| The most severe occupational exposures to styrene occur in the reinforced-plastics industry where styrene-containing resins are used in the manufacture of products such as boats, shower stalls, and camper shells. Workers in this industry are also exposed to small amounts of airborne styrene-7,8-oxide (SO), the primary in vivo metabolite of styrene. Animal studies have generally implicated styrene as toxic to the nervous system and SO as a carcinogen. To assess the relative risk posed by exposure to SO, we investigated the relationship between styrene and SO exposure and blood-SO in a cohort of 328 workers in 17 reinforced-plastics plants in the Pacific Northwest. Since trace methods had not been reported for measurement of airborne SO in the presence of other oxidation products of styrene, we developed air-sampling methods and applied them to this cohort. We also developed a sensitive method for measurement of SO in blood. The results showed that styrene and SO significantly influence blood-SO levels. To determine the relative contribution of each compound and gain insight into the physiological and biochemical factors affecting bioavailability, we employed a physiologically-based pharmacokinetic (PBPK) model that describes the distribution of styrene and SO in humans following inhalation. The model's structure included metabolism of styrene to SO and a first-pass hydrolysis of SO, catalyzed by epoxide hydrolase. The cohort data provides a means for assigning realistic exposure distributions as input to the model (SO and styrene in air) and validation of output SO in blood. We concluded that the highly efficient first-pass hydrolysis of SO greatly reduces the systemic availability of metabolic SO (from styrene). In contrast, low-level airborne SO, absorbed via inhalation, is immediately available to systemic circulation. Thus, despite its relatively low concentration, airborne SO appears to present a hazard that is comparable to that of styrene. This work suggests that future studies should assess the risk of exposure to airborne SO as well as styrene. |
