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PubMed1999

Characterization of hepatocellular resistance and susceptibility to styrene toxicity in B6C3F1 mice.

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.

Administration, Inhalation↗
PubMed1999

Metabolism of styrene by mouse and rat isolated lung cells.

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.

Animals↗
PubMed2005

T(H1)-directed modulation of in vitro cytokine production in human peripheral blood mononuclear cells by styrene-7.8-oxide.

Styrene and its chiral main metabolite styrene-7.8-oxide are well characterized regarding their cytotoxic, genotoxic and neurotoxic properties. To our knowledge, no data exist on the influence of styrene and styrene-7.8-oxide on immune reactions. Epidemiological studies suggest that exposure to environmental pollutants, specifically volatile organic compounds (VOCs), including styrene is one factor contributing to increasing prevalence rates of allergic diseases. In this study, we investigated the modulation of the immune system by styrene-7.8-oxide in vitro. Human peripheral blood mononuclear cells were incubated with styrene-7.8-oxide, either as (S)-enantiomer, (R)-enantiomer, or racemic styrene-7.8-oxide. Subsequently, the secretion of T(H1)-cytokines IFNgamma and IL-12 as well as T(H2)-cytokines IL-4 and IL-5 were measured by ELISA. We introduced a novel mathematical approach to quantify and compare cytokine responses. The results revealed a stimulation of cytokine secretion with emphasis on T(H1)-cytokines IFNgamma and IL-12. The stimulating effects were elicited at concentrations of styrene-7.8-oxide comparable to what would be encountered at industrial workplaces where styrene is processed. Therefore, we conclude that styrene-7.8-oxide exhibits immunomodulating capacities, which can be of clinical relevance for individuals with high styrene exposure.

Air Pollutants, Occupational↗
PubMed1997

Influence of duration of exposure to styrene oxide on sister chromatid exchanges and cell-cycle kinetics in cultured human blood lymphocytes in vitro.

Styrene-7,8-oxide, an intermediate of styrene, is a known alkylating mutagen. The present study was carried out to investigate the influence of duration of exposure to styrene-7,8-oxide (styrene oxide) on induction of sister chromatid exchanges (SCEs) and inhibition of cell-cycle kinetics using cultured human blood lymphocytes in vitro. Phytohemagglutinin-stimulated whole-blood lymphocyte cultures obtained from heparinized whole blood from healthy donors were exposed to 100 microM styrene oxide for 22, 36, 48 and 72 h. A reduction of SCEs induction with increase in duration of exposure to styrene oxide was observed, i.e. a clear significant inverse relationship between exposure time and frequencies of SCEs induction due to styrene oxide was obtained. Styrene oxide induces significant elevations in unscheduled DNA synthesis DNA repair as well as S-phase synthesis in human blood lymphocytes in vitro, depending on the duration of exposure. The decrease in the induction of SCEs due to styrene oxide with increasing duration of its exposure may be principally due to an increased DNA repair and partly due to an increasing metabolic transformation to styrene glycol with increasing duration of its exposure as well as to some extent due to cell death at the maximum period of exposure. i.e. 72 h. Although the proliferations of lymphocytes exposed to 100 microM styrene oxide were significantly inhibited at different durations of exposure, no linear relationship between the replication index and the duration of exposure was noticed (r = 0.47, p > 0.05). Similarly, there was no relationship between replication index and SCE frequency (r = -0.36, p > 0.05), suggesting that these two parameters may reflect two different endpoints for the cytogenotoxic effects of styrene oxide.

Cell Cycle↗
PubMed1994

Effects of styrene oxide on differentiation and viability of rodent embryo cultures.

Epidemiological investigations on the reproductive and developmental outcomes of rubber and plastic industry workers have focused on the potential developmental toxicity of styrene, an important occupational chemical, and its metabolite, styrene oxide using two in vitro culture systems: micromass cell cultures and whole embryo culture (WEC). Further, we have compared the effects of styrene oxide in both culture systems to the developmental toxicity of styrene in the micromass system. The ability of styrene oxide to affect the differentiation of rat embryo midbrain (CNS) and limb bud (LB) cells was compared to general cytotoxicity over 5 days in high-density micromass cultures. The IC50 for differentiation was 9.2 micrograms/ml (76 microM) for CNS and 6.7 micrograms/ml (56 microM) for LB. The LC50 for cytotoxicity was 9.6 micrograms/ml (80 microM) and 27.5 micrograms/ml (228 microM) for CNS and LB, respectively. The values for CNS sensitivities suggest that inhibition of differentiation is probably a consequence of high levels of cytotoxicity. In contrast, effects of styrene oxide on LB endpoints of differentiation were evident at concentration levels which had minimal effects on cell viability. Styrene alone or in the presence of an exogenous monooxygenase system had minimal effects when tested at concentrations 4-12 times the highest IC50 values seen with styrene oxide alone. In whole embryo culture experiments, styrene oxide produced growth retardation and embryo malformations (primarily neural) with an MC50 value of 20 micrograms/ml (167 microM). The LC50 value for styrene oxide was approximately 1.7-fold higher (33.2 micrograms/ml, 276 microM). Our in vitro studies suggest that further evaluations of the relationship of developmental toxicity and generalized cytotoxicity of styrene and its metabolite are needed, especially given the low concentrations at which effects were seen.

Animals↗
PubMedDate not supplied

Effect of subchronic ethanol ingestion on styrene-induced damage to the tracheal and pulmonary epithelium of the rat.

Previous studies have indicated that ethanol may affect styrene metabolism and toxicity in target tissues (e.g. brain). Morphological and biochemical changes have been reported in the respiratory tract of laboratory animals exposed to styrene either by inhalation or i.p. injection. The aim of the present study was, therefore, to investigate the influence of subchronic ethanol administration (5% in a Lieber-DeCarli liquid diet) on the morphological alterations of the respiratory tract induced by styrene inhalation (300 ppm, 6 h day(-1), 5 days a week for 2 weeks) in rats. Levels of reduced glutathione (GSH) in lung and liver tissues as well as in erythrocytes and whole blood were studied as indicators of overall GSH status, and urinary levels of the styrene metabolites-mandelic acid and phenylglyoxylic acid-were also measured as indicators of styrene-absorbed dose. Rats exposed to 300 ppm styrene presented morphological alterations throughout the respiratory tract. Electron microscopy analysis showed diffuse cell damage involving the tracheal, bronchiolar and alveolar epithelium. These abnormalities were accompanied by 40% depletion of GSH in the lung tissue and also 35% depletion in hepatic GSH in the absence of alteration of the GSH content in blood. Styrene metabolism was apparently induced by subchronic ethanol treatment, as indicated by an increased excretion of urinary mandelic (+140%, P < 0.05) and phenylglyoxylic (+50%) acids. However, repeated ethanol administration did not exacerbate the lung GSH depletion nor the damaging effect to the respiratory tract induced by the 2-week exposure to styrene alone. The lack of effects of ethanol on styrene pulmonary toxicity after combined exposure may be due to the different tissue distribution of the cytochrome P-450 isoforms involved in the styrene biotransformation to styrene-7,8-oxide, and their different induction by ethanol.

Administration, Oral↗
PubMed2000

A review of the developmental and reproductive toxicity of styrene.

The reproductive and developmental toxicity of styrene has been studied in animals and humans. The animal studies on styrene have diverse study designs and conclusions. Developmental or reproductive toxicity studies have been conducted in rats, mice, rabbits, and hamsters. In most cases, high doses are required to elicit effects, and the effects are not unique to reproduction or development. In a number of the reports, either the experimental designs are limited or the descriptions of the designs and the endpoints measured are insufficient to draw conclusions about the toxicity of styrene. The more complete and better-reported studies show that styrene does not cause developmental toxicity at dose levels that are not maternally toxic. Some neurochemical or neurobehavioral effects have been reported at high exposures. Styrene does not affect fertility or reproductive function. Considerable animal toxicity data on styrene support the conclusion that styrene is neither an endocrine-active substance nor an endocrine disrupter. Human studies often suffer from either inadequate exposure data or exposure to a wide variety of materials, so that attribution of effects to styrene exposure is impossible. Furthermore, investigators often have failed to account for other exposures in the workplace or for other potentially confounding factors in their studies. Menstrual cycle irregularities and congenital abnormalities were initially reported; however, the better and more recent reports do not show that styrene causes developmental or reproductive effects in humans. Human studies also support the conclusion that styrene is not an endocrine disrupter. Although some study authors have concluded that styrene is either a human or an animal reproductive or developmental toxicant, careful review demonstrates that such conclusions are not justified.

Abnormalities, Drug-Induced↗
PubMed2006

Effects of subchronic exposure to styrene on the extracellular and tissue levels of dopamine, serotonin and their metabolites in rat brain.

At present, there is controversy over the neurotoxic potential of styrene. Several epidemiological and clinical studies have shown that styrene exposure causes alterations of central nervous system functions in humans. Neurotransmitters have been implicated in the pathogenesis of styrene neurotoxicity in rodents. Several studies carried out on postmortem brain tissue suggest that styrene may alter dopaminergic neurotransmission in rabbit or rat brain. Moreover, in vitro studies suggest that both styrene and styrene oxide inhibit the uptake of dopamine (DA) in purified synaptic vesicles prepared from rat brain striata. To date, biochemical studies on animals have explored global tissue levels of neurotransmitters with sub-acute exposures to styrene. However, extracellular levels of neurotransmitters are more closely related to behaviour than are global tissue levels. The present study determined changes in the extracellular concentrations of DA, serotonin (5-HT) and their acid metabolites, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA), in striatal dialysates from freely moving adult male rats after exposure to 750 and 1,000 ppm styrene, 6 h per day, 5 days per week for 4 weeks. We also determined the concentrations of DA, 5-HT and their acid metabolites in striatum, nucleus accumbens and prefrontal cortex obtained postmortem from similarly exposed rats. Exposure to 1,000 ppm of styrene caused a significant decrease in extracellular acid metabolite concentrations. Tissue levels of acid metabolites were also decreased to a lesser extent. The effects were observed 72 h after discontinuing exposure but had vanished 17 days later. There was no change in DA or 5-HT concentrations either in the dialysates or tissues. Exposure to 750 ppm styrene caused no changes in the concentrations of DA, 5-HT and their acid metabolites either in the dialysates or tissues. The possibility that the effect of styrene is mediated by monoamine oxidase (MAO) inhibition is discussed.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2005

The ototoxicity of styrene: a review of occupational investigations.

OBJECTIVES: The objective of this study was to review critically a number of occupational investigations of the exposure and effect relation between inhaled styrene vapour and hearing loss. There is concern that workers' hearing may be impaired by exposure to styrene, as used in industries making plastics and fibreglass-reinforced products. METHODS: Seven occupational studies, each dealing with the ototoxicity of styrene, were examined. Factors assessed included the experimental design and number of subjects within exposure groups, measurement of the styrene-in-air concentration, confirmation of the styrene exposure by blood or urine analysis, determination of the hearing threshold levels for the exposure and control groups, and measurement of any occupational noise in the subjects' workplaces. Consideration was also given to statistical relations between high-frequency hearing loss and lifetime exposure indices for styrene and noise. RESULTS: The results are equivocal. Four investigations failed to find any effect of styrene on hearing thresholds. In contrast, other investigations claimed to have demonstrated styrene-induced hearing loss in industrial populations, with synergism between styrene and noise. However, these reports exhibited shortcomings of experimental design and data analysis. CONCLUSIONS: Considering the body of evidence as a whole, hearing deficits due to occupational exposure to styrene at low concentrations have not been demonstrated by scientifically reliable argument. There is some suggestion of an association between styrene exposure, occupational noise, and hearing dysfunction. Further studies in humans are necessary to clarify this question.

Denmark↗
PubMed2005

SPE-GC-MS for the sampling and determination of unmetabolized styrene in urine.

The urinary excretion of unmetabolized styrene can be a very good indicator for biomonitoring styrene in occupationally exposed people. The use of a new urine sampling system, involving a solid-phase extraction cartridge, offers several advantages for determining styrene. The advantages are especially related to the pre-analytical phase of styrene determination, which may be influenced by many variables. The effect on styrene recovery of sorbent type, eluting solvent, elution volume, elution flow-rate, and the addition of methanol to the washing solvent, was evaluated by experimental design methodology. As a result, Oasis HLB cartridges were selected for urine sampling, as well as 1.5 mL of ethyl acetate at 0.5 mL/min for eluting the retained styrene. These conditions were then applied to the validation of the solid-phase extraction combined with GC-MS method for the sampling and analysis of unmetabolized styrene in urine. The overall uncertainty was in the 12-22% range and the limit of detection was 2.2 microg/L for a 4 mL urine sample. The stability of styrene has been studied both in cartridges and in vials under different storage periods. After 1 month period the styrene stored on cartridges at room temperature remained stable, whereas this is not the case for styrene recovery from vials. The results obtained indicate that on-site solid-phase extraction of urine can provide a simple, accurate and reproducible sampling and analytical method for the biomonitoring of styrene in urine.

Chromatography, Liquid↗
PubMed2001

The role of cytochromes P-450 in styrene induced pulmonary toxicity and carcinogenicity.

Exposure of CD-1 mice to atmospheres of 40 and 160 ppm styrene, daily for up to 10 days, caused pulmonary toxicity characterised by focal loss of cytoplasm and focal crowding of non-ciliated Clara cells, particularly in the terminal bronchiolar region. The toxicity was accompanied by an increase in cell replication rates in terminal and large bronchioles of mice exposed for 3 days or longer. The toxicity and increased cell replication were no longer apparent after a 2-day break in exposure, but re-occurred when exposure was resumed. Similar effects were seen in mice given oral doses of 10, 100 or 200 mg/kg styrene, daily for 5 days. Increases in cell replication rates were seen in the terminal bronchioles in mice dosed with 100 and 200 mg/kg styrene, but not 10 mg/kg. Toxicity was limited to 3 to 10 animals in the 200 mg/kg group. Neither morphological nor cell proliferation effects were seen in the alveolar region of the mouse lung in any of these studies, nor were any effects observed in the lungs of CD rats exposed to 500 ppm styrene for up to 10 days. The pulmonary toxicity and increased cell division seen in mice, but not rats, correlates with the known species differences in pulmonary carcinogenicity of styrene, suggesting that the acute and chronic responses are causally related. 5-Phenyl-1-pentyne was shown to inhibit the pulmonary cytochrome P-450 metabolism of styrene in vivo. Cell replication rates in the lungs of mice treated with this inhibitor and exposed to styrene were comparable with controls demonstrating that the pulmonary effects of styrene on the mouse lung are caused by a metabolite of styrene, probably styrene oxide. The risks associated with exposure to styrene appear to correlate well with the metabolic capacity of the lung.

Administration, Inhalation↗
PubMed2000

Combined effects of exposure to styrene and ethanol on the auditory function in the rat.

In order to study the auditory effects of a metabolic interaction between ethanol and styrene, a first group of rats was gavaged once a day with ethanol (4 g/kg), a second group was exposed to 750 ppm styrene by inhalation, and a third group was exposed to both ethanol and styrene (5 days/week, 4 weeks). Auditory function was tested by recording brainstem (inferior colliculus) auditory evoked potentials, and cochlear hair cell loss was estimated by light microscopy. Cytochrome P450 2E1 and the main urinary styrene metabolites, namely mandelic, phenylglyoxylic and hippuric acids, were measured by high-performance liquid chromatography to check the effects of ethanol on styrene metabolism. In our experimental conditions, ethanol alone did not have any effect on auditory sensitivity, whereas styrene alone caused permanent threshold shifts and outer hair cell damage. Hearing and outer hair cell losses were larger after the exposure to both ethanol and styrene than those induced by styrene alone, indicating a clear potentiation of styrene ototoxicity by ethanol. As expected, metabolic data showed that ethanol alters styrene metabolism and can therefore be considered a modifying factor of styrene toxicokinetics.

Administration, Inhalation↗
PubMedDate not supplied

Improving the cytochrome P450 enzyme system for electrode-driven biocatalysis of styrene epoxidation.

Cytochrome P450 enzymes catalyze a vast array of oxidative and reductive biotransformations that are potentially useful for industrial and pharmaceutical syntheses. Factors such as cofactor utilization and slow reaction rates for nonnatural substrates limit their large-scale usefulness. This paper reports several improvements that make the cytochrome P450cam enzyme system more practical for the epoxidation of styrene. NADH coupling was increased from 14 to 54 mol %, and product turnover rate was increased from 8 to 70 min(-1) by introducing the Y96F mutation to P450cam. Styrene and styrene oxide mass balance determinations showed different product profiles at low and high styrene conversion levels. For styrene conversion less than about 25 mol %, the stoichiometry between styrene consumption and styrene oxide formation was 1:1. At high styrene conversion, a second doubly oxidized product, alpha-hydroxyacetophenone, was formed. This was also the exclusive product when Y96F P450cam acted on racemic, commercially available styrene oxide. The alpha-hydroxyacetophenone product was suppressed in reactions where styrene was present at saturating concentrations. Finally, styrene epoxidation was carried out in an electroenzymatic reactor. In this scheme, the costly NADH cofactor and one of the three proteins (putidaredoxin reductase) are eliminated from the Y96F P450cam enzyme system.

Camphor 5-Monooxygenase↗
PubMed1999

Effect of styrene on monoamine oxidase B activity in rat brain.

Previous studies have indicated that workers exposed to styrene present a decreased activity of platelet monoamine oxidase B (MAO B), suggesting that this biochemical assay may represent a biomarker for styrene-induced neurotoxicity. This study was undertaken to determine whether exposure to styrene would cause changes in MAO B activity in the target organ--the brain. Groups of rats were exposed to styrene by inhalation at concentrations of 300 ppm for 4 wk or 50 ppm for 13 wk. Both treatments caused significant decreases of MAO B activity in several brain areas, while MAO A activity was not affected. Decreases in MAO B activity were also found in brainstem of rats given styrene (400 mg/kg) or styrene oxide (100 mg/kg) by i.p. injection for 2 wk. Styrene, styrene oxide, and other styrene metabolites (mandelic acid, phenylglyoxylic acid, and styrene glycol) had no direct inhibitory effect on brain MAO B activity when tested in vitro. These results indicate that exposure to low concentrations of styrene alters MAO B activity in rat brain, suggesting that the observed changes in human platelets may reflect alterations in the nervous system.

Administration, Inhalation↗
PubMedDate not supplied

The effect of spraying and rolling process factors on styrene emission during the application of unsaturated polyester resins.

In recent years the awareness of the problems caused by styrene emission during the processing of unsaturated polyester resins has enlarged. The spray-up application of gel coats is especially problematic, and it produces high styrene emission rates. The emission of styrene has been reduced through material changes, work practice controls, and add-on controls. However, the influence of the spray-up process factors on styrene emission has not been studied before. The aim of this study was to examine possibilities to reduce styrene emission by optimization of spray-up process factors. The following factors were studied under controlled laboratory conditions: orifice size and angle of the spray gun tip, spraying pressure, distance between spray gun and mold, and shape of the mold. The influence of the rolling pattern during lamination was also studied. Several significant factors were found. High pressure and long spraying distance increased both the unit styrene emission and the emission rate. The orifice size had two effects; a large orifice decreased the amount of styrene emitted per sprayed amount of resin but increased the emission rate of styrene. The shape of the mold did not affect the styrene emission. Styrene emission is greater if the entire mold area is rolled. To achieve lower emission is it necessary to roll an area as small as possible; this is especially important if a large mold is laminated. The results showed that emission of styrene can be reduced significantly by an optimal selection of the spray gun settings and the way of working. Optimal settings also increased the transfer efficiency resulting in decreased material loss.

Air Pollutants↗
PubMedDate not supplied

Occupational asthma in the furniture industry: is it due to styrene?

BACKGROUND: Styrene, a volatile monomer, has been reported as a cause of occupational asthma in a few case reports. OBJECTIVE: The aim of this study was to investigate the risk for asthma in relation to exposure to styrene in a large number of workers. METHODS: A total of 47 workers with a history of exposure to styrene were included in the study. To establish whether asthma was present, each patient underwent a clinical interview, pulmonary function testing and bronchial challenge with methacholine. Specific bronchial challenges with styrene and serial peak expiratory flow (PEF) measurement at home and at work were carried out in subjects with a diagnosis of asthma to evaluate the relationship between their asthma and exposure to styrene in the workplace. RESULTS: Among the 47 subjects, 5 workers had given a history of work-related symptoms, and 3 of them had a positive methacholine challenge test. Specific bronchial challenges with styrene and serial PEF measurement were subsequently carried out in these 3 subjects. Although provocation tests with styrene were negative in the 3 workers, 1 worker had PEF rate records compatible with occupational asthma. CONCLUSION: We established one patient with occupational asthma from a group of people who have excessive styrene exposure. This finding may be suggestive but is not conclusive about the causative role of styrene in occupational asthma. Since styrene is a frequently used substance in the furniture industry, it is worth performing further studies to investigate the relationship between styrene and occupational asthma.

Adult↗
PubMed2001

Metabolic capacity and interindividual variation in toxicokinetics of styrene in volunteers.

The aim of the present study was to assess the interindividual variation in styrene toxicokinetics and to correlate this variation with the individual metabolic capacity for cytochrome P450 (CYP), CYP2E1, CYP1A2 and CYP2D6. Twenty male volunteers were exposed on separate occasions to 104+/-3 and 360+/-20 mg/m3 of styrene for 1 h while performing 50 W physical exercise on a bicycle ergometer. Styrene concentrations in blood and mandelic (MA) and phenylglyoxylic acid (PGA) in urine were measured. The metabolic capacity was assessed by phenotyping with chlorzoxazone (CYP2E1), caffeine (CYP1A2), dextromethorphan (CYP2D6) and antipyrine (CYP450). In addition, for the main styrene-metabolising enzyme, CYP2E1, genotyping for the genetic polymorphisms of the gene was performed. The average pulmonary retention of styrene was 62 +/- 7% at both exposure concentrations, and the 24-h excretion of MA and PGA accounted for 58% of the dose at both concentrations. The interindividual variation in styrene kinetics ranged from 19% for the terminal half-life (t(1/2,beta)) of styrene to 41% for the cumulative excretion of MA and PGA. However, no correlation between the apparent blood clearance of styrene (CLapp), t(1/2,beta) of styrene or excretion of MA and PGA on one hand, and the individual metabolic capacity on the other hand was found. Although other explanations cannot be excluded, this lack of correlation might be due to the high apparent blood clearance (1.4 l/min) of styrene, indicating that styrene metabolism is liver-blood-flow-dependent.

Adolescent↗
PubMed1989

Review of the toxicology of styrene.

Styrene is used in the production of plastics and resins, which include polystyrene resins, acrylonitrile-butadiene-styrene resins, styrene-acrylonitrile resins, styrene-butadiene copolymer resins, styrene-butadiene rubber, and unsaturated polyester resins. In 1985, styrene ranked in the top ten of synthetic organic chemicals produced in the U.S. This review focuses on various aspects of styrene toxicology including acute and chronic toxicity, carcinogenicity, genotoxicity, pharmacokinetics, effects on hepatic and extrahepatic xenobiotic-metabolizing enzymes, pharmacokinetic modeling, and covalent interactions with macromolecules. There appear to be many similarities between the toxicity and metabolism of styrene in rodents and humans. Needed areas of future research on styrene include studies on the molecular dosimetry of styrene in terms of both hemoglobin and DNA adducts. The results of such research should improve our ability to assess the relationship between exposure to styrene and surrogate measures of "effective dose", thereby improving our ability to estimate the effects of low-level human exposures.

Animals↗