delic acid, and the workplace air concentration has been developed (ACGIH 1991). A commonly used BEI for styrene is based on that urinary measure. Different equations are available to convert urinary concentration from milligrams per liter of urine or from milligrams per gram of creatinine back to a time-weighted average inhaled concentration. The urinary biomarker has been used to test correlations between styrene exposure and adverse effects in worker populations with respect to sperm DNA abnormalities, neurologic effects, and renal effects (Lindstrom et al. 1976a,b; Harkonen 1977; Vyskocil et al. 1989; Migliore et al. 2002).

The empirical relationship between urinary biomarker and ambient concentration has utility for screening worker populations, but less utility for risk assessment in the general population. The equations are valid only if urine is collected after an 8-hour workshift. Furthermore, the relationship between amount in urine and air concentration will depend on level of exertion and respiratory rate, which may differ between the workplace and the general population. Those limitations will generally occur with any occupation-based algorithm for relating urinary biomonitoring results to air concentration or exposure dose. However, such empirical data can be used to calibrate pharmacokinetic models that can take into account exposure and physiologic variables and thus can be applicable to both the workplace and the general population. The example described elsewhere for the chlorpyrifos metabolite is a case in point.

Regarding styrene, the variety of controlled human oral and inhalation studies that relate dose to urinary concentration and the existence of a pharmacokinetic model (Droz and Guillemin 1983) could facilitate interpretation of mandelic acid concentration in urine. A caveat in this regard is that other chemical exposures can produce mandelic acid in urine, such as ethyl benzene, acetophenone, and phenylglycine (ACGIH 1991). Those “background” sources would be more likely to confound low-level general-population biomarker results than workplace end-of-shift results.

It is noteworthy that the styrene reference concentration (RfC) in the Integrated Risk Information System is based on the biomarker-response relationship found in workers (Mutti et al. 1984; EPA 1998). The Environmental Protection Agency (EPA) used the relationship of urinary biomarker to ambient-air concentration of workers to develop an RfC that was adjusted for the difference in exposure time between the workplace and the general population. That is a valid approach because it derives a workplace concentration-toxicity relationship in workers, which can then be adjusted for the general population to account for differences in exposure time and can take uncertainty factors into account. It is different from direct adjustment of the styrene BEI to evaluate human population biomonitoring data on styrene metabolites in urine, which would have the uncertainties described above and in Chapter 5.



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