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.     

Evaluation of the dose of mercury in exposed and control subjects

OBJECTIVES: The aim of this paper was to analyse the concentrations of HgU and HgB in three different groups: 122 workers exposed, 18 workers formerly exposed and 196 subjects not occupationally or environmentally exposed to mercury. METHODS: All the subjects filled out a questionnaire concerning personal data, lifestyle, occupational or non-occupational exposure to Hg and medical history. The amalgam fillings area was measured by a standardised method. RESULTS: Urinary mercury excretion was significantly greater in the group of the exposed workers respect to the group of subjects not occupationally exposed (Median value of 8.3 micrograms/g creatinine and the 5 degrees and 95 degrees percentile respectively of 2.66 e 23.50 micrograms/g creatinine against Median value of 1.2 micrograms/g creatinine and the 5 degrees and 95 degrees percentile respectively of 0.18 and 5.42 micrograms/g creatinine). U-Hg in formerly exposed workers were comparable to U-Hg in non-occupationally exposed subjects, with a median value of 1.6 micrograms/g creatinine. B-Hg values were similar in the three groups: the median value was 3.1 micrograms/l in the non-occupationally exposed, 4.0 micrograms/l in the exposed workers and 3.9 micrograms/l in the past exposed. These value were not significantly different. Among the considered variables (amalgam fillings, fish consumption, age, sex, alcohol intake, chewing-gum and smoking) dental amalgam and fish consumption were significantly related with the Hg urinary excretion and the B-Hg levels. This is particularly true considering the subjects altogether: for the exposed workers, indeed, the occupational exposure was the most relevant variable. CONCLUSIONS: The results of the present research confirmed that the U-Hg excretion in non-occupationally exposed subjects is influenced by amalgam dental fillings. Furthermore, in our study Hg urinary excretion was significantly related with fish consumption. This fact can be explained, according to several recent experimental human and animal trials, considering that methylmercury contained in fish is partially converted, through breakage of the carbon-Hg bond, into Hg inorganic forms, which accumulate in the kidney and have a urinary excretion pathway.     

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.     

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.     

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.     

Markers of early renal changes induced by industrial pollutants. I. Application to workers exposed to mercury vapour.

Several markers of renal changes have been measured in a cohort of 50 workers exposed to elemental mercury (Hg) and in 50 control workers. After application of selection criteria 44 exposed and 49 control workers were retained for the final statistical analysis. Exposed workers excreted on average 22 micrograms Hg/g creatinine and their mean duration of exposure was 11 years. Three types of renal markers were studied--namely, functional markers (creatinine and beta 2-microglobulin in serum, urinary proteins of low or high molecular weight); cytotoxicity markers (tubular antigens and enzymes in urine), and biochemical markers (eicosanoids, thromboxane, fibronectin, kallikrein, sialic acid, glycosaminoglycans in urine, red blood cell membrane negative charges). Several bloodborne indicators of polyclonal activation were also measured to test the hypothesis that an immune mechanism might be involved in the renal toxicity of elemental Hg. The main renal changes associated with exposure to Hg were indicative of tubular cytotoxicity (increased leakage of tubular antigens and enzymes in urine) and biochemical alterations (decreased urinary excretion of some eicosanoids and glycosaminoglycans and lowering of urinary pH). The concentrations of anti-DNA antibodies and total immunoglobulin E in serum were also positively associated with the concentration of Hg in urine and in blood respectively. The renal effects were mainly found in workers excreting more than 50 micrograms Hg/g creatinine, which corroborates our previous estimate of the biological threshold of Hg in urine. As these effects, however, were unrelated to the duration of exposure and not accompanied by functional changes (for example, microproteinuria), they may not necessarily represent clinically significant alterations of renal function.     

Chronic psychological effects of exposure to mercury vapour among chlorine-alkali plant workers

BACKGROUND: Quantitative assessment of nervous system function is essential in characterising the nature and extent of impairment in individuals experiencing symptoms following work-place mercury vapour exposure. OBJECTIVES: The purpose of this study was the application of standardised tests of behavioural, psychomotor and memory function to understand the neuropsychological effects of mercury in occupationally exposed chlorine-alkali plant workers. SUBJECTS AND METHODS: The study comprised 45 workers at a chlorine-alkali plant with the mean age of 39.36 +/- 5.94 years, who had been exposed to daily inhalation of mercury vapour over long-term employment of 16.06 +/- 4.29 years. The cumulative mercury index was 155.32 +/- 95.02 micrograms/g creatinine, the mean of urinary mercury concentrations on the first day of the study was 119.50 +/- 157.24 micrograms/g creatinine, and the mean of urinary mercury concentrations 120 days after cessation of exposure was 21.70 +/- 26.07 micrograms/g creatinine. The analysis included tests of behavioural, psychomotor and memory function. The behavioural test battery consisted of: Environmental Worry Scale (EWS), Minnesota Modified Personal Inventory (MMPI-2), Purdue standard 25 minute test, and adapted, 10 minutes test, Bender's Visual-Motor Gestalt test (BGT), and Eysenck Personality Inventory (EPQ). The data were compared to a control group of 32 not directly exposed workers. RESULTS: In the mercury vapour exposed workers with relatively high level exposure to inorganic mercury vapour (TWA/TLV = 0.12 mg/m3/0.025 mg/m3) we identified somatic depression-hypochondria symptoms with higher scores for scales: hysteria (P < 0.001), schizoid and psycho-asthenia (MMPI-2). The mercury-exposed workers had introvert behaviour (EPQ, MMPI-2). The cognitive disturbances in mercury-exposed workers were identified as: concentration difficulty, psychomotor, perceptual and motor coordination disturbances, and brain effects. We identified fine tremor of the hands in 34 out of 45 mercury-exposed workers (BGT). CONCLUSIONS: The results point to a relationship between the duration of mercury exposure and the long-term, probably irreversible, psychological disturbances.     

Health effects of long-term mercury exposure among chloralkali plant workers

BACKGROUND: Inorganic mercury is toxic to the nervous system, kidneys, and reproductive system. We studied the health effects of mercury exposure among former employees of a chloralkali plant that operated from 1955 to 1994 in Georgia. METHODS: Former plant workers and unexposed workers from nearby employers were studied. Exposure was assessed with a job-exposure matrix based on historical measurements and personnel records. Health outcomes were assessed with interviews, physical examinations, neurological and neurobehavioral testing, renal function testing, and urinary porphyrin measurements. Exposure-disease associations were assessed with multivariate modeling. RESULTS: Exposed workers reported more symptoms, and tended toward more physical examination abnormalities, than unexposed workers. Exposed workers performed worse than unexposed subjects on some quantitative tests of vibration sense, motor speed and coordination, and tremor, and on one test of cognitive function. Few findings remained significant when exposure was modeled as a continuous variable. Neither renal function nor porphyrin excretion was associated with mercury exposure. CONCLUSIONS: Mercury-exposed chloralkali plant workers reported more symptoms than unexposed controls, but no strong associations were demonstrated with neurological or renal function or with porphyrin excretion.     

铝熔铸作业工人神经行为功能的研究

为探讨铝对作业工人神经系统的影响，寻找对铝作业工人健康监护的早期指标，对３６名铝熔铸作业工人（车间空气中铝尘和铝浓度分别为１．６５ｍｇ／ｍ３和０．２５ｍｇ／ｍ３（ＴＷＡ））和４０名对照工人，应用ＷＨＯ－ＮＣＴＢ进行了神经行为功能测定；同时测定了尿铝、尿中高香草酸（ＨＶＡ）和香草扁桃酸（ＶＭＡ）的含量。结果发现：铝接触工人注意力、手的运动协调能力、视感知记忆力下降，反应时的标准差和最慢反应时间延长（Ｐ＝０．００２５，Ｐ＝０．００６６），提转捷度测试得分降低（Ｐ＝０．０２６），数字译码和Ｂｅｎ－ｔｏｎ视觉保留测试得分降低（Ｐ＝０．０２３，Ｐ＝０．００３）。分层分析发现：后３项分测试得分随接触时间延长而降低，铝作业工人尿ＶＭＡ和尿铝含量高于对照组。提示：铝可能对作业工人的神经系统产生影响。神经行为测试和尿ＶＭＡ测定可用于检测铝的不良效应     

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.     

Effects of elemental mercury exposure at a thermometer plant

This study compares 84 mercury-exposed workers at a thermometer manufacturing facility with 79 unexposed workers for evidence of chronic mercury toxicity. Personal breathing-zone air concentrations of mercury ranged from 25.6 to 270.6 micrograms/m3 for thermometer workers. Urinary mercury levels in the study population ranged from 1.3 to 344.5 micrograms/g creatinine, with eight (10%) participants exceeding 150 micrograms/g creatinine and three workers exceeding 300 micrograms/g creatinine, which indicates increased absorption of mercury among the thermometer workers. All urine mercury levels in the comparison group were compatible with normal background levels in unexposed adults (less than 10 micrograms/g creatinine). Thermometer plant workers reported more symptoms than did controls; in general, these differences were not statistically significant and could not be specifically associated with mercury exposure. Static tremor, abnormal Romberg test, dysdiadochokinesia, and difficulty with heel-to-toe gait were more prevalent among thermometer workers than control workers, which could not be associated with recent mercury exposure; there was some suggestion of an association with chronic exposure. There were no intergroup differences for the standard clinical tests of renal function except for a significantly higher mean specific gravity among the thermometer workers. A positive correlation was found, however, between urinary N-acetyl-b-D-glucosaminidase (NAG) and urinary mercury. There was no consistent evidence for intergroup differences in proximal renal tubule function, as measured by urinary beta 2-microglobulin (B2M) or retinol binding protein (RBP).     

Effects of low exposure to inorganic mercury on psychological performance

The effects of low exposure to inorganic mercury on psychological performance was investigated: the study groups included eight chronically exposed workers and 20 who were only occasionally exposed. These were compared with a control group of 22 subjects from the same plant who were not exposed to mercury. All subjects were administered the WHO test battery to detect preclinical signs of central nervous system impairment: the battery includes the Santa Ana (Helsinki version) test, simple reaction time, the Benton test, and the Wechsler digit span and digit symbol. In addition, the Gordon test was used to study personality profiles and the clinical depression questionnaire. Urinary mercury was used as indicator for internal dose. To this effect, urinary mercury observed in workers examined from 1979 to 1987 was evaluated. Of the pyschic functions explored by behavioural tests, only short term auditory memory was found to be impaired in the chronically exposed workers (p less than 0.05 compared with the controls). The chronically exposed workers were also found to be more depressed than those in the two other groups. No changes of visual motor functions were observed. The personality of the occupationally exposed workers was found to be considerably changed compared with that of the control group. On the basis of the results obtained and in view of urinary mercury mean concentrations in the exposed group which were 30-40 micrograms/l over the years, it is suggested that the TLV-TWA for mercury should be lowered to 0.025 mg/m3 and that the biological urinary exposure indicator for biological monitoring should be 25 micrograms/l.     

Effects of low exposure to inorganic mercury on psychological performance.

The effects of low exposure to inorganic mercury on psychological performance was investigated: the study groups included eight chronically exposed workers and 20 who were only occasionally exposed. These were compared with a control group of 22 subjects from the same plant who were not exposed to mercury. All subjects were administered the WHO test battery to detect preclinical signs of central nervous system impairment: the battery includes the Santa Ana (Helsinki version) test, simple reaction time, the Benton test, and the Wechsler digit span and digit symbol. In addition, the Gordon test was used to study personality profiles and the clinical depression questionnaire. Urinary mercury was used as indicator for internal dose. To this effect, urinary mercury observed in workers examined from 1979 to 1987 was evaluated. Of the pyschic functions explored by behavioural tests, only short term auditory memory was found to be impaired in the chronically exposed workers (p less than 0.05 compared with the controls). The chronically exposed workers were also found to be more depressed than those in the two other groups. No changes of visual motor functions were observed. The personality of the occupationally exposed workers was found to be considerably changed compared with that of the control group. On the basis of the results obtained and in view of urinary mercury mean concentrations in the exposed group which were 30-40 micrograms/l over the years, it is suggested that the TLV-TWA for mercury should be lowered to 0.025 mg/m3 and that the biological urinary exposure indicator for biological monitoring should be 25 micrograms/l.     

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.     

Neuroendocrine and neurobehavioral effects associated with exposure to low doses of mercury from habitual consumption of marine fish

OBJECTIVES: To evaluate neuroendocrine and neurobehavioral effects possibly associated with increased dietary intake of organic mercury (Hg), a group of 22 subjects living on the island of Carloforte (south-west Sardinia) was examined, who were regular consumers of tuna fish with relatively high Hg content. This group, never exposed occupationally to either Hg or to other neurotoxic substances, was compared with 22 age-matched controls employed at a chemical plant in Portotorres (northern Sardinia). METHODS: Hg in urine (HgU) and serum prolactin (PRL) were measured in all cases, whereas measurements of total (HgB) and organic blood mercury were available only for 10 subjects from Carloforte and 6 controls. Data about working history and lifestyle (education, smoking habit, alcohol and sea fish consumption) were collected by an interviewer using a standardised questionnaire. Neurotoxic symptoms were evaluated by a self-administered questionnaire, whereas a test battery, including some computerised tests of the Swedish Performance Evaluation System (SPES) to assess vigilance and psychomotor performance, some tests on motor coordination (Luria-Nebraska and Branches Alternate Movement Task) and one memory test for numbers (Digit Span) was administered to assess neurobehavioral changes associated with exposure to dietary intake of organic mercury. In all cases, characteristics of hand tremor were evaluated by the CATSYS System 7.0. RESULTS: HgU values were significantly higher in the Carloforte group (median 6.5, range 1.8-21.5 micrograms/g creatinine) compared with controls (median 1.5, range 0.5-5.3 micrograms/g creatinine). Serum PRL was significantly higher among subjects from Carloforte and correlated with both urine and blood Hg levels. The scores of each item of the questionnaire investigating neurological symptoms were not statistically different in the two groups. In some tests of the SPES battery (Color Word Vigilance, Digit Symbol and Finger Tapping) the performance of the Carloforte group was significantly worse than that of controls, whereas in the other neurobehavioral tests poorer performances by the Carloforte group were not statistically significant. None of the tremor parameters was significantly different comparing the two groups. Multivariate analysis--controlling for education level and other covariates--carried out for the Symbol-Digit Reaction Time and for the Branches Alternate Movement Task (BAMT) showed that organic Hg concentration in blood was the most significant factor negatively affecting individual performance in these tests. Serum PRL was correlated with some neurobehavioral tests (Digit Symbol, Finger Tapping and BAMT). CONCLUSIONS: Some of the neurobehavioral tests were sensitive enough to discriminate groups with different Hg body burden, even in the low-dose range. However, the pattern of results suggests adverse neurobehavioral effects, especially on psycho-motor coordination, with a significant dose-effect relationship, mostly associated with long-term exposure to low levels of organic mercury due to the usual consumption of large fish with relatively high levels of Hg in the flash.     

Relation between exposure related indices and neurological and neurophysiological effects in workers previously exposed to mercury vapour.

A cross sectional study of aspects of their neurology was carried out on 77 chloralkali workers previously exposed to mercury (Hg) vapour and compared with 53 age matched referents. The chloralkali workers had been exposed for an average of 7.9 years at a concentration of 59 micrograms Hg/m3 in the working atmosphere. The individual mean urinary concentration of Hg for each year of exposure was 531 nmol Hg/1. On average the exposure had ceased 12.3 years before the examinations. Both the median sensory nerve conduction velocity and the amplitude of the sural nerve were associated with measures of cumulative exposure to Hg. An association was also found between years since first exposure to Hg and aspects of the visual evoked response. Previously exposed subjects with postural tremor or impaired coordination also had alterations in visual evoked response. These results may indicate an effect of previous exposure to mercury vapour on the nervous system, possibly in the visual pathway, cerebellum, and the peripheral sensory nerves.     

Biological aspects of occupational exposure to cadmium and several other metals

We have performed several cross-sectional epidemiological surveys among workers exposed to cadmium, mercury vapour or manganese in order to assess : their early biological or functional effects; the biological tests allowing an assessment of the amount of metal absorbed or stored in the body; the acceptable exposure levels. Studies have also been carried out among persons exposed to inorganic arsenic in order to define its inactivation mechanism and to develop a biological test of exposure. The kidney is the main critical organ following long-term exposure to cadmium. To prevent the occurrence of renal changes in the majority of male workers exposed to cadmium, its concentration in renal cortex should not exceed 215 micrograms/g (wet weight), and that in urine : 10 micrograms/g creatinine. A blood cadmium level of 1 microgram/100 ml has been suggested as maximum tolerable level for long-term exposure. Prolonged exposure to mercury vapour may lead to renal and neurological disturbances. The preclinical signs of nephrotoxicity are correlated with the amount of mercury absorbed which may be assessed by monitoring the mercury level in urine. The neurotoxic effects (particularly tremor) are mainly related to the integrated exposure (duration and intensity). A maximal permissible level of 50 micrograms Hg/g urinary creatinine is proposed to prevent the occurrence of these toxic effects. An exposure to manganese dust for 7 years on the average at a level below the maximum allowable airborne concentration (5 mg/m3) recommended by the ACGIH in the USA may still lead to a slight reduction in psychomotor and spirometric performances and interfere with calcium metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)     

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     

Chronic mercury exposure examined with a computer-based tremor system

Tremor is being increasingly evaluated by quantitative computer-based systems to differentiate its causes. In this study, a group of mercury-exposed workers were assessed to determine whether tremor characteristics differed by exposure level. Workers were classified into two groups: those with an average urine mercury concentration below the American Conference of Government Industrial Hygienist Biological Exposure Index of 35 micrograms/g creatinine, and those with an average urine mercury concentration above the Biological Exposure Index. Tremor characteristics (including intensity, harmonic index, center frequency, standard deviation of the center frequency, and tremor index) were measured and recorded with a computer-based tremor system. Sixteen of 17 workers who were potentially exposed to mercury participated in the study. Three workers had a mean urine mercury concentration of 27.0 micrograms/g-creatinine and were assigned to the low-exposure group, and 13 workers had a mean urine mercury concentration of 200.2 micrograms/g-creatinine and were assigned to the high-exposure group. There was a statistically significant difference in the tremor index (which compiles five individual tremor parameters into a single value) between the two groups (P = 0.04; Wilcoxon's rank sum test). Other tremor characteristics did not differ significantly between the groups. Tremor index may be more useful than measures of individual tremor parameters in differentiating normal from subclinical pathological tremors among groups of workers with chronic mercury exposure.