Renal and immunologic markers for chloralkali workers with low exposure to mercury vapor

OBJECTIVES: The aim of this study was to investigate renal function and immunologic markers among chloralkali workers with long-term low exposure to mercury vapor. METHODS: Forty-seven currently exposed workers were compared with reference workers matched for age in a cross-sectional design. RESULTS: The mean urinary mercury concentration was 5.9 (range 1.1-16.8) nmol/mmol creatinine (Cr) for the exposed workers and 1.3 (range 0.2-5.0) nmol/mmol Cr for the referents. The chloralkali workers had been exposed for an average of 13.3 (range 2.8-34.5) years. The activity of N-acetyl-beta-D-glucosaminidase in urine (U-NAG) was higher in the exposed workers (mean 0.18 U/mmol Cr versus 0.14 U/mmol Cr, P=0.02). Associations between current urinary mercury, cumulative urinary mercury, and cumulative urinary mercury per year (intensity) and U-NAG, autoantibodies to myeloperoxidase (anti-MPO) and proteinase 3 in serum, respectively, were observed. The activity of U-NAG and anti-MPO was increased in the workers with the highest exposure, as assessed by their mean intensity of exposure. The highest activity of U-NAG was observed in the exposed workers with the lower concentrations of selenium in whole blood. CONCLUSIONS: The study indicates an effect of exposure on the kidney proximale tubule cells, possibly modified by individual selenium status, and an effect mediated by neutrophil granulocytes.     

Renal function of chloralkali workers after the cessation of exposure to mercury vapor

OBJECTIVES: The aims of the study were to assess renal function in chloralkali workers previously exposed to mercury vapor and to assess the impact of selenium status on the biomarkers of kidney function. METHODS: Forty-nine chloralkali workers previously exposed to mercury vapor were compared with 49 age-matched referents in a cross-sectional study. Selected biomarkers of kidney function and biomarkers of selenium status were measured. The index group had been exposed for 13.1 (range 2.8-34.5) years on the average at a mean urinary mercury excretion of 9.3 (range 4.0-25.4) nmol/mmol creatinine a year. The exposure had ceased on an average of 4.8 (range 4.2-10.0) years prior to the examinations. RESULTS: No statistically significant differences were found between the groups for the measured biomarkers of kidney function. The serum selenium concentration and serum glutathione peroxidase activity were associated with the activity of N-acetyl-beta-D-glucosaminidase in urine (U-NAG). The results indicate that having higher glutathione peroxidase activity or a higher serum selenium concentration results in a lower excretion of U-NAG. This effect was the most pronounced in the oldest third of the participants. Apparently the well-known association between U-NAG and age could only be found for the participants with a lower selenium status. CONCLUSIONS: Increased activities of U-NAG during ongoing exposure to mercury vapor appear to be reversible upon cessation of exposure. Selenium status has a substantial impact on U-NAG activity and should be considered in studies of U-NAG excretion.     

Cardiovascular reflexes and low long-term exposure to mercury vapour

Summary Subjective symptoms related to autonomic dysfunction and quantitative non invasive tests measuring both sympathetic and parasympathetic functions of the autonomic nervous system were studied among a group of 41 chlorine-alkali workers with low long-term exposure to mercury (Hg') vapour and their matched referents. The test battery included measurements of pulse rate variation in normal and deep breathing, in the Valsalva manoeuvre and in vertical tilt as well as blood pressure responses during standing and isometric work. The exposure time had been 16 years on average, and the mean exposure to Hg vapour was estimated to have been about 30 g/m³ of air. Only a tendency for a subtle reduction of cardiovascular reflex responses and a slight increase of subjective symptoms were seen in the exposed group, but no significant autonomic dysfunction was associated with the low level of exposure.     

Microenvironmental exposure to mercury vapor

Work area and breathing zone samples were collected in a factory utilizing metallic mercury and analyzed for mercury vapor content. Breathing zone samples averaged several fold higher in concentration than concurrent area samples, reflecting a "microenvironmental" exposure to mercury vapor, presumably from contaminated clothing and hands. Blood and corrected total urine mercury values correlated well with the average microenvironmental exposure level for each worker. Measurements of unbound mercury in urine samples were sensitive at picking up minimal exposures. Excessive amounts of unbound mercury were not found in the urine, even with wide day-to-day swings in microenvironmental mercury vapor levels, suggesting that the human body can adapt to a chronic, moderate exposure to mercury vapor.     

Evaluation of mercury in urine as an indicator of exposure to low levels of mercury vapor

We conducted a pooled analysis to investigate the relationship between exposure to elemental mercury in air and resulting urinary mercury levels, specifically at lower air levels relevant for environmental exposures and public health goals (i.e., < 50 microg/m3 down to 1.0 microg/m3). Ten studies reporting paired air and urine mercury data (149 samples total) met criteria for data quality and sufficiency. The log-transformed data set showed a strong correlation between mercury in air and in urine (r = 0.774), although the relationship was best fit by a series of parallel lines with different intercepts for each study R2 = 0.807). Predicted ratios of air to urine mercury levels at 50 microg/m3 air concentration ranged from 1:1 to 1:3, based on the regression line for the studies. Toward the lower end of the data set (i.e., 10 microg/m3), predicted urinary mercury levels encompassed two distinct ranges: values on the order of 20 microg/L and 30-60 microg/L. Extrapolation to 1 microg/m3 resulted in predicted urinary levels of 4-5 and 6-13 microg/L. Higher predicted levels were associated with use of static area air samplers by some studies rather than more accurate personal air samplers. Urinary mercury predictions based primarily on personal air samplers at 1 and 10 microg/m3 are consistent with reported mean (4 microg/L) and upper-bound (20 microg/L) background levels, respectively. Thus, although mercury levels in air and urine are correlated below 50 microg/m3, the impact of airborne mercury levels below 10 microg/m3 is likely to be indistinguishable from background urinary mercury levels.     

Effects of mercury vapor exposure on neuromotor function in Chinese miners and smelters

Objectives Current risk assessment of elemental mercury vapor is based on the tremor toxicity. To clarify the neuromotor effects of occupational exposure to mercury vapor, hand tremor and postural sway were measured in 27 miners and smelters (i.e., exposed workers) and 52 unexposed subjects. Methods Urine samples were collected and total mercury and creatinine concentrations were determined. Data of the tremor and postural sway were analyzed using the fast Fourier transformation. Results The geometric means of the urinary mercury level (UHg) were 228 (range 22.6–4,577) μg/g creatinine for the exposed workers and 2.6 (1.0–17.4) μg/g creatinine for the unexposed subjects. Total tremor intensity and frequency-specific tremor intensities at 1–6 and 10–14 Hz were significantly larger in the exposed workers than in the unexposed subjects (P < 0.05), but they were not significantly related to the UHg among the exposed workers (P > 0.05). In contrast, there were no significant differences in any postural sway parameters between the above two groups (P > 0.05), but the transversal sway with eyes open was positively related to the UHg among the exposed workers in using multiple regression analysis (P < 0.05). Conclusions These findings suggest that postural sway, as well as hand tremor, may be affected by elemental mercury vapor exposure, but the former test seems to be less sensitive to mercury than the latter one.     

慢性汞暴露对接触者人群肾小球功能影响

目的 探讨慢性空气汞暴露对人群肾小球功能的影响。方法 选择某温度计厂为研究现场,根据生产车间空气汞监测数据,将全厂职工划分为暴露组(n=101)和对照组(n=85);测定186名职工发汞、尿汞以及肾小球功能,并对职工进行问卷调查。结果 暴露组空气汞浓度、尿汞、发汞和累积暴露量明显高于对照组(P<0.01);暴露组血清肌酐浓度为(81.6±43.9)μmol/L,明显高于对照组(65.6±36.6)μmol/L;暴露组内生肌酐清除率(81.6±39.7)mL/min,明显低于对照组(113.4±45.4)mL/min;多元分析结果显示,随发汞的升高,血清肌酐明显升高,内生肌酐清除率明显降低;随累积接触量增加,血清肌酐和血清尿素氮均明显升高。结论 肾小球滤过功能指标的改变与反映长期暴露量的发汞和累积暴露量关系密切,可作为反映汞暴露对肾脏功能长期损害的指标。     

Gestational mercury vapor exposure and diet contribute to mercury accumulation in neonatal rats

Exposure of pregnant Long-Evans rats to elemental mercury (Hg0) vapor resulted in a significant accumulation of Hg in tissues of neonates. Because elevated Hg in neonatal tissues may adversely affect growth and development, we were interested in how rapidly Hg was eliminated from neonatal tissues. Pregnant rats were exposed to 1, 2, or 4 mg Hg0 vapor/m3 or air (controls) for 2 hr/day from gestation day 6 (GD6) through GD15. Neonatal brain, liver, and kidney were analyzed for total Hg at various times between birth and postnatal day 90 (PND90). Milk was analyzed for Hg between birth and weaning (PND21). Before weaning, the Hg levels in neonatal tissues were proportional to maternal exposure concentrations and were highest in kidney followed by liver and then brain. There was no elimination of Hg between birth and weaning, indicating that neonates were exposed continuously to elevated levels of Hg during postpartum growth and development. Consumption of milk from exposed dams resulted in a slight increase in kidney Hg concentration during this period. Unexpectedly, neonatal Hg accumulation increased rapidly after weaning. Increased Hg was measured in both control and exposed neonates and was attributed to consumption of NIH-07 diet containing trace levels of Hg. By PND90, tissue Hg levels equilibrated at concentrations similar to those in unexposed adult Long-Evans rats fed the same diet. These data indicate that dietary exposure to trace amounts of Hg can result in a significantly greater accumulation of Hg in neonates than gestational exposure to high concentrations of Hg0 vapor.     

Psychological performance and long-term exposure to mercury vapors

In a cross-sectional study the psychological test performances of a group of 36 male chlorine-alkali workers were compared with the level of exposure to mercury and to the corresponding results of referents. The mercury exposure had lasted for at least 10 years and had been controlled by regular health examinations and urine analyses. Several dose indicators were calculated. The more heavily exposed workers performed more poorly on the verbal intelligence test (Similarities) than the referents did. Impairments in the memory tests showed a statistically significant correlation with the actual exposure level, especially with the actual concentration of mercury in blood. The monitoring of mercury in blood can be useful in health surveillance programs. The level of mercury in the air was calculated from the dose indicators. The results support the recommended exposure limit of 25 micrograms/m3 for metallic mercury vapor in the air as a level avoiding adverse effects in exposed workers.     

Assessing elemental mercury vapor exposure from cultural and religious practices

Use of elemental mercury in certain cultural and religious practices can cause high exposures to mercury vapor. Uses include sprinkling mercury on the floor of a home or car, burning it in a candle, and mixing it with perfume. Some uses can produce indoor air mercury concentrations one or two orders of magnitude above occupational exposure limits. Exposures resulting from other uses, such as infrequent use of a small bead of mercury, could be well below currently recognized risk levels. Metallic mercury is available at almost all of the 15 botanicas visited in New York, New Jersey, and Pennsylvania, but botanica personnel often deny having mercury for sale when approached by outsiders to these religious and cultural traditions. Actions by public health authorities have driven the mercury trade underground in some locations. Interviews indicate that mercury users are aware that mercury is hazardous, but are not aware of the inhalation exposure risk. We argue against a crackdown by health authorities because it could drive the practices further underground, because high-risk practices may be rare, and because uninformed government intervention could have unfortunate political and civic side effects for some Caribbean and Latin American immigrant groups. We recommend an outreach and education program involving religious and community leaders, botanica personnel, and other mercury users.     

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.     

Effects of occupational exposure to mercury vapor on lymphocyte micronuclei

For 26 chloralkali workers exposed to inorganic mercury and 26 age-matched, occupationally unexposed referents, the frequency and size distribution of micronuclei were determined in peripheral lymphocytes stimulated with either phytohemagglutinin or pokeweed mitogen. For the exposed workers the mean concentrations of mercury in urine, plasma, and erythrocytes were 16 nmol/mmol of creatinine, 48 nmol/l, and 78 nmol/l, respectively, and their mean exposure time was 10 years. Neither the frequency nor the size of micronuclei was significantly different in the two groups; nor were there any correlations to current mercury levels. However, in the exposed group, and with phytohemagglutinin as the mitogen, a statistically significant correlation between previous exposure to mercury (cumulative exposure or number of blood mercury peaks) and the frequency of micronuclei was found. This association was also present when the effects of age and smoking were allowed for, and it may indicate an accumulation of cytogenetic effects in T-lymphocytes.     

Glutathione level after long-term occupational elemental mercury exposure

Many in vitro and in vivo studies have elucidated the interaction of inorganic mercury (Hg) and glutathione. However, human studies are limited. In this study, we investigated the potential effects of remote long-term intermittent occupational elemental Hg vapour (Hg degrees ) exposure on erythrocyte glutathione levels and some antioxidative enzyme activities in ex-mercury miners in the period after exposure. The study included 49 ex-mercury miners divided into subgroups of 28 still active, Hg degrees -not-exposed miners and 21 elderly retired miners, and 41 controls, age-matched to the miners subgroup. The control workers were taken from "mercury-free works". Reduced glutathione (GSH) and oxidized disulphide glutathione (GSSG) concentrations in haemolysed erythrocytes were determined by capillary electrophoresis, while total glutathione (total GSH) and the GSH/GSSG ratio were calculated from the determined values. Catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities in erythrocytes were measured using commercially available reagent kits, while urine Hg (U-Hg) concentrations were determined by cold vapour atomic absorption (CVAAS). No correlation of present U-Hg levels, GSH, GSSG, and antioxidative enzymes with remote occupational biological exposure indices were found. The mean CAT activity in miners and retired miners was significantly higher (p<0.05) than in the controls. No differences in mean GPx activity among the three groups were found, whereas the mean GR activity was significantly higher (p<0.05) in miners than in retired miners. The mean concentrations of GSH (mmol/g Hb) in miners (13.03+/-3.71) were significantly higher (p<0.05) than in the control group (11.68+/-2.66). No differences in mean total GSH, GSSG levels, and GSH/GSSG ratio between miners and controls were found. A positive correlation between GSSG and present U-Hg excretion (r=0.41, p=0.001) in the whole group of ex-mercury miners was observed. The significantly lower GSH level (p<0.05) determined in the group of retired miners (9.64+/-1.45) seems to be age-related (r= -0.39, p=0.001). Thus, the moderate but significantly increased GSH level, GR and CAT activity in erythrocytes in the subgroup of miners observed in the period after exposure to Hg degrees could be an inductive and additive response to maintain the balance between GSH and antioxidative enzymes in interaction with the Hg body burden accumulated during remote occupational exposure, which does not represent a severely increased oxidative stress.     

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.