G. Pezzagno

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.

Trans, trans-muconic acid, a biological indicator to low levels of environmental benzene: Some aspects of its specificity

BACKGROUND The specificity of trans,trans-muconic acid (MA) as a biomarker of exposure to low benzene levels and the role of sorbic acid (SA) as a confounding factor were evaluated. MA, a urinary ring-opened metabolite of benzene, has been recently proposed for the biological monitoring of populations exposed to low levels of this chemical. The usual presence of MA in urine of non-occupationally exposed people is generally attributed to benzene world-wide contamination (mainly by smoking habits, urban pollution, and maybe by food contamination). However, the scientific literature reveals that the common food preservative and fungistatic agent SA is converted into MA though in trace amounts. METHODS Urinary benzene and MA before and after administration of SA were measured in smokers and non-smokers. Benzene dissolved in urine was analyzed injecting a headspace sample in a gas-chromatografic system. Urinary MA was measured by means of a HPLC apparatus. RESULTS The mean background values of MA were about 60 mg/L (or 50 mg/g creat.); after experimental administration of SA (447 mg), the mean urinary MA concentration became more than 20 times higher. The biotransformation rates of SA into MA after ingestion of 447 mg of SA ranged from 0.05 to 0.51%. The ratio between unmetabolized benzene in the two groups of smokers and non-smokers was significantly different from the ratio between MA in the same two groups. DISCUSSION Other sources of MA excretion, different from benzene, influence the urinary concentration of the metabolite: only 25% of MA background values can be attributed to benzene. The urinary MA induced by 100 mg of ingested MA is 77% of that expected after an 8-hour benzene exposure to 0.5 ppm (current threshold limit value according to ACGIH). In conclusion, MA is not a sufficiently specific biomarker of low benzene exposure; a significant effect of SA ingestion is predictable.

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).

The Specificity of trans,trans- Muconic Acid as a Biological Indicator for Low Levels of Environmental Benzene

trans, trans -Muconic acid (MA), a urinary ring-opened metabolite of benzene, is a newly proposed biological indicator of benzene exposure which should enable the assessment of low levels of exposure to this ubiquitous environmen tal pollutant. The presence of MA in the urine of non-occupationally exposed people is generally attributed to world-wide contamination of the environ ment by benzene (arising from such sources as smoking and other combustion, urban pollution from vehicles and maybe by food contamination). But, exami nation of the scientific literature reveals that a common food preservative and fungistatic agent, sorbic acid (SA), is also converted into MA, although in trace amounts. The permitted maximum concentration of SA in food ranges from 0.2 to 2 g·kg -1 and the acceptable daily intake (ADI-FAO/WHO) is 25 mg. kg -1 of body weight. The question, therefore, is whether the amount of MA excreted as a metabolite of SA can make a significant contribution to the total MA excreted. If so, the specificity of MA as a biological indicator for benzene exposure assessment is in doubt. Four experiments in 2 subjects were set up to try to clarify the effect on the urinary excretion of MA of the experimental ingestion of SA (2 doses of 447 and 44.7 mg); urine samples were collected, in fractions as voided, for 24 h before and 48 (or 60 h) after SA ingestion. The total amounts of MA excreted during the 24 h before ingestion of SA were respectively 79 and 34 mg in the 2 subjects; after ingestion of 447 or 44.7 mg of SA the total excretion of MA was at least respectively 20 and 2 times the background levels (when the single dose of SA was ingested) and at least 10 and 3 times (when the SA was given in divided doses). The elimination of MA after ingestion of SA was complete in 24 h; the peak concentrations always appeared in the first urine sample after the ingestion of the substance and they were more than 90 times and more than 3 times the basal levels respectively for a single ingestion of 447 and 44.7 mg of SA. The rate of biotransformation of SA into MA was, on average, 0.34 and 0.21 % in the 2 subjects; on the basis of these levels of biotransformation, it appears that 0.3-0.5 g of ingested SA would suffice to lead to excretion of 1 mg of MA, a quantity corresponding to that believed to derive from benzene exposure at levels greater than 1 ppm. Only in urine collected many hours after the last meal can a possible additive effect of MA from SA be ignored.

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).

Biological Monitoring of Occupational Exposure to Enflurane (Ethrane) in Operating Room Personnel

Abstract Biological monitoring of occupational exposure to enflurane (ethrane) can be achieved by measuring concentrations of inorganic fluorides in the blood and urine and of enflurane in alveolar air and venous blood. Measurement of these concentrations, however, has limitations. Another method for monitoring exposure to enflurane is to measure its concentration in urine throughout the period of exposure. In this study, we measured the environmental and urinary concentrations of enflurane. Enflurane in the ambient atmosphere was determined in 18 operating theaters of eight hospitals in Italy. Ambient air concentrations exceeded the National Institute for Occupational Safety and Health-recommended time-weighted average exposure level of 1 ppm (median: 1.31 ppm). Enflurane was detected in urine of 159 exposed subjects (anesthetists, surgeons, and nurses). A significant correlation was found between enflurane concentration in urine produced during the shift and environmental concentration (r = 0.77, p = .0...