Environmental and Occupational Epidemiology - Assignment Example

ENVIRONMENTAL AND OCCUPATIONAL EPIDEMIOLOGY INTRODUCTION The community under epidemiological investigation has been exposed to manyenvironmental contaminants including Bis-Chloromethyl Ether, Benzene, Dichloroethane, Styrene, Vinyl chloride (VC), Polyvinylchloride (PVC) and Polycyclic Aromatic Hydrocarbons (PAH). The present study aims to investigate the carcinogenicity of three of these contaminants namely Bis-Chloromethyl ether, Benzene and Styrene. Investigation: Epidemiological studies show that approximately 15% of lung cancers in men and 5% of lung cancers in women are caused by such environmental exposures. As per the rating system based on animal and human data by The International Agency for Research on Cancer, where an agent, mixture, or exposure circumstance is assigned to one of five categories, Bis chloromethyl ether, Benzene and Styrene belong to group 1, which means that the agents are carcinogenic to humans (Gottschall et.al, 2002). Of the three, Benzene is the most potential carcinogen causing carcinoma of various internal organs and tissues. It is followed by Bis -chloromethyl ether in potency, which is a known carcinogen of the lungs and Styrene known for its mutagenic effects. The Bologna experiments at the Bentivoglio Experimental Unit of the Bologna Institute of Oncology proved for the first time that benzene is an experimental carcinogen. These experiments demonstrated that benzene was carcinogenic when administered by ingestion and by inhalation and could cause tumors in the various tested animal models. They also showed that benzene is a multipotential carcinogen, as it produces a variety of neoplasias in one or more of the tested animal models, including Zymbal gland carcinomas, carcinomas of the oral cavity, nasal cavities, skin, fore stomach, and mammary glands, as well as angiosarcomas of the liver, hemolymphoreticular neoplasias, tumors of the lung, and possibly hepatomas. The Bologna experiments have also provided a clear-cut dose-response relationship in benzene carcinogenesis (Maltoni et.al, 1989). Bis-Chloromethyl ether has been proved to cause lung cancer (Weiss et.al, 1997) and the Epidemic curve of respiratory cancer due to chloromethyl ethers has been established (Weiss, 1982). Styrene oxide (SO), a reactive metabolite of styrene, has been shown to modify DNA at several nucleophilic sites and thus styrene is a carcinogenic mutagen (Mikko et.al, 2001). HEMATOLOGICAL MALIGNANCY Molecular Epidemiology is a new and evolving area of research, combining laboratory measurement of internal dose, biologically effective dose, biologic effects, and influence of individual susceptibility with epidemiological methodologies. Biomarkers evaluated are selected according to basic scheme: biomarkers of exposure-metabolites in urine, DNA adducts, protein adducts, and Comet assay parameters; biomarkers of effect-chromosomal aberrations, sister chromatid exchanges, micronuclei, mutations in the hypoxanthine-guanine phospho ribo- syltransferase gene, and the activation of oncogenes coding for p53 or p21 proteins as measured on protein levels (Radim et.al, 2000). Tissue Distribution of DNA Adducts and their persistence in Blood of Mice Exposed to Benzene have been well documented (Guilan Li et.al, 1996). The studies have demonstrated that benzene could induce DNA adducts in bone marrow, liver, and white blood cells dosed with benzene and that measurement of adducts in white blood cells may be useful as a biomarker to predict hematological carcinogenic risk of benzene in human beings. The role of Benzene in hematological malignancy has been documented (Rothman et.al, 1999). Benzene has been proved to cause leukemia, particularly acute nonlymphocytic leukemia and other hematologic neoplasms (Hayes et.al, 1997). The results of this study have also shown that even exposure levels of less than 10 ppm can cause cancer. Although Bis-Chloromethyl ether is a known carcinogen of the lung tissues, their hematological carcinogenicity has been proved by microarray studies (Dupuy et.al, 2006). OSHA has also reviewed a number of human epidemiological studies that have examined the mortality experience of styrene-butadiene. These studies have consistently reported an elevated relative risk of leukemia-or lymphoma-related death among BD-exposed population (www.osha.gov). This includes the studies of Dalzell et al. who have found a positive and statistically significant dose-response relationship between cumulative exposure to styrene and increased leukemia mortality, which remained statistically significant even after controlling for the potential confounder of concurrent styrene exposure (www.osha.gov). Chemical carcinogen Availability of In Vitro data Availability of In Vivo data Bis-Chloromethyl ether Yes Mice/ human Benzene Yes Mice/human Styrene Yes Mice / human The nine Bradford-Hill Criterion of Strength and association, consistency specificity, temporality, dose response Bio-gradient, Biological plausibility, Biological coherence, Experimental evidence and Analogy for assessment of carcinogenesis is met with in case of these three chemicals in the sense that there has been consistent, published reports of carcinoma induced by them; with each inducing organ specific carcinoma with chronic dose specific exposure without conflicting the already known mechanism of carcinogenesis with evidence of mutagenesis in vitro and in vivo. REFERENCE Dupuy A, Simon RM., "Critical review of published microarray studies for cancer outcome and guidelines on statistical analysis and reporting". J Natl Cancer Inst 2006; 99:148-58. N Rothman, MT Smith, RB Hayes, RD Traver, B Hoener, Benzene Poisoning, a Risk Factor for Hematological Malignancy, Is Associated with the NQO1 609C-> T Cancer Research, 1997 - AACR. Weiss W. Epidemic curve of respiratory cancer due to chloromethyl ethers. J Natl Cancer Inst. 1982 Dec; 69(6): 1265-70. Weiss, William MD; Nash, Denis, "An Epidemic of Lung Cancer Due to Chloromethyl Ethers: 30 Years of Observation", Journal of Occupational & Environmental Medicine. 39(10): 1003-1009, October 1997. Gottschall, E. Brigitte., "Occupational and Environmental Thoracic Malignancies. Imaging of Occupational Lung Disease", Journal of Thoracic Imaging. 17(3): 189-197, July 2002. Mikko Koskinen et.al, "32P-postlabelling/HPLC analysis of various styrene-induced DNA adducts in mice", Biomarkers, Volume 6, Issue 3 May 2001 , pages 175 - 189. Y S Lin et.al, 'Air samples versus biomarkers for Epidemiology', Occupational and Environmental Medicine 2005; 62:750-760. Assieh A. Melikian, Ray O'Connor, Agasanur K. Prahalad, Peifeng Hu, Heyi Li, Mark Kagan and Seth Thompson, "Determination of the urinary benzene metabolites S-phenylmercapturic acid and trans, trans-muconic acid by liquid chromatography-tandem mass spectrometry", Carcinogenesis, Vol. 20, No. 4, 719-726, April 1999. Yusuke Hiraku and Shosuke Kawanishi, 'Oxidative DNA Damage and Apoptosis Induced by Benzene Metabolites', Cancer Research 56, 5172-5178, November 15, 1996. Stephen M. Rappaport, 'Albumin Adducts of Benzene Oxide and 1,4-Benzoquinone as Measures of Human Benzene Metabolism;, Cancer Research 62, 1330-1337, March 1, 2002. C Maltoni, A Ciliberti, G Cotti, B Conti, and F Belpoggi, 'Benzene, an experimental multipotential carcinogen: results of the long-term bioassays performed at the Bologna Institute of Oncology'. Environ Health Perspect. 1989 July; 82: 109-124. Guilan Li, Chunguang Wang, Weidong Xin, Songnian Yin, "Tissue Distribution of DNA Adducts and Their Persistence in Blood of Mice Exposed to Benzene", Environmental Health Perspectives, Vol. 104, Supplement 6: Benzene Toxicity, Carcinogenesis, and Epidemiology (Dec., 1996), pp. 1337-1338. Radim J. Sram, Blanka Binkova, "Molecular Epidemiology Studies on Occupational and Environmental Exposure to Mutagens and Carcinogens, 1997-1999", Environmental Health Perspectives, Vol. 108, Supplement 1: Reviews in Environmental Health 2000 (Mar., 2000), pp. 57-70. Lorenzo tomatis, Primary Prevention Protects Public Health, Annals of the New York Academy of Sciences 982:190-197 (2002). A S Whittemore, "Cancer risk assessment and prevention: where do we stand" Environ Health Perspect. 1989 May; 81: 95-101. Harri Vainio, Michel Coleman, Julian Wilbourn, Carcinogenicity Evaluations and Ongoing Studies: The IARC Databases, Environmental Health Perspectives, Vol. 96, Dec., 1991 (Dec., 1991), pp. 5-9 Lorenzo Tomatis, "Etiologic evidence and primary prevention of cancer", Drug Metabolism Reviews, Volume 32, Issue 2 April 2000 , pages 129 - 137. Richard J. Waxweiler, "Epidemiologic Problems Associated with Exposure to Several Agents", Environmental Health Perspectives, Vol. 42, Dec., 1981 (Dec., 1981), pp. 51-56. Stuart H.Yuspa, 'Overview of carcinogenesis: past, present and future', Carcinogenesis, Vol. 21, No. 3, 341-344, March 2000. Francis J. C. Roe, "Review: Laboratory Studies in the Prediction of Lung Cancer Risk", Indoor and Built Environment, Vol. 5, No. 4, 196-204. http://www.osha.gov/pls/oshaweb/owadisp.show_documentp_id=748&p_table=PREAMBLES. Read More