Urinary Styrene Research Articles

Inter- and intra-individual sources of variation in levels of urinary styrene metabolites.

Given the paucity of studies that have examined variability in biological measures of exposure to workplace contaminants, we quantified the intra- and inter-individual sources of variation in urinary levels of mandelic acid (MA) and phenylglyoxylic acid (PGA) among workers exposed to styrene. A secondary objective was to examine effects of job task and the timing of sampling during the workweek on the variation in workers' urinary styrene metabolite levels. As part of routine biological monitoring, a total of 1,714 measurements of MA and PGA collected from 331 workers between 1985 and 1999 from eight reinforced-plastics plants were abstracted from laboratory reports. To evaluate sources of variation in levels of urinary styrene metabolites, we applied random-effects models. The influence of job task and day of sampling on metabolite levels was examined using mixed-effects models. PGA levels were characterized by less variation than levels of MA, as were metabolite levels expressed in terms of urinary creatinine concentration. The relative magnitude of the inter-individual to the intra-individual source of variation was generally higher for post-shift urine samples than for pre-shift urine samples. As expected, urinary metabolite levels were highest for laminators and for samples collected at the latter end of the workweek. Owing to the effects of variation from day-to-day, estimates of workers' exposures that rely on single measurements would generally perform poorly in a regression analysis designed to examine effects resulting from chronic exposure. However, the bias in an observed slope coefficient would be diminished if a second or third urine sample were collected. Quantification of the intra- and inter-individual sources of variation provides useful information that can be used to design optimal sampling strategies, which would allow for the collection of sufficient data to estimate workers' exposures reliably when evaluating health risks associated with occupational contaminants.

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

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

Time to pregnancy among male workers of the reinforced plastics industry in Denmark, Italy and The Netherlands. ASCLEPIOS.

The relationship between occupational styrene exposure and male fecundity was examined. Among 1560 Danish, Italian, and Dutch reinforced plastics workers, 220 styrene-exposed workers and 382 unexposed referents who had fathered a child were identified. A total of 768 historical styrene measurements conducted in 1970-1996 in the study companies formed the basis for semiquantitative exposure assessment in combination with measurements of urinary styrene metabolite levels. All the subjects were interviewed about work conditions and other factors potentially related to reduced fecundity. Fecundity was measured as the reported time to pregnancy (number of months a couple needed to conceive their youngest child). A statistically nonsignificantly reduced fecundity was observed for the styrene-exposed workers [fecundity ratio 0.79, 95% confidence interval (95% CI) 0.59-1.05]. But no consistent pattern of a detrimental effect on fecundity was found when time to pregnancy was related to worktasks indicating higher styrene exposure levels or semiquantitative or quantitative measures of styrene exposure. The workers with high exposure showed a fecundity ratio of 1.09 (95% CI 0.69-1.72). It is unlikely that styrene exposure has a strong effect on male fecundity.

Purge-and-trap gas chromatographic determination of styrene in urine and blood: Application to exposed workers

A simple purge-and-trap gas chromatographic method with flame ionization detection was developed for the determination of styrene in urine and blood. Styrene present in a 5 ml sample at room temperature was swept by helium at 40 ml/min for 11 min, trapped on a Tenax trap, desorbed by heating, cryofocused, and injected by flash heating into a DB-5 capillary GC column. The oven temperature program was from 80°C, held for 8 min, to 120°C at 5°C/min, and then held for 2 min. The detector temperature was 250°C. The calibration curves were linear in the range of 2.5–15 ppb styrene in urine and 25–150 ppb in blood. The detection limits calculated were 0.4 μg/l in urine and 0.6 μg/l in blood. The coefficients of variations within the day and day-to-day were 3 and 3.1%, respectively, for 2.5 ppb of styrene in urine, and 1 and 1.6% for 25 ppb of styrene in blood. The results obtained from samples taken from workers exposed to styrene were reported.

Urinary excretion of specific mercapturic acids in workers exposed to styrene.

Styrene is an important chemical of wide industrial use, particularly in the manufacture of polymers and reinforced plastics. Environmental and occupational exposures to styrene occur predominantly via inhalation. Styrene undergoes biotransformation mainly by side chain oxidation catalyzed by cytochrome P-450 enzymes to its reactive metabolite, styrene oxide. The (R)- and (S)-enantiomers of styrene oxide can be conjugated with glutathione to both (R)- and (S)-diastereoisomers of specific mercapturic acids, N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine (M2). We conducted this biomonitoring study with the aim of evaluating the association between excretion of specific mercapturic acids (M1 and M2) and level of exposure to styrene among occupationally exposed people. The mean time-weighted average (TWA) exposure was about one-half the current threshold limit value, the range of the values varied from 44 to 228 mg/m3. Geometric mean (GM) concentrations of 650, 1,084, and 31.8 micrograms/g creatinine were measured, respectively, for M1-S, M2, and M1-R. The environmental styrene concentration exhibited a significant correlation with total specific mercapturic acid (Mtot = sum of M1-R, M1-S, and M2), making it possible for the first time to calculate the approximate relationship between styrene uptake and excretion of these substances. The M2 mercapturic acid had a better correlation (r = 0.56) with respect to M1-R and M1-S. Significant correlations were found also between the excretion of specific mercapturic acids and biological exposure indices (i.e., mandelic and phenylglyoxylic acids and urinary styrene).

Purge-and-trap method for the determination of styrene in urine

A purge-and-trap method for biological monitoring of styrene in urine was developed. Sorbent tubes packed with Tenax TA were used to trap styrene vapour purged from urine. Thermal desorption-gas chromatography was used for sorbent tubes analysis. The detection limit (0.70 μg/l), linearity range, recovery (>94% for spike urine samples) and repeatability for urine from occupational exposed workers show the suitability of the method for the determination of styrene in urine. One specific advantage of this method is the possibility of storage of the charged sorbent tubes during long periods of time without a significant loss of styrene. This approach can be used, with slight modifications, for urinary determination of several others organic contaminants commonly present in occupational exposures.

Biological monitoring of exposure to low concentrations of styrene.

A field study was conducted on 39 male workers exposed to styrene at concentrations below 40 ppm (time weighted average, TWA). Analyses were carried out on environmental air, exhaled air, blood, urine, and two major urinary metabolites of styrene: mandelic acid (MA) and phenylglycoxylic acid (PGA). Head space gas chromatography (GC) with a flame ionization detector (FID) was used for determination of styrene in blood and urine. Postexposure exhaled air was analyzed using capillary GC. Environmental styrene exposure was measured by personal sampling using carbon cloth personal samplers. Urinary metabolites of styrene were determined by high pressure liquid chromatograph (HPLC). When the end-of-shift breath, blood, and urine styrene levels were compared with environmental TWA values, blood styrene correlated best with styrene in air (r = 0.87), followed by breath styrene (r = 0.76). Poor correlation (r = 0.24) was observed between environmental styrene exposure and urine styrene. When styrene metabolites were compared with environmental styrene, the sum of urinary MA and PGA correlated better with styrene in air than MA or PGA alone. The correlations between urinary metabolites and environmental styrene improved when corrected for the specific gravity of urine. Even better correlations were observed when the urinary metabolites were corrected for creatinine. The correlation coefficients for environmental styrene and end-of-shift MA, PGA, and MA+PGA were 0.83, 0.84, and 0.86, respectively. The correlation coefficients between environmental styrene and next morning urinary metabolites fell to 0.47, 0.61, and 0.65 for MA, PGA, and MA+PGA, respectively. These results suggest that determination of the total MA and PGA in urine samples is preferred than separate measurements of MA or PGA. The good correlation between environmental exposure and styrene in the exhaled air also suggests that breath styrene level can be a useful indicator for low level styrene exposure, as the method is specific, noninvasive, and rapid. Urinary styrene seems to be a less reliable indicator for low level styrene exposure.

Urinary styrene in the biological monitoring of styrene exposure.

The urinary excretion of styrene represents a promising indicator of exposure to this solvent. Nevertheless extensive research under field conditions is scant. In this investigation 214 styrene-exposed workers from 10 fiberglass-reinforced plastics factories were studied. Environmental monitoring was performed by personal passive sampling. Blood styrene and the urinary excretion of styrene and its main metabolites, mandelic acid (MA) and phenylglyoxylic acid (PGA), were measured. The correlation coefficient between the time-weighted average of environmental styrene and the mean urinary excretion of styrene was 0.88 (0.91 after logarithmic transformation), compared with the 0.82 and 0.78 of the end-of-shift MA and PGA values, respectively. A high correlation (0.86) was also found between styrene in the blood and urine. The results, obtained under field conditions with a large group of exposed workers, confirm the usefulness of the urinary excretion of styrene as an exposure index for the biological monitoring of styrene exposure.

Sister-chromatid exchanges in lymphocytes from styrene-exposed boat builders

Sister-chromatid exchanges (SCE) were measured in peripheral blood lymphocytes from 40 workers in the boat-building trade. Twenty of these workers were exposed to significant amounts of styrene. The mean air concentration of styrene in the breathing zone of the boat builders was 209 mg/m 3 in the 7 exposed current smokers and 230 mg/m 3 in the 13 exposed non-smokers. Urinary styrene metabolites were also measured and the mean mandelic acid/creatinine ratios in the exposed, smokers was 275 mg/g, and in the exposed, non-smokers 323 mg/g. The SCE frequency in lymphocytes from the styrene-exposed group did not differ from that in the controls, although smoking significantly induced SCE in these workers.

Biological Monitoring of Occupational Exposure to Styrene

Abstract Styrene concentration in venous blood and in urine and urinary mandelic acid were measured in 64 subjects occupationally exposed to styrene. Samples were collected before and after each half of the shift at the beginning and end of the working week. The styrene concentration in venous blood and in urine and the urinary mandelic acid were correlated with the mean-weighted environmental concentration of styrene, measured in the breathing zone by means of passive personal samplers. The results indicate that the urinary styrene concentration can be used as a biological index of exposure to styrene. This parameter could be considered complementary to measurements of mandelic acid in urine, styrene in mixed-exhaled air, phenylglyoxylic acid in urine, and styrene in blood.

Influence of occupational styrene exposure on memory and attention

Short-term memory, perceptual speed, attention and psychomotor function were studied in 55 workers professionally exposed to styrene. The subjects were grouped according to their urinary styrene metabolites. Those with higher styrene exposure showed a significant impairment of short-term memory only.

Biological monitoring of styrene: a review.

Recent literature about the biological monitoring of styrene-exposed workers is reviewed. Styrene primarily exhibits its toxicity on the central and peripheral nervous systems, although its mutagenicity and chromosome damaging ability also may be relevant. Uptake, transformation and excretion of styrene show that beside the usual biological indicators, such as urinary mandelic and phenylglyoxylic acids (main metabolites), other indicators also may be of interest. These include styrene in expired air, in blood or in urine. Moreover, intermediate or final metabolites such as styrene glycol or mandelic acid in blood also have been proven to be useful in the interpretation of individual values. The most widely used analytical methods for these indicators are gas or high performance liquid chromatography. Correlations between exposure and the different biological indicators mentioned above show that the most reliable indicators are mandelic acid (MA) in urine sampled at the end of the work shift (but not the first day of the week) and the sum of mandelic and phenylglyoxylic acids (MA + PGA) in urine sampled 16 hr after exposure (before the next shift). The biological exposure limit values corresponding to the threshold limit value-time-weighted average (TLV-TWA) of 50 ppm of styrene are 850 mg MA/g creatinine in the end-of-shift sample and 330 mg MA + PGA/g creatinine in the next-morning sample. Other biological indexes, such as styrene glycol (phenyl ethylene glycol) in blood or styrene in urine, look promising but require further research in field situations.

Toluene and Styrene in Urine as Biological Exposure Indices

Abstract The concentration of toluene and styrene in urine was determined in 121 subjects occupationally exposed to toluene (median value: 75 mg/m3) and in 69 subjects exposed to styrene (109 mg/m3) in a chemical factory. The analyses were performed by the head space method, using a Hewlett-Packard 5880-A Gas Chromatograph with a Hewlett-Packard 5970-A Mass Selective Detector. A significant correlation was found between the toluene and styrene environmental concentrations (Ci, mg/m3) and the toluene and styrene urine concentration (Cu, μg/L) (toluene: Cu = 0.598 × Ci − 1.01, r = 0.87; styrene: Cu = 0.32 × Ci + 16.1, r = 0.89). The authors suggest a Biological Exposure Index (BEI) of 195 μg/L for toluene (in end-of-shift urine) corresponding to the TLV of 375 mg/m3 (100 ppm) for toluene in air, and a BEI of 75 μg/L for styrene (in end-of-shift urine) corresponding to the TLV of 215 mg/m3 (50 ppm) for styrene in air. These values could be considered complimentary to the ACGIH BEI for toluene: hippuric acid ...

Simultaneous determination of the major metabolites of styrene and acetaminophen, and of unchanged acetaminophen in urine by ion-pairing high-performance liquid chromatography

An improved isocratic high-performance liquid chromatographic method for the quantitative determination of the major urinary metabolites of styrene in urine is described. The high separation efficiency of an ion-pairing system using tetrabutyl ammonium chloride allows also the simultaneous determination of acetaminophen and its three major metabolites with those of styrene in rat urine. Simplicity, reproducibility and a short analysis time provide a useful tool for the toxicokinetic studies of these two hepatorenotoxic xenobiotics after their co-administration. An aliquot of the diluted urine is directly injected into the liquid chromatograph. The limits of sensitivity and detection of the metabolites of styrene are better than those reported before. Preliminary works indicate that the method would also be applicable for analysis of these metabolites in human urine and would therefore be useful in monitoring styrene exposure to workers especially when they take acetaminophen.

Urinary elimination of styrene in experimental and occupational exposure.

Twenty human volunteers were exposed to styrene vapor at 273-1 654 mumol/m3 (28.4-172.3 mg/m3) for a period of 1 to 3 h at rest (15 cases) and during light physical exercise (5 cases). Subsequently 51 workers occupationally exposed to styrene were studied during a workweek (median value 1 138 mumol/m3, geometric standard deviation 2.23). As expected, the relative uptake averaged about 65%, and the ratio of the alveolar concentration to the time-weighted average of the environmental concentration averaged about 0.15. Both in the experimentally exposed subjects and in the occupationally exposed workers the urinary styrene concentration showed a linear relationship to the corresponding environmental time-weighted average concentration. The correlation coefficients of the regression lines ranged between 0.88 (occupationally exposed group) and more than 0.93 (experimentally exposed groups). The regression coefficients were closely linked to the amount of styrene taken up and to the exposure times. The findings show that the urinary styrene concentration can be used as an appropriate biological exposure indicator whose meaning differs from that of other suggested indices. As an example, in occupationally exposed subjects performing moderate work the urinary styrene concentration corresponding to the time-weighted average of the threshold limit value is 815 nmol/l, and the 95% lower confidence limit (biological threshold) is 740 nmol/l.

Biological indicators of exposure in styrene polymerization workers. Styrene in blood and adipose tissue and mandelic and phenylglyoxylic acids in urine.

The concentrations of mandelic and phenylglyoxylic acids, urinary metabolites of styrene, and styrene in blood were determined for 491 styrene polymerization workers. Styrene in subcutaneous fat was determined for 25 workers. The levels of styrene exposure were estimated to be less than 10 ppm, and urinary metabolite and blood styrene concentrations indicated that significant recent exposure (within 4 h) had occurred among workers in areas of styrene polymerization and styrene monomer production. Styrene analysis of subcutaneous fat suggested that the monomer may have been present for as long as 3 d after exposure, a time when urinary metabolites and blood styrene were almost invariably undetectable. All three biological parameters were correlated with recency of exposure and estimated intensity of exposure within job categories.

ガスクロマトグラフによるStyreneの尿中代謝産物の定量

ガスクロマトグラフによるStyreneの尿中代謝産物の定量