1 and I2H shift metabolism away from to8icity. T\=1 metabolizes
benzo)uinone toward polyphenols #counteracting the e:ect of +&6$. I2H is in%ol%ed with the
formation of phenylmercapturic acid.[52] [82]
Ienetic polymorphisms in these enzymes may induce loss of function or gain of function. @or
e8ample, mutations in C[&.11 increase acti%ity and result in increased generation of to8ic
metabolites. T\=1 mutations result in loss of function and may result in decreased
deto8iAcation. +yelopero8idase mutations result in loss of function and may result in
decreased generation of to8ic metabolites. I2H mutations or deletions result in loss of
function and result in decreased deto8iAcation. 4hese genes may be targets for genetic
screening for susceptibility to benzene to8icity.;0!
$olecular to%icology[edit]
4he paradigm of to8icological assessment of benzene is shifting towards the domain of
molecular to8icology as it allows understanding of fundamental biological mechanisms in a
better way. Ilutathione seems to play an important role by protecting against benzene"
induced -T? brea*s and it is being identiAed as a new biomar*er for e8posure and e:ect.
;3!Benzene causes chromosomal aberrations in the peripheral blood leu*ocytes and bone
marrow e8plaining the higher incidence of leu*emia and multiple myeloma caused by chronic
e8posure. 4hese aberrations can be monitored using(uorescent in situ hybridization #@I2H$
with -T? probes to assess the e:ects of benzene along with the hematological tests as
mar*ers of hematoto8icity.;5! Benzene metabolism in%ol%es enzymes coded for by
polymorphic genes. 2tudies ha%e shown that genotype at these loci may in(uence
susceptibility to the to8ic e:ects of benzene e8posure. Indi%iduals carrying %ariant of
T?-#&$HL)uinone o8idoreductase 1 #T\61$, microsomal epo8ide hydrolase #1&HM$ and
deletion of the glutathione 2"transferase 41 #I2441$ showed a greater fre)uency of -T?
single"stranded brea*s.;6!
Biological o%idation and carcinogenic activity[edit]
6ne way of understanding the carcinogenic e:ects of benzene is by e8amining the products
of biological o8idation. &ure benzene, for e8ample, o8idizes in the body to produce an
epo8ide, benzene o8ide, which is not e8creted readily and can interact with -T? to produce
harmful mutations.
ummary[edit]
?ccording to the ?gency for 4o8ic 2ubstances and -isease /egistry #?42-/$ #.==9$, benzene
is both an anthropogenically produced and naturally occurring chemical from processes that
includeL %olcanic eruptions, wild Ares, synthesis of chemicals such as phenol, production of
synthetic Abers, and fabrication of rubbers, lubricants, pesticides, medications, and dyes. 4he
major sources of benzene e8posure are tobacco smo*e, automobile ser%ice stations, e8haust
from motor %ehicles, and industrial emissionsD howe%er, ingestion and dermal absorption of
benzene can also occur through contact with contaminated water. Benzene is hepatically
metabolized and e8creted in the urine. +easurement of air and water le%els of benzene is
accomplished through collection %ia acti%ated charcoal tubes, which are then analyzed with a
gas chromatograph. 4he measurement of benzene in humans can be accomplished %ia urine,
blood, and breath testsD howe%er, all of these ha%e their limitations because benzene is
rapidly metabolized in the human body into by"products called metabolites.;9!
62H? regulates le%els of benzene in the wor*place.;;! 4he ma8imum allowable amount of
benzene in wor*room air during an ;"hour wor*day, 3="hour wor*wee* is 1 ppm. Because
benzene can cause cancer, TI62H recommends that all wor*ers wear special breathing
e)uipment when they are li*ely to be e8posed to benzene at le%els e8ceeding the
recommended #;"hour$ e8posure limit of =.1 ppm.;<!