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."

The Toxicology of Mercury and Its Chemical Compounds

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(06)69665-7.pdf

Developmental neurotoxicity of industrial chemicals

The paper builds on existing literature, highlighting current understanding and identifying unresolved issues about MeHg exposure, health effects, and risk assessment, and concludes with a consensus statement. Methylmercury is a potent toxin, bioaccumulated and concentrated through the aquatic food chain, placing at risk people, throughout the globe and across the socioeconomic spectrum, who consume predatory fish or for whom fish is a dietary mainstay. Methylmercury developmental neurotoxicity has constituted the basis for risk assessments and public health policies. Despite gaps in our knowledge on new bioindicators of exposure, factors that influence MeHg uptake and toxicity, toxicokinetics, neurologic and cardiovascular effects in adult populations, and the nutritional benefits and risks from the large number of marine and freshwater fish and fish-eating species, the panel concluded that to preserve human health, all efforts need to be made to reduce and eliminate sources of exposure.

Methylmercury exposure and health effects in humans: a worldwide concern.

Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults.

The balance of contaminant risk and nutritional benefit from maternal prenatal fish consumption for child cognitive development is not known. Using data from a prospective cohort study of 341 mother-child pairs in Massachusetts enrolled in 1999-2002, the authors studied associations of maternal second-trimester fish intake and erythrocyte mercury levels with children's scores on the Peabody Picture Vocabulary Test (PPVT) and Wide Range Assessment of Visual Motor Abilities (WRAVMA) at age 3 years. Mean maternal total fish intake was 1.5 (standard deviation, 1.4) servings/week, and 40 (12%) mothers consumed >2 servings/week. Mean maternal mercury level was 3.8 (standard deviation, 3.8) ng/g. After adjustment using multivariable linear regression, higher fish intake was associated with better child cognitive test performance, and higher mercury levels with poorer test scores. Associations strengthened with inclusion of both fish and mercury: effect estimates for fish intake of >2 servings/week versus never were 2.2 (95% confidence interval (CI): -2.6, 7.0) for the PPVT and 6.4 (95% CI: 2.0, 10.8) for the WRAVMA; for mercury in the top decile, they were -4.5 (95% CI: -8.5, -0.4) for the PPVT and -4.6 (95% CI: -8.3, -0.9) for the WRAVMA. Fish consumption of < or =2 servings/week was not associated with a benefit. Dietary recommendations for pregnant women should incorporate the nutritional benefits as well as the risks of fish intake.

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Maternal fish intake during pregnancy, blood mercury levels, and child cognition at age 3 years in a US cohort.

Maternal fish consumption brings both risks and benefits to the fetus from the standpoint of methylmercury (MeHg) and n-3 PUFA (polyunsaturated fatty acids). MeHg is one of the most risky substances to come through fish consumption, and mercury concentrations in red blood cells (RBC-Hg) are the best biomarker of MeHg exposure. Docosahexaenoic acid (DHA, C22:6n-3), which is one of the most important fatty acids for normal brain development and function, is also derived from fish consumption. Our objective in this study was to examine the relationships between RBC-Hg and plasma fatty acid composition in mother and fetus at parturition. Venous blood samples were collected from 63 pairs of mothers and fetuses (umbilical cord blood) at delivery. In all cases, fetal RBC-Hg levels were higher than maternal RBC-Hg levels. The geometric mean of fetal RBC-Hg was 13.4 ng/g, which was significantly (p < 0.01) higher than that of maternal RBC-Hg (8.41 ng/g). While the average fetal/maternal RBC-Hg ratio was 1.6, the individual ratios varied from 1.08 to 2.19, suggesting considerable individual differences in MeHg concentrations between maternal and fetal circulations at delivery. A significant correlation was observed between maternal and fetal DHA concentrations (r = 0.37, p < 0.01). Further, a significant correlation was observed between RBC-Hg and plasma DHA in fetus (r = 0.35, p < 0.01). These results confirm that both MeHg and DHA which originated from fish consumption transferred from maternal to fetal circulation and existed in the fetal circulation with a positive correlation. Pregnant women in particular need not give up eating fish to obtain such benefits. However, they would do well to at least consume smaller fish, which contain less MeHg, thereby balancing the risks and benefits from fish comsumption.

Maternal and fetal mercury and n-3 polyunsaturated fatty acids as a risk and benefit of fish consumption to fetus.

Objectives: A cross-sectional study was carried out to assess the effects of methylmercury exposure on neurodevelopment in Japanese children, in relation to the Madeiran cross-sectional study, and to estimate benchmark dose (BMD) levels using the data of two studies. Methods: Mercury levels in hair samples obtained from 327 Japanese mothers and their 7-year-old children, and methylmercury levels in the umbilical cord, were determined. Neurodevelopmental examinations, including the brainstem auditory evoked potential (BAEP), were performed on the children. Results: The medians of hair mercury were 1.63 (0.11–6.86) μg/g for mothers and 1.65 (0.35–6.32) μg/g for children, and a significant correlation was seen between the hair mercury levels in mothers and children. The maternal hair mercury was significantly correlated with the methylmercury in the umbilical cords obtained from 49 children. In 210 children whose mothers had not changed their dietary habits since pregnancy, most of the neurodevelopmental variables were not significantly related to hair mercury levels. The BAEP latencies were significantly shorter in the Japanese children than in the 113 Madeiran 7-year-old children, whose mothers had hair mercury of 1.12–54.5 (median 10.9) μg/g. Significant relationships between the maternal hair mercury level and BAEP latencies (peaks III and V, and interpeak I–III) were found only in the merged data of Japanese and Madeiran children. When the lower 95% confidence limit of BMD (BMDL) was calculated, the BMDLs of mercury exposure for BAEP latencies in the merged data were between 6.9 and 10.5 μg/g, and lower than those in the Madeiran children. Conclusions: It is suggested that Japanese children may ingest similar doses per body weight of methylmercury to their mothers. If maternal hair mercury was used as a proxy for mercury exposure at birth, no significant dose–effect associations with the BAEP latencies were observed in Japanese children with exposure levels below 6.9 μg/g of hair mercury, but only when higher-level exposures from Madeiran children were included. The BMDL was lower for the merged data than for Madeiran children alone.

Effects of methylmercury on neurodevelopment in Japanese children in relation to the Madeiran study.

Objectives: The subclinical effects of prenatal exposure to methylmercury from fish consumption on the cardiac autonomic function were assessed in 136 Japanese 7-year-old children recruited for this study. Methods: Samples of child’s hair and dry umbilical cord preserved were collected, and hair mercury and cord tissue methylmercury concentrations were determined as current and prenatal exposure biomarkers, respectively. Cardiac autonomic indicators of parasympathetic and sympathetic activities were calculated from the electrocardiographic RR intervals measured. Results: In the children, the cord tissue methylmercury (0.017–0.367, median 0.089 μg/g) was not significantly correlated with the hair mercury (0.43–6.32, median 1.66 μg/g). The cord tissue methylmercury was related negatively to parasympathetic components of cardiac autonomic indicators (P<0.05) and positively to sympathovagal indices (P<0.05), even after correction for possible confounders such as age and sex, although the hair mercury was not significantly correlated with any cardiac autonomic indicators. Conclusions: Despite the potential limitations involved in the retrospective study, these findings suggest that prenatal methylmercury exposure (median of estimated maternal hair mercury at parturition, 2.24 μg/g) may be associated with reduced parasympathetic activity and/or sympathovagal shift.

Subclinical effects of prenatal methylmercury exposure on cardiac autonomic function in Japanese children

Objectives
Exposure misclassification is a major obstacle to obtain accurate dose-response relationships. In order to solve this problem, the impact of hair treatment on total mercury in hair was assessed in Japanese women.

Xiao Jie Liu

Papers

Maternal and fetal mercury and n-3 polyunsaturated fatty acids as a risk and benefit of fish consumption to fetus.

Effects of methylmercury on neurodevelopment in Japanese children in relation to the Madeiran study.

Subclinical effects of prenatal methylmercury exposure on cardiac autonomic function in Japanese children

Effects of Hair Treatment on Hair Mercury-The Best Biomarker of Methylmercury Exposure?