Abstract
Styrene is one of the most important organic chemicals used worldwide. In humans, styrene metabolism involves oxidation by cytochrome P450 monooxygenases (CYPs) to styrene-7,8-oxide, an epoxide thought to be responsible for the genotoxic effects of styrene exposure, and detoxification by means of epoxide hydrolase (mEH) and glutathione S-transferases (GSTs). The objective of this study was to investigate if genetic polymorphisms of metabolic enzymes modulate the level of urinary styrene metabolites and styrene oxide adducts with N-terminal valine of human globin (SO-Hb) in 75 workers occupationally exposed to styrene and 77 unexposed controls. The mean air concentration of styrene in the breathing zone of workers (30.4ppm) was higher than the threshold limit value of 20ppm recommended by the American Conference of Governmental Industrial Hygienists (ACGIH), and the biological exposure index adopted by the ACGIH for exposure to styrene prior to the next shift (MA+PGA=400mg/g creatinine) was exceeded, indicating that styrene exposure for this group of workers was higher than recommended. A highly significant correlation was observed between styrene concentration in the breathing zone and the MA+PGA in urine of workers (r=0.85, P<0.001). The levels of SO-Hb adducts in exposed workers were significantly increased as compared with controls, although no difference was observed between subjects stratified as high and medium exposure categories based on MA+PGA excretion. Regarding the effect of the genetic polymorphisms we found that the level of SO-Hb adducts might be modulated by the predicted mEH enzymatic activity in the exposed workers. From our data we conclude that SO-Hb adduct measurement is a complementary method to MA+PG measurement for assessing exposure to styrene at occupational and environmental levels, which reflects a more extensive exposure period.
Highlights
Styrene is a monomer widely used in the production of plastics, synthetic rubber and polyester resins
The mean air concentration of styrene in the breathing zone of workers (30.4 ppm) was higher than the threshold limit value of 20 ppm recommended by the American Conference of Governmental Industrial Hygienists (ACGIH), and the biological exposure index adopted by the ACGIH for exposure to styrene prior to the shift (MA+phenylglyoxylic acid (PGA)= 400mg/g creatinine) was exceeded, indicating that styrene exposure for this group of workers was higher than recommended The levels of SO-Hb adducts were significantly higher (P
- In order to respond to the first comment of the referee, I agree that the last sentence of the abstract is a little bit strong, as we show that mandelic acid (MA)+PGA correlated with styrene in air but Hb adducts did not
Summary
Styrene is a monomer widely used in the production of plastics, synthetic rubber and polyester resins. The highest human exposure to styrene occurs during the production of fiberglass-reinforced polyester products (Miller et al, 1994), where unsaturated resins containing about 40% styrene as a reactive diluent are commonly used, and as much as 10% of it can evaporate into the workroom air during lamination by hand procedures. Styrene metabolism has been well characterised (Sumner and Fennell, 1994). The first step of styrene metabolism is oxidation by cytochrome P450 enzymes (CYP) including CYP2E1, CYP2B6, CYP1A2 and other isozymes (Nakajima et al., 1994) to styrene-7,8-oxide (SO), which is a highly reactive epoxide and has been classified as a probable human carcinogen (Group 2A) (IARC, 1994). A minor metabolic pathway is the conjugation of SO with glutathione via glutathione-S-transferases (GSTs), resulting in subsequent formation of phenyl hydroxyethyl mercapturic acids (PHEMAs) (Sumner and Fennell, 1994)
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