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PubMed1995

Assessment of long-term styrene exposure: a comparative study of a logbook method and biological monitoring.

In a recent joint European research project "Biomonitoring of human populations exposed to genotoxic environmental chemicals: biomonitoring of styrene exposed individuals", a logbook method for assessment of long-term styrene exposure was applied in two Danish factories manufacturing glass fibre-reinforced polyester. The method was based on work process identification, assignment of work process concentrations and logbook keeping. Measures of exposure calculated by this method were compared with results from simultaneous measurements of styrene in blood and the metabolites mandelic acid and phenylglyoxylic acid in urine. Correlations were comparable with those obtained by use of personal samplers as published in the literature. Styrene in blood, however, only correlated with logbook concentrations at the time of sampling. Exposures were moderate to low. Mean personal 8-h time-weighted average concentration (8hTWAC) was 76 mg/m3 styrene (SD 54 mg/m3, range 2-230 mg/m3). The Danish 8hTWAC threshold limit value for styrene in air, 105 mg/m3 (25 ppm), was exceeded on 17% of personal days. The summed urinary metabolites, mandelic acid and phenylglyoxylic acid, had a mean personal value of 138 mg/g creatinine (SD 84 mg/g creatinine) on the day of sampling. Blood styrene mean value was 129 micrograms/l (SD 74 micrograms/l, range 66-358 micrograms/l). It is concluded that the logbook method offers a technique for testing whether measurements are performed on representative days and may be recommended as a tool supplementary to biological monitoring in the assessment of long-term exposure.

Adult↗
PubMed1990

Pulmonary toxicity of inhaled styrene in acetone-, phenobarbital- and 3-methylcholanthrene-treated rats.

Pulmonary changes in glutathione (GSH) indicated by the concentration of non-protein sulphydryls showed a decrease of 43% in rats exposed for 5 h per day three times to 500 cm3/m3 (2100 mg/m3) styrene vapour. In these rats, only a marginal decrease was observed in the pulmonary cytochrome P450 oxidative metabolism. Following a single 24-h inhalation exposure to 500 cm3/m3 styrene, the decreases in GSH were 66% in lung but only 16% in liver. On the other hand, a multifold increase in the disposition of thioether compounds was found in urine. Pulmonary cytochrome P450-dependent metabolism was decreased, shown by low residual activities of 7-ethoxyresorufin (less than 20%), 7-ethoxycoumarin (53%) and 7-pentoxyresorufin O-dealkylases (76%). Epoxide hydrolase and GSH S-transferase enzyme activities which catalyze styrene detoxification were not decreased. Styrene exposure (24 h) of acetone-, phenobarbital- or 3-methylcholanthrene-pretreated rats resulted in pulmonary effects different from each other and from those of styrene alone. Acetone potentiated the lung effect and elevated 1.5-fold urine thioether output. Inducer pretreatment seemed to be a factor aggravating styrene toxicity; in effect this was clearest in acetone-induced rats. In general, GSH depletion accompanied by inhibition of cytochrome P450-dependent oxidative drug metabolism were the earliest biochemical lesions manifested in styrene-exposed lung.

Acetone↗
PubMed1998

Albumin and hemoglobin adducts as biomarkers of exposure to styrene in fiberglass-reinforced-plastics workers.

OBJECTIVE: The purpose of this work was to compare levels of styrene-7,8-oxide (SO) adducts of albumin (Alb) and hemoglobin (Hb) with those of two urinary metabolites of styrene, mandelic acid (MA) and phenylglyoxylic acid (PGA), among workers exposed to styrene in the reinforced-plastics industry and in unexposed subjects. We also wished to determine whether cigarette smoking influenced adduct levels among these subjects. METHODS: A group of 22 male workers was selected on basis of an expectedly high level of exposure to styrene, and a group of 15 controls was selected from hospital blood donors and hospital staff. In the exposed group, MA and PGA were quantified by high-performance liquid chromatography (HPLC) analysis of urine samples collected prior to the work shift. The SO adducts were cleaved from cysteine residues by reaction with Raney nickel to give 1-phenylethanol (1-PE) and 2-phenylethanol (2-PE), which, after derivatization, were measured using gas chromatography-mass spectrometry (GC-MS) in the negative-chemical-ionization (NCI) mode. RESULTS: The estimated mean levels of MA and MA + PGA were 74 and 159 mg/g creatinine, respectively. Using the levels of urinary metabolites, an average styrene concentration of about 100 mg/m3 in the workplace air was estimated. The mean levels of 2-PE and 1-PE adducts in exposed workers were 2.84 and 0.60 nmol/g Alb and 5.44 and 0.43 nmol/g Hb, respectively. When subjects were stratified by level of urinary metabolites [zero (controls), low-level exposure (MA + PGA < or = 159 mg/g creatinine), and high-level exposure (MA + PGA > 159 mg/g creatinine)] and smoking status (smokers versus nonsmokers), a difference in Alb adduct levels was found among the groups (2-PE P = 0.002, I-PE P = 0.052). The difference in 2-PE-Alb levels was related to exposure category, to smoking status, and to their interaction. Correlations at or near a 0.05 level of significance were observed among the workers (n = 22) between individual levels of SO-protein adducts and MA + PGA (2-PE Alb, r = 0.54, 2-PE Hb, r = 0.40). CONCLUSION: Our data suggest that only exposure to relatively high levels of styrene allows a clear relationship to be detected between styrene exposure and SO adducts, due in part to the effects of cigarette consumption and to the high background levels of these adducts observed in unexposed subjects.

Adult↗
PubMed1993

Sister-chromatid exchanges in lymphocytes are increased in relation to longitudinally measured occupational exposure to low concentrations of styrene.

A longitudinal investigation of styrene exposure was conducted among 48 workers employed at a reinforced plastic boat manufacturing facility. 8-h time-weighted average (TWA) exposures to styrene and concentrations of styrene in the breath were determined for each individual on 7 randomly chosen days during 1 year. Peripheral blood lymphocytes from each subject were analyzed for sister chromatid exchanges (SCEs) 2 times and micronuclei (MN) 4 times during this period. Individual mean SCEs ranged from 4.7 to 9.5 SCEs per cell with a population mean of 6.4 +/- 0.2 SCEs per cell. SCEs were found to be significantly increased with an overall observed increase of 11.7% related to increasing exposure to styrene (mean air concentration 64.2 mg/m3 +/- 71.5; range 0.88-235 mg/m3) and with cigarette smoking. Examination of the relative contribution of each variable to regression of SCEs showed that smoking contributed about 62% and styrene exposure contributed about 25% of the total variability. Intra-individual lymphocyte MN frequencies did not vary significantly over time nor was a gradient toward increased MN observed with styrene exposure. However, significant inter-individual differences in MN frequencies were observed. Females had significantly higher MN frequencies than did males; MN were also increased with age. This study is highly unusual in that it illustrates the ability to separately quantify the relative contribution of each of two variables--smoking and styrene exposure--to an increase in SCEs in lymphocytes of an exposed human population.

Adult↗
PubMedDate not supplied

Neurobehavioral effects of acute styrene exposure in fiberglass boatbuilders.

A field investigation of the effects of acute exposure to styrene among fiberglass boatbuilders was performed. Personal samples of styrene in breathing zone air and postshift urinary mandelic acid were collected for 105 workers exposed and not exposed to styrene in 6 fiberglass boatbuilding companies in New England. Three tests from the computerized Neurobehavioral Evaluation System (NES) were performed by the subjects in the morning before exposure to styrene, near midday, and at the end of the work day. Duration of exposure averaged 2.9 years (SD = 4.6), 8-hour TWA styrene exposure averaged 29.9 ppm (SD = 36.2), and urinary mandelic acid averaged 347 mg/g creatinine (SD = 465). Regression analyses indicated a statistically significant relationship between postshift performance on the Symbol-Digit test and both acute styrene exposure and mandelic acid. Other analyses comparing workers exposed to less than 50 ppm and greater than 50 ppm styrene also showed a significant effect on Symbol-Digit performance. All three NES tests showed test-retest correlation coefficients above .80, and ease of use for collection of neurobehavioral data under field conditions was demonstrated.

Adult↗
PubMed1995

Biomarkers of styrene exposure in lamination workers: levels of O6-guanine DNA adducts, DNA strand breaks and mutant frequencies in the hypoxanthine guanine phosphoribosyltransferase gene in T-lymphocytes.

Occupational exposure to styrene was studied in nine workers of a hand lamination plant in Bohemia. Personal dosimeters were used to monitor the styrene workplace exposure, and the levels of styrene in blood and mandelic acid in urine were measured. Blood samples were taken at four occasions during a 7 month period to determine styrene-specific O6-guanine DNA adducts in lymphocytes and granulocytes, DNA strand breaks and hypoxanthine guanine phosphoribosyltransferase (HPRT) mutant frequency in T-lymphocytes. Seven administrative employees in the same factory (factory controls) and eight persons in a research laboratory (laboratory controls) were used as referents. DNA adduct levels determined by the 32P-postlabelling method in lymphocytes of laminators were remarkably constant and significantly higher (P < 0.0001) than in factory controls at all four sampling times. HPRT mutant frequencies (MF) measured by the T-cell cloning assay were higher in the laminators (17.5 x 10(-6), group mean) than in the factory controls (15.7 x 10(-6), group mean) at three of the four sampling times, but the differences were not statistically significant. However, a statistically significant (P = 0.021) difference between MF in the laminators (18.0 x 10(-6), group mean) and laboratory controls (11.8 x 10(-6), group mean) was observed at sampling time 4 (the only sampling time when this latter group was studied). This result indicates that styrene exposure may induce gene mutation in T-cells in vivo. DNA strand breaks were studied by the 'Comet assay' at the fourth sampling time. The laminators were found to have significantly higher levels of DNA strand breaks than the factory controls (P = 0.032 for tail length, TL; P = 0.007 for percentage of DNA in tail, T%; and P = 0.020 for tail moment, TM). A statistically significant correlation was also found between the levels of lymphocyte DNA adducts and all three DNA strand break parameters (TL P = 0.046; T% P = 0.026 and TM P = 0.034). On the contrary, no significant correlations were found between DNA adduct levels and the HPRT mutant frequencies or between the mutant frequencies and DNA strand breaks. Taken together, these results add further support to the genotoxic and possibly mutagenic effects of styrene exposure in vivo. However, no simple quantitative relationship seems to exist between the levels of styrene-induced DNA damage and frequency of HPRT mutation in T-lymphocytes.

Adult↗
PubMed1994

Styrene: toxicity studies--what do they show?

Styrene is efficiently metabolized to styrene oxide, which is itself readily detoxified by the same enzymes as those involved in the metabolism of various foodstuffs. Styrene oxide, like many intermediate metabolites of foodstuffs, is genotoxic and, if introduced directly into the stomachs of rodents in high doses/concentrations, gives rise to cancers of the forestomach. Exposing mice to doses of styrene high enough to overwhelm the capacity of the body to detoxify styrene oxide has been reported to increase lung tumor incidence in mice. The findings in eight epidemiological studies provide reassurance that occupational exposure to styrene is not associated with increased cancer risk. Tests for reproductive toxicity have given negative results, but effects on blood dopamine and hypothalamic and pituitary function and menstrual cycling under conditions of very high exposure have been reported. In light of all the available information, it is concluded that migration of styrene from food-wrapping materials is not a matter for toxicological concern.

Animals↗
PubMed1981

Distribution and elimination of 14C-styrene in rat.

Male rats were exposed to about 45 ppm of radioactively labeled styrene in the inspired air for 1--8 h. The distribution and elimination of styrene and its metabolites in different organs and tissues were studied. To get an idea of the ratio between unmetabolized and metabolized styrene in organs and tissues, a supplementary study was performed in which five male rats were exposed to about 250 ppm of radioactively labeled styrene. The largest amounts of styrene and its metabolites were found in the subcutaneous fat, and the concentration displayed a sharp rise during the first 4 h of exposure in comparison with the following 4 h. The concentration of styrene and its metabolites in the cerebrum, cerebellum and muscles paralleled the arterial blood concentration throughout the entire period of exposure and amounted to about 70% of the arterial blood value. In the supplementary study an accumulation of styrene metabolites in subcutaneous fat was disclosed; it ranged from 15 to 20% during exposure.

Animals↗
PubMedDate not supplied

Biological monitoring of fluctuating occupational exposures to styrene.

Nine workers occupationally exposed to styrene producing refrigerator lorries were analyzed. The styrene exposure was monitored 8 hours a day, for 5 days a week, for 1 week. We collected from workers a urine sample before and after each work shift. Moreover, alveolar air samples were obtained at the end of all work shifts. On Thursday afternoon and on Friday morning blood samples were taken from workers. The relationship between styrene exposure and biological data is reported and discussed. Alveolar, urinary and blood concentrations of styrene were comparable, suggesting similar kinetics. Biological styrene concentrations were significantly correlated with the mean daily environmental concentrations, but higher correlation coefficients were found with afternoon exposures. A narrow linear relationship between alveolar (Y) and urinary (X) styrene concentrations was found (Y = 0.359; r = 0.8579; n = 45; p less than 0.001). Urinary concentrations of mandelic acid (Y) confirmed a good relationship with the mean styrene exposure (X) (Y = 2.7 x +169; r = 0.4677 n = 45; p less than 0.01).

Air Pollutants, Occupational↗
PubMed1985

Epoxidation of styrene by hemoglobin and myoglobin. Transfer of oxidizing equivalents to the protein surface.

Methemoglobin and metmyoglobin catalyze the H2O2-dependent oxidation of styrene to styrene oxide and benzaldehyde. The formation of styrene oxide requires molecular oxygen as well as H2O2 but does not, as shown by inhibitor studies, involve the superoxide or hydroxyl radicals. Approximately 38, 67, and 78% of the oxygen in styrene oxide derives from 18O2 in the reactions catalyzed, respectively, by bovine hemoglobin, sperm whale myoglobin, and equine heart myoglobin, whereas 70, 55, and 35% of the oxygen can be shown to be derived from [18O]H2O2. However, a larger fraction of the epoxide oxygen than suggested by the labeling data (perhaps all) derives from molecular oxygen rather than H2O2 because the hemoproteins produce molecular oxygen from the peroxide. The epoxidation of styrene by methemoglobin gives equal amounts of the R and S enantiomers and, as shown by studies with trans-[1-2H]styrene, proceeds with partial (33%) loss of the olefin stereochemistry. The results are rationalized by H2O2-dependent formation of a protein radical that combines with molecular oxygen to give a protein-peroxy radical that oxidizes styrene.

Animals↗
PubMed1993

Genetic toxicity of 1,3-butadiene and styrene.

1,3-Butadiene and styrene (vinyl benzene) are indirect genotoxins, which require metabolic activation to an epoxide form in order to bind covalently to DNA. Styrene 7,8-oxide, the active metabolite of styrene, is a carcinogen in rodents and has been shown to be genotoxic in most in-vitro test systems and at various genetic endpoints. The few studies available on the genotoxicity of styrene 7,8-oxide in vivo have yielded negative or (in mice) weakly positive results. Styrene is not usually genotoxic in vitro in assays employing a microsomal preparation from rat liver for metabolic activation, but positive effects have been obtained when other sources of metabolic activation, such as human erythrocytes, were provided. In vivo, styrene has been found repeatedly to be weakly genotoxic in the assay for sister chromatid exchange, especially in mice. Cytogenetic damage (usually chromosomal aberrations) has been reported in many studies of workers, mainly from the reinforced plastics industry where ambient concentrations of styrene may be high (50-100 ppm), while most negative findings are associated with exposure to lower levels. Butadiene is metabolized to two reactive forms, 1,2-epoxy-3-butene and further to 1,2:3,4-diepoxybutane, both of which are genotoxic in various test systems in vitro. The lowest effective dose of the latter is 1-2 orders of magnitude higher than that of the respective monoepoxide. Butadiene itself has not been tested extensively for genotoxicity in vitro. A species-specific difference in the responses of mice and rats at various cytogenetic end-points is seen in vivo, the lowest effective concentrations in rats being clearly higher than those in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Exposure to styrene in the general Canadian population.

As part of an environmental health assessment in Canada, estimates of the intake of styrene by the general population were derived. Concentrations of styrene reported in air, water, soil and foods in Canada were reviewed in detail. Data on ambient air, collected by Environment Canada, showed mean concentrations of 0.09-2.35 micrograms/m3 at 18 sites across the country. In a national pilot study of indoor air in 757 homes across Canada, the mean styrene concentration was found to be 0.28 microgram/m3. The range of mean concentrations of styrene in treated water from 80 supplies in Ontario's Drinking Water Surveillance Program was 0.050-0.250 microgram/L. In limited testing of uncontaminated urban soils in southern Ontario, the styrene levels were less than 10 micrograms/kg. In a small Canadian survey, the compound was not detected (limits of detection, 1.0 microgram/L for liquids and 0.005 microgram/g for solids) in composite samples of 34 groups of food purchased in Windsor, Ontario. On the basis of these monitoring data, daily intakes of styrene were estimated for the general population. Intakes from ambient air ranged from 0.004 to 0.17 microgram/kg body weight per day and those from indoor air from 0.07 to 0.10 microgram/kg body weight per day for various age groups: infants, toddlers, school-age children, teenagers and adults. Intake from food was calculated to range from < 0.11 to < 0.58 microgram/kg body weight per day. The estimated intakes from drinking-water and soil were negligible. Potential exposure from cigarette smoke, on the basis of the styrene reported in mainstream smoke (10 micrograms per cigarette) and a smoking rate of 20 cigarettes per day, was estimated to be 2.86 micrograms/kg body weight per day for adults.

Adolescent↗
PubMed1993

A pharmacokinetic model to describe toxicokinetic interactions between 1,3-butadiene and styrene in rats: predictions for human exposure.

Co-exposure to vapours of 1,3-butadiene and styrene occurs in the styrene-butadiene polymer manufacturing industry. Both compounds are biotransformed during a first step by cytochrome P450-dependent mono-oxygenases to epoxides--intermediates which are proven carcinogens. In a previous publication, we reported that metabolism of butadiene in rats was inhibited by simultaneous exposure to styrene, whereas butadiene had no effect on the kinetics of styrene. In order to translate these results into conditions of human exposure, we developed a physiologically based pharmacokinetic (PBPK) model, which is presented here. Maximal metabolic rates (Vmax) and Ostwald's partition coefficients were obtained using liver microsomes and tissues from rat and man. Apparent Michaelis (Km) and inhibition (Ki) constants were derived from previously published data on rats and were considered to be species-independent. The model was used to simulate human exposure to atmospheric mixtures of 5 and 15 ppm butadiene with 0.20 and 50 ppm styrene. It predicts that the presence of styrene significantly inhibits butadiene metabolism in man: At exposures up to 15 ppm, the amounts of butadiene metabolized can be expected to be reduced to 81 and 63% with co-exposure to styrene at 20 and 50 ppm, respectively.

Administration, Inhalation↗
PubMed1993

Kinetics of urinary excretion and effects on colour vision after exposure to styrene.

We evaluated the influence of the body burden of styrene on biological indices of exposure and the effects of this solvent on colour perception. The exposure of 19 workers was followed during a working week by personal sampling and biological monitoring. Although no significant difference in daily exposure was observed, pre-shift values of urinary styrene and urinary mandelic acid increased significantly during the week, and the regression line between external dose and biological exposure indices changed correspondingly. These data suggest that body burden can influence the results of biological monitoring of styrene. The effect of styrene on colour vision was evaluated in two further groups: 73 exposed workers and 53 referents and 36 pairs of workers and controls. A dose-related impairment was observed, which appeared to be synergistic with age and was not significantly improved by a one-month interruption of exposure. Our data show the need to improve biological monitoring of exposure to styrene and, in particular, to establish dose-effect and dose-response relationships between exposure and early effects. Urinary excretion of styrene and colour vision assessment represent, respectively, promising indices of exposure to and an effect of styrene.

Adult↗
PubMed2003

Olfactory function in workers exposed to styrene in the reinforced-plastics industry.

BACKGROUND: Impairment of olfactory function in humans has been associated with occupational exposure to volatile chemicals. To investigate whether exposure to styrene was associated with olfactory impairment, olfactory function was examined in workers with a minimum of 4 years exposure to styrene in the reinforced-plastics industry (current mean exposure: 26 ppm, range: 10-60 ppm; historic mean dose: 156 ppm-years, range: 13.8-328 ppm-years) and in a group of age- and gender-matched, unexposed controls. METHODS: Olfactory function was assessed using a standardized battery that included tests of threshold sensitivity for phenylethyl alcohol (PEA), odor identification ability, and retronasal odor perception. Odor detection thresholds for styrene were also obtained as a measure of specific adaptation to the work environment. RESULTS: No differences were observed between exposed workers and controls on tests of olfactory function. Elevation of styrene odor detection thresholds among exposed workers indicated exposure-induced adaptation. CONCLUSIONS: The present study found no evidence among a cross-section of reinforced-plastics industry workers that current or historical exposure to styrene was associated with impairment of olfactory function. Taken together with anatomical differences between rodent and human airways and the lack of evidence for styrene metabolism in human nasal tissue, the results strongly suggest that at these concentrations, styrene is not an olfactory toxicant in humans.

Adaptation, Physiological↗
PubMed1991

Assessment of the peripheral, central, and autonomic nervous system function in styrene workers.

To investigate the effects of styrene exposure on peripheral, central, and autonomic nervous system functions in man, we measured the distribution of nerve conduction velocities (DCV), short-latency somatosensory evoked potentials (SSEP), and variability in electrocardiographic R-R interval (CVRR) as well as conventional sensory and motor median nerve conduction velocities (SCV and MCV) in eleven styrene-exposed workers. The styrene workers' urinary phenylglyoxylic acid levels ranged from 31 to 419 (mean 169) mg/g creatinine at the end of the work shift on the examination day (estimated exposure to styrene of 22 ppm in air). Control subjects, matched to each styrene worker by sex and age, were selected from healthy adults without cardiovascular, neurologic and other potentially confounding disorders. In the styrene workers, we found that the V80 velocity of the DCV, below which 80% of active nerve fibers lie, and the SCV were both significantly slowed; the CVRR was also significantly reduced. There were no significant differences in SSEP latencies, MCV, or heart rate between the exposed workers and controls. These data, despite the small sample size, suggest that styrene affects the faster myelinated fibers of the peripheral sensory nerves, and that it also affects autonomic nervous activity.

Adult↗
PubMed2001

Stereochemical metabolism of styrene in volunteers.

OBJECTIVES: To study the stereochemistry of styrene metabolism in volunteers, and its interindividual variability. METHODS: Twenty healthy male volunteers (aged 18-37 years) were exposed to 360 mg/m3 styrene for 1 h while they performed 50 W physical exercise. Venous blood was drawn during and for up to 2 h after exposure. Urine was collected at time-intervals up to 24 h after exposure. The following parameters were determined: styrene, free and conjugated styrene glycol (SG) in blood, and conjugated SG, mandelic acid (MA) and phenylglyoxylic acid (PGA) in urine. RESULTS: Average pulmonary retention of styrene was 62%. Excretion of the acidic metabolites MA and PGA accounted for 58% of the pulmonary uptake. The average maximum concentration (Cmax) and area under the curve (AUC) of free (R)-SG in blood were 1.3 and 1.7 times higher than those of (S)-SG respectively; the half-life of (R)-SG was longer (82 vs 62 min, P < 0.005). Cmax and AUC of the conjugated SG enantiomers in blood did not differ, but again half-life for (R)-SG was longer (72 vs 64 min, P < 0.05). Cumulative excretion and renal clearance of conjugated (S)-SG in urine were three and four times higher, respectively, than that of (R)-SG. Cumulative excretion of (S)-MA was 1.6 times higher than (R)-MA. Interindividual differences in the kinetic parameters of the metabolites were two- to threefold. CONCLUSIONS: The enantiomeric excess found was different for each metabolite under study, implying different enantioselectivity and/or enantiospecificity of the enzymes and carrier-proteins involved in the biotransformation and excretion. The use of these metabolites as biological indicators for prediction of the enantiomeric excess of the toxic metabolite styrene-7,8-oxide (SO) is therefore not justified. Interindividual differences in the stereochemical metabolism of styrene are moderate.

Adolescent↗
PubMed2002

New aspects in the biomonitoring of occupational exposure to styrene.

OBJECTIVE: Based on our previous studies we analysed DNA and haemoglobin adducts, single-strand breaks in DNA, chromosomal aberrations and HPRT mutant frequencies in styrene-exposed workers, in relation to employment time, with respect to markers of individual susceptibility. In our study the risk assessment of genotoxic styrene in occupationally exposed humans is reviewed in the light of adaptation and/or population selection. Various styrene-induced DNA adducts (representing important integral measures of DNA damage) are discussed as potential powerful biomarkers of styrene exposure, with respect to DNA repair. METHODS: The complexity of followed markers required multiple methodological approaches, including modified (32)P-post-labelling assay, PCR-based methods for genotyping, cytogenetic analysis, T-cell cloning assay, comet assay and tests for DNA repair capacity, and statistical tests. RESULTS: Haemoglobin and DNA adducts, single-strand breaks in DNA, chromosomal aberrations and mutant frequencies at the HPRT gene were assessed with respect to the duration of exposure. No apparent accumulation of these biomarkers was found to be dependent on the years of employment, suggesting that adaptive processes play a role in chronically exposed workers. Statistically significant differences between the exposed and control individuals were found for the deduced epoxide hydrolase activity ( P=0.041) and the frequency of heterozygous Ala/Val genotype in GSTP1, exon 5 ( P=0.025). Significantly increased DNA repair capacity was found in styrene-exposed laminators compared with control individuals. CONCLUSIONS: In the light of present knowledge well-designed population studies on styrene genotoxicity are needed. Such studies should cover important areas of individual susceptibility (metabolising and repair enzymes, distributions of genetic polymorphisms) and possible role of adaptation, as well as the crucial role of DNA repair. Additionally, genotoxic effects of in-vivo formed 3,4-styrene oxide should be also addressed.

DNA Adducts↗