Toxic effects, benzene

Inhalation of 3,000 ppm benzene can be tolerated for 0.5—1 h 7,500 ppm causes toxic effects in 0.5—1 h and 20,000 ppm is fatal in 5—10 min (123). The lethal oral dose for an adult is approximately 15 mL (124). Repeated skin contact is reported to cause drying, defatting, dermatitis, and the risk of secondary infection if fissuring occurs. 

Toxic Effects on the Blood-Forming Tissues Reduced formation of erythrocytes and other elements of blood is an indication of damage to the bone marrow. Chemical compounds toxic to the bone marrow may cause pancytopenia, in which the levels of all elements of blood are reduced. Ionizing radiation, benzene, lindane, chlordane, arsenic, chloramphenicol, trinitrotoluene, gold salts, and phenylbutazone all induce pancytopenia. If the damage to the bone marrow is so severe that the production of blood elements is totally inhibited, the disease state is termed aplastic anemia. In the occupational environment, high concentrations of benzene can cause aplastic anemia. 

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

Field spray studies have been carried on using benzene hexachloride and similar insecticides. In Brazil benzene hexachloride appeared to have a toxic effect on coffee trees. It has been the source of a bad flavor in coffee in Africa and also in Brazil, which was a further reason for abandoning its use. Work with so-called deodorized benzene hexachloride compounds and other insecticides is now in progress. 

Thus, modeling the kinetics of benzene and phenol metabolism involves considering an array of compounds which may themselves be responsible for any observed toxic effects. 

Phenol is a hydrolyzed metabolite of benzene and is itself further hydrolyzed or conjugated to produce other compounds. Therefore, the toxic effects of phenol exposure may be due to a combination of the parent compound and its metabolites. The major tissues in which metabolism appears to occur are the liver, gut, lung, and kidney (Cassidy and Houston 1984 Powell et al 1974 Quebbemann and Anders 1973 Tremaine et al. 1984). Since phenol, benzene, and their major metabolites all seem to compete for the same P450 and conjugating enzymes, metabolic reactions are presumed to be saturable. 

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. 

There are indications that pure naphthalene (a constituent of mothballs, which are, by definition, toxic to moths) and alkylnaphthalenes are from three to 10 times more toxic to test animals than are benzene and alkylbenzenes. In addition, and because of the low water solubility of tricyclic and polycyclic (polynuclear) aromatic hydrocarbons (i.e., those aromatic hydrocarbons heavier than naphthalene), these compounds are generally present at very low concentrations in the water-soluble fraction of oil. Therefore, the results of this smdy and others conclude that the soluble aromatics of crude oil (such as benzene, toluene, ethylbenzene, xylenes, and naphthalenes) produce the majority of its toxic effects in the enviromnent. 

Benzene is shipped in tank cars, tank trucks, barges, and drums. Transfers from one vessel to another are in dosed systems because benzene is a poisonous substance with acute toxic effects. It ll kill you in 5—10 minutes if you breathe too much. Red DOT flammable liquid labels are required. 

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. 

The exact mechanism of action of most volatile substances remains unknown. Altered function of ionotropic receptors and ion channels throughout the central nervous system has been demonstrated for a few. Nitrous oxide, for example, binds to NMDA receptors and fuel additives enhance GABAa receptor function. Most inhalants produce euphoria increased excitability of the VTA has been documented for toluene and may underlie its addiction risk. Other substances, such as amyl nitrite ("poppers"), primarily produce smooth muscle relaxation and enhance erection, but are not addictive. With chronic exposure to the aromatic hydrocarbons (eg, benzene, toluene), toxic effects can be observed in many organs, including white matter lesions in the central nervous system. Management of overdose remains supportive. 

Chronic exposure to benzene can result in very serious toxic effects, the most significant of which is bone marrow injury. Aplastic anemia, leukopenia, pancytopenia, and thrombocytopenia occur at higher levels of exposure, as does leukemia. 

Aromatic hydroxylation. Aromatic hydroxylation such as that depicted in Figure 4.3 for the simplest aromatic system, benzene, is an extremely important bio transformation. The major products of aromatic hydroxylation are phenols, but catechols and quinols may also be formed, arising by further metabolism. One of the toxic effects of benzene is to cause aplastic... 

Tunek, A., Hogstedt, B. Olofsson, T. (1982) Mechanism of benzene toxicity. Effects of benzene... 

Groups of 90 male and 90 female Sprague-Dawley rats, 12 weeks of age, were exposed to concentrations of 5,10, 50 or 250 ppm [20,40,200 or 1000 mg/ni ] 1,2-dichloroethane (purity, 99.82% 1,1-dichloroethane, 0.02% carbon tetrachloride, 0.02% trichloroethylene, 0.02% tetrachloroethylene, 0.03% benzene, 0.09%) in air for 7 h per day on five days per week for 78 weeks. After several days of exposure to 250 ppm, the concentration was reduced to 150 ppm because of severe toxic effects. A group of 90 males and 90 females kept in an exposure chamber under the same conditions for the same amount of... 

Tunek, A., Hflgstedt. B. Olofsson, T. (1982) Mechanism of benzene toxicity. Effects of benzene and benzene metabolites on bone marrow cellularity, number of granulopoietic stem cells and frequency of micronuclei in mice. Chem.-biol. Interact., 39, 129-138... 

NOXIOUS CAS. Any natural or by-product gas or vapor that has specific toxic effects on humans or animals (military poison gases are not included in this group). Examples of noxious gases are ammonia, carbon monoxide, nitrogen oxides, hydrogen sulfide, sulfur dioxide, ozone, fluorine, and vapors evolved by benzene, carbon tetrachloride, and a number of chlorinated hydrocarbons. Oases that act as simple asphyxiants are not classified as noxious. See also Pollution (Air). 

Benzene is widely used for its solvent properties and as an intermediate in the synthesis of other chemicals. The 1999-2000 recommended threshold limit values are given in Table 57-1. The acute toxic effect of benzene is depression of the central nervous system. Exposure to 7500 ppm for 30 minutes can be fatal. Exposure to concentrations larger than 3000 ppm may cause euphoria, nausea, locomotor problems, and coma vertigo, drowsiness, headache, and nausea may occur at concentrations ranging from 250 to 500 ppm. No specific treatment exists for the acute toxic effect of benzene. 

More animal than human data are available from which to determine LOAEL or NOAEL values of benzene hematotoxicity. The data show that animal responses to benzene exposure are variable and may depend on factors such as species, strain, duration of exposure, and whether exposure is intermittent or continuous. Wide variations have also been observed in normal hematological parameters, complicating statistical evaluation. The studies show that benzene exerts toxic effects at all phases of the hematological system, from stem cell depression in the bone marrow, to pancytopenia, to histopathological changes in the bone marrow. The following studies demonstrate these adverse hematological effects in animals. Effects on leukocytes, lymphocytes, and bone marrow are also discussed in Section 2.2.1.3. 

The Medinsky model (Medinsky et al. 1989a, 1989b, 1989c) is one of the original benzene PBPK models developed to describe and ultimately predict the fate of benzene in mice and rats and to determine if the observed differences in toxic effects could be explained by differences in pathways for metabolism of benzene or by differences in uptake of benzene. 

The most characteristic toxic effect of benzene in both human and animal models is the depression of the bone marrow, leading ultimately to aplastic anemia (Rozen and Snyder 1985 Snyder and Kocsis 1975 Snyder et al. 1993b). Rozen and Snyder (1985) have noted that abnormalities of humoral and cell-mediated immune responses following benzene exposure of C57BL mice by inhalation are presumably caused by a defect in the lymphoid stem cell precursors of both T- and B-lymphocytes. They also observed that bone marrow cellularity and the number of thymic T-cells increased, presumably as a compensatory response in these cell lines in response to benzene exposure. This compensatory proliferation may play a role in the carcinogenic response of C57BL mice to inhaled benzene. 

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. 

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