Benzenes chronic effects

Chronic Health Effect A chronic health effect is an adverse health effect resulting from long-term exposure to a substance. The effects could be a skin rash, bronchitis, cancer, or any other medical condition. An example would be liver cancer from inhaling low levels of benzene at your workplace over several years. The term is also applied to a persistent (months, years, or permanent) adverse health effect resulting from a short-term (acute) exposure. Chronic effects from long-term exposure to chemicals are fairly common. Recognize the PEL (permissible exposure level) for each substance in your workplace and minimize your exposure whenever possible. 

Long-term (chronic) potential hazards of lighter, more volatile, and water-soluble aromatic compounds include contamination of groundwater. Chronic effects of benzene, toluene, and xylene include changes in the liver and harmful effects on the kidneys, heart, lungs, and nervous system. 

Toluene (methylbenzene) does not possess the myelotoxic properties of benzene, nor has it been associated with leukemia. It is, however, a central nervous system depressant and a skin and eye irritant. It is also fetotoxic. See Table 56-1 for the TLVs. Exposure to 800 ppm can lead to severe fatigue and ataxia 10,000 ppm can produce rapid loss of consciousness. Chronic effects of long-term toluene exposure are unclear because human studies indicating behavioral effects usually concern exposures to several solvents. In limited occupational studies, however, metabolic interactions and modification of toluene s effects have not been observed in workers also exposed to other solvents. Less refined grades of toluene contain benzene. 

Coincident with the development of sampling procedures were the constant iterative improvements in extraction, separation, identification and quantitation of organic compounds. Special emphasis was placed on selected compound classes such as the polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), chlorinated benzenes, and chlorinated dibenzo-p-dioxins (dioxins). The best available procedures were used to determine these components because they have known acute or chronic effects and previous studies suggested that they might be present in effluents from the combustion of coal alone and combination coal/RDF. 

Kahn H, Muzyka V. 1973. The chronic effect of benzene on porphyrin metabolism. Work Environ Health 10 140-143. 

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. 

All the BTEXs cause neurological effects. Neurological effects are the basis for MRLs for both acute and chronic exposures to toluene and mixed xylenes, and for intermediate exposures to benzene neurological effects are not as sensitive for ethylbenzene. The neurological effects consist primarily of central nervous system depression. Toluene s neurotoxicity also includes ototoxicity. Evidence of hearing loss has been seen in both occupationally exposed humans and in animals. There is limited evidence that chronic inhalation exposure to benzene may affect the peripheral nervous system this evidence is from a single study of occupationally exposed humans who also had aplastic anemia. 

The determinative factor in acute health effects is the dose of the pollutant. Most of the acute effects are temporary, but may also cause coma and death. Relatively low concentrations exposures of the human body to pollutants, longer and/or repeated periods may cause chronic health effects. The period of time between the first exposure and the development of the disorder (leukemia, cancer, cirrhosis, scarring of the lung or kidneys) is called latency period. The same pollutant (i.e. benzene) may cause acute effects (encephalophaty - central nervous system disorders) and/or chronic effects (leukemia - a type of cancer affecting the bone marrow and the blood cells) (Reese, 2003). 

Aliphatic hydrocarbons exhibit mild toxicity but primarily an anesthetic effect. Higher fatty alcohols are nontoxic. Aromatic hydrocarbons are narcotics. Benzene exhibits both acute and chronic toxicity. The chronic effects — anemia, abnormal increase... 

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. 

Toluene is metabolized to benzoic acid and finally, to hippuric acid and benzoylglu-curonide. The latter two are excreted in urine along with small amounts of cresols, formed by direct hydroxylation of toluene. Chronic exposure may cause some accumulation of toluene in fatty tissues, which may be eliminated over a period of time. The chronic effects of toluene are much less severe to benzene. It is not known to cause bone marrow depression or anemia. Animal tests showed no carcinogenic effects. 

B. Benzene is also known for its chronic effects on the hematopoietic system, which are thought to be mediated by a reactive toxic intermediate metabolite. 

There are two different kinds of vapour toxicity and these may occur with the same solvent. Narcotic effects are those of drunkenness or poisoning, which wear off as the solvent is eliminated from the body, e.g. ethanol. Long-term effects may occur after the solvent has been absorbed, either as poisoning, e.g. methanol, or carcinogenic, e.g. benzene. With wider use of solvents, it is being found that chronic effects are much more common than had been realized. 

Chronic Effects on Body Organs. Many organs of the body may be adversely affected by solvents, the most important being the liver and the peripheral and central nervous systems. Benzene is unique amongst the solvents in adversely affecting the bone marrow. 

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,... 

Aplastic anemia and leukemia are not the only health effects ascribed to benzene exposure. A number of recent studies have associated benzene exposure with chromosomal changes (aberrations) (118). Other studies have shown abnormalities in porphyrin metabolism and decrease in leucocyte alkaline phosphatase activity in apparendy healthy workers exposed to 10—20 ppm benzene (119,120). Increases in leukoagglutinins, as well as increases in blood fibrinolytic activity, have also been reported and are believed to be responsible for the persistent hemorrhages in chronic benzene poisoning (121,122). 

Ocular Effects. A case-control study of office workers was conducted by Baj et al. (1994) to evaluate the risks of chronic exposures to inhaled formaldehyde, phenol and isomers of organic chlorohydrocarbons from Ksylamit which is a widely used liquid wood preservative reported to consist of a mixture of chlorinated benzenes, pentachlorophenol, alpha-chloronaphthalene, chloroparafifin, and kerosene . Twenty-two workers (18 women and 4 men) exposed for at least 6 months were the cases, and 29 non-exposed, non-smoking volunteers matched for age, sex, and place of residence were the controls. The authors indicate that all of the exposed workers developed chronic complaints, among them burning eyes, but that no remarkable increase in morbidity was found during the 6 months of exposure to Ksylamit , nor during the 3-year follow-up study (details of which were not provided). The authors attribute these symptoms to the irritant effect of the inhaled Ksylamit probably (based on the references provided) due to the formaldehyde vapor they assert emanates from the woodpreserving liquid. 

Blood dyscrasias have been noted in humans acutely and chronically exposed to gasoline, but these effects are most likely due to benzene, and the incidence of these findings has decreased as the benzene content in gasoline has decreased. ... 

Before 1940, most reports on the possible chronic toxicity of xylene also involved exposure to solvents that also contained high percentages of benzene or toluene as well as other compounds. Consequently, the effects attributed to xylene in these reports are questionable. Blood dyscrasias, such as those reportedly caused by benzene exposure, have not been associated with the xylenes. ... 

Benzene, a component of motor fuel that is also widely used as an industrial solvent and as a starting material in organic synthesis, is a hematopoietic toxin. Chronic exposure to benzene vapors leads to pancytopenia, that is, decreased production of all types of blood cells (erythrocytes, leukocytes, and platelets). The long-term effect of benzene exposure is acute leukemia. 

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. 

---