Acute Toxicity of Benzene

Cases of severe, acute benzene toxicity have now become rare [3,12,197,198,224, 237]. Benzene affects the central nervous system [12, 224, 238], and death occurs as a result of circulatory failure at relatively high exposure rates of 5,000-45,000 ppm benzene [197, 198]. Concentrations of 500-1,500 ppm cause unconsciousness [198, 239], those of 150 ppm a state of euphoria [3]. The euphoric component can, in persons so disposed, lead to benzene addiction [198]. Taken orally and following aspiration, benzene at an LD50 of 1-6 g/kg [3,197,224] causes nonspecific pneumonia [3]. In the case of acute toxicity, no changes are noted in the blood when examined under the microscope - even if the benzene content is 0.1-2 mg/100 ccm [198]. Acute toxicity gives no indications of the chronic effects [198]. Benzene has practically no warning effect, and its odour is not unpleasant [3]. Eye irritations do not occur until exposure rates of approx. 3,000 ppm benzene [3]. 

Chronic Effects of Benzene Cytogenicity, Carcinogenicity, Leukaemia, 

Haematoxicity, particularly pancytopenia (diminution of all formed elements in the blood), has been observed in both humans and animals following exposure to benzene [12, 13, 196, 198, 224, 242-248]. Benzene-induced pancytopenia and aplastic bone marrow indicate a greater risk to acute myelogenous leukaemia and erythroleukaemia [196]. The effect of increase in red blood cell levels of delta-aminolevulinic acid (a precursor in the haeme biosynthetic pathway) and the effect of decrease in the mean serum complement of the blood occur at benzene occupational exposure levels of 3-15 ppm, and may also have a potential significance [196]. According to a study of the hypofunction of different blood systems, disorders occur at benzene exposure rates of 2-500 ppm [3, 12, 13, 198]. Isolated cases of abnormal blood composition due to minimum exposure levels of 2-3 ppm have been reported from Italy and France [249, 250]. 

The population risk to ambient benzene exposures has been extrapolated from the first three of these four studies [196]. 

It has been calculated from a model that the number of leukaemia cases per annum in the general population of the USA due to atmospheric benzene (see [132]) could be about 90 with a 95% confidence interval [228]. This is about 1% of the total leukaemia deaths in the United States, based on 1973 vital statistics [228]. 

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Gute, B. D., Basak, S. C. Predicting acute toxicity of benzene derivatives using theoretical molecular descriptors A hierarchical QSAR approach. SAR QSAR Environ. Res. 1997, 7, 117-131. 

Drew, R.T. and Fonts, J.R. The lack of effects of pretreatment with phenobarbital and chlorpromazine on the acute toxicity of benzene in rats, Toxicol. Appl. Pharmacol, 27 1) 183-19Z, 1974. 

Gute, B.D. and Basak, S.C. (1997). Predicting Acute Toxicity of Benzene Derivatives Using Theoretical Molecular Descriptors A Hierarchical QSAR Approach. SAR QSAR Environ.Res., 7,117-131. 

Roy K, Ghosh G. QSTR with extended topochemical atom (ETA) indices. VI. Acute toxicity of benzene derivatives to tadpoles. J Mol Model 2006 12(3) 306-16. 

Huang, H Wang, X., Ou, W., Zhao, J., Shao, Yand Wang, L.-S. (2003) Acute toxicity of benzene derivatives to the tadpoles Ranajaponica) and QSAR analyses. Chemosphere, 53, 963-970. 

A very valuable table of acute toxicity of benzene, toluene, xylenes, ethylbenzene, trimethylbenzenes, naphthalene and methylated naphthalenes to freshwater and marine animals (bay shrimp, pink salmon try and striped bass are especially sensitive) is given by. J. M. Neff Polycyclic Aromatic Hydrocarbons in the Aquatic Environment , table 82. Applied Science Publ. 1979. Naphthalenes are about 10 times as toxic as benzenes. 

The safety factor scale takes into account the volatility as well as the toxicity of the substance. It is an acute intoxication factor. As a result, the long term toxicity of benzene, which is carcinogenic, is hardly taken into account. This is a variant of the author s approach. 

At the initial stages of a release, when the benzene-derived compounds are present at their highest concentrations, acute toxic effects are more common than they are later. These noncarcinogenic effects include subtle changes in detoxifying enzymes and liver damage. Generally, the relative aquatic acute toxicity of petroleum will be the result of the fractional toxicities of the different hydrocarbons present in the aqueous phase. Tests indicate that naphthalene-derived chemicals have a similar effect. 

Naphthalene and its homologs are less acutely toxic than benzene but are more prevalent for a longer period during oil spills. The toxicity of different crude oils and refined oils depends not only on the total concentration of hydrocarbons but also the hydrocarbon composition in the water-soluble fraction (WSF) of petroleum, water solubility, concentrations of individual components, and toxicity of the components. The water-soluble fractions prepared from different oils wiU vary in these parameters. Water-soluble fractions (WSFs) of refined oils (e.g.. No. 2 fuel oil and bunker C oil) are more toxic than water-soluble fraction of crude oil to several species of fish (killifish and salmon). Compounds with either more rings or methyl substitutions are more toxic than less substituted compounds, but tend to be less water soluble and thus less plentiful in the water-soluble fraction. 

Burden, F. R., and Winkler, D. A. (2000) A quantitative structure-activity relationships model for the acute toxicity of substituted benzenes to Tetrahymena pyriformis using Bayesian-regularized neural networks. Chem. Res. Toxicol. 13,436-440. 

Kaiser, K.L.E., Palabrica, V.S., Ribo, J.M. (1987) QSAR of acute toxicity of mono-substituted benzene derivatives to photobacterium phosphoreum. In QSAR in Experimental Toxicology II. Kaiser, K.L.E., Editor, pp. 153-168, D. Reidel Publishing Co., Dordrecht, Holland. 

Karabunarliev, S., Mekenyan, O.G., Karcher, W., Russom, C.L., and Bradbury, S.P., Quantum-chemical descriptors for estimating acute toxicity of substituted benzenes to the guppy (Poecilia reticulata) and fathead minnow (Pimephales promelas), Quant. Struct.-Act. Relat., 15, 311-320, 1996b. 

Toxicity. Toluene has about the same acute toxicity as benzene but is a less serious industrial hazard. The maximum permissible atmospheric concentration of toluene is 100 ppm. Exposure to air concentrations of 10000 to 30 000 ppm may cause unconsciousness within a few minutes. A blood concentration of more than lOpg/ml may be lethal although higher concentrations have been found in habitual abusers. 

The literature on the toxicity of benzene in humans is extensive. The acute effects of benzene exposure generally differ markedly from the chronic effects. Acute exposure to high doses of benzene in air (at concentrations in excess of 3000 ppm) causes symptoms typical of organic solvent intoxication. Symptoms may progress from excitation, euphoria, headache, and vertigo, in mild cases, to central nervous system depression, confusion, seizures, coma, and death from respiratory failure in severe cases. The rate of recovery depends on the initial exposure time and concentration, but, following severe intoxication, the symptoms may persist for weeks. 

Many of the effector functions of the immune system are dependent on a multitude of cell types, which all share a common precursor, the pluripotent stem cell. Therefore, any damage to the stem cell would be expected to have devastating consequences, several of which would extend beyond the immune system, most notably involving the red blood cell. Fortunately, the stem cell is refractory to xenobiotic-in-duced perturbation and is only affected by high doses of radiation. However, subsequent steps of hematopoiesis are affected by exposure to chemicals, with benzene being a classic example. Acute toxicity to benzene is associated with pancytopenia, aplastic anemia, and, at high doses, immunosuppression and leukemia. 

Holcombe G et al., The acute toxicity of selected substituted phenols, benzenes and benzoic acid esters to fathead minnows Pimephales pmmelas, Environ. Poll. (Ser. A), 35, 367, 1984. 

The acute toxicity of soft electrophiles such as substituted benzenes, phenols, and anilines has been correlated with MNDO-calculated descriptors [118] ... 

The acute toxicity of mononuclear aromatics is low. Inhalation of vapors at high concentrations in air may cause narcosis with symptoms of hallucination, excitement, euphoria, distorted perception, and headache. Under severe intoxication these may progress to depression, stupor, and coma. The narcotic effects of alkylbenzenes are somewhat greater than the alkanes with the same number of carbon atoms. Benzene is the only mononuclear aromatic that is a confirmed human carcinogen and also manifests other severe chronic effects. 

The acute toxicity of toluene is similar to that of benzene. The exposure routes are inhalation, ingestion, and absorption through the skin and the organs affected from its exposure are the central nervous system, liver, kidneys, and skin. At high concentrations it... 

The acute toxicity of ethyl benzene is low. At high concentrations its exposure produces narcotic effects similar to benzene and toluene. A 4-hour exposure to a concentration of 4000 ppm proved fatal to rats. The lethal dose varies with species. Deaths resulted from intense congestion and edema of the lungs. 

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