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PubMedDate not supplied

Induction of chromosome aberrations by styrene and vinylacetate in cultured human lymphocytes: dependence on erythrocytes.

Two vinyl monomers, styrene and vinylacetate, were tested for their ability to induce chromosome aberrations in cultured human lymphocytes. The effects of a 24-h treatment (48 h after culture initiation) were studied both in whole-blood cultures (with 2 X 10(8) erythrocytes/ml) and in isolated lymphocytes (with 4000 erythrocytes/ml). Styrene produced a clear dose-dependent increase in chromatid-type aberrations in whole-blood cultures (0.5-6 mM) and a weaker effect in cultures of isolated lymphocytes (1-4 mM). A statistically significant elevation in aberrations was observed at 2 mM in the former culture type and at 1 mM in the latter. These results support earlier studies on the importance of erythrocytes in the metabolic activation of styrene, but also suggest that a part of this activation occurs in the lymphocytes themselves. Vinylacetate (0.125-2 mM), the more potent clastogen of the two monomers tested, induced a distinct dose-dependent increase in chromatid-type aberrations and a slight elevation in chromosome-type breaks in both culture types. The lowest concentration giving a positive result was 0.25 mM. The clastogenic effects of vinylacetate were somewhat more pronounced in isolated lymphocytes than in whole blood. Vinylacetate is known to be rapidly hydrolyzed in vitro to acetaldehyde, which probably explains the positive result.

Biotransformation↗
PubMed1995

Chromosomal aberrations and micronuclei in reinforced plastics workers exposed to styrene.

The aim of this study was to investigate the cytogenetic changes induced in humans exposed to styrene in a reinforced plastics plant. Blood and urine samples were collected from 18 styrene exposed workers and 18 age and sex matched control subjects from the administrative department of the same factory. Chromosome aberrations (CAs) and micronuclei (MN) (cytokinesis block method) were analyzed in blood lymphocytes. All of the subjects included in the study were male non-smokers. The duration of employment ranged from 10 to 22 years (14.3 +/- 4.4). In order to monitor exposure to styrene, urinary mandelic acid (MA) levels were measured using a standard colorimetric method. The level of thioethers in the urine was also determined colorimetrically. The mean level of mandelic acid was significantly higher in the exposed workers (328.44 +/- 266.21 mg/g creatinine) compared with that of the controls (50.09 +/- 16.84 mg/g creatinine) (p < 0.05). The level of urinary thioethers was found to be higher among the exposed workers. The number of cells with chromosomal aberrations was significantly higher in the workers (6.06 +/- 4.41) compared with the controls (3.44 +/- 2.28) (p < 0.05). There was no significant increase in the frequency of micronuclei in the exposed workers compared to controls. Our results support earlier findings on increased rates of chromosomal aberrations in reinforced plastics workers.

Adult↗
PubMed1987

Chromosome aberrations, micronuclei and sister-chromatid exchanges in blood lymphocytes after occupational exposure to low levels of styrene.

Chromosome aberrations, micronuclei and sister-chromatid exchanges were analysed in blood lymphocytes of 21 reinforced plastic workers, exposed to styrene from 1 to 25 years, and 21 control persons. Occupational hygienic measurements showed personal exposure to styrene to range from 34 to 263 mg/m3 air, the average was 98 mg/m3. Urinary mandelic acid levels of the workers varied from below detection limit to 7 mM/1 l urine. No increase was detected in the frequency of any of the cytogenetic endpoints studied. No correlations between the number of aberrations, micronuclei or SCEs on one hand and the extent or duration of exposure to styrene on the other could be detected.

Adult↗
PubMed1987

Studies of nephrotoxicity due to mixed exposure to styrene and toluene.

Adult male Sprague-Dawley rats were treated simultaneously with 4 mmol styrene per kg i.p., twice a day at an interval of 4 h, and 10 mmol toluene per kg once a day, 5 days a week for 4 consecutive weeks. After the last day of treatment, the rats were placed in metabolism cages for collection of urines for 24 h and then were sacrificed. Such mixed exposure produced significant increases in the urinary excretion of gamma-glutamyl transpeptidase, glucose and proteins as compared to those with either solvent alone. An increase, but not significant, in the urinary excretion of N-acetyl-beta-D-glucosaminidase was also noticed due to such exposure. Electron microscopic examination of renal cortex 24 h after the mixed exposure showed the appearance of many vacuoles of various sizes surrounded by a single membrane, which were not seen in rats treated with either styrene or toluene alone. Metabolism studies showed only a significant increase in the urinary excretion of hippuric acid due to mixed exposure. These data indicate that under certain conditions, mixed subchronic exposure to styrene and toluene may have the potential to increase further the nephrotoxic response as compared to that of either solvent alone.

Animals↗
PubMed1990

Persistent effects of chronic exposure to styrene on the affinity of neostriatal dopamine D-2 receptors.

We have investigated whether chronic exposure to styrene could inflict persistent effects on the binding characteristics of dopamine D-2 agonist binding sites in rat neostriatal membranes. Styrene exposure (1000 ppm, 6 months, 16 h/d overnight, and left without exposure for another 5 months) caused a marked increase (+160%) in the IC50 value of dopamine without significantly affecting the total amount of specifically bound [3H]raclopride. The specific [3H]raclopride binding in membranes from subcortical limbic areas was too low to yield acceptable displacement curves. These data indicate that chronic exposure to styrene can induce a persistent decrease in affinity of the neostriatal dopamine D-2 agonist binding sites, possibly mediated by membrane perturbations.

Animals↗
PubMed1997

The catalytic activity of cytochrome P450cam towards styrene oxidation is increased by site-specific mutagenesis.

The styrene oxidation activity of cytochrome P450cam, has been greatly improved by rational protein engineering. Compared to the wild-type enzyme, the active-site mutants Y96A and Y96F bound styrene more tightly, consumed NADH more rapidly, and were more efficient at utilising reducing equivalents for product formation. Styrene oxide formation rates were enhanced 9-fold in the Y96A mutant relative to wild-type, and 25-fold in the Y96F mutant, thus demonstrating the effectiveness of active-site redesign in improving the activity of a haem monooxygenase towards an unnatural substrate.

Binding Sites↗
PubMed1997

Ring test for the determination of N-terminal valine adducts of styrene 7,8-oxide with haemoglobin by the modified Edman degradation technique.

A ring-test was organised between three laboratories using different versions of the modified Edman degradation technique for the gas chromatographic-mass spectrometric determination of N-terminal valine adducts of styrene 7,8-oxide. The analyses were performed on a sample of human haemoglobin reacted in vitro with styrene 7,8-oxide and on a set of five haemoglobin samples from mice dosed by i.p. injection of styrene. Strong correlations between the haemoglobin adduct determinations of the different laboratories were observed. However, covariance analysis revealed different slopes for the dose-response curves, indicating differences for the calibration of the reference globin or reference peptide.

Alkylation↗
PubMed1984

Control of styrene vapor in a large fiberglass boat manufacturing operation.

An evaluation of a control system for worker protection from styrene vapor was performed at a manufacturer of large fiberglass reinforced plastic yachts. The manufacturing operations included five tiltable boat hull mold stations. Each station had a floor air slot located beneath the mold which was exhausting about 17 000 CFM. The building had an overall ventilation rate of 10-15 air changes per hour. An attempt was made to improve the performance of this control system by blowing air into the hull mold and by blocking air flow from the back of the mold to induce greater flow from the front of the mold. Consecutive short term breathing zone samples were collected in an effort to show the effect of different job tasks and work modes on exposures. ANOVA was performed to determine levels of significance of several variables. A significant exposure difference was found between right and left tilts of the 46-foot hull mold. The TWA styrene exposure values for the 3-day period of the 4 hull lamination workers were low, ranging from 17 ppm to 25 ppm, and demonstrating that styrene levels can be effectively controlled by means of strategically located high volume exhaust vents for the process studied.

Acetone↗
PubMed1993

32P-postlabeling of DNA adducts of styrene-exposed lamination workers.

Lamination workers are exposed to high concentrations of styrene. A postlabeling method was developed for the detection of styrene-specific DNA adducts of the workers. To synthesize a standard, styrene oxide was reacted with 2'-deoxyguanosine 3'-monophosphate (dGMP) and the O6-dGMP-adduct was isolated and characterized. The human samples were assayed by the nuclease P1 version of the 32P-postlabeling technique, using magnet transfer of the adducts in chromatography. The human samples were spiked with the standards to ensure identification and quantitation. In lamination workers the O6-adducts, adjusted for adduct recovery, were detected at a level of 5 adducts/10(8) nucleotides, over five times the level in the controls.

Chromatography, Thin Layer↗
PubMed1994

32P-post-labeling detection of DNA adducts in mononuclear cells of workers occupationally exposed to styrene.

32P-Post-labeling was used to analyze for the presence of DNA adducts in 47 workers exposed to styrene in a boat manufacturing facility. Individual airborne exposures measured several times over the course of 1 year ranged from 1 to 235 mg/m3 with a mean value of 65.6 mg/m3. Two adducts were detected in the DNA of mononuclear cells of these workers. The following levels of adducts were detected: adduct 1, range 0.6-102 x 10(-8) (mean 15.8 x 10(-8); adduct 2, range 0.1-70.9 x 10(-8) (mean 14.2 x 10(-8). Significant linear relationships were found between styrene exposure and both DNA adducts (adduct 2, r = 0.330, P = 0.012; adduct 1, r = 0.244, P = 0.049). Co-chromatography experiments identified DNA adduct 1 in the exposed samples as N2-(2-hydroxy-1-phenylethyl)-2'-deoxyguanosine-3',5'-bisphosphate. DNA adduct 2 remains unidentified. No significant linear relationships were observed between the level of DNA adducts and sister chromatid exchanges, possibly because of the poor precision of the 32P-post-labeling assay (the estimated coefficients of variation for adducts 1 and 2 were 2.54 and 1.96, respectively). These results demonstrate that occupational exposure to styrene results in the formation of DNA adducts in human mononuclear cells.

DNA↗
PubMed1995

Confined space hazards: combined exposure to styrene, fiberglass, and silica.

Work in confined spaces continues to present hazards to workers. The magnitude of this problem was recently addressed by the Occupational Safety and Health Administration in its Final Rule for "Permit-Required Control Spaces for General Industry" (29 CFR Parts 1910). Although illness and injury are typically due to asphyxiation, explosion, and drowning, toxic exposures also are an important risk. We describe herein four workers engaged in erosion-proofing enclosed chemical tanks with minimal ventilation and no respiratory protection. They were exposed to styrene-based solvents, styrene-based resins, silica, and fiberglass dust. Each experienced acute neurological effects and bronchitis. One worker developed a life-threatening pneumonia that resulted in numerous complications. The severity of the illness, which would likely not have otherwise occurred, resulted from impaired lung defense mechanisms due to the combined exposures. Several studies support the association of styrene exposure and respiratory illness that may be compounded by co-exposure to fiberglass in unique circumstances. To prevent the hazards of confined space, recommended procedures should be followed, including those established by the National Institute for Occupational Safety and Health and the Occupational Safety and Health Administration.

Adult↗
PubMed1997

Purification and characterization of phenylacetaldehyde reductase from a styrene-assimilating Corynebacterium strain, ST-10.

A novel phenylacetaldehyde reductase was purified about 50-fold to homogeneity from Corynebacterium sp. strain ST-10, which can assimilate gaseous styrene as the sole carbon and energy source. The enzyme was inductively synthesized when grown on gaseous styrene and had an important role in styrene metabolism in vivo. The enzyme had a molecular weight of 155,000 and was composed of four identical subunits (molecular weight, 42,000). The enzyme catalyzed the reduction of not only phenylacetaldehyde but also various aldehydes and ketones; however, it did not catalyze the reverse reaction, the dehydrogenation of 2-phenylethanol. The enzyme required NADH as a cofactor and showed no activity with NADPH; therefore, it was defined as an NADH-dependent phenylacetaldehyde reductase. The enzyme stereospecifically produced (S)-(-)-1-phenylethanol from acetophenone; therefore, it would be useful as a biocatalyst.

Acetaldehyde↗
PubMed1984

Raised serum bile acid concentrations after occupational exposure to styrene: a possible sign of hepatotoxicity?

Fasting serum concentrations of conjugated bile acids were investigated in 23 men who had been exposed to styrene and compared with the concentrations in 60 non-exposed individuals. Eleven of the exposed subjects had raised concentrations of either cholic acid or chenodeoxycholic acid or both. There were no indications of alcohol abuse, drug intake, or undiagnosed liver disease. It is possible, therefore, that the raised bile acid concentrations were due to exposure to styrene. This would support the concept that occupational exposure to styrene may affect the liver and point to the possibility that raised serum bile acid concentrations might be a sensitive and early indicator of hepatic injury in individuals exposed to organic solvents.

Adult↗
PubMed1990

Neurotoxic effects of styrene: further evidence.

The relation of exposure to styrene to measures of nervous system function was investigated in 70 men working in four factories in the Montreal area of Quebec. Mild sensory nerve conduction deficits were found, the proportion with such deficits rising from 23% in those exposed to less than 50 ppm to 71% in those exposed to more than 100 ppm. Reaction time was slower for those with a larger body burden, as indicated by area under the excretion curve, and for those who failed to clear the metabolite during the weekend. No slowing in conduction time was found among a small group of five men exposed to more than 100 ppm for less than four weeks. There was some evidence that both central and peripheral slowing recovered when workers were removed from exposure. Uptake, storage, or elimination of styrene was influenced by the physical demands of the work, skinfold thickness, cumulative exposure, and alcohol consumption. Nevertheless, only the wearing of a mask and current consumption of alcohol were associated with a lower risk of sensory conduction deficit. While there was no clear indication that neurotoxic effects were related to individual differences in the capacity to metabolise high concentrations of styrene, measurement of urinary metabolites may be helpful in identifying those at highest risk.

Adolescent↗
PubMed1992

Abnormal auditory brainstem responses and cochlear pathology in rats induced by an exaggerated styrene exposure regimen.

Groups of 12 male 42-day-old rats were exposed to 0 or 800 ppm styrene vapors for 14 hr/day, 5 days/week for 3 weeks. Tone-pip auditory brainstem responses (ABRs) at 4, 8, 16, and 30 kHz were obtained after the last exposure. ABRs were minimally affected at 4 kHz and moderately to severely affected at 8, 16, and 30 kHz as indicated by waveforms which had a decreased amplitude and increased latency as compared to the controls. Missing outer hair cell(s) were evident in the basal and lower middle turns of the organ of Corti. Outer hair cell loss was least in the first row and greatest in the second and third rows. Occasional inner hair cells were also missing in regions of severe outer hair cell loss. The distribution of hair cell loss within the cochlea was consistent with the pattern of ABR alterations. These data document mid-frequency auditory dysfunction in styrene-exposed young adult rats with significant damage to the organ of Corti following an exaggerated styrene exposure regimen.

Animals↗
PubMed1992

Altered activity of hepatic mixed function oxidase, cytochrome P-450 and glutathione-S-transferase by styrene in rat fetal liver.

The effect of in utero exposure to styrene 200 or 400 mg/kg/day orally was studied on mixed function oxidase activities, cytochrome P-450 and glutathione contents and on the glutathione-S-transferase activity in rat fetal liver. Activities of aminopyrene-N-demethylase, aniline hydroxylase, aryl hydrocarbon hydroxylase and the cytochrome P-450 contents were significantly decreased in the fetal liver. A significant decrease in the glutathione contents and the glutathione-S-transferase activity was also observed in the liver of the fetuses of styrene exposed animals. The current data show that prenatal exposure to styrene could adversely affect the developing biotransformation process.

Animals↗
PubMed1989

Cytogenetic and hematological effects in plastics workers exposed to styrene.

For 20 glass-reinforced plastics workers exposed to styrene and 22 unexposed referents, the frequency and size distribution of micronuclei were determined for lymphocytes stimulated with phytohemagglutinin or pokeweed mitogen, and white blood cell counts were made. Furthermore, chromosome aberrations were scored for 11 of the exposed subjects and 15 of the referents. The mean level of styrene in the breathing zone of the workers was 56 mg/m3. Workers exposed to styrene did not show an increase in any of the cytogenetic end points studied when the effect of age and smoking was allowed for in a multiple regression analysis. A significant 30% increase in the number of peripheral monocytes was observed for the exposed workers. No correlations between the cytogenetic and hematological tests on one hand and the length of exposure time on the other could be detected.

Adolescent↗
PubMed1992

Effect of styrene on testicular enzymes of growing rat.

Effect of styrene (100 or 200 mg/kg body wt/day) for 60 days was observed on testicular enzymes of postnatally maturing rats. A significant decrease in epididymal spermatozoa count was observed only at 200 mg/kg body weight dose. Activities of testicular sorbitol dehydrogenase and acid phosphatase decreased while activities of lactate dehydrogenase, beta-glucuronidase, glucose-6-phosphate dehydrogenase, and gamma-glutamyl transpeptidase significantly increased only in animals exposed to styrene at a dose of 200 mg/kg body weight. The results suggest that exposure to high dose of styrene during developmental period alters the activities of enzymes associated with specific cell type of testis.

Animals↗