Biological monitoring of environmental exposure to polycyclic aromatic hydrocarbons in subjects living in the vicinity of a creosote impregnation plant

Objective: This study was undertaken to evaluate the environmental exposure to polycyclic aromatic hydrocarbons (PAHs) in nonsmoking adult subjects living in the vicinity of a creosote impregnation plant in Delson, Canada. Urinary metabolites of naphthalene, α- and β-naphthol, and pyrene metabolite 1-hydroxypyrene (1-OHP), were used as biomarkers of exposure. Methods: Morning and evening urine samples were collected in mid-August from 30 exposed individuals living at a distance of 50–360 m downwind of the plant and from a control group in the adjoining municipality residing at a distance of 1.9–2.7 km upwind of the plant. Metabolites were measured by gas chromatography/mass spectrometry. Results: Excretion values of α- and β-naphthol were significantly higher in the exposed group than in controls (P < 0.04), after accounting for possible confounding variables by multivariate analyses. The respective geometric mean concentrations (5th and 95th percentiles) of α-naphthol for the exposed and nonexposed groups were 2.04 (0.55–6.00) and 1.37 (0.39–7.02) μmol/mol creatinine for evening samples, and 2.49 (0.77–8.43) and 1.17 (0.37–6.88) μmol/mol creatinine for morning samples. Corresponding values for β-naphthol were 1.78 (0.82–3.67) and 1.36 (0.63–5.07) μmol/mol creatinine for evening samples, and 1.94 (1.03–4.96) and 1.08 (0.49–5.05) μmol/mol creatinine for morning samples. On the other hand, no significant difference in 1-OHP excretion was observed between the exposed and the control group (P>0.5). The respective geometric mean concentrations (5th and 95th percentiles) of 1-OHP for these groups were 0.05 (0.01–0.17) and 0.06 (0.01–0.48) μmol/mol creatinine for evening samples, and 0.05 (0.02–0.12) and 0.05 (0.01–0.42) μmol/mol creatinine for morning samples. Conclusions: The measurement of α- and β-naphthol urinary concentrations appears to be an approach sufficiently sensitive to reveal differences in low exposure levels of volatile PAHs due to creosote impregnation plant emissions. However, uptake of pyrene due to the plant was too small to contribute significantly to 1-OHP excretion. Received: 13 June 2000 / Accepted: 21 April 2001     

Biomonitoring of manganese in blood, urine and axillary hair following low-dose exposure during the manufacture of dry cell batteries

Objectives: A cross-sectional study was carried out on 100 workers from three different workplace areas in a dry cell battery manufacturing plant and on 17 currently nonexposed referents, to examine the relationship between the external exposure to manganese dioxide (MnO₂) and the body burden of manganese in blood, urine and hair. Methods: Inhalable dust was measured gravimetrically after stationary active sampling. Manganese was analyzed in dust samples, blood, urine and axillary hair by atomic absorption spectro- metry. Results: The average air concentrations of manganese in the three workplace areas were 4 μg/m³ (range: 1–12 μg/m³), 40 μg/m³ (12–64 μg/m³) and 400 μg/m³ (137–794 μg/m³). Manganese in blood and axillary hair correlated with airborne manganese in group-based calculations but not on an individual level. The manganese concentrations varied between 3.2 μg/l and 25.8 μg/l in the blood (mean: 12.2 ± 4.8 μg/l) and between 0.4 μg/g and 49.6 μg/g in hair (mean: 6.2 ± 6.2 μg/g in the proximal sequence), respectively. The results for the nonexposed referents were 7.5 ± 2.7 μg/l (mean) in the blood (range: 2.6–15.1 μg/l) and 2.2 ± 1.8 μg/g (mean) in axillary hair (range: 0.4–6.2 μg/g). In these matrices, manganese differed significantly between the highly exposed workers and both the reference and the low-exposure group. Manganese in blood revealed the lowest background variance. No differences for manganese in urine were observed between workers (mean: 0.36 ± 0.42 μg/l, range: 0.1–2.2 μg/l) and referents (mean: 0.46 ± 0.47 μg/l, range: 0.1–1.7 μg/l). Conclusions: Manganese in blood is a specific and suitable parameter for the biomonitoring of MnO₂ exposure, although its validity is limited to group-based calculations. Urinary manganese failed to allow a differentiation between exposed workers and referents. The suitability of manganese analysis in hair for biomonitoring purposes suffers from a relatively great background variation as well as from analytical problems. Received: 11 December 1998 / Accepted: 17 July 1999     

Occupational exposure to polycyclic aromatic hydrocarbons in a fireproof stone producing plant: biological monitoring of 1-hydroxypyrene, 1-, 2-, 3- and 4-hydroxyphenanthrene, 3-hydroxybenz(a)anthracene and 3-hydroxybenzo(a)pyrene

Objectives: Assessment of external and internal exposure to polycyclic aromatic hydrocarbons (PAH) in a fireproof stone producing plant. Methods: Five personal and four stationary air measurements were performed to determine the concentrations of benz(a)anthracene, benzo(a)pyrene, benzo(b)fluoranthene, chrysene, dibenz(a,h)anthracene, fluoranthene, phenanthrene and pyrene, in air. To estimate internal exposure, we determined the urinary excretion of 1-hydroxypyrene, 1-, 2-, 3-, and 4-hydroxyphenanthrene, 3-hydroxybenz(a)anthracene and 3-hydroxybenzo(a)- pyrene in 19 workers, using a sensitive and reliable high-performance liquid chromatographic method with fluorescence detection. Results: During the production of fireproof stones, the German technical exposure limit (TRK) for benzo(a)pyrene of 2 μg/m³ was exceeded in two cases. The mean values of the sum of eight PAHs were 12.6 μg/m³ (stationary air measurement) and 22.2 μg/m³ (personal air measurement). Urinary 1-hydroxypyrene excretion predominated, with a median of 11.1 μg/g creatinine (creat.), followed by 3-hydroxyphenanthrene (median 2.2 μg/g creat.), 1-hydroxyphenanthrene (median 1.9 μg/g creat.) and 2-hydroxyphenanthrene (median 1.6 μg/g creat.). 4-Hydroxyphenanthrene (median 0.3 μg/g creat.) and 3-hydroxybenz(a)anthracene (median 0.17 μg/g creat.) were found in far lower concentrations, while 3-hydroxybenzo(a)pyrene was found only in very low concentrations (median 0.014 μg/g creat.). No correlations could be detected for a relationship between external and internal exposure. A significant correlation between urinary metabolite concentrations could be calculated only for 3-hydroxybenz(a)anthracene and 1-hydroxypyrene. Conclusions: In comparison with other industries, the internal PAH exposure at workplaces in a fireproof stone producing plant is high. This is probably caused by dermal PAH-absorption. Therefore, biological monitoring must be performed in the health surveillance of fireproof stone producing workers. The urinary PAH metabolites should be determined: 3-hydroxybenz(a)anthracene could probably be used as a biomarker representing the group of carcinogenic PAH. Received: 3 November 1999 / Accepted: 26 January 200     

Environmental exposure of small children to polycyclic aromatic hydrocarbons

Objectives: The aim of the study was to assess the intake (by various routes of exposure) of polycyclic aromatic hydrocarbons (PAH) by children living in a Czech city, and its effect on excretion of 1-hydroxypyrene (1-OHP) in summer and winter periods. Methods: Four groups of children (3–6 years old) were chosen: (1) two groups from a kindergarten situated in the city center with a higher traffic density (“polluted” area); (2) two groups from a kindergarten situated in a green zone of the same city (“non-polluted” area). Food consumption was recorded in all children and PAH intake from foodstuffs was estimated. Ambient air samples were collected from the playground and inside the kindergartens. Soil samples were collected too. Morning and evening urine samples were collected during sampling days. Results: In both seasons, the mean outdoor total PAH concentration (sum of 12 individual PAH) in the “polluted” area was approximately three-times higher than that in the “non-polluted” area. Indoor concentration in the “polluted” area was more than six-times higher than that in the “non-polluted” area in summer, and almost three-times higher in winter. The same trend was observed for pyrene and for the sum of carcinogenic PAH. The contribution to the total pyrene absorbed dose from food consumption was much more important than that from inhalation and from ingestion of soil dust. Significantly higher urinary concentrations of 1-OHP (evening samples) were found in children from the “polluted” kindergarten in both seasons. The number of significant relationships between 1-OHP and pyrene absorbed dose was weak. Conclusions: Food seems to be the main source of total pyrene and total PAH intake in small children, even under relatively higher air PAH exposure in the city. Estimated pyrene ingestion from soil had a negligible contribution to the total pyrene absorbed dose. Urinary 1-OHP seems to be an uncertain (non-sensitive) marker of the environmental inhalation exposure to pyrene (PAH) if the pollution of air by pyrene (PAH) is not excessive and the pyrene (PAH) dose by this route is much less than by ingestion. Usefulness of the urinary 1-OHP as an indicator of overall environmental exposure to PAH needs further investigation. Received: 18 September 2000 / Accepted: 20 February 2001     

Exposure to polycyclic aromatic hydrocarbons in occupational versus urban environmental air

To evaluate the balance between occupational and environmental exposure to suspended particulate matter (SPM) and polycyclic aromatic hydrocarbons (PAHs), comparison measurements were performed in a coal-fired power plant and the urban atmosphere from the town nearby. Methods: The analysis of SPM for PAH content was done according to a high-performance liquid chromatography (HPLC)-based method. The microscopic assessment was performed using scanning electron microscopy (SEM) by silver coverage of the samples derived by air filter. Results: Contrary to expectations, the results showed low levels of particle-bound PAHs in the occupational environment (<1 ng benzo(a)pyrene/m³ air) and high levels in urban air (range 80–1250 ng benzo(a)pyrene/m³). The SPM collected from the power plant exhibited non-respirable characteristics (particles larger than 10 μm), whereas urban SPM almost exclusively contained respirable airborne particles (<3 μm). Conclusions: The PAH burden, combined with the enhanced probability of respiratory absorption, confers a much greater hazard potential to the urban SPM. Under these conditions, in areas or countries in which old technologies remain in use, occupational exposure to SPM containing PAHs might represent a severe underestimation of the total risk as it does not take into account the background air pollution. Received: 6 December 1997 / Accepted: 12 June 1998     

Urinary N -acetyl-β-glucosaminidase as an indicator of renal dysfunction in electroplating workers

Objectives: To investigate chromium-induced renal dysfunction in electroplating workers. Methods: A cross-sectional study was used to evaluate four biochemical markers of renal function. A total of 178 workers were divided into 3 comparable groups consisting of 34 hard-chrome plating workers, 98 nickel-chrome electroplating workers, and 46 aluminum anode-oxidation workers, who represented the reference group. Ambient and biological monitoring of urinary chromium were performed to measure exposure concentrations. Results: Overall, urinary chromium concentrations were highest among hard-chrome plating workers (geometric mean 2.44 μg/g creatinine), followed by nickel-chrome electroplating workers (0.31 μg/g creatinine) and aluminum workers (0.09 μg/g creatinine). Airborne chromium concentrations were also highest in the hard-chrome plating area (geometric mean 4.20 μg/m³), followed by the nickel-chrome electroplating area (0.58 μg/m³) and the aluminum area (0.43 μg/m³). A positive correlation was found between urinary chromium and airborne concentrations (r = 0.54, P < 0.01). Urinary concentrations of N-acetyl-β-d-glucosaminidase (NAG) were also highest among hard-chrome plating workers (geometric mean 4.9 IU/g creatinine), followed by nickel-chrome workers (3.4 IU/g creatinine) and aluminum workers (2.9 IU/g creatinine). The prevalence of “elevated” NAG (>7 IU/g creatinine) was significantly highest among hard-chrome plating workers (23.5%), then among nickel-chrome workers (7.1%) and aluminum workers (8.7%). Differences in β₂-microglobulin, total protein, and microalbumin were not significant. Conclusion: The author's evidence indicates that NAG is an early indicator of renal dysfunction in hard-chrome plating workers.     

Biological monitoring of controlled toluene exposure

Objectives: Widespread exposure to toluene occurs in the printing, painting, automotive, shoemaking, and speaker-manufacturing industries. The relationship between air concentrations and the absorbed dose is confounded by dermal exposure, personal protective devices, movement throughout the workplace, and interindividual differences in toluene uptake and elimination. Methods: To determine the best biological indicator of exposure we examined the blood and alveolar breath concentrations of toluene as well as the urinary excretion rates of hippuric acid and of o-, m-, and p-cresols from 33 controlled human inhalation exposures to 50 ppm for 2 h. Results: Among the metabolites, o-cresol was least influenced by background contributions, whereas the p-cresol and hippuric acid rates were obscured by endogenous and dietary sources. Toluene levels in alveolar breath proved to be the most accurate and noninvasive indicator of the absorbed dose. A physiologic model described blood and breath data using four measured anthropometric parameters and the fit values of extrahepatic metabolism and adipose-tissue blood flow. Conclusions: After breathing rate and extrahepatic metabolism had been set to conservative (protective) values (the 97.5th and 2.5th percentiles, respectively) the model predicted that pre-final-shift breath levels of ≤10 μmol/m³ and post-final-shift levels of ≤150 μmol/m³ corresponded to average workplace exposure levels of ≤50 ppm toluene. Alternately, we used the distributions and covariances of the measured and fit model parameters to yield conservative pre-final-shift levels of ≤7.3 μmol/m³ and post-final-shift breath levels of ≤120 μmol/m³ that were reflective of workplace exposure levels of ≤50 ppm toluene. Received: 30 December 1997 / Accepted: 12 June 1998     

Carcinogenicity assays of wood dust and wood additives in rats exposed by long-term inhalation

Objective: This study evaluates whether wood dust and/or wood preservatives develop a carcinogenic potential against the tissues of the airways of rats. Methods: The formation of tumors of the respiratory tract after exposure to wood dust was studied in six groups of approximately 60 female Fischer 344 rats exposed by long-term inhalation to mean concentrations of (1) 18 mg/m³ of untreated oak wood dust, (2) wood preservatives containing ca. 1 μg/m³ lindane and 0.2 μg/m³ of pentachlorophenol (PCP) in the exposure air, or lindane and 18 μg/m3 of PCP (group lindane/PCP vapors, and group oak wood treated with lindane/PCP), (3) 21 or 39 μg/m³ of sodium dichromate (calculated as CrO₃, group chromate aerosol and group oak wood with chromate), and 72 μg/m³ of N-nitrosodimethylamine vapors as positive control. The negative control group consisted of 115 animals (sham-exposed). Results: Tumors of the nasal cavity developed in two rats exposed to chromate aerosol or in combination with wood dust (2/102, 2%). Malignant tumors of the lower respiratory tract were induced only in exposed groups of rats (three adenocarcinomas of the lung and four bronchiolar lung carcinomas, 7/254, 2.8%). More respiratory tract tumors were observed in rats exposed to chromate or wood with chromate (5/102, 5%), also in groups exposed to oak wood dust (oak untreated, oak + chromate, oak + lindane/PCP; together 5/155, 3.2%). Analysis of `unpreserved' oak wood dust revealed up to 5 μg/m³ of chromate. When this exposure was taken into account, eight of nine animals with respiratory tract tumors (including nasal cavity) had exposure to chromate, while only one tumor occurred in the group lindane/PCP. Otherwise the incidence of systemic tumors was increased in animals exposed to lindane/PCP, due in particular to a significantly increased incidence of liver tumors (OR=3.7; 1.24–11.3; P=0.019). Fatal (mucoepidermoid) tumors were induced by N-nitrosodimethylamine (NDMA) in the positive control (14/46, 30%). No such tumors of the respiratory tract were observed in the negative control. Conclusions: Tumors in the respiratory tract were found only in exposed animals, predominantly in the groups which inhaled oak wood dust and chromate stain. Chromate may play a decisive role for the etiology of tumors of the nasal cavity in wood workers. This assumption should be supported by further dose-response studies. Received: 23 May 2000 / Accepted: 13 September 2000     

1-Hydroxypyrene as a biomarker of PAH exposure among subjects living in two separate regions from a steel mill

Objective Steel mills are known to be a source of ambient polycyclic aromatic hydrocarbons (PAHs), and increased cancer risk has been reported among neighborhoods previously. In this study, we tried to assess the exposure to PAHs among residents nearby to a large steel mill in Korea by measuring urinary 1-hydroxypyrene (1-OHP). Methods Two separate areas at different distances from a steel mill but on the same wind direction were chosen to evaluate the environmental exposures to polycyclic aromatic hydrocarbons. Three-hundred and fifty children living in the vicinity of steel plant (“nearby” group) and 606 children residing much farther from the factory (“remote” group) participated. Urine was collected on three consecutive days, and questionnaires about exposure to passive smoking and food consumption as well as demographics were obtained. Routine monitoring data of ambient pollutants were obtained and particulate matter less than 10 μm (PM₁₀) was analyzed with multiple regressions to assess the associations with urinary 1-OHP. Results The geometric mean concentration of urinary 1-OHP among nearby group (0.048 ± 1.878 μmol/mol creatinine, GM ± GSD) was approximately 1.3 times higher than that among remote group (0.036 ± 2.425 μmol/mol creatinine, GM ± GSD), and using multiple regression techniques, the difference was significant (P < 0.0001) after adjusting for confounding variables. When different periods before the sampling of urine were examined, PM₁₀ averages over 2 days, 3 days, and 1 week prior to urine sampling showed significant associations with urinary 1-OHP levels. Conclusion Our findings are consistent with the interpretation that residents nearby to a steel mill are exposed to PAHs through ambient exposures.     

Comparison between blood and urinary toluene as biomarkers of exposure to toluene

Objectives: To compare blood toluene (TOL-B) and urinary toluene (TOL-U) as biomarkers of occupational exposure to toluene, and to set a suitable procedure for collection and handling of specimens. Method: An assay based on headspace solid-phase microextraction (SPME) was used both for the determination of toluene urine/air partition coefficient (λ_urine/air) and for the biological monitoring of exposure to toluene in 31 workers (group A) and in 116 non-occupationally exposed subjects (group B). Environmental toluene (TOL-A) was sampled during the work shift (group A) or during the 24 h before specimen collection (group B). Blood and urine specimens were collected at the end of the shift (group A) or in the morning (group B) and toluene was measured. Results: Toluene λ_urine/air was 3.3 ± 0.9. Based on the specimen/air partition coefficient, it was calculated that the vial in which the sample is collected had to be filled up to 85% of its volume with urine and 50% with blood in order to limit the loss of toluene in the air above the specimen to less than 5%. Environmental and biological monitoring of workers showed that the median personal exposure to toluene (TOL-A) during the work-shift was 80 mg/m³, the corresponding TOL-B was 82 μg/l and TOL-U was 13 μg/l. Personal exposure to toluene in environmentally exposed subjects was 0.05 mg/m³, TOL-B was 0.36 μg/l and TOL-U was 0.20 μg/l. A significant correlation (P < 0.05) was observed between TOL-B or TOL-U and TOL-A (Pearson's r=0.782 and 0.754) in workers, but not in controls. A significant correlation was found between TOL-U and TOL-B both in workers and in controls (r=0.845 and 0.681). Conclusion: The comparative evaluation of TOL-B and TOL-U showed that they can be considered to be equivalent biomarkers as regards their capacity to distinguish workers and controls and to correlate with exposure. However, considering that TOL-U does not require an invasive specimen collection, it appears to be a more convenient tool for the biological monitoring of exposure to toluene. Received: 20 October 1999 / Accepted: 4 March 2000     

Dust exposure in Munich public transportation: a comprehensive 4-year survey in buses and trams

Objectives: Published data obtained from outdoor stationary sampling stations cannot be applied directly to the exposure situation in vehicles. The aim of this study, therefore, was to assess the dust exposure relevant to passengers and drivers in public buses and trams. Method: In the years 1993 to 1996, PM₁₀ samples were taken during 201 journeys of typically 4 h duration on 14 routes (nine bus routes, five tramways) which were representative for the overall Munich transportation system with respect to area characteristics and traffic density. The concentrations of the samples were compared with those collected at the same time at sampling stations of the Bavarian State Office for Environmental Protection (OEP). Dust exposure was continuously and synchronously recorded by means of a tyndallometric device. Traffic and passenger density, weather conditions, special events, etc. were noted by our personnel, travelling on every journey. Results: The average PM₁₀ dust concentration for all rides was 155 μg/m³ (single journey max. 686 μg/m³, min. 13 μg/m³). Interior concentrations were 1.7 to 4.0 times above those collected at the static outdoor stations. We found only minor associations between dust concentrations and traffic density or time of day. During several journeys continuous recording disclosed anomalies, dependence on weather conditions and cyclic track characteristics. Conclusions: Interior PM₁₀ particulate concentrations were comparable to those found elsewhere in truck drivers' cabs and are in the region of German regulative limits established for the general population's long term outdoor exposure. Indoor concentrations were well above the values found at stationary outdoor stations. Additional continuous recording of dust concentrations proved to be helpful in unveiling anomalies and dependencies on external effectors. Received: 10 August 1999 / Accepted: 20 November 1999     

Assessment of biological chromium among stainless steel and mild steel welders in relation to welding processes

Air and biological monitoring were used for assessing external and internal chromium exposure among 116 stainless steel welders (SS welders) using manual metal arc (MMA), metal inert gas (MIG) and tungsten inert gas (TIG) welding processes (MMA: n = 57; MIG: n = 37; TIG: n = 22) and 30 mild steel welders (MS welders) using MMA and MIG welding processes (MMA: n = 14; MIG: n = 16). The levels of atmospheric total chromium were evaluated after personal air monitoring. The mean values for the different groups of SS welders were 201 μg/m³ (MMA) and 185 μg/m³ (MIG), 52 μg/m³ (TIG) and for MS welders 8.1 μg/m³ (MMA) and 7.3 μg/m³ (MIG). The curve of cumulative frequency distribution from biological monitoring among SS welders showed chromium geometric mean concentrations in whole blood of 3.6 μg/l (95th percentile = 19.9), in plasma of 3.3 μg/l (95th percentile = 21.0) and in urine samples of 6.2 μg/l (95th percentile = 58.0). Among MS welders, mean values in whole blood and plasma were rather more scattered (1.8 μg/l, 95th percentile = 9.3 and 1.3 μg/l, 95th percentile = 8.4, respectively) and in urine the value was 2.4 μg/l (95th percentile = 13.3). The analysis of variance of chromium concentrations in plasma previously showed a metal effect (F = 29.7, P < 0.001), a process effect (F = 22.2, P < 0.0001) but no metal–process interaction (F = 1.3, P = 0.25). Concerning urinary chromium concentration, the analysis of variance also showed a metal effect (F = 30, P < 0.0001), a process effect (F = 72, P < 0.0001) as well as a metal–process interaction (F = 13.2, P = 0.0004). Throughout the study we noted any significant differences between smokers and non-smokers among welders. Taking in account the relationships between chromium concentrations in whole, plasma or urine and the different welding processes, MMA-SS is definitely different from other processes because the biological values are clearly higher. These higher levels are due to the very significant concentrations of total soluble chromium, mainly hexa- valent chromium, in welding fumes. Received: 9 May 1996 / Accepted: 14 March 1997     

Measured exposures by personal monitoring for respirable suspended particles and environmental tobacco smoke of housewives and office workers resident in Bremen, Germany

Objective : Exposures to respirable suspended particles (RSP) and environmental tobacco smoke (ETS) were assessed in Bremen, Germany, as part of a European air quality study. The range and level of personal exposures were assessed for housewives and office workers. Design : Nonsmokers were randomly selected from a representative sample of the population of Bremen. Housewives were recruited into one group primarily for assessment of exposures in the home and office workers, into a second group for assessment of the contribution of the workplace to overall exposure. Methods : A total of 190 subjects collected air samples from areas close to their breathing zone by wearing personal monitors for 24 h. Samples collected were analysed for RSP, ultraviolet-absorbing particulate matter (UVPM), fluorescing particulate matter (FPM), solanesol-related particulate matter (SolPM), nicotine and 3-ethenylpyridine (3-EP). Saliva cotinine levels for all subjects were also established. Results : Overall the levels found were quite low, with the majority of results being below the limit of quantification. Workers both living and working with smokers were exposed to the highest 24-h median quantities of RSP (789 μg) and ETS particles (128 μg) measured by FPM. The highest nicotine levels, based on median 24-h time-weighted average concentrations, were experienced by office workers working with smokers (0.69 μg m⁻³). These workers were also found to have␣the highest median cotinine levels (1.6 ng ml⁻¹). Conclusions: The most highly exposed workers, both living and working with smokers, would potentially inhale over 20 cigarette equivalents (CE) per annum as based on the upper decile levels. Housewives living with smokers could inhale up to 11 CE per annum as based on the upper decile levels. Locations outside the workplace, including the home, contribute most to overall RSP and ETS particle exposure. Consideration should be given to extending the personal monitoring period in cities where levels appear to be quite low. Received: 9 May 1997 / Accepted: 17 October 1997     

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     

Exposure-response relationships in rhinitis and conjunctivitis caused by methyltetrahydrophthalic anhydride

Objective: To examine exposure-response relationships in the occurrence of symptoms of the eyes and airways in workers exposed to methyltetrahydrophthalic anhydride (MTHPA). Methods: A population of 111 workers from 2 condenser plants (A and B) using epoxy resin with MTHPA underwent a questionnaire survey and serology investigations, and data obtained on 95 subjects in assembly and inspection lines were analyzed for this study. Results: In all, 24 (65%) of 37 workers in plant A and 38 (66%) of 58 workers in plant B had positive MTHPA-specific IgE. The air levels of MTHPA detected in assembly and inspection lines were higher in plant A than in plant B (geometric mean 25.5–63.9  and 4.93–5.49 μg/m³, respectively). IgE-sensitized workers in each plant had significantly (P < 0.05) more complaints regarding the eyes and nose than did unsensitized workers, suggesting that there is an IgE-mediated mechanism in most of these symptoms. The sensitized workers in plant A had higher frequencies for symptoms of the eyes, nose, and pharynx than did those in plant B (P < 0.02). Furthermore, only 15% of persons often displayed work-related symptoms among the 20 symptomatic workers in plant B as compared with 73% of the 26 symptomatic workers in plant A (P < 0.0001). These results can be explained by the difference in the MTHPA levels measured in the lines between the two plants. In plant B the minimal level of MTHPA that was associated with work-related symptoms was 15–22 μg/m³, which was lower than the geometric mean levels detected in assembly and inspection lines in plant A. Conclusions: These results suggest that MTHPA exposure at levels above 15 μg/m³ should be avoided to prevent the development of occupational allergic diseases in most workers. Received: 4 May 1998 / Accepted: 4 August 1998     

Urinary beryllium – a suitable tool for assessing occupational and environmental beryllium exposure?

Objectives: The reasons for the slow progress and lack of new knowledge in the biological monitoring of beryllium (Be) are to be found in the presumed small number of working activities involving exposure to the metal, and the lack of adequate analytical methods. The reference values for urinary Be reported earlier in the literature appear to be too high, due to the poor specificity and sensitivity of the adopted methods. The aim of this study was to correlate Be air concentrations and Be urinary levels to ascertain whether the biological indicator was suitable for assessing occupational exposure to the metal. Methods: To investigate the relationship between the Be concentrations in air and those excreted in urine, we examined 65 metallurgical workers exposed to very low levels of the metal, and 30 control subjects. The exposed workers were employed in two electric steel plants and two copper alloy foundries. The alloys were produced in electric furnaces, starting with scrap containing Be as an impurity. The Be concentrations in the air were monitored by area samplers and the levels of Be in the urine of the workers were determined in samples taken at the end of the shift. Both determinations were carried out by ICP-MS. Results: The median airborne Be concentrations in the copper alloy plants were 0.27 μg/m³ in the furnace area and 0.31 μg/m³ in the casting area. Median values of 0.03 to 0.12 μg/m³ were determined in the steel plants, the relatively wide range probably due to differing amounts of Be in the scrap. Regression analysis was performed on the median values from four work areas and the corresponding urinary samples. A significant correlation was found for the relationship between external and internal exposure. The urinary Be levels were in the range between 0.12 and 0.15 μg/l with observation of the recommended TLV-TWA for inhalable dust of 0.2 μg/m³ (0.2 μg/l at the upper 95th percentile). Conclusions: Sufficient data are not currently available to be able to propose a BEI for urinary Be. Our results show that new investigations are necessary to improve the evaluation of dose indicators and the relationship between external and internal exposure to Be. Received: 15 May 2000 / Accepted: 8 September 2000     

Exposure to cobalt and nickel in the hard-metal production industry

Objective The shortage of cobalt (Co) on the metal market forced the industry to add nickel (Ni) to Co as a binding agent for the sintering of hard metal. This change enabled us to study (1) the exposure to Ni powder and (2) the effect of Ni on Co uptake (and vice versa). Methods Equal amounts of Co and Ni were used in the mixture in a plant employing 50 workers. Both personal ambient-air samples and single-void urine samples were taken twice in the same week, i.e., on Monday and Thursday. Atomic absorption spectroscopy (AAS) was used for analyses. Results The airborne availability of Ni (mean value 41.65 ± 6.29 μg/m³) was 2-fold that of Co (mean value 21.85 ± 24.25 μg/m³), although the two series of data (n = 20) were significantly correlated. Even if the Co and Ni urinary concentration values (n = 45) recorded on Monday morning and Thursday evening were significantly correlated, at the end of the week there was a 3-fold increase, specifically, from 7.3 to 22.28 μg/l, in Co elimination (a significant difference) and a 30% increase in Ni elimination from 11.98 to 15.83 μg/l. Moreover, on Monday morning, 90% of Ni urinary concentration values were higher than those of Co as opposed to only 33% on Thursday evening. In the six cases in which both airborne and urine determinations were performed on the 2 days, no significant relationship was found between external exposure and biological monitoring data. Conclusions Although Ni uptake was variable, it was generally low, whereas Co uptake was substantial, as had previously been observed in the same plant when Co was the only binder under use. It was therefore possible to rule out any influence of Ni exposure on Co uptake and to suggest the contrary, as has been demonstrated in bacterial species and in rats using everted intestinal sacs. Received: 18 March 1997 / Accepted: 2 October 1997     

Urban air pollution: a representative survey of PM2.5 mass concentrations in six Brazilian cities

In urban areas of Brazil, vehicle emissions are the principal source of fine particulate matter (PM_2.5). The World Health Organization air quality guidelines state that the annual mean concentration of PM_2.5 should be below 10 μg m⁻³. In a collaboration of Brazilian institutions, coordinated by the University of S?o Paulo School of Medicine and conducted from June 2007 to August 2008, PM_2.5 mass was monitored at sites with high traffic volumes in six Brazilian state capitals. We employed gravimetry to determine PM_2.5 mass concentrations, reflectance to quantify black carbon concentrations, X-ray fluorescence to characterize elemental composition, and ion chromatography to determine the composition and concentrations of anions and cations. Mean PM_2.5 concentrations and proportions of black carbon (BC) in the cities of S?o Paulo, Rio de Janeiro, Belo Horizonte, Curitiba, Recife, and Porto Alegre were 28.1 ± 13.6 μg m⁻³ (38% BC), 17.2 ± 11.2 μg m⁻³ (20% BC), 14.7 ± 7.7 μg m⁻³ (31% BC), 14.4 ± 9.5 μg m⁻³ (30% BC), 7.3 ± 3.1 μg m⁻³ (26% BC), and 13.4 ± 9.9 μg m⁻³ (26% BC), respectively. Sulfur and minerals (Al, Si, Ca, and Fe), derived from fuel combustion and soil resuspension, respectively, were the principal elements of the PM_2.5 mass. We discuss the long-term health effects for each metropolitan region in terms of excess mortality risk, which translates to greater health care expenditures. This information could prove useful to decision makers at local environmental agencies.     

Assessment of environmental tobacco smoke and respirable suspended particle exposures for nonsmokers in Prague using personal monitoring

Objective: Exposures to respirable suspended particles (RSP) and environmental tobacco smoke (ETS) were assessed in Prague, Czech Republic, to determine the range and degree of personal exposure by means of personal monitoring over a 24-h period. Design: Self-reported nonsmokers were randomly selected from a representative sample of the population of Prague. Housewives were recruited into one group, primarily for assessment exposures in the home, and office workers were recruited into a second group for assessment of the contribution from the workplace. Methods: A total of 238 randomly selected nonsmoking subjects collected air samples near their breathing zone by wearing personal monitors for 24 h. Samples collected were analyzed for RSP, nicotine, 3-ethenylpyridine, and ETS particles (using ultraviolet absorbance, fluorescence, and solanesol measurements). Saliva cotinine analyses were also undertaken to confirm the nonsmoking status of the subjects. Results: The most highly exposed subjects in this study were office workers both living and working with smokers. Median time-weighted average exposure concentrations of 60 μg m⁻³ RSP, 16 μg m⁻³ ETS particles, and 1.6 μg m⁻³ nicotine were determined for these subjects, who also had the highest median saliva cotinine level of 2.4 ng ml⁻¹. Housewives living in nonsmoking households were the least exposed subjects in this study, showing levels of 32 μg m⁻³ RSP, 0.17 μg m⁻³ ETS particles, and 0.15 μg m⁻³ nicotine. As based upon median levels of ETS particles and nicotine, no group would potentially inhale or be exposed to more than 10 cigarette equivalents per year (CE/y) and the least exposed would inhale less than 1 CE/y. The most highly exposed (90th percentile levels) nonsmokers in this study, who both worked and lived with smokers, would potentially inhale up to 29 CE/y. Overall, the workplace was estimated to contribute between 45% and 49% of the annual exposure to nicotine and ETS particles, respectively. On the basis of determined saliva cotinine concentrations, a misclassification rate of between 1.7% and 2.5% was calculated. Conclusions: Highest exposures were apparent for office workers both working and living in smoking environments, and our findings suggest a significant contribution to overall ETS particle and nicotine levels from the workplace where smoking takes place. Overall, the rates at which subjects were determined to have misclassified their smoking status in this study were the lowest observed in any of the European cities investigated to date. Clearly, a more sensitive method of analysis for cotinine in body fluids is needed for more accurate determination of the levels expected for nonsmokers. Received: 19 November 1997 / Accepted: 26 February 1998     

Exposure of gasoline road-tanker drivers to methyl tert-butyl ether and methyl tert-amyl ether

Organic oxygenates, namely, methyl tert-butyl ether (MTBE) and methyl tert-amyl ether (MTAE), are added to gasoline to reduce carbon monoxide in exhausts and to enhance the octane number. The aim of this study was to investigate road-tanker drivers' exposure to oxygenate vapors during road-tanker loading and unloading as well as to evaluate the measurements of these ethers and their metabolites in the urine as a means of assessing the uptake of the ethers. A total of 11 drivers in different parts of Finland were trained to monitor their exposure with personal samplers, to report their working conditions, and to collect their whole-day urine samples. Charcoal tubes of the air samples were analyzed for MTBE, MTAE, benzene, toluene, and aliphatic hydrocarbons. For biological monitoring purposes the two main oxygenates, tertiary ethers MTBE and MTAE, as well as their main metabolites, tertiary alcohols tert-butanol (TBA) and tert-amyl alcohol (TAA), were determined in urine specimens. On average the drivers were exposed to vapors for short periods (21 ± 14 min) three times during a work shift. The mean concentrations of MTBE and MTAE (mean ± SD) were 8.1 ± 8.4 and 0.3 ± 0.4 mg/m³. The total MTBE uptake during the shift was calculated to be an average of 106 ± 65 μmol. The mean concentrations of MTBE, TBA, MTAE and TAA detected in the first urine after the work shift were 113 ± 76, 461 ± 337, 16 ± 21, and 40 ± 38 nmol/l, and those found the next morning, 16 h later, were 18 ± 12, 322 ± 213, 9 ± 10, and 20 ± 27 nmol/l. The good relationship (r = 0.84) found between MTBE exposure and postshift excretion suggests that urinary MTBE can be used for biological monitoring of exposure, but at the present low level of exposure the corresponding metabolite TBA is not equally reliable. The determination of MTAE and its metabolite TAA in urine is sensitive enough to detect the low degree of exposure to MTAE, but in this study the data were too scarce to allow calculation of the correlations due to very low levels of MTAE exposure. Received: 10 February 1997 / Accepted: 2 July 1997