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PubMed1975

Metabolism and toxicity of styrene.

The absorption, blood levels, distribution, excretion, and biotransformation of styrene in man and experimental animals are briefly reviewed. The acute toxicity of styrene appears to be unrelated to its biotransformation. Reports of organ toxicity upon chronic exposure to styrene are rare; however, since the chief intermediate in styrene metabolism is an epoxide, hepatotoxicity due to covalent binding at the site of formation appears to be a possibility.

Animals↗

PubMed2005

Human neurobehavioral effects of long-term exposure to styrene: a meta-analysis.

Many reports in the literature suggest that long-term exposure to styrene may exert a variety of effects on the nervous system, including increased choice reaction time and decreased performance of color discrimination and color arrangement tasks. Sufficient information exists to perform a meta-analysis of these observations quantifying the relationships between exposure (estimated from biomarkers) and effects on two measures of central nervous system function: reaction time and color vision. To perform the meta-analysis, we pooled data into a single database for each end point. End-point data were transformed to a common metric of effect magnitude (percentage of baseline). We estimated styrene concentration from biomarkers of exposure and fitted linear least-squares equations to the pooled data to produce dose-effect relationships. Statistically significant relationships were demonstrated between cumulative styrene exposure and increased choice reaction time as well as increased color confusion index. Eight work-years of exposure to 20 ppm styrene was estimated to produce a 6.5% increase in choice reaction time, which has been shown to significantly increase the probability of automobile accidents. The same exposure history was predicted to increase the color confusion index as much as 1.7 additional years of age in men.

Accidents, Traffic↗

PubMed1976

Quantitative analysis of styrene monomer in polystyrene and foods including some preliminary studies of the uptake and pharmacodynamics of the monomer in rats.

A variety of food containers, drinking cups and cutlery, fabricated from polystyrene (PS) or polystyrene-related plastic, were analyzed for their styrene monomer content. Samples of yogurt, packaged in PS cups, were similarly analyzed and the leaching of styrene monomer from PS containers by some food simulants was also determined. Blood level studies with rats, dosed with styrene monomer by various routes, illustrated uptake phenomena that were dependent on the dose and route of administration and were also affected by the vehicle used to convey the styrene monomer.

Animals↗

PubMed1990

Toxicity of styrene vapor in hepatocyte monolayers at low oxygen tensions.

Hepatocyte monolayer cultures were exposed to 6000 ppm styrene vapor at 20%, 2%, or 1% O2 and assayed for signs of cell damage immediately following the 2-hr exposure and then 24 hr later. Oxygen concentrations were used that were previously shown to maximize lipid peroxidation and to predispose hepatocyte monolayers to chemical injury. The use of two time points allowed assessment of acute injury as well as injury that requires several hours to manifest itself. The uptake of styrene into the buffer in the culture dishes was measured by gas chromatography and was found to be 0.49, 0.68, and 0.74 mM at 15, 60, and 120 min, respectively. However, as measured by release of aspartate aminotransferase and inclusion of trypan blue, no toxicity was evident at either time point, irrespective of the oxygen concentration. This study shows that despite the weakening of hepatocyte defense mechanisms by hypoxia, styrene is not acutely toxic to these cells. Furthermore, if any damage to DNA, RNA, or the capability for protein synthesis occurs during exposure to styrene, it is insufficient to cause lysis within 24 hr.

Animals↗

PubMed2003

Styrene hepatotoxicity in rats treated by inhalation or intraperitoneally: a structural investigation.

The purpose of this study was to investigate the toxicity of styrene in the liver of adult rats treated either by inhalation of styrene vapour (300 ppm, 6 h/d, 5 d/wk, for 2 wk) or intraperitoneally with different styrene doses (4, 40, 400 mg/Kg) for 3 consecutive days. Using a light microscope, some alterations of liver parenchyma and sinusoid dilation were noticed, more marked in the group treated with the intraperitoneal administration of the chemical. Using an electron microscope, some additional changes were observed (once again, more marked in the latter group of rats): a) an increase in the content of lipids inside hepatocytes, and b) the rise of intracytoplasmic, intercellular and perisinusoidal collagen fibres. Therefore, cell damage and functional disturbance of sinusoids due to perisinusoidal fibrosis are apparent in the liver of both groups of rats exposed to styrene treatment, but these changes are definitely more significant in those subjected to intraperitoneal administration.

Administration, Inhalation↗

PubMed2000

Impairment of neurobehavioral function and color vision loss among workers exposed to low concentration of styrene--a review of literatures.

Recently many studies on the health effects of workers who exposed to low-concentration styrene have been published. In this paper firstly we mentioned the reasons why nervous system was critical organ for evaluating the toxicity of organic solvents both in the acute and chronic exposure phases. Then we indicated how neurobehavioral test batteries were useful to detect subclinical adverse health effects of workers exposed to organic solvents. Secondly we reviewed many epidemiological studies on the impairment of neurobehavioral function, i.e., perceptual speed, memory, cognition, personality and mood, and the loss of color vision among styrene workers. Finally, we showed our recent data on the relationship between color vision loss and the concentration of urine metabolites among styrene workers. It can conclude that styrene may cause damage on nervous system, even at the low exposure level such as 50 ppm which used to be the Threshold Limit Value (TLV) recommended by Japan Society for Occupational Health (until 1999) and American Conference of Industrial Hygienists (until 1997).

Affect↗

PubMed1980

Phenaceturic acid, a new urinary metabolite of styrene in the rat.

1. After administration of styrene to rat, phenaceturic acid, a new metabolite, was isolated. After administration of d8-styrene to rat, deuterium-labelled phenaceturic acid was excreted in the urine. 2. Two metabolic pathways are proposed, based on mass spectra of the deuterium-labelled phenaceturic acid. 3. After a single dose of styrene (250 mg/kg), the excreted phenaceturic acid originating from styrene in the urine amounted to 1.4% dose.

Animals↗

PubMed1998

Preparation and analysis of styrene oligomers containing migrates from various polystyrenes used in food packaging.

An oligostyrene-like product (F2L5250) was reported to have estrogen-like activity (statistically significant increases in means for absolute uterine weight and the ratios of the uterine weight to terminal body weight) in juvenile female rats provided a dietary concentration of 100 ppm F2L5250 for four consecutive days. The highest no-effect-level (NOEL) for estrogenic activity was 80 ppm in the diet, corresponding to a daily intake of 13.3 mg F2L5250/kg. Although it is unlikely that such estrogenic tetramers would occur in commercial polystyrene, the Styrene Steering Committee (SSC) of the European Chemical Industry Council (CEFIC) sponsored the current extensive project to address any concern that human consumption of styrene oligomers migrating from polystyrene containers into food, e.g., from packaged yoghurt, or from the use of EPS coffee cups and related products, might affect human health. To ensure confidentiality and compliance with the highest scientific and regulatory standards, the entire project was conducted without knowledge of the oligomer migrates tested, and all activities were managed and audited under a contract between the SSC and a third party, Argus International. This paper describes the preparation and analyses of the 23 representative polystyrenes [9 general purpose polystyrenes (GPPS), 8 high impact polystyrenes (HIPS) and 6 expandable polystyrenes (EPS)] evaluated for estrogenicity in an in vivo uterotrophic assay in immature female rats. The polystyrene samples were chosen to represent food packaging applications. They were obtained from participating European Polystyrene Manufacturers, coded at the TNO Nutrition and Food Research Institute, Utrecht, The Netherlands (TNO) and sent to BASF, Ludwigshafen, Germany for preparation of test bars (GPPS and HIPS) or test foam parts (EPS). The prepared polystyrene test bars or test foam parts were submitted to elution with 50% aqueous (v/v) ethanol for 10 days at 40 degrees C, a procedure which simulates an exposure at ambient temperature for several weeks and represents an exaggeration in comparison with yogurt, for which directive 85/572/EEC1 defines 3% aqueous acetic acid as the official food simulant. To further exaggerate the potential concentration of the possible migrates, the surface/volume ratio selected for elution was the maximum experimentally possible, i.e., approximately 56 dm2/kg food for the GPPS and HIPS bars and approximately 38 dm2/kg food for the EPS foam, representing a multiple of approximately 9 (GPPS and HIPS) and 6 (EPS), times the conventional surface/volume ratio of 6 dm2/kg. These obtained styrene oligomer migrates were then diluted to 25% aqueous (v/v) ethanol, a concentration that could be tolerated by the test animals. After dilution, the low and high concentrations represented multiples of 0.5 and 4.6 (GPPS and HIPS) and 0.5 and 3.2 (EPS) the conventional surface/volume ratio, respectively. These levels simulated daily human consumption of 500 or 5,000 g of food for the GPPS and HIPS samples and of 500 or 3,150 g of food for the EPS samples, respectively. The results of the homogeneity, stability and concentration analyses of the styrene dimers and trimers in the migrates indicated that the concentrations of migrants were highest as the result of 50% aqueous ethanol extraction of HIPS test bars followed by GPPS test bars and EPS test foam parts.

Animals↗

PubMed1996

Clonal chromosome aberrations in myeloid leukemia after styrene exposure.

OBJECTIVES: The purpose of the study was to determine the risk of myeloid leukemia subclassified according to clonal chromosome aberrations in styrene-exposed workers. METHODS: A nested case-referent study was carried out on 19 myeloid leukemia patients, of which 12 showed clonal chromosome aberrations, and 57 referents ascertained within the Danish reinforced plastics industry and similar industries with no styrene exposure. RESULTS: A 2.5-fold increased risk for myeloid leukemia with clonal chromosome aberrations (95% confidence interval 0.2-25.0) was found among workers of companies with styrene exposure. CONCLUSIONS: The results suggest that styrene may cause leukemia through a clastogenic effect. But similar findings could also have been found if the exposure was associated with a specific subtype of leukemia prone to develop the chromosome aberrations in question. Due to the few observations and the lack of detailed exposure data, additional studies are needed to corroborate or refute the present suggestive findings.

Adult↗

PubMed1985

Mortality of styrene production, polymerization and processing workers at a site in northwest England.

The mortality of 622 men who worked for at least one year in the production, polymerization, and processing of styrene at a chemical site in the United Kingdom during the period 1945-1974 was surveyed up to the end of 1978; 3 072 male manual workers at the same site but unexposed to styrene were also studied. A statistically significant excess of lymphoma deaths was found in the exposed population, and two of the three deaths observed occurred in men less than 40 years of age. The small number of deaths and the lack of any evidence for an association with duration or level of exposure to styrene are reasons for interpreting this result cautiously. However, the otherwise normal pattern of mortality in the exposed population and the absence of any excess of lymphomas in the reference group lend some support to suggestions that exposure to styrene may be associated with lymphomas in man. An analysis of cancer registrations for the exposed population revealed no further cases of lymphoma but identified one case of lymphatic leukemia. An excess of laryngeal cancer registrations was found. As this effect has not been previously postulated and because of the small number of registrations, too much weight should not be attached to this one observation.

Adult↗

PubMed1984

Neuroendocrine effects of styrene on occupationally exposed workers.

The serum levels of prolactin (PRL), human growth hormone (HGH), thyroid-stimulating hormone (TSH), and the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured in 30 females exposed to about 130 (range 65-300) ppm of styrene in the air and in 30 age-matched referents to show whether styrene exposure influences the dopaminergic tuberoinfundibular system (TIDA). The exposed subjects' serum levels of PRL were more than double the reference values and were significantly related to the urinary excretion of styrene metabolites, ie, to the sum of mandelic acid (MA) and phenylglyoxylic acid (PGA) in the "next-morning" urine spot sample. Such a relationship still proved to be statistically significant after the removal of the effects of age and duration of exposure with the method of partial correlation. The serum concentrations of HGH in the exposed workers were also higher than in the reference group. Though within the reference levels, the TSH values of the exposed subjects were significantly related to the urinary excretion of MA and PGA. These results are consistent with the dose-dependent depletion in tuberoinfundibular dopamine after experimental styrene exposure of rabbits.

Adult↗

PubMed1980

Study of some hepatic effects (induction and toxicity) caused by occupational exposure to styrene in the polyester industry.

This study describes an occupational health survey carried out in the polyester industry in order to investigate the hepatic effects caused by exposure to styrene. Fifty-seven workers underwent a medical examination. They were submitted to blood and urine sampling for the determination of the degree of exposure, by the analysis of urinary mandelic and phenylglyoxylic acids (styrene metabolites), and the intensity of induction and/or hepatic effects, by the analysis of urinary glucaric acid and plasma enzyme activities (gamma glutamyl transferase, ornithine carbamoyl transferase, alanine aminotransferase, and aspartate aminotransferase). The results showed that styrene does not give rise to measurable autoinduction. With regard to the hepatic tests, exposure to styrene caused an increase in the plasma enzyme activities, a phenomenon illustrating a possible damaging effect on liver cells. This effect appears with exposure below 100 ppm (time-weighted average).

Adult↗

PubMed1978

Exposure-response relationship between styrene exposure and central nervous functions.

For the study of the relationship between styrene exposure and symptoms and signs of central nervous dysfunctions, 98 male workers occupationally exposed to styrene were given clinical, neurophysiological and psychological examinations; also a symptom survey was made. Urinary mandelic acid concentrations, measured once a week during five consecutive weeks, were used to express the exposure intensity. Different unexposed groups were used for reference. No exposure-response relationship was observed between symptoms of ill health and the urinary mandelic acid concentration, although the exposed group as a whole expressed significantly more symptoms than the reference group. The occurrence of abnormal electroencephalograms was about 10% in the group of workers with mandelic acid concentrations below 700 mg/l, but it was 30% among those whose mandelic acid concentration exceeded 700 mg/l, a level corresponding to the 8-h time-weighted average (TWA) of styrene exposure of about 30 ppm. With regard to psychological functions, the first change in visuomotor accuracy became discernible when the urinary mandelic acid concentration exceeded 800 mg/l. A more pronounced decrement appeared in both visuomotor accuracy and psychomotor performance when the mandelic acid concentration exceeded 1,200 mg/l, which corresponds to an 8-h TWA of styrene exposure of about 55 ppm.

Adolescent↗

PubMed2003

[A study on biomarkers of styrene].

OBJECTIVE: To study the biomarkers of styrene and to provide theoretical basis for bio-monitoring of styrene. METHODS: Urinary mandalic acid (MA), phenylglyoxalic acid (PGA) and mercapturic acid (MUA) of styrene were examined by high performance liquid chromatography (HPLC). RESULTS: The correlation regression equations between exposure dose and MA, PGA and MUA level in morning urinary samples were: ŷ = 2.58x + 70.82; ŷ = 1.66x + 37.42; ŷ = 0.05x + 0.55 respectively. The correlation regression equations between exposure dose and MA, PGA and MUA level in post-shift urinary samples were: ŷ = 1.85x + 89.02; ŷ = 1.33x + 4.32; ŷ = 0.04x + 0.68 respectively. All showed close dose-response relationship. CONCLUSIONS: The level of MA, PGA and MUA in morning or post-shift urinary samples may be used as bio-monitoring indexes of styrene.

Acetylcysteine↗

PubMed1986

[Changes in the peripheral blood of workers engaged in ethylbenzene-styrene and synthetic rubber and latex manufacture].

A total of 67 workers were examined from the production of "Ethyl benzene-styrene" and 184 workers from the production of "Synthetic rubber and latex", as well as a control group of 59 employees. The workers from the first production are exposed to the effect of styrene, ethyl benzene and toluene. The concentrations of the substances surpass MAC, with several times, at the majority of the working places. The workers with a length of service over 10 years predominate. The workers from the second production are exposed to the combined effect of styrene and divinyl, their concentrations fluctuating from 2 to 8 times over MAC. The workers with a length of service over 10 years are 71.7%. The deviations, established in the hematological indices studied are compared with the results from a study on the workers from those productions of 6 years ago. Dynamics in the changes was established among the workers from the production of "Synthetic rubber and latex", associated with the duration of occupational exposure to styrene and divinyl. In case of a shorter length of service, the deviations are functional (reduction of peroxidase activity in granulocytes), increase of hemoglobin and hematocrit, associated with the adaptive reaction of organism. Pronounced anemic syndrome was established in a considerable number (24 workers) after an exposure of 10 years as well as lymphocytosis (35 subjects) and leukopenia (9 subjects).

Absenteeism↗

PubMed1983

Antipyrine clearance during occupational exposure to styrene.

Animal experiments have indicated that styrene, which is a widely used organic solvent, may induce the microsomal enzyme function of the liver. Thirteen workers with long-term exposure to styrene in a polyester plant were investigated. They worked at air concentrations about the maximal allowed time-weighted average concentration of styrene in most Western countries (50 ppm). The clearance of antipyrine was determined from saliva concentrations before and after three weeks free of exposure and then again three weeks after returning to work. Thirteen matched controls were investigated with similar intervals and methods. No significant differences were found between the half life, apparent volume of distribution, or clearance of antipyrine either within the groups or between the groups. The data exclude (95% confidence limit) the possibility that occupational exposure to styrene at concentrations about 50 ppm stimulates the microsomal enzyme function of the liver to a degree compatible with an increase in antipyrine clearance of more than 2 ml x min-1 (3%). While the first antipyrine estimation was carried out under medical supervision, the workers themselves managed to perform the antipyrine test correctly after verbal and written instructions. This has broadened the application of the antipyrine test.

Adolescent↗

PubMed1982

[Prognosis and determination of the threshold of chronic effect of carbon disulfide and styrene].

Two series of studies were carried out: I--in workers exposed to four different mean annual CS2 concentrations--6 mg/m3; 12 mg/m3; 51 mg/m3 and 247 mg/m3 and II series-in workers exposed to three styrene concentrations--I mg/m3; 40 mg/m3 and 400 mg/m3. The results obtained in series I show the role of the primary toxic effect (inhibition of oxidases with mixed function) and of the adaptation reactions to it with a view to accurate specifying the threshold of chronic CS2 effect. The mathematical expression of the correlation between styrene concentration in air and blood, of phenyl-glyoxylic and mandelic acid in the urine of the exposed subjects enables the prognosis that the threshold of the noxious styrene effect is within the range of 150 mg/m3 to 250 mg/m3. A reduction on CS2 MAC is proposed--from 10 mg/m3 to I mg/m3 and the correction of styrene MAC--from 5 mg/m3 to 30-50 mg/m3.

Adult↗

PubMed1997

Synthesis and antimicrobial activity of beta-[(2-benzimidazolyl)thio]-beta-benzoyl styrene derivatives.

In this study some new beta-[(2-benzimidazolyl)thio]-beta-benzoyl styrene derivatives have been synthesized by reacting 2-(phenacetylthio)benzimidazole and substituted benzaldehydes in piperidine/dry benzene. Structures were verified by microanalysis, IR and NMR spectral analysis. Antimicrobial activities of the compounds were investigated by the microdilution susceptibility test; Muller-Hinton Broth and Sabouraud Dextrose Broth were used for the determination of antibacterial and antifungal activity. Test organisms: Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 as Gram (+) bacteria, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATTC 27853 as Gram (-) bacteria, and Candida albicans, Candida pseudotropicalis, Candida parapsilosis and Candida stellatoidea as yeast-like fungi. All the compounds showed good antimicrobial effect, especially against gram (+) bacteria. Among the compounds tested beta-[(2-benzimidazolyl)thio]-beta-benzoyl-4-chloro styrene (compound 9), beta-[(2-benzimidazolyl)thio]-beta-benzoyl-4-nitro styrene (compound 10) and beta-[(2-benzimidazolyl)thio]-beta-benzoyl-4-acetylamino styrene (compound 11) showed the most favorable activity.

Anti-Bacterial Agents↗