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Mercury (Hg) toxicity continues to represent a global health concern. Given that human populations are mostly exposed to low chronic levels of mercurial compounds (methylmercury through fish, mercury vapor from dental amalgams, and ethylmercury from vaccines), the need for more sensitive and refined tools to assess the effects and/or susceptibility to adverse metal-mediated health risks remains. Traditional biomarkers, such as hair or blood Hg levels, are practical and provide a reliable measure of exposure, but given intra-population variability, it is difficult to establish accurate cause-effect relationships. It is therefore important to identify and validate biomarkers that are predictive of early adverse effects prior to adverse health outcomes becoming irreversible. This review describes the predominant biomarkers used by toxicologists and epidemiologists to evaluate exposure, effect and susceptibility to Hg compounds, weighing on their advantages and disadvantages. Most importantly, and in light of recent findings on the molecular mechanisms underlying Hg-mediated toxicity, potential novel biomarkers that might be predictive of toxic effect are presented, and the applicability of these parameters in risk assessment is examined.

Common technological devices (e.g., mobile phones, mobile base stations, and magnetic resonance imaging machines and other wireless devices) produce electromagnetic fields (EMFs). Neurobehavioral and neurodevelopmental symptoms such as retarded memory, learning, cognition, and attention have been attributed to EMF exposure.[4] Of note, these symptoms are also attributed to ASD and attention deficit hyperactivity disorders. A recent in vivo study observed autism-relevant social abnormalities in mice exposed to extremely low-frequency EMFs during perinatal development.[5] This may indicate a potential direct link between EMFs and the prevalence of autism in specific window/s of vulnerability that would deserve further investigation. An indirect link might be also plausible since high-field magnetic resonance and microwave radiation emitted by common mobile phones have been reported to increase the release of mercury from dental amalgam fillings.[6,7] These recent evidence (2014), far from being conflictive, is consistent with our previous cumulative Hg exposure-based hypothesis of ASD (2011) and could be included as the fifth (v) additional environmental factor, synergistically contributing to the release of Hg in mothers with dental amalgam fillings, and increasing the probability of developing and/or aggravating autism among children. Nevertheless, this updated version of our hypothesis would require more extensive clinical confirmation and supporting evidence.

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.