7 Benzene Benzene is a toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. Chronic benzene exposure produces hematotoxicity, bone marrow dysplasia (Displasia is a pre-neoplastic or pre-cancerous change). (A7669). It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and is carcinogenic. It was formerly used as parasiticide. 71-43-2 241 C6H6 78.046950 Colorless liquid. 5.5°C 80.1 °C 0.8786 g/cm3 1.79 mg/mL at 25°C [MAY,WE et al. (1983)] 0.88 −11 °C 75 mmHg at 20 °C Inhalation (L5) DNA Hemoglobin subunit alpha (P69905) Hemoglobin subunit beta (P68871) Hemoglobin subunit gamma-1 (P69891) Hemoglobin subunit gamma-2 (P69892) Hemoglobin subunit delta (P02042) Hemoglobin subunit epsilon (P02100) Hemoglobin subunit mu (Q6B0K9) Hemoglobin subunit theta-1 (P09105) Hemoglobin subunit zeta (P02008) Serum albumin (P02768) Histone H4 (P62805) Histone H3.1 (P68431) Histone H3.1t (Q16695) Histone H3.2 (Q71DI3) Histone H3.3 (P84243) DNA polymerase subunit gamma-1 (P54098) DNA polymerase subunit gamma-2 (Q9UHN1) Ribonucleoside-diphosphate reductase large subunit (P23921) Ribonucleoside-diphosphate reductase subunit M2 (P31350) Ribonucleoside-diphosphate reductase subunit M2B (Q7LG56) Tubulin alpha-1A chain (Q71U36) Tubulin alpha-1B chain (P68363) Tubulin alpha-1C chain (Q9BQE3) Tubulin alpha-3C/D chain (Q13748) Tubulin alpha-3E chain (Q6PEY2) Tubulin alpha-4A chain (P68366) Tubulin alpha-8 chain (Q9NY65) Tubulin beta chain (P07437) Tubulin beta-1 chain (Q9H4B7) Tubulin beta-2A chain (Q13885) Tubulin beta-2B chain (Q9BVA1) Tubulin beta-2C chain (P68371) Tubulin beta-3 chain (Q13509) Tubulin beta-4 chain (P04350) Tubulin beta-6 chain (Q9BUF5) Tubulin beta-8 chain (Q3ZCM7) Tubulin delta chain (Q9UJT1) Tubulin gamma-1 chain (P23258) Tubulin gamma-2 chain (Q9NRH3) Tubulin epsilon chain (Q9UJT0) DNA topoisomerase 2-alpha (P11388) DNA topoisomerase 2-beta (Q02880)(L5) The toxic agents of benzene are its metabolites. Benzene is able increase its toxicity by inducing cytochrome P450 2E1, its main metabolic enzyme. Benzene's primary toxic effects are decreases in haematological cell counts and bone marrow cellularity. The decrease in blood cell count may be due to the binding of metabolites such as benzene oxide to the blood proteins albumin and haemoglobin. In the bone marrow, phenolic metabolites can be metabolized by bone marrow peroxidases to highly reactive semiquinone radicals and quinones that stimulate the production of reactive oxygen species. This and direct metabolite binding leads to damage to tubulin, histone proteins, and topoisomerase II. Some metabolites also exert mutagenic effects by inhibiting other DNA associated proteins, such as mitochondrial DNA polymerase and ribonucleotide reductase, as well as covalently binding to DNA itself, causing effects such as strand breakage, mitotic recombination, chromosome translocations, and aneuploidy. (L5) Benzene is absorbed readily following inhalation or oral exposure. It enters the bloodstream and is rapidly distributed throughout the body, tending to accumulate in fatty tissues. Benzene is exhaled unchanged by the lungs, as well as metabolized in the liver to benzene oxide by cytochrome P450 enzymes. Benzene oxide is further converted into phenol, catechol, and hydroquinone, which are excreted in the urine as glucuronide or sulfate conjugates. (T7) LD50: 3306 mg/kg (Oral, Rat) (T14) LD50 340 mg/kg (Intraperitoneal, Mouse) (T14) LC50: 9980 ppm (Inhalation, Mouse) (T14) 50-500 mg/kg (oral) or 20 000 ppm (inhaled) for an adult human. (L138) 1, carcinogenic to humans. (L135) Benzene is often used as an intermediate to make chemicals needed for the production of plastics, resins, and nylon and other synthetic fibers. It is also used to make some types of rubbers, lubricants, dyes, detergents, drugs, and pesticides. Natural sources of benzene include emissions from volcanoes, forest fires, crude oil, gasoline, and cigarette smoke. (L5) Acute Inhalation: 0.009 ppm (L134) Intermediate Inhalation: 0.006 ppm (L134) Chronic Inhalation: 0.003 ppm (L134) Chronic Oral: 0.0005 mg/kg/day (L134) Benzene causes harmful effects on the bone marrow and also decreases blood cell counts, leading to blood disorders such as anemia. It can also cause excessive bleeding and affect the immune system, increasing the chance for infection. Benzene is also a known carcinogen, as chronic exposure to high levels has been shown to cause leukemia, particularly acute myelogenous leukemia. (L5) Breathing benzene can cause drowsiness, dizziness, rapid heart rate, headaches, tremors, confusion, and unconsciousness. Ingestion can result in vomiting, irritation of the stomach, dizziness, sleepiness, convulsions, and rapid heart rate. (L5) There is no known antidote for benzene and poisoning is first treated by preventing further exposure. If inhaled, respiratory assist may be necessary. If ingested, gastric lavage may be performed, or activated charcoal can be administered. (T8) 2009-03-06T18:57:54Z 2014-12-24T20:20:50Z Cytochrome P450 2E1 (P05181) (L5) http://en.wikipedia.org/wiki/benzene C01407 111300 16716 BENZENE D001554 Benzene BNZ 136 true Cytochrome P450 2E1 (P05181) (L5) C1=CC=CC=C1 C6H6 InChI=1S/C6H6/c1-2-4-6-5-3-1/h1-6H InChIKey=UHOVQNZJYSORNB-UHFFFAOYSA-N 78.1118 78.046950192 Exogenous Liquid 2.13 HMDB01505 CHEMBL277500 236 Copisarow, Maurice; Long, Cyril N H. The Friedel-Crafts' reaction. II. Migration of halogen atoms in the benzene nucleus. Journal of the Chemical Society, Transactions (1921), 119 442-7.