Determination of leukemogenic benzene exposure concentrations: refined analyses of the Pliofilm cohort. 1996

A R Schnatter, and M J Nicolich, and M G Bird
Exxon Biomedical Sciences, Inc., East Millstone, New Jersey 08875-2350, USA.

Biologic data on benzene metabolite doses, cytotoxicity, and genotoxicity often show that these effects do not vary directly with cumulative benzene exposure (i.e., concentration times time, or c x t). To examine the effect of an alternate exposure metric, we analyzed cell-type specific leukemia mortality in Pliofilm workers. The work history of each Pliofilm worker was used to define each worker's maximally exposed job/department combination over time and the associated long-term average concentration associated with the maximally exposed job (LTA-MEJ). Using this measure, in conjunction with four job exposure estimates, we calculated SMRs for groups of workers with increasing LTA-MEJs. The analyses suggest that a critical concentration of benzene exposure must be reached in order for the risk of leukemia or, more specifically, AMML to be expressed. The minimum concentration is between 20 and 60 ppm depending on the exposure estimate and endpoint (all leukemias or AMMLs only). We believe these analyses are a useful adjunct to previous analyses of the Pliofilm data. They suggests that (a) AMML risk is shown only above a critical concentration of benzene exposure, measured as a long-term average and experienced for years, (b) the critical concentration is between 50 and 60 ppm when using a median exposure estimate derived from three previous exposure assessments, and is between 20 and 25 ppm using the lowest exposure estimates, and (c) risks for total leukemia are driven by risks for AMML, suggesting that AMML is the cell type related to benzene exposure.

UI MeSH Term Description Entries
D007938 Leukemia A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006) Leucocythaemia,Leucocythemia,Leucocythaemias,Leucocythemias,Leukemias
D007948 Leukemia, Monocytic, Acute An acute myeloid leukemia in which 80% or more of the leukemic cells are of monocytic lineage including monoblasts, promonocytes, and MONOCYTES. Leukemia, Monoblastic, Acute,Leukemia, Myeloid, Acute, M5,Leukemia, Myeloid, Schilling-Type,Monoblastic Leukemia, Acute,Monocytic Leukemia, Acute,Myeloid Leukemia, Acute, M5,Myeloid Leukemia, Schilling-Type,Leukemia, Acute Monocytic,Leukemia, Myeloid, Schilling Type,Acute Monoblastic Leukemia,Acute Monoblastic Leukemias,Acute Monocytic Leukemia,Acute Monocytic Leukemias,Leukemia, Schilling-Type Myeloid,Leukemias, Acute Monoblastic,Leukemias, Acute Monocytic,Monoblastic Leukemias, Acute,Monocytic Leukemias, Acute,Myeloid Leukemia, Schilling Type,Schilling-Type Myeloid Leukemia
D008297 Male Males
D008452 Maximum Allowable Concentration The maximum exposure to a biologically active physical or chemical agent that is allowed during an 8-hour period (a workday) in a population of workers, or during a 24-hour period in the general population, which does not appear to cause appreciable harm, whether immediate or delayed for any period, in the target population. (From Lewis Dictionary of Toxicology, 1st ed) Maximum Permissible Exposure Level,MPEL,Maximum Permissible Exposure Concentration,Allowable Concentration, Maximum,Allowable Concentrations, Maximum,Concentration, Maximum Allowable,Concentrations, Maximum Allowable,MPELs,Maximum Allowable Concentrations
D009784 Occupational Diseases Diseases caused by factors involved in one's employment. Diseases, Occupational,Occupational Illnesses,Disease, Occupational,Illnesse, Occupational,Illnesses, Occupational,Occupational Disease,Occupational Illnesse
D009820 Ohio State bounded on the north by Michigan and Lake Erie, on the east by Ohio River and Pennsylvania, on the south by Ohio River, and on the west by Indiana.
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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