Substance identification : CAS Registry Number: 71-43-2

EINECS Number : 200-753-7

Synonyms:

(6)-Annulene; benzol; benzole; benzolene; bicarburet of hydrogen; carbon oil; coal naphtha;

cyclohexatriene; mineral naphtha; motor benzol; phene hydride; pyrobenzol; pyrobenzole

Molecular Formula: C6H6

References:

- IARC (1982) IARC Monographs on the evaluation of the carcinogenic risk of chemicals in humans, Some industrial chemicals and dyestuffs, Chemical, Environmental and Experimental Data, Lyon- IPCS (1993) Environmental Health Criteria 150 Benzene, WHO, Geneva- http://www.chemfinder.com

BENZENE: SUBSTANCE IDENTIFICATION AND PHYSICO-CHEMICAL PROPERTIES

Benzene, also known as benzol, is a colorless liquidwith a sweet odor. Benzene evaporates intoair very quickly and dissolves slightly in water. Benzeneis highly flammable. Benzene is found in air, water, andsoil.

Natural sources of benzene, which include gasemissions from volcanoes andforest fires, also contribute to the presence of benzene inthe environment. Benzene is alsopresent in crude oil and gasoline (approximately 1–2%)and cigarette smoke.

Most people can begin to smell benzene in air at 1.5–4.7parts of benzene per million parts of air (ppm)

Isolato da Faraday nel 1825 da un liquido ottenuto per condensazione di combustibili gassosi

sintetizzato per la prima volta da Mitscherlich nel 1833 per distillazione dell’acido benzoico.

Fine anni 20 la sua struttura chimica, ad anello esagonale con doppi legami alternati, grazie a una geniale intuizione del chimico Kekulè.

1881 grandi quantità di benzene per distillazione del carbone fossile e petrolio1930 le prime sperimentazioni del processo di cracking catalitico 1941 produzione di benzene su scala industriale da petrolio 1950 fu messo a punto un processo che usava catalizzatori come Pt e Pd per la deidrogenazione delle cicloparaffine.catalytic reforming, fonte primaria di prodotti aromatici.

Prima della seconda guerra mondiale benzene come additivo per carburanti, dato il suo elevato potere antidetonante, oppure come solvente in molteplici attività industriali ed artigianali (produzione della gomma e di sostanze come collanti, pitture, vernici).

Benzene ranks in the top 20 most abundantly produced chemicals in the world. Currently, benzene is commercially recovered from both coal and petroleum sources. More than 98% ofthe benzene is derived from the petrochemical and petroleum refining industries. These sources include refinery streams (catalytic reformats), pyrolysis gasoline, and toluene hydrodealkylation. Catalytic reformat is the major source of benzene which accounts for approximately 44–50% of the total benzene production. During catalytic reforming, cycloparaffins (also known by the obsolescent term "naphthenes") such as cyclohexane, methyl cyclohexane, and dimethylcyclohexane are converted to benzene by isomerization, dehydrogenation, and dealkylation, and paraffins in naphtha (such as hexane) are converted to benzene by cyclodehydrogenation.

Benzene has been used extensively as a solvent in the chemical and drug industries, as a starting materialand intermediate in the synthesis of numerous chemicals, and as a gasoline additive The major uses of benzene are in the production of ethylbenzene, cumene, and cyclohexane. Ethylbenzene (55% of benzene production volume) is an intermediate in the synthesis of styrene, which is used to make plastics and elastomers. Cumene (24%) is used to produce phenol and acetone. Phenols are used in the manufacture of phenolic resins and nylon intermediates; acetone is used as a solvent and in the manufacture of pharmaceuticals.

cumene

GREGGIO = C1-C34 MAX C60

BENZINA = C4-C12 DISTILLAZIONE 25-220 °C

DIESEL = C9-C20 DISTILLAZIONE 163-357 °C

MTBE (Metil terz-butil etere)

BENZENE IS A COMMON COMBUSTION PRODUCT

SMOKING ACCOUNTS FOR APPROXIMATELY HALF OF THE TOTALBENZENE EXPOSURE OF THE GENERAL POPULATION

SMOKERS STUDY HAD A MEAN BREATH CONCENTRATION OF 15 µG/M3 (4.7PPB), ALMOST 10 TIMES THE LEVEL OF 1.5–2 µG/M3 (0.47–0.63 PPB) OBSERVEDIN MORE THAN NONSMOKERS .

SMOKERS ALSO HAD ABOUT 6–10 TIMES AS MUCH BENZENE IN THEIR BLOODAS NON-SMOKERS .

IN 10 OF 11 HOMES INHABITED BY TOBACCO SMOKERS, MEANINDOOR AND PERSONAL BENZENE CONCENTRATIONS WERE 2–5TIMES HIGHER THAN OUTDOOR LEVELS .

ON THE ASSUMPTION THAT INTAKE OF BENZENE FROM EACHCIGARETTE IS 30 µG, HAS CALCULATED THAT A SMOKER WHOCONSUMES TWO PACKS OF CIGARETTES PER DAY WILL HAVE ANADDITIONAL DAILY INTAKE FROM 1.2 TO 1.8 MG/DAY (AT LEAST 10TIMES THE AVERAGE NONSMOKER'S INTAKE)

•the production of gasoline and light fuel oils (petroleum refineries),

•the distribution of petroleum products (tanker loading and unloading operations, filling operations at service stations),

•the distillation of coal tar in the coke oven industry

•the dismantling of vehicles’ fuel filters,

•the extraction of natural essences (perfume industry)

HIGHEST OCCUPATIONAL EXPOSURES TO BENZENE

Assuming an average benzene concentration of 40µg/m3 (12.5 ppb) for a moving automobile and anexposure duration of 1 hour/day,the calculated intake for driving or riding in anautomobile is 40 µg/day (1ppb=3.2 µg/m3)

In USA ,approximately 10,000 workers were estimatedto be exposed to TWA concentrations in excess of the1 ppm standard

now lowered to 0.5 ppm ( ACGIH 2005).

•active smoking of tobacco, •passive smoking,•riding in automobiles, •having a home-attached garage, •indoor exposure to consumer products, •outdoor pollution by vehicle exhaust and industrial emissions

•.

GENERAL POPULATION EXPOSURES TO BENZENE

insalata di cavolo

Smell of benzene in water at 2 ppm. Mostpeople can begin to taste benzene in waterat 0.5–4.5 ppm.One part per million is approximatelyequal to one drop in 150 litres

Benzene in the atmosphere exists predominantly inthe vapor phase . The most significant degradationprocess for benzene is its reaction with atmospherichydroxyl radicals. The rate constant for the vaporphase reaction of benzene with photochemicallyproduced hydroxyl radicals has been determined to be1.3x10-12 cm /molecule-second, which correspondsto a residence time of 8 days at an atmospherichydroxyl radical concentration of 1.1x106molecules/cm3 . With a hydroxyl radicalconcentration of 1x108 molecules/cm3, correspondingto a polluted atmosphere, the estimated residence timeis shortened to 2.1 hours

ASSORBIMENTO

DEL BENZENE

Inhalation exposure is probably the major route of human exposure to benzene, although oral and dermal exposure are also important. Benzene is readily absorbed following inhalation or oral exposure. Although benzene is also readily absorbed from the skin, a significant amount of a dermal application evaporates from the skin surface. About half of the benzene you breathe in passes through the lining of your lungs and enters your bloodstream. Respiratory uptake was determined to be approximately 48% for the high dose and 52% for the low dose

A small amount through your skin

Studies of occupational exposure to benzene suggest that absorption occurs both by inhalation and dermally in many workplace settings.Exposure to benzene-contaminated water can also provide an opportunity for both inhalation and dermal absorption.

-dermal route: Benzene is absorbed through the human skin as indicated by studies conducted in vivo and in vitro. One average 0.02-0.05% of the benzene applied to skin was absorbed; the remainder quickly volatilised. An hourly absorption of 0.4 mg/cm2 has also been reported when the forearm was bathed in liquid benzene.

-oral route: Definitive scientific data on the rate of absorption after ingestion of benzene in humans are not available. However case studies of accidental or intentional poisoning indicate that it is absorbed readily. Animal studies support the view that absorption after oral exposure occurs readily and rapidly

(>90% of oral doses).

Absorbed benzene is rapidly distributed throughoutthe body and tends to accumulate in fatty tissues,since benzene is lipophilic. The liver serves animportant function in benzene metabolism, whichresults in the production of several reactivemetabolites. During inhalation exposure of rats to 500ppm, benzene levels reached a steady-stateconcentration within 4 hours in blood (11.5 µg/mL), 6hours in fat (164.4 µg/g), and less than 2 hours inbone marrow (37.0 µg/g), with levels in bone marrowexceeding the respective levels in blood.

METABOLISMODEL BENZENE

Results of several studies provide strong evidencefor the involvement of CYP2E1 in the oxidation ofbenzene. CYPs involved in benzene metabolism arefound in all tissues. However, the predominantrepository is the liver, which is considered to be theprimary site of benzene metabolism CYP2E1 can beinduced by alcohol.

Pretreatment with inducers of metabolism increasedboth benzene metabolism and toxicity

Inhibition of benzene metabolism reduced itstoxicity

elettrofilico

NAD(P)H: quinone oxidoreductase NQO1)

Myeloperoxidase (MPO)

GST

The first step is the cytochrome P-450 2E1 (CYP2E1)catalyzed oxidation of benzene to form benzene oxide(, which is in equilibrium with its oxepin . Severalpathways are involved in the metabolism of benzeneoxide. The predominant pathway involvesnonenzymatic rearrangement to form phenol, themajor initial product of benzene metabolism. Phenolis oxidized in the presence of CYP2E1 to catechol orhydroquinone, which are oxidized viamyeloperoxidase (MPO) to the reactive metabolites1,2- and 1,4-benzoquinone, respectively . Bothcatechol and hydroquinone may be converted to thereactive metabolite 1,2,4-benzenetriol via CYP2E1catalysis.

The reverse reaction (reduction of 1,2- and 1,4-benzoquinone to catechol and hydroquinone,respectively) is catalyzed by NAD(P)H:quinoneoxidoreductase (NQ01).

TOSSICOLOGIA

Two mechanisms have been commonly postulated as being responsible for benzene toxicity.

Initial biotransformation of benzene takes place primarily in the liver. Most models postulate that cytochromes P450 catalyze the addition of a single oxygen atom to the benzene ring forming benzene oxide. Some of the benzene oxide becomes conjugated to glutathione via glutathione-S-transferase (GST), forming a pre-phenyl mercapturic acid that is then further biotransformed to phenyl mercapturic acid. The remaining benzene oxide is conjectured to be removed by two main pathways. At high benzene doses, most benzene oxide spontaneously rearranges to form phenol. The rest is converted to dihydrodiol intermediates by epoxide hydrolase, which are then converted to catechol by dehydrogenases.

A second path that could lead to catechol is addition by P450 of another oxygen atom to phenol. Alternatively, the second OH-group may be attached across the benzene ring from the first, creating hydroquinone. P450 may add another oxygen atom to catechol converting it to 1,2,4-trihydroxybenzene. Hydroquinone can be oxidized probably via a peroxidase-catalyzed reaction, to p-benzoquinone. Catechol and benzenoxide may also be converted to trans-trans muconaldehyde which involves an opening of the benzene ring. A detoxication product of trans-trans muconaldehyde is muconic acid. Other phase II conjugation pathways are also extremely important in benzene metabolism and toxicity: e.g. extensive glucuronidation and sulphation of phenols (Cox, 1991; Medeiros et al,

1997; Ross, 1996; Snyder and Hedli, 1996; Yardley-Jones et al, 1991).

Partial hepatectomy decreased both benzenemetabolism and toxicity. Benzene derivatives,such astoluene and xylene, can inhibit the enzymatic activityof the isozyme.Mice lacking CYP2E1 expression were notsusceptible to benzene levels known to causemyelotoxicity and cytotoxicity in wild type mice .

Occupationally-exposed workers with a phenotypecorresponding to rapid CYP2E1 metabolism were moresusceptible to benzene hematotoxicity than thoseexpressing slow CYP2E1 metabolism. The enzymeNAD(P)H:quinone oxidoreductase (NQ01) maintainsquinones in reduced form where they are more readilyconjugated and excreted , thus protecting cells fromoxidative damage by preventing redox cycling. Between22% (Caucasian) and 45% (Asian) of the population ishomozygous for an NQ01 allele whereby NQ01 productionis negligible. It was found that workers homozygous for anNQ01 allele (wild type) exhibited a 2.4-fold increased riskfor benzene hematotoxicity than workers with the normalgenotype. Greater than 7-foldincreased risk of benzene hematotoxicity was noted inworkers who expressed both rapid CYP2E1metabolism and the NQ01 wild type.

Polymorphisms have also been described for many ofthe glutathione genes, the myeloperoxidase gene, andthe epoxide hydrolase gene , which are known to beinvolved in benzene metabolism. However, thepotential involvement of such polymorphisms inbenzene toxicity have not been demonstrated inbenzene-exposed workers.

The combination of hydroquinone and muconaldehydewas the most potent in inhibiting erythropoiesisSeveral reactive metabolites of benzene have beenproposed as agents of benzene hematotoxic andleukemogenic effects.

These metabolites include benzene oxide, reactiveproducts of the phenol pathway (catechol, hydroquinone,and 1,4-benzoquinone), and trans,trans-muconaldehyde.

The most characteristic systemic effect resulting from intermediateand chronic benzene exposure isarrested development of blood cells. Early biomarkers of exposureto relatively low levels of benzeneinclude depressed numbers of one or more of the circulating bloodcell types. A common clinical findingin benzene hematotoxicity is cytopenia, which is a decrease invarious cellular elements of the circulatingblood manifested as anemia, leukopenia, or thrombocytopenia inhumans and in animals. Benzene associatedcytopenias vary and may involve a reduction in one (unicellularcytopenias) to all three(pancytopenia, erythrocytes, leukocytes, and platelets) cellularelements of the blood.

Benzene also causes a life-threatening disorder called aplasticanemia in humans and animals. Thisdisorder is characterized byreduction of all cellular elements in the peripheral blood and inbone marrow,leading to fibrosis, an irreversible replacement ofbone marrow. Aplastic anemia can progress to a type of leukemiaknown as acute myelogenous leukemia

Decreases in erythrocyte and leukocyte countshave been used as an indicator of highoccupational exposures. Monitoring ofbenzene workers has included monthly bloodcounts, with workers being removed fromareas of high benzene exposure whenleukocyte counts fell below 4,000/mm3 orerythrocyte counts fell below 4,000,000/mm3

ACUTE MYELOID LEUKEMIA (AML)

Epidemiological studies and case reports provide clearevidence of a causal relationship between occupationalexposure to benzene and benzene-containing solvents and theoccurrence of acutenonlymphocytic leukemia (ANLL), particularly the myeloidcell type (acute myelogenous leukemia,AML) Some of the studies also provide suggestive evidenceof associations betweenbenzene exposure and non-Hodgkin’s lymphoma (NHL) andmultiple myeloma

GENOTOSSICOLOGIADEL BENZENE

Genotoxicity:

Benzene and/or its metabolites are genotoxic , specifically clastogenic (i.e., capable of breaking the DNA molecule in a manner observable at the chromosome level), causing primarly chromosomal aberrations.

The oxidation by bone marrowmyeloperoxidase of polyphenols to reactivequinones, semiquinones, and oxygenradicals, lead to strand breaks andinhibition of topoisomerases andmicrotubule assembly, which could resultin chromosome damage

Benzene is a human clastogen

Chromosomal aberrations(hypo- and hyperdiploidy,deletions, breaks, and gaps.) in peripheral lymphocytes andbone marrow cells are the predominant effects seen inhumans

Benzene-induced cytogenetic effects, include also sisterchromatid exchanges, and micronuclei

Chromosome abnormalities were detected in workers exposedto high concentrations of benzene, sufficient to produce blooddyscrasias

The leukemia observed in some benzene-exposed personsmay result from the appearance of a clone of chromosomallyabnormal cells in the bone marrow.

With respect to genetic effects, no safe human exposure levelcan be determined from availableepidemiological data.

EPIDEMIOLOGIA

CANCEROGENESI SPERIMENTALE

Carcinogenicity:

acute myelogenous leukaemia (AML) also called acute nonlymphocytic leukaemia (ANLL)

acute lymphocytic leukaemianon-Hodgkin's lymphoma.

The exact mechanism of benzene carcinogenicity isnot known, but it has been postulated that somebenzene metabolites are capable of forming adductswith DNA and are responsible for reduced immunefunction which could potentially lead to cancer. Theclastogenic properties of benzene may be play arolein its carcinogenicity.

The strongest evidence for the leukemogenic potential of benzenecomes from series of cohort mortality studies on workers exposedto benzene in Ohio (the Pliofilm study) and China (the NCI/CAPMstudy).

The Pliofilm study investigated workers exposed to benzene inthree rubber hydrochloride(‘Pliofilm’) manufacturing plants. therisk of AML increased with increasing cumulative exposure above200 ppm-years.

The NCI/CAPM study, a collaboration between the NationalCancer Institute and the Chinese Academyof Preventive Medicine, evaluated lymphohematopoieticmalignancies and other hematologic disorders in74,828 benzene-exposed workers employed in 672 factories in 12cities in China. Findings included increased risks for all leukemias,acute nonlymphocytic leukemia (ANLL), and combined ANLL andprecursor myelodysplastic syndromes. These risks were increasedat average exposure levels of 10–24 ppm and cumulative exposurelevels of 40–99 ppm-years, and tended to increase withincreasingaverage and cumulative levels of exposure.

Benzene crosses the human placenta and is present in thecord blood in amounts equal to or greater than those inmaternal blood.Reproductive disorders (spontaneous abortions, menstrualdisturbances, and ovarian atrophy ) are suggested in womenoccupationally exposed to benzene.

No studies indicate whether children may be at greater riskthan adults for benzene toxicity, but CYP2E1, a majorenzyme involved in benzene metabolism, is not present inthe fetus

Benzene levels ranging from 0.01 to 0.18 µg/kg have beendetected in samples of human breast milk

Benzene has been shown to be a multiplesite animal carcinogen followinginhalation and oral exposure producing avariety of tumors, including thymiclymphomas, myelogenous leukemias,and Zymbal gland, ovarian, and lungtumors

BENZENE

Working Group IARC, 1987 There is sufficient evidence that benzene is carcinogenic to humans

(Group 1)

MONITORAGGIO BIOLOGICODELLA ESPOSIZIONE

A BENZENE

Benzene is excreted both unchanged via the lungsand as metabolites (but also as parentcompound in small amounts) in the urine.

ELIMINAZIONE

NON METABOLIZZATO

the major route for elimination of unmetabolized benzene isvia exhalation(16.4–41.6%)greatest during the first hour.

Only 0.07–0.2% of the retained benzene was excreted in theurine

benzene nell’aria espirata è stato tra i primi metodi di monitoraggio biologico:marcatore di esposizioni in atto o recenti : al cessare dell’esposizione la concentrazione dei vapori nell’aria espirata decresce esponenzialmentetempo esatto di campionamento, modalità di raccolta del campione conservazione del campione è critica ( possibilità di contaminazione da parte del benzene ambientale)

urinary benzene appears to be the most sensitivebiomarker for low-level exposure to benzene

benzene urinario

benzene non metabolizzato nel sanguerappresenta l’esposizione corrente: il benzene ematico è in equilibrio con il benzene nell’aria inalata ed in quella espirata.

Metodo sensibile, specifico e non invasivo di monitoraggio biologico. Tecnica dello spazio di testa

Il benzene urinario è risultato abbastanza ben correlato con il benzeneematico, e anche con la concentrazione nell’aria espirata. marcatore per le esposizioni professionali e non professionali, (esposizioni a basse concentrazioni di benzene). fumatori dai non fumatori.

limiti:grandi quantità di urina (50 ml) attenti alle contaminazioni

benzene nell’urina

Each of the phenolic metabolites of benzene (phenol,catechol, hydroquinone, and 1,2,4-benzenetriol) can undergosulfonic or glucuronic conjugation; the conjugates of phenoland hydroquinone are major urinary metabolites of benzene.

Other pathways of benzene oxide metabolism include: (1)reaction with glutathione (GSH) to form S-phenylmercapturicacid and (2) ironcatalyzed ring-opening conversion totrans,trans-muconic acid, presumably via the reactivetrans,transmuconaldehyde intermediate.

METABOLITI URINARI

Most of the metabolites of benzene leave the body inthe urine within 48 hours after exposure

At low exposure levels, benzene is rapidlymetabolized and excretedpredominantly as conjugated urinary metabolites.

Principali metaboliti urinari del benzene

fenolo

acido trans trans muconico

acido fenil mercapturico

metabolita più importante. 20% del benzene metabolizzato nelle urine come fenolo libero oppure come glucuronideo coniugato con il solfato. buone correlazioni fra la concentrazione urinaria del fenolo e l’esposizione professionale al benzene: la correlazione è valida però solo per esposizioni a valori superiori a 10 ppm.

Per livelli inferiori non è più un valido marcatore in quanto manca di specificità; esso, infatti, viene introdotto anche con la dieta oltre ad essere un prodotto comune del metabolismo di aminoacidi aromatici.

Essendo gli attuali livelli di esposizione professionalimolto inferiori a 10 ppm, il fenolo non trova più impiego nel

monitoraggio biologico

fenolo

The benzene urinary metabolites TTMA and SPMA are consideredto be very sensitive reproducible and relatively accurate endpointsfor monitoring benzene exposure at low levels. Many laboratoriesstudying human benzene exposure use these metabolites asbiomarkers of benzene exposure. However, the analytical proceduresavailable for determining PMA are time consuming and have a highlevel of complexity. Furthermore, standardisation of the analyticalmethodology has not been achieved. For TTMA, it is also necessaryto exclude non benzene sources such as the ingestion of sorbic acid(SA) from the diet. This has not been routinely done to date, and amethod for the simultaneous detection of TTMA, SPMA and SAwould be extremely valuable.

Valori limite degli indicatori biologici del benzene

BEI ACGIH acido S-fenilmercapturico 25 µg/g creatininaBEI ACGIH acido t,t-muconico 500 µg/g creatinina

fine turno giornaliero di lavoro, NOTA B

La notazione “B” con cui i valori vengono riportati, sottolinea che esiste un background di escrezione di questi metaboliti e che pertanto concentrazioni non nulle si possono rilevare anche in soggetti non esposti professionalmente al benzene

L’S-PMA è il prodotto di una via metabolica secondaria del benze-ne, pertanto le concentrazioni urinarie sono in genere molto basse,dell’ordine dei µg/l;

la percentuale della dose di benzene assorbitache viene convertita a S-PMA risulta dipendente dalla dose.

su popolazioni professionalmente esposte hanno permessodi stimare la percentuale di conversione nell’uomo;

0,11% della dose di benzene quando viene calcolata sulla basedella differenza della concentrazione di S-PMA nell’urina fra fine edinizio, mentre è risultata pari allo 0,9% se il calcolo della quantità diS-PMA escreto è fatto sulle urine raccolte nelle 24 ore successive al-l’esposizione

l’acido S-fenilmercapturico è in grado di riflettere bene le esposizioni professionali al benzene anche a concentrazioni inferiori a 1 ppm.

Studi recenti affermano la possibilità di impiegare l’indicatore per determinare esposizioni professionali al benzene finoa 0,3 ppm, quindi a un valore inferiore all’attuale limite di esposizione professionale fissato dall’ACGIH (0.5 ppm)

LIMITI

A limitation of many biomarker studies on benzene is thatthe levels of exposure were estimated solely on the basis ofenvironmental measurements, while internal dose indicators(concentration of the substance or its metabolites inbiological fluids, or adducts of hemoglobin, plasma proteinsand DNA) were not taken into account. In addition, theinfluence of metabolic polymorphisms on individualsusceptibility to benzene-induced genotoxic effects has notbeen investigated in a coordinated way in any large study.

While evidence has been provided that benzene and itsmetabolites can cause DNA damage , and that cytogenetic effectsoccur in peripheral lymphocytes and bone marrow cells ofbenzene-exposed workers, elevated levels of such damage havebeen observed at relatively high exposure levels. Thus,chromosomal damage (as measured by chromosome aberrations,sister chromatid exchanges and micronuclei) does not seem themost sensitive biological indicator of genotoxic risk deriving fromenvironmental or occupational exposure to benzene.

BENZENE OXIDE-PROTEIN ADDUCTS

BENZENE OXIDE HEMOGLOBIN ANDALBUMIN ADDUCTS HAVE BEEN DETECTEDIN THE BLOOD OF HUMANSEXPOSURE-RELATED INCREASES IN BLOODLEVELS OF ALBUMIN ADDUCTS OF BENZENEOXIDE AND 1,4-BENZOQUINONE WERENOTED AMONG WORKERSOCCUPATIONALLY EXPOSED TO BENZENEAIR CONCENTRATIONS RANGING FROM 0.07TO 46.6 PPM

Composti omisturecomplesse

Biomarcatoreanalizzato

Genotipi conaumentatobiomarcatore

Benzene /occupazionalee ambientale

Acido t,t-muconico(t,t-MA)

Acido S-f enilmercapturico(PMA)

EPHX *1/ *1GSTM1 *0/ *0GSTT1 *0/ *0

CYP2D6 (EM)NQO1*2/ *2

POLIMORFISMI DEI GENI METABOLICI E MONITORAGGIO BIOLOGICO

RISK ASSESSMENT

Numerous earlier studies of benzene-exposed workersdemonstrated that benzene air concentrations of10 ppm or more resulted in adverse hematological effects,which increased in severity with increasingbenzene exposure levels, but more recent epidemiologicalstudies(China) reports significantreductions in WBC, RBC, and platelet counts) in workerschronically exposed to benzene levels below10 ppm, and even as low as 1 ppm or less ranging in thislatter case from approximately 8 to 15% lower thancontrols

The study of workers of shoe manufacturingindustries in China identified the lowestLOAEL for hematotoxicity and was selectedas the principal study for deriving a chronic-duration inhalation MRL of 0.003 ppm forbenzene.

Based on human leukemia data, EPA deriveda range of inhalation unit risk values of2.2x10-6–7.8x10-6 (µg/m3)-1 for benzene.For risks ranging from 1x10-4 to 1x10-7, thecorresponding air concentrations range from13.0–45.0 µg/m3 (4–14 ppb) to 0.013–0.045µg/m3 (0.004–0.014 ppb),respectively

EMOTOSSICITA’

CANCEROGENICITA’

EPA has set 5 ppb as the maximumpermissible level of benzene in drinking water.EPA has seta goal of 0 ppb for benzene in drinking waterand in water such as rivers and lakes becausebenzene can cause leukemia. EPA estimatesthat 10 ppb benzene in drinking water that isconsumed regularly or exposure to 0.4 ppb inair over a lifetime could cause a risk of oneadditional cancer case for every 100,000exposed person