Significance of biological indicators of mercury exposure

BACKGROUND: It was considered appropriate to update of the significance and use of the different mercury exposure indicators. OBJECTIVE: The aim of the this paper was to correctly select biological media and sampling time and to understand the toxic kinetics of mercury for assessment of accurate biological monitoring. RESULTS: It was confirmed that mercury in blood (B-Hg) is a good indicator of recent exposure, while urinary mercury (U-Hg) indicates current exposure when mercury reaches the renal steady state. B-Hg values are greatly influenced by fish consumption, while the variables influencing U-Hg values are amalgam fillings, commercial gamma-globulin preparations, vaccines, topical remedies, environmental pollution and hobbies, occupational exposure and, partly, fish consumption. The speciation of mercury (Hg0, Hg++, methylmercury and ethylmercury) in biological media, should provide additional and important information in evaluating mercury toxicity. CONCLUSION: It was stressed that the appropriate choice of exposure indicators has to take account of the different variability factors and the characteristics of the toxic kinetics of mercury. The results of biological monitoring must be compared with references values, which are generally in the order of several micrograms/g creatinine, and limit values such as ACGIH BEI (U-Hg 35 micrograms/g creatinine and B-Hg 15 micrograms/l) or the DFG BAT (U-Hg 100 micrograms/l and B-Hg 25 micrograms/l).     

Urinary and blood markers of internal mercury dose in workers from a chlorakali plant and in subjects not occupationally exposed: relation to dental amalgam and fish consumption

OBJECTIVES: The aim of this paper was both to evaluate the internal dose of Hg in occupationally exposed workers (35 Chloralkali workers) compared to that of non occupationally exposed controls (40 workers of the same plant of Portotorres and 22 residents on the island of Carloforte, usual consumers of local fish, mostly tuna fish with relatively high Hg levels) and to assess the relevance of environmental and individual exposure factors linked to lifestyle, sea fish consumption and amalgam fillings. METHODS: All subjects filled out a questionnaire concerning the working history and lifestyle. The amalgam fillings area was measured by medical inspection using a standardised schedule attached to the questionnaire. Mercury in urine (HgU) was measured in all cases, while in a subgroup of our study total blood mercury (HgB) and its organic and inorganic component were also assessed. Furthermore, for 8 of the Carloforte group mercury in hair was also available. RESULTS: Values of urinary mercury excretion of the Chloralkali workers were significantly higher (median value of 15.4, range 4.8-35.0 micrograms/g creatinine, 94.3% of the cases having values > 5 micrograms/g creatinine) than those observed both among the reference group (median value of 1.9, range 0.4-5.6 micrograms/g creatinine, 12.5% of the cases having values a little greater than 5 micrograms/g creatinine) and among the residents in Carloforte (median value of 6.5, range 1.8-21.5 micrograms/g creatinine, 59.1% of the cases having values > 5 mcg/g creatinine). The HgU values observed in this group were in turn significantly higher than those of the non occupationally exposed workers living near Sassari (p = 0.03). Only in this last group were the HgU concentrations statistically significantly related to the extension of the amalgam fillings area (Pearson r = 0.53, p < 0.01). In the Carloforte group HgU was significantly related to the number of fish meal consumed per week (Pearson r = 0.48, p < 0.02). HgB (median value of 5.9, range 3.4-21.6 micrograms/l) as well as its inorganic component (median value of 2.4, range 1.8-4.6 micrograms/l) were significantly higher in the Chloralkali group compared to the other two groups. In all cases of the Carloforte group the ratio between the organic component and the total HgB was higher than 85%, while this ratio was significantly lower in the other two groups. The relationship between HgU and HgB was statistically significant, considering both total blood mercury and the inorganic and the organic components separately. A statistically significant relationship between the sea fish consumption per week and both total HgB (Pearson r = 0.82) and the organic component in this matrix (Pearson r = 0.84, p < 0.001) was observed among 16 non-occupationally exposed subjects. However, the significant relationship between organic blood mercury and sea fish consumption was almost entirely supported by the data observed in the Carloforte group. Total hair mercury levels analysed in 8 subjects of the Carloforte group were high (median value of 9.6, range 1.4-34.5 micrograms/g) and significantly related to sea fish consumption, and to both the individual Hg urinary excretion (Pearson r = 0.83) and to the organic component of blood mercury (Pearson r = 0.87). CONCLUSIONS: According to several experimental human and animal trials and to some recent studies on methylmercury toxicokinetic models, our results suggest that the organic compounds absorbed by usual sea fish consumption may be partially demethylated, increasing the inorganic Hg concentration in the kidney and consequently its urinary excretion, as was observed in the Carloforte group.     

People with high mercury uptake from their own dental amalgam fillings.

OBJECTIVES--To describe people with high mercury (Hg) uptake from their amalgam fillings, and to estimate the possible fraction of the occupationally unexposed Swedish population with high excretion of urinary Hg. METHODS--Three case reports are presented. The distribution of excretion of urinary Hg in the general population was examined in pooled data from several sources. RESULTS--The three cases excreted 23-60 micrograms of Hg/day (25-54 micrograms/g creatinine), indicating daily uptake of Hg as high as 100 micrograms. Blood Hg was 12-23 micrograms/l, which is five to 10 times the average in the general population. No other sources of exposure were found, and removal of the amalgam fillings resulted in normal Hg concentrations. Chewing gum and bruxism were the probable reasons for the increased Hg uptake. Extrapolations from data on urinary Hg in the general population indicate that the number of people with urinary excretion of > or = 50 micrograms/g creatinine could in fact be larger than the number of workers with equivalent exposure from occupational sources. CONCLUSION--Although the average daily Hg uptake from dental amalgam fillings is low, there is a considerable variation between people; certain people have a high mercury uptake from their amalgam fillings.     

Biological monitoring of environmental and occupational exposure to mercury

Summary Biological monitoring was used to assess mercury exposure from occupational and environmental sources in a group of chloralkali workers (n = 89) and in a control group (n = 75). In the control group, the median value for blood mercury (B-Hg) was 15 nmol/l, that for serum mercury (S-Hg) was 4 nmol/l and that for urinary mercury (U-Hg) was 1.1 nmol/mmol creatinine. Corresponding levels in the chloralkali group were 55 nmol/l, 45 nmol/l and 14.3 nmol/mmol creatinine, respectively. In the control group, there were statistically significant relationships between fish consumption and both B-Hg and S-Hg values (P < 0.001), whereas U-Hg correlated best with the individual amalgam burden (P < 0.01). In the chloralkali group, the mercury levels in blood and urine were significantly related to the type of work (P < 0.001) but not to the length of employment, to fish consumption or to the quantity of dental amalgam fillings. In both groups there were poor correlations between smoking or alcohol intake and the mercury levels in blood and urine. The results strongly suggest that fish is an important source of methylmercury exposure and that amalgam fillings are probably the most important source of inorganic mercury exposure among occupationally unexposed individuals. In the chloralkali group, mercury exposure from fish and amalgam was overshadowed by occupational exposure to inorganic mercury.     

Mercury and selenium in workers previously exposed to mercury vapour at a chloralkali plant.

The concentrations of total mercury (B-Hg), inorganic mercury (B-IHg), and methyl mercury (B-MeHg) in whole blood, urinary mercury (U-Hg), and selenium in urine (U-Se) and whole blood (B-Se) were determined in 74 chloralkali workers previously exposed to Hg vapour, and compared with 51 age matched referents. Dental amalgam state, fish consumption, and exposure related indices were studied with regard to the determined elements. A significant relation between the surface of dental amalgam and U-Hg (Pearson's r = 0.63, p < 0.001) was found among the referents. Mean U-Se was significantly lower (p < 0.001) among the subjects previously exposed to Hg (34.1 nmol/mmol creatinine) compared with that for the referents (42.6 nmol/mmol creatinine). A significant negative relation between the cumulative Hg dose and U-Se was also found. The mechanisms and the clinical significance of these findings are not clear. No relation between current U-Hg and previous occupational exposure to Hg was found among subjects in whom exposure had ceased more than one year before the study.     

Endocrine function in mercury exposed chloralkali workers.

OBJECTIVE--The aim was to study whether functional impairment of the pituitary, thyroid, testes, and adrenal glands of humans occupationally exposed to mercury (Hg) vapour can be shown as a result of accumulation of Hg in these glands. METHODS--Basal concentrations of thyrotrophin (TSH), prolactin, free thyroxine (free T4), free 3,5,3'-triiodothyronine (free T3), antibodies against thyroperoxidase, and testosterone in serum, as well as cortisol in morning urine were measured in 41 chloralkali workers exposed (10 years on average) to Hg vapour, and in 41 age matched occupationally unexposed referents. The chloralkali workers had a mean urinary Hg concentration (U-Hg) of 15 nmol/mmol (27 micrograms/g) creatinine, and a mean blood Hg concentration (B-Hg) of 46 nmol/l. For the reference group U-Hg and B-Hg were 1.9 nmol/mmol (3.3 micrograms/g) creatinine and 17 nmol/l respectively. RESULTS--The serum free T4 concentration and the ratio free T4/free T3 were slightly, but significantly, higher in the subgroups with the highest exposure, and the serum free T3 was inversely associated with cumulative Hg exposure. This indicates a possible inhibitory effect of mercury on 5'-deiodinases, which are responsible for the conversion of T4 to the active hormone T3. Serum total testosterone, but not free testosterone, was positively correlated with cumulative Hg exposure. Prolactin, TSH and urinary cortisol concentrations were not significantly associated to exposure. CONCLUSION--Apart from inhibition of the deiodination of T4 to T3, the endocrine functions studied seem not to be affected by exposure to Hg vapour at the exposure levels of the present study. Growth hormone secretion was not studied.     

Renal effects of low doses of mercury

OBJECTIVES: The present study was aimed at investigating early markers of renal damage and dysfunction in subjects exposed to low doses of mercury from different sources. Different groups of subjects were examined with urinary Hg excretion (HgU) ranging from 0.1 to 35.0 micrograms/g creatinine: 122 occupationally exposed workers, 22 subjects living in a non-polluted area, but consuming large amounts of tuna and sword fish, and 197 controls. METHODS: Several markers of renal changes were measured in urine (albumin, fibronectin, beta 2-microglobulin, retinol-binding protein, tubular antigens, N-acetyl-beta-D-glucosaminidase activity) and serum (beta 2-microglobulin and cystatin C). Serum autoantibodies towards collagen, laminin and tubular antigens were assessed in subjects with abnormal renal markers. The role of glutathione-S-tranferases GSTT1 and GSTM1 polymorphisms in the inter-individual variability of biological response to Hg was also investigated. RESULTS: Renal markers were not correlated with HgU. None of such markers differed significantly between exposed workers and controls, except for urinary beta 2-microglobulin, which was decreased in Hg-exposed workers (GM = 55.8 vs 86.6 micrograms/g creatinine), in the absence of any changes in serum concentration. Subjects usually eating tuna and sword fish showed an increased urinary excretion of beta 2-microglobulin, albumin and fibronectin. Serum titres of auto-antibodies did not differ between the groups. Neither in controls nor in exposed workers were the observed differences modified by the GSTM1 and GSTT1 genotypes. CONCLUSION: The present study did not provide evidence of any changes in kidney integrity and function in subjects exposed to very low levels of inorganic Hg resulting in urinary Hg lower than 35 micrograms/g creatinine. Nor did we obtain evidence of Hg-induced autoimmunity towards kidney components. The potential modifying role of GST polymorphisms could not be clarified in the absence of effects associated with exposure to the risk factor, i.e., to inorganic Hg. Preliminary data suggesting nephrotoxic effects of organic Hg from a diet rich in large fish resulting in increased levels of both blood and urinary Hg--which however did not exceed 20 micrograms/g creatinine--deserves further investigation.     

A study of autoantibodies and circulating immune complexes in mercury-exposed chloralkali workers

Inorganic mercury may cause immunologically mediated disease: e.g., glomerulonephritis, acrodynia, and contact allergy. Animal models have demonstrated the importance of genetic factors in determining susceptibility and resistance to autoimmunity, as well as the specific manifestation of the autoimmune response. Findings in groups of workers with occupational exposure to inorganic mercury have been inconsistent. Objective: To investigate whether an immune response, caused by exposure to inorganic mercury (Hg), could be shown in occupationally exposed workers. Methods: Immunoglobulin G (IgG), antinuclear autoantibodies, antibodies against thyroid, stomach or kidney antigens using indirect immunofluorescence, antibodies against glomerular basement membrane using ELISA, and circulating immune complexes in serum, and albumin in urine, were examined in Hg-exposed workers and controls. The two groups, 41 male chloralkali workers exposed to Hg vapour (mean exposure time 9 years) and 41 unexposed controls were age-matched and recruited from the same company. Hg concentrations in whole blood (B-Hg), plasma (P-Hg), and urine (U-Hg) were determined using cold vapor atomic spectrometry. Design: Cross-sectional study. Results: The mean B-Hg, P-Hg and U-Hg levels were 46 nmol/l, 37 nmol/l, and 27 μg/g creatinine in the exposed group, and 17 nmol/l, 6.9 nmol/l, and 3.4 μg/g creatinine in the referents. No statistically significant differences were found regarding IgG levels, urinary albumin excretion, prevalence of abnormal titers of autoantibodies or circulating immune complexes. There were no statistically significant associations between autoantibodies or immune complexes on the one hand and mercury exposure indices on the other. Conclusion: The results indicate that, if and when lasting autoimmune response occurs at the mercury exposure levels of the present study, it is uncommon. A small fraction of humans may, however, be susceptible to the development of autoimmunity, and there is also a possible “healthy worker” selection. Thus cross-sectional studies of moderate numbers of active workers will have low power to demonstrate autoimmune effects. Received: 2 September 1996 / Accepted: 3 January 1997     

Status of mercury and selenium in dental personnel: impact of amalgam work and own fillings

Urinary mercury (U-Hg) and plasma mercury (P-Hg) levels were higher in 244 dental personnel than in 81 matched referents (U-Hg: 1.8 and 1.1 mumol/mol creatinine, respectively; p less than .001; P-Hg: 6.7 and 6.2 nmol/l, respectively; p = .03). The amalgam in the mouth influenced mercury levels in whole blood (B-Hg), plasma, and urine. The association was nonlinear: the more amalgam, the larger the relative increase in mercury levels. The number of amalgam surfaces accounted for more of the variance in blood and urine mercury levels than did the number of fillings (e.g., U-Hg: 44% and 36%, respectively). The estimated increases in mercury level with rising amalgam load were 3.0%, 2.0%, and 0.8% per filled surface for U-Hg, P-Hg, and B-Hg, respectively (p less than .0001 in all cases). The impact of occupational exposure on U-Hg in the dental personnel corresponded to approximately 19 amalgam surfaces. Ceramo metallic restorations were associated with higher (31%) U-Hg.     

Scalp hair and urine mercury content of children in the Northeast United States: the New England Children's Amalgam Trial

Children may be at particular risk from toxic effects of mercury (Hg). Previous studies of hair (organic) and urine (inorganic) Hg levels in US children were unable to assess Hg levels while accounting for exposure to amalgam dental restorations. This analysis describes, over a 5-year period, levels and correlates/predictors of scalp hair (H-Hg) and urinary (U-Hg) mercury in 534 New England Children's Amalgam Trial (NECAT) participants, aged 6-10 years and without exposure to dental amalgam at baseline. RESULTS: Mean H-Hg levels were between 0.3 and 0.4 microg/g over 5 years. 17-29% of children had H-Hg levels > or = 0.5 microg/g, and 5.0 to 8.5% of children had levels > or = 1 microg/g, in any given study year. In adjusted models, fish consumption frequency was the most robust predictor of high H-Hg. U-Hg mean levels were between 0.7 and 0.9 microg/g creatinine over two years. The percentage of those with U-Hg > or 2.3 microg/g creatinine ranged from 4% to 6%. Number of amalgam restorations had a significant dose-response relationship with U-Hg level. Daily gum chewing in the presence of amalgam was associated with high U-Hg.     

Neurotoxic effect of exposure to low doses of mercury

OBJECTIVES: To assess early effects on the Central Nervous System due to occupational exposure to low levels of inorganic mercury (Hg) in a multicenter nationwide cross-sectional study, including workers from chloro-alkali plants, chemical industry, thermometer and fluorescent lamp manufacturing. The contribution of non-occupational exposure to inorganic Hg from dental amalgams and to organic Hg from fish consumption was also considered. METHODS: Neuropsychological and neuroendocrine functions were examined in a population of 122 workers occupationally exposed to Hg, and 196 control subjects, not occupationally exposed to Hg. Neuropsychological functions were assessed with neurobehavioral testing including vigilance, motor and cognitive function, tremor measurements, and with symptoms concerning neuropsychological and mood assessment. Neuroendocrine functions were examined with the measurement of prolactin secretion. The target population was also characterized by the surface of dental amalgams and sea fish consumption. RESULTS: In the exposed workers the mean urinary Hg (HgU) was 10.4 +/- 6.9 (median 8.3, geometric mean 8.3, range 0.2-35.2) micrograms/g creatinine, whereas in the control group the mean HgU was 1.9 +/- 2.8 (median 1.2, geometric mean 1.2, range 0.1-33.2) micrograms/g creatinine. The results indicated homogeneous distribution of most neurobehavioral parameters among exposed and controls. On the contrary, finger tapping (p < 0.01) and the BAMT (Branches Alternate Movement Task) coordination test (p = 0.05) were associated with occupational exposure, indicating an impairment in the exposed subjects. Prolactin levels resulted significantly decreased among the exposed workers, and inversely related to HgU on an individual basis (p < 0.05). An inverse association was also observed between most neuropsychological symptoms and sea fish consumption, indicating a "beneficial effect" from eating sea fish. On the contrary, no effects were observed as a function of dental amalgams. CONCLUSIONS: In conclusion, this study supports the finding of early alterations of motor function and neuroendocrine secretion at very low exposure levels of inorganic Hg, below the current ACGIH BEI and below the most recent exposure levels reported in the literature.     

Long-term mercury excretion in urine after removal of amalgam fillings

The long-term urinary mercury excretion was determined in 17 28- to 55-year-old persons before and at varying times (up to 14 months) after removal of all (4–24) dental amalgam fillings. Before removal the urinary mercury excretion correlated with the number of amalgam fillings. In the immediate post-removal phase (up to 6 days after removal) a mean increase of 30% was observed. Within 12 months the geometric mean of the mercury excretion was reduced by a factor of 5 from 1.44 g/g (range: 0.57–4.38 g/g) to 0.36 g/g (range: 0.13–0.88 g/g). After cessation of exposure to dental amalgam the mean half-life was 95 days. These results show that the release of mercury from dental amalgam contributes predominantly to the mercury exposure of non-occupationally exposed persons. The exposure from amalgam fillings thus exceeds the exposure from food, air and beverages. Within 12 months after removal of all amalgam fillings the participants showed substantially lower urinary mercury levels which were comparable to those found in subjects who have never had dental amalgam fillings. A relationship between the urinary mercury excretion and adverse effects was not found. Differences in the frequency of effects between the pre- and the post-removal phase were not observed.     

Effect of mercury vapour exposure on urinary excretion of calcium, zinc and copper: relationship to alterations in functional and structural integrity of the kidney

BACKGROUND: The kidney has a remarkable capacity to concentrate mercury (Hg) and as such is a primary target organ when exposure to Hg occurs, and it is also an organ for Hg excretion. OBJECTIVE: The present work aims to investigate the effect of occupational Hg vapour exposure on the urinary excretion of calcium (Ca), zinc (Zn) and copper (Cu), and the possible association of this excretion to work duration as well as renal alterations. METHODS: 83 non-smoker participants (36 referents, age: 35.6 +/- 9.5 years; 27 Hg vapour-exposed workers with < or = 10 years work duration, age: 33.0 +/- 5.1 years; and 20 Hg vapour-exposed workers with > or = 11 years work duration, age: 39.50 +/- 8.50 years) were included in the present study. Urinary levels of microalbumin (U-Malb) and retinol-binding protein (U-RBP) as well as cytosolic glutathione S-transferase activity (U-GST) were measured to assess the glomerular and proximal tubular reabsorption functions as well as structural integrity of proximal tubules; respectively. In addition, blood Hg (B-Hg), serum levels of Hg (S-Hg) and Ca (S-Ca), and urinary levels of Hg (U-Hg), Ca (U-Ca), Zn (U-Zn), Cu (U-Cu) and creatinine (U-cr) were estimated. RESULTS: In comparison to referents, all investigated parameters showed significant increase (except S-Ca and U-Zn/U-Cu ratio that significantly decreased among the workers as one group, S-Ca and U-Zn/U-Cu ratio that significantly and nonsignificantly decreased; respectively among workers with < or = 10 years work duration, S-Ca and U-Zn/U-Cu ratio that significantly decreased among workers with > or = 11 years work duration). In addition, B-Hg was nonsignificantly increased and S-Ca was significantly decreased; also, both U-Hg and U-Zn/U-Cu were nonsignificantly decreased among workers with > or = 11 years work duration in comparison to those with < or = 10 years work duration. Also, each of U-Hg, U-Ca, U-Zn and U-Cu was related to one another, while each of U-Ca, U-Zn and U-Cu was related to each of U-Malb, U-RBP and U-GST (except U-Zn was not related to U-GST). CONCLUSION: Hg vapour exposure leads to renal alterations which may parallel the change in proteinuria and enzymuria as well as the increased loss in urine of each of Ca, Zn and Cu. The urinary assessment of these metals may be used as a good indicator for renal dysfunction.     

Renal and immunological effects of occupational exposure to inorganic mercury.

Seven parameters of renal dysfunction (urinary excretion of albumin, orosomucoid, beta 2-microglobulin, N-acetyl-beta-glucosaminidase (NAG), and copper; serum creatinine concentration, and relative clearance of beta 2-microglobulin) were examined in a group of chloralkali workers exposed to mercury vapour (n = 89) and in an unexposed control group (n = 75). Serum concentrations of immunoglobulins (IgA, IgG, IgM) and auto-antibodies towards glomeruli and other tissues were also determined. The parameters examined were compared between the two groups and related to different exposure parameters. In the chloralkali group median blood mercury concentration (B-Hg) was 55 nmol/l, serum mercury (S-Hg) 45 nmol/l, and urine mercury concentration (U-Hg) 14.3 nmol/mmol creatinine (25.4 micrograms/g creatinine). Corresponding concentrations for the control group were 15 nmol/l, 4 nmol/l, and 1.1 nmol/mmol creatinine (1.9 micrograms/g creatinine) respectively. None of the parameters of renal dysfunction differed significantly between the two groups, but there was a tendency to increased excretion of NAG in the exposed group compared with the controls. Also, a statistically significant relation existed between U-Hg and U-NAG (p less than 0.001). Serum immunoglobulin concentrations did not differ between the groups, and serum titres of autoantibodies (including antiglomerular basement membrane and antilaminin antibodies) were low in both groups. Thus the results gave no evidence of glomerular damage or of a tubular reabsorption defect at the current relatively low exposures. The findings still indicate slight, dose related tubular cell damage in the mercury exposed group. There were no signs of a mercury induced effect on the immune system.     

Renal and immunological effects of occupational exposure to inorganic mercury.

Seven parameters of renal dysfunction (urinary excretion of albumin, orosomucoid, beta 2-microglobulin, N-acetyl-beta-glucosaminidase (NAG), and copper; serum creatinine concentration, and relative clearance of beta 2-microglobulin) were examined in a group of chloralkali workers exposed to mercury vapour (n = 89) and in an unexposed control group (n = 75). Serum concentrations of immunoglobulins (IgA, IgG, IgM) and auto-antibodies towards glomeruli and other tissues were also determined. The parameters examined were compared between the two groups and related to different exposure parameters. In the chloralkali group median blood mercury concentration (B-Hg) was 55 nmol/l, serum mercury (S-Hg) 45 nmol/l, and urine mercury concentration (U-Hg) 14.3 nmol/mmol creatinine (25.4 micrograms/g creatinine). Corresponding concentrations for the control group were 15 nmol/l, 4 nmol/l, and 1.1 nmol/mmol creatinine (1.9 micrograms/g creatinine) respectively. None of the parameters of renal dysfunction differed significantly between the two groups, but there was a tendency to increased excretion of NAG in the exposed group compared with the controls. Also, a statistically significant relation existed between U-Hg and U-NAG (p less than 0.001). Serum immunoglobulin concentrations did not differ between the groups, and serum titres of autoantibodies (including antiglomerular basement membrane and antilaminin antibodies) were low in both groups. Thus the results gave no evidence of glomerular damage or of a tubular reabsorption defect at the current relatively low exposures. The findings still indicate slight, dose related tubular cell damage in the mercury exposed group. There were no signs of a mercury induced effect on the immune system.     

Decrease in mercury concentration in blood after long term exposure: a kinetic study of chloralkali workers.

The elimination of mercury (Hg) in blood was investigated in 14 chloralkali workers exposed to metallic Hg vapour for 1-24 (median 10) years. Blood and urine samples were collected on several (median eight) occasions during a period of 17-26 days. The initial Hg concentrations were about 80 nmol/l in whole blood (B-Hg) and 17 nmol/mmol creatinine in urine (U-Hg). The decrease in Hg in whole blood, plasma (P) and erythrocytes (Ery) was best characterised by a two compartment model. In a model with a common half life for all subjects, the best fit for B-Hg was obtained with half lives of 3.8 days for a fast phase and 45 days for a slow phase. The half life of the fast phase was shorter for P-Hg than for Ery-Hg, whereas the opposite was the case for the slow phase. The half lives of the slow phases in whole blood and plasma were longer, and the relative fractions of the slow phases were higher (about 50%) after long term exposure than those (about 20%) reported after brief exposure. Slower elimination indicates higher accumulation of Hg in organs with long half lives, and possibly the presence of at least one additional, even slower compartment. The U-Hg fluctuated substantially during the sampling period, and average concentrations decreased only slightly.     

Evaluation of the neurotoxic and nephrotoxic effects following long-term exposure to metallic mercury in employed at a chlorine/sodium-hydroxide plant

OBJECTIVES: Within the frame work of a wide multicentre study, a sub-study was developed in order to explore the occurrence of early effects on the central nervous system, on the kidney and on the neuro-immune system in the workers of a chloro-alkali production plant exposed to metallic mercury at airborne concentration levels lower than 0.025 mg/m3 (TLV-TWA). They were compared to a control population of employees of the same huge petrochemical plant with different job that did not implicate exposure to mercury vapors. Specifically, the study aimed at revealing the occurrence of early effects on the central nervous system related with mercury exposure, as can be assessed through neurophysiological and neurobehavioral tests. METHODS: The excretion of urinary mercury was measured by atomic absorption spectrometry. The study of renal function was assessed by measurement of the urinary excretion of some high and low molecular weight protein markers (albumin, beta 2-microglobulin, retinol-binding protein, fibronectin, specific proximal tubule brush border antigens, N-acetyl-beta-D-glucosaminidase). The neurobehavioral status of the study subjects was assessed by means of several test parameters (Simple Reaction Time, Color Word Vigilance Test, Symbol Digit, Finger Tapping, Mood Scale of Kjellberg and Iwanowski, Subjective symptoms questionnaire (QSS), Luria Nebraska Motor Scale, Branches Alternate Movement Task and Tremometry). RESULTS: The values of urinary excretion averaged 12 +/- 8 micrograms Hg/g of creatinine for the exposed workers group (n = 38), while for the reference group (n = 34 cases) urinary excretion was statistically lower, averaging 4 +/- 6 micrograms Hg/g of creatinine. Neither the parameters selected for the assessment of renal functions, nor those chosen to probe the neurobehavioral status of the probands revealed statistically reliable differences between the group of exposed workers (length of exposure: range 1-34 years) and the control group. Nevertheless, some minor but still statistically reliable correlations were found between some neurobehavioral parameters and some demographic variables describing the whole group of tested workers, but not to the level of occupational exposure to mercury. CONCLUSIONS: The results of the study confirm the lack of toxic effects of clinical importance on the central nervous system and on the kidney for values of mercury urinary excretion lower than the suggested index of biological exposure (IBE) of 35 micrograms Hg/gram of creatinine.     

Surveillance of workers exposed to mercury vapour:validation of a previously proposed biological threshold limit value for mercury concentration in urine

A cross-sectional epidemiological study was carried out among subjects exposed to mercury (Hg) vapour, ie, a group of 131 male workers (mean age: 30.9 yr; average duration of exposure, 4.8 yr) and a group of 54 female workers (mean age, 29.9 yr; average duration of exposure 7 yr). The results were compared with those obtained in well-matched control groups comprising 114 and 48 male and female workers, respectively. The intensity of current Hg vapour exposure was rather moderate as reflected by the levels of mercury in urine (HgU) (mean and 95th percentile: males 52 and 147 micrograms/g creatinine; females 37 and 63 micrograms/g creatinine) and of mercury in blood (mean and 95th percentile: males 1.4 and 3.7 micrograms/dl; females 0.9 and 1.4 microgram/dl). Several symptoms mainly related to the central nervous system (memory disturbances, depressive feelings, fatigue, irritability) were more prevalent in the Hg-exposed subjects. They were, however, not related to exposure parameters. In both male and female Hg-exposed workers no significant disturbances were found in short-term memory (audioverbal), simple reaction time (visual), critical flicker fusion, and colour discrimination ability. Only slight renal tubular effects were detected in Hg-exposed males and females, ie, an increased urinary beta-galactosidase activity and an increased urinary excretion of retinol-binding protein. The prevalence of these preclinical renal effects was more related to the current exposure intensity (HgU) than to the duration of exposure and was detected mainly when HgU exceeds 50 micrograms/g creatinine. Changes in hand tremor spectrum recorded with an accelerometer were found in the Hg-exposed males only. The prevalence of abnormal values for some hand tremor parameters (total velocity and total displacement in the 2-50-Hz band) was mainly increased in male workers exposed for more than 10 yr. Unlike the renal tubular effects, the preclinical signs of tremor were more related to the integrated exposure than to the current exposure. Since the female workers, who have been exposed to Hg vapour levels usually insufficient to increase their HgU levels above 50 micrograms/g creatinine, did not exhibit any change in hand tremor pattern, the results of the present study tend to validate our previously proposed biological threshold limit value of a HgU of 50 micrograms/g creatinine for workers chronically exposed to mercury vapour.     

Blood and urine levels of Pb, Cd and Hg in the general population of the Czech Republic and proposed reference values

The Human Biological Monitoring (HBM) project was launched in the Czech Republic in 1994 as a part of the nation-wide Environmental Health Monitoring System to assess the exposure of the Czech general population to a broad spectrum of environmental contaminants. Over the years 2001-2003, the concentrations of lead (Pb), cadmium (Cd), and mercury (Hg) were determined in whole blood of 1188 adults (blood donors) and 333 children and in urine of 657 adults and 619 children. In adults, the median blood lead (B-Pb) level was 33microg/l. Men had higher B-Pb levels than women (medians 37microg/l vs. 25microg/l). Significantly higher B-Pb levels were observed in smokers compared to non-smokers (36microg/l vs. 31microg/l). In children, no sex-dependent differences were observed (median 31microg/l). In total, the median blood Cd level (B-Cd) in adults was 0.5microg/l. Smokers showed a median B-Cd level about 3 times as high as non-smokers (1.3microg/l vs. 0.40microg/l). Neither sex- nor age-related differences were observed in B-Cd levels. In 65% of children, B-Cd levels were below the limit of detection (LOD). The overall median urinary cadmium level (U-Cd) in adults was 0.31microg/g creatinine. Significantly higher U-Cd levels were found in women (median 0.39microg/g creatinine) compared to men (0.29microg/g creatinine). No significant differences were found between smokers and non-smokers. In more than 50% of children, the U-Cd level was below the LOD (=0.2microg/l). The median blood mercury (B-Hg) level in adults was 0.89microg/l. Significant differences were found between smokers (0.80microg/l) and non-smokers (0.92microg/l), and between men and women (0.86microg/l vs. 0.94microg/l). The median B-Hg level in children was 0.42microg/l and no sex-related differences were observed. The median urinary mercury (U-Hg) levels were 0.63microg/g creatinine in adults and 0.37microg/g creatinine in children. Significantly higher U-Hg levels were obtained in women and non-smokers compared to men and smokers, respectively. The B-Pb, B-Hg, U-Cd, and U-Hg levels significantly correlated with age. The following reference values were recommended for the period 2001-2003: 80, 65 and 55microg/l for B-Pb and 3.1, 4.0 and 1.5microg/l for B-Hg in men, women and children, respectively; 1.1microg/l and 1.2microg/g creatinine for B-Cd and U-Cd, respectively, in adult non-smokers; 5.4 and 12.0microg/g creatinine for U-Hg in men and women, respectively, and 3.7 and 5.5microg/g creatinine for U-Hg in boys and girls, respectively. The previous reference values for B-Pb and B-Cd needed revision and were reduced.     

Enzymuria in workers exposed to inorganic mercury

Summary Urinary excretion of beta-hexosaminidase (NAG = N-acetyl-beta-glucosaminidase) and albumin was examined in 41 chlor-alkali workers exposed to inorganic mercury and 41 age-matched controls. Either U-HG or B-Hg levels for these workers were available dating from the 1960s to the present. Increased U-NAG was seen in workers with a U-Hg today of more than 4g/mmol creat (about 50g/l; 35 g/g creat). Multiple linear regression analysis showed that U-NAG was correlated to U-Hg and integrated dose but not to the present B-Hg level. No albuminuria (detection limit 12.5 mg/1) was found in any of the subjects. In a longitudinal study, no decrease in UNAG levels was seen in 15 chlor-alkali workers after their vacation (x = 20 d). In five workers followed for ten months after a short exposure period, no definite time trend could be seen. The results show that there is a slight effect on renal tubules even at rather low levels of exposure to mercury vapour. The clinical significance of the enzymuria levels found here is, however, debatable.