Minimal immunological effects on workers with prolonged low exposure to inorganic mercury.

OBJECTIVES: This study was carried out to investigate possible immunological changes in workers with prolonged low exposure to inorganic mercury in a fluorescent light bulb factory. METHODS: 29 immunological variables were examined in 34 workers with prolonged low level exposure to inorganic mercury (exposed workers) and 35 unexposed workers as the controls. The selected indicator of mercury exposure was concentration of mercury in the urine (U-Hg), which declined progressively from 36.0 micrograms/l in 1978 to 6.0 micrograms/l in the study year 1994. RESULTS: None of the exposed workers had ever shown signs of either acute or chronic inorganic mercury toxicity or had shown any form of hypersensitivity. The only changes found in the exposed workers, compared with the controls, were a reduction of the cells that express cluster differentiation (CD25,(T activation antigen (Tac antigen))) and concentrations of tumour necrosis factor-alpha (TNF-alpha) in serum. However, the decrease of cells that express CD25 was unrelated to occupational exposure and was, in all likelihood a chance finding. Conversely, the decline in serum TNF-alpha was closely associated with occupational exposure. However, no dose-response relation was found between U-Hg and TNF-alpha concentrations; nor were TNF-alpha concentrations affected by cumulative occupational exposure to inorganic mercury in over 20 years. CONCLUSIONS: Tentatively, we suggest that reduced serum TNF-alpha concentrations might be indicative of an in vivo functional defect of the monocyte macrophage system in this particular group of workers even though they were clinically asymptomatic.     

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.     

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.     

Symptoms of intoxication in dentists associated with exposure to low levels of mercury

The present study examined the effects of occupational exposure of a group of dentists to low levels of mercury. The study population consisted of 106 dentists and 94 general practitioners (referent group), from private and public clinics in Shiraz city. Subjects were requested to complete a questionnaire on demographic variables, suspicious symptoms of intoxication and work practices. Additionally, atmospheric and urinary concentrations of mercury were measured by Atomic Absorption Spectroscopy technique. The data were analysed by χ(2) test, independent sample t-test and multivariate logistic regression analysis, where applicable. Both groups were similar as far as most demographic and socioeconomic variables, but age and number of personal amalgam fillings, were concerned. Median of atmospheric concentration of mercury was found to be 3.35 μg/m(3). Likewise, the urinary concentration of mercury in dentists was estimated to be 3.16 μg/g creatinine. This value was significantly higher than that of the referent group. Similarly, analysis of the data revealed that neuropsychological, muscular, respiratory, cardiovascular and dermal symptoms were more prevalent in dentists. Our findings indicate that occupational exposure of dentists to mercury, even at low levels, is associated with a significant increase in the prevalence of symptoms of intoxication.     

Uptake and excretion of inorganic mercury in the lobster Homarus gammarus (L.) White 1847: long-term effects of exposure to low levels of the metal

The uptake and accumulation of inorganic mercury by lobsters, from seawater containing levels of 10 to 100 ppb, was studied over periods of up to 50 days, using radiochemical neutron activation analysis. These results were amplified by the use of radioisotope tracer experiments. It was found that the gills and the green glands accumulated the most mercury and that the metal could be excreted via the urine. Histological studies showed that long-term exposure to mercury resulted in progressive necrosis of the green glands, whereas other organs were unaffected.     

Mortality from cardiovascular diseases and exposure to inorganic mercury

OBJECTIVE—To study the mortality from cardiovascular and other chronic non-neoplastic diseases after long term exposure to inorganic mercury. Limited information is available on the effect of chronic exposure to mercury on the cardiovascular system.
METHODS—The mortality was studied among 6784 male and 265 female workers from four mercury mines and mills in Spain, Slovenia, Italy, and the Ukraine. Workers were employed between 1900 and 1990; the follow up period lasted from the 1950s to the 1990s. The mortality of the workers was compared with national reference rates.
RESULTS—Among men, there was a slight increase in overall mortality (standardised mortality ratio (SMR) 1.08, 95% confidence interval (95% CI) 1.04 to 1.12). An increased mortality was found from hypertension (SMR 1.46, 95% CI 1.08 to 1.93), heart diseases other than ischaemic (SMR 1.36, 95% CI 1.20 to 1.53), pneumoconiosis (SMR 27.1, 95% CI 23.1 to 31.6), and nephritis and nephrosis (SMR 1.55, 95% CI 1.13 to 2.06). The increase in mortality from cardiovascular diseases was not consistent among countries. Mortality from hypertension and other heart diseases increased with estimated cumulative exposure to mercury; mortality from ischaemic heart disease and cerebrovascular diseases increased with duration of employment, but not with estimated exposure to mercury. Results among women were hampered by few deaths.
CONCLUSION—Despite limited quantitative data on exposure, possible confounding, and likely misclassification of disease, the study suggests a possible association between employment in mercury mining and refining and risk in some groups of cardiovascular diseases.


     

Occupational exposure to inorganic mercury vapour and reproductive outcomes

The effect of exposure to inorganic mercury on the pregnantwoman and her foetus has received little attention. Transportof elemental inorganic mercury into foetal tissues has beenreported, and prior studies indicate a higher incidence of adversepregnancy outcome. The effects of occupational exposure to inorganicmercury on pregnancy were investigated among 46 exposed womenworkers; controls were 19 women working in non-production areasof the same factory. There were 104 recorded total pregnanciesduring the period 1948–77. The study revealed a higherfrequency of adverse reproductive outcomes, especially congenitalanomalies, among the women exposed to inorganic mercury levelsat or substantially lower than 0.6 mg/m³; no significant differencesin the stillbirth or miscarriage rates were noted between thetwo groups of women. The overall foetal death rate in this studywas similar to New York state (USA) and national levels forthe same period.     

Health effects in the Flemish population in relation to low levels of mercury exposure: From organ to transcriptome level

Due to possible health risks, quantification of mercury accumulation in humans was included in the Flemish biomonitoring programmes FLEHS I (2002–2006) and FLEHS II (2007–2011). The general objective of FLEHS I was to assess regional exposure levels in order to link possible differences in these internal exposure levels to different types of local environmental pressure. Therefore, Hg and MMHg (methylmercury) were only measured in pooled blood samples per region and per age class. In FLEHS II, mercury concentrations were measured in hair of each participant. About 200 adolescents and 250 mothers (reference group) and two times 200 adolescents (2 hotspots) were screened. The main objectives of the FLEHS II study were: (1) to determine reference levels of mercury in hair for Flanders; (2) to assess relations between mercury exposure and possible sources like fish consumption; (3) to assess dose–effect relations between mercury exposure and health effect markers. The results showed that mercury concentrations in the Flemish population were rather low compared to other studies. Mercury levels in the Flemish populations were strongly related to the age of the participants and consumption of fish. Significant negative associations were observed between mercury in hair and asthma, having received breast feeding as a newborn, age at menarche in girls, allergy for animals and free testosterone levels. Significant correlations were also observed between mercury in hair and genes JAK2, ARID4A, Hist1HA4L (boys) and HLAdrb5, PIAS2, MANN1B1, GIT and ABCA1 (girls).     

Renal mechanisms in the cardiovascular effects of chronic exposure to inorganic mercury in rats.

Male weanling Wistar rats received 200 micrograms/ml of mercury (Hg), as HgCl2, in drinking water for 180 days. At the end of the treatment, systemic arterial blood pressure was augmented, cardiac inotropism was reduced, and heart rate was unchanged. Light and electron microscopical studies of the kidney showed a mesangial proliferative glomerulonephritis in about 80% of the glomeruli. Tubular cells showed reduction of the acid phosphatase activity, which was related to functional abnormalities of the lysosomes. In the 24 hour urine samples of the Hg exposed rats, there was slight reduction of kallikrein activity, but evident proteinuria was not present in all samples. Plasma renin activity was reduced, that of angiotensin I-converting enzyme was augmented, and plasma aldosterone concentrations were unchanged. Mercury was accumulated mostly in the kidney of the Hg treated animals; and the content of Hg in the heart was higher than in the brain. These data show that chronic exposure to Hg acts on the kidney with complex mechanisms of toxicity; these contribute to modify systemic haemodynamics.     

Renal mechanisms in the cardiovascular effects of chronic exposure to inorganic mercury in rats.

Male weanling Wistar rats received 200 micrograms/ml of mercury (Hg), as HgCl2, in drinking water for 180 days. At the end of the treatment, systemic arterial blood pressure was augmented, cardiac inotropism was reduced, and heart rate was unchanged. Light and electron microscopical studies of the kidney showed a mesangial proliferative glomerulonephritis in about 80% of the glomeruli. Tubular cells showed reduction of the acid phosphatase activity, which was related to functional abnormalities of the lysosomes. In the 24 hour urine samples of the Hg exposed rats, there was slight reduction of kallikrein activity, but evident proteinuria was not present in all samples. Plasma renin activity was reduced, that of angiotensin I-converting enzyme was augmented, and plasma aldosterone concentrations were unchanged. Mercury was accumulated mostly in the kidney of the Hg treated animals; and the content of Hg in the heart was higher than in the brain. These data show that chronic exposure to Hg acts on the kidney with complex mechanisms of toxicity; these contribute to modify systemic haemodynamics.     

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.