Benzene Metabolism and Toxicity

Chronic exposure to benzene leads to blood dyscrasias characterized by progressive depression in the levels of circulating leukocytes, thrombocytes, and/or erythrocytes, eventually leading to pancytopenia and aplastic anemia (1). The literature contains many descriptions of human benzene toxicity following chronic inhalation (2–4) and the process has been reproduced in several animal species either by exposing animals to atmospheric benzene (5,6) or by parenteral administration of benzene (7,8). The mechanism by which benzene produces bone marrow depression has been explored in a series of studies by Kissling and Speck (9,10) and by Boje et al. (11), who demonstrated that nucleic acid synthesis in bone marrow was inhibited in chronic benzene toxicity, but the molecular site of action is as yet unknown.

[1]  F. Marks,et al.  Metabolism and mechanism of action of oestrogens. XII. Structure and mechanism of formation of water-soluble and protein-bound metabolites of oestrone in rat-liver microsomes in vitro and in vivo. , 1969, Biochimica et biophysica acta.

[2]  H. Bolt,et al.  Irreversible protein binding of metabolites of ethynylestradiol in vivo and in vitro. , 1973, Steroids.

[3]  Schwartz,et al.  The Action of Benzol , 1917 .

[4]  E. Bernal,et al.  The hemopoietic tissue toxicity of benzene vapors. , 1963, Toxicology and applied pharmacology.

[5]  R. T. Williams,et al.  Studies in detoxication. 20. The metabolism of benzene. II. The isolation of phenol, catechol, quinol and hydroxyquinol from the ethereal sulphate fraction of the urine of rabbits receiving benzene orally. , 1949, The Biochemical journal.

[6]  M. Ikeda.  ENZYMATIC STUDIES ON BENZENE INTOXICATION. , 1964, Journal of biochemistry.

[7]  H. Heiniger,et al.  [Leukopoiesis in the bone marrow of the rat after chronic benzol inhalation]. , 1970, Blut.

[8]  R Snyder,et al.  Current concepts of chronic benzene toxicity. , 1975, CRC critical reviews in toxicology.

[9]  R. T. Drew,et al.  Species differences in benzene hydroxylation to phenol by pulmonary and hepatic microsomes. , 1975, Drug metabolism and disposition: the biological fate of chemicals.

[10]  E. Browning.  Toxicity and metabolism of industrial solvents , 1965 .

[11]  L. Selling.  Benzol as a leucotoxin : studies on the degeneration and regeneration of the blood and haematopoietic organs , 1913 .

[12]  K. Nomiyama.  STUDIES ON POISONING BY BENZENE AND ITS HOMOLOGUES:(7) TOXICITY OF BENZENE METABOLITES TO HEMOPOIESIS , 1964 .

[13]  M. Ikeda,et al.  In vivo suppression of benzene and styrene oxidation by co-administered toluene in rats and effects of phenobarbital. , 1972, Xenobiotica; the fate of foreign compounds in biological systems.

[14]  R. Snyder,et al.  Benzene metabolism in mouse liver microsomes. , 1973, Toxicology and applied pharmacology.

[15]  R. Girdwood.  Blood disorders due to drugs and other agents , 1973 .

[16]  M. Aksoy,et al.  Details of blood changes in 32 patients with pancytopenia associated with long-term exposure to benzene , 1972, British journal of industrial medicine.

[17]  E. Dybing,et al.  Metabolic Activation of Methyldopa by Cytochrome P450-Generated Superoxide Anion , 1977 .

[18]  R. Snyder,et al.  The metabolism of benzene in vitro , 1967 .

[19]  R. T. Williams,et al.  Studies in detoxication , 1941 .

[20]  P. Dustin.  The action of mitotic poisons on normal and pathological blood-cell formation. , 1950, Le Sang.

[21]  D. Parke,et al.  Studies in detoxication. 54. The metabolism of benzene. (a) The formation of phenylglucuronide and phenylsulphuric acid from [14C]benzene. (b) The metabolism of [14C]phenol. , 1953, The Biochemical journal.

[22]  R. T. Drew,et al.  The lack of effects of pretreatment with phenobarbital and chlorpromazine on the acute toxicity of benzene in rats. , 1974, Toxicology and applied pharmacology.

[23]  M. Ikeda,et al.  Phenobarbital-induced protection against toxicity of toluene and benzene in the rat. , 1971, Toxicology and applied pharmacology.

[24]  D. Jerina,et al.  Arene oxides: a new aspect of drug metabolism. , 1974, Science.

[25]  R. Snyder,et al.  Dimethyl sulfoxide , 1968, Science.

[26]  H. G. Weiskotten,et al.  The Action of Benzol : VI. Benzol Vapor Leucopenia (Rabbit). , 1920, The Journal of medical research.

[27]  D. Parke,et al.  Studies in detoxication. XLIX. The metabolism of benzene containing (14C1) benzene. , 1953, The Biochemical journal.