Biological monitoring of triethylamine among cold-box core makers in foundries

Objectives: The objectives of the study were to assess triethylamine (TEA) exposure in cold-box core making and to study the applicability of urinary TEA measurement in exposure evaluation. Methods: Air samples were collected by pumping of air through activated-charcoal-filled glass tubes, and pre- and postshift urine samples were collected. The TEA concentrations were determined by gas chromatography. Design: Tea was measured in air and urine samples from the same shift. Breathing-zone measurements of 19 workers in 3 foundries were included in the study, and stationary and continuous air measurements were also made in the same foundries. Pre- and postshift urine samples were analyzed for their TEA and triethylamine-N-oxide (TEAO) concentrations. Results: The TEA concentration range was 0.3–23 mg/m³ in the breathing zone of the core makers. The mean 8-h time-weighted average exposure levels were 1.3, 4.0, and 13 mg/m³ for the three foundries. Most of the preshift urinary TEA concentrations were under the detection limit, whereas the postshift urinary TEA concentrations ranged between 5.6 and 171 mmol/mol creatinine. The TEAO concentrations were 4–34% (mean 19%) of the summed TEA+TEAO concentrations. The correlation between air and urine measurements was high (r = 0.96, P < 0.001). A TEA air concentration of 4.1 mg/m³ (the current ACGIH 8-h time-weighted average threshold limit value) corresponded to a urinary concentration of 36 mmol/mol creatinine. Conclusions: The TEA exposure levels of foundries and their core makers vary greatly. Stationary air measurements in factories are not sufficient to assess TEA exposure; instead, personal sampling is needed. The biological monitoring of TEA in postshift urine samples provides a practical and accurate method for assessing exposure. Received: 9 May 1997 / Accepted: 27 August 1997     

Respiratory health and fluoride exposure in different parts of the modern primary aluminum industry

Objective: The aim of this cross-sectional study was to investigate possible acute and long-term respiratory health effects of work at different working places in the primary aluminum industry. Method: A cross-sectional study was carried out on 78 potroom workers, 24 foundry workers, and 45 carbon-plant workers (n = 147, exposed group), and 56 control workers (watchmen, craftsmen, office workers, laboratory employees) of a modern German prebake aluminum plant. The survey consisted of pre- and postshift spirometric and urinary fluoride measurements. Results: Potroom workers had significantly lower preshift results with regard to forced vital capacity (FVC, 99.5% versus the 107.2% predicted; P < 0.05) and peak expiratory flow (PEF, 85.2% versus the 98.4% predicted; P < 0.01) as compared with controls. In a multiple regression model a small but significant negative correlation was found between postshift urinary fluoride concentrations and FVC, FEV₁, and PEF. Across-shift spirometric changes were observed only in FVC among carbon-plant workers (103.0 ± 13.3% predicted preshift value versus 101.2 ± 13.6% predicted postshift value; P < 0.05). Conclusions: The results suggest that lung function impairment in the modern primary aluminum industry may be only partly due to fluoride exposure and that working in aluminum carbon plants may cause acute lung function changes. Received: 8 July 1998 / Accepted: 31 October 1998     

Biological monitoring of workers exposed to N,N-dimethylformamide in the synthetic fibre industry

Objectives: Monitoring of workplace air and biological monitoring of 23 workers exposed to N,N-dimethylformamide (DMF) in the polyacrylic fibre industry was carried out on 4 consecutive days. The main focus of the investigation was to study the relationship between external and internal exposure, the suitability of the metabolites of DMF for biological monitoring and their toxicokinetic behaviour in humans.Methods: Air samples were collected using personal air samplers. The limit of detection (LOD) for DMF using an analytical method recommended by the Deutsche Forschungsgemeinschaft (DFG) was 0.1 ppm. The urinary metabolites, N-hydroxymethyl-N-methylformamide (HMMF), N-methylformamide (NMF), and N-acetyl-S-(N-methylcarbamoyl)-cysteine (AMCC), were determined in one analytical run by gas chromatography with thermionic sensitive detection (GC/TSD). The total sum of HMMF and NMF was determined in the form of NMF. The LOD was 1.0 mg/l for NMF and 0.5 mg/l for AMCC. Results and conclusions: The external exposure to DMF vapour varied greatly depending on the workplace (median 1.74 ppm, range <0.1–159.77 ppm). Urinary NMF concentrations were highest in post-shift samples. They also covered a wide range (<1.0–108.7 mg/l). This variation was probably the result of different concentrations of DMF in the air at different workplaces, dermal absorption and differences in the protective measures implemented by each individual (gloves, gas masks etc.). The urinary NMF concentrations had decreased almost to zero by the beginning of the next shift. The median half-time for NMF was determined to be 5.1 h. The concentrations of AMCC in urine were determined to be in the range from <0.5 to 204.9 mg/l. Unlike the concentrations of NMF, the AMCC concentrations did not decrease during the intervals between the shifts. For the exposure situation investigated in our study, a steady state was found between the external exposure to DMF and the levels of AMCC excreted in urine about 2  days after the beginning of exposure. AMCC is therefore excreted more slowly than NMF. The half-time for AMCC is more than 16 h. Linear regression analysis for external exposure and urinary excretion of metabolites was carried out for a sub-group of 12 workers. External exposure to 10 ppm DMF in air (the current German MAK value) corresponds to an average NMF concentration of about 27.9 mg/l in post-shift urine from the same day and an average AMCC concentration of 69.2 mg/l in pre-shift urine from the following day. NMF in urine samples therefore represents an index of daily exposure to DMF, while AMCC represents an index of the average exposure over the preceding working days. AMCC is considered to be better suited for biomonitoring purposes because (1) it has a longer half-time than NMF and (2) its formation in humans is more closely related to DMF toxicity. Received: 25 June 1999 / Accepted: 2 October 1999     

Biological monitoring of occupational exposure to N,N -dimethylformamide – the effects of co-exposure to toluene or dermal exposure

Objectives: The objective of this study is to assess the exposure and intake dose of N,N-dimethylformamide (DMF) and the correlation between them, according to the type of exposure for the workers in the DMF industry. Methods: We monitored 345 workers occupationally exposed to DMF, from 15 workshops in the synthetic fiber, fiber coating, synthetic leather and paint manufacturing industries. Ambient monitoring was carried out with personal samplers to monitor the external exposure. Biological monitoring was done to determine the internal dose by analyzing N-methylformamide (NMF) in end-shift urine. Work procedure and exposure type of each DMF workshop was carefully surveyed, to classify workers by exposure type according to work details. Workers were classified into three groups (Group A: continuous and direct exposure through inhalation and skin; Group B: intermittent and short-term exposure through inhalation and skin; Group C: continuous and indirect exposure mostly through inhalation). Results: Geometric mean of DMF concentration in air was 2.62 (GSD 5.30) ppm and that of NMF in urine was 14.50 (GSD 3.89) mg/l. In the case of continuous absorption through inhalation and dermal exposure (Group A), the value of NMF in urine corresponding to 10 ppm of DMF was 45.3 mg/l (r=0.524, n=178), 39.1 mg/g creatinine (r=0.424), while it was 37.7 mg/l (r=0.788, n=37), 24.2 mg/g creatinine (r=0.743) in the case of absorption mostly through inhalation (Group C). Creatinine correction reduced the correlation between two parameters. Conclusion: The NMF in urine corresponding to 10 ppm DMF, of the dermal and inhalation exposure group was 39.1 mg/g creatinine (r=0.424, n=178), while that of the inhalation exposure-only group was 24.2 mg/g creatinine (r=0.743, n=37). Co-exposure with toluene reduced the NMF excretion in urine. Received: 4 October 1999 / Accepted: 25 April 2000     

N,N-Dimethylformamide: significance of dermal absorption and adjustment method for urinary N-methylformamide concentration as a biological exposure item

Objectives: To clarify the potential for dermal absorption of N,N-dimethylformamide (DMF) (CAS No. 68-12-2) vapor, and the appropriate adjustment method and the half-lives of urinary concentrations of N-methylformamide (NMF) as the biological exposure item of DMF. Methods: Thirteen healthy male volunteers (mean age: 22.7 years, range: 20–27) were exposed to DMF vapor twice, via both the skin and the lung, for 4 h at concentrations below 10 ppm, the recommended occupational exposure limit set by the Japan Society for Occupational Health, the American Conference of Governmental and Industrial Hygienists, and Deutsche Forschungsgemeinschaft, under conditions of 27 °C and 44% humidity. Each volunteer was exposed to DMF via the skin in a whole-body type exposure chamber and, outside the chamber, via the lung by a respirator connected to the chamber. Exposure levels were 6.2 ± 1.0 ppm in dermal exposure and 7.1 ± 1.0 ppm in inhalation exposure. Urine samples were collected at every opportunity until 72 h after exposure; and NMF, as well as volume, creatinine, and specific gravity were measured. Dermal and inhalation intakes were compared after adjusting concentrations. Results and Conclusions: DMF vapor absorptions via the skin and the lung were estimated to be 40.4 and 59.6%, respectively. Workers need to be aware of the risk of dermal absorption of DMF vapor as well as of the liquid. Though NMF concentrations adjusted by creatinine, specific gravity, and urinary volume showed good correlation with total NMF excretion and the absolute amount of NMF at each sampling time, creatinine-adjusted NMF concentration correlated better than the others. The biological half-life of urinary NMF after dermal exposure, 4.75 ± 1.63 h, was longer than that after respiratory exposure, 2.42 ± 0.63 h. Received: 14 June 2000 / Accepted: 5 October 2000     

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     

N,N- Dimethylformamide – influence of working conditions and skin penetration on the internal exposure of workers in synthetic textile production

Objectives: This study examined the external and internal exposure to the solvent N,N-dimethylformamide (DMF) of 126 workers from a factory producing synthetic fibers. Methods: Air measurements were carried out using personal air samplers with diffusion tubes (Dräger, ORSA 5). For the purpose of biological monitoring the levels of N-methylformamide (NMF) in urine were measured in preshift and postshift samples. Determinations were carried out using gas chromatography. Anamnestic data were collected with standardized questionnaires, including personal data, working history and current working conditions, and former and current illness with regard to the effects of DMF. Skin diseases were documented by a dermatologist. Results: DMF concentrations measured in the air ranged between <0.1 and 37.9?ppm (median 1.2?ppm). Concentrations of NMF varied from 0.05 to 22.0?mg/l (preshift values) and from 0.9 to 100.0?mg/l (postshift values). The creatinine-related values (0.02–44.6?mg/g preshift; 0.4–62.3 postshift) were subject to less variation and therefore represented the level of exposure better than the values related to volume. Additional investigation of a subcollective (n?=?31) over a period of 4 days showed that NMF did not accumulate in the organism. The positive but relatively weak association observed between the DMF concentrations measured in the workplace air and the values recorded for internal exposure in this study can be explained by influencing factors such as dermal absorption or protective clothing. Interindividual differences in internal exposure were found for the specific work areas. The German BAT value (15?mg NMF/l urine) was exceeded in 36 persons (29%) despite the use of breathing protection and protective gloves, without increased values being measured in the air. Increased absorption without higher-level exposure could particularly also be observed in employees with eczema. Conclusions: From the point of view of the prevention of disease, biological monitoring is the best instrument for exposure assessment of workers exposed to DMF.     

Dermal absorption of N,N-dimethylacetamide in human volunteers

Objectives: We investigated the potential for the dermal absorption of N,N-dimethylacetamide (DMAC: CAS No. 127-19-5) vapor, the biological half-life of N-methylacetamide (NMAC) in urine as the biological exposure item of DMAC, and the adjustment method for urinary concentrations. Methods: Twelve healthy male volunteers (mean age 25.2 years, range 21–43 years) were exposed to DMAC for 4 h on two occasions at intervals of 96 h or above. Each volunteer sat inside a whole-body-type exposure chamber for the dermal exposure experiment or outside the chamber for the inhalation exposure experiment. The temperature and relative humidity in the chamber were controlled at approximately 26 °C and 40% in order to keep the skin (90% naked) of the volunteers dry. DMAC concentrations were 6.1 ± 1.3 ppm for dermal exposure and 6.1 ± 1.3 ppm for inhalation exposure. Urine samples were collected from 0 h through 36 h and at 48 h and 72 h after the exposure. Extrapolations from exposure concentrations for 4 h to 10 ppm for 8 h were performed. Results: Mean dermal absorption was estimated to be 40.4% of the total DMAC uptake. The biological half-lives of urinary NMAC were 9.0 ± 1.4 h and 5.6 ± 1.3 h via skin and lung, respectively. Mean NMAC in urine just after 5 consecutive workdays (8 h/day) at 10 ppm DMAC exposure was assumed to be 33.7 mg/g · Cr (18.6–70.0 mg/g · Cr). Creatinine-adjusted NMAC concentration in urine for each volunteer within 12 h after the exposure was more closely correlated with the total excretion amount of NMAC up to 36 h than with urinary-volume-adjusted or specific-gravity-adjusted NMAC concentration in both the dermal and inhalation exposure experiments. Conclusions: DMAC vapor was significantly absorbed through the skin. Estimated NMAC values indicate that 20 mg/g · Cr NMAC seems to be appropriate as the biological exposure index. Received: 6 August 1999 / Accepted: 9 September 1999     

Isopropanol and methylformate exposure in a foundry: exposure data and neurobehavioural measurements

Objectives: The aim of this study was to determine the dose-effect relationship between solvent exposure and acute neurobehavioural effects at the worksite. Methods: In a balanced design, ten workers in a Swiss foundry were monitored for 15 days at ten different times during work. Urine samples were taken in the morning and at the time of examination, and personal exposure to isopropanol and methylformate was measured with active samplers. Neurobehavioural tests such as postural balance (bipedal, bipedal blind, monopedal), simple reaction time and digit span of the Neurobehavioural Evaluation System (NES2) and a combined memory and reaction-time test, the combi-test, were performed. A rating of well-being, and the last consumption of alcohol, caffeine, nicotine and medication were reported. Results: Average environmental concentrations of isopropanol were at 44 ppm (±16 ppm), and at 36 ppm (±21 ppm) for methylformate. Maximum values of personal exposure to isopropanol reached barely the maximal allowable concentration (MAC) value (400 ppm); the methylformate personal exposure of three workers exceeded the MAC value (100 ppm). Urine concentrations of methanol were high (3.1 ± 2.3 mg/l in the morning, 7.8 ± 4.9 mg/l after exposure) compared with the results of other studies; concentrations of isopropanol were rather low (0.88 ± 0.73 mg/l after exposure). Conclusions: Nevertheless, between personal exposure and biomonitoring, linear correlation was found. Methylformate exposure correlated with methanol and formic acid concentration in the urine, and isopropanol exposure with its concentration in the urine. With the neurobehavioural tests used, no solvent effect in relation to the dose could be determined. Received: 21 January 2000 / Accepted: 20 May 2000     

Correspondence between occupational exposure limit and biological action level values for alkoxyethanols and their acetates

Objectives: The Finnish occupational exposure limit (OEL) values for alkoxyethanols and their acetates were lowered in 1996. A reevaluation of the correspondence between the new OEL value and the biological action level (BAL) was thus needed. This study was conducted in silkscreen printing enterprises, where 2-alkoxyethanols and their acetates are mainly used as solvents. The air/urine correlations between 2-methoxyethylacetate, 2-ethoxyethylacetate, 2-butoxyethanol, 2-butoxyethylacetate, and 2-methoxyacetic (MAA), 2-ethoxyacetic (EAA), and 2-butoxyacetic acid (BAA) were evaluated on an individual and time-related basis at four different enterprises. Methods: Inhalation exposure to alkoxyalcohols and their acetates was monitored with diffusion badges (n = 38) for an entire work week. Urinary excretion of alkoxyacetic acids immediately after the shift and at 14–16 h after exposure (n = 112) was analyzed by a gas chromatograph equipped with a flame-ionization detector. Results: Inhalation exposure to 2-methoxyethylacetate at 0.5 cm³/m³ corresponded to MAA excretion of 3 mmol/mol creatinine in urine at 14 to 16 hours after exposure. The next-morning urinary EAA excretion of 37 mmol/mol creatinine corresponded to an 8-h 2-ethoxyethylacetate exposure of 2 cm³/m³ when all collected data were included. This average EAA excretion was 69% of the German BAT value and only 34% of the American biological exposure index (BEI) value. Urinary EAA excretion was 30–40% lower at the beginning of the work week than at the end of the work week. On the other hand, EAA excretion was 10–20% higher than that measured at 14–16 h after exposure. Urinary BAA excretion of 75 mmol/mol creatinine in postshift urine corresponded to an 8-h 2-butoxyethanol and 2-butoxyethylacetate exposure of 5 cm³/m³. This BAA excretion was 87% of the German BAT value. Conclusion: According to these results, it seems that the BAL for MAA and EAA should be 3 and 50 mmol/mol creatinine as measured at 14–16 h after exposure, respectively. The BAL value for BAA seems to be 70 mmol/mol creatinine in postshift samples. These recommendations are valid only if samples are collected at the end of the work week. Received: 29 January 1997 / Accepted: 2 July 1997     

Insertion polymorphism of CYP2E1 and urinary N -methylformamide after N,N - dimethylformamide exposure in Japanese workers

Objectives: This study examined whether consideration of the *1C/*1D CYP2E1 insertion polymorphism is important for interpreting the biological monitoring of exposure to N,N-dimethylformamide (DMF) in Japanese workers. Methods: The insertion genotype, airborne DMF exposure on the last day of a work week, and NMF in urine sampled just after the last workshift of the week were determined in 44 male and female Japanese workers. Results and conclusions: The allelic frequency of this CYP2E1 polymorphism was 0.261 in this Japanese population of workers. The CYP2E1 insertion polymorphism did not contribute to NMF levels even after consideration of BMI or alcohol intake. The results indicate that CYP2E1 insertion polymorphism does not appear to be an important determinant for the interpretation of biological exposure to DMF by the measurement of urinary NMF. Received: 26 September 2000 / Accepted: 7 May 2001     

Risk of lung cancer in workers producing stainless steel and metallic alloys

Objectives: The mortality of workers involved in the production of stainless and alloyed steel from 1968 to 1992 was studied, in order to investigate the risk of lung cancer due to exposure to metals, i.e. iron oxides, chromium and/or nickel compounds. Methods: The study design was a historical cohort mortality study and a nested case-control study concerning lung cancer. Standardized mortality ratios (SMRs) were computed using regional mortality rates as an external reference for comparing observed and expected numbers of deaths, adjusting for age, sex and calendar time. Conditional logistic regression was used to estimate odds ratios (ORs). Occupational exposure was assessed through the complete job histories of cases and controls and a specific job-exposure matrix. Results: The cohort comprised 4,288 male and 609 female workers. The observed overall mortality was significantly lower than expected [649 deaths; SMR = 0.91; 95% confidence interval (CI) 0.84–0.98]. No significant SMR was observed for mortality from lung cancer (54 deaths; SMR = 1.19; CI 0.88–1.55). The case-control study was based on 54 cases and 162 individually matched controls. Smoking habits were available for 71%. No lung cancer excess was observed for exposure to (1) metals and/or their compounds, i.e. iron (OR = 0.94, CI 0.48–1.86), chromium and/or nickel (OR = 1.18, CI 0.62–2.25), and cobalt (OR = 0.64, CI 0.33–1.25), (2) acid mists (OR = 0.43, CI 0.17–1.10), and (3) asbestos (OR =  1.00, CI 0.54–1.86). With respect to exposure to polycyclic aromatic hydrocarbons (PAHs) and silica, which are often found together in workplaces, (1) high and statistically significant lung cancer excesses were observed, the ORs being 1.95 (CI 1.03–3.72) and 2.47 (CI 1.28–4.77) respectively, (2) quantitative exposure parameters revealed upward trends reaching statistical significance (P < 0.05), and (3) adjustments for tobacco consumption did not reveal any confounding factors from smoking. Conclusion: This study failed to detect any relationship between lung cancer and exposure to iron, chromium, nickel and/or their compounds. High and statistically significant relative risks, along with increasing trends, were observed for simultaneous exposure to PAHs and silica. Received: 12 April 1999 / Accepted: 2 October 1999     

Blood benzene concentrations in workers exposed to oxygenated fuel in Fairbanks,Alaska

 Objective: In November 1992 residents of Fairbanks, Alaska became concerned about the potential health effects of an oxygenated fuel program during which 15% (by volume) methyl tertiary butyl ether (MTBE) was added to gasoline. To address those concerns, we earlier completed a survey of occupational exposure to MTBE. We conducted a follow-up survey of workers’ exposure to benzene from gasoline in Fairbanks. Design: Cross-sectional exposure survey. Methods: We examined blood concentrations of benzene from a convenience sample of workers taken in December 1992 during the oxygenated fuel program and from another convenience sample of workers taken in February 1993 after the program was suspended. Results: In December, the median blood benzene concentration of samples taken from four mechanics after their workshift (postshift) was 1.32  μg/l (range, 0.84–2.61 μg/l), and seven nonmechanics (drivers and other garage workers) had a median postshift blood benzene concentration of 0.27 μg/l (range, 0.09– 0.45 μg/l). In February, nine mechanics had a median postshift blood benzene concentration of 1.99 μg/l (range, 0.92–3.23 μg/l), and nine nonmechanics had a median postshift blood benzene concentration of 0.26 μg/l (range, 0.2–0.46 μg/l). Conclusion: Mechanics had higher blood benzene concentrations than did nonmechanics, but further study is needed to determine the impact of the oxygenated fuel program on exposure to benzene. Received: 6 November 1995/Accepted: 2 April 1996     

Urinary nickel as bioindicator of workers' Ni exposure in a galvanizing plant in Brazil

Objectives: We measured urinary nickel (U-Ni) in ten workers (97 samples) from a galvanizing plant that uses nickel sulfate, and in ten control subjects (55 samples) to examine the association between occupational exposure to airborne Ni and Ni absorption. Methods: Samples from the exposed group were taken before and after the work shift on 5 successive workdays. At the same time airborne Ni (A-Ni) was measured using personal samplers. Ni levels in biological material and in the airborne were determined by a graphite furnace atomic absorption spectrometry validated method. In the control group the urine samples were collected twice a day, in the before and after the work shift, on 3 successive days. Results: Ni exposure low to moderate was detected in all the examined places in the plant, the airborne levels varying between 2.8 and 116.7 μg/m³ and the urine levels, from samples taken postshift, between 4.5 and 43.2 μg/g creatinine (mean 14.7 μg/g creatinine). Significant differences in U-Ni creatinine were seen between the exposed and control groups (Student's t test, P ≤ 0.01). A significant correlation between U-Ni and A-Ni (r = 0.96; P ≤ 0.001) was detected. No statistical difference was observed in U-Ni collected from exposed workers in the 5 successive days, but significant difference was observed between pre- and postshift samples. Conclusions: Urinary nickel may be used as a reliable internal dose bioindicator in biological monitoring of workers exposed to Ni sulfate in galvanizing plants regardless of the day of the workweek on which the samples are collected. Received: 28 January 1999 / Accepted: 10 July 1999     

Albumin, transferrin and α2-macroglobulin in bronchoalveolar lavage fluid following exposure to organic dust in healthy subjects

Objectives: The purpose of the present study was to investigate leakage of plasma proteins in connection with the inflammatory airway reaction following exposure to dust in a pig house. Inhalation of swine-house dust causes intense inflammation with influx of inflammatory cells, predominantly neutrophils, into the airways. The aim of the study was to compare the concentration of three different proteins in bronchoalveolar lavage (BAL) fluid as markers for the inflammation. Methods: In twenty healthy, non-allergic, non-smokers, not previously exposed to farm dust, BAL was performed ≈2 weeks before and 24 h after 3 h of exposure to swine dust in a swine-confinement building. Differential cell count and protein concentration were assessed in BAL fluid. Albumin (66.5 kDa) and α₂-macroglobulin (720 kDa) were quantified by the use of enzyme-linked immunosorbent assay (ELISA) techniques, and transferrin (80 kDa) by zone immunoelectrophoresis assay. The coefficient of variation for repeated protein measurements was <9%. Results: α₂-Macroglobulin concentration increased six-fold, from 68.0 (36.1–99.9) μg/l, mean (95% CI) before exposure to 411.2 (254.0–568.4) μg/l after exposure (P < 0.001). Transferrin and albumin increased from 19.7 (16.2–23.1) mg/l and 1.8 (1.4–2.2) mg/l, 2.6 and 1.9 times, respectively (P < 0.001). There was significant correlation between the exposure-induced increased protein levels in BAL fluid, although α₂-macroglobulin was a better discriminator of pre- and post-exposure concentrations than were albumin and transferrin. There was a significant correlation between the exposure-induced BAL-fluid neutrophilia and the increase in α₂-macroglobulin and transferrin, but not for albumin. This correlation was found only when pre- and post- differences, but not ratios, of plasma proteins were compared. Conclusions: The levels of plasma proteins increased in BAL fluid following exposure to swine-house dust. α₂-Macroglobulin was a better marker of this plasma leakage than were albumin and transferrin. Received: 25 July 2000 / Accepted: 10 November 2000     

Normal liver function in women in the general Japanese population subjected to environmental exposure to cadmium at various levels

Objectives: Whereas it is well established that environmental exposure to cadmium (Cd) may induce kidney dysfunction, less attention has been paid to the possible disturbance of liver function by Cd exposure. The possibility that liver function is adversely affected by current levels of environmental exposure to Cd as investigated in women in the general population in Japan, where the background level of exposure to Cd is known to be high. Methods: From 1991 to 1997, 24-h food duplicate, peripheral blood and morning spot urine samples were collected from 607 non-smoking and non-habitually drinking women (age range 19–78 years) at 30 survey sites (with no known environmental pollution from heavy metals) throughout Japan. Liver function parameters in serum were examined by conventional methods. After wet-ashing, the food duplicate, blood and urine samples were analyzed for Cd intake via food (Cd-F), Cd in blood (Cd-B), and Cd in urine (Cd-U) by inductively-coupled plasma mass spectrometry. Results: The geometric mean values for Cd-F, Cd-B, and Cd-U were 24.7 (27.1) μg/day, 1.76 (2.07) μg/l, and 3.94 (4.61) μg/g creatinine (values in parentheses for 41- to 60 year-old women), respectively. It as found that the three parameters of ALP, ALT, and AST activity were positively and significantly related to the age of the subjects (whereas no association as detected in cases of γ-GTP, LAP, and albumin). Accordingly, a further analysis as made with 367 women selected by age (41–60 years; about 60% of the total population). Essentially, no Cd dose-dependent changes in liver function parameters were observed in the selected population of this narrower age range. Conclusions: Overall, it seemed prudent to conclude that liver function as not disturbed by the current environmental exposure to Cd in Japan. Received: 16 March 1999 / Accepted: 17 July 1999     

R-rated Movie Viewing,Growth in Sensation Seeking and Alcohol Initiation: Reciprocal and Moderation Effects

The current study employed parallel process and discrete time hazard regressions to examine the interplay among exposure to R-rated movies, sensation seeking, and initiation of alcohol use in a national U.S. sample (N = 6255) of adolescents, ages 10–14, who were followed over four waves spanning 2 years. There was a short-term reciprocal relation between watching R-rated movies and sensation seeking, but over the 2-year observation period, exposure to R-rated movies was associated with increases in sensation seeking and not vice versa. Sensation seeking also moderated the effect of watching R-rated movies on initiation of alcohol consumption such that exposure was associated with greater increases in initiation of alcohol use among low sensation than among high sensation seeking adolescents. The study provides empirical evidence of an environmental media effect on sensation seeking, and important new information about the relations among sensation seeking, media exposure, and adolescent alcohol use.     

Thyroid function in lead smelter workers: absence of subacute or cumulative effects with moderate lead burdens

Objective: To evaluate the effect of low to moderate occupational lead exposure on thyroid function we conducted a cross-sectional study of 151 male lead smelter workers. Methods: Parameters of thyroid function were assessed in relation to both subacute and cumulative lead exposure over a 10-year employment period. Blood lead levels, obtained from plant surveillance records, were used to establish four ordinal levels of current and cumulative exposure (<15, 15–24, 25–39, and ≥40 μ g/dl). Results: Mean values for the lowest as compared with the highest current exposure group were similar for thyroxine (T₄: 6.8 versus 6.1 μ g/dl), estimated free thyroxine (EFT₄: 1.6 ng/dl in both groups), and thyroid-stimulating hormone (TSH: 1.8 versus 1.7 mIU/l); there was no evidence of a significant trend for diminished thyroid function associated with increasing current lead exposure. Similarly, no significant difference was observed for T₄, EFT₄, or TSH in relation to the 10-year cumulative exposure or for adjusted analyses controlling for potential confounders, including age and alcohol use. Conclusion: In contrast to studies observing thyroid dysfunction in the setting of high lead exposure and related clinical poisoning, our findings weigh against a significant physiologic effect on thyroid function at lower levels (<60 μ g/dl) of occupational lead exposure. Received: 3 August 1997 / Accepted: 8 July 1998     

Case-referent study on occupational risk factors for bladder cancer in southern Israel

Objective: To evaluate the possible association between occupational exposures (risk factors) and male bladder cancer in the Negev region (southern Israel) to enable preventive strategies to be applied. Methods: A total of 92 male bladder cancer patients, diagnosed at a regional medical center between 1989 and 1993, were studied by interview and compared with 92 males without oncological disease after matching by age and country of origin. A special questionnaire was developed to gather information on demography, life-time occupational history, smoking habits, coffee consumption, and health status. Statistical analysis of the case-referent data was done using the SPSS-5 package for performance of the chi-square test, conditional logistic regression, and multiple classification analysis. Results: Significant associations were found between bladder cancer occurrence and (1) three different groups of occupational exposures [a – solvents (P = 0.002, OR not computed due to the lack of exposed persons among referents), b – dusts (P = 0.02; OR = 4.67), and c – exposure to multiple chemicals (P < 0.001, OR = 6.25); (2) nephrolithiasis (P = 0.02, OR = 11.00); and (3) cigarette smoking (P = 0.01, OR = 1.87). Conclusions: Certain types of occupational exposure, different from that to aromatic amines and dyes, may be considered as contributing factors in the epidemiology of bladder cancer. Better identification of these chemicals and the work processes where they are used may help in abating such exposures, thus leading to a reduction in the risk for this relatively common cancer. Received: 6 April 1998 / Accepted: 16 January 1999     

Determination of N-nitrosodiethanolamine in urine by gas chromatography thermal energy analysis: application in workers exposed to aqueous metalworking fluids

 Objective: The aim of this study was to describe a detailed and validated methodology designed for the analysis of carcinogenic N-nitrosodiethanolamine (NDELA) down to sub-μg/l levels in urine and its application to a number of workers exposed to NDELA-contaminated aqueous metalworking fluids (MWF). Methods: Following a work-up procedure based on solid-phase extraction of NDELA, the urinary extracts were analysed without derivatization by gas chromatography on a polar wide-bore column with chemiluminescent detection using a thermal energy analyser (TEA). N-Nitroso-(2-hydroxypropyl)amine was used as an internal standard. The method was applied to 12 workers using “nitrite-free” or “nitrite-formulated” MWF and to 15 unexposed subjects. The NDELA content of the MWF was also determined using a similar, but simpler method able to easily quantify NDELA down to at least 0.1 mg/l. Results: Contamination by NDELA traces of some chemicals used for the sample preparation, particularly ethyl formate, must be carefully checked since it can give rise to false-positive results of up to 1 or 2 μg/l. The response was linear in the range of 0–500 μg/l. Between 0.5 and 10 μg/l, the recovery rate was close to 95%, while repeatability ranged from 12.5 to 6.4% (n = 5). The detection limit was 0.3 μg/l (Signal/noise = 3). No detectable NDELA could be observed in the control workers. There was no significant increase in NDELA levels at the end of shift spot samples from an exposed worker over 1 week. Higher NDELA concentrations were found in two workers (4.3 and 10.7 μg/l) exposed to “nitrite-formulated” fluids (contaminated with 65 and 18 mg NDELA per l, respectively) than in nine workers (range, 0.4–1.3 μg/l exposed to “nitrite-free” fluids with lower levels of NDELA (range, 0.5–6.6 mg/l). Conclusion: The detailed methodology described in this work and applied to a limited industrial situation was found to be suitable for monitoring NDELA in the urine of workers exposed to aqueous MWF. A much larger screening has been undertaken with the aim of obtaining better information on the real exposure of workers sometimes exposed to “nitrite-formulated” fluids that are still used. Received: 8 December 1998 / Accepted: 3 April 1999