Occupational exposure to hexahydrophthalic anhydride: air analysis,percutaneous absorption,and biological monitoring

Summary Urinary hexahydrophthalic acid (HHP acid) levels were determined in 20 workers occupationally exposed to hexahydrophthalic anhydride (HHPA) air levels of 11–220g/m³. The levels of HHP acid in urine increased rapidly during exposure and the decreases were also rapid after the end of exposure. The elimination half-time of HHP acid was 5h, which was significantly longer than in experimentally exposed volunteers, possibly indicating distribution to more than one compartment. There was a close correlation between time-weighted average levels of HHPA in air and creatinine-adjusted levels of HHP acid in urine collected during the last 4 h of exposure (r = 0.90), indicating that determination of urinary HHP acid levels is suitable as a method for biological monitoring of HHPA exposure. An air level of 100 g/m³ corresponded to a postshift urinary HHP acid level of ca. 900 nmol/mmol creatinine in subjects performing light work for 8h. Percutaneous absorption of HHPA was studied by application of HHPA in petrolatum to the back skin of three volunteers. The excreted amounts of HHP acid in urine, as a fraction of the totally applied amount of HHPA, were within intervals of 1.4%–4.5%, 0.2%–1.3%, and 0%–0.4% respectively, indicating that the contribution from percutaneous absorption is of minor importance in a method for biological monitoring.     

Phthalic acid excretion as an indicator of exposure to phthalic anhydride in the work atmosphere

Summary The concentration of phthalic acid was determined in the urine of nine subjects occupationally exposed to phthalic anhydride. For the determination, the urine samples were acidified, extracted with dimethyl ether, esterified with boron trifluoride/methanol and measured by electron capture gas chromatography. Environmental air samples were collected in Tenax tubes, eluted with methyl-t-butyl ether and assayed by electron capture gas chromatography. Significant correlations were found between the concentration in urine samples (range: 0.3–14.0 mol/mmol creatinine), collected at different times of the day, and the time-weighed average atmospheric concentrations (range: 0.03–10.5 mg/m³). No conjugation of phthalic acid in the urine was observed. The detection limit for urine samples (10 ml) was 0.05 mol/l) and that for air samples 0.4 g/m³. The method has potential for biological monitoring of workers exposed to phthalic anhydride. It was found that at atmospheric anhydride concentrations of about 30% of the hygienic reference value (6 mg/m³). which is applied in many market economies, a body-burden was caused which was not eliminated overnight.     

Methyltetrahydrophthalic acid in urine as an indicator of occupational exposure to methyltetrahydrophthalic anhydride

Objective: To investigate whether methyltetrahydrophthalic acid (MTHP acid) in urine can be used as a biomarker for exposure to methyltetrahydrophthalic anhydride (MTHPA). Methods: Workers occupationally exposed to MTHPA were studied in combination with one of the authors, who was experimentally exposed to MTHPA. Air levels of MTHPA were determined by personal sampling in the breathing zone. The MTHPA in air was sampled by silica gel and analyzed by gas chromatography (GC) with electron-capture detection. Urinary levels of MTHP acid, a metabolite of MTHPA, were determined in 15 subjects in total. Urine was collected from 14 workers immediately before the start of the work shift and then after 4 and 8 h, and from one of the authors at intervals during 24 h. MTHP acid in urine was analyzed by GC with mass spectrometric detection. Results: The time-weighted average (TWA) air levels ranged from 1.0 g to 200 g MTHPA/m³ during 8 h work shifts. The urinary levels of MTHP acid increased during exposure and decayed after the end of exposure, with an estimated half-time of about 3 h. A close correlation was found between the TWA air levels of MTHPA and creatinine-adjusted MTHP acid levels in urine collected at the end of the shift (r=0.955; P<0.0001). The current occupational exposure limit of 50 g MTHPA/m³ (Japan Society for Occupational Health) corresponded to about 1300 g MTHP acid/g creatinine, which was equivalent to about 900 nmol/mmol creatinine in the International System of Units (SI). Conclusions: These results indicate that the determination of MTHP acid in urine is suitable for use in the biological monitoring of MTHPA exposure.     

Detection and clinical relevance of a type I allergy with occupational exposure to hexahydrophthalic anhydride and methyltetrahydrophthalic anhydride

Summary Hexahydrophthalic anhydride (HHPA) and methyltetrahydrophthalic anhydride (MTHPA) belong to the group of the acid anhydrides and, among other applications, are used in the production of epoxy resins. These substances are known as potent low-molecular allergens and induce predominantly type I allergies according to Coombs and Gell. We examined 110 employees exposed to HHPA and MTHPA. With all of them a RAST was carried out with the commercially available conjugates of phthalic anhydride (PA) and a skin prick test with 1% and 5% acetonic solutions of PA. In 109 of these sera a radio allergo sorbent test (RAST) was carried out with the not commercially available conjugates of HHPA and of MTHPA. With complaints connected with the workplace the working materials used (HHPA, MTHPA) were also checked by means of the skin prick test. With at least one positive immunological finding (in the RAST and/or skin prick test) in connection with complaints at the workplace, we performed a workplace-related inhalation test under experimental conditions. Specific IgE against acid anhydrides was detected in a total of 17 (15.4%) persons. In the challenge test, six (5.4%) sensitisations were shown to be clinically relevant. On inclusion of borderline positive findings with PA conjugates the RAST produced three false negative and one false positive finding compared with a RAST with HHPA and MTHPA conjugates. With the conjugates of trimellitic anhydride, in no case could specific IgE be detected. The skin prick test led, in comparison with the RAST, to three false positive and three false negative findings. With all clinically relevant sensitisations the skin prick test was regarded as positive. RASTs with conjugates of PA and skin prick tests with native acid anhydrides can, according to our investigations, validly ascertain workplace-related sensitisations to HHPA and MTHPA.     

Experimental human exposure to N,N-dimethylbenzylamine: generation of a controlled atmosphere and biological monitoring

The aim of the present study was to develop a method for generation of dimethylbenzylamine (DMBA) atmospheres in an exposure chamber and to investigate the possibility of using urinary DMBA metabolites for biological monitoring of exposure to DMBA. A DMBA atmosphere was generated by use of the gas-permeation principle. Six healthy male volunteers were exposed for 8 h to DMBA at air levels of 20, 45, and 80 μm/m³. Air levels of DMBA were analyzed by gas chromatography (GC). The total urinary amount of DMBA (U-SumDMBA; DMBA and metabolites that can be reduced to DMBA, e.g., DMBAO) was analyzed using GC-mass spectrometry (MS). The exposure chamber maintained very low (0–130 μg/m³) and steady concentrations for several weeks. DMBA uptake by inhalation was 76%. The amine was quickly distributed and biotransformed to nearly 100%. DMBA was eliminated in the urine with a half-time of 4.3 h. More than 50% was eliminated within 2 h of exposure. However, at all exposure levels the subjects continued to excrete DMBA the next morning. There was a significant correlation between the exposure to DMBA and the U-SumDMBA. Thus, U-SumDMBA may become an important biomarker for monitoring of industrial exposure to DMBA. Received: 7 January 1997 / Accepted: 5 May 1997     

Determination of 3,4-dimethylhippuric acid as a biological monitoring index for trimethylbenzene exposure in transfer printing workers

Summary The relationship between exposure to 1,2,4-trimethylbenzene (1,2,4-TMB) and urinary concentration of 3,4-dimethylhippuric acid (3,4-DMHA), one of its metabolites, was studied in workers involved in transfer printing. Airborne TMBs were sampled by an organic vapor monitoring badge and analyzed by capillary gas chromatography. Urinary 3,4-DMHA and creatinine were analyzed under the same conditions of high-performance liquid chromatography. The exposure concentration of 1,2,4-TMB among workers was around 25 ppm, the threshold limit value (TLV). The urinary concentration of 3,4-DMHA was low at the start of each shift and high at the end. Exposure to the TLV (25 ppm) of 1,2,4-TMB results in a urinary 3,4-DMHA concentration of 410 mg/g creatinine (r = 0.897, P < 0.001). Urinary 3,4-DMHA concentration could be used as a biological monitoring index for 1,2,4-TMB exposure.     

Biological monitoring of methylhexahydrophthalic anhydride by determination of methylhexahydrophthalic acid in urine and plasma from exposed workers

Objective: To investigate whether methylhexahydrophthalic acid (MHHP acid) in urine and plasma can be used as a biomarker for exposure to methylhexahydrophthalic anhydride (MHHPA). Methods: MHHPA in air was sampled by Amberlite XAD-2 and analysed by gas chromatography (GC) with flame ionisation detection. MHHP acid in urine and plasma was analysed by GC with mass spectrometric detection. Workers occupationally exposed to MHHPA were studied. Air levels of MHHPA were determined by personal sampling in the breathing zone. Urinary levels of MHHP acid, a metabolite of MHHPA, were determined in 27 workers. In eight workers all urine was collected at intervals during 24 h. Plasma levels of MHHP acid were determined in 20 workers. Results: The time-weighted average (TWA) air levels ranged from 5 to 60 μg MHHPA/m³ during 8-h work-shifts. The urinary levels of MHHP acid increased during exposure and decayed after the end of exposure with an estimated half-life of about 6 h. A correlation was found between the TWA air levels of MHHPA and creatinine-adjusted MHHP acid levels in urine collected during the last 4 h of exposure. A correlation was also seen between the TWA air levels of MHHPA and the plasma concentrations of MHHP acid. An exposure to 20 μg MHHPA/m³ corresponded to about 140 nmol MHHP acid/mmol creatinine and about 40 nmol MHHP acid/l plasma. Conclusion: The results indicate that MHHP acid in urine or plasma may be used for biological monitoring of the exposure to MHHPA. Received: 4 October 1996 / Accepted: 2 January 1997     

Formic acid excretion in comparison with methanol excretion in urine of workers occupationally exposed to methanol

Summary A semiautomated head-space gas chromatographic (GC) method was developed for measuring formic acid in urine. The method consists of heating 1 ml urine sample in a 20-ml air-tight vial in the presence of 1 ml sulfuric acid and 2 ml ethanol at 60°C for 30 min for ethyl esterification and air-liquid equilibrium, followed by automatic injection of 1 ml head-space air into a flame ionization detector GC. The detection limit was 1 mg/l for formic acid. The method was applied to measure formic acid in the shift-end urine samples from 88 workers exposed to methanol at 66.6 ppm (as geometric mean) and in urine samples from 149 nonexposed controls. Methanol concentrations were also determined. Regression analysis showed that urinary formic acid concentrations, as observed or corrected for either creatinine concentration or specific gravity of urine (1.016), correlated significantly with time-weighted average intensities of exposure to methanol vapor. Men excreted significantly more formic acid than women. Comparison with methanol excretion suggested, however, that urinary formic acid is less sensitive than urinary methanol as an indicator of methanol vapor exposure, primarily because the background level for formic acid (26 mg/l as arithmetic mean, or 23 mg/l as geometric mean) is more than ten times higher than the level for methanol (1.9 mg/l as arithmetic mean, or 1.7mg/l as geometric mean). After theoretical methanol exposure at infinite concentration, the urinary formic acid/methanol ratio should be about 0.4.     

Determination of dimethylhippuric acid isomers in urine by high-performance liquid chromatography

 In order to analyse metabolites in urine after trimethylbenzene (TMB) exposure a method based on high-performance liquid chromatography (HPLC) for determination of the six dimethylhippuric acids (2,3-DMHA, 2,6-DMHA, 2,5-DMHA, 2,4-DMHA, 3,4-DMHA and 3,5-DMHA) in urine has been developed. In contrast to earlier published methods, the present method allows detection of all possible isomers of DMHA in a single analysis. The DMHAs were extracted from urine with dichloromethane. After evaporation, the residue was dissolved in mobile phase and analysed by a stepwise gradient HPLC system with ultraviolet (UV) detection at 225 nm. Mobile phase A (1.25% acetonitrile and 0.3% acetic acid in water) was used up to a retention time of 59.5 min and mobile phase B (5% acetonitrile in water containing 0.3% acetic acid) was used for completion of the analysis at approximately 90 min. The DMHA isomers were chromatographed on a reversed phase Radial-Pak C₁₈ column (4 μm; 100 mm×5 mm inner diameter). The detection limit for the six isomers was 1.5 μg/ml (range 0.5–3.4, 100 μl injection volume). The precision of the method was 4.2% relative standard deviation (range 3.8–4.4; 100 μg/ml). Standard curves of the DMHAs were linear over the interval 10–500 μg/ml in human urine. Individual DMHAs or the sum of DMHA isomers may be used as biological indicators of occupational exposure to TMBs. Received: 18 January 1996/Accepted : 7 June 1996     

Serum fluoride as an indicator of occupational hydrofluoric acid exposure

Summary To define the relationship between ionic fluoride concentration in the serum of workers and the amount of hydrofluoric acid (HF) in the work environment, pre-and postshift serum and urine samples of 142 HF workers and 270 unexposed workers were examined. The maximum and minimum concentrations of HF in the air in each workshop varied from the mean by less than 30%. The pre-exposure levels of serum and urinary fluoride in HF workers were higher (P < 0.001) than the control values. This suggests that fluoride excretion from the body continues for at least 12 h. The postshift serum and urinary fluoride concentrations of these workers were significantly higher (P < 0.001) than the preshift concentrations. A good correlation (r = 0.64) was obtained between postshift serum fluoride and postshift urine fluoride. There was a linear relationship between mean serum fluoride concentration and HF concentration in the workshop. A mean fluoride concentration of 82.3 g/l with a lower fiducial limit (95%, P = 0.05) of 57.9 g/l was estimated to correspond to an atmospheric HF concentration of 3 ppm. This is the maximum allowable environmental concentration recommended by the Japanese Association of Industrial Health, and it is also the threshold limit value suggested by the American Conference of Governmental Industrial Hygienists. The results demonstrate that exposure to HF can be monitored by determining the serum fluoride concentration.     

Urinary methoxyacetic acid as an indicator of occupational exposure to ethylene glycol dimethyl ether

Objective: To investigate whether methoxyacetic acid (MAA) is the metabolite of ethylene glycol dimethyl ether (EGdiME) in humans and whether its metabolite in urine can be used as a biomarker for exposure to EGdiME. Methods: Workers occupationally exposed to EGdiME, as well as nonexposed controls, were studied. Urine samples were collected from 20 control subjects and, on Friday postshift, from 14 workers. The identification and quantification of the metabolite were performed by gas chromatography/mass spectrometry (GC/MS) and GC/FID, respectively. Air samples were collected on activated charcoal tubes by area sampling with battery-operated pumps. The glycol ether was analyzed by GC/FID. Results: GC/MS clearly showed the metabolite of EGdiME to be MAA. Urinary MAA levels in the control subjects (background levels) were 0.0–0.3 mg/g crea. The levels of urinary MAA in the solvent-exposed workers were significantly (P<0.0001) higher than those in the control subjects. In the eight workers exposed to an average of 0.3 ppm of EGdiME and the six workers exposed to an average of 2.9 ppm, the mean urinary MAA level was 1.08 (range 0.6–1.5) mg/g crea and 9.33 (range 5.7–18.1) mg/g crea, respectively. These results can be explained by differences in the exposure intensity. Conclusions: Our results suggest that MAA is the metabolite of EGdiME, and that MAA in urine may be used for biological monitoring of EGdiME exposures.     

Urinary metabolite levels in workers handling p-tert-butylphenol as an index of personal exposure

Summary Occupational exposure to p-tert-butylphenol (PTBP) was studied in a workplace where workers were engaged in packing this alkylphenol in bags or transporting the bags by fork-lift. The geometrical mean of eight-hour-time-weighted-average (8 h-TWA) value for personal ambient PTBP level of the packers was 0.39 mg/m³ (n = 15), higher than that of the carriers (0.10 mg/m³, n = 5). Amounts of PTBP collected in the respirators used by the workers were in proportion to the 8 h-TWA values but lower than the estimated theoretical amounts; considerable amounts of PTBP were assumed to be absorbed through the respiratory tract. The urine excreted during the latter half of the shift showed the highest levels of PTBP (geometrical mean: packer, 5.07 g/ml, n = 20; carrier, 3.03 g/ml, n = 8). When the workers were away from the workplace, PTBP levels decreased; most was excreted within 24 h. Correlation between the urinary PTBP levels and 8 h-TWA values was significant (r = 0.46, n =19, P < 0.05), but its extent was weak. The total amounts of urinary PTBP excreted for 24 h after the start of the shift were two to three times higher than the estimated respiratory absorption of PTBP; PTBP was assumed to be absorbed not only through the respiratory tract but also through intact skin. It was concluded that the personal ambient PTBP level is not a suitable index for personal exposure, and biological monitoring via the PTBP level in the urine excreted at the end of the each shift is useful for the evaluation of personal exposure.     

Urinary excretion of 3,4-dimethylhippuric acid in workers exposed to 1,2,4-trimethylbenzene

Summary The urinary excretion of 3,4-dimethylhippuric acid (34DMHA), a 1,2,4-trimethylbenzene (124TMB) metabolite, was investigated in workers exposed to 124TMB vapor. The time-weighted average of exposure to 124TMB was determined with a diffusive sampler. For biological monitoring of exposure, urine samples were collected from individual workers and analyzed for metabolites by high-pressure liquid chromatography. The concentration of urinary 34DMHA had a positive correlation with the level of exposure to 124TMB (r = 0.72). The data suggest that 34DMHA is one of the useful indicators for biological monitoring of 124TMB exposure.     

Experimental human exposure to toluene

Summary The relationship between the individual toluene uptake and the urinary hippuric acid excretion was studied under experimental conditions. Six healthy male subjects were exposed to various concentrations in inspired air (50, 100, 125, 150, and 200 ppm) at rest or under different levels of physical effort.The hippuric acid excretion near the end of the exposure appeared under all circumstances directly proportional to the time-weighted uptake rate of toluene. The correlation between respiratory uptake rate and the rate of metabolite excretion near the end of the exposure period proved not to be systematically influenced by personal factors such as body weight, amount of body fat, urine flow rate and urinary pH. The relatively pronounced differences in background excretion of hippuric acid and, perhaps, distribution phenomena of toluene between different tissues under heavy workload conditions, can partly explain the greater variability in metabolite excretions as compared to the individual uptake rates.The correlation between the individual uptake rate of toluene and the hippuric acid excretion proved substantially better when using the end exposure excretion rate as exposure parameter as compared with the end exposure hippuric acid concentration, even after correcting the latter for urine density.Reasonable biological limit values complying to an acceptable time-weighted toluene dose were found to be 3000–3500 mg/l and 2.0–2.5 mg/min, resp. for average hippuric acid concentrations and excretion rates in spot samples during the second half of a complete work shift.     

Urinary methanol and formic acid as indicators of occupational exposure to methyl formate

Objective: To evaluate the validity of methanol (MeOH) and formic acid (FA) in urine as biological indicators of methyl formate (MF) exposure in experimental and field situations. Methods: The subjects were 28 foundrymen and two groups of volunteers (20 control and 20 exposed). Exposure assessment of the workers was performed by personal air and biological monitoring. Methyl formate vapour collected on charcoal tube was analysed by gas chromatography. The concentration of MF in the exposure chamber (volunteer-study) was monitored by two independent methods [flame ionisation detection (FID) and Fourier transformation infra-red detection (FTIR)]. Urinary metabolites (MeOH and FA) were analysed separately by head-space gas chromatography. Results: The volunteers exposed to 100 ppm MF vapour at rest for 8 h excreted 3.62 ± 1.13 mg MeOH/l (mean ± SD) at the end of the exposure. This was statistically different (P < 0.001) from pre-exposure MeOH excretion (2.15 ± 0.80 mg/l), or from that of controls (1.69 ± 0.48 mg/l). The urinary FA excretion was 32.2 ± 11.3 mg/g creatinine after the exposure, which was statistically different (P < 0.001) from pre-exposure excretion (18.0 ± 9.3 mg/g creatinine) or that of controls (13.8 ± 7.9 mg/g creatinine). In foundrymen, the urinary FA excretion after the 8 h workshift exposure to a time weighted average (TWA) concentration of 2 to 156 ppm MF showed a dose-dependent increase best modelled by a polynomial function. The highest urinary FA concentration was 129 mg/g creatinine. The pre-shift urinary FA of the foundrymen (18.3 ± 5.6 mg/g creatinine) did not differ from that of controls (13.8 ± 7.9 mg/g creatinine). The urinary MeOH excretion of the foundrymen after the shift, varied from <1 to 15.4 mg/l, while the correlation with the preceding MF exposure was poor. The foundrymen excreted more (P=0.01) FA (2.12 ± 3.56 mg/g creatinine) after the workshift than experimentally, once-exposed volunteers (0.32 ± 0.11 mg/g creatinine) at a similar inhaled MF level of 1 ppm). Conclusions: In spite of its high background level in non-exposed subjects, urinary FA seems to be a useful biomarker of methyl formate exposure. The question remains as to what is the reason for the differences in chronic and acute exposure respectively. Received: 27 September 1999 / Accepted: 25 March 2000     

Study on biological monitoring of fenpropathrin exposure in application by utilizing urinary 3-phenoxybenzoic acid level

To estimate pesticide exposure faced by applicators, an investigation of exposure-absorption was conducted on two applicators under routine working conditions and using regular procedures during pesticide spraying of greenhouse strawberries with fenpropathrin. The authors hypothesized that 3-phenoxybenzoic acid (3-PBA) is a urinary excreted metabolite of fenpropathrin, a synthetic pyrethroid pesticide with 3-phenoxybenzyl moiety, and its determination would help to improve the assessment of fenpropathrin exposure-absorption in applicators. The extent of exposure-absorption was evaluated by the determination of urinary level of 3-PBA (biological monitoring), the amount of the chemical adhered to clothes and permeated to the skin surface, and its concentration in the air of the greenhouse. The results showed that the fenpropathrin concentration in the air was less than 0.1 μg/m³. The amount of adhesion was less than 0.001 to 10.25 μg/cm², and there was very little permeation. However, the urinary 3-PBA concentration by biological monitoring appeared to be approximately twice that of pre-exposure levels in both applicators. This finding demonstrates that the applicators were exposed to fenpropathrin and absorbed it during spraying. We conclude that the fenpropathrin exposure-absorption in application could be estimated by the determination of urinary 3-PBA. This method of biological monitoring may be more useful indicator to accurately evaluate the working conditions in application.     

N-Methylsuccinimide in plasma and urine as a biomarker of exposure to N-methyl-2-pyrrolidone

Objective: N-Methyl-2-pyrrolidone (NMP) is a selective and powerful organic solvent. The aim of this study was to investigate whether the NMP metabolite N-methylsuccinimide (MSI) in plasma and urine can be used as a biomarker of exposure to NMP. Methods: Six healthy subjects were exposed to 10, 25, and 50 mg NMP/m³ in an exposure chamber for 8 h. The air levels were monitored by XAD-7 solid sorbent sampling, and analysed by gas chromatography (GC). Plasma and urine were sampled for two days following the exposure, and the levels of MSI were analysed by GC with mass spectrometric detection. Results: The concentration of MSI in plasma and urine rose during the exposure, and reached a peak at about 4 h after the end of the exposure. The concentration then decayed according to a one-compartment model with a half-time of approximately 8 h. About 1% of the inhaled NMP was excreted in urine as MSI. There were very close correlations between the NMP air levels and, on the one hand, the MSI concentrations in plasma collected at the end of exposure (r=0.98), or the urinary MSI concentration collected during the last 2 h of exposure (r=0.96), on the other. Conclusions: MSI in plasma or urine is applicable as a biomarker of exposure to NMP. The concentration in plasma and urine mainly reflects the exposure over one day. Received: 5 May 2000 / Accepted: 1 November 2000     

Methanol in urine as a biological indicator of occupational exposure to methanol vapor

Summary The exposure-excretion relationship and possible health effects of exposure to methanol vapor were studied in 33 exposed workers during the second half of 2 working weeks. Urinary methanol concentrations were also determined in 91 nonexposed subjects. The geometric mean value for methanol in urine samples from the latter was < 2 mg/1 (95% upper limit of normal, < 5 mg/l) when log-normal distribution was assumed. Among the exposed workers, the methanol level in urine samples collected prior to the work shift exceeded the 95% upper limit of normal. The time-weighted average intensity of exposure to methanol vapor was measured using personal sampling devices (in which water severed as an absorbent) in 48 cases of methanol exposure (i.e., 2 of the 33 exposed workers failed to provide urine samples, whereas 17 subjects were examined twice). Methanol concentrations in urine were determined in samples collected at the end of the shift from the 48 exposed cases as well as from 30 nonexposed controls. There was a significant correlation between the exposure to methanol vapor at concentrations of up to 5,500 ppm and the levels of methanol measured in the shift-end urine samples. The calculation indicated that a mean level of 42 mg methanol/l urine (95% confidence range, 26–60 mg/kg) was excreted in the shift-end urine sample following 8 h exposure to methanol at 200 ppm (the current occupational exposure limit). Dimmed vision and nasal irritation were among the most frequent symptoms complained during work. Three cases showing clinical signs of borderline significance were identified.     

Saliva as an analytical tool to measure occupational exposure to toluene

OBJECTIVE: To describe a sensitive and rapid method for the determination of toluene in saliva. Biomonitoring of toluene exposure is commonly performed by determination of urinary hippuric acid, o-cresol or toluene itself. The analysis of blood toluene has been verified as another method for biomonitoring. However, drawing blood is invasive and can often not be performed at the workplace for hygienic reasons. Sampling of saliva may be non-invasive, easy to perform and a viable alternative for biomonitoring in the workplace. METHODS: We measured the solvent concentration in saliva specimens of 5 healthy volunteers studied in the laboratory and a group of 36 workers exposed to toluene in the synthetic leather industry. Saliva was collected into Salivette (Sarstedt, Germany) devices by sterile cotton rolls placed in the mouth and then squeezed into pre-weighted vials. Environmental toluene was collected for the duration of a work-shift by Radiello (FSM, Italy) passive samplers. Toluene in urine and saliva (head space analysis) and in environmental samples was measured by GC-MS. RESULTS: Environmental toluene levels ranged from 0.22 to 57.20 mg/m(3), while the concentrations of the solvent in saliva and urine ranged from 0.12 to 18.30 mug/L, and from 0.47 to 26.64 mug/L, respectively. The correlation coefficients (r) between biological and environmental levels of toluene were 0.77 and 0.93, respectively, for saliva and urine samples. CONCLUSION: This preliminary study suggests that saliva may offer many advantages over 'classical' biological fluids such as blood as it is readily accessible and collectible: therefore saliva toluene may be considered as a possible biomarker of exposure to toluene.     

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.