Toluene in blood as a marker of choice for low-level exposure to toluene

The validity of two new biological exposure markers of toluene in blood (TOL-B) and toluene in urine (TOL-U) was examined in comparison with that of the traditional marker of hippuric acid in urine (HA-U) in 294 male workers exposed to toluene in workroom air (TOL-A), mostly at low levels. The exposure was such that the geometric mean for toluene was 2.3 ppm with a maximum of 132 ppm; the workers were also exposed to other solvents such as hexane, ethyl acetate, styrene, and methanol, but at lower levels. The chance of cutaneous absorption was remote. Higher correlation with TOL-A and better sensitivity in separating the exposed workers from the nonexposed subjects were taken as selection criteria. When workers exposed to TOL-A at lower concentrations (< 50 ppm, < 10 ppm, < 2 ppm, etc.) were selected and correlation with TOL-A was examined, TOL-B showed the largest correlation coefficient which was significant even at TOL-A of < 1 ppm, whereas correlation of HA-U was no longer significant when TOL-A was < 10 ppm. TOL-U was between the two extremes. The sensitivities of TOL-B and TOL-U were comparable; HA-U showed the lowest sensitivity. Thus, it was concluded that TOL-B is the indicator of choice for detecting toluene exposure at low levels.     

Comparative evaluation of biomarkers of occupational exposure to toluene

Objectives This study was initiated to make comparative evaluation of five proposed urinary markers of occupational exposure to toluene, i.e., benzyl alcohol, benzylmercapturic acid, o-cresol, hippuric acid and un-metabolized toluene. Methods In practice, six plants in Japan were surveyed, and 122 Japanese workers (mostly printers; all men) together with 12 occupationally nonexposed control subjects (to be called controls; all men) agreed to participate in the study. Surveys were conducted in the second half of working weeks. Time-weighted average exposure (about 8 h) to toluene and other solvents were monitored by diffusive sampling. End-of-shift urine samples were collected and analyzed for the five markers by the methods previously described; simultaneous determination of o-cresol was possible by the method originally developed for benzyl alcohol analysis. Results The toluene concentration in the six plants was such that the grand geometric mean (GM) for the 122 cases was 10.4 ppm with the maximum of 121 ppm. Other solvents coexposed included ethyl acetate (26 ppm as GM), methyl ethyl ketone (26 ppm), butyl acetate (1 ppm) and xylenes (1 ppm). By simple regression analysis, hippuric acid correlated most closely with toluene in air (r = 0.85 for non-corrected observed values) followed by un-metabolized toluene (r = 0.83) and o-cresol (r = 0.81). In a plant where toluene in air was low (i.e., 2 ppm as GM), however, un-metabolized toluene and benzylmercapturic acid in urine showed better correlation with air-borne toluene (r = 0.79 and 0.61, respectively) than hippuric acid (r = 0.12) or o-cresol (r = 0.17). Benzyl alcohol tended to increase only when toluene exposure was intense. Correction for creatinine concentration or specific gravity of urine did not improve the correlation in any case. Multiple regression analysis showed that solvents other than toluene did not affect the levels of o-cresol, hippuric acid or un-metabolized toluene. Levels of benzylmercapturic acid and un-metabolized toluene were below the limits of detection [limit of detections (LODs); 0.2 and 2 μg/l, respectively] in the urine from the control subjects. Conclusions In over-all evaluation, hippuric acid, followed by un-metabolized toluene and o-cresol, is the marker of choice for occupational toluene exposure. When toluene exposure level is low (e.g., 2 ppm), un-metabolized toluene and benzylmercapturic acid in urine may be better indicators. Detection of un-metabolized toluene or benzylmercapturic acid in urine at the levels in excess of the LODs may be taken as a positive evidence of toluene exposure, because their levels in urine from the controls are below the LODs. The value of benzyl alcohol as an exposure marker should be limited.     

Perceived odor and irritation of isopropanol: a comparison between naïve controls and occupationally exposed workers

OBJECTIVES: To assess sensory irritation levels from isopropanol (IPA) unconfounded by subjective evaluations of odor for comparison against the recommended exposure limits (400 ppm threshold limit value (TLV); American Conference of Governmental Industrial Hygienists). METHOD: The lateralization method was used to assess intra-nasal irritation thresholds for IPA, while odor detection thresholds were also measured. Thresholds for 1-butanol and phenyl ethyl alcohol (PEA) were obtained as positive and negative irritant controls. To compare potency and hedonic characteristics, subjects provided subjective ratings of odor, irritation and annoyance intensity for three concentrations of each chemical. Workers occupationally exposed to IPA ( n=26) were compared with previously unexposed controls ( n=26). RESULTS: The (geometric) mean odor detection threshold for IPA was slightly higher among exposed workers than controls (39 ppm vs. 11 ppm). Lateralization thresholds measuring intra-nasal irritation were elevated when compared with controls (6,083 ppm in exposed workers vs. 3,361 ppm in na?ve controls), with a significantly higher proportion of phlebotomists being unable to lateralize the maximum concentration regarded as safe, than controls. Calculations of the 6th percentile for lateralization thresholds revealed that 95% of the sample did not experience sensory irritation below 512 ppm. Thus, while odor detection thresholds were well below the current recommended exposure limits, the irritation thresholds were well above these values. The odor, irritation and annoyance from IPA was perceived, on average, as between weak and almost strong, from lowest to highest concentration. CONCLUSIONS: The results indicate that current exposure guidelines would be adequately protective of the acute adverse effect of nasal sensory irritation, as operationally defined by the intra-nasal lateralization threshold. Exposures to higher concentrations should perhaps be evaluated on the basis of existing knowledge about systemic, rather than local (e.g., irritation), toxic effects. IPA appears to be a weak sensory irritant and occupational exposure to IPA appears to elicit small changes in sensitivity that do not generalize to other odorants (e.g., PEA and 1-butanol) and are likely to be reversible.     

Biological monitoring of occupational exposure to methyl ethyl ketone in Japanese workers

The relationship between occupational exposure to methyl ethyl ketone (MEK) and its concentration in urine and blood was studied in a group of 72 workers in a printing factory. Personal exposure monitoring was carried out with passive samplers during the workshifts. The time weighted average (TWA) concentration of MEK ranged from 1.3 to 223.7 ppm, with a mean concentration of 47.6 ppm. In addition to MEK, toleuene, xylene, isopropyl alcohol, and ethyl acetate were detected as the main contaminants in all samples.At the end of the workshift, urine samples were collected to determine the urinary MEK, hippuric acid (HA), and creatinine, and blood samples were also collected at the same time for determination of MEK. The concentrations of urinary MEK ranged from 0.20 to 8.08 mg/L with a mean of 1.19 mg/L and significantly correlated with TWA concentrations of MEK in the air with a correlation coefficient of 0.889 for uncorrected urine samples. The concentration of MEK in the blood was also significantly correlated with the TWA concentration of MEK with a correlation coefficient of 0.820.From these relationships, MEK concentrations in urine and blood corresponding to the threshold limit value-TWA (200 ppm; ACGIH 1992) were calculated to be 5.1 mg/L and 3.8 mg/L as a biological exposure index (BEI), respectively. Although the BEI for urinary MEK obtained from the present study was higher than that of previous reports and ACGIH's recommendation (2.0 mg/L), the BEI agreed well with a previous study in Japan. On the other hand, the relationship between toluene exposure and urinary HA level, an index of toluene exposure, was also studied at the same time. The urinary concentration of HA corresponding to TWA at 100 ppm was 2.6 g/g creatinine as BEI. This value agreed well with both ACGIH's recommendation (2.5 g/g creatinine) and the values reported by Japanese researchers who have studied Japanese workers. Ethnic differences of MEK metabolism may affect the relationship between exposure and BEI.     

Biological monitoring for occupational exposure to toluene

A study was undertaken to examine the relationship between exposure of workers to toluene in the work environment and biological indicators of toluene exposure. The biological indicators studied were toluene in expired air, toluene in blood obtained by the finger prick method, and urinary hippuric acid. The study was undertaken in a factory in Singapore that manufactures speakers for audio systems. A total of 86 female workers exposed to toluene at the workplace and a control group of workers not exposed to toluene were examined. All of them were teetotalers, were nonsmokers, and gave no history of chronic drug usage. The 8-hr time-weighted average exposure level of toluene ranged from 1.6 ppm to 263 ppm. The study showed the expected toluene levels in finger prick blood was 1.4 micrograms/mL after an 8-hr exposure to 100 ppm of toluene. Toluene concentration in expired air of 16 ppm after an 8-hr exposure to 100 ppm compared favorably with other studies. The toluene in blood/expired air ratio was observed to be lower than in other studies. In this study, the expected urinary hippuric acid level for a 100-ppm exposure to toluene was 2.7 g/g creatinine. This level is higher than that recorded in other studies. The results showed that at low levels of toluene, urinary hippuric acid is not a valuable indicator of exposure. Toluene in expired air is the most reliable biological indicator of exposure to toluene.     

Effects of acute exposure of toluene and methyl ethyl ketone on psychomotor performance

Summary Organic solvents are used frequently in industry and workers are often exposed to various combinations of these chemicals. Several are CNS depressants, and the purpose of this experiment was to assess the behavioral effects of 4-hour inhalation exposures to two solvents, toluene and methyl ethyl ketone (MEK) alone and combined. Ethanol at 0.08% blood levels was used as a positive control. A total of 144 paid volunteers were randomly assigned to one of eight treatment combinations in a series of four two-group between subjects studies. Testing was carried out in an exposure chamber, and participants were tested before, during, and after the treatment or control condition on three performance tasks. The tasks measured alertness and psychomotor function and produced a total of 28 measures on each individual over the approximate 8 h of testing. Results indicated that toluene at 100 ppm produced a small but significant impairment on one measure of a visual-vigilance task by lowering the percentage of correct hits. MEK at 200 ppm produced no interpretable significant effects on any of these measures. Additivity was not evident when individuals were exposed to MEK (100 ppm) and toluene (50 ppm) in combination, as no significant performance differences were noted. Ethanol, at 0.08%, affected both the visual-vigilance and a choice-reaction time task at statistically significant levels on two measures, confirming the sensitivity of these two tasks to CNS depressants.     

Psychomotor performance and subjective symptoms at low level toluene exposure

Objectives: Possible effects of long term occupational exposure to toluene below the level of 100 ppm on psychomotor performance and subjective symptoms were investigated in a cross sectional approach.

Methods: From German rotogravure printing plants 278 male workers, mean age 39.8 years, mean duration of employment 14.9 years, were examined. A mean lifetime weighted average exposure (LWAE) of 45.1 ppm toluene in ambient air was found for 154 exposed workers (rotogravure printing area), with a mean current exposure of 24.7 ppm. The corresponding data for a second group of 124 workers with very low exposure (endprocessing area) had LWAE of 9.3 ppm and a current exposure of 3.3 ppm toluene. Psychomotor performance (steadiness, line tracing, aiming, tapping, and peg board) and subjective symptoms were examined.

Results: No significant differences between the two exposure groups were found by analysis of variance (ANOVA). By stepwise linear regression analyses there were weak associations of LWAE with one performance variable and two symptoms scales, but the results were not significant after correction for the α error. Psychomotor performance was mostly affected by age (maximum explained variance up to 13%), and handedness (up to 9%), whereas subjective symptoms are mostly affected by anxiety (up to 38%).

Conclusions: The weak associations between long term exposure to toluene should be used to indicate further longitudinal investigations. The results of this cross sectional study show no obvious dose response relation for psychomotor functions and subjective symptoms among workers exposed to toluene at a current exposure level of 1–88 ppm.

     

Comparative evaluation of blood and urine analysis as a tool for biological monitoring of n-hexane and toluene

Blood and urine samples were collected from 57 male Japanese solvent workers [exposed to n-hexane (Hex-A), ethyl acetate, and toluene (Tol-A) at 1.5, 2.3, and 2.3 ppm as GM-TWA, respectively] and also from 20 male nonexposed workers at the end of a 8-h shift, and analyzed for n-hexane (Hex-B) and toluene (Tol-B) in blood, and n-hexane (Hex-U), toluene (Tol-U), 2,5-hexanedione [both with (HD-U/cHYD) and without hydrolysis (HD-U/sHYD)] and hippuric acid (HA-U) in urine. Regression analysis showed that both Hex-B and Tol-B correlated significantly with corresponding exposure to the solvents. Solvents in urine (Hex-U and Tol-U) also correlated with solvents in air but with smaller correlation coefficients than the solvents in blood. Both HD-U/cHYD and HD-U/sHYD showed significant correlation with Hex-A, but HA-U failed to do so with Tol-A. Based on the correlation among biological exposure indicators and solvent concentration in air, sensitivity as an exposure indicator was compared between the solvent in blood and the metabolite in urine in terms of the lowest solvent concentration at which the exposed can be separated (with statistical significance) from the nonexposed (the lowest separation concentration; LSC). The LSC was 3.9 ppm for Hex-B, 1 to 2 ppm for HD-U/sHYD and 10 to 30 ppm for HD-U/cHYD, suggesting that HD-U/sHYD is superior even to Hex-B in detecting low n-hexane exposure; this high sensitivity of HD-U/sHYD is due to the absence of HD-U/sHYD in the urine from the nonexposed. In contrast, Tol-B (with LSC of 2.4 ppm) was more sensitive than HA-U; no LSC for HA-U could be obtained because of lack of correlation with Tol-A at low toluene exposure.     

Coexposure of man to m-xylene and methyl ethyl ketone. Kinetics and metabolism

In a study of the kinetics and metabolic interaction of xylene and methyl ethyl ketone (MEK) eight male volunteers were exposed to m-xylene (100 ppm) and MEK (200 ppm). The exposures to the two compounds were carried out both separately and in combination. Respiratory uptake and blood concentration, as well as urinary metabolites (methyl hippuric acid and 2,3-butanediol), were monitored. Coexposure to xylene and MEK resulted in inhibited xylene metabolism. The xylene concentration in blood increased significantly, and the urinary excretion of methyl hippuric acid decreased. The combined exposure did not cause any change in the concentration of MEK in the blood or the excretion of 2,3-butanediol in the urine. Exposure to MEK 20 h before the m-xylene exposure had no detectable effect on the kinetics of m-xylene.     

Monitoring of workers exposed to a mixture of toluene,styrene and methanol vapours by means of diffusive air sampling,blood analysis and urinalysis

Summary Exposure of 34 male workers to combined toluene, styrene and methanol was monitored by personal diffusive sampling of solvent vapours in breathing zone air, analysis of shift-end blood for the 3 solvents and analysis of shift-end urine for hippuric, mandelic and phenylglyoxylic acids and methanol. The exposure of most of the workers was below current occupational exposure limits. Regression analysis showed that a linear correlation exists for each of the 3 solvents between any pairs of the concentrations in air, blood and urine. Namely, toluene, styrene and methanol concentrations in blood obtained at the end of a shift are linearly related to the time-weighted average intensity of exposure to corresponding solvents, and also hippuric, mandelic and phenylglyoxylic acids as well as methanol in shift-end urine. The concentrations of hippuric, mandelic and phenylglyoxylic acids as well as methanol in urine correlated with the respiratory exposure intensity. Comparison of the present results with the exposure — excretion relationship after occupational exposure to the individual solvent showed that no modification in metabolism is induced by the combined exposure when exposure is low, as in the present case.     

A new derivatization procedure for the analysis of hippuric acid and m-methyl-hippuric acid by gas chromatography

Summary The industrial solvents, toluene and xylene, have physicochemical properties that can be hazardous to the workers exposed. Since hippuric acid and m-methyl-hippuric acid represent the products of toluene and xylene biotransformation in urine, they are used as biological markers in studies on occupational exposure to these solvents. Several methods have been used to determine hippuric acid and m-methyl-hippuric acid —either based on gas chromatography or on high-performance liquid chromatography. In this study we propose the derivatization of hippuric acid and methyl-hippuric acid using methanol in acid medium (HCl), a low-cost reagent with a low level of toxicity. The method has been routinely used in our laboratory for 1 year and has proven to be a reliable procedure for the biological control of occupational exposure to toluene and/or xylene.     

甲苯的慢性危害和尿中的马尿酸作为职业性接触的生物学监测指标探讨

本文对１４０名接触以甲苯为主的有机溶剂的包漆工（平均接触工龄８．３９年）进行了横断面调查，发现头昏、头痛、失眠、乏力、腹隐痛等症状的出现率，神衰综合征和慢性咽炎的患病率明显高放对照组（Ｐ＜０．０５或Ｐ＜０．０１）。常规肝功能和血清碱性磷酸酶（Ｓ－ＡＫＰ）无明显改变（Ｐ＞０．０５）。包漆工班末尿马尿酸平均浓度显著高於班前和对照组班末的平均浓度（分别Ｐ＜０．０５，Ｐ＜０．０１）。男、女包漆工班末尿马尿酸平均浓度均高于班前（分别Ｐ＜０．０５，Ｐ＜０．０１）。空气中苯系物的浓度均在最高允许浓度范围内。结果提示，长期接触低浓度的以甲苯为主的有机溶剂，对中枢神经系统有不利影响。尿中马尿酸水平可作为反映工人接触低浓度甲苯的有用的、生物学监测指标。     

Chronic occupational exposure to toluene

Summary Chronic occupational exposure to toluene was studied in a factory preparing tarpaulins. Seventy-eight workers were studied; 46 were exposed to various concentrations of toluene in air (20–200 ppm), 32 were unexposed workers in the same factory. In many cases the exposure had lasted for 10–20 years. The urinary hippuric acid excretion at the end of work shift showed good correlations to toluene concentrations in air, and it seems to be a good measure of exposure. The hippuric acid in urine samples collected overnight showed that elimination of toluene still occurs several hours after exposure. Most of the biological parameters measured showed no correlation to toluene exposure. The blood leukocyte count did show slight positive correlations to toluene exposure, but even this parameter stayed inside the range of normal values. The occurrence of chronic diseases, drug using habits, and drinking and smoking habits did not show any correlations to toluene exposure.This study has been supported by the grant of Y. Jahnsson Foundation in Finland     

Acute sensory irritation from exposure to isopropanol (2-propanol) at TLV in workers and controls: objective versus subjective effects

OBJECTIVES: Phlebotomists occupationally exposed to isopropanol (IPA) (2-propanol) and na?ve controls (n = 12 per group) were exposed to the time-weighted average threshold limit value of 400 p.p.m. IPA for 4 h in an environmental chamber to investigate: (i) acute effects of sensory irritation using subjective health symptom reports and objective, physiological end-points; and (ii) differences in measured effects in relation to exposure history. METHODS: Before, during and after exposure subjects gave self-reports of health complaints. During exposure subjects rated the intensity of the odor, sensory irritation and annoyance. Objective end-points of ocular hyperemia, nasal congestion, nasal secretion and respiration were obtained at various times before, during and after exposure. Results were compared with exposure to phenylethyl alcohol (PEA), a negative control for irritation, and to clean air (CA), a negative control for odor and irritation, using a within-subjects design. RESULTS: Significantly higher intensity ratings of odor, irritation and annoyance were reported during the exposure to IPA, when compared with exposure to CA or PEA. Nevertheless, the overall level of reported sensory irritation to IPA was low and perceived as 'weak' on average. Health symptom ratings were not significantly elevated for IPA as compared with PEA or CA exposure. The only physiological end-point that showed a change exclusively in the IPA condition was respiration frequency: relative to baseline, respiration frequency increased in response to IPA in both groups. No differences were encountered between the occupationally exposed and the control groups. CONCLUSIONS: The increase in respiration frequency in response to IPA may reflect either a reflexive change due to sensory irritation (an autonomic event) or a voluntary change in breathing in response to perception of an unpleasant, solvent-like odor (a physiological event caused by cognitive mediation). Our findings on objective end-points, including nasal and ocular sensory irritation, did not confirm subjective irritation reports. Irritation reports and odor intensity decreased, rather than increased, over time, lending credence to the cognitive argument and suggesting that the elevated subjective responses to IPA may be mediated by responses to its odor.     

Risk of chronic effects on the central nervous system at low toluene exposure

This study evaluates the chronic effects on the central nervous system of exposure to low concentrations of toluene (TWA < 20 ppm) on workers in a rotogravure plant. Ninety-eight male workers from a selection pool of 107 (92%) were examined neuropsychologically using a Cognitive Function Scanner, and neurologically by computerized methods measuring co-ordination ability, tremor and position stability. In addition measures of symptoms and former exposure were obtained by questionnaire. The workers were divided into three groups: Group 0 with no exposure to organic solvents (n = 19); Group 1 with exposure to TWA < 20 ppm of toluene for less than 13 years (n = 30) and Group 2 with exposure for more than 12 years (n = 49). Within Group 2, 37 (75%) had been exposed at levels exceeding 100 ppm for 10+ years before 1983. No significant differences were found between Group 0 and Group 1 regarding symptoms and results of the applied tests. Group 2 differed significantly from the two other groups in scoring higher on a symptom index (p = 0.04), particularly regarding concentration ability, reduced memory and fatigue. Group 2 scored significantly poorer on tests for visuospatial function, number learning and word recognition, while no differences regarding neurological functions were observed. The study showed no differences regarding neuropsychological and neurological functions between a non-exposed group of male workers and workers exposed to toluene less than 13 years at TWA < 20 ppm. However, long-term exposure to TWA (time weighted average) of toluene exceeding 100 ppm was associated with impaired neuropsychological function.     

Urinary hippuric acid and orthocresol excretion in man during experimental exposure to toluene.

It is not known whether urinary excretion of hippuric acid (HA) or orthocresol (O-Cr) is to be preferred for the biological monitoring of workers with occupational exposure to toluene. To study this, 42 printing trade workers with more than 10 years' exposure to a mixture of organic solvents including toluene (0-20 ppm) and 43 control subjects matched by age, smoking habits, and living accommodation were investigated. Each matched pair was randomised to an experimental exposure of either 100 ppm or 0 ppm toluene for 6.5 hours under controlled conditions in an exposure chamber. Urinary excretion of HA and O-Cr was determined by high pressure liquid chromatography from samples obtained before exposure, during the first three hours, and during the last 3.5 hours of exposure. No difference in HA and O-Cr excretion was found between printing trade workers and controls. The median O-Cr excretion increased 29 times during exposure, whereas the HA excretion increased only five times. Thus only 3% of the O-Cr excretion originated from other sources than toluene whereas the corresponding value for HA was 19%. Standardisation of the concentrations of HA and O-Cr in relation to urinary creatinine reduced the relative variation by 29% and 56% respectively. This was not reduced further by expressing the excretions as average excretion rates based on total volume of urine collected. Background urinary O-Cr excretion was three to four times higher among smokers than non-smokers, probably due to the content of O-Cr in cigarettes. The O-Cr excretion in unexposed smokers was, however, 10 times lower that that of the non-smokers during the end of the experimental exposure to 100 ppm toluene.     

Occupational toluene exposure induces cytochrome P450 2E1 mRNA expression in peripheral lymphocytes

Print workers are exposed to organic solvents, of which the systemic toxicant toluene is a main component. Toluene induces expression of cytochrome P450 2E1 (CYP2E1), an enzyme involved in its own metabolism and that of other protoxicants, including some procarcinogens. Therefore, we investigated the association between toluene exposure and the CYP2E1 response, as assessed by mRNA content in peripheral lymphocytes or the 6-hydroxychlorzoxazone (6OH-CHZ)/chlorzoxazone (CHZ) quotient (known as CHZ metabolic ratio) in plasma, and the role of genotype (5 -flanking region RsaI/PstI polymorphic sites) in 97 male print workers. The geometric mean (GM) of toluene concentration in the air was 52.80 ppm (10-760 ppm); 54% of the study participants were exposed to toluene concentrations that exceeded the maximum permissible exposure level (MPEL). The GM of urinary hippuric acid at the end of a work shift (0.041 g/g creatinine) was elevated relative to that before the shift (0.027 g/g creatinine; p < 0.05). The GM of the CHZ metabolic ratio was 0.33 (0-9.3), with 40% of the subjects having ratios below the GM. However, the average CYP2E1 mRNA level in peripheral lymphocytes was 1.07 (0.30-3.08), and CYP2E1 mRNA levels within subjects correlated with the toluene exposure ratio (environmental toluene concentration:urinary hippuric acid concentration) (p = 0.014). Genotype did not alter the association between the toluene exposure ratio and mRNA content. In summary, with further validation, CYP2E1 mRNA content in peripheral lymphocytes could be a sensitive and noninvasive biomarker for the continuous monitoring of toluene effects in exposed persons.     

Delayed and Competitively Inhibited Excretion of Urinary Hippuric Acid in Field Workers Coexposed to Toluene,Ethyl Benzene,and Xylene

The purpose of this study was to investigate whether the metabolic suppression of hippuric acid (HA) occurs in field workers coexposed to toluene, xylene and ethyl benzene. Eleven male spray painters were recruited into this study and monitored for 2 weeks using a repeated-measures study design. The sampling was conducted for 3 consecutive working days each week. Toluene, ethyl benzene, and xylene in the air were collected using 3M 3500 organic vapor monitors. Urine samples were collected before and after work shift, and urinary HA, methyl hippuric acid, mandelic acid, and phenylgloxylic acid concentrations were determined. In the first week, toluene concentrations were 2.66 ± 0.95 (mean ± SE) ppm, whereas ethyl benzene and xylene concentrations were 27.84 ± 3.61 and 72.63 ± 13.37 ppm, respectively, for all subjects. Pre–work shift HA concentrations were 230.23 ± 37.31 mg/g creatinine, whereas pre–work shift HA concentrations were 137.81 ± 14.15 mg/g creatinine. Mean urinary HA concentration was significantly greater in the pre–work shift samples than in the pre–work shift samples (p = 0.043). In the second week, toluene concentrations were much lower (0.28 ppm), whereas ethyl benzene and xylene were 47.12 ± 8.98 and 23.88 ± 4.09 ppm, respectively, for all subjects. Pre–work shift HA concentrations were 351.98 ± 116.23 mg/g creatinine, whereas pre–work shift HA concentrations were 951.82 ± 116.23 mg/g creatinine. Mean urinary HA concentration was significantly greater in the pre–work shift samples than in the pre–work shift samples (p <0.01); a significant correlation (r = 0.565; p = 0.002) was found between pre–work shift urinary HA levels and ethyl benzene exposure. This study showed that urinary HA peak was delayed to next morning for workers coexposed to toluene, ethyl benzene, and xylene; xylene and ethyl benzene probably played competitive inhibitors for metabolism of toluene. The study also presumed that urinary HA became the major metabolite of ethyl benzene at the end of work shift, when the exposure concentrations of ethyl benzene were 2.0 times those of xylene.     

The contributions to solvent uptake by skin and inhalation exposure.

Solvent exposures were assessed among 97 auto body repair workers in order to determine whether skin contact represented a significant route of exposure. Each subject's cumulative skin exposure was ranked categorically based on simple observation: 49 none, 33 incidental or low, and 15 moderate or high. The median time-weighted average air exposure to solvents was 8.4% of the American Conference of Governmental Industrial Hygienists (ACGIH) combined solvent threshold limit value (TLV) with a range of 0-62% TLV, including toluene (median 4 ppm) and xylenes (median 0.9 ppm). Urine methyl hippuric acids (MHAs, metabolites of xylenes) were low compared to the ACGIH biological exposure index (BEI) with a median of 2% and a range of 0-12% BEI but were strongly correlated with both the level of airborne xylenes and skin exposure when considered simultaneously by using analysis of covariance (R = 0.91, p less than 0.0001). MHA excretion attributable to skin exposure for 15 min or more generally was comparable to or greater than that from associated air exposure over the full work shift. This study had limited ability to assess quantitatively the contributions of toluene exposures, but there was evidence that skin exposures also contributed significantly to toluene absorption. Air sampling will substantially underestimate a worker's total solvent dose in the setting of moderate or high skin exposure. Simple observation was effective in identifying workers in this sample who appeared to have sufficient skin exposure to produce a measurable increase in solvent uptake.     

Effects of mixed organic solvents on neuromotor functions among workers in Buddhist altar manufacturing factories

To clarify the neuromotor effects of long-term exposure to mixed organic solvents, postural sway and tremor were measured in 62 solvent workers of four Buddhist altar manufacturing factories who had worked for 1-46 (mean 12) yr. By using the passive gas sampler, 8-h time-weighted average concentrations in the workers were estimated to be 0.02-8.7 ppm for toluene, 0.02-7.7 ppm for xylene, 0.02-5.5 ppm for styrene and 0.02-40.5 ppm for n-hexane. Sagittal sway and sway area of the posturography with eyes closed were significantly larger in the solvent workers than in 35 age-matched controls (p<0.05), and there was a significant difference in Romberg quotient of sagittal sway between the two groups (p<0.05). Also, tremor intensities at 1.0-5.9 Hz, 6.0-9.9 Hz and 10.0-13.9 Hz with the right hand, and at 6.0-9.9 Hz with the left hand were significantly stronger in the solvent workers than in the controls. Among the solvent workers, transversal and sagittal sways with eyes open and tremor intensity at 10.0-13.9 Hz were significantly related to toluene exposure (p<0.05), which may have been due to the acute effects of such solvents. These findings suggest that long-term exposure to mixed organic solvents may impair neuromotor functions as measured by postural sway and tremor.