Mercury

“Here, we investigated thiol-redox-mediated phospholipase D (PLD) signaling as a mechanism of mercury cytotoxicity in mouse aortic endothelial cell (MAEC) in vitro model utilizing the novel lipid-soluble thiol-redox antioxidant and heavy metal chelator, N,N’-bis(2-mercaptoethyl)isophthalamide (NBMI) and the novel PLD-specific inhibitor, 5-fluoro-2-indolyl des-chlorohalopemide (FIPI). Our results demonstrated (i) mercury in the form of mercury(II) chloride, methylmercury, and thimerosal induced PLD activation in a dose- and time-dependent manner; (ii) NBMI and FIPI completely attenuated mercury- and oxidant-induced PLD activation; (iii) mercury induced upstream phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2) leading to downstream threonine phosphorylation of PLD(1) which was attenuated by NBMI; (iv) mercury caused loss of intracellular glutathione which was restored by NBMI; and (v) NBMI and FIPI attenuated mercury- and oxidant-induced cytotoxicity in MAECs. For the first time, this study demonstrated that redox-dependent and PLD-mediated bioactive lipid signaling was involved in mercury-induced vascular EC cytotoxicity which was protected by NBMI and FIPI.”

“The risks and benefits of using mercury (Hg) in dental amalgam have long been debated. This study was designed to estimate Hg body burden and its association with dental amalgam fillings in 182 children (ages: 5-15 years) living in Taif City. Hg was measured in urine (UHg), hair (HHg) and toenails (NHg) by the Atomic Absorption Spectrophotometer with Vapor Generator Accessory system. Urinary Hg levels were calculated as both micrograms per gram creatinine (µg/g creatinine) and micrograms per liter (µg/L). We found that children with amalgam fillings (N=106) had significantly higher UHg-C levels than children without (N=76), with means of 3.763 µg/g creatinine versus 3.457 µg/g creatinine, respectively (P=0.019). The results were similar for UHg (P=0.01). A similar pattern was also seen for HHg, with means of 0.614 µg/g (N=97) for children with amalgam versus 0.242 µg/g (N=74) for those without amalgam fillings (P=0). Although the mean NHg was higher in children without amalgam (0.222 µg/g, N=61) versus those with (0.163 µg/g, N=101), the relationship was not significant (P=0.069). After adjusting for many confounders, the multiple logistic regression model revealed that the levels of UHg-C and HHg were 2.047 and 5.396 times higher, respectively, in children with dental amalgam compared to those without (P<0.01). In contrast, a significant inverse relationship was seen between NHg levels and dental amalgam fillings (P=0.003). Despite the controversy surrounding the health impact of dental amalgam, this study showed some evidence that amalgam-associated Hg exposure might be related with symptoms of oral health, such as aphthous ulcer, white patches, and a burning-mouth sensation. Further studies are needed to reproduce these findings. The present study showed that significant numbers of children with or without amalgam had Hg levels exceeding the acceptable reference limits. The detrimental neurobehavioral and/or nephrotoxic effects of such an increased Hg on children should be a cause of concern, and further investigation is warranted. Our results are alarming and indicate an urgent need for biomonitoring and assessment of exposure. Changes in dental practices involving amalgam, especially for children, are highly recommended in order to avoid unnecessary exposure to Hg.”

“INTRODUCTION:

It is well-known that prenatal or postnatal exposure to methylmercury can produce neurological signs in adults and children, exemplified by a case of large-scale poisoning in Minamata, Japan, in the 1950s. However, evidence regarding whether pre- or postnatal exposure to methylmercury causes psychiatric symptoms (e.g., impairment of intelligence and mood and behavioral dysfunction) is still limited-excluding cases of fetal Minamata disease patients.

METHODS:

We evaluated the effects of pre- or postnatal exposure to methylmercury on psychiatric symptoms using data derived from a 1971 population-based survey in Minamata and neighboring communities. We adopted residential areas as an exposure indicator and psychiatric symptoms as the outcome. Then, we estimated the adjusted prevalence odds ratio (POR) and confidence interval (CI) of psychiatric symptoms in relation to residential area.

RESULTS:

There were 904 participants in Minamata (high exposure area), 1700 in Goshonoura (middle exposure area), and 913 in Ariake (low exposure area). Compared to the Ariake area, participants in the Minamata area manifested psychiatric symptoms more frequently: PORs for impairment of intelligence and mood and behavioral dysfunction were 5.2 (95% CI: 3.7-7.3) and 4.4 (95% CI: 2.9-6.7), respectively. Furthermore, participants with psychiatric symptoms in the Minamata area more frequently had neurological signs. Peaks in prevalence of psychiatric symptoms occurred around age 20 and in older age adults in the area. These findings did not change when we excluded those who had been officially certified as Minamata disease patients by that time.

CONCLUSIONS:

The present study suggests a relationship between pre- or postnatal exposure to methylmercury and psychiatric symptoms among the general population in Minamata even after excluding officially certified patients.”

“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 ?(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 ?g/m(3). Likewise, the urinary concentration of mercury in dentists was estimated to be 3.16 ?g/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.”

“The neurotoxic organomercurial thimerosal (THIM), used for decades as vaccine preservative, is a suspected factor in the pathogenesis of some neurodevelopmental disorders. Previously we showed that neonatal administration of THIM at doses equivalent to those used in infant vaccines or higher, causes lasting alterations in the brain opioid system in rats. Here we investigated neonatal treatment with THIM (at doses 12, 240, 1440 and 3000 ?g Hg/kg) on behaviors, which are characteristically altered in autism, such as locomotor activity, anxiety, social interactions, spatial learning, and on the brain dopaminergic system in Wistar rats of both sexes. Adult male and female rats, which were exposed to the entire range of THIM doses during the early postnatal life, manifested impairments of locomotor activity and increased anxiety/neophobia in the open field test. In animals of both sexes treated with the highest THIM dose, the frequency of prosocial interactions was reduced, while the frequency of asocial/antisocial interactions was increased in males, but decreased in females. Neonatal THIM treatment did not significantly affect spatial learning and memory. THIM-exposed rats also manifested reduced haloperidol-induced catalepsy, accompanied by a marked decline in the density of striatal D? receptors, measured by immunohistochemical staining, suggesting alterations to the brain dopaminergic system. Males were more sensitive than females to some neurodisruptive/neurotoxic actions of THIM. These data document that early postnatal THIM administration causes lasting neurobehavioral impairments and neurochemical alterations in the brain, dependent on dose and sex. If similar changes occur in THIM/mercurial-exposed children, they could contribute do neurodevelopmental disorders.”

“Recent studies suggest that genetic polymorphisms may influence inter-individual differences observed in toxicokinetics of mercury (Hg), a potent toxicant of concern to the general population and occupationally exposed workers (e.g., dentists). This work hypothesized that polymorphisms in glutathione pathway and selenoprotein genes would associate with Hg biomarker levels, modify the impact of Hg on blood pressure, and alter enzyme activity of encoded proteins. We utilized a multi-dimensional approach by considering two forms of Hg (methylmercury from fish consumption; elemental Hg from dental amalgams) through measurement in biomarkers and 23 polymorphisms in two populations- the Michigan Dental Association cohort (MDA, n=511) and the Early Life Exposures in Mexico to Environmental Toxicants cohort (ELEMENT, n=353 mothers, 368 children).”

“It was claimed by the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) in a report to the EU-Commission that ‘….no risks of adverse systemic effects exist and the current use of dental amalgam does not pose a risk of systemic disease…’ [1, available from: http://ec.europa.eu/health/ph_risk/committees/04_scenihr/docs/scenihr_o_016.pdf]. SCENIHR disregarded the toxicology of mercury and did not include most important scientific studies in their review. But the real scientific data show that:(a) Dental amalgam is by far the main source of human total mercury body burden. This is proven by autopsy studies which found 2-12 times more mercury in body tissues of individuals with dental amalgam. Autopsy studies are the most valuable and most important studies for examining the amalgam-caused mercury body burden.(b) These autopsy studies have shown consistently that many individuals with amalgam have toxic levels of mercury in their brains or kidneys.(c) There is no correlation between mercury levels in blood or urine, and the levels in body tissues or the severity of clinical symptoms. SCENIHR only relied on levels in urine or blood.(d) The half-life of mercury in the brain can last from several years to decades, thus mercury accumulates over time of amalgam exposure in body tissues to toxic levels. However, SCENIHR state that the half-life of mercury in the body is only ’20-90 days’.(e) Mercury vapor is about ten times more toxic than lead on human neurons and with synergistic toxicity to other metals.(f) Most studies cited by SCENIHR which conclude that amalgam fillings are safe have severe methodical flaws.”

“Even though neuronal toxicity due to organomercury compounds is well known, thimerosal, an organomercury compound, is widely used in pediatric vaccine preservation. In the present study, we examined whether embryonic exposure to thimerosal affects early development of serotonergic neurons. Thimerosal (1mg Hg/kg) was intramuscularly administered to pregnant rats on gestational day 9 (susceptible time window for development of fetal serotonergic system), and fetal serotonergic neurons were assessed at embryonic day 15 using anti-serotonin antibodies. A dramatic increase in the number of serotonergic neurons localized to the lateral portion of the caudal raphe was observed in thimerosal group (1.9-fold increase, p<0.01 compared to control). These results indicate that embryonic exposure to thimerosal affects early development of serotonergic neurons.”

“Dental amalgam is 50% metallic mercury (Hg) by weight and Hg vapour continuously evolves from in-place dental amalgam, causing increased Hg content with increasing amalgam load in urine, faeces, exhaled breath, saliva, blood, and various organs and tissues including the kidney, pituitary gland, liver, and brain. The Hg content also increases with maternal amalgam load in amniotic fluid, placenta, cord blood, meconium, various foetal tissues including liver, kidney and brain, in colostrum and breast milk. Based on 2001 to 2004 population statistics, 181.1 million Americans carry a grand total of 1.46 billion restored teeth. Children as young as 26 months were recorded as having restored teeth. Past dental practice and recently available data indicate that the majority of these restorations are composed of dental amalgam. Employing recent US population-based statistics on body weight and the frequency of dentally restored tooth surfaces, and recent research on the incremental increase in urinary Hg concentration per amalgam-filled tooth surface, estimates of Hg exposure from amalgam fillings were determined for 5 age groups of the US population. Three specific exposure scenarios were considered, each scenario incrementally reducing the number of tooth surfaces assumed to be restored with amalgam. Based on the least conservative of the scenarios evaluated, it was estimated that some 67.2 million Americans would exceed the Hg dose associated with the reference exposure level (REL) of 0.3 µg/m(3) established by the US Environmental Protection Agency; and 122.3 million Americans would exceed the dose associated with the REL of 0.03 µg/m(3) established by the California Environmental Protection Agency. Exposure estimates are consistent with previous estimates presented by Health Canada in 1995, and amount to 0.2 to 0.4 µg/day per amalgam-filled tooth surface, or 0.5 to 1 µg/day/amalgam-filled tooth, depending on age and other factors.”