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Mercury poisoning still occurs as a result of accidental and occupational exposure. For the general population, however, the main concern is the possible adverse effect of exposure to mercury through fish consumption and the receipt of dental amalgams and thimerosal, a preservative used in vaccines. This review summarizes both the facts and the controversies surrounding exposure to methyl mercury, mercury vapor, and the ethyl mercury in thimerosal. Mercury has been used commercially and medically for centuries. In the past it was a common constituent of many medications. It is still used in hospitals in thermometers and blood-pressure cuffs and commercially in batteries, switches, and fluorescent light bulbs. Large quantities of metallic mercury are employed as electrodes in the electrolytic production of chlorine and sodium hydroxide from saline. These uses still give rise to accidental and occupational exposures. 1 Today, however, exposure of the general population comes from three major sources: fish consumption, dental amalgams, and vaccines. Each has its own characteristic form of mercury and distinctive toxicologic profile . . .

Samples of fresh and fixed tissues from infants with exomphalos treated by thiomersal application were analysed for mercury content. The results showed that thiomersal can induce blood and organ levels of organic mercury which are well in excess of the minimum toxic level in adults and fetuses. The analysis of fresh and fixed tissues must be carefully controlled against normal tissues in order to interpret mercury levels accurately.

This review covers the toxicology of mercury and its compounds. Special attention is paid to those forms of mercury of current public health concern. Human exposure to the vapor of metallic mercury dates back to antiquity but continues today in occupational settings and from dental amalgam. Health risks from methylmercury in edible tissues of fish have been the subject of several large epidemiological investigations and continue to be the subject of intense debate. Ethylmercury in the form of a preservative, thimerosal, added to certain vaccines, is the most recent form of mercury that has become a public health concern. The review leads to general discussion of evolutionary aspects of mercury, protective and toxic mechanisms, and ends on a note that mercury is still an \"element of mystery.\"

Although the molecular mechanisms underlying methylmercury toxicity are not entirely understood, the observed neurotoxicity in early-life is attributed to the covalent binding of methylmercury to sulfhydryl (thiol) groups of proteins and other molecules being able to affect protein post-translational modifications from numerous molecular pathways, such as glutamate signaling, heat-shock chaperones and the antioxidant glutaredoxin/glutathione system. However, for other organomercurials such as ethylmercury or thimerosal, there is not much information available. Therefore, this review critically discusses current knowledge about organomercurials neurotoxicity—both methylmercury and ethylmercury—following intrauterine and childhood exposure, as well as the prospects and future needs for research in this area. Contrasting with the amount of epidemiological evidence available for methylmercury, there are only a few in vivo studies reporting neurotoxic outcomes and mechanisms of toxicity for ethylmercury or thimerosal. There is also a lack of studies on mechanistic approaches to better investigate the pathways involved in the potential neurotoxicity caused by both organomercurials. More impactful follow-up studies, especially following intrauterine and childhood exposure to ethylmercury, are necessary. Childhood vaccination is critically important for controlling infectious diseases; however, the safety of mercury-containing thimerosal and, notably, its effectiveness as preservative in vaccines are still under debate regarding its potential dose-response effects to the central nervous system.

The controversy regarding the once widely used mercury-containing preservative thimerosal in childhood vaccines has raised many historical questions that have not been adequately explored. Why was this preservative incorporated in the first place? Was there any real evidence that it caused harm? And how did thimerosal become linked in the public mind to the “autism epidemic”? I examine the origins of the thimerosal controversy and their legacy for the debate that has followed. More specifically, I explore the parallel histories of three factors that converged to create the crisis: vaccine preservatives, mercury poisoning, and autism. An understanding of this history provides important lessons for physicians and policymakers seeking to preserve the public’s trust in the nation’s vaccine system.

Vaccines containing thiomersal as a preservative, such as diphtheria, tetanus, and pertussis vaccine and influenza vaccine, were excluded from the list of banned products in the Convention, partly in light of the extensive studies supporting the safety of minute amounts (<50 ?g per dose) of thiomersal,10 but also because of the population-level risks of removing thiomersal.11 Removing thiomersal from vaccines would have serious repercussions for the global supply of vaccines--particularly for resource-poor countries.12 Replacing the present multidose vaccine vials that need the preservative with single dose vials that do not is estimated to increase costs from 200% to more than 500%.11 Additionally, the increased number of vials would need expanded cold-chain capacity and would create far more waste.

On July 9, 1999, the CDC and the American Academy of Pediatrics asked pharmaceutical companies to remove thimerosal from vaccines. Dr. Paul Offit writes that the alarm caused by the removal of thimerosal from vaccines has been quite harmful. In 1997, Frank Pallone, a U.S. congressman from New Jersey, attached a simple, 133-word amendment to a Food and Drug Administration (FDA) reauthorization bill. This amendment gave the FDA 2 years to “compile a list of drugs and foods that contain intentionally introduced mercury compounds and [to] provide a quantitative and qualitative analysis of the mercury compounds in the list.” 1 The bill — the FDA Modernization Act of 1997 — was signed into law on November 21, 1997. Neither the press nor the public took notice. Eighteen months later, in May 1999, the FDA found that by 6 months of . . .

Beside partial coverage in three reviews so far (1994, 2009, 2019), there is no review on genotoxic studies dealing with mercury (Hg) and human exposure using the most usual genotoxic assays: sister chromatid exchanges (SCE), chromosomal aberrations (CA), cytochalasin B blocked micronucleus assay (CBMN), and single-cell gel electrophoresis (SCGE or alkaline comet assay). Fifty years from the first Hg genotoxicity study and with the Minamata Convention in force, the genotoxic potential of Hg and its derivatives is still controversial. Considering these antecedents, we present this first systematic literature overview of genotoxic studies dealing with Hg and human exposure that used the standard genotoxic assays. To date, there is not sufficient evidence for Hg human carcinogen classification, so the new data collections can be of great help. A review was made of the studies available (those published before the end of October 2021 on PubMed or Web of Science in English or Spanish language) in the scientific literature dealing with genotoxic assays and human sample exposure ex vivo, in vivo, and in vitro. Results from a total of 66 articles selected are presented. Organic (o)Hg compounds were more toxic than inorganic and/or elemental ones, without ruling out that all represent a risk. The most studied inorganic (i)Hg compounds in populations exposed accidentally, occupationally, or iatrogenically, and/or in human cells, were Hg chloride and Hg nitrate and of the organic compounds, were methylmercury, thimerosal, methylmercury chloride, phenylmercuric acetate, and methylmercury hydroxide.