Substance identification : C AS Registry Number: 71-43-2 EINECS Number : 200-753-7 Synonyms :

1. BENZENE: SUBSTANCE IDENTIFICATION AND PHYSICO-CHEMICAL PROPERTIES 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

3. 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 petrolio 1930 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).

4. 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% of the 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.

5. Benzene has been used extensively as a solvent in the chemical and drug industries, as a starting material and 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

7. GREGGIO = C1-C34 MAX C60 BENZINA = C4-C12 DISTILLAZIONE 25-220 °C DIESEL = C9-C20 DISTILLAZIONE 163-357 °C

9. MTBE (Metil terz-butil etere)

11. HIGHEST OCCUPATIONAL EXPOSURES TO BENZENE • 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)

15. GENERAL POPULATION EXPOSURES TO BENZENE • 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 • .

16. insalata di cavolo

21. ASSORBIMENTO DEL BENZENE

22. 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.

23. -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).

25. METABOLISMO DEL BENZENE

28. elettrofilico GST Myeloperoxidase (MPO) NAD(P)H: quinone oxidoreductase NQO1)

30. TOSSICOLOGIA

31. 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).

41. GENOTOSSICOLOGIA DEL BENZENE

42. 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.

47. EPIDEMIOLOGIA CANCEROGENESI SPERIMENTALE

48. Carcinogenicity: acute myelogenous leukaemia (AML) also called acute nonlymphocytic leukaemia (ANLL) acute lymphocytic leukaemianon-Hodgkin's lymphoma.