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.     

Urinary excretion of mercury after occupational exposure to mercury vapour and influence of the chelating agent meso-2,3-dimercaptosuccinic acid (DMSA).

The spontaneous and chelator mediated excretion of mercury in urine was investigated in male subjects occupationally exposed to mercury vapour (alkaline battery and chloralkali plants) who did not exhibit any sign of kidney damage. The time course of the spontaneous elimination of mercury in urine was examined in seven workers (age 22-40) who had been removed from exposure to mercury vapour (average duration of exposure 4.4 years) because their urinary mercury concentrations repeatedly exceeded 100 micrograms/g creatinine. The post exposure observation period started 10 to 29 days after the date of removal and lasted about 300 days (slow HgU elimination phase). For each worker, the kinetics of the spontaneous HgU decline followed a first order process; the biological half life ranged from 69 to 109 days (mean 90 days). The increased urinary excretion of mercury after a single oral administration of 2 g meso-2,3-dimercaptosuccinic acid (DMSA) was investigated in 16 control workers (group A; age 23 to 49), in 11 workers removed from exposure for at least two years (group B; age 27 to 41), and in 16 workers currently exposed to mercury vapour (group C; age 21 to 58). In group C, the DMSA experiment was repeated twice (three weeks before and three weeks after a holiday) after measures had been taken to reduce the mercury emission. The urinary mercury excretion was significantly higher during the 24 hours after DMSA administration in all groups compared with that in the 24 hours before. The bulk (50-70%) of the DMSA stimulated mercury excretion appeared within the first eight hours. In each group, the amount of mercury (microgram Hg/24h) excreted after DMSA was significantly correlated with that before administration of DMSA. The groups whose exposure had ceased, however, exhibited much higher correlation for coefficients (r=0.97 for group B and 0.86 for group C after three weeks of holiday) than those currently exposed to mercury vapour (r-0.66 for group C before and 9.58 after reduction of exposure). The data suggest that after a few days of cessation of occupational exposure to mercury vapour the HgU before and after administration of DMSA mainly reflects the amount of mercury stored in the kidney, which represents a mercury pool with a slow turnover.     

Urinary excretion of mercury after occupational exposure to mercury vapour and influence of the chelating agent meso-2,3-dimercaptosuccinic acid (DMSA).

The spontaneous and chelator mediated excretion of mercury in urine was investigated in male subjects occupationally exposed to mercury vapour (alkaline battery and chloralkali plants) who did not exhibit any sign of kidney damage. The time course of the spontaneous elimination of mercury in urine was examined in seven workers (age 22-40) who had been removed from exposure to mercury vapour (average duration of exposure 4.4 years) because their urinary mercury concentrations repeatedly exceeded 100 micrograms/g creatinine. The post exposure observation period started 10 to 29 days after the date of removal and lasted about 300 days (slow HgU elimination phase). For each worker, the kinetics of the spontaneous HgU decline followed a first order process; the biological half life ranged from 69 to 109 days (mean 90 days). The increased urinary excretion of mercury after a single oral administration of 2 g meso-2,3-dimercaptosuccinic acid (DMSA) was investigated in 16 control workers (group A; age 23 to 49), in 11 workers removed from exposure for at least two years (group B; age 27 to 41), and in 16 workers currently exposed to mercury vapour (group C; age 21 to 58). In group C, the DMSA experiment was repeated twice (three weeks before and three weeks after a holiday) after measures had been taken to reduce the mercury emission. The urinary mercury excretion was significantly higher during the 24 hours after DMSA administration in all groups compared with that in the 24 hours before. The bulk (50-70%) of the DMSA stimulated mercury excretion appeared within the first eight hours. In each group, the amount of mercury (microgram Hg/24h) excreted after DMSA was significantly correlated with that before administration of DMSA. The groups whose exposure had ceased, however, exhibited much higher correlation for coefficients (r=0.97 for group B and 0.86 for group C after three weeks of holiday) than those currently exposed to mercury vapour (r-0.66 for group C before and 9.58 after reduction of exposure). The data suggest that after a few days of cessation of occupational exposure to mercury vapour the HgU before and after administration of DMSA mainly reflects the amount of mercury stored in the kidney, which represents a mercury pool with a slow turnover.     

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.     

Comparison of renal function and psychomotor performance in workers exposed to elemental mercury

Summary Renal function and psychomotor performance (eye-hand coordination, arm-hand steadiness) of a group of 43 workers exposed to mercury vapor were examined. Their mean age and average duration of exposure to mercury were 38 and 5 years, respectively. The results were compared with those obtained in a matched group of 47 control workers. Increased proteinuria and albuminuria were found slightly more prevalent in the Hg-exposed group than in the control workers. These results are in agreement with those found during a previous study carried out in another group of workers also exposed to elemental mercury (Bucket et al. 1980). The scores of the psychomotor tests were less satisfactory in the Hg workers than in the control workers, the arm-hand steadiness test being more discriminative than the eye-hand coordination test. Preclinical changes in psychomotor function can be detected independently of the presence of signs of renal dysfunction. No clear-cut relationships were found between the prevalence of abnormal psychomotor scores and the level of mercury in blood (HgB) or in urine (HgU). Increased prevalences of abnormal psychomotor scores seem however to occur for HgB between 1 and 2 g/100 ml and for HgU between 50 and 100 g/g creatinine. Therefore, a biologic threshold limit value of 50 g/g creatinine is proposed for urinary mercury to prevent the development of preclinical effects on the central nervous system. A similar critical HgU level based on renal dysfunction prevalences has been suggested in a previous study.This study was supported by a grant from the Commission of the European Communities     

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.     

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.     

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)     

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.     

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.     

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).     

Tremor in workers with low exposure to metallic mercury

In a fluorescent lamp production factory, a newly developed lightweight balance-tremormeter was used to measure postural tremor of the finger in 21 workers (ages 28 to 61) exposed for 0.5-19 yr to metallic mercury. In addition, tremor was measured in an indirect way by means of a "hole-tremormeter." The excretion of mercury in urine was 9-53 (average 20) mumol/mol creatinine. With increasing mercury excretion, the following parameters increased: the acceleration of the tremor, the contribution of the neuromuscular component (8-12 Hz) to the power spectrum of the acceleration, the width of the power-spectrum and the score on the hole-tremormeter. The study indicates that exposure to metallic mercury below the current TLV (50 micrograms/m3) may increase the tremor of the finger.     

Search for anti-laminin antibodies in the serum of workers exposed to cadmium,mercury vapour or lead

Summary Anti-laminin antibodies were sought for in the serum of workers exposed to mercury vapour (Hg, n = 58), lead (Pb, n = 38) or cadmium (Cd, n = 47). Thirty-one workers removed from Cd exposure for an average of eight years were also examined. Compared with control workers matched for age and socio-economic status, the prevalence of circulating anti-laminin antibodies was not increased in workers exposed to Hg (mean duration of exposure: 7.9 years and mean urinary excretion of Hg: 72 g/g creatinine) nor in those exposed to Pb (mean duration of exposure: 10.6 years and mean Pb levels in blood: 535 g/l). In contrast, anti-laminin antibodies were significantly more prevalent in Cd-exposed workers whose urinary Cd exceeded 20 g/g creatinine. This observation was made in both currently exposed workers and in workers removed from Cd exposure (mean duration of exposure: 9.4 and 24.6 years and mean urinary Cd: 7.8 and 13.4 g/g creatinine respectively). These autoantibodies were found in Cd workers with normal renal function as well as in those with increased proteinuria.     

Cytogenetic examination of leucocytes of workers exposed to mercury vapour

Summary Cytogenetic observations have been performed on male subjects occupationally exposed to elemental mercury in a plant where mercury is amalgamated with zinc and in a chloralkali plant [n=22; average level of mercury in urine was 117 g/g creatinine and of mercury in blood 3.1 g/100 ml; mean duration of Hg exposure 4 years (range: 0.3–15.3)]. The exposure to mercury vapour did not result in an increased yield of structural chromosomal aberrations in peripheral blood lymphocytes of the workers. These negative results are in agreement with the findings reported for other eukaryotic systems and confirm that population monitoring based on cytogenetic examination of peripheral blood lymphocytes does not always represent a good indicator of damage to genetic material produced by a chemical.     

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     

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.     

Normal pituitary hormone response to thyrotrophin and gonadotrophin releasing hormones in subjects exposed to elemental mercury vapour.

Exposure to elemental mercury (Hg) vapour results in an accumulation of Hg in the pituitary, the thyroid, and the testis. In this study, basal serum concentrations of pituitary hormones (thyrotrophin (TSH), prolactin (PRL), follicle stimulating hormone (FSH), and luteinising hormone (LH] or their response after administration of thyrotrophin and gonadotrophin releasing hormones did not differ between 11 male workers (mean urinary Hg (U Hg) concentration 26 nmol/mmol creatinine) and nine male dentists (U Hg concentration 1.3 nmol/mmol creatinine) exposed to elemental Hg vapour when compared with matched referent groups (U Hg concentration 0.6 and 0.4 nmol/mmol creatinine). Thus there was no evidence of an effect of Hg on the pituitary. Neither was there any association between exposure to Hg and serum concentrations of free thyroid hormones (S FT3, S FT4), testosterone, or cortisol. Increased plasma concentrations of selenium (Se) were associated with increased basal serum concentrations of TSH, decreased concentrations of basal serum cortisol, and decreased release of FSH.     

Normal pituitary hormone response to thyrotrophin and gonadotrophin releasing hormones in subjects exposed to elemental mercury vapour

Exposure to elemental mercury (Hg) vapour results in an accumulation of Hg in the pituitary, the thyroid, and the testis. In this study, basal serum concentrations of pituitary hormones (thyrotrophin (TSH), prolactin (PRL), follicle stimulating hormone (FSH), and luteinising hormone (LH] or their response after administration of thyrotrophin and gonadotrophin releasing hormones did not differ between 11 male workers (mean urinary Hg (U Hg) concentration 26 nmol/mmol creatinine) and nine male dentists (U Hg concentration 1.3 nmol/mmol creatinine) exposed to elemental Hg vapour when compared with matched referent groups (U Hg concentration 0.6 and 0.4 nmol/mmol creatinine). Thus there was no evidence of an effect of Hg on the pituitary. Neither was there any association between exposure to Hg and serum concentrations of free thyroid hormones (S FT3, S FT4), testosterone, or cortisol. Increased plasma concentrations of selenium (Se) were associated with increased basal serum concentrations of TSH, decreased concentrations of basal serum cortisol, and decreased release of FSH.