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BIOMARKERS IN CZECH WORKERS EXPOSED TO 1,3-BUTADIENE: A TRANSITIONAL EPIDEMIOLOGIC STUDY
Impact/Purpose:
Butadiene is a four-carbon gaseous chemical synthesized for the manufacture of resins, plastics, and synthetic rubber. It is also produced by combustion; butadiene is present in cigarette smoke and emissions from motor vehicles and some stationary sources. The highest exposures, those that occur in occupational settings, may present a health concern because butadiene is known to be carcinogenic in rats and mice and some epidemiologic studies have implicated it as a human carcinogen by inhalation. Those studies have indicated that workers exposed to butadiene in rubber-producing factories also have an increased incidence of two types of cancer: cancers of the lymphatic system and cancers of the organs and systems of the body that produce blood cells. More recent and comprehensive studies of the same workers have indicated an increased risk of leukemia (but not other types of cancers) in workers with a long duration of employment in the rubber industry. On the basis of these epidemiologic studies, various government and international agencies have conducted risk assessments of butadiene’s carcinogenicity and designated it as “potentially carcinogenic to humans,” “a probable human carcinogen,” and a “known human carcinogen.”
Epidemiologic studies have encountered two primary difficulties in assessing exposure to carcinogenic agents. First, because the incidence of certain cancers is low, they have needed to study large populations to find an association between exposure and disease. Second, it is often difficult to accurately assess the level or time course of exposure to a possible cancer-causing agent in order to link past exposures to recent disease occurrences. In contrast with this, populations known to have been exposed to certain chemicals (such as groups of workers in a specific industry) show relatively high levels of biomarkers. Therefore, if biomarkers can accurately reflect the level or timing of exposure to a suspected carcinogen, they may be able to enhance exposure assessment in epidemiologic studies.
Dr Richard Albertini at the University of Vermont in Burlington organized groups of researchers from his own laboratory and laboratories in Galveston, Texas; Chapel Hill, North Carolina; Prague, Czech Republic; Amsterdam and Leiden, The Netherlands; and Sheffield, United Kingdom. Each group had expertise in identifying different biomarkers that appear after butadiene exposure. Dr Radim Šrám of the Laboratory of Genetic Ecotoxicology in Prague provided contact with butadiene-exposed workers in two production units of a factory near Prague.
Description:
All the biomarkers of exposure were correlated with the measurements of butadiene recorded by the air samplers. Although the correlation between hemoglobin adducts and exposure levels was strongest, urinary metabolites were also found to be very useful measures of butadiene exposure.
No statistically significant correlations were found between any of the biomarkers of effect and butadiene exposure. Although these biomarkers were investigated, they were evaluated against exposure, not against health outcomes. Thus, no conclusions about health outcomes can be drawn from these results.
This very important and valuable study established the linkage between exposure to butadiene, as measured by comprehensive conventional sampling techniques, and several biological markers of such exposures. The integration of a comprehensive exposure assessment with a series of logical biomarker analyses was an outstanding feature of this complex international study. Of the many biomarkers analyzed, the biomarkers of exposure (particularly hemoglobin adducts) may prove to be valuable in future epidemiologic studies of the health effects of butadiene exposure.