Benzene/Leukemia risk higher than previously thought

Research studies on wood smoke and other air pollution.

Benzene/Leukemia risk higher than previously thought

Postby Wilberforce » Sun Jan 24, 2010 12:26 pm

Evidence That Humans Metabolize Benzene via Two Pathways
Rappaport et al ... hp.0800510

Recent evidence has shown that humans metabolize benzene more efficiently at environmental air
concentrations than at concentrations > 1 ppm. This led us to speculate that an unidentified metabolic
pathway was mainly responsible for benzene metabolism at ambient levels.

We statistically tested whether human metabolism of benzene is better fitted by a kinetic model having
two pathways rather than one.

We fit Michaelis-Menten-like models to levels of urinary benzene metabolites and the corresponding air
concentrations for 263 nonsmoking Chinese females. Estimated benzene concentrations ranged from less
than 0.001 ppm to 299 ppm, with 10th and 90th percentile values of 0.002 ppm and 8.97 ppm, respectively.

Using values of Akaike’s information criterion obtained under the two models, we found strong statistical
evidence favoring two metabolic pathways, with respective affinities (benzene air concentrations analogous
to Km values) of 301 ppm for the low-affinity pathway (probably dominated by cytochrome P450
enzyme 2E1) and 0.594 ppm for the high-affinity pathway (unknown). The exposure-specific metabolite
level predicted by our two-pathway model at nonsaturating concentrations was 184 µM/ppm of benzene,
a value close to an independent estimate of 194 µM/ppm for a typical nonsmoking Chinese female.
Our results indicate that a nonsmoking woman would metabolize about three times more benzene from
the ambient environment under the two-pathway model (184 µM/ppm) than under the one-pathway
model (68.6 µM/ppm). In fact, 73% of the ambient benzene dose would be metabolized via the
unidentified high-affinity pathway.

Because regulatory risk assessments have assumed nonsaturating metabolism of benzene in persons
exposed to air concentrations well above 10 ppm, our findings suggest that the true leukemia risks could
be substantially greater than currently thought at ambient levels of exposure—
about 3-fold higher among
nonsmoking females in the general population.

Benzene is an important industrial chemical that is also present in gasoline, engine exhausts, wood smoke, and tobacco smoke [International Agency for Research on Cancer (IARC) 1989]. In fact, benzene is truly ubiquitous in the environment, with air concentrations ranging from parts per billion in rural and urban settings to parts per million in some workplaces (IARC 1989; Wallace 1996). This is worrisome because benzene causes leukemia and probably other lympho-hematopoietic cancers in humans (Hayes et al. 1997; Infante et al. 1977; Rinsky et al. 1987), and there is evidence that benzene is hematotoxic at levels < 1 ppm (3.2 mg/m3) (Lan et al. 2004), the current permissible exposure limit in the United States (Occupational Safety and Health Administration 1987). Benzene also produces malignant tumors at multiple sites in rodents (Huff et al. 1989; Maltoni et al. 1989).

The toxicology of few chemicals has been pursued as vigorously as that of benzene. A PubMed search of the keywords “benzene” and “toxicity” returned more than 2,700 publications. Reports of benzene’s propensity to damage human blood-forming tissues emerged as early as 1897 (Santesson 1897), and the first evidence of its leukemogenicity was published in 1928 (Delore and Borgomano 1928).
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Re: Benzene/Leukemia risk higher than previously thought

Postby Tomfirth » Sun Jan 24, 2010 5:05 pm

My dad died of acute myeloid leukemia at age 72. He was a smoker until age 50 and a dedicated woodburner all his life.
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