Toxicity of benzene

StarekA. 1991. [The effect of trichloroethylene on the metabolism and toxicity of benzene in rats.] Folia Medica Cracoviensia 32 169-184. (Polish)... 

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. 

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. 

Physiologically based pharmacokinetic models regarding phenol have typically been developed as part of the attempt to understand the toxicity of benzene, of which phenol is the primary metabolite. Human exposure to... 

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. 

Snyder, C.A., Goldstein, B.D., Sellakumar, A., Bromberg, L, Laskin, S., AND Albert, R.E. (1980). The inhalation toxicity of benzene incidence of hematopoietic neoplasm and hematotoxicity in AKR/J and C57BL/6J mice, Tfaxicol. Appl. Pharmacol 54,323. 

Caution. Owing to the toxicity of benzene, the chromatographic separation should be carried out in an efficient fume hood. 

The heme iron in the peroxidase is oxidized by the peroxide from III+ to V4- in compound I. The compound I is reduced by two sequential one-electron transfer processes giving rise to the original enzyme. A substrate-free radical is in turn generated. This may have toxicological implications. Thus the myeloperoxidase in the bone marrow may catalyze the metabolic activation of phenol or other metabolites of benzene. This may underlie the toxicity of benzene to the bone marrow, which causes aplastic anemia (see below and chap. 6). The myeloperoxidase found in neutrophils and monocytes may be involved in the metabolism and activation of a number of drugs such as isoniazid, clozapine, procainamide, and hydralazine (see below). In in vitro systems, the products of the activation were found to be cytotoxic in vitro. 

The experimental details were kindly supplied by Professor D. H. R. Barton, F.R.S. and Dr W. Rigby because of the toxicity of benzene this chromatographic column should be set up in the fume cupboard. 

CAUTION Owing to the carcinogenic properties of methyl iodide and the toxicity of benzene all operations should be conducted with great care and in an efficient fume cupboard. 

As discussed in Section 13.5, benzene-1,2-oxide is an intermediate in the biochemical oxidation of benzene. It is probably responsible for the toxicity of benzene. It is hydrolyzed by the action of epoxide hydratase to the dihydrodiol shown below ... 

Schoeters et al. (1995) evaluated the hematopoietic and osteogenic toxicity of benzene, phenol, hydroquinone, and catechol in vitro using murine bone marrow cultures. Evaluation of toxicity to 3T3-fibroblasts was included to determine specific toxicity to marrow cells. Benzene and phenol showed little effect. However, hydroquinone inhibited proliferation of 3T3 cells and marrow precursor cells, and calcification of bone cells, although it was more specific for marrow cells. Catechol inhibited all cells, and showed no specificity. 

Studies have been conducted on the interaction of benzene with other chemicals, both in vivo and in the environment. Benzene metabolism is complex, and various xenobiotics can induce or inhibit specific routes of detoxification and/or activation in addition to altering the rate of benzene metabolism and clearance from the body. Toluene, Aroclor 1254, phenobarbital, acetone, and ethanol are known to alter the metabolism and toxicity of benzene. 

Exxon. 1986. Initial submission Determination of material toxicity fetal toxicity of benzene in rats following oral exposure (final report) with cover letter (sanitized). EPA/OTS Doc 88-920001029S. 

Longacre SL, Kocsis JJ, Snyder R. 1981a. Influence of strain differences in mice on the metabolism and toxicity of benzene. Toxicol Appl Pharmacol 60 398-409. 

Nakajima T, Okuyama S, Yonekura I, et al. 1985. Effects of ethanol and phenobarbital administration on the metabolism and toxicity of benzene. Chem-Biol Interact 55 23-38. 

Sammett D, Lee EW, Kocsis JJ, et al. 1979. Partial hepatectomy reduces both the metabolism and toxicity of benzene. J Toxicol Environ Health 5 785-792. 

Seidel HJ, Bader R, Weber L, et al. 1990. The influence of ethanol on the stem cell toxicity of benzene in mice. Toxicol Appl Pharmacol 105(1) 13-18. 

Lovley, D.R., Anaerobic benzene degradation, Biodegradation 11, 107—116, 2000 Snyder, R., Xenobiotic metabolism and the mechanism(s) of benzene toxicity. Drug Metab. Rev. 36, 531—547, 2004 Rana, S.V. and Verma, Y., Biochemical toxicity of benzene, J. Environ. Biol. 26,157—168, 2005 Lin, Y.S., McKelvey, W., Waidyanatha, S., and Rappaport, S.M., Variability of albumin adducts of 1,4-benzoquinone, a toxic metabolite of benzene, in human volunteers. Biomarkers 11,14-27, 2006 Baron, M. and Kowalewski, V.J., The liquid water-benzene system, J. Phys. Chem. A Mol. Spectrosc. Kinet. Environ. Gen. Theory 100, 7122-7129, 2006 Chambers, D.M., McElprang, D.O., Waterhouse, M.G., and Blount, B.C., An improved approach for accurate quantiation of benzene, toluene, ethylbenzene, zylene, and styrene in blood, Anal. Chem. 78, 5375-5383, 2006. 

Remember that solvents are hazardous materials and beware particularly of the flammability of the hydrocarbons and ethers, the toxicity of benzene, chloroform, and carbon tetrachloride, and the possibility of peroxide contamination of ethereal solvents. 

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