Immunologic effects of exposure to low levels of inorganic mercury

OBJECTIVE: The immune system is a target for the toxic effects of inorganic mercury, both in humans and animals. In humans it has been observed that occupational and environmental exposure to inorganic mercury may cause both clinical (autoimmunity, hypersensitivity) and subclinical effects (cellular and humoral immunologic variable modifications). To obtain a better definition of these effects with respect to the exposure levels, a multicentre study was performed on 117 workers exposed to very low doses of inorganic mercury and 172 subjects from the general population of the same geographical area with environmental exposure to mercury from dental amalgams and dietary fish intake. RESULTS: The white blood cell count was included in the normality range for all subjects and there was no difference between exposed and non exposed subjects. The immunologic variables studied showed an increase of the CD4+ and CD8+ number in exposed workers compared to non-exposed subjects, with a statistically significance only for CD4+, while no difference was observed regarding CD4+, CD8+, NK+ percentage and CD4+/CD8+ ratio. A significative decrease of serum IL-8 and an inverse correlation between serum levels of this cytokine and HgU were observed in exposed workers compared to non exposed subjects. No association between immunologic variables and both dental amalgams and dietary fish intake was found in subjects not occupationally exposed to inorganic mercury. DISCUSSION: The decrease in IL-8 serum levels observed in exposed workers might suggest an immunosuppressive effect of occupational exposure to very low doses of inorganic mercury. This result suggests the need to revise of current HgU BEI after further definition of its prognostic significance.     

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.     

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.     

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.     

Evaluation of the effects following low doses of inorganic mercury from environmental and occupational exposures

AIMS: This paper reviews the studies, both in vivo and in vitro, carried out for the project on low-dose effects of inorganic mercury, financed by the Italian Ministry of Universities and Scientific and Technological Research. RESULTS, COMMENTS AND PROPOSAL: The results offer both innovative aspects and potential practical applications. Particular attention is drawn to the reliability of biomarkers of exposure [mercury in urine (HgU) and blood (HgB), possibility of speciation] as well as to the availability of guidance values for risk assessment (reference value, action level, biological threshold value). In the general population, HgU and HgB levels are significantly related to the presence of dental amalgams and to fish consumption; nevertheless, such exposure levels do not elicit adverse health effects on renal, immune and nervous functions, according to the markers evaluated in the studies. The present biological threshold values for occupational exposure appear adequate to prevent health effects, considering the immune system, kidney and central nervous system as the target organs. However, possible effects of low doses of mercury on immune and neuroendocrine functions should be further examined; moreover, consideration should be given to the risk of consuming fish species with high Hg content, particularly concerning the renal and central nervous system effects. Finally, further studies should be planned on other potentially important effects, that could not be considered in this study, such as those on prenatal development, the cardiovascular system and the thyroid gland.     

Introduction: scope and purpose of the multicenter project " Assessment of effects due to low doses in inorganic mercury following environmental and occupational exposure: human and in vitro studies on specific toxicity mechanisms"

The principal aims of the project financed by the Italian Ministry of University and Scientific and Technological Research were: to verify if at the current limit values early biological effects can be demonstrated; to identify the levels of internal dose that can cause early effects; to evaluate the non-occupational factors that can contribute to the levels of internal dose. In particular, the mercury intake derived from dental amalgams and fish consumption was considered. The internal dose was measured with the traditional biological indicators (urinary and blood mercury) and with the speciation of a large percentage of biological samples by ICP-MS. The central nervous system, neuroendocrine function, kidney and the immune system were considered as target organs and were examined using previously standardized indicators of effects. Two groups of subjects were included in the study: workers with occupational exposure to inorganic mercury in different industrial settings and control subjects identified from the general population. The first group was characterized by an exposure level to inorganic mercury clearly below the current limit values; whereas the HgU levels of a relevant number of control subjects were similar to those measured in the exposed subjects. The in vitro studies covered several issues: the percutaneous absorption of mercury using skin derived from human post-mortem samples in a standardized model; the release of the metal from dental amalgams in different physiological conditions of the oral cavity; the effects of increasing doses of mercury chloride on tubular renal cells. The project was realized with the cooperation of seven Research Units from six Italian Universities. Researchers belonging to Departments of Occupational Medicine, Industrial Hygiene, General Pathology, Biochemistry, Odontology, and Biostatistics were involved to achieve a multidisciplinary approach. The results of this research project are described and discussed in the following papers.     

Mercury levels in urine and hair of children in an Andean gold-mining settlement

This field study investigated mercury (Hg) levels in urine and hair of Andean children of indigenous Saraguro and Metizo gold miners in the Nambija, Ecuador gold mining settlement. Spot samples of urine and hair samples were collected concurrently from 80 children each. Urine samples were used to determine the inorganic Hg burden, while hair samples were used as an index of methylmercury (MeHg) exposure from consumption of Hg contaminated fish. The mean level of Hg in urine (HgU) was 10.9 microg/L, and the mean level in hair (HgH) was 6.0 microg/g. Regression analysis showed a significant association (r = 0.404, p = 0.0007) between matched HgU and HgH samples. Mean HgU and HgU levels tended to be higher for children aged 6-14 years than for a younger group. The wide range of Hg levels in the urine and hair of Andean children of gold miners may place them at risk for neurodevelopmental and learning disorders.     

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.     

TNT接触对神经行为功能影响的研究

目的 为探讨ＴＮＴ接触对神经行为功能的影响。方法 采用ＷＨＯ神经行为核心测试组合（ＮＣＴＢ）并结合因子分析方法研究ＴＮＴ接触对神经行为的功能的影响,ＴＮＴ接触工人共５９名,平均尿ＤＮＡＴ浓度为２．７７ｍｇ／Ｌ对照工人共５３名,平均尿ＤＮＡＴ浓度为０．６３ｍｇ／Ｌ,结果 ＴＮＴ接触对工人的记忆力及心理运动有影响,尿ＤＮＡＴ水平与第三因子得分存在剂量－反应关系。结论 提示ＴＮＴ对心理运动稳定度的影响有     

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.     

Organic and Inorganic Mercury in Neonatal Rat Brain after Prenatal Exposure to Methylmercury and Mercury Vapor

Background

Many populations are exposed to multiple species of mercury (Hg), predominantly organic Hg as methylmercury (MeHg) from fish, and inorganic Hg as Hg vapor from dental amalgams. Most of our knowledge of the neurotoxicity of Hg is based on research devoted to studying only one form at a time, mostly MeHg.

Objectives

In this study we investigated the effects of prenatal exposure to MeHg and Hg vapor on Hg concentrations in the brain of neonatal rats.

Methods

Female Long-Evans hooded rats were exposed to MeHg (0, 3, 6, or 9 ppm as drinking solution), Hg vapor (0, 300, or 1,000 μg/m³ for 2 hr/day), or the combination of both, from 30 days before breeding through gestational day 18. On postnatal day 4, whole brains were taken from one male and one female from each of four litters in each treatment group to assess organic and inorganic Hg in the brain by cold vapor atomic absorption spectrometry.

Results

Statistical analysis using linear mixed effects models showed that MeHg dose was the primary determinant of both organic and inorganic brain Hg levels. For both outcomes, we also found significant interactions between MeHg and Hg vapor exposure. These interactions were driven by the fact that among animals not exposed to MeHg, animals exposed to Hg vapor had significantly greater organic and inorganic brain Hg levels than did unexposed animals.

Conclusion

This interaction, heretofore not reported, suggests that coexposure to MeHg and Hg vapor at levels relevant to human exposure might elevate neurotoxic risks.     

乙苯对职业人群神经行为的影响

目的 评价乙苯对职业人群神经行为的影响.方法 选择某石化公司苯乙烯合成原料车间246名乙苯上料工为接触组,相应的公司办公人员122名作为对照组,通过问卷调查,收集乙苯职业接触的基本信息.通过WHO神经行为核心测试组合(NCTB)法,测试对象的个体神经行为功能.结果 接触组和对照组的4项消极情绪状态(紧张、抑郁、愤怒、困惑)得分之间差异无统计学意义(P＞0.05),接触组的积极情绪状态(有力)得分(16.29±8.61)明显低于对照组(18.46±9.52),疲劳得分(9.23±1.27)明显高于对照组(7.16±1.15),(P＜0.05).接触组的平均反应时、数字广度得分明显高于对照组,手提转敏捷度、视觉记忆、目标追踪-Ⅱ正确打点数得分明显低于对照组,差异有统计学意义(P＜0.05).按不同的工龄分段,接触组各工龄段间视觉记忆、目标追踪-Ⅱ正确打点数得分的差异无统计学意义(P＞0.05),3～、4～和5～年工龄段的5项消极情绪状态(紧张、抑郁、愤怒、疲劳、困惑)得分及平均反应时得分均明显高于0～和2～年工龄段.3～、4～年工龄段的数字广度和3～、4～和5～年工龄段的手提转敏捷度、数字译码得分皆明显低于0～和2～年工龄段,差异均有统计学意义(P＜0.05).结论 乙苯可降低接触工人神经行为功能,工人神经行为功能在工龄为3年时发生了明显变化,工龄3年左右工人为乙苯神经行为损害的易感人群.

Abstract：

Objective To evaluate the influence of ethylbenzene on the neurobehavior of occupationally exposed workers. Methods The exposure group consisted of 246 workers occupationally exposed to ethylbenzene and 172 staffs from the offices served as controls. The basic information on ethylbenzene exposure was collected by the questionnaire. The nervous behavior and function of workers were evaluated by Neurobehavioral Core Test Battery (NCTB). Results There were no differences of the scores for four emotional states (tension, depression, angry and bewilderment) between exposure group and control group (P＞0.05). The score of emotion (vigor) in exposure group was significantly lower than that in control group (P＜0.05), but the fatigue score in exposure group was significantly higher than that in control group (P＜0.05).The score of mean reaction time in exposure group was significantly higher than that in control group (P＜0.05), the scores of digital span, manual dexterity, visual retention and target tracking in exposure group were significantly lower than those in control group (P＜0.05). The exposure group was divided into 5 sub-groups,according to working duration. There were no differences for the scores of visual retention and target tracking among 5 sub-groups (P＞0.05). The scores of five emotional states (tension, depression, angry, fatigue and bewilderment) in 3 sub-groups exposed to ethylbenzene for 3～, 4～ and 5～ years were significantly higher than those in 2 sub-groups exposed to ethylbenzene for 0～ and 2 ～ years (P＜0.05). The scores of digital span in 2 sub-groups exposed to ethylbenzene for 3～ or 4～ years and the scores of manual dexterity and digital symbol in 3 sub-groups exposed to ethylbenzene for 3 ～, 4～ and 5～ years were significantly lower than those in 2 subgroups exposed to ethylbenzene for 0～ and 2 ～ years (P＜0.05). Conclusion Ethylbenzene can depress the neurobehavioral functions of exposed workers. The neurobehavioral functions of workers exposed to ethylbenzene for 3 years changed significantly. The workers exposed to ethylbenzene for 3 years may be the susceptible population of neurobehavioral function impairment.     

Occupational and environmental toxicology of mercury and its compounds

Mercury exists in various chemical forms. The important forms from a toxicological viewpoint are the metallic form, also called the elemental form, the divalent inorganic forms and methylmercury compounds. Elemental (Hg0) mercury has a high vapor pressure and the vapor causes a number of cases of poisoning via inhalation. Classical mercury poisoning is characterized by a triad of signs, namely tremors, erethism and gingivitis. Mercurial erethism, which is characterized by behavioral and personality changes such as extreme shyness, excitability, loss of memory, and insomnia are also observed. Recently, the effects of mercury exposure at levels around 0.05 mg/m3 or lower have been of concern and may include minor renal tubular damage, increased complaints of tiredness, memory disturbance and other symptoms, subclinical finger tremor, abnormal EEG by computerized analysis and impaired performance in neurobehavioral or neuropsychological tests. Abnormal gait, dysarthria, ataxia, deafness and constriction of the visual field are typical of the symptoms of methylmercury poisoning observed in Minamata and Iraqi outbreaks, as well as in occupational methylmercury poisoning cases. Furthermore, an infant born to a mother with excessive methylmercury consumption showed various neurological disturbances and delayed development. Since several populations are believed to be still exposed to methylmercury through the consumption of fish and sea mammals, neurobehavioral deviations in children of these populations have recently been investigated.     

Neuropsychological function in solvent-exposed South African paint makers

Neuropsychological and neurological function were investigated in 228 organic solvent exposed paint manufacturing workers in two factories. Solvent exposure was expressed as both American Conference of Governmental Industrial Hygienists 1990 Threshold Limit Value equivalents and total hydrocarbon parts per million. The World Health Organization (WHO) neurobehavioral core test battery, the Neurobehavioural Evaluation System--2 (NES-2), and the UNISA Neuropsychological Assessment Procedure (UNAP) were used to measure outcomes, and a Vibratron II was used to measure peripheral vibration sensation. Exposures were generally below the Threshold Limit Value, and no exposure effect was found. Possible explanations for this finding are discussed, including low exposure, exposure, and outcome misclassification, together with inappropriateness, nonvalidity, and relative insensitivity of neuropsychological tests. Only age predicted Vibratron score. Some tests were clearly inappropriate for use in developing countries. Neuropsychological tests were sensitive to educational level, age, alcohol consumption, and cultural indicators. The WHO tests in particular showed good construct validity for neuropsychological functions and should be more formally validated for use in developing countries. Nevertheless, a major problem of cultural dependence is evident for all neuropsychological tests used in this study, and methods for bypassing this problem in less developed settings are discussed.     

Comparison of neurobehavioral function in workers exposed to a mixture of organic and inorganic lead and in workers exposed to solvents

The neurobehavioral effects of lead (organic and inorganic) and organic solvents were compared in 386 U.S. workers (52 reference, 190 lead, and 144 solvent workers). The association between neurobehavioral test performance and duration of exposure to lead or solvents was also examined and compared. The neurobehavioral test battery consisted of examiner and computer-administered neurobehavioral tests, a test of olfactory function, and questionnaires that assessed neuropsychiatric symptoms. Adjusted mean differences on the neurobehavioral test scores were estimated by comparing the exposed group to the referent group using linear regression and adjusting for premorbid intellectual ability, age, and race. Both lead and solvents were associated with diminished neurobehavioral performance in all neurobehavioral areas tested. Specifically, while lead and solvent exposure had the same magnitude of adverse effects on tests of manual dexterity, lead exposure was associated with greater adverse effects on memory and learning tests but with less adverse effects on executive/motor tests and on a test of olfaction than solvent exposure. An elevated number of neuropsychiatric symptoms was reported by 7% of the referent group, 43% of the lead group, and 15% of the solvent group. For exposure duration of ?10 years, more neurobehavioral decrements were found in the solvent group relative to the lead group. However, for exposure duration of ?18 years, the lead group showed more decrements than the solvent group. Overall, these data suggest differences in neurobehavioral functioning between the lead (organic and inorganic) and solvent exposed workers examined in this study.     

Neuropsychological function among workers exposed to aluminum – a mini-review

Aluminum (Al) is the most common element in nature after oxygen and silicon. Aluminum has been proposed to be a causative agent in the development of neurodegenerative diseases. Aluminum made available via the lungs, as it is in occupational settings, is probably better absorbed than that entering the body via the gastrointestinal tract. Neuropsychological tests are sensitive methods for detecting subtle functional impairment of the nervous system. This minireview is based on a systematic literature search for studies on workers occupationally exposed to aluminum. The tests were categorized as belonging to one of 12 different neuropsychological functions. The level of significance was set at p<0.05. Among the 559 papers identified, 24 fulfilled the inclusion criteria. There were no clear, consistent findings of occupational aluminum exposure being correlated with neuropsychological deficits. However, there was a weak tendency toward worse performances on tests related to information processing speed and a slight tendency toward weaker performances on memory tests for workers exposed to aluminum. The limited number of studies in this field makes it difficult to draw a clear conclusion regarding whether occupational exposure to aluminum increases the risk of altered neuropsychological function.     

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     

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

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