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PubMed1993

Cytogenetic studies of workers exposed to styrene: a review.

In 17 of 50 cytogenetic studies (on chromosomal aberrations, micronucleus formation and sister chromatid exchange) in peripheral blood lymphocytes from a total of 667 workers in industries in which there is exposure to styrene, significant increases in the frequency of chromosomal damage have been reported when compared with unexposed controls. The positive or negative outcome of these studies is, however, unrelated to the extent of exposure to styrene. Furthermore, in the 17 investigations in which positive results were found, there is no convincing evidence of a positive dose-response relationship, in spite of the wide ranges of exposure and different methods of measurement. There are also serious discrepancies between findings on the chromosomal damaging effects of styrene in human lymphocytes in vitro and the types of damage reported in exposed workers. The findings are not consistent with the interpretation that styrene is responsible for the observed effects in workers. Several other chemicals identified in the environment of styrene workers have been reported to induce chromosomal damage in vitro and/or in vivo.

Chromosome Aberrations↗
PubMed1993

Critical assessment of epidemiological studies on the carcinogenicity of 1,3-butadiene and styrene.

1,3-Butadiene. The consistent finding in five epidemiological studies of workers occupationally exposed to butadiene is excess mortality from lymphohaematopoietic malignancy. This highly reproducible finding is noted despite methodological limitations in each of the published studies that tend to diminish the likelihood of observing an etiological association: (i) lack of detailed data on individual exposures to butadiene; and (ii) increasing longevity of many patients with lymphohaematopoietic malignancies, owing to treatment with modern therapeutic regimens, which results in their not being included in analysis of mortality. The observed excess in cancer mortality is most clearly evident in subpopulations heavily exposed to butadiene: production and maintenance workers as well as African-American workers. These epidemiological data strongly suggest an etiological association between exposure to butadiene and human cancer. The data amply fulfil all of Bradford Hill's criteria for causality. It is reasonable to conclude that there now exists convincing evidence for the carcinogenicity of butadiene to humans. Styrene. Epidemiological data on styrene suggest the possibility of an association with lymphohaematopoietic malignancy, although the finding has not been consistent. The most recent epidemiological study, an analysis of 35,000 European workers, suggests, however, an association between these malignancies and time elapsed since first occupational exposure to styrene. Preliminary data from a nested case-control study within the cohort also suggest an association with cumulative exposure to styrene. Although the current classification of the human carcinogenicity of styrene within the IARC Monographs programme appears to be reasonable, if the new findings are confirmed it may become necessary in the near future to revise the classification. Downgrading of the IARC classification is clearly contraindicated in light of current epidemiological and toxicological data.

Butadienes↗
PubMedDate not supplied

[Interference of acetone in styrene metabolism in subjects exposed to both solvents].

Thirty-seven workers exposed to styrene and acetone in fiberglass industry were monitored on Monday and Thursday for 8 hours (two subsequent samplings of 4 hours each) using passive dosimeters (mod. TK200). The charcoal disks of the passive dosimeters were analysed by gas-chromatography. Urine samples were collected at the end of the workshift and before the start of the workshift the next morning (Tuesday and Friday). Mandelic acid (MA) and phenylglyoxylic acid (PGA) were measured in the urine, using a HPLC method; values were expressed in mg/g of creatinine. The 8-h TWA exposure values ranged from 10 to 522 and 13 to 1581 mg/m3 on Monday and 8 to 423 and 10 to 579 mg/m3 on Thursday for styrene and acetone, respectively. Styrene TWA exposure values significantly correlated with the sum of metabolites at the end of workday (r = 0.72 on Monday and r = 0.91 on Thursday) and also the next morning (r = 0.88 on Tuesday and r = 0.85 on Friday). A calculated styrene exposure level of 213 mg/m3 (ACGIH-TLV) was associated with an excretion of metabolites (MA+PGA) higher on Thursday (814 mg/g creat.) than on Monday (600 mg/g creat.). The same observation was made on Friday (409 mg/g creat.) as compared with Tuesday (302 mg/g creat.). In conclusion, the TLV of styrene was associated with different values of metabolites at the beginning and at the end of the work-week. Moreover our data show that the simultaneous exposure to acetone does not modify the excretion of MA.

Acetone↗
PubMed1996

Color vision loss among styrene-exposed workers neurotoxicological threshold assessment.

Styrene represents nowadays one of the most used organic solvent. The current exposure limit proposed for this chemical differs significantly from country to country: the Threshold Limit Value-Time Weighted Average (TLV-TWA) proposed by the American Conference of Governmental Industrial Hygienists (ACGIH) is 50 ppm while the German, Finnish and Swedish occupational exposure limit is 20 ppm. Nevertheless, effects on the nervous system were recently reported in workers exposed at TWA styrene levels below the current TLV. Neuro-optic pathways have been shown to be particularly vulnerable to organic solvent exposure. Analysis and measurements of visual functions can provide important information on early neurotoxic effects. Previous studies support the hypothesis that styrene exposure can induce a dose-dependent color vision loss. The aim of this study is to assess a threshold level below which no detectable effect occurs for color vision. We applied a sub-application of the change point problem in two-phase regression considering one phase as a constant line. In accordance with this model the maximum-likelihood technique was used as a method to examine the dose- effect relationship between external styrene exposure and chromatic discrimination. The present article presents a joint analysis of data from two previously published studies, one carried out in Canada and the other in Italy. The age and seniority of the workers from both countries were remarkably similar, as were the process type, the chemicals used and the work-tasks of exposed subjects. The mathematical method presented here shows the existence of a statistically significant threshold. This finding shows that, in fiberglass-reinforced plastics industry, visual color impairment could be significantly detected above 4 ppm (upper limit of the confidence interval at 5% = 26 ppm). The exact clinical meaning of this effect, and also the progress of the impairment in exposed workers, is still to be assessed in further studies. The results of our study support the need of a reduction of the occupational limits for styrene in workplaces to values close to or lower than German, Finnish or Swedish exposure limits.

Adult↗
PubMed1996

Interaction of styrene and ethylmethylketone in the induction of cytochrome P450 enzymes in rat lung, kidney and liver after separate and combined inhalation exposures.

The present study compares the induction of different cytochrome P450 forms (CYP1A1/2, 2B1, 2E1) after pretreatment with styrene, ethylmethylketone separately or in combined exposures. Combined exposures lead to cumulative elevation of CYP levels, except for CYP1A1 and 2B1. Induction of CYP1A1 was higher in liver and kidney respectively and did not change significantly with the pretreatment mode. Styrene produced two times higher induction of CYP1A2 in the lung and kidney than ethylmethylketone. The simultaneous application of both inducers lead to significantly higher induction of CYP1A2 than that estimated after pretreatment with each of the inducers separately. CYP2B1 was induced by styrene to higher extent in the liver, where it was almost indetectable in controls. Major form of cytochrome P450 induced by styrene proved to be CYP2E1--about 3-fold induction of chlorzoxazone hydroxylation activity in the liver and 2.5 times in the lung. Ethylmethylketone significantly potentiated the CYP2E1 induction ability of styrene. This induction of CYP2E1-dependent catalytic activity correlates with the enzyme levels detected by immunoblotting.

Animals↗
PubMed1998

Effects of styrene exposure on middle latency auditory evoked potentials and glial cells in rat.

Neurophysiological and neurochemical effects of treatment with styrene at 400 mg/kg and 800 mg/kg per day for two weeks were investigated. Significant delay in latencies of No, Po, Na, and Pa components of middle latency auditory-evoked potentials (MAEPs) was observed in dose- and time-dependent manner after exposure. Moreover, the peak to peak intervals of No-Po, Po-Na, and Na-Pa components were also prolonged in the 800 mg/kg styrene-treated group compared with those in both the 400 mg/kg styrene-treated group and the control. However, no significant change of amplitudes was observed. Furthermore, brain tissue damage was examined by measuring the expression of glial fibrillary acidic protein (GFAP) immunocytochemistry using confocal laser scanning microscopy. Both styrene-treated groups had a marked increase of GFAP expression in cerebral cortex and hippocampus compared to those in the control group. These results of delay in the latency and the peak to peak interval of (MAEPs) components and increased expression of GFAP in cerebral cortex and hippocampus indicate that the effects of styrene on the central nervous system were not only in electrophysiological changes but also in the structure of cerebral cortex and hippocampus.

Animals↗
PubMed2003

Genetic polymorphism of drug-metabolizing enzymes and styrene-induced DNA damage.

A cross-sectional study was carried out on 48 workers exposed to styrene and 14 unexposed healthy controls in order to investigate the genotoxic potential of styrene exposure. DNA damage was assessed in peripheral blood leukocytes (WBCs) by the comet assay. Polymorphisms in glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and the gene encoding microsomal epoxide hydrolase (EPHX) were characterized to assess their possible modifying role in styrene metabolism and subsequent DNA damage. Exposed workers showed significantly higher levels of DNA damage compared to controls. Among workers, the GSTM1 and GSTT1 polymorphisms significantly affected comet parameters. Subjects bearing a GSTM1pos genotype showed a significantly higher proportion of damaged nuclei compared to people lacking GSTM1-1 expression (GSTM1null), whereas GSTT1pos workers showed significantly lower DNA damage than GSTT1null individuals. Styrene-7,8-oxide (SO)-induced DNA damage was assessed in vitro in WBCs isolated from the healthy controls. A clear dose-response relationship at micromolar doses of SO was found for the whole group. WBCs collected from subjects bearing the homozygous wildtype GSTP1 genotype showed a significant protection compared to cells from subjects bearing at least one GSTP1 variant allele. The field survey confirms that styrene exposure is associated with increased DNA damage and indicates a modulating role for GSTM1 and GSTT1 genotypes. In vitro experiments suggest that the extent of SO-induced DNA strand breaks depends, at least in part, on interindividual differences in GSH-conjugation capabilities.

Adult↗
PubMed2001

Effects of styrene monomer and trimer on gonadal sex differentiation of genetic males of the frog Rana rugosa.

To ascertain whether styrene monomer and trimer induce an estrogen-like effect, all-male tadpoles of Rana rugosa were exposed to dilute solutions of styrene monomer and trimer (2,4,6-tripfenyl-1-hexene) at concentrations of 0.1, 1, or 10 microM during days 19-23 after fertilization, which is the critical period of gonadal sex differentiation. As positive and vehicle controls, tadpoles were exposed to dilute solutions of estradiol-17beta at concentrations of 0.01, 0.1, or 1 microM and 0.01% ethanol, respectively, during the same period. The influence was estimated by examining the inner structure of the gonads of 40-day-old tadpoles. All the gonads of tadpoles in the vehicle and untreated controls showed histological characteristics of testes, whereas all those of tadpoles treated with 1 microM estradiol-17beta showed a structure typical for ovaries, having an ovarian sac and many meiotic germ cells. Of the genetically male tadpoles treated with styrene monomer and trimer, 97 and 96%, respectively, showed normal testicular structure of the gonads. In contrast, the remaining tadpoles had gonads showing coexistence of testicular and ovarian structure, irrespective of the strength of styrene concentration. These findings suggest that the styrene monomer and trimer induced a weak estrogen-like effect on the pathways of testicular differentiation in genetically male tadpoles.

Animals↗
PubMed1982

Human exposure to styrene. IV. Industrial hygiene investigations and biological monitoring in the polyester industry.

An industrial hygiene study of 10 glassfiber reinforced polyester plants (including 90 workers) was undertaken to investigate the styrene exposure in this industry and to estimate biological limit values (BLV's) for the urinary metabolites of styrene: mandelic (MA) and phenylglyoxylic acids (PGA). Time weighted average (TWA) styrene exposures were found ranging from 2 to 200 ppm. The urinary elimination of metabolites correlated well with exposure and the BLV's corresponding to an 8-h exposure at 100 ppm were consistent with earlier laboratory findings (end-of-shift sample: MA 1640, PGA 510, MA + PGA 2150; next-morning sample: MA 330, PGA 330, MA + PGA 660 mg/g creat.). Total metabolites (MA + PGA) in the next-morning sample or mandelic acid in the end-of-shift sample are recommended for routine monitoring of exposure to styrene. The study revealed the need for further research on how to reduce styrene exposure in this industry.

Air↗
PubMed1994

Intervention study on the influence of reduction of occupational exposure to styrene on sister chromatid exchanges in lymphocytes.

An intervention study was performed on 28 workers exposed by inhalation to styrene in the reinforced plastics industry and 20 controls not occupationally exposed to the compound. The workers involved were 14 laminators exposed to a time-weighted average of approximately 40 ppm styrene and 14 formers exposed to an average of about 10 ppm styrene. Ambient air monitoring data and the concentration of mandelic acid in the urine were used for the assessment of exposure. From each subject, peripheral blood lymphocytes were analysed for sister chromatid exchanges (SCEs). In the laminators, the mean SCE frequency was significantly higher than in the controls in both the group of smokers (9.59 +/- 0.77 SCEs/cell vs 7.23 +/- 1.00 SCEs/cell) and the group of non-smokers (10.25 +/- 1.08 SCEs/cell vs 5.98 +/- 0.60 SCEs/cell). The mean SCE frequency of the formers (7.42 +/- 128 SCEs/cell in smokers) did not differ statistically from the controls (7.23 +/- 1.00 SCEs/cell in smokers). No evaluation was made for non-smoking formers since all but one worker in this group were smokers. In order to comply with a lowering of the occupational exposure limit (MAK value) for occupational exposure to styrene in the Federal Republic of Germany from 100 ppm to 20 ppm, considerable technical and hygienic improvements were made at the work site of the laminators. This intervention led to a reduction of average exposure of these workers by inhalation from 40 ppm to approximately 20 ppm. One year after these improvements were made, a second investigation was performed. In all but one of the laminators, the concentration of mandelic acid in urine had dropped considerably. The SCE frequency in blood lymphocytes of the laminators had likewise dropped significantly to 7.74 +/- 0.59 SCEs/cell in the non-smokers. In the smokers, it was also lower than on the first occasion (9.02 +/- 1.19), yet statistical evaluation was not possible due to insufficient numbers. Overall, the results of the intervention study show that the lowering of the occupational exposure limit for styrene to 20 ppm in Germany was justified and that a reduction of occupational exposure to the chemical has led to a prevention of adverse cytogenetic effects.

Adult↗
PubMed1977

Effects of chronic styrene inhalation on rat brain protein metabolism.

Adult male rats were exposed to 7.9 mumol/1 (300 ppm) of styrene for 2--11 weeks 6 h daily excluding Saturdays and Sundays. The exposures caused a marked styrene accumulation in brain and perinephric fat, and the accumulation tended to increase upto the 4th week. The body styrene content decreased thereafter gradually towards the end of the experiment to reach half of the styrene content of the 4th week. Serum creatine kinase activity increased at the initial stage of the exposures while serum non-specific cholinesterase was below the control range at the same time. Earliest biochemical changes were detected at the 9th week of exposure, and they included increased activity of lysosomal acid proteinase. Increased enzyme activity prevailed to the end of the exposures. Simultaneous minor alterions could be detected in spinal cord axonal protein pattern whereas water-soluble protein composition in cerebellum did not change. Biochemical alterations in brain were not accompanied by significant changes in serum enzyme activities. It is concluded that marked metabolic adaptation to inhaled styrene takes place. Serum enzyme determinations may prove valuable in the adaptation period whereas they may not reflect beginning chronically neurotoxic effects.

Acetylcholinesterase↗
PubMed2006

Microbial degradation of styrene: biochemistry, molecular genetics, and perspectives for biotechnological applications.

Large quantities of the potentially toxic compound styrene are produced and used annually by the petrochemical and polymer-processing industries. It is as a direct consequence of this that significant volumes of styrene are released into the environment in both the liquid and the gaseous forms. Styrene and its metabolites are known to have serious negative effects on human health and therefore, strategies to prevent its release, remove it from the environment, and understand its route of degradation were the subject of much research. There are a large number of microbial genera capable of metabolizing styrene as a sole source of carbon and energy and therefore, the possibility of applying these organisms to bioremediation strategies was extensively investigated. From the multitude of biodegradation studies, the application of styrene-degrading organisms or single enzymes for the synthesis of value-added products such as epoxides has emerged.

Bacteria↗
PubMed1983

Chromosomal aberrations and sister-chromatid exchanges in workers exposed to styrene.

Few studies exist about chromosomal damage in workers occupationally exposed to styrene. In the present study, chromosomal aberrations and SCEs were analyzed from cultures of peripheral lymphocytes of workers employed in 6 different reinforced-plastics industries with styrene air exposure levels ranging from 30 to 400 mg/mc. A control group was selected on the base of sex, age and smoking habit. We examined 50-h cultures (for chromosomal-aberrations) and 72-h cultures (for SCEs) for each individual. All workers exposed to styrene, as compared with controls, showed significantly increased frequencies of chromosomal aberrations, while SCEs were significantly increased at 4 of the 6 plants. High SCE values appeared with styrene air concentrations higher than 200 mg/mc. Apart from the possible presence and role of other interfering chemicals in the various plants, chromosomal aberrations seem to be more sensitive than SCEs for the detection of chromosomal damage caused by exposure to low doses of styrene.

Chromosome Aberrations↗
PubMed2005

Characteristics of styrene degradation by Rhodococcus pyridinovorans isolated from a biofilter.

A novel strain (PYJ-1) of Rhodococcus pyridinovorans that was isolated from a biofilter was able to degrade styrene at a maximum rate of 0.16 mg (mg protein)(-1) h(-1) in batch culture at 97 mg l(-1) of initial styrene gas concentration. The optimum pH and temperature for styrene degradation were 7 and 32 degrees C, respectively. The degradation kinetic constants were obtained using substrate inhibition kinetics. In a perlite-packed biofilter the maximum styrene removal rate by the strain was 279 gm(-3)h(-1). Styrene removal in the biofilter was more sensitive to the temperature than in the batch culture.

Aluminum Oxide↗
PubMed2005

Real time monitoring of hazardous airborne chemicals: a styrene investigation.

The low level detection of air pollutants requires reliable sampling and calibration techniques, as well as using sophisticated analytical instrumentation. Incorporating these requirements into a mobile platform allows for accurate, curb side measurement of airborne ambient chemicals in real time. In this case study, air emissions from two manufacturing facilities in close proximity to each other were monitored with a mobile unit to chemically characterize and differentiate the emissions from each facility. Based upon the downwind fingerprinting and concentration levels, the mobile unit was able to isolate the source of the emissions to the responsible facility. A few chemicals which were detected by the TAGA had never been reported by the companies. Real time proximity monitoring was accomplished by using a triple quadrupole mass spectrometer (TAGA IIe). The TAGA IIe interfaces with a low pressure chemical ionization source that operates at 3 Torr and 100 microA. By monitoring the response of specific parent/daughter ion pairs, the TAGA IIe unit was able to determine the point-of-impingement concentrations of styrene and other ambient airborne chemicals. Positive identification and quantitation of styrene was accomplished by multiple measurements of the following ion pairs: 104/78, 104/77, 104/65 and 104/52. By optimizing various parameters of the TAGA IIe a method detection limit of 1.1 microg/m(3) was achieved for styrene. A daily multi-point calibration was performed using a liquid standard. The maximum half-hour average concentration of styrene measured downwind of the two facilities was 2300 microg/m(3) and the maximum instantaneous level was measured at 15,000 microg/m(3). The mobile capability of the unit was also utilized in determining the ambient airborne concentration of styrene at various distances from the companies with the maximum levels measured at close proximity to the emission sources.

Air Pollutants↗
PubMed2001

Association between genetic polymorphisms and biomarkers in styrene-exposed workers.

A comprehensive approach to evaluate genotoxic effects induced by styrene exposure was employed in 44 hand-lamination workers in comparison with 18 unexposed controls. The acquired data on single-strand breaks in DNA (SSBs), frequency of chromosomal aberrations and HPRT mutant frequency in peripheral blood lymphocytes were compared to the results on genotyping of some of the xenobiotic-metabolising enzymes (CYP1A1, CYP2E1, epoxide hydrolase and GSTM1, GSTP1 and GSTT1). Multifactorial regression analysis indicated that SSB in DNA were significantly associated with styrene exposure and with heterozygosity in CYP2E1 (5'-flanking region and intron 6; r(2)=0.614). The frequency of chromosomal aberrations (CA), as analysed by linear multiple regression analysis, significantly correlated with years of employment (P=0.004) and with combinations of epoxide hydrolase (EPHX) genotypes (exon 3, Tyr/His and exon 4, His/Arg), where individuals with low and medium activity EPHX genotypes exhibited higher frequencies of CA than those with high activity genotypes (P=0.044, r(2)=0.563). Moderately higher HPRT mutant frequencies were detected in styrene-exposed individuals (20.2 +/- 25.8 x 10(-6)) as compared to controls (13.3 +/- 6.3 x 10(-6)), but this difference was not significant. ANOVA (in the whole set of data) revealed that mutant frequencies at the HPRT gene were significantly associated with years of employment (F=6.9, P=0.0001), styrene in blood (F=10.1, P=0.0001), and heterozygosity in CYP2E1 (intron 6; F=13.5, P=0.0008) and GSTP1 (exon 5; F=3.6, P=0.038). In conclusion, our present data suggest that analysed biomarkers of DNA damage may be modulated by polymorphic CYP2E1, EPHX and GSTP1. In our study, styrene-specific DNA and haemoglobin adducts are under investigation. Completing these data with the results of genotyping of metabolising enzymes may provide a useful tool for individual genotoxic risk assessment.

Adult↗
PubMed2001

Assessment of styrene oligomers eluted from polystyrene-made food containers for estrogenic effects in in vitro assays.

Recently, several substances from among the huge numbers of chemicals used by mankind have been implicated as instigators of disrupted endocrine function and related human health problems. Polystyrene (PS) is one of the most frequently used resins in the world, and the styrene oligomer dissolved out from PS has been designated as a potential trigger of estrogen-like activity in the Wingspread Declaration and the Japan Environment Agency's SPEED98 [JEA (Japan Environment Agency) Strategic Problem on Environmental Endocrine Disruptors '98 (SPEED) '98), http://www.env.go.jp/en/pol/speed98/sp98.html]. In order to assess the endocrine disrupting effect of styrene oligomers, we tested one styrene monomer (SM), three styrene dimers (SDs) and seven styrene trimers (STs), newly isolated from optical isomers, known to dissolve in small amounts from cup noodle containers made of polystyrene by the estrogen receptor binding assay, luciferase reporter gene assay, and human breast cancer cell MCF-7 proliferation assay. In all three tests, none of the SM, SDs and STs showed any significant activity. Accordingly, we concluded that these substances have no estrogenic activity.

Animals↗
PubMed2003

Evaluation of styrene oligomers eluted from polystyrene for estrogenicity in estrogen receptor binding assay, reporter gene assay, and uterotrophic assay.

Styrene dimers (SDs) and styrene trimers (STs) eluted a little from polystyrene have been suspected of having estrogenic activity in the Wingspread Declaration [Our Stolen Futures, 1996] despite the lack of scientific analysis. Therefore, we have studied and reported styrene oligomers to have no endocrine disrupting effects [J. Food Hygienic Soc. Japan 40 (1999) 36; 41 (2000) 109; Yuki Goseikagaka Kyokaishi 57 (1999) 58; Bunseki Kagaku 49 (2000) 493, 857; Food Chem. Toxicol. 39 (2001) 1233; 40 (2002) 129]. However, Ohyama et al. reported that certain styrene oligomers have estrogenic effects in E-SCREEN and estrogen receptor (ER) binding assay [Environ. Health Perspect. 109 (2001) 699]. Recently, several assay systems have been developed, and a few of them can show false positive reactions at the high concentrations to which test compounds are precipitated [J. Health Sci. 48 (2002) 83]. In order to assess the estrogenic effect of SDs and STs in more detail, we examined the accuracy of the binding assay system and tested SDs and STs by three types of ER binding assay. In one ER binding assay, the same method that Ohyama et al. performed, SDs and STs showed a little estrogenic activity at high concentration; they did not dissolve, but this assay system tended to detect false positive effects at high concentration. In contrast, in the other assay systems, SDs and STs did not show any binding affinity to ER. In addition, luciferase reporter gene assay in HeLa cells transfected with ER expression plasmid and reporter plasmid, as a newly developed standard assay, and immature rat uterotrophic assay were conducted. In these tests, styrene oligomers showed no estrogenic activity.

Animals↗