Development of Liquid Chromatography; Electrospray Ionization; Tandem Mass211 Spectrometry Methods for Determination of Urinary Metabolites of Benzene in 211 Humans

摘要

Occupational exposure to benzene is associated with the development of leukemia211u001eand other blood disorders; however, the effects of exposure to low levels of 211u001ebenzene are not well understood. In 1994, the Health Effects Institute (HEI) 211u001einitiated a research program (the HEI Air Toxics Program) to address 211u001euncertainties in the health effects resulting from exposure to ambient levels of 211u001etoxic air pollutants including benzene. One of the goals of this program was to 211u001edevelop and validate biomarkers of exposure to benzene. There are a number of 211u001echallenges in identifying suitable markers of recent benzene exposure that are 211u001eappropriate for epidemiologic studies. First, benzene can be metabolized along a 211u001enumber of different pathways, and some products of benzene metabolism can also be 211u001ederived from the metabolism of other compounds. Second, data on benzene 211u001emetabolism in humans are limited, particularly in response to low-dose exposures, 211u001eand it has been difficult to extrapolate results of controlled exposure studies 211u001ein animals to the human situation. Third, it is difficult to detect and measure 211u001ereproducibly the low levels of many benzene metabolites. In response to these 211u001econcerns, HEI funded Dr. Melikian and colleagues to develop and validate a novel, 211u001epractical method for assaying metabolites of benzene in humans.