δ-Aminolevulinic acid in plasma or whole blood as a sensitive indicator of lead effects,and its relation to the other home-related parameters

 To evaluate the subclinical effect of lead exposure, we determined δ-aminolevulinic acid (ALA) levels in plasma (ALA-P), blood (ALA-B), and urine (ALA-U) and the activity of δ-aminolevulinic acid dehydratase (ALAD) in lead workers. Almost all of the ALA molecules in blood were present in plasma and not in blood cells, irrespective of the blood lead concentration (Pb-B). ALA-P or ALA-B levels increased slowly at Pb-B levels below 40 μg/dl (slow phase) and rapidly at levels above 40 μg/dl (rapid phase). In both phases, ALA-P and ALA-B were well correlated with Pb-B and ALAD activity. The threshold value (no-effect level) of Pb-B for elevation of the ALA-P or ALA-B level was coincident with that for ALAD inhibition; the value was around 5 μg/dl. In the rapid phase, ALA-P increased continuously up to 100 μg/dl of Pb-B, while ALAD activity reached a plateau. Receiver operative characteristic (ROC) plot analyses indicated that ALA-P and ALAD activity [ALAD(u)] had a similar diagnostic value at Pb-B levels between 10 and 40 μg/dl, although ALAD(%), the remaining ALAD activity as a percentage of the whole activity restored by zinc and dithiothreitol, had the most powerful diagnostic efficiency at these Pb-B levels. By contrast, ALA-U and zinc protoporphyrin were less effective for the diagnosis of lead exposure than ALAD and ALA-P. These findings indicate that ALA-P is the best discriminators of lead exposure form baseline to high levels of exposure. Received: 18 October 1994/Accepted: 11 September 1995     

The epidemiology and surveillance of blood lead in Taiwan (R.O.C.): A report on the PRESS-BLL project

 To monitor the lead hazards in industries and to investigate the prevalence of elevated blood lead levels (BLLs) in lead-exposed workers, a lead surveillance system (PRESS-BLLs) has been established and operated in Taiwan, Republic of China, since July 1993. A cohort of lead-exposed workers who received a periodic annual health examination at 55 accredited hospital laboratories was constructed. A total of 9807 separate BLL measurements were reported to the system in 1994. The mean BLL was 15.8 μg/dl in male workers and 11.6 μg/dl in female workers. The mean BLL of lead-exposed workers was significantly (P<0.05, z-test) higher than that of the general Taiwanese population (8.6 μg/dl for males and 6.7 μg/dl for females). In addition, the BLLs of 983 (10.0%) workers exceeded the regulatory action level (40 μg/dl for males; 30 μg/dl for females). The workplaces and homes of 57% of the workers with elevated BLLs were thoroughly investigated to determine the sources of lead contamination. These actions identified the causes of elevated BLLs and set up strategies to reduce workers’ lead exposure. The establishment of this occupational lead surveillance system represents a method for monitoring of lead hazards from occupational and environmental settings to prevent lead poisoning. The information acquired from the system can help in the setting up of a priority of prevention and the development of control measures. It is also useful for further monitoring of changes in the BLLs of the lead-exposed-worker cohort. The Health Department of Taiwan can use this information to evaluate the effectiveness of current industrial hygiene practice. Subjects with elevated BLLs have been medically treated and placed on long-term follow-up for sequelae. Received: 2 September 1996/Accepted: 29 November 1996     

Internal exposure to hazardous substances of persons from various continents: investigations on exposure to different organochlorine compounds

 The aim of the study was to investigate the concentration of organochlorine compounds of environmental-medical relevance in biological materials from refugees with regard to their countries of origin and to compare these concentrations with the internal exposure of the German general population. Methods: During medical examination after entry to Germany specimens could be taken from the refugees to determine the following parameters of biological monitoring: 1,1-dichloro-2,2-bis(-chlorophenyl)-ethylene (DDE-P), polychlorinated biphenyls (PCB-P), pentachlorophenol (PCP-P) and the beta- and gamma-hexachlorocyclohexanes (β-HCH-P, γ-HCH-P) in plasma and the excretion of chlorophenols (4-MCP-U, 2,4-DCP-U, 2,5-DCP-U, 2,4,5-TCP-U, 2,4,6-TCP-U, 2,3,4,5-TeCP-U, 2,3,5,6-TeCP-U) in urine. One hundred and three men (13 from former Yugoslavia, 29 from the former USSR, 33 Africans and 28 Asians) ranging from 16 to 53 years of age (median 27 years) were investigated. Thirty four male Germans without occupational exposure to these substances and a similar age structure (age 25–36 years; median 26 years) served as a control group. Results: A much higher level of internal exposure was found for the DDT meta bolite, DDE, for those persons from Asia, the former USSR and Africa compared with the German controls (medians: 16.9 μg/l, 11.9 μg/l, 10.9 μg/l and 1.1 μg/l). The levels of PCB in plasma were below the detection limit in the majority of refugees. In the control group, however, the PCB levels were higher (ΣPCB: median: 2.1 μg/l, maximum: 13.3 μg/l). The highest β-HCH concentrations, up to a maximum of 15.5 μg/l, were detected in the persons from the former USSR and Asia. The five groups do not differ with regard to internal exposure to PCP and γ-HCH. Renal excretion of 4-MCP, 2,4-DCP and TeCP did not differ between the five groups. The concentrations of 2,5-DCP in urine, however, were significantly lower in the Germans than the refugees from the four regions investigated. The median for the Germans was 3.0 μg/l and for the refugees between 10.8 and 14.7 μg/l. Also the levels of 2,4,5-TCP and 2,4,6-TCP in urine were lower in the German controls than in the men from the former USSR, Africa and Asia. Conclusions: Organochlorine compounds exist worldwide due to their extensive use. There are, however, regional differences for the various substance groups, which during biological monitoring are seen in the different background exposures of the general population. Particularly characteristic are markedly higher levels of DDE in plasma from the refugees compared with the German population. Received: 11 July 1996/Accepted: 16 September 1996     

Urinary cobalt as a measure of exposure in the wet sharpening of hard metal and stellite blades

 The measurement of urinary cobalt as an estimator of exposure to airborne cobalt was evaluated during the wet sharpening of hard metal and stellite blades. The following possible confounding factors were also studied: smoking habits, personal hygiene, cobalt absorption through the skin, beer drinking, and vitamin B₁₂ consumption. The study was conducted in 16 different workplaces manufacturing or maintaining blades and in laboratory experiments. Cobalt contamination and its removal from workers’ hands were studied with different hand-washing methods, and cobalt from used gloves was also analyzed. The Finnish biomonitoring action level of 600 nmol/l (35.4 μg/l) was exceeded in 4 of the 16 workplaces, and the mean concentration of urinary cobalt was 241 (8–2705) nmol/l [14.2 (0.5–160)  μg/l]. The coefficient of correlation between the cobalt concentrations in the air and in the workers’ urine was 0.753. The urinary cobalt concentration corresponding to the Finnish occupational exposure limit for airborne cobalt (0.05 mg/m³) was 686 nmol/l (40.5 μg/l). The level of personal hygiene affected the urinary cobalt concentrations, and cobalt was absorbed through the skin. Beer and vitamin B₁₂ consumption did not have any effect on the urinary levels of cobalt. The workers who smoked had higher urinary concentrations of cobalt than the nonsmoking workers. High concentrations of cobalt in coolants contaminated the workers’ skin, and hand-washing did not remove cobalt very effectively. The results indicate that urinary cobalt can be used reliably to assess workers’ exposure to airborne cobalt when wet-tip grinding processes are used. The results also show that workers’ exposure to cobalt can be reduced by improving skin protection and personal hygiene in workplaces. Received: 29 January 1996 / Accepted: 2 May 1996     

Urinary excretion of dimethylhippuric acids in humans after exposure to trimethylbenzenes

 The aim of this study was to determine the urinary excretion of dimethylhippuric acids (DMHAs) in humans after experimental chamber exposure to trimethylbenzene (TMB) vapor. The DMHAs have been put forward as suitable biomarkers of exposure to products containing TMBs such as white spirit and petrol. Ten healthy male volunteers were exposed to TMB vapor in an exposure chamber for 2 h at a work load of 50 W. The subjects were exposed on four occasions, to 25 ppm of 1,2,4-TMB, 1,2,3-TMB, and 1,3,5-TMB, respectively, and to 2 ppm of 1,2,4-TMB. Urine was collected from the onset of exposure until the following morning. All six possible DMHA isomers were analyzed by high-performance liquid chromatography. About 22% of the inhaled amount of 1,2,4-TMB was excreted as DMHAs within 24 h, mainly as 3,4-DMHA. The 24-h recovery of 1,2,3-TMB as DMHAs was 11%. Only 3% of the absorbed amount of 1,3,5-TMB was excreted as 3,5-DMHA. The half-times of the different DMHA isomers ranged from 4 to 16 h. In addition to analysis of DMHAs, the excretion of unconjugated dimethylbenzoic acids in urine was estimated to account for approximately 3% of the dose of all TMBs. In conclusion, the urinary excretion of DMHA isomers may serve as a good indicator of TMB exposure. In this controlled short-term-exposure study the sum of excretion rate of several DMHA isomers reflected exposure more closely than did the excretion rate of any single DMHA. Received: 1 July 1996/Accepted: 8 November 1996     

Determination of platinum in workroom air and in blood and urine from nursing staff attending patients receiving cisplatin chemotherapy

 Aim: A cross-sectional investigation was carried out to assess possible relations between styrene-induced changes in three peripheral markers of catecholaminergic dysfunction and self-reported symptoms of neurotoxicity. Subjects: Male workers (n=46) aged 14–60 (mean 29.5) years who had been exposed to styrene for an average of 6 (0.2–29) years were recruited in glassfiber reinforced plastics plants. A control group of 30 blue-collar workers aged 22–52 (mean 35) years and with no history of exposure to chemicals was recruited from local industries. Styrene exposure ranged from 5 to 120 ppm (8 h-TWA), the median level being relatively low (25 ppm, 8 h-TWA). Styrene metabolites, mandelic and phenylglycoxylic acids (MAPGA) in the “next morning” urine spot samples ranged from 32.0 to 931.1 mg/g creatinine (median 186.5). Methods: Platelet monoamine oxidases B (MAO B) and dopamine β-hydroxylase (DBH) activities were assessed using methods based on HPLC and electrochemical detection. Plasma prolactin (PRL) was measured by a commercially available immunoassay. Questionnaire 16 (Q16) was used to survey self-reported symptoms. Results: Although there was no difference in DBH activity between exposed workers and controls, the most highly exposed workers had significantly lower activity than control subjects. A tendency to lower platelet MAO B activity in exposed than in control subjects was observed. The prevalence of plasma DBH and platelet MAO B values below the lower reference limit was similar in the two groups. PRL values exceeding the upper reference limit were higher (14/46 vs 2/30) among styrene-exposed workers, who also exhibited significantly higher median levels (10.0 vs 5.7 μg/l) than control subjects. Although the number of reported symptoms was similar among exposed and control subjects, in the exposed group it was positively associated with urinary MAPGA (Rho=0.30, P=0.04). Of the three peripheral markers of catecholaminergic dysfunction, plasma DBH was the only parameter negatively related to both urinary MAPGA (F=9.56, P=0.003) and the number of reported symptoms (Rho=0.23, P=0.05). Conclusions: Plasma PRL appears to be a sensitive marker of styrene-induced tubero-infundibular dopaminergic dysfunction in male subjects. DBH in plasma and MAO B in platelets seem to be less suitable markers for biomonitoring effect at the individual level, although DBH was related to the number of reported symptoms and to internal dose. Further studies on a larger and more exposed population are necessary to clarify the significance of these markers for health and their predictive value with regard to both subjective disturbances and concurrently administered performance tests. Received: 9 January 1996/Accepted: 11 April 1996     

Occupational exposure to polycyclic aromatic hydrocarbons in a graphite-electrode producing plant: biological monitoring of 1-hydroxypyrene and monohydroxylated metabolites of phenanthrene

 Objective. The objective of this study was to assess external and internal exposure to polycyclic aromatic hydrocarbons (PAHs) of workers who are employed in a graphite-electrode producing plant. Additionally we wanted to contribute to the question of biological limit values in order to reduce exposure to tolerable levels. Methods. At five different working places 12 stationary and 16 personal air measurements were carried out to determine the concentrations of phenanthrene, fluoranthene, pyrene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[a]pyrene and dibenz[a, h]anthracene in air. In addition, we investigated the excretion of 1-, 2+9-, 3- and 4-hydroxyphenanthrene and of 1-hydroxypyrene in the urine of 67 workers by a very sensitive and practical high-performance liquid chromatographic (HPLC) method with fluorescence detection; 2- and 9-hydroxyphenanthrene could not be separated with our analytical method. Results. During the production of graphite electrodes significantly higher PAH exposures were found in the baking and impregnation area than in the crushing, graphitisation and conditioning area. The results of personal air measurements (mean values of the sum of eight PAHs) are: 29.3 (baking), 23.4 (impregnation), 5.2 (crushing), 1.3 (graphitisation) and 0.4 μg/m³ (conditioning). Stationary air measurements yielded similar concentrations. Workers employed in the baking and impregnation areas excreted the highest amount of PAH metabolites in urine. The 1-hydroxypyrene concentrations (median) were: 23.4 (baking), 22.0 (impregnation), 9.6 (crushing), 1.8 (graph itisation) and 2.3 μg/g creatinine (conditioning). The corresponding concentrations of the sum of monohydroxylated phenanthrene metabolites (median) were: 23.1, 36.0, 10.4, 4.6 and 7.6 μg/g creatinine. Within the monohydroxylated phenanthrene metabolites 3-hydroxyphenanthrene predominates with a percentage of 43%. Our results showed that a benzo[a]pyrene concentration in air of 2 μg/m³ would lead to 1-hydroxypyrene concentrations in urine of 20–74 μg/g creatinine. That means that corresponding values in the literature which lie between 4.4 and 6.2 μg/g creatinine are due to other conditions of exposure and cannot be applied to graphite-electrode producing plants. Conclusions. Although to date there are no obligatory biological exposure limits for metabolites of PAHs in urine, it must be concluded that the internal PAH exposure is too high at some work places in this plant, as is generally the case in graphite-electrode producing plants. This is probably caused by skin absorption of PAHs. So for the prevention of health hazards by PAH, internal exposure must be measured using biological monitoring. Although it has not been possible to establish biological exposure limits for PAHs until now, we suggest a reduction in skin contact with these substances and thereafter use of the 90th percentile of the results of biological monitoring as “action levels” for corrective measures. Received: 20 May 1996/Accepted: 18 July 1996     

Dose-dependent elimination kinetics for mercury in urine: observations in subjects with brief but high-level exposure

  Objectives –To study the elimination kinetics for mercury in urine (U-Hg) after brief but high-level exposure. Methods –U-Hg was examined in 11 workers after 2–10 days of exposure to inorganic Hg and after symptoms and signs of Hg intoxication had appeared. Initial U-Hg excretion varied between 60 and 2360 μg/g creatinine. The subjects were followed up for 1–11 months. In each subject, one- and two-compartment models were fitted to the U-Hg values, assuming an exponential decrease, by weighted non-linear least-squares regression (weight=1/U-Hg). Results –The data indicated two elimination phases in subjects with initial U-Hg above 600 μg/g. In the two-compartment models, there was a fast phase with a half-time of 2–16 days, and a slow phase with a half-time of more than a month. The fast phase contributed 70–90% to the sum of the Y intercepts. Conclusions –The kinetics of U-Hg excretion after cessation of exposure seems to be dose-dependent and, at least in certain cases, to have two phases. The explanation for the fast phase may be that the capacity of certain binding sites in the kidney was exceeded. Received: 10 October 1995/Accepted: 18 January 1996     

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     

Correlation Between Lead Exposure Indicators and Sister Chromatid Exchange (SCE) Frequencies in Lymphocytes from Inorganic Lead Exposed Workers

Inorganic lead exposure was studied in 31 volunteers employed in storage battery plant. The genotoxicity of lead was measured in terms of sister chromatid exchange (SCE). Erythrocyte δ-aminolevulinic acid dehydrogenase (ALAD) activity, urinary δ-aminolevulinic acid (U-ALA), and blood lead levels (PbBs) were also determined to evaluate some possible relations between these lead exposure indicators and the observed SCE frequencies. Blood lead concentration of 36.31 μg/dl was determined as an average level in the workers. Consequently decreased ALAD activity in erythrocytes and increased U-ALA excretion was observed in statistically higher PbBs when compared with the control group. A statistically significant correlation was observed between the PbBs and SCE frequencies (p < 0.05). Moreover, the correlation between U-ALA excretion and SCE frequencies (p < 0.01) was relatively higher than the correlation between PbBs and SCE frequencies. These results might indicate a possible mechanism of ALA mediation in the genotoxic effects of lead. Received: 7 September 2000/Accepted: 25 February 2001     

Monitoring of occupational exposure to 1-butanol by diffusive sampling and urinalysis

 Objectives: To investigate the possibility of applying diffusive air sampling and urinalysis (for mother compound and metabolites) to the monitoring of exposure of factory workers to 1-butanol. Methods: The performance of carbon cloth in adsorbing 1-butanol vapor in air was studied by experimental exposure of the cloth to 1-butanol at 50, 100, 200 or 400 ppm for up to 10 h. 1-Butanol in the exposed cloth was extracted with carbon disulfide and this was followed by gas-chromatographic (GC) analysis. Urine samples were collected from factory workers occupationally exposed to 1-butanol and from rats exposed experimentally to 1-butanol vapour (up to 200 ppm). The urine samples were analyzed by GC without any pretreatment, or after treatment with hydrochloric acid or hydrolase preparation. Results: The performance of the carbon cloth was such that it adsorbed 1-butanol in proportion to the concentration (up to 400 ppm) and the duration (up to 10 h) of exposure, and responded quantitatively to a 15-min exposure up to 400 ppm. The amount of 1-butanol (after enzymic or acid hydrolysis) in post-exposure urine samples from rats was proportional to the exposure intensity. The proportion of free 1-butanol in total 1-butanol (i.e., free+conjugated) in urine was higher after 100 or 200 ppm exposure (35–40%) than after 50 ppm exposure (about 8%). There was a significant increase in total 1-butanol concentration (but not in free 1-butanol) in shift-end urine samples of workers exposed to 1-butanol at concentrations up to 3 ppm. Conclusions: Diffusive sampling with carbon cloth as an adsorbent can be applied to ambient air monitoring of exposure to 1-butanol. Urinalysis for 1-butanol after hydrolysis is sensitive enough to detect occupational 1-butanol vapour exposure at 3 ppm. Received: 29 January 1996 / Accepted: 3 May 1996     

Biological monitoring of vehicle mechanics and other workers exposed to low concentrations of benzene

 It has been suggested that the threshold limit value (TLV) for the time-weighted average (TWA), of benzene be lowered because of its possible leukemogenic effect at low exposure concentrations. This requires the development of new methods of biological monitoring. In this cross-sectional study the diagnostic power of blood and breath benzene and of urinary phenol, catechol, hydroquinone, S-phenylmercapturic acid, and muconic acid were compared in a population of 410 male workers exposed to benzene in garages, in two coke plants, and in a by-product plant. Benzene exposure was assessed by personal air sampling (charcoal tube and passive dosimeter). In all, 95% of the workers were exposed to less than 0.5 ppm benzene. According to the multiple regression equation, the muconic acid and S-phenylmercapturic acid concentrations detected in nonsmokers exposed to 0.5 ppm benzene were 0.3 mg/g and 6 μg/g, respectively (range 0.2–0.6 mg/g and 1.2–8.5 μg/g, respectively). With muconic acid very few false-positive test results were found, and this determination remained reliable even around a cutoff level of 0.1 ppm benzene. Moreover, the diagnostic power of this test proved to be good even when diluted or concentrated urine samples were not excluded. S-Phenylmercapturic acid (S-PMA) also performed fairly well. Blood and breath benzene as well as urinary phenol (PH) and hydroquinone (HQ) were clearly less suitable biomarkers than muconic acid (MA). Catechol (CA) was not associated with occupational benzene exposure. According to the results of biological monitoring, the skin resorption of benzene from gasoline or other fuels seems negligible. Correlation, multiple regression, and likelihood ratios consistently showed that MA and S-PMA concentrations were fairly good indicators of benzene exposure in the 0.1- to 1-ppm range, even in a population comprising both smokers and nonsmokers. PH, HQ, CA, and blood and breath benzene were less suitable, if at all, in the same exposure range. Received: 31 July 1996/Accepted: 29 November 1996     

Determination of dimethylhippuric acid isomers in urine by high-performance liquid chromatography

 In order to analyse metabolites in urine after trimethylbenzene (TMB) exposure a method based on high-performance liquid chromatography (HPLC) for determination of the six dimethylhippuric acids (2,3-DMHA, 2,6-DMHA, 2,5-DMHA, 2,4-DMHA, 3,4-DMHA and 3,5-DMHA) in urine has been developed. In contrast to earlier published methods, the present method allows detection of all possible isomers of DMHA in a single analysis. The DMHAs were extracted from urine with dichloromethane. After evaporation, the residue was dissolved in mobile phase and analysed by a stepwise gradient HPLC system with ultraviolet (UV) detection at 225 nm. Mobile phase A (1.25% acetonitrile and 0.3% acetic acid in water) was used up to a retention time of 59.5 min and mobile phase B (5% acetonitrile in water containing 0.3% acetic acid) was used for completion of the analysis at approximately 90 min. The DMHA isomers were chromatographed on a reversed phase Radial-Pak C₁₈ column (4 μm; 100 mm×5 mm inner diameter). The detection limit for the six isomers was 1.5 μg/ml (range 0.5–3.4, 100 μl injection volume). The precision of the method was 4.2% relative standard deviation (range 3.8–4.4; 100 μg/ml). Standard curves of the DMHAs were linear over the interval 10–500 μg/ml in human urine. Individual DMHAs or the sum of DMHA isomers may be used as biological indicators of occupational exposure to TMBs. Received: 18 January 1996/Accepted : 7 June 1996     

In vivo measurements of lead in fingerbone in active and retired lead smelters

 Object. The aim of this study was to determine the bone lead concentration in lead smelters and reference subjects, relate them to the lead concentration in blood (B-Pb) and urine (U-Pb), and to use the measured bone lead to calculate a biological half-life for lead in bone. Method and design. The lead concentration in the second phalanx of the left index finger (bone-Pb) was determined in vivo using an X-ray fluorescence technique. The study population comprised 89 smelters with a history of long-term exposure to lead (71 active and 18 retired) and 35 reference subjects (27 active and 8 retired) with no known occupational exposure to lead. Bone-Pb was related to the previous lead exposure, estimated as a time-integrated B-Pb (CBLI). Results. The retired smelters had the highest bone-Pb (median value 55 μg/g wet weight, as against 23 μg/g in active smelters) and 3 μg/g in the reference subjects. A strong positive correlation was observed between the bone-Pb and the CBLI among both active (r _s =0.73; P<0.001) and retired (r _s =0.71; P=0.001) smelters. The corresponding correlations between the bone-Pb and the period of employment were of the same magnitude. For retired workers, there were positive correlations between the bone-Pb and the B-Pb (r _s =0.58; P=0.011) and U-Pb (r _s =0.56; P=0.02). Multiple regression analyses showed that bone-Pb was best described by the CBLI, which explained 29% of the observed variance (multiple r ²) in bone-Pb in active workers and about 39% in retired workers. The estimated biological half-life of bone-Pb among active lead workers was 5.2 years (95% confidence interval 3.3–13.0 years). Conclusions. The high bone-Pb seen in retired workers can be explained by the long exposure periods, the higher exposure levels in earlier decades, and the slow excretion of lead accumulated in bone. The importance of the skeletal lead pool as an endogenous source of lead exposure in retired smelters was indicated by the associations between the B-Pb or U-Pb, on the one hand, and the bone-Pb, on the other. In active workers, the ongoing occupational exposure was dominant. The in vivo X-ray fluorescence technique is still mainly a research tool, and more work has to be done before it can be used more widely in clinical practice. However, over the next decade we can anticipate retrospective, prospective and cross-sectional epidemiological studies in which bone lead determinations reflecting the previous lead exposure in both occupationally and nonoccupationally lead exposed populations are related to various types of adverse health outcomes. Such studies will improve our knowledge of dose–response patterns and provide data that will have an impact on hygienic threshold limit values and prevention of lead-induced diseases. Received: 2 October 1995/Accepted: 8 March 1996     

Biological monitoring of styrene exposure and possible interference of acetone co-exposure

 The object of this study is the evaluation of some of the toxicokinetic effects of exposure to low concentrations of styrene, and the possible influence of simultaneous exposure to acetone. To this end we studied 19 workmen simultaneously exposed to both solvents. During a week of 4-h work shifts, the workmen underwent daily personal environmental monitoring and the collection of urine samples, at both the beginning and the end of the work period, for the determination of mandelic acid (MA) and phenylglyoxylic acid (PGA). The presence of the solvents in the atmosphere was evaluated using passive personal monitoring and gas chromatography. Average exposure to styrene and acetone were respectively 72.2 mg/m³ and 225.7 mg/m³. MA and PGA were quantified by high-performance liquid chromatography (HPLC). The daily urinary concentration averages, both at commencement and at the end of work shifts, of both the metabolites studied and of the sum of the two, were in statistically significant linear correlation with the average daily styrene exposure. Concentrations of MA and PGA in urine samples collected at the start of the work shift averaged 61.5 mg/g creatinine and 45.2 mg/g creatinine respectively, representing 41% and 72% of those at the end of the work shift which were 148.3 and 62.6 mg/g creatinine, respectively. With equal exposure to styrene, the average urinary concentrations of MA and PGA at both the beginning and end of the work shift increased significantly (P<0.001) during the working week. Moreover, we found that with equal exposure to styrene, urinary excretion of MA, PGA and MA+PGA at the end of the shift was inversely correlated with the intensity of acetone exposure (r=0.4659, 0.3410 and 0.4542 respectively, P<0.001). In conclusion, these results express slower urinary kinetics of styrene metabolites than is usually described in the literature, and favor a tendency to accumulate MA and PGA in the organism as a consequence of the retardation of urinary excretion kinetics. Acetone apparently represents one of the determining factors in this interference. Received: 3 July 1996/Accepted: 20 September 1996     

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     

Background exposure of urban populations to lead and cadmium: comparison between China and Japan

Objectives: To assess and compare the background exposure of the general population to lead (Pb) and cadmium (Cd) in China and in Japan. Methods: Food duplicates and peripheral blood samples were collected from nonoccupationally exposed subjects, viz 202 Chinese women in four Chinese cities (Beijing, Shanghai, Nanning, and Tainan) and 72 Japanese women in three Japanese cities (Tokyo, Kyoto, and Sendai) in the years 1993–1995. Wet-ashing and graphite furnace atomic absorption spectrometric methods were used for the determination of Pb and Cd levels in food and blood samples. Results: Geometric mean (GM) dietary Pb intake (25.8 μg/day) and the GM Pb concentration in blood (56.7 μg/l) in Chinese were significantly higher than in Japanese women (11.6 μg/day in food and 32.1 μg/l in blood), whereas Cd in food (32.1 μg/day) and Cd in blood (1.92 μg/l) in Japanese were significantly higher than in Chinese women (9.9 μg/day in food and 1.07 μg/l in blood). The intake of Pb and Cd via boiled rice accounted for 3.6% and 31.1% of the total dietary burden in Chinese, and 12.1% and 32.7% in Japanese, respectively. The Cd burden was acquired almost exclusively through the dietary route, whereas the Pb burden came from both air and food, especially in the case of the Chinese population. Conclusions:  The background Pb exposure in the Chinese population was higher than that in the Japanese population, whereas Cd exposure was lower in Chinese women than in their Japanese counterparts. Received: 4 March 1996 / Accepted 3 May 1996     

A study of ethylene glycol exposure and kidney function of aircraft de-icing workers

 Ethylene glycol levels were measured in 154 breathing zone air samples and in 117 urine samples of 33 aviation workers exposed to de-icing fluid (basket operators, de-icing truck drivers, leads and coordinators) studied during 42 worker-days over a winter period of 2 months at a Montreal airport. Ethylene glycol as vapour did not exceed 22 mg/m³ (mean duration of samples 50 min). Mist was quantified at higher levels in 3 samples concerning 1 coordinator and 2 basket operators (76–190 mg/m³, 45–118 min). In 16 cases workers’ post-shift or next-morning urine contained quantities of ethylene glycol exceeding 5 mmol/mol creatinine (up to 129 mmol/mol creatinine), with most of these instances occurring in basket operators and coordinators, some of whom did not wear paper masks and/or were accidentally sprayed with de-icing fluid. Diethylene glycol was also found in a few air and urinary samples at levels around one tenth those of ethylene glycol. Urinary concentrations of albumin, β-N-acetyl-glucosaminidase, β-2-microglobulin and retinol-binding protein were measured and compared over various periods, according to subgroups based on exposure level and according to the frequency of extreme values. These analyses did not demonstrate acute or chronic kidney damage that could be attributed to working in the presence of ethylene glycol. In conclusion, this study does not suggest important health effects of exposure to de-icing fluid in this group of workers. Potential for overexposure exists, however, in certain work situations, and recommendations on preventive measures are given. In addition, these results suggest that other routes of absorption than inhalation, such as the percutaneous route, may be important and that urinary ethylene glycol may be a useful indicator of exposure to ethylene glycol. Received: 10 March 1996/Accepted: 11 April 1996     

delta-Aminolevulinic acid dehydratase genotype modifies four hour urinary lead excretion after oral administration of dimercaptosuccinic acid.

OBJECTIVES: Previous research suggests that binding of lead by delta-aminolevulinic acid dehydratase (ALAD) may vary by ALAD genotype. This hypothesis was tested by examining whether ALAD genotype modifies urinary lead excretion (DMSA chelatable lead) after oral administration of dimercaptosuccinic acid (DMSA). METHODS: 57 South Korean lead battery manufacturing workers were given 5 mg/kg oral DMSA and urine was collected for four hours. Male workers were randomly selected from two ALAD genotype strata (ALAD1-1, ALAD1-2) from among all current workers in the two plants (n = 290). Subjects with ALAD1-1 (n = 38) were frequency matched with subjects with ALAD1-2 (n = 19) on duration of employment in the lead industry. Blood lead, zinc protoporphyrin, and plasma aminolevulinic acid concentrations, as well as ALAD genotype, duration of exposure, current tobacco use, and weight were examined as predictors or effect modifiers of levels of DMSA chelatable lead. RESULTS: Blood lead concentrations ranged from 11 to 53 micrograms/dl, with a mean (SD) of 25.4 (10.2) micrograms/dl. After 5 mg/kg DMSA orally, the workers excreted a mean (SD) 85.4 (45.0) micrograms lead during a four hour urine collection (range 16.5-184.1 micrograms). After controlling for blood lead concentrations, duration of exposure, current tobacco use, and body weight, subjects with ALAD1-2 excreted, on average, 24 micrograms less lead during the four hour urine collection than did subjects with ALAD1-1 (P = 0.05). ALAD genotype seemed to modify the relation between plasma delta-aminolevulinic acid (ALA) and DMSA chelatable lead. Workers with ALAD1-2 excreted more lead, after being given DMSA, with increasing plasma ALA than did workers with ALAD1-1 (P value for interaction = 0.01). CONCLUSIONS: DMSA chelatable lead may partly reflect the stores of bioavailable lead, and the current data indicate that subjects with ALAD1-2 have lower stores than those with ALAD1-1. These data provide further evidence that the ALAD genotype modifies the toxicokinetics of lead-for example, by differential binding of current lead stores or by differences in long-term retention and deposition of lead.     

trans,trans-Muconic acid as a biomarker of non-occupational environmental exposure to benzene

 Excretion of trans,trans-muconic acid (2,4-hexadienedioic acid; t,t-MA), a potential biomarker of low-level exposure to benzene, was determined in 32 smokers and 82 nonsmokers. In smokers the median background excretion of t,t-MA was 0.13 (0.06–0.39) mg/g creatinine and was significantly higher (P<0.05) than the value of 0.065 (0.02–0.59) mg/g creatinine in nonsmokers. For nonsmokers, the correlation between t,t-MA excretion and environmental exposure to benzene in ambient air, which was determined during the 8-day study period by personal diffusion samplers, was not significant (r=0.164, P=0.18). Nonsmokers living in the city tended to have higher t,t-MA excretion rates than nonsmokers living in the suburbs. However, the difference was only significant for nonsmokers from nonsmoking homes. For the same location (suburb or city), smoking at home leads to a marginal increase in t,t-MA excretion of the nonsmoking members of the household. In a further study with eight nonsmokers we found that dietary supplementation with 500 mg sorbic acid significantly increased (P<0.001) the mean urinary t,t-MA excretion from 0.08 (0.04–0.12) to 0.88 (0.57–1.48) mg/24 h. Under study conditions 0.12% of the sorbic acid dose was excreted in urine as t,t-MA, thereby indicating that a typical dietary intake of 6–30 mg/day sorbic acid accounts for 10–50% of the background t,t-MA excretion in nonsmokers, and for 5–25% in smokers. As a consequence, sorbic acid in the diet is a significant confounding factor in assessing low-level benzene exposure if t,t-MA excretion in urine is used as a biomarker. Received: 10 October 1995 / Accepted: 26 February 1996