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PubMed1988

Biological exposure index of styrene suggested by a physiologico-mathematical model.

We used a physiologico-mathematical model to study the biological exposure index of styrene correlated to the Threshold Limit Value (TLV) suggested by the ACGIH for 1986-87. This model allows the solvent concentrations in blood, alveolar air, fat tissue, and in other biological media to be estimated and simultaneously the kinetics of its metabolites to be followed when a specific exposure is settled. The comparison between the results obtained from the mathematical model and the numerous research projects documented in the literature suggests a reciprocal validation. Moreover, some biological parameters (particularly the alveolar ventilation) can explain the variability of results obtained from studies concerning the solvent pollution of the factories, which used biological monitoring. The ranges of styrene concentrations in blood and alveolar air and the urinary concentrations of its metabolites (mandelic and phenylglioxylic acids) are discussed in connection with the exposure at 215 mg/m3. Important differences correlated to the definition of set-levels of TLV and Biological Exposure Index (BEI) have been found: particularly the TLVs lead to different solvent uptakes according to some biological parameters; the BEI can better explain the individual solvent uptake and body burden.

Environmental Exposure↗
PubMed1989

Lack of nephrotoxicity of styrene at current TLV level (50 ppm).

Biochemical markers of kidney damage were examined in 37 female workers exposed to an average concentration of 225 mg/m3 of styrene. The concentration of mandelic acid in urine was on the average 759 mg/g creatinine. The mean duration of employment of the exposed subjects was 11 years. The results were compared to those obtained in 35 control female workers matched for age and a number of demographic and lifestyle factors and with no history of exposure to organic solvents. No difference was found in the urinary excretion of albumin, beta 2-microglobulin, retinol-binding protein, total proteins, glucose, lysozyme, lactate dehydrogenase and beta-N-acetyl-D-glucosaminidase. The present study provides thus further evidence that exposure to styrene at the current TLV (215 mg/m3) does not entail any detectable risk for the renal function.

Adult↗
PubMed1983

Human styrene exposure. V. Development of a model for biological monitoring.

The use of biological indicators to monitor workers' exposure to styrene requires a good understanding of the kinetics of the solvent in the organism. The absorption, distribution and elimination of styrene (STY), as well as the kinetics of formation and excretion of its metabolites (mandelic [MA] and phenylglyoxylic [PGA] acids) are simulated using a mathematical model. The results obtained compare well with experimental data for pulmonary (STY) and urinary (MA and PGA) excretion obtained during controlled human exposures. The model is then used to predict the behaviour of STY, MA and PGA during repeated occupational exposure. It is shown that the results are comparable to the data collected during field surveys in the polyester industry, if the level of physical activity of the workers is taken into account. This latter parameter appears to have a great influence on the urinary excretion of the metabolites. Based on the results obtained, biological limits of exposure are proposed (referenced to a TLV [threshold limit value] of 50 ppm) for MA and MA + PGA excretions in urine collected at the end of the shift (800 and 1000 mg/g creat.) and the next morning (150 and 300 mg/g creat.). Their validity is tested against experimental data obtained under field conditions.

Environmental Exposure↗
PubMed1993

Analysis and stability of phenylglyoxylic and mandelic acids in the urine of styrene-exposed people.

In this work a high-performance liquid chromatographic method is described that is reliable and practical for use in routine biological monitoring of exposure to styrene. The method uses a modern diode array detection technique by which mandelic and phenylglyoxylic acids can be measured simultaneously using different wavelengths. The liquid chromatographic method was compared to a gas chromatographic method developed for the analysis of mandelic, phenylglyoxylic and para-hydroxymandelic acids. The methods gave results consistent with each other. These two methods were then used to check the stability of the main metabolites of styrene, especially of phenylglyoxylic acid, in urine samples stored at +6 degrees C or at -18 degrees C for periods up to 70 days. None of the frozen samples showed any significant decrease in the phenylglyoxylic acid concentration, whereas at 6 degrees C one of the samples showed a reduction of 46% after 1 month.

Chromatography, Gas↗
PubMed1984

Molecular characterization of a plasmid from Pseudomonas fluorescens involved in styrene degradation.

In this paper evidence is given that in a strain of Pseudomonas fluorescens able to grow on styrene as the sole carbon source, the degradation pathway of styrene is inducible and plasmid dependent. The plasmid, which we have called pEG is self-transmissible between Pseudomonas strains and has a size of 37 kb. A restriction map has been constructed and evidence for an inducible transcription of two separate regions of the plasmid has been obtained.

Chromosome Mapping↗
PubMedDate not supplied

The neurobehavioral effects of chronic styrene exposure in the rat.

Groups of rats were exposed by inhalation to either clear air (controls) or styrene monomer (STY) at 350, 700 or 1400 ppm for 16 hr/day, 5 days/week for 18 weeks. At preselected intervals, animals were evaluated for changes in: 1) spontaneous activity, 2) grip-strength, 3) coordinated hindlimb movement, 4) performance on a discrete-trial two-choice visual discrimination task, and 5) peripheral nerve conduction velocity. Compared to controls, STY-treated rats showed a mild but somewhat inconsistent reduction in activity and gripstrength during the course of exposure. Coordinated movement and peripheral nerve conduction time were unaffected. With respect to discrimination performance, exposure on Day 1 produced marked deficits in response speed and accuracy. By Day 2, deficits in discrimination performance were reduced by greater than 50% and the performance of STY-treated rats continued to improve as exposure continued. Finally, during the last weeks of exposure, the performance of STY-treated rats was equivalent to that of controls and no styrene-related deficits could be measured in the postexposure period.

Animals↗
PubMedDate not supplied

Effects of toluene, styrene, trichloroethylene, and trichloroethane on the vestibulo-and opto-oculo motor system in rats.

The acute effects of inhalation of four solvents on the central vestibular system of rats were analyzed by recording eye movements upon different stimuli. The dose-response relationship was investigated. Optokinetic stimulation was obtained by placing the animals in front of a surrounding visual pattern, moving at different velocities. The slow-phase eye velocity (SPV) of nystagmus was calculated and divided by the stimulus velocity, giving the gain. All the solvents caused a decrease of the gain. Vestibular stimulation was performed on a turntable by an angular acceleration/deceleration in darkness. The SPV and the duration of the post-stimulatory nystagmus were calculated. The shape of the SPV dose-response curves differed among the four solvents. Toluene, styrene, and trichloroethylene prolonged the duration of nystagmus while trichloroethane did not. A conflicting vestibular and optokinetic stimulation was performed by an angular acceleration/deceleration with a surrounding visual pattern moving with the turntable. All solvents decreased the ability to cancel nystagmus, elicited by vestibular stimulation in conflict with a visual input. Quick movements of the eyes, saccades, were elicited by tactile stimulation. Toluene, styrene, and trichloroethylene changed the generation of the saccades while trichloroethane did not. Most of the findings indicate a common site of action in the central vestibular system, viz, the cerebellar-vestibular circuit. However, within this domain, there are evident differences in the effects among the solvents. This findings, together with previous results obtained in other experimental models of the central nervous system (CNS), suggest that different solvents should be considered as individual compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Excretion of N-acetyl-S-(1-phenyl-2-hydroxyethyl)-cysteine and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-cysteine in workers exposed to styrene.

Styrene (S) has been shown to be responsible for neurotoxic effects, including behavioural changes and neuroendocrine disturbances. The initial step of S metabolism is conversion to styrene 7,8-epoxide (SO), which is present in two enantiomeric forms [(R)(+)-SO and (S)(-)-SO]; this electrophilic intermediate is considered to be directly responsible for most toxic effects of S. The major urinary metabolites derived from the biotransformation of SO in man are mandelic acid (MA) and phenylglyoxylic acid (PGA). In rats an alternative pathway has been demonstrated, which involves the conjugation of SO to glutathione (GSH), leading to the excretion of two specific mercapturic acids, N-acetyl-S-(-(1-phenyl-2-hydroxyethyl)-cysteine [M1] and N-acetyl-S-(2-phenyl-2-hydroxy-ethyl)-cysteine [M2]; a close relationship has been found between exposure to S and urinary excretion of M1 and M2 in rats. As a consequence of the chiral nature of SO, both M1 and M2 consist of two diastereoisomers (M1-'R', M1-'S', M2-'R' and M2-'S'). Early reports have shown that the conversion of S to mercapturic acids is much lower in man (below 1% of the absorbed dose) than in rats (about 10%). We propose an analytical method for the determination of urinary M1 and M2 in man, which involves a urine clean-up by a chromatographic technique with a short reversed-phase pre-column; purified samples are then deacetylated with porcine acylase and deproteinized by centrifugal ultrafiltration. A derivatization is then performed with o-phthaldialdehyde and 2-mercaptoethanol and the fluorescent derivatives are separated on a reversed-phase analytical column. The mobile phase consists of acetate buffer and methanol mixed at variable proportions, the fluorescence detector is set at 330 nm (exc.) and 440 nm (em.). M1-'S' and M1-'R' are separated (retention times = 52.8 and 73.7 min, respectively) while the diastereoisomers of M2 coelute as a single peak at 70.5 min. The detection limit is about 7 micrograms/l, the coefficients of variation are below 7% and the error percentages are less than 6%. The method was applied to 25 urine samples from workers exposed to S: significant correlations were found between mercapturic acids and MA and PGA, the best correlation being between M2 and PGA (r = 0.79). Urine samples form unexposed subjects showed no detectable amounts of the analytes. A high stereoselectivity is shown by the enzymes involved in the metabolism of S to mercapturic acids: M1-'S', which derives from (S)-SO, is excreted in much higher amounts than M1-'R', which derives from (R)-SO.

Acetylcysteine↗
PubMed1997

The evidence for conjugated mandelic and phenylglyoxylic acids in the urine of rats dosed with styrene.

Male Wistar rats were dosed intraperitoneally with styrene (400 mg/kg). Urine samples were collected over phosphate buffer, pH 6.5 for 24 h. Excretion of mandelic (MA) and phenylglyoxylic acid (PGA) amounted to 1.66 +/- 0.62 and 5.21 +/- 2.44% of dose, respectively, as determined by ion-pair HPLC. After acidic hydrolysis, the amount of MA and PGA found in urine increased to 2.10 +/- 0.84 and 6.81 +/- 3.20% (mean +/- S.D.; n = 7), respectively. A similar increase was observed after alkaline hydrolysis of urine samples. Differences between hydrolysed and non-hydrolysed samples were significant in the paired t-test (P < 0.05). Further, urine samples were fractionated by HPLC. Fractions were subjected to acidic hydrolysis and analysed by HPLC and GC/MS. Both MA and PGA were detected in the fraction which did not contain any of these metabolites before hydrolytic treatment. Thus, MA and PGA, which are used as biomarkers of exposure to styrene, form hydrolysable conjugates in the rat. At least a minor part of the total urinary MA and PGA is bound in these conjugates.

Animals↗
PubMed1986

The effect of aerosol on estimates of inhalation exposure to airborne styrene.

Exposure to volatile organic contaminants usually is attributed to vapors alone; samples are collected on charcoal tubes or by passive dosimeters. This study demonstrated that aerosols, generated during the spraying of polyester resin solution, can contribute significantly to the exposure to volatile organic contaminants. Four spraying experiments were performed during which 64 samples were collected and analyzed to determine the styrene air concentrations. The results from the four spraying experiments showed that aerosols represented 30% +/- 3% of the total air concentration of styrene. The contribution of aerosols to inhalation exposure needs to be considered in other industrial situations where spray processes are used.

Aerosols↗
PubMed1993

Covalent binding of styrene to DNA in rat and mouse.

Covalent binding of [7-3H]styrene (S) to DNA in vivo was measured and evaluated in a quantitative manner in order to investigate whether DNA adduct formation could form a mechanistic basis for tumor induction in a carcinogenicity bioassay. [7-3H]S was administered by inhalation in a closed chamber to male and female CD rats and B6C3F1 mice. After 4.5-6 h (rats) and 6-9 h (pools of four mice), S doses of 23-39 and 85-110 mg/kg respectively had been metabolized. DNA was purified to constant specific radioactivity which was measurable in all samples. DNA was enzymatically degraded to the 3'-nucleotides which were separated by HPLC for the detection of radiolabeled nucleotide-S adducts. The fractions with the normal nucleotides contained most of the radioactivity. In mouse liver DNA, a minute but significant level of adduct radioactivity was also detected. In the units of the Covalent Binding Index CBI = (mumol adduct/mol DNA nucleotide)/(mmol chemical/kg body wt), values of 0.05-0.09 and 0.07-0.18 were calculated for males and females respectively. In the rat, no DNA adducts were detectable in the liver at a limit of detection of 0.1 CBI units. Two of the four lung samples of the female rats showed adduct-related radioactivity corresponding to 0.07 CBI units. The CBI values are compatible with styrene 7,8-oxide as the reactive intermediate. The data are compared with CBI values and carcinogenic potencies of established genotoxic carcinogens. It is concluded that the DNA-binding potency of S is so low that significant tumor induction in a standard bioassay for carcinogenicity is unlikely to be due to DNA adduct formation alone. Consequences for a human risk estimation are discussed.

Animals↗
PubMed1997

Lymphohematopoietic cancers and butadiene and styrene exposure in synthetic rubber manufacture.

The described nested case-control study of lymphohematopoietic cancers occurring in a cohort of synthetic rubber production workers was conducted to determine the associations of these cancers with exposure to butadiene and styrene. Cases have been confirmed through hospital record review of 95 percent of the cancers. Exposures are based on measured values of the two chemicals from personal monitoring data in seven of the eight plants under study. The results indicate that the risk of leukemia increases with exposure to a time-weighted average butadiene measure. The odds ratio at only 1 ppm average butadiene exposure is 1.50 (95% CI 1.07, 2.10). Work in specific areas also contributes to the risk, possibly because these areas have not been completely characterized for differences in butadiene exposure. Hodgkins disease is also associated with butadiene exposure. Multiple myeloma, lymphosarcoma, and all lymphomas are associated with exposure to styrene. Since workers in this industry are apparently exposed to two carcinogenic agents, further effort must be made to distinguish the exposures to each chemical over time and to characterize their interrelationship with the risk of cancers of the lymphohematopoietic system.

Butadienes↗
PubMed1986

Choice reaction time in workers exposed to styrene vapour.

Behavioural effects of occupational exposure to vapour from styrene-based resin were investigated in 10 female workers with a portable test of choice reaction time. Testing was carried out both at the beginning and end of the day's shift. Uptake and metabolism of styrene were assessed by monitoring post-shift urinary mandelic acid excretion rates. By using these data workers were allocated to three groups reflecting zero, low or high exposure. After exposure slowing of reaction times was found in those with the highest mandelic acid excretion rates, whereas a slight improvement or no change was found in those with low or zero exposure. Subsequent improvements in extraction and ventilation in the workroom were shown to be associated with both decreased mandelic acid excretion and absence of long reaction times in those previously most heavily exposed.

Air Pollutants, Occupational↗
PubMed1993

Use of the glycophorin A human mutation assay to study workers exposed to styrene.

The glycophorin A (GPA) assay is a human mutation assay that is potentially useful for large epidemiological studies. The assay is rapid and requires a minimal amount of blood, which can be stored before analysis. The data presented here were collected from workers exposed to styrene in a boat manufacturing plant. This study was the first to apply the GPA assay to an occupationally exposed population. Subjects with a mean styrene exposure of 30 ppm had a higher frequency of GPA N phi variant cells than subjects with mean exposure of 1 ppm, but the subjects differed in respect to smoking and age distribution. Results indicate that the original 1-W-1 version of the assay may not be suitable for studies of small numbers of exposed subjects due to variability and artifacts. The newer BR6 version, however, has much lower variability and shows promise for use in the occupational setting.

Evaluation Studies as Topic↗
PubMed1986

Behavioral technology for reducing occupational exposures to styrene.

We conducted a test of the usefulness of behavioral methods to control occupational health problems by reducing workers' exposures to toxic chemicals. Four plastics workers were trained in nine behaviors selected for potential to reduce their exposures to styrene, a common chemical with multiple toxic effects. Behavioral measures indicated that the workers quickly came to emit most of the behaviors. Measures of air samples indicated that large decreases in exposures to styrene accompanied the changes in behaviors for the three workers who had been selected because they most needed relief from their exposures and because they had opportunities to control their exposures by the ways they behaved.

Behavior Therapy↗
PubMed1997

Determination of specific mercapturic acids as an index of exposure to environmental benzene, toluene, and styrene.

Methods were developed for the determination of urinary phenylmercapturic acid (PMA), a metabolite specific for benzene, benzylmercapturic acid (BMA), a metabolite of toluene and phenylhydroxyethylmercapturic acids (PHEMAs), specific for styrene, in human beings. Methods involved sample clean up followed by deacetylation and derivatization of the compounds with o-phthaldialdehyde and 2-mercaptoethanol. The fluorescent derivatives were separated on reversed-phase columns with gradient runs and detected by a fluorescence detector. The detection limits were 0.5 microgram/l for PMA and BMA, and 7 micrograms/l for PHEMAs. The background levels of PMA were higher in smokers than in nonsmokers, while no difference was found in the levels of BMA and PHEMAs. Coexposure to ethanol enanched the excretion of BMA in subjects experimentally exposed to toluene. Correlations were found between environmental benzene (r = 0.74, log transformed data), toluene (r = 0.74) or styrene (r = 0.56) and specific mercapturic acids in workers. The usefulness of PMA, BMA and PHEMAs as biomarkers is critically evaluated.

Acetylcysteine↗
PubMed1993

Immunomodulation due to coexposure to styrene and dioctyl phthalate in mice.

Pathomorphological and immunological alterations caused by a mixture of styrene and dioctyl phthalate were studied in albino mice following oral administration of 0.02, 0.03, 0.05 x LD50 of the mixture. The chemicals were mixed together proportionate to their respective LD50 values and fed in ground nut oil, 5 d/wk for 4 weeks. Histological examination of spleen revealed considerable depletion of cellular population of lymphoid follicles which corresponded to the dose dependent decrease in splenic mononuclear cell population count. The thymic lobules revealed slight atrophy but accompanied by a significant increase in thymocyte population. Correspondingly few significant histological changes were observed in mesenteric and peripheral lymph nodes. The treatment caused impairment of primary humoral immune response to SRBC (IgM) but there was a significant increase in response of splenocytes to B-cell mitogen LPS. There was a suppression of cutaneous delayed type hypersensitivity and increase in splenic lymphocyte response to T-cell mitogen PHA. Simultaneously, indirect immunity represented by decreased phagocytosis and enhanced metabolic function of reducing NBT by peritoneal exudate cells was observed. The in vitro exposure of vero cells to the mixture caused dose dependent protective effect. The results of present study indicate that subchronic exposure to low doses of mixture of styrene and dioctyl phthalate under certain conditions may modulate some of the immune functions as compared to exposure to either chemicals alone.

Adjuvants, Immunologic↗