Benzene WHO working group Environmental Health Criteria Vol:150 (1993) 156pIdentity, physical and chemical properties: Benzene is a stable colourless liquid at room temperature and normal atmospheric pressure. It has a characteristic aromatic odour, a relatively low boiling point (80.1 C) and a high vapour pressure (Vp=13.3 KPa), which causes it to evaporate rapidly at room temperature, and is highly flammable. It is slightly soluble in water (Wsol=1800 mg/l at 25 C) but miscible with most other organic solvents. Environmental transport, distribution and transformation: Benzene in air exists predominantly in the vapour phase, with residence times varying between a few hours and a few days, depending on environment and climate, and on the concentration nf hydroxyl radicals, as well as nitrogen and sulfur dioxides. Degradation of benzene in air occurs mainly by the reaction with hydroxy radicals. A of 5.3 days was calculated for benzene. It can be removed from air by rain, leading to contamination of surface and ground water, in which it is soluble at about 1000 mg/litre. Due primarily to volatilization, the residence time of benzene in water is a few hours, with little or no adsorption to sediments. Benzene in soil can be transported to air via volatilization and to surface waters by run off. If benzene is buried or is released well below the surface, it will be transported into ground water. With a Koc of 60-83, benzene is considered fairly mobile in soil. Under aerobic conditions, benzene in water or soil is rapidly (within hours) degraded by bacteria to lactate and pyruvate through phenol and catechol intermediates. However, under anaerobic conditions (for example, in ground water) bacterial degradation is measured in weeks and months rather than hours. In the absence of bacterial degradation benzene can be persistent. It has not been shown to bioconcentrate or bioaccumulate in aquatic or terrestrial organisms (log Pow = 1.56-2.15). Effects on laboratory mammals and in vitro test systems: Systemic toxicity. Benzene appears to be of low acute toxicity in various animal species, with LD50 values after oral exposure ranging between 3000 and 8100 mg/kg body weight in the rat. Reported LC50 values range from 15 000 mg/m3 (8 h) in mice to 44 000 mg/m3 (4 h) in rats. Benzene is a moderate eye irritant and is irritating to rabbit skin after multiple applications of the undiluted chemical. No information is available on the skin-sensitizing potential of benzene. Exposure of mice to benzene by inhalation results in a significant lowering of blood parameters such as haematocrit, haemoglobin level, and erythrocyte, leucocyte and platelet counts. Long-term exposure at high doses results in bone marrow aplasia. Similar, but less severe, findings were noted in rats. Genotoxicity and carcinogenicity. Benzene has given negative results in mutagenicity assays in vitro. In vivo studies, benzene or its metabolites cause both structural and numerical chromosome aberrations in humans and laboratory animals. In addition, benzene administration results in the production of sister chromatid exchanges and polychromatic erythrocytes with micronuclei. Benzene can reach germ cells, after intraperitoneal dosing, as shown by the production of abnormalities in sperm head morphology. Benzene has been reported to cause the production of several types of neoplasms in both rats and mice after either oral dosing or inhalation exposures. These include various types of epithelial neoplasms, e.g., Zymbal gland, liver, mammary tissue and nasal cavity neoplasms, and a few lymphomas and leukaemias. In those inhalation studies where a positive carcinogenic response was reported, exposure levels were between 100 and 960 mg/m3 for 5-7 h/day, 5 days/week. Oral benzene doses of between 25 and 500 mg/kg body weight in mice and rats resulted in the production of neoplasms. The length of exposure was usually 1-2 years. Reproductive toxicity, embryotoxicity and teratogenicity. Benzene crosses the placental barrier freely. There are no data showing that it is teratogenic after numerous experiments in experimental animals even at maternally toxic doses. However, it has been shown to be fetotoxic following inhalation exposure in mice (1600 ug/m3, 7 h/day, gestation days 6-15) and in rabbits. Immunotoxicity. Benzene depresses the proliferative ability of B- and T-cell lymphocytes. Host resistance to infection in several laboratory species has been reduced by exposure to benzene. Effects on humans: It is known that benzene produces a number of effects. The most frequently reported health effect of benzene is bone marrow depression leading to aplastic anemia. At high levels of exposure a high incidence of these diseases is probable. Benzene is a well-established human carcinogen. Epidemiological studies of benzene-exposed workers have demonstrated a causal relationship between benzene exposure and the production of myelogenous leukaemia. A relationship between benzene exposure and the production of lymphoma and multiple myeloma remains to be clarified. The Task Group was of the opinion that evidence is not capable of distinguishing between a) a small increase in mortality from leukaemia in workers exposed to low levels of benzene, and b) a non-risk situation. < ANIMAL > acute toxicity subacute toxicity subchronic toxicity chronic toxicity irritancy immunotoxicity carcinogenicity carcinogens genetic toxicity mutagens reproductive and developmental tests embryo-fetal toxicity toxicokinetics eye skin blood immune system liver mammary gland nervous system dose effect < HUMAN > epidemiological study occupational exposure acute effect carcinogenic effect genetic effect solvents automobile exhaust tobacco smoke < ENVIRONMENT > ENVIRONMENTAL CONCENTRATIONS air water soil/sediment BIOACCUMULATION DEGRADATION MOBILITY 71-43-2 eng 199401 1993RISKLINE/1994010029 RISKLINE/1994010029