Invited Review ArticleCurrent understandings and perspectives on non-cancer health effects of benzene: A global concern
Introduction
Benzene (C6H6) is an organic hydrocarbon commonly used as a solvent in industries. Benzene is one of the most widely used chemicals in the synthesis of various polymers, resins, and synthetic fibers (Velasco Lezama et al., 2001).
Human life is surrounded by a wide range of environmental volatile organic compounds (VOCs) among which benzene has been known to have deleterious health effects (Karakitsios et al., 2007). Benzene is released to our environment from industry effluents, combustion of gasoline and other petrochemicals used in our cars and industries. Cigarette smoke is the main source for indoor benzene exposure (Wallace, 1996a, Wallace, 1996b). Being extensively used chemical in petroleum industries, and due to its subsequent presence in the environment from other sources, human exposure to benzene is unavoidable and the possible adverse health effects associated with benzene chronic or acute exposure remain a matter of great concern for public (Snyder, 2012). Humans are exposed to benzene most frequently through inhalation of vapors in the workplace and environment and by eating processed foods such as smoked and canned fish (Medeiros Vinci et al., 2012). Apart from above-mentioned sources, an additional quantity of approximately 10 kg/ton of benzene is released to our environment during manufacturing, transferring and storage (Etzel and Ashley, 1994).
Occupations dealing with leather, petrochemicals (refining, service station operators), scientific laboratories, rubber industries, coal based coke production, steel manufacturing, printing and plastic manufacturing industries have a possibility of their personnel to be highly exposed to benzene (Galbraith et al., 2010).
Benzene has long been known to act as carcinogen of human blood components. A first case of “benzene associated lymphoma” was reported by French researchers in 1947. According to recent studies, benzene at 3.19 mg/m3 exposure in air has been accounted to induce hematological effects in humans (Lan et al., 2004, Qu et al., 2002). It has been reported from China, Italy, and Turkey that occupational benzene exposure in the range of 638.8 to 5110.8 mg/m3 has caused acute myeloid leukemia, myelodysplastic syndrome, non-Hodgen lymphoma and possibly childhood leukemia (Brandt, 1992, Eden, 2010, Mchale et al., 2012).
Aromatic hydrocarbons are added to gasoline for maintaining high octane number and for best anti-knock properties. Refined petroleum products generally contain 2–3% benzene by volume (Wong and Fu, 2005). Due to hazardous effects of lead (Pb) on human health, the content of its additives in gasoline has been reduced and almost eliminated since the last decade, but for anti-knocking purposes, benzene is mixed with gasoline, so that the contents of benzene in gasoline have reached to more than 5% in some countries (Verma and Des Tombe, 2002, Karakitsios et al., 2007). In the USA, Australia, and Europe the concentration of benzene in gasoline has been reduced to 1% by volume (Verma and des Tombe, 2002), but in other regions like Russia, India, Malaysia, UAE, Bangladesh, Saudi Arabia, Egypt, Libya and some African countries, concentration of benzene in gasoline is estimated to be in the range of 3–7% volume. Pakistan, Iran, Iraq, Turkmenistan, Uzbekistan, Syria, and Sudan are the countries where no monitoring is exercised over benzene contents and any standard for benzene concentration in gasoline has not been set yet (Fig. 1). Information regarding benzene gasoline ration in different parts of the world taken from “International Fuel Quality Center, August 2013 and Hart Energy Research and Consulting” have been brought in Table 1.
As recommended by the U.S. Environmental Protection Agency, current threshold limit for benzene is 1.59 mg/m3 at workplace and 0.01597 mg/m3 for drinking water (Galbraith et al., 2010). In the Western and European countries, the concentration of benzene in the ambient air has fallen since 1990. As reported, the annual atmospheric concentration of benzene in European cities is in the range of few μg/m3 to 0.050 mg/m3 in busy streets and areas with high traffic density (Skov et al., 2001).
However, this concern regarding other countries particularly the developing ones is increasing, so that health hazards of exposure to benzene need more attentions for management from side of environmental health scientists and agencies.
Section snippets
Chronic exposure
The toxic effects of benzene exposure on blood components have been studied in detail. Both in experimental and epidemiologic studies, it has been reported that chronic exposure to benzene is associated with decrease in HB, platelet count, and WBC count (Hsieh et al., 1990, Travis et al., 1994). Neutrophils and mean platelet volume (MPV) in the blood have been reported as the most affected parameters by benzene exposure in workers exposed to benzene in a factory in China, where the recorded
Neurological effects
Long-term exposure to benzene may cause neurological abnormalities. Baslo and Aksoy (1982) published a cohort study of eight patients previously exposed to solutions containing benzene (9–88%). Six patients showed neurological abnormalities in the form of atrophy of lower extremities and neuropathy of upper extremities (Baslo and Aksoy, 1982). That study suggested that benzene may produce some toxic effects on the peripheral nerves. The limitation of this study was the possibility of patients'
Acute exposure
Acute exposure to benzene has been shown to possess toxic effects on respiratory system in humans. Avis and Hutton (1993) have published a case report of accidental exposure to benzene vapors at high concentration which caused three fatalities. Hemorrhagic and edematous lungs were reported by autopsy of the victims (Avis and Hutton, 1993). Winek and Collom (1971) have published a report of benzene poisoning of 18 year old male. On autopsy they found bronchitis and massive hemorrhages of the
Chronic exposure
Many synthetic and natural compounds exist in the environment affecting the much sensibly-regulated hormonal messenger system of the body. In this way, they have been categorized as endocrine disrupting chemicals (EDCs) which have been a major topic of debate for environmental scientists since long (Verma and Rana, 2009, Uzma et al., 2008). Many organic compounds and industrial solvents have been shown to act as endocrine disruptors for humans and wildlife (Colborn et al., 1993). Benzene is an
Acute exposure
Liver and pancreas are the two principal organs responsible for glucose homeostasis. In animal studies, a single dose of 800 mg/kg orally has altered the activity of the main enzyme of glycolytic pathway. Acute benzene exposure is suspected to have caused an increase in hexokinase level of intestine and liver, and decrease in hexokinase amount of brain, renal cortex and medulla (Khan and Yusufi, 2009). Decreased activity of glucose 6-phosphatase and fructose-1,6-biphosphatase, main enzymes
Chronic exposure
Environmental pollutants such as benzene are of primary concern in causing chronic diseases; however limited epidemiologic data are available to describe benzene as one of the causative agents of hypertension. An epidemiologic study published by Wiwanitkit (2007) indicated that hypertension is more prevalent in benzene-exposed group as compared to control. However, this study failed to monitor the concentration and duration of benzene exposure (Wiwanitkit, 2007). Another epidemiologic study
Acute exposure
Liver is more vulnerable organ to the toxic effects of hydrocarbons. Chronic exposure to hydrocarbons including benzene has been reported to produce adverse effects on liver enzymes (Perez et al., 2006). The metabolites of benzene, in addition to adduct formation with DNA and RNA also attach to the proteins of liver, kidney, bone marrow and stomach (Lindstrom et al., 1997, Snyder and Hedli, 1996). Dere and Ari (2009) reported that acutely exposed rats at dose 100 mg/kg benzene orally show an
Chronic exposure
Exposure to halogenated hydrocarbons, petroleum distillates, ethylene glycol, and dioxane may cause oliguria and azotemia (Lauwerys et al., 1985, Roy et al., 2008). Khan and Yusufi (2009) reported the nephrotoxic effects of benzene by examining 33% increase in blood urea nitrogen (BUN) and 30% increase in serum creatinine in rats exposed to benzene at dose 800 mg/kg for 30 days (Khan and Yusufi, 2009). Viau et al. (1987) published a cross sectional study of 53 male oil refinery workers exposed to
Formation of reactive oxygen species (ROS) and oxidative stress
After being metabolized in the liver and bone marrow by CYP4502E1 oxidation pathways, benzene produces free radicals and quinone metabolites like phenol, hydroquinone, benzoquinone, and 1,2,4-benzenetriol. Studies suggest that benzene exerts its cytotoxicity via these critically toxic metabolites and free radicals (Atkinson, 2009, Kolachana et al., 1993, Smith, 1996a). In the course of an experimental study on HL60 human leukemia cells, Shen et al. (1996) have found benzoquinone and
Discussion & conclusion
The concern of the existence of chemical air pollutants and their possible role in causing various chronic diseases is very long, but due to lack of comprehensive monitoring system, health outcomes associated with air pollutants are poorly characterized (Briggs, 2003).
Benzene is one of the chemical air pollutants and is ubiquitous in our environment released from various sources posing a silent threat to human health. It is worth mentioning that in most of the countries, where benzene is being
Conclusion
The current study presents accumulated data both experimental and epidemiologic on benzene-induced health toxicities with particular emphasis on non-cancerous health effects. Based on the mechanism of toxicity of benzene, it could reasonably be said that benzene may be one of the risk factors in the incidence of chronic diseases such as diabetes, and lung and breast cancers in the developing countries. There are enough evidences available which suggest that environmental pollutants are among
Conflicts of interest
The authors declare that there are no conflicts of interest.
Acknowledgment
This invited paper is the outcome of a financially non-supported study.
References (130)
- et al.
Detection of DNA damage in human lymphocytes by alkaline single cell gel electrophoresis after exposure to benzene or benzene metabolites
Mutat. Res.
(1997) A review of the role of benzene metabolites and mechanisms in malignant transformation: summative evidence for a lack of research in nonmyelogenous cancer types
Int. J. Hyg. Environ. Health
(2009)- et al.
Neurological abnormalities in chronic benzene poisoning. A study of six patients with aplastic anemia and two with preleukemia
Environ. Res.
(1982) Exposure to organic solvents and risk of haematological malignancies
Leuk. Res.
(1992)Induction of micronuclei and aneuploidy by the quinone-forming agents benzene and o-phenylphenol
Toxicol. Lett.
(1993)Aetiology of childhood leukaemia
Cancer Treat. Rev.
(2010)- et al.
Effects of benzene on splenic, thymic, and femoral lymphocytes in mice
Toxicology
(1997) - et al.
Global prevalence of dementia: a Delphi consensus study
Lancet
(2005) - et al.
Benzene inhibits RNA synthesis in mitochondria from liver and bone marrow
Chem. Biol. Interact.
(1982) - et al.
Contribution to ambient benzene concentrations in the vicinity of petrol stations: estimation of the associated health risk
Atmos. Environ.
(2007)