Biomarkers of Environmental Benzene Exposure

Abstract

Environmental exposures to benzene result in increases in body burden that are reflected in various biomarkers of exposure, including benzene in exhaled breath, benzene in blood and urinary trans-trans-muconic acid and S-phenylmercapturic acid. A review of the literature indicates that these biomarkers can be used to distinguish populations with different levels of exposure (such as smokers from nonsmokers and occupationally exposed from environmentally exposed populations) and to determine differences in metabolism. Biomarkers in humans have shown that the percentage of benzene metabolized by the ring-opening pathway is greater at environmental exposures than that at higher occupational exposures, a trend similar to that found in animal studies. This suggests that the dose-response curve is nonlinear; that potential different metabolic mechanisms exist at high and low doses; and that the validity of a linear extrapolation of adverse effects measured at high doses to a population exposed to lower, environmental levels of benzene is uncertain. Time-series measurements of the biomarker, exhaled breath, were used to evaluate a physiologically based pharmacokinetic (PBPK) model. Biases were identified between the PBPK model predictions and experimental data that were adequately described using an empirical compartmental model. It is suggested that a mapping of the PBPK model to a compartmental model can be done to optimize the parameters in the PBPK model to provide a future framework for developing a population physiologically based pharmacokinetic model.

Inhalation exposure or body burden? Better way of estimating risk – An application of PBPK model

“…Fustinoni et al (2005) reviewed a range of 3-18%. Weisel et al (1996) reported that in exposure level below 100 ppm, the fraction of metabolite excreted as t,t-MA (f t,t-MA ) is 21% of the total metabolite.…”

“…So a lower value of f t,t-MA give rise to higher estimated body burden. Hence to avoid over estimation we have used the highest reported value by Weisel et al (1996) in our calculation. Such fraction of urinary excretion for a targeted biomarker has been used previously to estimate internal dose of Benzene using pharmacokinetic model (Schettgen et al, 2010).…”

“…e Ke is calculated from t,t-MA excretion half life (t 1/2 ) of 5 h (Boogaard and Sittert, 1996) using the equation, Ke = ln 2/t 1/2 . f Weisel et al (1996).…”

Biomonitoring: Is body burden relevant to public health?

“…Any of these quantities could be considered a "biomarker of exposure." Examples of the kinds of analytical tests performed to measure biomarkers of exposure include obtaining serum lead levels, measuring trans, trans muconic acid in urine to test for benzene exposure, or obtaining breath samples to detect benzene directly (Weisel et al, 1996). Frequently these analytical tests are performed to gauge the level of "biologic plausibility" of relating an exposure to a particular chemical to the Wnding of a disease state or other negative outcome.…”

Epidemiologie in der Arbeitswelt

“…Sie können Substanzen, Strukturen oder Prozesse umfassen, wobei 3 verschiedene Typen unterschieden werden [35]: [36]. Biomarker können eine sorgfältige Expositionsermittlung nicht generell ersetzen.…”