Urinary Mandelic Acid Concentrations Research Articles

Influence of genetic polymorphisms of epoxide hydrolase 1 on metabolism of styrene in body

To investigate the role of genetic polymorphisms of epoxide hydrolase 1 (EPHX1) in the metabolism of styrene in vivo. Fifty-six styrene-exposed workers, who worked in the painting workshop of an enterprise for manufacturing glass fiber-reinforced plastic yachts in Shandong Province, China for over one year and were protected in approximately the same way, were selected as study subjects. The 8-hour time-weighted average concentration (8 h-TWA) of styrene and the concentrations of mandelic acid (MA) and phenyl glyoxylic acid (PGA) as urinary metabolites were measured. The genetic polymorphisms of EPHX1 were detected by polymerase chain reaction-restriction fragment length polymorphism analysis. The urinary concentrations of MA and PGA were 177.25±82.36 mg/g Cr and 145.91±69.73 mg/g Cr, respectively, and the 8 h-TWA of styrene was 133.28±95.81 mg/m3. Urinary concentrations of MA and PGA were positively correlated with 8 h-TWA of styrene (R=0.861, P < 0.05; R=0.868, P < 0.05). The subjects were divided into high-exposure group (8 h-TWA >50 mg/m(3)) and low-exposure group (8 h-TWA ≤ 50 mg/m(3), and in the two groups, the urinary concentrations of MA and PGA were significantly higher in the individuals carrying high-activity genotypes of EPHX1 than in those carrying low-activity genotypes of EPHX1 (P < 0.05). Genetic polymorphisms of EPHX1 play an important role in the metabolic process of styrene in vivo.

Study of Urinary Concentrations of Mandelic Acid in Employees Exposed to Styrene

Mandelic acid (MA) is an important metabolite of styrene. In humans, measurement of its concentration in urine provides an important assessment of the overall level of styrene exposure in workers of the reinforced plastic manufacturing industry. The aim of our study was to investigate in these workers the relationship between MA concentration and styrene exposure time and intensity as well as its dependence on work occupation. The concentration of MA in the urine samples of 35 employees was analyzed with HPLC (high performance liquid chromatography). Out of 35 workers, 11 performed laminating, 11 milling and finalizing, 6 laying-up and spraying-up, and 7 worked in background support. Urinal samples were obtained twice a day over the course of three weeks, at the beginning and the end of the work shift. We found a significant increase in MA concentrations during a work shift in all tested days (Wilcoxon test p < 0.05). Employees working in elevated atmospheric concentrations of styrene (93.77-159.88 mg/m3) had significantly higher MA concentrations in urine compared to other groups at both the beginning and the end of the shift (Kruskal Wallis test p < 0.001) (p < 0.001). Only samples from laminating workers exceeded the biological limit of MA concentration (640 mg/L) at the end of the shift. Normalisation of MA concentration to body mass index (BMI, normal range: 21.7 +/- 3.2 kg/m2) refined differences within groups (Kruskal-Wallis analysis p < 0.001). The accumulation of MA at the end of the work shift for measured time period was not significant for the measured time period (Friedman analysis p > 0.11). Our results confirmed that MA is a sensitive metabolic marker of styrene exposure without cumulative effect. However, normalization of MA concentrations to BMI can improve the accuracy of styrene exposure estimates in certain groups of employees.

Exposure to Styrene in Fiberglass-Reinforced Plastic Manufacture

The aim of the work is to define occupational exposure to styrene in fiberglass manufacture; the phase of stretching styrene resins needs some manual handling and leads workers to be exposed to styrene. We surveyed 20 workers in two companies manufacturing fiberglass, checking environmental levels and urinary concentrations of mandelic acid (MA), and phenylglioxylic acid (PGA). Workers completed a questionnaire collecting their medical history. Environmental monitoring showed some styrene concentrations higher than the threshold limit value-time-weighted average. Biological monitoring confirmed these findings and four workers had levels of urinary PGA and MA concentrations higher than the Biological Exposure Indices of the American Conference of Governmental Industrial Hygienists. This picture confirms that, even though the risk is known and the manufacturing cycle is well-defined, workers nevertheless risk exposure. More research is needed to optimize the work processes and the protection systems to lower this risk.

Thyroid Function and Exposure to Styrene

Many natural substances and drugs have long been known to cause goiter or thyroid dysfunction. More recently, several environmental pollutants, such as pesticides and industrial compounds, have been investigated for their thyroid-disrupting activity and related adverse effects on human health. The aim of this study was to evaluate the effects of styrene on the thyroid axis in occupationally exposed workers. Thirty-eight exposed (E) and 123 nonexposed (NE) male workers (controls) were assessed. Serum concentrations of thyrotropin (TSH; basal and after thyrotropin-releasing hormone [TRH] administration.), free thyroxine (FT(4)), free triiodothyronine (FT(3)), anti-thyroglobulin, thyroid peroxidase antibody, and calcitonin were measured. Thyroid ultrasound examination was also performed. In E workers, urinary creatinine, mandelic acid (MA), and phenylglyoxylic acid (PGA) were also measured. No significant differences between E and NE workers were demonstrated, as far as thyroid volume, nodularity, serum thyroid antibodies, and calcitonin were analyzed. However, in the E group a positive correlation between duration of exposure and thyroid volume was detected. After exclusion of subjects with nodular or autoimmune thyroid diseases, serum concentrations of FT(4), FT(3), and TSH did not differ between the two groups. In E workers there was a positive correlation between the urinary concentrations of styrene metabolites (MA plus PGA) and FT(4) or FT(4)/FT(3) ratio (p < 0.05; r = 0.45 and p < 0.005; r = 0.61, respectively), while no correlation was observed between urinary concentrations of MA plus PGA and serum TSH (either basal and stimulated). Chronic exposure to styrene is not associated with an increase in nodular or autoimmune thyroid diseases. However, styrene could interfere with peripheral metabolism of thyroid hormones by inhibiting T(4) to T(3) conversion. Whether this is a direct effect on iodothyronine deiodinases or a consequence of a general distress, such as in nonthyroidal illnesses, remains to be established. Further studies in a larger population of exposed workers are needed to confirm these preliminary observations.

Aggression in boat builders: a search for altered mood states in boat builders exposed to styrene.

Published reviews and industrywide anecdotal reports have suggested an association between exposure to some volatile organic compounds (VOCs) and altered mood states. In this paper we report a unique study of boat-builders exposed to styrene. Two hundred and thirteen employees exposed to solvents and 144 who were not exposed completed questionnaires related to mood states. Additionally, for 23 of the 213 employees, the air concentrations of styrene were measured at their workplaces, and urinary concentrations of mandelic acid (a metabolite of styrene) were determined in order to assess biological exposure. Special features of this study included the use of the Prolife of Mood States (POMS) questionnaire and the availability of sound historical data. A weak association is demonstrated between styrene exposure and aggression/hostility. That this is found to be most marked in the earliest years of exposure suggests that selection characteristics might be a more important association than solvent exposure.

Study of urinary mandelic acid concentration and peripheral nerve conduction among styrene workers

The relationship between exposure to styrene and nerve conduction velocities was investigated in 32 workers occupationally exposed to styrene. There was a dose-dependent relationship between urinary mandelic acid and ulnar and peroneal motor distal latencies (MDLs). The ulnar and peroneal MDLs of subgroup B (urinary mandelic acid ≥250 mg/l) were significantly longer than those of subgroup A (urinary mandelic acid <250 mg/l) (p < 0.05), and the referent group (p < 0.03). After adjusting confounding factors, urinary mandelic acid had a significant positive relationship with ulnar and peroneal MDL. Our study suggests that a low level of styrene, below the 50 ppm exposure limit of the American Conference of Governmental Industrial Hygienists (ACGIH), involves the risk of inducing adverse effects on the peripheral nervous system. The study also indicated that motor distal latency is a sensitive parameter of toxic peripheral neuropathy. © 1996 Wiley-Liss, Inc.

Study of urinary mandelic acid concentration and peripheral nerve conduction among styrene workers.

The relationship between exposure to styrene and nerve conduction velocities was investigated in 32 workers occupationally exposed to styrene. There was a dose-dependent relationship between urinary mandelic acid and ulnar and peroneal motor distal latencies (MDLs). The ulnar and peroneal MDLs of subgroup B (urinary mandelic acid > or = 250 mg/l) were significantly longer than those of subgroup A (urinary mandelic acid < 250 mg/l)(p < 0.05), and the referent group (p < 0.03). After adjusting confounding factors, urinary mandelic acid had a significant positive relationship with ulnar and peroneal MDL. Our study suggests that a low level of styrene, below the 50 ppm exposure limit of the American Conference of Governmental Industrial Hygienists (ACGIH), involves the risk of inducing adverse effects on the peripheral nervous system. The study also indicated that motor distal latency is a sensitive parameter of toxic peripheral neuropathy.

A Sensitive HPLC Method for Determination of Mandelic Acid in Urine, and Its Application to Biological Monitoring of Ethylbenzene-exposed Chinese Workers

AbstractA highly sensitive high-pressure liquid chromatography (HPLC) method was developed for determination of mandelic acid (MA) in urine as a marker of exposure to ethylbenzene at low concentrations. This was achieved by the use of a mobile phase (acetonitrile: 60% perchloric acid: water = 50 ml: 100 μl: 950 ml) that has no absorption at 200 nm, the wavelength at which MA shows intense absorption. The detection limit was 0.07 mg/L urine, and the recovery rate was 101% (CV: 2.7%) when MA was added at 250 mg/L to ten urine samples from non exposed subjects. The method was applied for MA determination, in parallel to a method previously developed, to 641 urine samples (from 360 ethylbenzene-exposed workers and 281 nonexposed subjects), and the results were analyzed by regression analysis to examine the relationship between ethylbenzene exposure concentrations and urinary MA concentrations. A smaller intercept on the axis (essentially zero) and a larger correlaiion coefficient (about 0.7) indicate that the...

Cytogenic analysis of lymphocytes from fiberglass-reinforced plastics workers occupationally exposed to styrene

In this study a group of 52 workers employed in a plant manufacturing fiberglass -reinforced plastic (FRP) pipes and cisterns, and therefore daily exposed to styrene, were monitored. As a control group 24 non-exposed workers from another factory producing and repairing pallets volunteered to participate. The airborne styrene during the monitoring ranged from 2.2 to 110.1 mg/m 3. As a metabolic marker for styrene exposure mandelic acid was measured in the urine and ranged from 11 to 649 mg/g creatinine. From 43 exposed and 15 control workers sister-chromatid exchanges (SCE) and high frequency cell (HFC) data and from 49 exposed and 23 control workers micronucleus (MN) data from peripheral lymphocytes are reported. Although the two groups of workers could clearly be distinguished on the basis of the airborne styrene concentrations and urinary mandelic acid concentrations no differences in any of the cytogenetic markers were found. Correlations between the cytogenetic data and the level of airborne styrene concentrations or urinary mandelic acid levels could also not be demonstrated. Otherwise smoking increased the SCE frequency. Grouping the workers according to smoking habits showed a statistically significant difference in SCE. Moreover, levels of urinary thiocyanate (SCN), which can be used as a metabolic marker for smoking, showed a significant positive correlation with the number of SCE. This indicates that SCE is a sensitive biomarker and might still be useful in biomonitoring. However, only chronic exposures over a long period would probably be detectable. In this study, where exposure was rather low and the number of working years was small (mean of 2.9 years), cytogenic effects are probably too low or rare to be detectable with an assay.

Monitoring occupational exposure to styrene from hemoglobin adducts and metabolites in blood.

Monitoring occupational exposure to styrene was achieved through quantification of adducts of styrene 7,8-oxide to N-terminal valine in hemoglobin (Hb) on the basis of the enrichment of adducted globin chains by ion-exchange chromatography and gas chromatographic-mass spectrometric analysis by the use of the N-alkyl Edman method. Application to blood samples from reinforced plastics workers exposed to styrene and from referents showed Hb adduct levels correlating with the blood styrene glycol and urinary mandelic acid concentrations. The blood styrene glycol and styrene 7,8-oxide levels of the exposed workers averaged 2.5 mumol.l-1 (17 subjects) and 0.09 mumol.l-1 (7 subjects), respectively. The blood styrene glycol and urinary mandelic acid content (mean 9.5 mmol.l-1, 17 subjects) suggested a styrene concentration of about 300 mg.m-3 (75 ppm) in the workplace air. The Hb adduct levels were low (mean 28 pmol.g-1), indicating rapid detoxification of styrene 7,8-oxide in humans.

Somatosensory evoked potentials in workers exposed to toluene and styrene.

Somatosensory evoked potentials (SEPs) were used to evaluate possible subclinical impairment of the nervous system due to occupational exposure to toluene and styrene. A group of 36 rotogravure printers with severe exposure to toluene, 20 workers with severe exposure to styrene in a glass laminate manufacturing plant, and a comparison group of healthy subjects were studied. The severity of exposure was documented by measurements of toluene and styrene concentrations in breathing zone air, by hippuric acid concentration in urine in the group exposed to toluene, and by urinary mandelic acid concentration in the group exposed to styrene. Somatosensory evoked potentials were measured by stimulation of the median nerve at the wrist and the tibial nerve at the ankle. Peripheral conduction velocities (CVs) in both extremities and central conduction time (CCT) after tibial nerve stimulation were significantly decreased in both exposed groups. Significantly prolonged latencies of peripheral and cortical SEPs to median nerve stimulation as well as cortical SEPs to tibial nerve stimulation were found in workers exposed to styrene. Some abnormalities in SEPs at peripheral or spinal and cortical levels were found in eight workers exposed to toluene and six workers exposed to styrene. Of these, in three workers exposed to toluene and two to styrene increased CCT and delayed latencies of cortical responses at normal conduction values in the periphery were found. A trend for increased frequency of abnormal SEPs with duration of exposure to toluene and styrene and alcohol abuse was found. Abnormalities in SEPs in the exposed groups are most probably of multifactorial origin. Central SEP abnormalities in both exposed groups could indicate early signs of subclinical dysfunction at spinal and cortical levels and could be due to toluene or styrene exposure probably potentiated by alcohol consumption in the group exposed to toluene.

Biomonitoring of Occupational Exposure to Styrene

Abstract To assess the most suitable biological indicators of styrene exposure, a comparison was made between air concentrations of the solvent and biological data in a group of 20 workers using polyester resins. The 8-hour styrene TWA was determined with personal sampling pumps and activated charcoal tubes, using four tubes to obtain four 2-hour samples over the workshift for each subject. The TWA values ranged from 17 to 199 mg/m3. A significant correlation was found between styrene TWA exposure and urinary concentrations of mandelic acid (MA) and phenylglyoxy lie acid (PGA) at the end of the workshift (for MA, r = 0.73; for PGA, r = 0.64; for MA + PGA, r = 0.74). The correlation was even better between styrene TWA and metabolites in the urine collected on the next morning (for MA, r = 0.84; for PGA, r = 0.78; for MA + PGA, r = 0.86). Regression analysis showed that a styrene exposure level of 215 mg/m3 corresponded to an excretion of metabolites (MA + PGA) of 1054 mg/g creatinine at the end of the work...

No acute behavioural effects of exposure to styrene: a safe level of exposure?

To determine whether exposure to low levels of styrene (below 110 mg/m3) causes acute behavioural effects and symptoms that may be related to concentrations of styrene in air or urinary mandelic acid or both, 12 men occupationally exposed to styrene were studied and compared with a reference group of 10 unexposed men. Simple reaction time was measured before and after work and information about symptoms was obtained by questionnaire. Active and passive sampling of airborne styrene was carried out and urinary mandelic acid concentrations were measured. Although the size of the study groups is small, the results indicate that exposure to styrene below 110 mg/m3 does not cause any acute adverse effects on the central nervous system.

Acute behavioral effects of styrene exposure: a further analysis.

Studies were carried out on two groups to styrene-based resin. Early morning urinary mandelic acid concentrations after two days without exposure correlated with reaction time measured on arrival at work. Men were found to differ considerably in their rate of clearance of mandelic acid-those with slow reaction times. After some months at reduced exposure, a small group of men with previously high mandelic acid concentrations has speeded up on the reaction time task.

The time course of mandelic and phenylglyoxylic acid excretion in workers exposed to styrene under model conditions.

Urinary excretion of mandelic and phenylglyoxylic acids by two technicians building glass-reinforced plastic boats has been measured over a 7-day period. Peak excretion of both metabolites occurred several hours after the end of exposure. There was little relationship between urinary mandelic acid concentrations measured at the end of shift and the maximum excretion observed in samples collected after this time. It is suggested that sampling strategies devised to monitor workers exposed to styrene should reflect maximum excretion rates of urinary mandelic acid.

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.

Relationship of symptoms to occupational styrene exposure and to the findings of electroencephalographic and psychological examinations.

Ninety-eight male laminating workers occupationally exposed to styrene were clinically examined, and their symptoms were clarified with the aid of a questionnaire. The mandelic acid concentration in urine was used as the measure of current exposure. The median mandelic acid concentration (mean of five determinations) of the exposed group was 808 mg/l (Q1 439, Q3 1390). The symptoms of the exposed group were compared with those of unexposed men (n=98) and also correlated to the mandelic acid concentration. Symptoms of fatigue, difficulties in concentration and symptoms of irritation occurred statistiscally significantly more often in the exposed group than in the unexposed one (p < 0.01). During the workday irritation and „prenarcotic” symptoms, e.g., nausea, dizziness and a drunken feeling, were reported significantly more often (p < 0.001) in the exposed group. When the relationship between symptoms, and also symptom scores, and the mandelic acid concentration was examined, no statistically significant correlation was found. Also a comparison of symptoms of the most and least exposed groups revealed no statistically significant difference. Earlier abnormal electroencephalographic (EEG) findings and abnormal psychological functions (lowered psychomotor accuracy and speed) had been found to statistically significantly correlate with urinary mandelic acid concentration. In the present investigation the symptoms and symptom scores of the groups with abnormal EEGs or psychological functions were compared to the group with corresponding normal findings, and no statistically significant difference was found. The clinical examination did not reveal any neurological deficits. In an attempt to determine whether mandelic acid causes uroepithelial atypias, a urinary cytologic examination was made; none of the 35 specimens showed any suspicious cellular changes. The results of the symptom survey indicate that the presence of symptoms can not be used as a predictor of exposure or as a predictor of abnormal findings in psychological and EEG examinations. They might also indicate that the symptoms and the objective findings describe different aspects of the effects of styrene exposure.

Urinary mandelic acid concentration after occupational exposure to styrene and its use as a biological exposure test.

Excretion of mandelic acid from workers in the reinforced polyester plastic industry was studied with the determination of urinary mandelic acid concentrations. The styrene exposure level at the workplaces was evaluated with measurements of the styrene concentration in the ambient air. Three different groups (I, II and III) were studied. In group I [n=9, median of the time-weighted average (TWA) of exposure = 23 ppmof styrene, postexposure observation period = 64 h] two excretion slopes were observed, the first with a median half-time of 9.4 h (postexposure period 0--18 h) and a second with a median half-time of 16.6 h (postexposure period 19--64 h). For group II (n=9, median TWA exposure = 248 ppm, postexposure observation period = 15 h) a half-time of 6.4 h was found. These results suggest that the excretion rate of mandelic acid is dependent on the styrene exposure level. In addition the mandelic acid concentrations of 29 workers (group III) before and after the work shift were analyzed. The urinary mandelic acid concentrations of groups I, II and III, sampled immediately after the 8-h work shift, correlated with the 8-h TWA of styrene exposure (n=47, r=0.93). Accordingly about 2,300 mg of mandelic acid per gram of creatinine corresponded to 100 ppm of styrene.