E. Capodaglio

The Urinary Concentration of Solvents as a Biological Indicator of Exposure: Proposal for the Biological Equivalent Exposure Limit for Nine Solvents

Organic solvents are generally volatile substances that are absorbed mainly through the lungs; they are eliminated chiefly through the lungs and kidneys. In urine they are present as metabolites and, in very little part, as parent compound. The urinary concentration of solvent (Cu) can be used for the biological monitoring of exposed subjects to evaluate their exposure and correlate with the Threshold Limit Value (TLV) during the working day. The authors report some results obtained with workers occupationally exposed to solvents. The results concern the correlation between urinary concentration (Cu, micrograms/L) vs. average environmental concentration (Ci, mg/m3) measured in the breathing zone. For each solvent studied (acetone, 2-cyclohexane, 1,2-dichloropropane, n-hexane, methyl ethyl ketone, perchloroethylene, styrene, toluene, 1,1,1-trichloroethane) the authors propose a Biological Equivalent Exposure Limit (BEEL) corresponding to the environmental TLV.

Determination of S-phenylmercapturic acid in urine as an indicator of exposure to benzene

S-phenylmercapturic acid (S-PMA) was measured in urine from 145 subjects exposed to low benzene concentrations in the air (C(I), benzene). The 8-h, time-weighted exposure intensity of individual workers was monitored by means of charcoal tubes and subsequent gas-chromatographic analysis after desorption with CS2. S-PMA excretion level in urine was determined by high-performance liquid chromatography with fluorescence detection. The following linear correlation was found between S-PMA concentrations in urine and benzene concentrations in the breathing zone: log(S-PMA, microg/g creatinine) = 0.712 log (C(I)-benzene, ppm) + 1.644 (n = 145, r = 0.74, P < 0.001). The geometric mean (GSD) of S-PMA concentrations in urine from 45 subjects occupationally not exposed to benzene but smoking more than 20 cigarettes/day was 7.8 microg/g creatinine (2.11), the corresponding value among non-smokers being 1.0 microg/g creatinine (2.18). It is concluded that the urinary level of S-PMA can be regarded as a useful indicator of exposure to benzene.

Urinary concentration, environmental concentration, and respiratory uptake of some solvents: effect of the work load.

The physical demands of the workplace differ depending on specific jobs. This implies that workers exposed to the same environmental level of an airborne contaminant can absorb different amounts of it depending on their pulmonary ventilation. Starting from the relationship between the uptake (U) and the urinary concentration of six solvents (Cu) (acetone, styrene, toluene, xylenes, methylchloroform, tetrachloroethylene) and from the equation expressing their lung uptake (U = K.V.CI.R.T) the expected values of a biological index after a given time of exposure can be derived. Such values are a function not only of the environmental level of exposure (CI) but also of the pulmonary ventilation (V - dependent solvent) and of the retention index (R) (V - R dependent solvent).

Urinary excretion of specific mercapturic acids in workers exposed to styrene

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

Anesthetic in urine as biological index of exposure in operating-room personnel.

The aim of this study was to determine if a relationship existed between some inhalation anesthetics airborne exposure levels (Cl) and the concentration of anesthetics in samples of urine produced throughout the exposure time (Cu). The concentrations of nitrous oxide (N2O), halothane (fluothane), enflurane (ethrane), and isoflurane (forane) in the ambient atmosphere were determined in 190 operating theaters of 41 hospitals in Italy. Nitrous oxide, halothane, enflurane and isoflurane were detected in the urine of 1521 exposed subjects (anesthetists, surgeons, and nurses). The environmental measurements were performed using personal passive samplers, and the biological measurements were performed using the head space method. Significant correlations were found between the anesthetics concentration in urine produced during the shift collected after a 4-h exposure (Cu, microgram/L) and anesthetics environmental concentration (Cl, ppm). The results show that the urinary anesthetic concentration can be used as an appropriate biological exposure index. The biological values (urinary concentration values) proposed are the following: nitrous oxide, 25 micrograms/L, for an environmental value of 50 ppm; halothane, 97 micrograms/L, corresponding to 50 ppm of environmental exposure; 6.2 micrograms/L, corresponding to 2 ppm of environmental exposure; enflurane, 145 micrograms/L for an environmental exposure of 75 ppm and 5.6 micrograms/L for an environmental exposure of 2 ppm; isoflurane, 5.3 micrograms/L for an environmental exposure of 2 ppm. The values proposed are the respectively 95% lower confidence limit and therefore should be considered as a protection for the individual, especially if each biological value is corrected according to analytical variability of the measurements. In our opinion, the method of choice in the assessment of occupational exposure to inhalation anesthetics is the measurement of the urinary anesthetic concentration.

Toluene and Styrene in Urine as Biological Exposure Indices

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

Urinary Excretion of Tetrachloroethylene (Perchloroethylene) in Experimental and Occupational Exposure

Fifteen human volunteers were exposed to tetrachloroethylene (perchloroethylene, tetrachloroethene) vapor at 3.6-316 mg/m3 for 2-4 hr at rest (10 cases) and during light physical exercise (5 cases). Subsequently, 55 workers who were occupationally exposed to tetrachloroethylene in eight commercial dry cleaning facilities were studied (median value, 66 mg/m3; geometric standard deviation, 3.15 mg/m3). In both the experimentally exposed subjects and occupationally exposed workers the urinary concentration of tetrachloroethylene showed a linear relationship to the corresponding environmental time-weighted average concentration. The findings indicate that the urinary concentration of tetrachloroethylene can be used as an appropriate biological exposure indicator. In occupationally exposed subjects performing moderate work, the urinary tetrachloroethylene concentration corresponding to the time-weighted average of the threshold limit value proved to be 120 mcg/L and its 95% lower confidence limit (biological threshold) 100 mcg/L. The effects of workload on the tetrachloroethylene urinary elimination are also accounted for.

Nitrous Oxide (N2O) in Urine as Biological Index of Exposure in Operating Room Personnel

Abstract The concentration of nitrous oxide (N2O) in urine was determined in 145 subjects (anesthetists, surgeons, and nurses) in operating theaters. The time-weighted average environmental concentration of N2O (breathing zone) was measured by means of personal passive samplers. The analyses were performed by the head space method, using a Hewlett-Packard 5880 A gas chromatograph with a Hewlett-Packard 5970 A Mass Selective Detector. A significant correlation was found between the N2O concentration in urine produced during the shift (C-u, μg/L) and N2O environmental concentration (C-I, ppm) (C-u = 0.582 C-I + 5.47; r = 0.89). The results show that the urinary concentration can be used as an appropriate biological exposure indicator. The authors suggest a Biological Exposure Index (BEI) of 55 μg/L of N2O in urine. This is the biological value obtained after four hours of an average environmental exposure to 100 ppm. Imbriani, M.; Ghittori, S.; Pezzagno, G.; Capodaglio, E.: Nitrous Oxide (N2O) in Urine as a...

n-Hexane urine elimination and weighted exposure concentration

SummaryThe concentration of n-hexane in urine was determined in 30 subjects occupationally exposed to n-hexane (median value 59.6 mg/m3) in a shoe factory. The measurement of the substance was performed by means of a Hewlett-Packard 5880 gas chromatograph supplied with a Hewlett-Packard 5970 Mass Selective Detector. The analyses were performed by the head space method (constant volume method, after determination of the urine partition coefficient by the multiple phase equilibration method). The authors found a significant correlation between the n-hexane urine concentrations (μg/1, Cu) and the n-hexane environmental concentrations (mg/m3, Ci) (r = 0.84; Cu = 0.0669 x Ci + 0.8396).

Determination of 2,5-hexandione by high-performance liquid chromatography after derivatization with dansylhydrazine

A sensitive method for the determination of free and total urinary 2,5-hexandione (2,5-HD) using high-performance liquid chromatography with fluorescence detection was developed. After purification of urine with a disposable C18 cartridge, 2,5-HD was derivatized with dansylhydrazine; 1,3-diacetyl benzene (1,3-DAB) was added to the samples, as internal standard, prior to extraction. The resulting fluorescent adducts were separated on a reversed-phase column with a gradient mobile phase of 25 mM phosphate buffer (pH 6.4) and acetonitrile. The retention times of the 2,5-HD and 1,3-DAB derivatives were 9.4 and 13.7 min, respectively. The derivatives were detected by a fluorescence detector (excitation 340 nm, emission 525 nm). The mean recoveries of 2,5-HD and 1,3-DAB were 92.0 and 94.0%, respectively; the detection limit of 2,5-HD (signal-to-noise ratio of 3) was 5 micrograms/l in urine without hydrolysis and ca. 12 micrograms/l in hydrolyzed samples. The method was applied to 39 urine samples from workers exposed to n-hexane; the mean values were 2.597 mg/l (S.D. = +/- 0.758) for total 2,5-HD and 0.179 mg/l (S.D. = +/- 0.086) for free 2,5-HD. Urine samples of 22 non-exposed subjects showed a mean concentration of 0.437 mg/l (S.D. = +/- 0.109) and 0.022 mg/l (S.D. = +/- 0.011) for total and free 2,5-HD, respectively.