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Evidence that humans metabolize benzene via two pathways
Stephen M Rappaport1, Sungkyoon Kim, Qing Lan
1School of Public Health, University of California at Berkeley, Berkeley, California 94720-7356, USA. srappaport@berkeley.edu
Environmental Health Perspectives
|July 11, 2009
Summary
Human benzene metabolism involves two pathways, not one. This suggests leukemia risks from environmental benzene exposure may be underestimated by threefold, particularly for women.
Area of Science:
- Environmental Health
- Toxicology
- Biochemistry
Background:
- Human benzene metabolism efficiency varies with concentration.
- Ambient benzene levels may engage a distinct, high-affinity metabolic pathway.
Purpose of the Study:
- To statistically evaluate if a two-pathway kinetic model better explains human benzene metabolism than a single pathway.
- To investigate benzene metabolism kinetics at environmentally relevant concentrations.
Main Methods:
- Michaelis-Menten-like models fitted to urinary benzene metabolites and air concentrations.
- Data from 263 non-smoking Chinese females with benzene exposures from <0.001 to 299 ppm.
Main Results:
- A two-pathway model showed strong statistical preference over a one-pathway model.
- Identified a high-affinity pathway (K(m) = 0.594 ppm) and a low-affinity pathway (K(m) = 301 ppm).
- The two-pathway model predicts 3x higher benzene metabolism at ambient levels compared to the one-pathway model, with 73% via the high-affinity pathway.
Conclusions:
- Current risk assessments may underestimate benzene's leukemia risk at ambient air concentrations.
- Leukemia risks for non-smoking females could be approximately threefold higher than previously estimated.
- An unidentified high-affinity metabolic pathway significantly contributes to benzene detoxification at low exposure levels.
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