Benzene Exposure and Lymphatic Cancer Development: Epidemiological Insights, Slides of Public Health

Download Benzene Exposure and Lymphatic Cancer Development: Epidemiological Insights and more Slides Public Health in PDF only on Docsity! Epidemiological Issues in Determining Whether Benzene Causes Lymphatic Cancer or A Toxicologist’s Defense Against the Pump Handle docsity.com The Three Laws of Toxicology 1. The dose makes the poison 2. Chemicals have specific effects 3. Humans are animals docsity.com The National Safety Council Congress….. In 1921 held a session on benzene poisoning. Dr. Lothar E. Weber of the Boston India Rubber Laboratory stated that benzene “has been criticized as very dangerous (and) very injurious… and, personally, I feel an injustice has been done to this particular substance.”… In response, C.F. Horan of the Hood Rubber Company replied that inhalation experiments with benzene, toluene, and xylene on guinea pigs and rabbits, showed acute toxicity of benzene compared to the other two compounds. Not persuaded, Weber rejoined that he was not going to change his opinion altogether on the basis of a few guinea pig experiments. Hounshell & Smith, 1988 docsity.com Benzene and Alkylbenzenes CH3 CH3 H3C C H CH3 Benzene CH3 Toluene Xylene CumeneEthylbenzene CH2 CH3 docsity.com PATHWAYS OF BENZENE METABOLISM LEADING TO TOXIC ; Oy MFO oH a feet Bsr t= a eet eee ca eh tial: epee ey Prostaglandin Eta eM lars melas ie (clay cs] fle OH Semiquinone Free Radical docsity.com Evidence Supporting Benzene Leukemogenesis 1. Biomedical Plausibility 2. Case Studies 3. Epidemiology A. Numerator Specific B. Denominator Specific docsity.com Table 1 Carcinogenic Potency of Benzene Calculated on the Basis of Nonlymphatic Leukemia Mortality Rates Observed in Three Epidemiologic Studies Estimated Estimated Lifetime risk Lifetime risk Database relative risk continuous exposure per ppm per git! Infante et al. (1977) 6.4 173 1.33 10°%ppm 4.09 x 10°* wei’ Aksoy (1974; 1976; 1977) 9% 1.2 1,82 % 10-%ppm 5.60 X 10* wpm’ Ott et al. (1977) 4D 017 4.64 x 10-4ppm 143% 10°? yet’ . Geometic mean = 2.23 X 10"%ppm 7.08 x 10-Yugén? docsity.com CS Carcinogenic potency of benzene calculated on the basis of animal data 7.3 x 10 –62.4 x 10 –2GEOMETRIC MEAN 4.3 x 10 –61.4 x 10 –2Male rats (Snyder, et. al, 1980) b 1.0 x 10 –53.3 x 10 –2Female rats (NTP, 1982) a 6.0 x 10 –62.0 x 10 –2Male rats (NTP, 1984) a 1.1 x 10 –53.4 x 10 –2 Female rats (Maltoni, et. al, 1982) a Lifetime risk per ug/m3 Lifetime risk per ppm Data Base docsity.com Case Control Study of Benzene Exposure and Leukemia in 36 British Male Oil Refinery Workers Logistic Models Matched on Year of Birth 1.24 – 7.202.99Benzene exposure plus length of service 1.01 – 1.432.26Benzene exposure plus year of entry 0.94 – 4.282.01Benzene exposure Confidence IntervalRelative Risk Benzene Exposure Rushton & Alderson, 1981 docsity.com Hematologic Effects of Benzene Causality Probable but Unproven – Acute Lymphatic Leukemia – Non-Hodgkin’s Lymphoma – Multiple Myeloma – Paroxysmal Nocturnal Hemoglobinuria – Chronic Myelogenous Leukemia docsity.com Hematologic Effects of Benzene Causality Possible –Hodgkin’s Disease –Chronic Lymphocytic Leukemia (and other Myeloproliferative Disorders) docsity.com Non-Hodgkin’s Lymphoma • Lymphocytic tumors diagnosed by exclusion - not Hodgkin’s disease nor lymphocytic leukemias • Broad and overlapping range of disease entities and etiologies. • Immune suppression common to a number of causative factors, including HIV infection. docsity.com Biological Plausibility of Causal Relationship of Benzene to Multiple Myeloma • Multiple myeloma is a tumor of plasma cells which are a form of B lymphocytes • Exposure to benzene destroys B lymphocytes and causes chromosomal abnormalities in B lymphocytes • Benzene is a known cause of leukemia, a bone marrow cancer, through a mechanism that leads to the presence of a carcinogenic metabolite within the bone marrow. • Multiple myeloma is a bone marrow tumor. docsity.com Role of Biological Plausibility in Determining Causal Relations of Benzene to Multiple Myeloma • Benzene causes the formation of a carcinogen that is specific to the organ at risk and that affects the basic cell type, including producing cytogenetic abnormalities. docsity.com Case control study • 309 matched pairs of hematopoietic and lymphoid neoplasms in Kanawha County, WV. • “association between chemical industry work and death due to non-Hodgkin’s lymphoma, multiple myeloma, and lymphoid leukemia…” • For NHL, OR 3.11, p = .003 for those who died at age <65 • For MM, OR 2.39, p = .039 for all age groups • For all hematopoietic and lymphoid neoplasms; OR 3.31, p = .001 docsity.com Case control study • 309 matched pairs of hematopoietic and lymphoid neoplasms in Kanawha County, WV. • “association between chemical industry work and death due to non-Hodgkin’s lymphoma, multiple myeloma, and lymphoid leukemia…” • For NHL, OR 3.11, p = .003 for those who died at age <65 • For MM, OR 2.39, p = .039 for all age groups • For all hematopoietic and lymphoid neoplasms; OR 3.31, p = .001 • Massoudi, Talbott, Day, Swerdlow, Marsh and Kuller. Amer J Indust Med, 1997 docsity.com