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PubMed1978

Teratologic evaluation of styrene given to rats and rabbits by inhalation or by gavage.

Pregnant Sprague-Dawley rats and New Zealand white rabbits inhaled 0, 300 or 600 ppm of styrene 7 h/day from days 6 through 15 (rats) and 6 through 18 (rabbits) of gestation. Additional groups of rats were given styrene by gavage at dose levels of 0, 90 or 150 mg/kg twice daily (0, 180 or 300 mg/kg, respectively) from days 6 through 15 of gestation. Embryotoxicity and fetotoxicity were not evident in rats or rabbits inhaling styrene or in rats given the compound orally. Maternal effects (decreased body weight gain and decreased food consumption) were noted in all groups of rats given styrene but none were observed in rabbits. No teratogenic effect was detected in either species inhaling styrene or in rats given styrene by gavage.

Aerosols↗

PubMed2000

Estimation of human exposure to styrene and ethylbenzene.

In the present studies, human exposure to styrene and to ethylbenzene (EB) is assessed on the basis of literature data. Total styrene and total EB exposure result from inhalation and from food intake. Styrene and EB inhaled represent the greatest proportion of the total intake. Styrene and EB content in food is mainly caused by migration from polymer packaging material. The daily styrene exposure is estimated to range from 18.2 to 55.2 microg/person, corresponding to an annual exposure of 6.7 to 20.2 mg/person. The daily EB exposure is estimated to be about 130 microg/person, corresponding to an annual exposure of 46 mg/person. Cigarette smoking is another important factor for styrene and EB intake by smokers.

Benzene Derivatives↗

PubMed2003

The role of various biomarkers in the evaluation of styrene genotoxicity.

We evaluated our data on the occupational exposure to styrene in lamination workers. The battery of parameters included markers of external and internal exposure and biomarkers of biological effects and susceptibility. DNA repair capacities have been determined in both exposed and control groups. Styrene workplace concentration significantly correlated with styrene concentration in blood, exhaled air and urinary mandelic acid. Haemoglobin and O(6)-styrene oxide (SO)-guanine DNA adducts were significantly higher in exposed subjects as compared to controls and correlated with exposure parameters. In styrene-exposed workers 1-SO-adenine DNA adducts were detected (2.6 per 10(9) dNp), while in controls these adducts were below the detection limit. 1-SO-adenine adduct levels were affected by both acute and cumulative exposure (P=0.001, F=86.0 and P=0.017, F=59.0, respectively) and associated with cytochrome P450 2E1 (CYP2E1) polymorphisms (R(2)=0.442). Mutant frequencies (MF) at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus appeared to accumulate with exposure over time and were associated with glutathione S-transferase P1 (GSTP1) polymorphism. DNA repair capacity increased with the exposure, except for the group exposed to the highest styrene concentration. In this particular group, increased DNA repair capacity to remove oxidative DNA damage was found.

Adult↗

PubMed2003

Genetic characterization of the styrene lower catabolic pathway of Pseudomonas sp. strain Y2.

Pseudomonas sp. strain Y2 is a styrene-degrading bacterium, which initiates the catabolism of this compound via its transformation into phenylacetate by the sequential oxidation of the vinyl side chain. The styrene upper catabolic gene cluster (sty genes) had been localized in a 9.2-kb chromosomal region. This report describes the isolation, sequencing and analysis of an adjacent 20.5-kb chromosomal region that contains the genes of the styrene lower degradative pathway (paa genes), which are involved in the transformation of phenylacetate into aliphatic compounds that can enter the Krebs cycle. Hence, Pseudomonas sp. strain Y2 becomes the first microorganism whose entire styrene catabolic cluster has been completely characterized. Analysis of the paa gene cluster has revealed the presence of 17 open reading frames as well as gene duplications and gene reorganizations that are absent in other phenylacetate catabolic clusters described so far. The functionality of these genes has been proved by means of both complementation experiments on Pseudomonas putida mutants and in vitro enzymatic assays. Moreover, a DNA cassette encoding the whole styrene lower pathway has been constructed and has been used to expand the ability of Pseudomonas strains to degrade phenylacetic acid. For the first time, two functional phenylacetate-CoA ligases have been identified in an aerobic phenylacetic acid degradation pathway. Although the upper and lower styrene catabolic clusters are adjacent in the Pseudomonas sp. strain Y2 chromosome, their particular base composition and codon usage suggest a distinct evolutionary history.

Base Sequence↗

PubMed2000

Purge-and-trap gas chromatographic determination of styrene in urine and blood. Application to exposed workers.

A simple purge-and-trap gas chromatographic method with flame ionization detection was developed for the determination of styrene in urine and blood. Styrene present in a 5 ml sample at room temperature was swept by helium at 40 ml/min for 11 min, trapped on a Tenax trap, desorbed by heating, cryofocused, and injected by flash heating into a DB-5 capillary GC column. The oven temperature program was from 80 degrees C, held for 8 min, to 120 degrees C at 5 degrees C/min, and then held for 2 min. The detector temperature was 250 degrees C. The calibration curves were linear in the range of 2.5-15 ppb styrene in urine and 25-150 ppb in blood. The detection limits calculated were 0.4 microg/l in urine and 0.6 microg/l in blood. The coefficients of variations within the day and day-to-day were 3 and 3.1%, respectively, for 2.5 ppb of styrene in urine, and 1 and 1.6% for 25 ppb of styrene in blood. The results obtained from samples taken from workers exposed to styrene were reported.

Calibration↗

PubMed2002

Use of DPOAEs for assessing hearing loss caused by styrene in the rat.

The study was carried out to test whether or not cubic distortion otoacoustic emissions were more sensitive than auditory-evoked potentials for assessing styrene-induced hearing losses in the Long-Evans rat. For the purposes of comparison, changes in cubic distortion product otoacoustic emissions (DeltaDPOAE), evoked potential permanent threshold shifts (PTS) and outer hair cell losses were measured in a population of styrene-treated rats. Each rat was exposed to either 650 or 750 ppm of styrene for 4 weeks, 5 days per week, 6 h per day. Only the 750 ppm exposure caused significant hearing losses. For this concentration, DPOAEs appeared as sensitive to styrene as the audiometry performed with evoked potentials, but not more. A high coefficient of correlation [0.84< or =r< or =0.91] between DeltaDPOAE and PTS was obtained across the styrene-induced effects for frequencies ranging from 5 to 12 kHz. This experiment demonstrates that DPOAEs can be used to monitor the ototoxicity induced by styrene even though they cannot be considered as a more sensitive index of cochlear pathology than the evoked potentials, at least under our experimental conditions. Likewise evoked potentials, normal DPOAEs may not guarantee a normal cochlear status and therefore results of DPOAE measurements should be interpreted cautiously. The use of both techniques and the determination of the ratio DeltaDPOAE/PTS may be useful in determining the cause of hearing loss: mechanical or chemical process. Moreover, because of its non-invasive and objective characteristics, the use of DPOAEs could play a greater role in a prevention policy.

Animals↗

PubMedDate not supplied

Comparison of toluene-induced and styrene-induced hearing losses.

Toluene and styrene are industrial solvents that can severely damage the auditory function in adult rats. In the present study, toluene (1000 to 2000 ppm) and styrene doses (500 to 1500 ppm) were investigated according to the same schedule: 6 hours per day, 5 days per week, for 4 consecutive weeks. The auditory function of the animals was tested by recording evoked potentials from the inferior colliculus over a frequency range from 2 to 32 kHz, whereas pathological data were evaluated by conventional histologic techniques. The permanent threshold shifts (PTS) were obtained with a styrene dose 2.4 times lower than that of the toluene. The slope of the regression line (PTS/doses) was 2.1 steeper with styrene than that obtained with toluene in the same experimental conditions. The sequence of histopathological events along the organ of Corti, especially the orderliness and the location of the traumas, was similar for paired concentrations of styrene and toluene, which were respectively 650 ppm, 1500 ppm for the first match, and 850 ppm, 1750 ppm for the second one. Both electrophysiological and histological findings point out the higher ototoxic potency of the styrene compared to that of the toluene. Assumptions concerning the ototoxic mechanism are addressed in the present paper.

Acoustic Stimulation↗

PubMed2005

Thermal chemistry of styrene on Si(100)2x1 and modified surfaces: electron-mediated condensation oligomerization and posthydrogenation reactions.

The room-temperature (RT) adsorption and surface reactions of styrene on Si(100)2x1 have been investigated by thermal desorption spectrometry, low-energy electron diffraction, and Auger electron spectroscopy. Styrene is found to adsorb on Si(100)2x1 at a saturation coverage of 0.5 monolayer, which appears to have little effect on the 2x1 reconstructed surface. The chemisorption of styrene on the 2x1 surface primarily involves bonding through the vinyl group, with less than 15% of the surface moiety involved in bonding through the phenyl group. Except for the 2x1 surface where molecular desorption is also observed, the adsorbed styrene is found to undergo, upon annealing on the 2x1, sputtered and oxidized Si(100) surfaces, different thermally induced processes, including hydrogen abstraction, fragmentation, and/or condensation oligomerization. Condensation oligomerization of styrene has also been observed on Si(100)2x1 upon irradiation by low-energy electrons. In addition, large postexposure of atomic hydrogen to the chemisorbed styrene leads to Si-C bond cleavage and the formation of phenylethyl adspecies. Hydrogen therefore plays a decisive role in stabilizing and manipulating the processes of different surface reactions by facilitating different surface structures of Si.

Adsorption↗

PubMed2001

Microbial treatment of a styrene-contaminated air stream in a biofilter with high elimination capacities.

A styrene-utilizing mixed microbial culture was isolated and utilized in a biofilter for the biological treatment of a contaminated air stream. Biofilter media consisted of composted wood bark and yard waste. The biofilters were acclimated at 120 s residence time and further evaluated at 60 and 30 s gas residence times. The biofilters received organic loading rates of up to 350 g/m(3) h. The styrene volumetric removal rate was a function of the organic loading rate and increased with increasing loading rates. Average volumetric removal rates of 69-118 g/m(3) h observed in our studies were higher than reported values for styrene biofilters. Average styrene removal efficiencies ranged from 65% to 75% (maximum 100%). Axial analysis of styrene concentration along the column indicated that the bulk of the styrene removal occurred in the first section of the biofilter. Analyses of the media indicated that the moisture content of the first section (50-55% w/w) was significantly lower than in the second and third sections (65-70% w/w). The pressure drops across the biofilter were low due to the high concentration of large media particles. The total pressure drops were 1-3, 4-6, and 10-16 mm for the 120-, 60-, and 30-s residence time periods, respectively.

Air↗

PubMed2004

Effects of 5-day styrene inhalation on serum LH and testosterone levels and on hypothalamic and striatal amino acid neurotransmitter concentrations in male rats.

The volatile chemical styrene may impair male fertility. Testicular testosterone (T) production is controlled by the hypothalamic/pituitary/gonadal axis. From the mediobasal hypothalamus (MBH), gonadotropin-releasing hormone (GnRH) is released, which stimulates luteinizing hormone (LH) secretion from the pituitary, which in turn enhances T production. GnRH release is controlled by glutamate (GLU) and gamma-aminobutyric acid (GABA). GLU and GABA neurons are regulated by T. Thus, reduced fertility of styrene-exposed male workers may result from altered GLU/GABA neurotransmission, causing insufficient GnRH, LH, and T secretion. Therefore, we compared LH and T levels of male rats that have inhaled styrene (0, 150, 500, 1500 ppm for 6 h on 5 consecutive days) to GLU and GABA concentrations in the MBH and striatum. Animals were killed directly following the last exposure (immediate group) or after 24 h (recovery group). No suppression of LH or T levels was observed after styrene inhalation. LH levels of the immediate groups with 500 or 1500 ppm exposure were slightly but significantly elevated. Hypothalamic GLU and GABA concentrations remained unchanged. Increased striatal GABA concentrations were determined in recovery groups with 500 or 1500 ppm exposure. Striatal GLU concentrations remained unaffected. Thus, we demonstrate slightly increased LH and T levels in styrene-exposed male rats after inhalation of the two higher doses. This effect did not correlate with hypothalamic GLU and GABA concentrations. With the limitations inherent to any animal model, these data obtained from a 5-day exposure study with rats suggest, but do not unequivocally prove, that styrene may have also no reproductive toxicity effects in men chronically exposed to this chemical.

Administration, Inhalation↗

PubMed1999

Evaluation of pollution prevention options to reduce styrene emissions from fiber-reinforced plastic open molding processes.

Pollution prevention (P2) options to reduce styrene emissions, such as new materials and application equipment, are commercially available to the operators of open molding processes. However, information is lacking on the emissions reduction that these options can achieve. To meet this need, the U.S. Environmental Protection Agency's (EPA) Air Pollution Prevention and Control Division, working in collaboration with Research Triangle Institute, measured styrene emissions for several of these P2 options. In addition, the emission factors calculated from these test results were compared with the existing EPA emission factors for gel coat sprayup and resin applications. Results show that styrene emissions can be reduced by up to 52% by using controlled spraying (i.e., reducing overspray), low-styrene and styrene-suppressed materials, and nonatomizing application equipment. Also, calculated emission factors were 1.6-2.5 times greater than the mid-range EPA emission factors for the corresponding gel coat and resin application. These results indicate that facilities using existing EPA emission factors to estimate emissions in open molding processes are likely to underestimate actual emissions. Facilities should investigate the applicability and feasibility of these P2 options to reduce their styrene emissions.

Air Pollutants, Occupational↗

PubMed1977

Styrene and related hydrocarbons in subcutaneous fat from polymerization workers.

Subcutaneous fat samples from 25 workers in a styrene polymerization plant have been analyzed for styrene, ethyl benzene, toluene, benzene, and benzaldehyde by gas chromatography. Styrene was found in samples from 13 of 17 workers who had been heavily exposed within the previous 3 days, 5 of 13 having been exposed 2-3 days earlier. Six workers 4-90 days removed from exposure and two 2-3 days removed from low (less than 5 ppm) exposures had no detectable styrene in fat tissue samples. Toluene and ethyl benzene were found in varying amounts in many samples, and benzene was observed in three samples. Benzaldehyde was observed at levels of 5-53 microng/g in all samples. Although urinary metabolites and breath levels of styrene are reported to be detectable for less than 24 hr following exposure, styrene was found in subcutaneous fat from the subjects of this study for as long as 3 days after the most recent occupational exposure. The combination exposures in such a setting are reflected in the variety of hydrocarbons found in fat samples of workers.

Adipose Tissue↗

PubMed2000

Uptake of styrene in the upper respiratory tract of the CD mouse and Sprague-Dawley rat.

Inspired styrene is an olfactory toxicant in the mouse and rat. To provide nasal dosimetric information, upper respiratory tract (URT) uptake efficiency (UE) of styrene was measured in the surgically isolated URT of the urethane-anesthetized CD mouse and Sprague Dawley rat throughout a 45-min exposure. In the first studies, the effect of inspiratory flow rate on styrene UE was examined. At flows of 12-, 24-, or 70-ml/min average UE of 17, 9.8, and 4.1%, respectively, were observed in the mouse. For the rat, UE averaged 14, 9.1 and 5.7% at flow rates of 70, 150, and 400 ml/min, respectively. In the second study, UE was measured at inspired concentrations of 5, 10, 25, 50, 100, or 200 ppm at a flow rate of 12 ml/min in the mouse and 70 ml/min in the rat in both naive and metyrapone (150 mg/kg sc) pretreated animals. In the rat, steady state UE decreased with increasing exposure concentration, averaging between 24 and 10% efficiency at 5 to 200 ppm (p < 0.0001). Metyrapone pretreatment resulted in statistically significant reductions in UE with steady-state UE averaging 10-14% at 5-200 ppm. Metyrapone pretreatment abolished the concentration dependence. In naive mice, styrene UE did not maintain a steady state, but steadily declined during exposure. The mechanisms of the non-steady state behavior are not known, but they appear to be due to a styrene metabolite, as evidenced by the fact that steady-state UE was observed in metyrapone-pretreated mice. In the mouse, UE averaged between 42 and 10% efficiency at 5 to 200 ppm (p < 0.0001). Metyrapone pretreatment resulted in statistically significant reductions in UE, with steady state UE averaging 20-10% at 5-200 ppm. As in the rat, metyrapone pretreatment abolished the concentration dependence. In toto, these data provide strong evidence that inspired styrene is metabolized in nasal tissues in the rat and mouse and that a metabolic basis exists for the observed inspired concentration dependence of UE.

Administration, Intranasal↗

PubMed2000

Quantification of DNA adducts formed in liver, lungs, and isolated lung cells of rats and mice exposed to (14)C-styrene by nose-only inhalation.

Bronchiolo-alveolar tumors were observed in mice exposed chronically to 160 ppm styrene, whereas no tumors were seen in rats up to concentrations of 1000 ppm. Clara cells, which are predominant in the bronchiolo-alveolar region in mouse lungs but less numerous in rat and human lung, contain various cytochrome P450s, which may oxidize styrene to the rodent carcinogen styrene-7,8-oxide (SO) and other reactive metabolites. Reactive metabolites may form specific DNA adducts and induce the tumors observed in mice. To determine DNA adducts in specific tissues and cell types, rats and mice were exposed to 160 ppm [ring-U-(14)C]styrene by nose-only inhalation for 6 h in a recirculating exposure system. Liver and lungs were isolated 0 and 42 h after exposure. Fractions enriched in Type II cells and Clara cells were isolated from rat and mouse lung, respectively. DNA adduct profiles differed quantitatively and qualitatively in liver, total lung, and enriched lung cell fractions. At 0 and 42 h after exposure, the two isomeric N:7-guanine adducts of SO (measured together, HPEG) were present in liver at 3.0 +/- 0.2 and 1.9 +/- 0.3 (rat) and 1.2 +/- 0.2 and 3.2 +/- 0.5 (mouse) per 10(8) bases. Several other, unidentified adducts were present at two to three times higher concentrations in mouse, but not in rat liver. In both rat and mouse lung, HPEG was the major adduct at approximately 1 per 10(8) bases at 0 h, and these levels halved at 42 h. In both rat Type II and non-Type II cells, HPEG was the major adduct and was about three times higher in Type II cells than in total lung. For mice, DNA adduct levels in Clara cells and non-Clara cells were similar to total lung. The hepatic covalent binding index (CBI) at 0 and 42 h was 0.19 +/- 0.06 and 0.14 +/- 0.03 (rat) and 0. 25 +/- 0.11 and 0.44 +/- 0.23 (mouse), respectively. The pulmonary CBIs, based on tissues combined for 0 and 42 h, were 0.17 +/- 0.04 (rat) and 0.24 +/- 0.04 (mouse). Compared with CBIs for other genotoxicants, these values indicate that styrene has only very weak adduct-forming potency. The overall results of this study indicate that DNA adduct formation does not play an important role in styrene tumorigenicity in chronically exposed mice.

Animals↗

PubMed1980

An investigation of the acute behavioural effects of styrene on factory workers.

A group of men exposed to styrene in a factory building glass-fibre boats performed a series of behavioural tests at the beginning and end of their shift, and the results were compared with those of a referent group from the same factory. Changes in mood were noted in both groups of workers but were greater in the exposed men; moreover, the change in mood was correlated with blood styrene concentration. In the styrene workers the morning reaction time was slower than that for the referents. During the day the reaction time of the men with low blood styrene concentration (less than or equal to 5.4 mumol/l) speeded up and in the afternoon was similar to that of the referents; the reaction time for the men with high blood styrene concentration (greater than or equal to 5.5 mumol/l) was unchanged. Data taken from a questionnaire indicated that the men exposed were much more likely than was the referent group to report feeling unduly tired. They also reported feeling more tired on Friday night than Monday night, suggesting that the styrene might have a cumulative effect through the week.

Behavior↗

PubMed1989

Clinical and neurobehavioural study of the acute and chronic neurotoxicity of styrene.

A cross sectional field study of workers exposed to styrene was performed to evaluate possible acute and chronic neurotoxic effects. A total of 36 workers of four companies handling polyester resin materials for one to 16 years (median: 7 years) and two control groups were each examined on a Monday. The control group 1 (formed to compare acute effects) consisted of 20 men from two companies with no exposure to neurotoxic chemicals. To compare chronic effects, a second control group was formed by "one to one matching" with respect to age, socioeconomic status, and pre-exposure intelligence level. Ambient air monitoring using active sampling (short time) and passive samplers (long time) showed styrene in air concentrations as follows: range 3-251 ppm (median: 18 ppm) and concentrations 140-600 ppm during lamination of the inside of boats. For biological monitoring the results were as follows (postshift samples: range/median): styrene in blood: 5-482 micrograms/dl (39 micrograms/dl), mandelic acid urine: 0.01-3.64 g/l (0.21 g/l), and phenylglyoxylic acid urine: 0.01-0.87 g/l (0.19 g/l). The clinical examination found no signs or symptoms of peripheral neuropathy or encephalopathy. The principal work related health complaints were acute, reversible irritation of the eyes that occurred after exposure to styrene concentrations of 200 ppm or more. The neurobehavioural tests showed no significant differences in acute effects (p greater than 0.05) between the two groups or between preshift and postshift testing. Nor were there any significant differences in the relevant neurobehavioural variables between the styrene workers and the controls. It is concluded that occupational exposure to styrene concentrations in air up to 100 ppm causes no adverse acute or chronic effects on the central nervous system.

Acute Disease↗

PubMed1995

Impaired colour discrimination among workers exposed to styrene: relevance of a urinary metabolite.

OBJECTIVES: To survey the loss of colour vision among Japanese workers who have been exposed to styrene concentrations currently considered low (about 20 ppm). Also to assess the effects of styrene by examination of the nature of the relation between disorder of colour vision and age, alcohol consumption, and other variables. METHODS: Colour discrimination was examined in 64 male workers exposed to styrene (mean age; 38.0, mean exposed years; 7.0) and in 69 controls (mean age; 38.0). A standardised questionnaire was adopted to collect work history, occupational or non-occupational solvent exposure, alcohol consumption, and drug use. Colour vision was evaluated by the Lanthony desaturated panel D-15 test. The results of the test were expressed as the colour confusion index (CCI). RESULTS: The mean atmospheric styrene concentration was about 20 ppm. The mean urinary concentration of mandelic acid was 0.22 g/l. There was a significant difference in CCI between exposed workers and age matched controls. Colour vision of workers whose concentration of urinary mandelic acid was > or = 0.42 g/l was significantly impaired when compared with workers whose concentration was < 0.42 g/l. Multiple linear regression analysis that controlled confounding variables such as age, alcohol consumption, smoking, and educational attainment showed that the CCI was significantly related to the concentration of urinary mandelic acid. In both exposed workers and controls, the types of defects were mostly blue-yellow loss, although a few subjects showed complex loss. No one showed only red-green loss. CONCLUSIONS: These findings suggest that exposure to moderate styrene concentrations can lead to impairment of colour vision, and that there is a significant correlation with the urinary metabolite of styrene.

Adult↗

PubMed2002

Effects of occupational exposure to styrene on expression of adhesion molecule on leukocytes.

Styrene is an indispensable chemical extensively used in plastic and synthetic rubber industries. Styrene is known to produce various types of hepatotoxic, neurotoxic, and genotoxic effects. Styrene may be immunotoxic by both direct and indirect mechanisms. Measurement of adhesion molecules is a new tool for the investigation of immune system modulation. The aim of this study was to evaluate the association of the expression of the adhesion molecules CD11a, CD11b, CD18, CD54, CD49d, and CD62-L in white blood cells and levels of soluble adhesion molecules ICAM-1 and L-selectin in serum with occupational exposure to styrene. Analyses by flow cytometry revealed elevated levels of most of the assessed adhesion molecules on surfaces of lymphocytes, monocytes, and granulocytes. Expression of the adhesion receptor antigens CD11a on lymphocytes, CD11b on monocytes, and CD18 on granulocytes were unaffected. Workers exposed to styrene had decreased concentrations of sICAM-1 and no changes in concentrations of sL-selectin. Styrene exposure appears to increase activation of the immune system and alter leukocyte adherence. This interaction is a critical first step in immune stimulation and leukocyte-endothelial interaction.

Adult↗