An investigation of factors contributing to styrene and styrene-7,8-oxide exposures in the reinforced-plastics industry.
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During the manufacturing of reinforced plastics, large amounts of styrene and trace quantities of styrene-7,8-oxide (SO) are released. Since previous work suggests that inhalation of even small amounts of SO might be an important health risk, we investigated several possible factors contributing to styrene and SO exposure during the manufacture of reinforced plastics. Factors related to job type, worker and the type and quantity of styrene-containing resins were investigated using mixed-effects multiple linear regression models. Overall, SO exposure levels were positively correlated with styrene exposure levels. However, this correlation was statistically significant only among hand laminators who had the highest exposures to both styrene and SO. An important factor for predicting both styrene and SO concentrations was the type of resin used, while the quantity of resin consumed was predictive of styrene but not of SO exposure. Since So exposure appears to be associated with factors other than coexposure to styrene, more effort should be placed on investigating emissions of SO per se. The type of mixed-models regression analysis employed in this study can be used for clarifying the underlying patterns for exposures to styrene and SO as well as for evaluating preventive measures. (+info)
Objectives, designs and populations of the European Asclepios study on occupational hazards to male reproductive capability.
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The main objective of the Asclepios program was to examine occupational risk factors for the male reproductive system. The program focused on occupational exposure to fungicides (farmers, greenhouse workers, and vineyard workers), styrene (laminators in the reinforced plastics industry) and inorganic lead (battery workers, foundry workers, and lead smelters). Questionnaire studies of time to pregnancy were combined with longitudinal and cross-sectional studies of semen quality. The 8 data-collecting centers addressed 6553 male workers and contributed time-to-pregnancy values on the 3077 most recent pregnancies. Data collection was by interview or self-collection. The average response rate across all exposures and centers was 69.8%. The Asclepios project is the first international multicenter research project on environmental risks to male reproductive function. A protocol for epidemiologic research on occupational risk factors to the male reproductive system was developed, and links between epidemiologic and experimental units were established. The majority, but not all, of the studies was completed within the given time frame. (+info)
Characterization of hepatocellular resistance and susceptibility to styrene toxicity in B6C3F1 mice.
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Short-term inhalation exposure of B6C3F1 mice to styrene causes necrosis of centrilobular (CL) hepatocytes. However, in spite of continued exposure, the necrotic parenchyma is rapidly regenerated, indicating resistance by regenerated cells to styrene toxicity. These studies were conducted to test the hypothesis that resistance to repeated styrene exposure is due to sustained cell proliferation, with production of hepatocytes that have reduced metabolic capacity. Male mice were exposed to air or 500 ppm styrene (6 h/day); hepatotoxicity was evaluated by microscopic examination, serum liver enzyme levels, and bromodeoxyuridine (BrdU)-labeling index (LI). Metabolism was assessed by measurement of blood styrene and styrene oxide. Both single and repeated exposures to styrene resulted in mortality by Day 2; in mice that survived, there was CL necrosis with elevated BrdU LI at Day 6, and complete restoration of the necrotic parenchyma by Day 15. The BrdU LI in mice given a single exposure had returned to control levels by Day 15. Re-exposure of these mice on Day 15 resulted in additional mortality and hepatocellular necrosis, indicating that regenerated CL cells were again susceptible to the cytolethal effect of styrene following a 14-day recovery. However, in mice repeatedly exposed to styrene for 14 days, the BrdU LI remained significantly increased on Day 15, with preferential labeling of CL hepatocytes with enlarged nuclei (karyomegaly). If repeated exposures were followed by a 10-day recovery period, CL karyomegaly persisted, but the BrdU LI returned to control level and CL hepatocytes became susceptible again to styrene toxicity as demonstrated by additional mortality and acute necrosis after a challenge exposure. These findings indicated a requirement for continued styrene exposure and DNA synthesis in order to maintain this resistant phenotype. Analyses of proliferating-cell nuclear-antigen (PCNA) labeling were conducted to further characterize the cell cycle kinetics of these hepatocytes. The proportion of cells in S-phase was increased by repeated exposure. However, PCNA analysis also revealed an even larger increase in the G1 cell compartment with repeated exposures, without a concurrent increase in G2 phase or in mitotic cell numbers. These data indicate that resistance to styrene-induced necrosis under conditions of repeated exposure is not due to sustained cell turnover and production of new, metabolically inactive cells, but rather is due to some other, as yet unknown, protective phenotype of the regenerated cells. (+info)
Mortality from nonmalignant diseases of the respiratory, genitourinary and nervous systems among workers exposed to styrene in the reinforced plastics and composites industry in the United States.
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OBJECTIVES: Mortality from diseases of the nervous system and nonmalignant diseases of the respiratory and genitourinary systems was examined for workers exposed to styrene. METHODS: Altogether 15,826 styrene-exposed workers in 30 plants in the reinforced plastics and composites industry were included. Vital status was ascertained through 31 December 1989. Individual exposure estimates were developed based on job functions, existing industrial hygiene data, process changes, engineering controls, work practices, and the use of personal protective equipment. Analyses were based on cause-specific standardized mortality ratios (SMR) and the Cox proportional hazards model. Mortality data were analyzed by latency, duration of exposure, average exposure, cumulative exposure, and process category. RESULTS: For diseases of the nervous system, the SMR was 0.56 [95% confidence interval (95% CI) 0.31-0.95]. Mortality from nonmalignant genitourinary diseases was not increased (SMR 0.87, 95% CI 0.46-1.50). Latency, duration of exposure, average exposure, cumulative exposure, and process category showed no association between styrene exposure and these 2 types of disease. A small increase in mortality from nonmalignant respiratory diseases was found (SMR 1.21, 95% CI 0.98-1.47), mainly due to "other nonmalignant respiratory diseases" (SMR 1.40, 95% CI 1.04-1.84). The highest increase occurred for short exposure duration (SMR 1.79 for <1 year's exposure) or low exposure (SMR 2.15 for <10 ppm-years); there were no increased risks in the high exposure categories. The Cox proportional hazard model revealed no association between styrene exposure and the diseases. CONCLUSIONS: No relationship was found between mortality from any of the diseases examined and any of the styrene exposure indices. The findings were compared with those reported in a European study of styrene-exposed workers. (+info)
Distribution and skewness of occupational exposure sets of measurements in the Norwegian industry.
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Aggregated occupational sets of exposure measurements from the Norwegian industry registered in the exposure database EXPO at The National Institute of Occupational Health, Oslo were examined with respect to distributions and skewness. Data for lead in blood show a truncated almost normal distribution because of regulations for workers with high lead in blood concentrations. The styrene, dichloromethane and acetone measurements show quasi log-normal distributions possibly because of over-representation of worst-case measurements. The other personal and stationary measurements are relatively good fitted to a log-normal model. The stationary measurements indicate generally lower mean levels than the corresponding personal measurements. The statistical parameter skewness is valuable in connection with an exposure database as a distribution test for raw data and log-transformed data. (+info)
Metabolism of styrene by mouse and rat isolated lung cells.
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Styrene is pneumotoxic in mice. It is metabolized by pulmonary microsomes of both mouse and rat to styrene oxide (SO), presumed to be the toxic metabolite of styrene, and known to be genotoxic. To determine which pulmonary cell types are responsible for styrene metabolism, and which cytochromes P450 are associated with the bioactivation of styrene, we isolated enriched fractions of mouse and rat Clara and type II cells in order to determine the rate of styrene metabolism, with and without chemical inhibitors. Mouse Clara cells readily metabolized styrene to SO. Diethyldithiocarbamate, a CYP2E1 inhibitor, caused less inhibition of SO formation in Clara cells isolated from mice than previously found with pulmonary microsomes. As in microsomes, 5-phenyl-1-pentyne, a CYP2F2 inhibitor, inhibited the formation of both enantiomers. alpha-Naphthoflavone, a CYP1A inhibitor, did not inhibit SO formation in Clara cells. alpha-Methylbenzylaminobenzotriazole, a CYP2B inhibitor, exhibited minimal inhibition of SO production at 10 microM and less at 1 microM. The microsomal and isolated cell studies indicate that CYP2E1 and CYP2F2 are the primary cytochromes P450 involved in pulmonary styrene metabolism. Styrene metabolizing activity was much greater in Clara cells than in type II pneumocytes, which demonstrated essentially no activity. Styrene-metabolizing activity was several-fold higher in the mouse than in rat Clara cells. The more pneumotoxic and genotoxic form, R-SO, was preferentially formed in mice, and S-SO was preferentially formed in rats. These findings indicate the importance of Clara cells in styrene metabolism and suggest that differences in metabolism may be responsible for the greater susceptibility of the mouse to styrene-induced toxicity. (+info)
Site-directed mutagenesis of two zinc-binding centers of the NADH-dependent phenylacetaldehyde reductase from styrene-assimilating Corynebacterium sp. strain ST-10.
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Phenylacetaldehyde reductase (PAR) with a unique and wide substrate range from styrene-assimilating Corynebacterium sp. strain ST-10, which is a useful biocatalyst producing chiral alcohols, has been found to belong to a family of zinc-containing, long-chain alcohol dehydrogenases (ADHs) on the basis of the primary structure similarity. The enzyme contains 2 moles of zinc per mole of subunit. The amino acid residues assumed to be three catalytic and four structural zinc-binding ligands were characterized by site-directed mutagenesis, compared with other zinc-containing, long-chain ADHs. Sixteen PAR mutants gave measurable but rather low activities toward phenylacetaldehyde, n-hexyl aldehyde, and 2-heptanone, although they maintained the activities of 8 to 16% of that of wild-type PAR for an acetophenone substrate except that the D153N mutant showed quite low activity. The results suggested that the seven residues present in PAR were probably zinc-binding ligands, and mutation in these residues caused a change in activities for some substrates. (+info)
Physiological analysis of the expression of the styrene degradation gene cluster in Pseudomonas fluorescens ST.
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The effects of different carbon sources on expression of the styrene catabolism genes in Pseudomonas fluorescens ST were analyzed by using a promoter probe vector, pPR9TT, which contains transcription terminators upstream and downstream of the beta-galactosidase reporter system. Expression of the promoter of the stySR operon, which codes for the styrene two-component regulatory system, was found to be constitutive and not subject to catabolite repression. This was confirmed by the results of an analysis of the stySR transcript in P. fluorescens ST cells grown on different carbon sources. The promoter of the operon of the upper pathway, designated PstyA, was induced by styrene and repressed to different extents by organic acids or carbohydrates. In particular, cells grown on succinate or lactate in the presence of styrene started to exhibit beta-galactosidase activity during the mid-exponential growth phase, before the preferred carbon sources were depleted, indicating that there is a threshold succinate and lactate concentration which allows induction of styrene catabolic genes. In contrast, cells grown on glucose, acetate, or glutamate and styrene exhibited a diauxic growth curve, and beta-galactosidase activity was detected only after the end of the exponential growth phase. In each experiment the reliability of the reporter system constructed was verified by comparing the beta-galactosidase activity and the activity of the styrene monooxygenase encoded by the first gene of the styrene catabolic operon. (+info)