Sergio Ghittori

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.

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, μg/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, μg/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.

Acquired dyschromatopsia among styrene-exposed workers.

We investigated the occurrence of color vision loss in 75 styrene-exposed workers and in 60 referents. Color vision was evaluated by adopting the Lanthony D 15 desaturated panel, a test specifically suited to detect mild acquired dyschromatopsia. The results of the test were expressed as Color Confusion Index. Styrene exposure was evaluated with both environmental and biological monitoring. Airborne levels of the solvent were 3.3 to 549.5 mg/m3. In styrene-exposed workers color vision was significantly impaired when compared with referents matched for age. A significative correlation was found between environmental and urinary levels of styrene and Color Confusion Index excluding the influence of age in multiple regression analysis, indicating the possibility of a dose-effect relationship. The findings suggest that styrene can induce an early appearance of a dose-dependent color vision loss.

Urinary excretion of unmetabolized benzene as an indicator of benzene exposure

Benzene concentrations in urine samples (Cu, ng/L) from 110 workers exposed to benzene in chemical plants and gasoline pumps were determined by injecting urine supernate into a gas chromatograph. The urine was saturated with anhydrous N2SO4 to facilitate the passage of benzene in the air over the urine. The solvent was stripped from the urine surface and concentrated on an adsorbent substrate (Carbotrap tube) by means of a suction pump (flow rate 150 ml/m). Wash-up of the head space was achieved by simultaneous intake of filtered air through charcoal. Benzene was thermically desorbed and injected in a column (thermal tube disorder, Supelco; 370 degrees C thermal flash; borosilicate capillary glass column SPB-1, 60 m length, 0.75 mm ID, 1 microns film thickness; GC Dani 8580-FID). Benzene concentrations in the urine from 40 non-exposed subjects (20 smokers > 20 cigarette/d and 20 nonsmokers) were also determined [median value of 790 ng/L (10.17 nmol/L) and 131 ng/L (1.70 nmol/L), respectively]. The 8-h time-weighted exposure intensity (Cl, micrograms/m3) of individual workers was monitored by means of charcoal tubes. The median value for exposure to benzene was 736 micrograms/m3 (9.42 mumol/m3) [geometric standard deviation (GSD) = 2.99; range 64 micrograms/m3 (0.82 mumol/m3) to 13,387 micrograms/m3) (171.30 mumol/m3)]. The following linear correlation was found between benzene concentrations in urine (Cu, ng/L) and benzene concentrations in the breathing zone (Cl, micrograms/m3): log(Cu) = 0.645 x log(Cl) + 1.399 r = .559, n = 110, p < .0001 With exclusion of workers who smoked from the study, the correlation between air benzene concentration and benzene measured in urine was: log(Cu) = 0.872 x log(Cl) + 0.6 r = .763, n = 63, p < .0001 The study results indicate that the urinary level of benzene is an indicator of occupational exposure to benzene.

The development of benthonic phytocoenosis on artificial substrates in the ticino river

SummaryChanges in the taxonomic composition, chlorophyll a concentration, dry weight, percentage organic carbon and nitrogen and several indices of diversity, including “Margalefs index” were followed during the development of phytobenthonic communities on glass slides. These data suggest that, in this environment, the algal community resembles the nearby natural community after 4 weeks. The taxonomic development can be divided into two phases. During the first 2 weeks the phytocoenosis is dominated by a rather diverse and variable diatom assemblage. Later Cyanophyta dominate. The diversity decreases during colonization as reflected by all indices considered.

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.

Biological monitoring of workers exposed to carbon disulfide (CS2) in a viscose rayon fibers factory

The exposure-excretion relationship to carbon disulfide (CS2) vapor in 407 exposed workers was studied during the second half of the working week. Carbon disulfide concentrations were also determined in 50 nonexposed subjects. The geometric mean value for CS2 in urine samples from the latter was: 0.23 microgram/l (95% upper limit = 0.52 microgram/l) when log-normal distribution was assumed. Among the exposed workers, the CS2 level in urine samples collected after the first half shift exceeded the 95% upper limit of nonexposed subjects in every case. The time-weighted average intensity of exposure to CS2 vapor was measured using personal diffusive samplers (in which carbon cloth served as an adsorbent). CS2 concentrations in urine were determined in samples collected at the end of the first half shift from the 407 exposed cases as well as from 50 nonexposed controls. There was a significant correlation (p < 0.0001) between the exposure to CS2 vapor at concentrations of up to 64 mg/m3 and the levels of CS2 measured in the urine samples after four hours of exposure. The correlation indicated that a mean level of 15.5 micrograms CS2/l urine (95% confidence range, 13.8-17.1 micrograms/l) was excreted following an exposure to CS2 at 31 mg/m3 (the current occupational exposure limit).