Journal of Toxiocology and Environmental Health (JTEH)

New Insights into Benzene:
Mechanisms, Models, and Managing Risks

The latest scientific proceedings concerning benzene, including recent developments on the mechanism of benzene-induced leukemia, recent evidence from human studies, and the application of these findings to the risk assessment process, are the focus of a special issue of the Journal of Toxicology and Environmental Health, Part A (Volume 61, Issues 5-6:305-552) in 2000.   

Benzene is a widely used, yet hazardous, chemical that is absorbed both rapidly and efficiently by the body. Benzene is most commonly associated with  exerting carcinogenic effects in mammals.  The IARC lists benzene as “known to be carcinogenic to humans” (Group 1). Benzene has been consistently associated with increased leukemia incidence.  However, benzene exposure also results in a suite of other serious health effects.  Breathing high levels of benzene produces effects ranging from drowsiness and a rapid heart rate, to a state of unconsciousness.  Ingesting high levels induce vomiting, convulsions, and death.  The most important consequences from long-term exposure to benzene are on the blood. Harmful effects on bone marrow, leading to a decrease in red blood cells and eventually anemia, result from chronic benzene exposure.  Further hazardous outcomes include adverse reproductive, immunological, genotoxic, and neurological effects.

Natural sources of benzene include volcanoes and forest fires.  A widely used solvent and precursor chemical in industry, benzene is important in the production of drugs, plastics, and dyes, among other uses.  Exposure of the general population to benzene occurs largely from crude oil, gasoline, and through various household products such as paints, adhesives, and health and beauty aids.  However, the major source of benzene exposure for the general population is usually cigarette smoking.   

The aim of this special issue of the Journal of Toxicology and Environmental Health, Part A was to summarize the proceedings of two 1998 workshops aimed at assessing the cancer risks associated with benzene exposure held at the University of Ottawa.   The first, the Benzene State-of-the-Science Workshop, focussed on the effects of chronic exposure to benzene including hematotoxicity, immunotoxicity, genotoxicity, and carcinogenicity.  Recent toxicological, epidemiological, and molecular research findings related to benzene were discussed by more than 70 scientists with an interest in the adverse health effects attributed to benzene.  The metabolism of benzene was highlighted as an important issue since once benzene enters the body and is broken down in the liver,, the resulting metabolites are the agents responsible for carcinogenesis.  Further, since benzene is ever-present and widespread in nature and the general population is routinely exposed to low levels, health effects from chronic low-level exposure are an important consideration in determining new or updating current risk management standards for benzene.  The issues of benzene metabolism and chronic effects of low-level exposure were identified as important further research needs, along with developing a better understanding of benzene leukemogenic mechanisms and improving biologically based models.

The proceedings of the next workshop, a satellite meeting on Hematotoxicity Modeling are also summarized in this issue.  The focus of the Workshop on Hematotoxicity Modeling was to critically evaluate the biologically based risk assessment model for cyclophosphamide hematotoxicity developed by Cox Associates for the American Petroleum Institute.  Since both benzene and cyclophosphamide impact hematosis in similar ways, understanding the mechanism for cyclophosphamide-induced toxicity may increase insight into the mechanisms of action of benzene on the hematopoietic system.  Experts ranging from scientists with experience in biologically based risk modeling to clinical hematologists specializing in hematopoietic disorders participated in the review of the risk assessment model.  Continued work in this area is expected to give valuable insight into benzene-induced leukemogenesis. 

Finally, scientific developments in benzene risk assessment since the workshop were reviewed.  Potential means for the refinement of current regulatory benzene cancer risk assessment were discussed.  The most important health effects, from a risk assessment point of view, were myelodysplasia and acute mylogenous leukemia.  Information from the two workshops, in addition to developments in risk assessment, provides critical new insights into benzene-related risks and risk management.

D. Krewski and R. Snyder. 2000. Special Issue on Benzene. Journal of Toxicology and Environmental Health, Part A 61(5-6):305-552.

Published twenty-four times per year, the Journal of Toxicology and Environmental Health, Part A features strictly refereed original research in the field of environmental toxicology in general as well as in special interest fields such as target organ toxicities, immunotoxicology, risk assessment, carcinogenesis, mutagenesis, ecotoxicology, environmental factors affecting health, and aquatic toxicology.

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