Mercury

Many published studies have illustrated that several of the present day neurological epidemics (autism, attention deficit disorder, Alzheimer’s) cannot be correlated to any single neurotoxicant. However, the present scientific examination of the numerous global blood monitoring databases for adults that include the concentrations of the neurotoxic elements, aluminum (Al), arsenic (As), lead (Pb), manganese (Mn), mercury (Hg), and selenium (Se) clearly indicate that, when considered in combination, for some, the human body may become easily over-burdened. This can be explained by changes in modern lifestyles. Similar data, solely for pregnant women, have been examined confirming this. All these elements are seen to be present in the human body and at not insignificant magnitudes. Currently suggested minimum risk levels (MRL) for humans are discussed and listed together with averages of the reported distributions, together with their spread and maximum values. One observation is that many distributions for pregnant women are not too dissimilar from those of general populations. Women obviously have their individual baseline of neurotoxin values before pregnancy and any efforts to modify this to any significant degree is not yet clearly apparent. For any element, distribution shapes are reasonably similar showing broad distributions with extended tails with numerous outlier values. There are a certain fraction of people that lie well above the MRL values and may be at risk, especially if genetically susceptible. Additionally, synergistic effects between neurotoxins and with other trace metals are now also being reported. It appears prudent for women of child-bearing age to establish their baseline values well before pregnancy. Those at risk then can be better identified. Adequate instrumental testing now is commercially available for this. In addition, directives are necessary for vaccination programs to use only non-neurotoxic adjuvants, especially for young children and all women of child-bearing ages. Additionally, clearer directives concerning fish consumption must now be reappraised.

Human exposure to mercury is still a major public health concern. In this context, children have a higher susceptibility to adverse neurological mercury effects, compared to adults with similar exposures. Moreover, there exists a marked variability of personal response to detrimental mercury action, in particular among population groups with significant mercury exposure. New scientific evidence on genetic backgrounds has raised the issue of whether candidate susceptibility genes can make certain individuals more or less vulnerable to mercury toxicity. In this review, the aim is to evaluate a new genetic dimension and its involvement in mercury risk assessment, focusing on the important role played by relevant polymorphisms, located in attractive gene targets for mercury toxicity. Existing original articles on epidemiologic research which report a direct link between the genetic basis of personal vulnerability and different mercury repercussions on human health will be reviewed. Based on this evidence, a careful evaluation of the significant markers of susceptibility will be suggested, in order to obtain a powerful positive “feedback” to improve the quality of life. Large consortia of studies with clear phenotypic assessments will help clarify the “window of susceptibility” in the human health risks due to mercury exposure.

To the Editor:
In his Commentary [2017], Dr. Chakraborty stresses the potential hazards of low-level long-term exposure to mercury and the increase of prevalence of Alzheimer’s disease in the general population of India, a view we wholeheartedly endorse. We applaud the tenor of the piece (Chakraborty, 2017) and we have some additional points to make as well.

BACKGROUND:
Dental workers are exposed to elevated levels of elemental mercury vapor substantially above the occupational exposure standards when placing or removing mercury/silver tooth restorations and disposing of mercury waste. This results in a significant increase in occupational exposure and risk of mercury intoxication.

METHODS:
To evaluate the occupational exposure of dental workers to amalgam in four dental clinics in Baghdad city, the concentrations of mercury vapor were measured seasonally from February to November 2016. Samples of blood and urine were collected from 30 dental workers (exposed individuals) and five non-occupationally exposed individuals. Biochemical parameters such as cholesterol, liver enzymes (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase), renal enzymes (urea and creatinine), total protein and reduced glutathione (GSH) were observed.

RESULTS:
The results indicated that mercury vapor levels varied from 84.7 ± 18.67 to 609.3 ± 238.90 µg/m3 and most concentrations were above the occupational exposure standards. The results of the biochemical parameters showed a significant increase in levels of cholesterol, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and no significant increase in blood urea and creatinine in dental workers in comparison with unexposed persons (control). Although the results showed a significant reduction in the levels of glutathione and total protein, there was no significant decrease in the levels of alkaline phosphatase (ALP) in exposed dental workers when compared with non-occupationally exposed individuals.

CONCLUSIONS:
It is concluded that mercury vapor concentrations in the indoor air of some dental clinics in Baghdad city are high and exceed the OSHA STEL(Occupational Safety and Health Administration Short Term Exposure Limit). The present data showed that altered biochemical parameters can be used as efficient bioindicators for mercury toxicity.

Metallic mercury may be self-injected for suicidal or self-harm purposes or sometimes for superstitious or other inadvisable reasons. Local tissue or systemic consequences such as mercurialism can frequently occur in cases of subcutaneous or deep injection, while death due to pulmonary embolism and cardiac, brain, hepatic or renal toxicity may occur in cases of high dosage intravenous administration. The aim of this review is to focus on the diagnostic difficulties facing coroners and forensic pathologists when the courts require confirmation that evidence of self-injection of metallic mercury is the result of suicide or self-harming. Forensic examination performed on the corpses of victims who died in or out of hospital or on surviving injured or intoxicated victims showing signs of mercurialism, demands the careful evaluation of the death scene, of all related circumstances and of the clinical and autopsy data. Close interaction between forensic pathologists and toxicologists is also needed to identify and quantify mercury levels in blood, urine and tissue.

BACKGROUND:
Although mercury is an established neurotoxin, only few longitudinal studies have investigated the association between prenatal and early childhood mercury exposure and autistic behaviors.

METHODS:
We conducted a longitudinal cohort study using an ongoing prospective birth cohort initiated in 2006, wherein blood mercury levels were measured at early and late pregnancy; in cord blood; and at 2 and 3years of age. We analyzed 458 mother-child pairs. Autistic behaviors were assessed using the Social Responsiveness Scale (SRS) at 5years of age. Both continuous SRS T-scores and T-scores dichotomized by a score of ≥60 or <60 were used as outcomes.

RESULTS:
The geometric mean of mercury concentrations in cord blood was 5.52μg/L. In adjusted models, a doubling of blood mercury levels at late pregnancy (β=1.84, 95% confidence interval [CI]: 0.39, 3.29), in cord blood (β=2.24, 95% CI: 0.22, 4.27), and at 2years (β=2.12, 95% CI: 0.54, 3.70) and 3years (β=2.80, 95% CI: 0.89, 4.72) of age was positively associated with the SRS T-scores. When the SRS T-scores were dichotomized, we observed positive associations with mercury levels at late pregnancy (relative risk [RR]=1.31, 95% CI: 1.08, 1.60) and in cord blood (RR=1.28, 95% CI: 1.01, 1.63).

CONCLUSION:
We found that blood mercury levels at late pregnancy and early childhood were associated with more autistic behaviors in children at 5years of age. Further study on the long-term effects of mercury exposure is recommended.

In this study, the associations between mercury (Hg) exposure and cholesterol profiles were analyzed, and increased Hg levels and cholesterol profiles according to the amount of fish consumption were evaluated. Data on levels of blood Hg, the frequency of fish consumption, total blood cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) in 3951 adults were obtained from the Korea National Health and Nutrition Examination Survey 2010-2011 database. To compare the distribution for each log-transformed indicator, Student’s t-test and analysis of variance were carried out, and the groups were classified according to the frequency of fish consumption through linear regression analysis; the association between Hg level and cholesterol profiles in each group was analyzed. The blood Hg levels (arithmetic mean, median, and geometric mean) for all target participants were 4.59, 3.66, and 3.74 µg/L, respectively. The high cholesterol group, low HDL-C group, and high TG group showed a statistically and significantly higher blood Hg level than the low-risk group. In both sexes, as the frequency of fish consumption increased, blood Hg level also increased, but TC, HDL-C, LDL-C, and TG did not show a similar trend. Increased blood Hg level showed a significant association with increased TC and LDL-C. This statistical significance was maintained in the group with less frequent fish consumption (<4 times per month), but the group with frequent fish consumption (>8 times per month) did not show a similar trend. The results of this study suggest that fish consumption increases the level of Hg exposure, and that as the level of Hg exposure increases, the levels of cholesterol profiles increase. However, this study also suggests that the levels of cholesterol profiles in those with frequent fish consumption can be diminished.

BACKGROUND:
Conflicting evidence concerning possible harm from mercury (Hg) in regard to offspring cognition if the woman eats fish has prompted this study to examine evidence from a British pre-birth cohort to investigate the relationship between the two.

METHODS:
Pregnant women (median prenatal blood mercury 1.86μg/L) resident in the study area with delivery between April 1991 and December 1992 were followed up and verbal, performance and total intelligence quotient (IQ) of 2062 offspring were measured at age 8. Analysis treated IQ as (a) continuous and (b) the lowest 25% of the distribution. Multiple and logistic regression analyses took account of social and demographic variables. Stratification considered children of fish eaters separately.

RESULTS:
Before adjustment, mean full-scale IQ increased with increasing Hg (change with 1SD of Hg=+2.02; 95%CI+1.40,+2.64 IQ points; P <0.0001); after adjustment effect size was reduced although still positive (+0.61;95%CI -0.06,+1.29 IQ points; P=0.073). The adjusted positive relationship was stronger when fish-eating mothers were considered separately (+0.84:95%CI +0.13,+1.56 IQ points; P=0.021) in comparison with the outcomes for non-fish eaters, where the adjusted relationship was negative (-2.22;95%CI -5.00,+0.56 IQ points; P=0.117). The binary outcome showed a similar pattern with the adjusted OR for non-fish-eaters 1.79 (95%CI 1.10,2.93; P=0.019) per SD of Hg, significantly different from that for fish consumers (0.94;95%CI:0.82,1.08)(Pinteraction<0.05). There were no differences between the sexes in the associations, nor did the level of the mother’s blood selenium change the effect sizes.

CONCLUSION:
The relationship between intrauterine exposure to mercury and offspring IQ appears to be benign provided the mother consumes fish.

India is an industrial giant with one of the fastest growing major economies in the world. Primary energy consumption in India is third after China and the USA. Greater energy production brings the burden of increasing emissions of mercury (Hg). India ranks second for Hg emissions. Rising atmospheric Hg release, high Hg evasion processes, and increasing monomethylmercury (highly neurotoxin) accumulations in marine food products increase the potential for human and ecosystem Hg exposure. Hg has been identified to increase the risk of getting Alzheimer’s disease (AD). There are increasing reports of AD and dementia in different age groups in India. The relationship between increasing Hg exposure and increasing neurodegenerative disorder in India is not known. This commentary points to the need for better understanding of the relationship between Hg release and AD in India, and other countries, and how to protect human health and the environment from the adverse effects of Hg.

Prenatal exposure to mercury, a known neurotoxic metal, is associated with lower cognitive performance during childhood. Disruption of fetal epigenetic programming could explain mercury’s neurodevelopmental effects. We screened for epigenome-wide methylation differences associated with maternal prenatal blood mercury levels in 321 cord blood DNA samples and examined the persistence of these alterations during early (n = 75; 2.9-4.9 years) and mid-childhood (n = 291; 6.7-10.5 years). Among males, prenatal mercury levels were associated with lower regional cord blood DNA methylation at the Paraoxonase 1 gene (PON1) that persisted in early childhood and was attenuated in mid-childhood blood. Cord blood methylation at the PON1 locus predicted lower cognitive test scores measured during early childhood. Methylation at the PON1 locus was associated with PON1 expression in an independent set of cord blood samples. The observed persistent epigenetic disruption of the PON1 gene may modulate mercury toxicity in humans and might serve as a biomarker of exposure and disease susceptibility.