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     

Urinary elimination of nickel and cobalt in relation to airborne nickel and cobalt exposures in a battery plant

Objective To estimate the relationship between Ni concentrations in the ambient air and in the urine, at a battery plant using nickel hydroxide. Methods Workers occupationally exposed to a mixture of nickel hydroxide, metallic cobalt and cobalt oxyhydroxide dust were studied during two consecutive workdays. Air levels of Ni and Co in total dust were determined by personal sampling in the breathing zone. Both metals in air were sampled by Teflon binder filters and analyzed by inductively coupled plasma absorption emission spectrophotometry. Urine was collected from 16 workers immediately before and after the work shift. Urinary Ni and Co concentrations were measured by electrothermal atomic absorption spectrometry. Results A poor correlation was seen between Co in the air and in post-shift urine (r = 0.491; P < 0.01), and no correlation was found between Ni in the air and in post-shift urine (r = 0.272; P = 0.15), probably due to the use of respiratory protection. The subjects were exposed to higher levels of Ni than Co (Ni (mg/m³) = −0.02 + 7.41 Co (mg/m³), r = 0.979, P < 0.0001). Thus, exposure to Co at 0.1 mg/m³ should produce a Ni level of 0.7 mg/m³. According to section XIII of the German list of MAK and BAT Values, a relationship between exposure to Co and urinary Co excretion, Co (μg/l) = 600 Co (mg/m³), has been established and the relationship between soluble or insoluble Ni salts in the air and Ni in urine was as follows: Ni (μg/l) = 10 + 600 Ni (mg/m³) or Ni (μg/l) = 7.5 + 75 Ni (mg/m³). Assuming nickel hydroxide to be soluble and to be insoluble, the Ni concentrations corresponding to Ni exposure at 0.7 mg/m³ were calculated as 430 and 60 μg Ni/l, respectively. Similarly, exposure to Co at 0.1 mg/m³ should result in Co urinary concentrations of 60 μg Co/l. On the other hand, a good correlation was found between Co and Ni in post-shift urine (Ni (μg/l) = 9.9 + 0.343 Co (μg/l), r = 0.833, P < 0.0001). On the basis of this relationship, the corresponding value found in our study was 0.343 × 60 μg Co/l + 9.9 = 30.5 μg Ni/l. This value was close to that calculated by the equation for a group of insoluble compounds, but about 14 times lower than that calculated by the equation for a group of soluble compounds. Conclusions Our results suggest that exposure to nickel hydroxide yields lower urine nickel concentrations than the very soluble nickel salts, and that the grouping of nickel hydroxide might be reevaluated. Therefore, to evaluate conclusively the relationship between nickel hydroxide dust in the air and Ni in post-shift urine, further studies are necessary.     

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     

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     

Exposure in welding of high nickel alloy

Summary Nickel (Ni) levels in air during welding of high-Ni alloy (75% Ni) were very high (mean 0.44 mg/m³, range 0.07–1.1 mg/m³; 20 person-days of measurements). In six welders the Ni level in urine after four weeks of vacation was slightly but statistically significantly enhanced as compared to ten unexposed controls (means 8.7 vs 5.1 g/l; P<0.005). The level on Monday mornings increased somewhat during a period of six weeks of high-Ni alloy welding (mean 13 g/l; P < 0.05). The level was slightly higher Thursday afternoon (mean 18 g/l; P < 0.0001). The data indicate the existence of a very slow pool of Ni in the body in addition to a faster one. There was no correlation between Ni levels in air and urine. Thus, in spite of the very high Ni levels in air, urinary Ni levels were thus of little use for biological monitoring of exposure and risk during high-Ni alloy welding. All eleven welders studied reported one or more symptoms (irritation of upper airways, headache, tiredness) as occurring more often (P < 0.006) during high-Ni welding than when welding ordinary stainless steel. Lung-functions studies were normal.     

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     

Indoor exposure to polycyclic aromatic hydrocarbons and carbon monoxide in traditional houses in Burundi

Objectives: Wood combustion is used as a major energy source in African countries and could result in indoor, pollution-related health problems. This exploratory study was undertaken to estimate polycyclic aromatic hydrocarbon (PAH) and carbon monoxide exposure in individuals living in traditional rural houses in Burundi. Methods: Standard methods were used to determine indoor air concentrations of 12 PAHs, and carbon monoxide. The urinary excretion of 1-hydroxypyrene (1-OHP) was measured in occupants of traditional houses, and compared with that of individuals living in the town of Bujumbura, the capital of Burundi. Results: Mean airborne concentration of four volatile PAHs, naphthalene, fluorene, phenanthrene and acenaphthene, exceeded 1 μg/m³, and that of benzo(a)pyrene was 0.07 μg/m³. Naphthalene was by far the main PAH contaminant, with a mean concentration (±standard deviation) of 28.7 ± 23.4 μg/m³, representing on average 60–70% of total PAH concentration. Carbon monoxide mean concentration (±standard deviation) was 42 ± 31 mg/m³, and correlated with total PAH concentration. Geometric mean urinary 1-OHP excretion (range) in people living in traditional houses was 1.50 (0.26–15.62) μmol/mol creatinine, a value which is on average 30 times higher than that of people living in the capital (0.05 (0.009–0.17) μmol/mol creatinine). Conclusions: It appears that the substantially high concentrations of the studied contaminants constitute a potential health hazard to the rural population of Burundi. Received: 15 July 1999 / Accepted: 20 November 1999     

Cadmium exposure of women in general populations in Japan during 1991–1997 compared with 1977–1981

Objectives: The Japanese people are known to have high environmental exposure to cadmium (Cd). The present survey was initiated to elucidate possible changes in the intensity of Cd exposure to the population by comparison of the present exposure level with the situation some 15 years ago. Methods: During 1991–1997, 24-h food-duplicate samples, peripheral blood specimens and morning spot urine samples were collected from 588 non smoking women from 27 survey sites in six regions, where food-duplicate and blood samples had also been obtained during 1977–1981 from 399 women. The samples were wet-ashed (after homogenization in the case of food-duplicates), and Cd in the wet-ashed samples was analyzed by inductively-coupled plasma mass spectrometry for Cd intake via foods (Cd-F), Cd concentration in blood (Cd-B) and Cd concentration in urine (Cd-U). The Cd-F and Cd-B were compared with the Cd-F and Cd-B obtained at the same sites in the 1977–1981 survey. Results: The exposure levels during 1991–1997 were such that Cd-F, Cd-B and Cd-Ucr (Cd–U after correction for creatinine concentration) were 25.5 μg/day, 1.90 μg/l and 4.39 μg/g creatinine. Comparison with the 1977–1981 survey results (i.e., 37.5 μg/day for Cd-F and 3.47 μg/l for Cd-B) showed that there were significant reductions (by 32 and 45%) in both parameters respectively during the last 15 years. The dietary route was an almost exclusive (i.e., 99% of the sum of dietary and respiratory uptake) route of Cd uptake, of which Cd in rice (11.7 μg/day) contributed about 40% of the total dietary intake. When compared among survey sites, inter-site variation in dietary Cd intake was primarily due to differences in the intake through boiled rice. Despite the recent reduction in Cd exposure, the current exposure level for Japanese people is still higher than the levels among other rice-dependent populations in Asia as well as in other parts of the world. Comparison was made between the present findings in general populations and observations among known Cd-pollution cases in Japan. Conclusions: Dietary uptake is an almost exclusive route of Cd exposure in the general Japanese population. Boiled rice is a strong determinant of variation in dietary Cd intake. Whereas there was a substantial reduction in Cd exposure among Japanese populations in the last 15 years, the current level is still high when compared internationally. Received: 1 March 1999 / Accepted: 17 July 1999     

Urinary cotinine concentration in flight attendants, in relation to exposure to environmental tobacco smoke during intercontinental flights

Objectives: To measure and compare the urinary cotinine concentration (U-cotinine) in non-smoking cabin attendants (C/A) working with the Scandinavian Airlines System, before and after work on intercontinental flights with exposure to environmental tobacco smoke (ETS). Methods: The study material consisted of 24 cabin attendants and one pilot, all volunteers and all without exposure to ETS in the home, working on 15 intercontinental flights. Information on age, gender and occupation was gathered, as well as possible sources of ETS exposure in other places, outside work and during previous flights, during a 3-day period prior to the investigation. Urine samples were taken before departure and after landing, on board, and were kept frozen (−20 °C) until analysis. Cotinine was analyzed by a previously developed gas chromatographic method, using mass spectrometry (MS) with selected-ion monitoring (SIM). The difference in U-cotinine before and after the flight was compared. Moreover, the change in U-cotinine during the flight was related to occupation (work in the forward or aft galley) and observed degree of smoking during each flight. Results: The median U-cotinine was 3.71 μg/g crea; 2.4 μg/l (unadjusted) (interquartile range 2.08–8.67 μg/g crea) before departure, and 6.37 μg/g crea; 7.1 μg/l (interquartile range 3.98–19 μg/g crea) after landing, a significant difference (P < 0.003). C/A in the aft galley had a significantly higher concentration of U-cotinine after landing than subjects working in the front of the aircraft (P=0.01). In C/A working in the aft galley, the median increase of U-cotinine was 3.67 μg/g crea; 3.2 μg/l (interquartile range 0.04–13.8 μg/g crea) during flight. In contrast, those seven subjects working in the forward part of the aircraft had no increase in U-cotinine during the flight (median increase 0.97 μg/g crea; 0.5 μg/l interquartile range 0.27–2.65 μg/g crea). Conclusion: Tobacco smoking in commercial aircraft may cause significant exposure to environmental tobacco smoke among C/A working in the aft galley, despite high air exchange rates and spatial separation between smokers and non-smokers. This agrees with earlier studies, as well as measurements on the aircraft, showing a higher degree of ETS-related air pollution in the aft galley than in the forward galley. The average cotinine concentration in urine was similar to that in other groups with occupational exposure to ETS, e.g., restaurant staff, police interrogators and office workers. Since smoking in commercial aircraft may result in an involuntary exposure to ETS among non-smokers, it should be avoided. Received: 1 February 1999 / Accepted: 29 May 1999     

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     

Nicotinamide adenine dinucleotide synthetase activity in erythrocytes as a tool for the biological monitoring of lead exposure

Objective: The objective of this study was to evaluate the usefulness of nicotinamide adenine dinucleotide synthetase (NADS) activity for the biological monitoring of lead exposure. Methods: The subjects were 76 male lead workers and 13 normal volunteers (7 males and 6 females). NADS activity and blood lead concentration (Pb-B) was determined in each subject. Delta-aminolevulinic acid dehydratase (ALAD) activity was determined in 58 lead workers out of 76 subjects. Results: NADS activity in the lead workers ranged from 0.08 to 1.1 μmol/h per g of hemoglobin (gHb) and decreased linearly (r = − 0.867) as Pb-B increased up to 81.6 μg/dl. The pattern of depressed activity of NADS was different from that of ALAD activity, which decreased rapidly and reached a plateau at the Pb-B level between 40 and 60 μg/dl. The Pb-B levels inducing 50% inhibition of the enzyme activities were calculated to be 43 μg/dl and 20 μg/dl for NADS and ALAD, respectively. At the Pb-B level of 40 μg/dl, NADS activity showed high validity (1.77) with predictivity of 0.92 at the cut-off level of 0.4 μmol/h per gHb, which were higher than those of ALAD activity. Conclusions: These results show an apparent dose-effect relationship of NADS activity versus Pb-B. NADS activity can be used for the biological monitoring of lead exposure. Received: 28 October 1996 / Accepted: 7 February 1997     

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.     

Reference values for cobalt, copper, manganese, and nickel in urine among women of the general population in Japan

Objective: The present study was initiated to establish the reference levels of Co, Cu, Mn, and Ni in urine of women in the general Japanese population. Methods: Stored urine samples were subjected to the analysis. The samples were collected from 1,000 adult women all over Japan, who had no occupational exposure to these elements. Co, Cu, Mn, and Ni in urine were analyzed by graphite furnace atomic absorption spectrometry. The concentrations were distributed log-normally, and were presented in terms of geometric mean (GM) and geometric standard deviation, as observed or after correction for creatinine concentration or a specific gravity of urine of 1.016. Results: The GM values of observed levels (i.e., with no correction for urine density) and of the levels after correction for creatinine (cr) concentration (values in parenthesis) were 0.68 g/l (0.60 μg/g cr) for Co, 13.4 g/l (11.8 g/g cr) for Cu, 0.14 μg/l (0.12 g/g cr) for Mn and 2.1 g/l (1.8 g/g cr) for Ni. There was a life-long age-dependent increase in Cu. Mn levels reached the maximum at 60 to 69 years of ages. In contrast, age-dependency was not substantial in Co and Ni. Conclusions: Comparison with values reported in literatures for other areas showed that Co and Ni levels in urine of Japanese women are higher than, Cu level is comparable with, and Mn level is lower than others. The reasons for high Co and Ni levels deserve further study.     

Skin absorption of the industrial catalyst dimethylethylamine in vitro in guinea pig and human skin, and of gaseous dimethylethylamine in human volunteers

Objectives: The aims of the study were threefold: to assess the skin uptake of the industrial catalyst dimethylethylamine (DMEA) (a) in vitro from water solutions by fresh guinea-pig and human skin specimens, (b) in gaseous form in vivo in human volunteers, and (c)␣to estimate the relevance of the uptake as an occupational hazard. Methods: Specimens from the in vitro and in vivo experiments were analysed by gas chromatography using a nitrogen-sensitive detector. Design: DMEA, diluted with water or isotonic saline solution was applied to fresh human or guinea-pig skin, mounted in Teflon flow-through cells with a perfusion fluid flow rate of 1.5 ml/h, samples being collected at 2-h intervals for 48 h. Three healthy male volunteers each had their right forearm exposed (in a Plexiglass chamber) for 4 h to DMEA at each of three different levels (250, 500 and 1000 mg/m³ air). Urine was collected up to 24 h after the start of each experiment. Results: DMEA penetrated both guinea-pig and human skin. The median steady-state flux and permeability coefficient (K _p) values, were 0.009 mg/cm² × h and 0.001 cm/h, respectively, for guinea-pig skin, and 0.017 mg/cm² × h and 0.003 cm/h, respectively, for human skin. The median uptake in the three volunteers at the different DMEA exposure levels (250, 500 or 1000 mg/m³) was 44, 64 and 88 μg, respectively. The median K _p for all experiments was 0.037 cm/h. Conclusion: Uptake of DMEA through the skin is of far less importance than simultaneous uptake via the airways. Thus, the amount of DMEA excreted in urine is a variable of limited use for the purposes of biological monitoring. Although a wide range of K _p values was obtained in the in vitro experiments, both for guinea-pig and human skin, there was no marked difference in median K _p values between the two types of skin. The K _p values were lower than those obtained for human forearm skin in vivo. However, future studies of other tertiary aliphatic amines may show the in vitro␣method to yield values predictive of those obtained in in vivo studies. Received: 20 May 1996 / Accepted: 10 March 1997     

Urinary lead as a possible surrogate of blood lead among workers occupationally exposed to lead

Objectives: The aim of the present study is to investigate whether lead (Pb) in urine (Pb-U) can be a valid surrogate of lead in blood (Pb-B), the traditional biomarker of exposure to lead in occupational health. Methods: Blood and spot urine samples were collected from 258 workers of both sexes occupationally exposed to lead. The samples were analyzed for lead by graphite furnace atomic absorption spectrometry, and the correlation between Pb-B and Pb-U was examined by linear regression analysis before and after logarithmic conversion. Results: The correlation coefficient (0.824; P < 0.01) was largest when the relationship between Pb-B and Pb-U was examined with 214 cases of one sex (i.e., men) after Pb-U was corrected for a specific gravity (1.016) of urine (Pb-Usg) and both Pb-B and Pb-Usg were converted to logarithms. The geometric means (GMs) of Pb-B and Pb-Usg for the 214 men were 489 μg/l and 81 μg/l, respectively. When Pb-Usg was assumed to be 100 μg/l in this set of correlations, the 95% confidence range of Pb-B for the group mean was narrow, i.e., 543–575 μg/l (with GM of 559 μg/l), whereas that for individual Pb-B values was as wide as 355–881 μg/l. Conclusions: The correlation of Pb-U with Pb-B among workers occupationally exposed to Pb was close enough to suggest that Pb-U may be a good alternative to Pb-B on a group basis, but not close enough to allow Pb-U to predict Pb-B on an individual basis. Received: 6 April 1999 / Accepted: 17 July 1999     

A comparison of different lead biomarkers in their associations with lead-related symptoms

Objectives: To evaluate whether dimercaptosuccinic acid (DMSA) -chelatable lead, an estimate of current bioavailable lead stores, is a better predictor of lead-related symptoms than are other commonly used lead biomarkers. Methods: A total of 95 male lead workers from three lead industries (one secondary lead smelting facility, one polyvinyl chloride-stabilizer manufacturing plant, and one lead-acid storage battery factory), and 13 workers without occupational lead exposure recruited from an occupational health institute, were studied. Blood lead, blood zinc protoporphyrin (ZPP), 4 h DMSA-chelatable lead (after oral administration of 10 mg/kg DMSA), urine lead, and urinary δ-aminolevulinic acid levels were evaluated as predictors of 15 lead-related symptoms, assessed by self-administered questionnaire, with linear and logistic regression controlling for covariates. Total symptoms and symptoms in three categories (gastrointestinal, neuromuscular, and general) were evaluated. Results: The mean (SD) 4 h DMSA-chelatable lead level was 288.7 (167.7) μg, with a range from 32.4 to 789 μg in the 95 lead workers. The mean (SD) in the non-exposed subjects was 23.7 (11.5) μg with a range from 10.5 to 43.5 μg. Blood lead, blood ZPP, and spot urine lead levels ranged from 21.4 to 78.4 μg/dl, 40 to 331 μg/l, and 7.5 to 153.0 μg/l, respectively, in the lead workers, and from 4.0 to 7.2 μg/dl, 27 to 52 μg/l, and 2.9 to 15.5 μg/l in the non-exposed controls, respectively. The overall mean symptom score (SD), derived as the sum of 0 or 1 point for absence or presence of 15 symptoms, of the lead workers was 3.7 (2.0), compared to 1.2 (1.5) for the non-exposed workers. DMSA-chelatable lead was the best predictor of symptom scores in both crude and adjusted analyses, compared with the other biomarkers. Lead workers with DMSA-chelatable lead values greater than the median (260.5 μg) were 6.2 times more likely to have frequent tingling or numbness of the arms or legs and 3.3 times more likely to have muscle pain than subjects with lower chelatable lead values. Three symptoms (tingling or numbness of arm or leg, muscle pain, and feeling irritation at the slightest disturbance) evidenced a dose-dependent relationship with DMSA-chelatable lead levels. Conclusions: DMSA-chelatable lead was found to be the best predictor of lead-related symptoms, particularly of both total symptom scores and neuromuscular symptoms, than were the other other lead biomarkers. Received: 27 January 1999 / Accepted: 29 January 2000     

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     

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     

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     

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