Human toxicokinetics of inhaled monochlorobenzene: latest experimental findings regarding re-evaluation of the biological tolerance value

Objective: The aim of this study was to obtain toxicokinetic data on the absorption and elimination of monochlorobenzene (MCB) in blood and its main metabolite 4-chlorocatechol (4-ClCat) as well as on the isomeric chlorophenols (o-ClPh, m-ClPh, and especially p-ClPh as the main ClPh metabolite) in urine for re-evaluation of the biological tolerance (BAT) value of MCB. Methods: Eight subjects performed 8-h inhalation tests daily over five successive days in an exposure chamber, at a maximum allowable concentration at the workplace (MAK) value of 10 ppm MCB. Five and two probands carried out the test series during physical activity levels of 75 and 50 W, respectively, for 10 min/h on a bicycle ergometer, and one subject was exposed continuously while at rest. MCB and its metabolites were analyzed by gas chromatography in combination with mass spectrometry. Results: The mean MCB blood concentration of the five subjects exposed during physical activity of 75 W was 217 ± 42 μg/l. The relationship of the mean blood concentration measured under the conditions of rest or 50 and 75 W activity levels was in a ratio of about 1:1.7:2.8. The half-life values in the first hour after ending the exposures were 53 min and 150 min for the ensuing period, with steady-state being reached after 45 min. The mean 4-ClCat concentration in urine at the end of the five days was 150 ± 13 mg/g creatinine in the case of the subjects exposed at 75 W, which decreased to 25 mg/g creatinine at the beginning of the next exposure. The analogous p-ClPh concentrations were 25 ± 2 and 9 ± 2 mg/g creatinine. The elimination half-life values of the ClPh isomers ranged from 12.4 to 16.5 h, and the half-life of 4-ClCat was 6.4 h. There was no apparent tendency for MCB and its metabolites to accumulate in blood or urine. Conclusions: The results are in accordance with relevant field and laboratory studies. Taken into consideration with the 95th percentile, the evaluated BAT values should be set at levels of 300 μg MCB/l blood, 175 mg 4-ClCat/g creatinine or alternatively at 30 mg p-ClPh/g creatinine in urine after the end of a shift. At the beginning of the next shift, the BAT values of the metabolites should be 35 and 15 mg/g creatinine, respectively. Received: 20 December 1999 / Accepted: 25 April 2000     

Evaluation of occupational exposure to benzene by urinalysis

Urinary phenol determinations have traditionally been used to monitor high levels of occupational benzene exposure. However, urinary phenol cannot be used to monitor low-level exposures. New biological indexes for exposure to low levels of benzene are thus needed. The aim of this study was to investigate the relations between exposure to benzene (Abenzene, ppm), as measured by personal air sampling, and the excretion of benzene (U-benzene, ng/l),trans,trans-muconic acid (MA, mg/g creatinine), andS-phenylmercapturic acid (PMA, g/g creatinine) in urine. The subjects of the study were 145 workers exposed to benzene in a chemical plant. The geometric mean exposure level was 0.1 ppm (geometric standard deviation = 4.16). After logarithmic transformation of the data the following linear regressions were found: log (U-benzene, ng/l) = 0.681 log (A-benzene ppm) + 4.018; log (MA, mg/g creatinine) = 0.429 log (A-benzen ppm) – 0.304; and log (PMA, g/g creatinine) = 0.712 log (A-benzene ppm) + 1.664. The correlation coefficients were, respectively, 0.66, 0.58, and 0.74. On the basis of the equations it was possible to establish tentative biological limit values corresponding to the respective occupational exposure limit values. In conclusion, the concentrations of benzene, mercapturic acid, and muconic acid in urine proved to be good parameters for monitoring low benzene exposure at the workplace.     

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 hydroxy-metabolites of naphthalene,phenanthrene and pyrene as markers of exposure to diesel exhaust

Objective The objective of this study was to assess the exposure of bus-garage and waste-collection workers to polycyclic aromatic hydrocarbons (PAHs) derived from diesel exhaust by the measurement of levels of seven urinary PAH metabolites: 2-naphthol, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, 1+9-hydroxyphenanthrene, 4-hydroxyphenanthrene and 1-hydroxypyrene.Subjects and methods One urine sample from each of 46 control persons, and one pre-shift and two post-shift spot urine samples from 32 exposed workers were obtained in winter and in summer. The metabolites were analysed after enzymatic hydrolysis by high performance liquid chromatography (HPLC) with fluorescence detection.Results The sum of seven PAH metabolites (mean 3.94±3.40 and 5.60±6.37 mol/mol creatinine in winter and summer, respectively) was higher [P=0.01, degrees of freedom (df) =61.2 and P=0.01, df=67.6 in winter and summer, respectively] in the exposed group than in the control group (mean 3.18±3.99 and 3.03±2.01 mol/mol creatinine in winter and summer, respectively). The mean concentrations of 2-naphthol among exposed and controls ranged between 3.34 and 4.85 mol/mol creatinine and 2.51 and 2.58 mol/mol creatinine, respectively (P<0.01 in winter, P<0.03 in summer). The mean level of the hydroxyphenanthrenes in the samples of exposed workers was between 0.40 and 0.70 mol/mol creatinine and in the control samples 0.40–0.60 mol/mol creatinine. The concentration of 1-hydroxypyrene was higher among exposed workers in both pre-shift and post-shift samples (mean 0.10–0.15 mol/mol creatinine) than in control group (mean 0.05–0.06 mol/mol creatinine) in winter (P=0.002, df=78) and in summer (P<0.001, df=68).Conclusions The urinary hydroxy-metabolites of naphthalene, phenanthrene and pyrene showed low exposure to diesel-derived PAHs; however, it was higher in exposed workers than in control group. Urinary PAH monohydroxy-metabolites measured in this study did not correlate with the PAHs in the air samples, reported earlier, in 2002 and 2003.     

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.     

Concentrations of urinary metabolites in workers exposed to monochlorobenzene and variation in the concentration during a workshift.

Urinary concentrations of metabolites of monochlorobenzene were examined in 10 male workers exposed to the compound while synthesising intermediate products for dyes. Their individual exposure concentrations were monitored for the whole workshift and samples of urine were collected at the start and end of the workshift, during it, and during the noon recess. The concentrations of four metabolites, 4-chlorocatechol and o-, m-, and p-chlorophenol, in the urine samples were measured. The investigation was performed on Monday and Tuesday in one week and on Tuesday and Wednesday in another week. The concentrations of 4-chlorocatechol in urine collected during the last four hours and at the end of the workshift were proportional to the eight hour time weighted average exposure to monochlorobenzene. The concentration in urine collected during the noon recess showed a linear correlation with the four hour time weighted average in the morning. Similarly, linear relations were obtained for urinary p-chlorophenol. The ratio (as monochlorobenzene) of p-chlorophenol to 4-chlorocatechol concentrations at the start of the workshift was 0.39 and at the end of the workshift was 0.22. The ratios of the urinary concentrations 15 hours after exposure to those at the end of exposure were 0.24 for 4-chlorocatechol and 0.44 for p-chlorophenol. The present study also showed that variations in exposure at the workplace were reflected by changes in concentrations of urinary metabolites during the workshift.     

Genotoxic risk assessment in white blood cells of occupationally exposed workers before and after alteration of the polycyclic aromatic hydrocarbon (PAH) profile in the production material: comparison with PAH air and urinary metabolite levels

Objective: Workers in various industries can be exposed to polycyclic aromatic hydrocarbons (PAHs). The relationship between biomarkers of genotoxic risk, PAH compounds in air (ambient monitoring) and PAH metabolites in urine (internal exposure) were studied in 17 workers exposed to PAHs in a fireproof-material producing plant before and 3 months after the PAH profile was altered in the binding pitch. Methods: Two biomarkers of exposure, specific DNA adducts of (±)-r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) and non-specific DNA adduct of 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodGuo) were determined in white blood cells (WBCs). In addition, DNA strand breaks were analysed in lymphocytes by single-cell gel electrophoresis in a genotoxic risk assessment. Sixteen PAH compounds in air were determined by personal air sampling, and hydroxylated metabolites of phenanthrene, pyrene and naphthalene were determined in urine. Results: After substitution of the binding pitch the concentrations of benzo[a]pyrene in air decreased (P<0.01). No changes could be observed for pyrene, while levels of phenanthrene (P=0.0013) and naphthalene (P=0.0346) in air increased. Consequently, median DNA adduct rates of anti-BPDE decreased after alteration of the production material (from 0.9 to <0.5 adducts/10⁸ nucleotides). No changes in the excretion of 1-hydroxypyrene in urine could be determined, whereas increased levels of 1-, 2+9-, 3- and 4-hydroxyphenanthrene (P<0.0001) and 1-naphthol and 2-naphthol (P=0.0072) were found in urine. In addition, a statistically significant increase in DNA strand break frequencies (P<0.01) and elevated 8-oxodGuo adduct levels (P=0.7819, not statistically significant) were found in the WBCs of exposed workers 3 months after the PAH profile in the binding pitch had been altered. Conclusion: The results presented here show that the increased concentration of naphthalene and/or phenanthrene in the air at the work place could induce the formation of DNA strand breaks and alkali-labile sites in WBCs of exposed workers.     

Lead in finger bone, whole blood, plasma and urine in lead-smelter workers: extended exposure range

Objectives: To assess the historical exposure and to study the relationships between lead concentrations in whole blood (B-Pb), plasma (P-Pb), urine (U-Pb), finger bone (Bone-Pb) and duration of employment in workers at a secondary lead smelter and to compare the relationships between B-Pb and P-Pb with results from previous studies of populations with a wide range of lead exposure. Methods: In 39 lead workers (29 active, ten retired), recruited from those with the highest exposure at a German secondary lead smelter, levels of B-Pb, P-Pb and U-Pb were determined by inductively coupled plasma mass spectrometry (ICP-MS). Bone-Pb was determined by in vivo X-ray fluorescence (XRF). Results were compared with data from a previous study on 90 workers (71 active, 19 retired) with lower exposure, from a Swedish secondary lead smelter, as well as with previously collected data from 42 active Russian lead workers and 34 Ecuadorian lead-exposed subjects. Results: The median values in the active/retired German lead workers were: age 44/59 years, duration of employment 20/38 years, Bone-Pb 71/150 g/g, B-Pb 500/330 g/l, P-Pb 2.7/1.1 g/l, and U-Pb 25/13 mol/mol creatinine. Bone-Pb increased with duration of employment by 4.2 g/g per year and 1.6 g/g per year in German and Swedish workers, respectively. The median Bone-Pb was three times higher in both active and retired German workers than in Swedish smelter workers with essentially the same age distribution and duration of employment. The linear regression equation between B-Pb and log P-Pb in the combined group of Ecuadorian, German, Russian and Swedish lead-exposed subjects (n=176) was B-Pb=545×log[P-Pb] + 258 (r_s=0.94; P<0.001). Conclusions: The high Bone-Pb values recorded for the German smelters implied a historical lead exposure of considerable magnitude. The long-term high lead exposure also showed up in the B-Pb levels for both active and retired workers, leading to the implementation of necessary industrial safety measures in order to respond to biological threshold limits. The suggested equation describing the relationship between B-Pb and P-Pb in the combined group of subjects with a wide range of lead exposure can be useful in future cross-sectional and longitudinal studies of lead-exposed populations, relating, e.g., lead exposure to adverse health outcomes.     

Occupational exposure to cadmium and kidney dysfunction

Summary Investigations were carried out in an alkaline battery factory. The study group consisted of 102 persons and the control group of 85 persons. Cadmium in blood (Cd-B) and cadmium in urine (Cd-U), as well as ₂-microglobulin (B₂-M), retinol binding protein (RBP), amino acids in urine were determined. Exposure to cadmium was high; Cd-B and Cd-U concentrations were higher than recommended, 10 gmg/l and 10 gmg/g creat. in 65% and 56% of workers, respectively. Excretion of B₂-M and RBP in urine was higher than the accepted upper limits of 380 and 130 I g/g creat. in about 20% of the workers. A significant correlation was observed between: log Cd-U log Cd-B (r = 0.85), log B₂-M log RBP (r = 0.66), log Cd-U · log B₂- M (r = 0.52), and log Cd-U · log RBP (r = 0.55). To evaluate the admissible period of occupational exposure to cadmium, an integrated exposure index (Cd-B × years of exposure) is proposed. According to the dose-response relationship, an increase of low molecular protein excretion in urine can be expected in 10% of the cases at Cd-U amounting to 10 to 15 g/g creat. and Cd-B × years of about 300 to 400.     

Biological monitoring of occupational exposure to methyl ethyl ketone

Summary This study was conducted to evaluate the usefulness of three commonly used methods of biological monitoring for worker exposed to methyl ethyl ketone (MEK) under field conditions using blood, breath and urine. Environmental MEK exposures were measured by personal sampling with carbon-felt dosimeters. The correlation coefficient (r) between the time-weighted average (TWA) MEK concentration in air and the MEK concentration in blood collected at the end of the work shift was 0.85. The correlation coefficient between the TWA MEK level in air and the concentration exhaled in the breath of workers at the end of the work shift was 0.71. The end-of-shift urinary MEK excretion correlated best with the environmental concentration (r = 0.89). Correlations became lower after urine samples had been corrected for urinary creatinine (r = 0.83) or specific gravity (r = 0.73). After 8 h exposure to 200 ppm MEK, the corresponding end-of-shift urinary excretion was 5.11ol/l or 4.11 mg/g creatinine. This value is higher than that previously found in some studies, the difference probably being due to the physical acitivites of the present workers and their extensive skin contact with the solvent. The kinetics of inhaled MEK was also studied in eight subjects. Breath and urine samples were collected during the 8-h work shift on 2 consecutive Mondays. The results showed that urinary MEK excretion rose steadily until the end of exposure, whereas the MEK concentration in exhaled air varied markedly throughout the day. These findings suggest that the determination of MEK levels in end-of-shift urine samples appears to be the most reliable biological indicator of occupational exposure.     

Biological monitoring of occupational exposure to cyclohexane by urinary 1,2- and 1,4-cyclohexanediol determination

Objectives: This article reports the results obtained with the biological and environmental monitoring of occupational exposure to cyclohexane using 1,2-cyclohexanediol (1,2-DIOL) and 1,4-DIOL in urine. The kinetic profile of 1,2-DIOL in urine suggested by a physiologically based pharmacokinetic (PBPK) model was compared with the results obtained in workers. Methods: Individual exposure to cyclohexane was measured in 156 workers employed in shoe and leather factories. The biological monitoring of cyclohexane exposure was done by measurement of 1,2-DIOL and 1,4-DIOL in urine collected on different days of the working week. In all, 29 workers provided urine samples on Monday (before and after the work shift) and 47 workers provided biological samples on Thursday at the end of the shift and on Friday morning. Another 86 workers provided biological samples at the end of the work shift only on Monday or Thursday. Results: Individual exposure to cyclohexane ranged from 7 to 617 mg/m³ (geometric mean value 60 mg/m³). Urinary concentrations of 1,2-DIOL (geometric mean) were 3.1, 7.6, 13.2, and 6.3 mg/g creatinine on Monday (pre- and postshift), Thursday (postshift) and Friday (pre-shift), respectively. The corresponding values recorded for 1,4-DIOL were 2.8, 5.1, 7.8, and 3.7 mg/g creatinine. A fairly close, statistically significant correlation was found between environmental exposure to cyclohexane and postshift urinary 1,2-DIOL and 1,4-DIOL on Monday. Data collected on Thursday and Friday showed only a poor correlation to exposure with a wide scatter. Both metabolites have a urinary half-life of close to 18 h and accumulate during the working week. Conclusions: Comparison between data obtained from a PBPK model and those found in workers suggests that 1,2-DIOL and 1,4-DIOL are urinary metabolites suitable for the biological monitoring of industrial exposure to cyclohexane. Received: 17 June 1998 / Accepted: 23 September 1998     

Quantitation of urinary chlorobenzene metabolites by HPLC: concentrations of 4-chlorocatechol and chlorophenols in urine and of chlorobenzene in biological specimens of subjects exposed to chlorobenzene

Summary A simple method for the determination of 4-chlorocatechol (ClCh, 4-chloro-1,2-benzenediol) and chlorophenols (ClPh), metabolites of monochlorobenzene (ClBz), in urine by high performance liquid chromatography (HPLC) is described. Enzymatic hydrolysates of urine were applied to a stainless-steel column packed with octadecyl-silanized silica gel, and a mixed solution of 20 mM potassium phosphate monobasic : acetonitryl (75:25, v/v) was used as a mobile phase. The procedures for ether extraction and evaporation of extract could be omitted. The accuracy and precision of the present HPLC method were satisfactory. The excretion kinetics of ClCh and p-ClPh were investigated over 35 h after cessation of ClBz inhalation. Proportional relationships between concentrations of ClBz in air and of its metabolites in urine were observed. The slopes of regression lines predicting the levels of ClCh, p-ClPh and total ClPh in urine taken during the last 2 h of exposure to ClBz in air were 6.56, 1.13 and 2.83 mg/g creatinine for 1 ppm ClBz respectively. ClBz in the blood and the end exhaled air of subjects at the end of exposure were identified by gas chromatography (GC) and mass spectrometry. A proportional relationship was observed between the concentration of ClBz in air and that in blood. The validity of the threshold limit value (TLV) for ClBz as evaluated from the subjective and objective symptoms is discussed.     

Occupational fluoride exposure and plasma fluoride levels in man

Summary The individual fluoride exposure and the corresponding body fluid levels were studied in 41 workers in an aluminium plant in Sweden. During the shift (8 h) personal air samplings were performed and plasma fluoride levels determined. Pre- and post-shift urine fluoride excretion were also measured. The average total fluoride exposure was 0.91 mg/m³ of which 34% was gaseous fluoride (mean value 0.31 mg/m³ The mean fluoride plasma level before the shift was 23 ng/ml (1.2 M/l) and increased on average to 48 ng/ml (range 14–151 ng/ml) at the end of the shift. The plasma levels found were in no case remarkably high. There was a high correlation between fluoride renal clearance and urinary flow (r = 0.481; n = 38; P = 0.00232). A high fluid intake during the shift will thus increase the capacity of the kidney to excrete fluoride and decrease the levels of fluoride in the body. There was a significant correlation between the amount of gaseous fluoride and the area under the plasma concentration-time curve (r = 0.459; n = 40; P = 0.0029) and also the amount of fluoride excreted (r = 0.530; n = 40; P = 0.0004). When fluoride exposure and body burden are to be studied on an individual basis these two parameters give better quantitative information and are to be recommended instead of urine fluoride concentration measurements. The prevention of fluoride inhalation by using a safety-mask during the shift was also demonstrated. The workers who used a safety-mask during the whole shift reduced the inhalation of fluoride to 30 to 40% compared to those who did not use any mask.Supported by grants from the Swedish Work Environment Fund, grant no. 81-1100 and the Swedish Medical Research Council, grant no 6002     

Concentrations of benzene in blood and S-phenylmercapturic and t,t-muconic acid in urine in car mechanics

Summary Different parameters of biological monitoring were applied to 26 benzene-exposed car mechanics. Twenty car mechanics worked in a work environment with probably high benzene exposures (exposed workers); six car mechanics primarily involved in work organization were classified as non-exposed. The maximum air benzene concentration at the work places of exposed mechanics was 13 mg/m³ (mean 2.6 mg/m³). Elevated benzene exposure was associated with job tasks involving work on fuel injections, petrol tanks, cylinder blocks, gasoline pipes, fuel filters, fuel pumps and valves. The mean blood benzene level in the exposed workers was 3.3 g/l (range 0.7–13.6 g/1). Phenol proved to be an inadequate monitoring parameter within the exposure ranges investigated. The muconic and S-phenylmercapturic acid concentrations in urine showed a marked increase during the work shift. Both also showed significant correlations with benzene concentrations in air or in blood. The best correlations between the benzene air level and the mercapturic and muconic acid concentrations in urine were found at the end of the work shift (phenylmercapturic acid concentration: r = 0.81, P < 0.0001; muconic acid concentration: r = 0.54, P < 0.05). In conclusion, the concentrations of benzene in blood and mercapturic and muconic acid in urine proved to be good parameters for monitoring benzene exposure at the workplace even at benzene air levels below the current exposure limits. Today working as a car mechanic seems to be one of the occupations typically associated with benzene exposure.     

Monitoring of occupational exposure to 1-butanol by diffusive sampling and urinalysis

 Objectives: To investigate the possibility of applying diffusive air sampling and urinalysis (for mother compound and metabolites) to the monitoring of exposure of factory workers to 1-butanol. Methods: The performance of carbon cloth in adsorbing 1-butanol vapor in air was studied by experimental exposure of the cloth to 1-butanol at 50, 100, 200 or 400 ppm for up to 10 h. 1-Butanol in the exposed cloth was extracted with carbon disulfide and this was followed by gas-chromatographic (GC) analysis. Urine samples were collected from factory workers occupationally exposed to 1-butanol and from rats exposed experimentally to 1-butanol vapour (up to 200 ppm). The urine samples were analyzed by GC without any pretreatment, or after treatment with hydrochloric acid or hydrolase preparation. Results: The performance of the carbon cloth was such that it adsorbed 1-butanol in proportion to the concentration (up to 400 ppm) and the duration (up to 10 h) of exposure, and responded quantitatively to a 15-min exposure up to 400 ppm. The amount of 1-butanol (after enzymic or acid hydrolysis) in post-exposure urine samples from rats was proportional to the exposure intensity. The proportion of free 1-butanol in total 1-butanol (i.e., free+conjugated) in urine was higher after 100 or 200 ppm exposure (35–40%) than after 50 ppm exposure (about 8%). There was a significant increase in total 1-butanol concentration (but not in free 1-butanol) in shift-end urine samples of workers exposed to 1-butanol at concentrations up to 3 ppm. Conclusions: Diffusive sampling with carbon cloth as an adsorbent can be applied to ambient air monitoring of exposure to 1-butanol. Urinalysis for 1-butanol after hydrolysis is sensitive enough to detect occupational 1-butanol vapour exposure at 3 ppm. Received: 29 January 1996 / Accepted: 3 May 1996     

Evaluation of biological monitoring among stainless steel welders

Summary Ten manual metal arc (MMA) high alloy stainless steel (SS) welders were studied during one week and the concentrations of chromium (Cr) and nickel (Ni) were determined in their urine and blood. Stationary and personal air samples were collected from the immediate work environment; they covered the entire work period. Spot urine samples were collected during the follow-up period. Whole blood and plasma samples were taken from the workers before and after one shift, and the retention rate of magnetic dust in the lungs was estimated with magnetopneumography. On the basis of the results, indices of short-term exposure to Cr and Ni were evaluated. Urinary Cr and Ni concentrations (corrected to creatinine) reflect both the body burden caused by long-term and short-term exposure to easily soluble fractions of these metals. The results indicated that the use of Cr and Ni urinary analyses as indices of short-term exposure is not as dependable as previously assumed. The Cr and Ni concentrations in whole blood and plasma did not correlate with the measured exposure, but the daily mean increase in the Cr concentration reflected exposure to total Cr and Cr (VI) very well. The large variation in the Cr concentration of the morning urine (0.01–2.7 mol/l) and blood (0.05–1.43 mol/l) indicated large personal variations of body burden among the exposed welders. The retention rate of magnetic dust in the lungs correlated well (P<0.01) with the daily mean increase of Cr in blood. Very good correlations (P<0.001) were found between the retention rate of magnetic dust and the personal air samples of Cr and Cr (VI).     

Occupational chronic exposure to organic solvents

Summary Seventeen persons (2 women and 15 men), who were exposed to glycolethers in a varnish production plant, were examined according to their external and internal solvent exposure. The workers in the production plant (n =12) were exposed to average concentrations of ethoxyethanol, ethoxyethyl acetate, butoxyethanol, 1-methoxypropanol-2, 2-methoxypropyl-1-acetate and xylene of 2.8; 2.7; 1.1; 7.0; 2.8 and 1.7 ppm. In the air of the store (n = 3) and in the laboratory (n = 2) only minor concentrations of xylene respectively xylene and ethoxyethyl acetate could be measured. Internal exposure was estimated by measuring butoxyethanol (BE) in blood as well as ethoxyacetic acid (EAA) and butoxyacetic acid (BAA) in urine samples. Urine samples were taken pre- and post-shift. As expected, the highest values were found in the varnish production. The average post shift concentrations of BE, EAA and BAA were 121.3 g/l; 167.8 and 10.5 mg/l. The relatively high concentrations of EAA and BAA in pre-shift samples can be explained by the long half-lives of these metabolites. According to our findings most of the glycolethers were taken up through the skin. Comparing our results with those reported in the literature we think that a future tolerable limit value for the concentration of ethoxyacetic acid in urine should be in the order of 100 to 200 mg/l.     

Mutagens in urine of carbon electrode workers

Summary Following previous work carried out in an Italian factory producing carbon electrodes and evaluating the occupational mutagenic-carcinogenic hazards, the authors studied the presence of mutagen metabolites in the urine of workers in the same factory who were exposed to petroleum coke and pitch and in the urine of a control group of unexposed workers. The urine samples were concentrated by absorption on XAD-2 columns and were tested using the Salmonella/microsome assay (strain TA 98, TA 100, TA 1535, TA 1538) with and without the addition of beta-glucuronidase and metabolizing system. The collection of urine samples was carried out twice, with an interval of 2 months; before working time, after working time, and also during Sunday. The results showed that (1) urine samples collected before occupational exposure (upon waking) or on Sunday revealed no mutagenic activity in either worker groups and (2) that the urine samples collected after or during occupational exposure revealed high mutagenic activity in the exposed workers, with a statistically significant difference (P<0.05) between the mean of the revertants/plate values for exposed and unexposed workers. On the basis of the previous and the present research, the authors suggest that application of the Salmonella/microsome test to work environments could offer useful and suitable tool for evaluating the health hazards due to mutagenic/carcinogenic substances from occupational exposure.     

Neuropsychological function in manganese alloy plant workers

Objectives The objective was to investigate potential nervous system effects of manganese (Mn) exposure in workers employed in manganese-alloy-producing plants.Methods One hundred male Mn alloy plant workers were compared with 100 age-matched referents. The subjects were examined with a comprehensive neuropsychological test battery. Exposure was assessed by measurement of Mn concentrations in the workroom air, blood and urine.Results The geometric mean (GM) concentration of inhalable Mn in workroom air was 301 g/m³. The GM concentration of Mn in whole blood (181 nmol/l vs 160 nmol/l) (P=0.002) and urine (0.9 nmol/mmol creatinine vs 0.4 nmol/mmol creatinine) (P<0.001) was higher among the exposed subjects than among the referents. The Mn-exposed subjects had increased postural tremor while conducting a visually guided tremor test (static steadiness test) compared with the referents (mean number of contacts 94 vs 59 (P= 0.001); duration of contacts (in seconds) 5.1 vs 3.5 (P=0.003)). The tremor had larger frequency dispersion, indicating that the tremor included a wider variety of frequencies, among the exposed subjects than among the referents, assessed by the TREMOR test system. Smoking habits (self-reported) influenced the tremor parameters significantly, the Mn-exposed smokers having more tremor than the non-smoking Mn-exposed subjects. No differences between the groups were found in tests for cognitive functions, reaction time or in symptom reporting.Conclusion The Mn-exposed subjects had increased hand tremor compared with their referents. The tremor was related to exposure parameters. Smoking habits (self-reported) influenced the tremor parameters.     

Study on the cytochrome P-450- and glutathione-dependent biotransformation of trichloroethylene in humans

Objectives: To investigate in humans the contribution of the cytochrome P-450- and glutathione-dependent biotransformation of trichloroethylene (TRI) under controlled repeated exposure in volunteers, and under occupational conditions. Methods: Volunteers were exposed to TRI, using repeated 15?min exposures at 50 and 100?ppm. This exposure schedule resulted in internal doses of 1.30 and 2.40?mmol of TRI respectively. Urine samples were collected for a minimum of 45?h. Urine samples were also collected from occupationally exposed workers. The samples were analysed for the known human metabolites of TRI, trichloroethanol (TCE), trichloroacetic acid (TCA) and both regio-isomeric forms of the mercapturic acid N-acetyl-S-(dichlorovinyl)-l-cysteine (DCV-NAC), and for (dichlorovinyl)-l-cysteine (DCVC). In order to further elucidate the metabolism of TRI in humans, we analysed samples for dichloroacetic acid and for the proposed break-down products of 1,2 and 2,2-dichlorovinyl-L-cysteine after deamination: the S-conjugates of 3-mercaptolactic acid, 3-mercaptopyruvic acid and 2-mercaptoacetic acid. Results: None of the glutathione metabolites was found in urine of volunteers. In workers occupationally exposed to TRI at levels between 0.4 and 21?ppm [8-h time-weighted average (TWA)], levels of DCV-NAC in urine samples collected at the end of the 4th working day and also next morning were below detection limit (0.04?μmol/l). This confirms the findings of Bernauer et?al. (1996) that these metabolites are excreted at very low levels in humans. Urinary levels of DCVC and six postulated metabolites of dichlorovinyl-S-cysteine conjugates via deamination were also below 0.04?μmol/l, indicating that at most 0.05% of the dose is excreted in the form of these metabolites. These data further strengthen the argument for a very low activity of glutathione-mediated metabolism for chronically exposed workers. Conclusions: This study gives additional data which indicate that glutathione-mediated metabolism is of minor importance in humans exposed to TRI. In spite of indications to the contrary, significant metabolism of the cysteine conjugate via ß-lyase, which could result in a toxic metabolite, cannot be ruled out completely.