Nutrition and neurodevelopment: the search for candidate nutrients in the Seychelles Child Development Nutrition Study.

This review examines the role of nutrients in child development and outlines the key nutrients identified as potentially important to neurodevelopment among high fish consumers in the Seychelles Child Development Nutrition Study (SCDNS). It describes the clinical assessment of these nutrients in the blood and breast milk samples collected from the cohort of 300 pregnant women who were recruited, at their first antenatal visit, on the SCDNS. These key nutrients include the long chain polyunsaturated fatty acids (LCPUFA), docosohexaenoic acid (DHA) and arachidonic acid (AA), both of which may affect neurodevelopment in the later stages of fetal growth. Only DHA, however, is strongly associated with fish consumption, the predominant source of the neurotoxicant methyl mercury (MeHg). Any benefits of increased selenium status on neurodevelopment are likely to accrue via detoxification of MeHg during fetal growth, while benefits of optimal iodine or thyroid status are likely to be directly related to neurodevelopment during late fetal growth. Unlike LCPUFA, Se, and I, the status of the B vitamins, folate, vitamin B12, vitamin B6, and riboflavin are unlikely to be closely related to fish consumption but the status of each of these B vitamins is likely to impinge on overall status of choline, which is expected to have direct effects on neurodevelopment both prenatally and postnatally and may also impact on MeHg toxicity. Choline status, together with the status of two other candidate nutrients, zinc and copper, which are also likely to have effects on neurodevelopment prenatally and postnatally, are expected to have some correlation with fish consumption.

Maternal PUFA status but not prenatal methylmercury exposure is associated with children's language functions at age five years in the Seychelles.

Evidence from the Seychelles Child Development Nutrition Study suggests that maternal nutritional status can modulate the relationship between prenatal methylmercury (MeHg) exposure and developmental outcomes in children. The aim of this study was to investigate whether maternal PUFA status was a confounding factor in any possible associations between prenatal MeHg exposure and developmental outcomes at 5 y of age in the Republic of Seychelles. Maternal status of (n-3) and (n-6) PUFA were measured in serum collected at 28 wk gestation and delivery. Prenatal MeHg exposure was determined in maternal hair collected at delivery. At 5 y of age, the children completed a comprehensive range of sensitive developmental assessments. Complete data from 225 mothers and their children were available for analysis. Multiple linear regression analyses revealed Preschool Language Scale scores of the children improved with increasing maternal serum DHA [22:6(n-3)] concentrations and decreased with increasing arachidonic acid [20:4(n-6)] concentrations, albeit verbal intelligence improved with increasing (n-6) PUFA concentrations in maternal serum. There were no adverse associations between MeHg exposure and developmental outcomes. These findings suggest that higher fish consumption, resulting in higher maternal (n-3) PUFA status, during pregnancy is associated with beneficial developmental effects rather than detrimental effects resulting from the higher concomitant exposures of the fetus to MeHg. The association of maternal (n-3) PUFA status with improved child language development may partially explain the authors' previous finding of improving language scores, as prenatal MeHg exposure increased in an earlier mother-child cohort in the Seychelles where maternal PUFA status was not measured.

Intakes and adequacy of potentially important nutrients for cognitive development among 5-year-old children in the Seychelles Child Development and Nutrition Study.

OBJECTIVE: To assess the nutritional adequacy of Seychellois children in relation to nutrients reported to be important for cognitive development. DESIGN: Dietary intakes were assessed by 4 d weighed food diaries and analysed using dietary analysis software (WISP version 3·0; Tinuviel Software, UK). Individual nutrient intakes were adjusted to usual intakes and, in order to investigate adequacy, were compared with the UK Estimated Average Requirements for children aged 4-6 years. SETTING: Children 5 years old were followed up as part of the Seychelles Child Development Nutrition Study (SCDNS), located in the high-fish-consuming population of Mahé, Republic of Seychelles. SUBJECTS: Analysis was carried out on a sample of 229 children (118 boys, 111 girls). RESULTS: Children consumed a diet of which fortified cereal and milk products contributed the most to nutrient intakes. The majority (≥80 %) of children met requirements for several nutrients important for child development including Fe, folate and Se. Adjusted dietary intakes of Cu, Zn, iodine, niacin and vitamin A were below the Estimated Average Requirement or Recommended Nutrient Intake. Mean adjusted energy intakes (boys 4769 kJ/d (1139·84 kcal/d), girls 4759 kJ/d (1137·43 kcal/d)) were lower than the estimated energy requirement (boys 5104 kJ/d (1220 kcal/d), girls 5042 kJ/d (1205 kcal/d)) for 88 % of boys and 86 % of girls. CONCLUSIONS: Nutrition was adequate for most children within the SCDNS cohort. Low intakes of some nutrients (including Zn, niacin and vitamin A) could reflect nutritional database inaccuracies, but may require further investigation. The study provides valuable information on the adequacy of intakes of nutrients which could affect the growth and development of Seychellois children.

Prenatal exposure to dental amalgam: evidence from the Seychelles Child Development Study main cohort.

BACKGROUND: Dental amalgams contain approximately 50 percent metallic mercury and emit mercury vapor during the life of the restoration. Controversy surrounds whether fetal exposure to mercury vapor resulting from maternal dental amalgam restorations has neurodevelopmental consequences. METHODS: The authors determined maternal amalgam restoration status during gestation (prenatal exposure to mercury vapor [Hg(0)]) retrospectively in 587 mother-child pairs enrolled in the Seychelles Child Development Study, a prospective longitudinal cohort study of the effects of prenatal and recent postnatal methylmercury (MeHg) exposure on neurodevelopment. They examined covariate-adjusted associations between prenatal maternal amalgam restoration status and the results of six age-appropriate neurodevelopmental tests administered at age 66 months. The authors fit the models without and with adjustment for prenatal and recent postnatal MeHg exposure metrics. RESULTS: The mean number of maternal amalgam restorations present during gestation was 5.1 surfaces (range, 1-22) in the 42.4 percent of mothers who had amalgam restorations. The authors found no significant adverse associations between the number of amalgam surfaces present during gestation and any of the six outcomes, with or without adjustment for prenatal and postnatal MeHg exposure. Results of analyses with the secondary metric, prenatal amalgam occlusal point scores, showed an adverse association in boys only on a letter- and word-identification subtest of a frequently used test of scholastic achievement, whereas girls scored better on several other tests with increasing exposure. CONCLUSIONS: This study's results provide no support for the hypothesis that prenatal Hg(0) exposure arising from maternal dental amalgam restorations results in neurobehavioral consequences in the child. These findings require confirmation from a prospective study of coexposure to MeHg and Hg(0).

Fish consumption and prenatal methylmercury exposure: cognitive and behavioral outcomes in the main cohort at 17 years from the Seychelles child development study.

INTRODUCTION: People worldwide depend upon daily fish consumption as a major source of protein and other nutrients. Fish are high in nutrients essential for normal brain development, but they also contain methylmercury (MeHg), a neurotoxicant. Our studies in a population consuming fish daily have indicated no consistent pattern of adverse associations between prenatal MeHg and children's development. For some endpoints we found performance improved with increasing prenatal exposure to MeHg. Follow up studies indicate this association is related to the beneficial nutrients present in fish. OBJECTIVES: To determine if the absence of adverse outcomes and the presence of beneficial associations between prenatal MeHg and developmental outcomes previously reported persists into adolescence. METHODS: This study was conducted on the Main Cohort of the Seychelles Child Development Study (SCDS). We examined the association between prenatal MeHg exposure and subjects' performance at 17 years of age on 27 endpoints. The test battery included the Wisconsin Card Sorting Test (WCST), the California Verbal Learning Test (CVLT), the Woodcock-Johnson (W-J-II) Achievement Test, subtests of the Cambridge Neuropsychological Test Automated Battery (CANTAB), and measures of problematic behaviors. Analyses for all endpoints were adjusted for postnatal MeHg, sex, socioeconomic status, maternal IQ, and child's age at testing and the child's IQ was added for problematic behavioral endpoints. RESULTS: Mean prenatal MeHg exposure was 6.9 ppm. There was no association between prenatal MeHg and 21 endpoints. Increasing prenatal MeHg was associated with better scores on four endpoints (higher W-J-II math calculation scores, reduced numbers of trials on the Intra-Extradimensional Shift Set of the CANTAB), fewer reports of substance use and incidents of and referrals for problematic behaviors in school. Increasing prenatal MeHg was adversely associated with one level of referrals to a school counselor. CONCLUSIONS: At age 17 years there was no consistent pattern of adverse associations present between prenatal MeHg exposure and detailed domain specific neurocognitive and behavioral testing. There continues to be evidence of improved performance on some endpoints as prenatal MeHg exposure increases in the range studied, a finding that appears to reflect the role of beneficial nutrients present in fish as demonstrated previously in younger subjects. These findings suggest that ocean fish consumption during pregnancy is important for the health and development of children and that the benefits are long lasting.

Varying coefficient function models to explore interactions between maternal nutritional status and prenatal methylmercury toxicity in the Seychelles Child Development Nutrition Study.

Maternal consumption of fish during the gestational period exposes the fetus to both nutrients, especially the long-chain polyunsaturated fatty acids (LCPUFAs), believed to be beneficial for fetal brain development, as well as to the neurotoxicant methylmercury (MeHg). We recently reported that nutrients present in fish may modify MeHg neurotoxicity. Understanding the apparent interaction of MeHg exposure and nutrients present in fish is complicated by the limitations of modeling methods. In this study we fit varying coefficient function models to data from the Seychelles Child Development Nutrition Study (SCDNS) cohort to assess the association of dietary nutrients and children's development. This cohort of mother-child pairs in the Republic of Seychelles had fish consumption averaging 9 meals per week. Maternal nutritional status was assessed for five different nutritional components known to be present in fish (n-3 LCPUFA, n-6 LCPUFA, iron status, iodine status, and choline) and associated with children's neurological development. We also included prenatal MeHg exposure (measured in maternal hair). We examined two child neurodevelopmental outcomes (Bayley Scales Infant Development-II (BSID-II) Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI)), each administered at 9 and at 30 months. The varying coefficient models allow the possible interactions between each nutritional component and MeHg to be modeled as a smoothly varying function of MeHg as an effect modifier. Iron, iodine, choline, and n-6 LCPUFA had little or no observable modulation at different MeHg exposures. In contrast the n-3 LCPUFA docosahexaenoic acid (DHA) had beneficial effects on the BSID-II PDI that were reduced or absent at higher MeHg exposures. This study presents a useful modeling method that can be brought to bear on questions involving interactions between covariates, and illustrates the continuing importance of viewing fish consumption during pregnancy as a case of multiple exposures to nutrients and to MeHg. The results encourage more emphasis on a holistic view of the risks and benefits of fish consumption as it relates to infant development.

Iron status in pregnant women in the Republic of Seychelles.

OBJECTIVE: To establish the Fe status of pregnant women and their neonates in the Republic of Seychelles. DESIGN: A prospective study. SETTING: Republic of Seychelles. SUBJECTS: Pregnant women were recruited and blood samples taken at enrolment and post-delivery along with cord blood samples. Ferritin and soluble transferrin receptor (sTfR) were measured in maternal (n 220) and cord blood (n 123) samples. RESULTS: Maternal Fe deficiency (ferritin < 15 ng/ml, sTfR > 28 nmol/l) was present in 6 % of subjects at enrolment and in 20 % at delivery. There was no significant decrease in maternal ferritin. A significant increase in sTfR was observed between enrolment and delivery (P < 0.001). Maternal BMI and use of Fe supplements at 28 weeks' gestation were associated with improved maternal Fe status at delivery, whereas parity had a negative effect on sTfR and ferritin at delivery. CONCLUSIONS: Fe status of pregnant Seychellois women was, on average, within normal ranges. The incidence of Fe deficiency throughout pregnancy in this population was similar to that in a Westernised population. Increased awareness of the importance of adequate Fe intake during pregnancy, particularly in multiparous women, is warranted.

The chemical nature of mercury in human brain following poisoning or environmental exposure.

Methylmercury is among the most potentially toxic species to which human populations are exposed, both at high levels through poisonings and at lower levels through consumption of fish and other seafood. However, the molecular mechanisms of methylmercury toxicity in humans remain poorly understood. We used synchrotron X-ray absorption spectroscopy (XAS) to study mercury chemical forms in human brain tissue. Individuals poisoned with high levels of methylmercury species showed elevated cortical selenium with significant proportions of nanoparticulate mercuric selenide plus some inorganic mercury and methylmercury bound to organic sulfur. Individuals with a lifetime of high fish consumption showed much lower levels of mercuric selenide and methylmercury cysteineate. Mercury exposure did not perturb organic selenium levels. These results elucidate a key detoxification pathway in the central nervous system and provide new insights into the appropriate methods for biological monitoring.

Postnatal exposure to methyl mercury from fish consumption: a review and new data from the Seychelles Child Development Study.

BACKGROUND: Fish is an important source of nutrition worldwide. Fish contain both the neurotoxin methyl mercury (MeHg) and nutrients important for brain development. The developing brain appears to be most sensitive to MeHg toxicity and mothers who consume fish during pregnancy expose their fetus prenatally. Although brain development is most dramatic during fetal life, it continues for years postnatally and additional exposure can occur when a mother breast feeds or the child consumes fish. This raises the possibility that MeHg might influence brain development after birth and thus adversely affect children's developmental outcomes. We reviewed postnatal MeHg exposure and the associations that have been published to determine the issues associated with it and then carried out a series of analyses involving alternative metrics of postnatal MeHg exposure in the Seychelles Child Development Study (SCDS) Main Cohort. METHODS: The SCDS is a prospective longitudinal evaluation of prenatal MeHg exposure from fish consumption. The Main Cohort includes 779 subjects on whom recent postnatal exposure data were collected at the 6-, 19-, 29-, 66-, and 107-month evaluations. We examined the association of recent postnatal MeHg exposure with multiple 66- and 107-month outcomes and then used three types of alternative postnatal exposure metrics to examine their association with the children's intelligence quotient (IQ) at 107 months of age. RESULTS: Recent postnatal exposure at 107 months of age was adversely associated with four endpoints, three in females only. One alternative postnatal metric was beneficially associated with 9-year IQ in males only. CONCLUSIONS: We found several associations between postnatal MeHg biomarkers and children's developmental endpoints. However, as has been the case with prenatal MeHg exposure in the SCDS Main Cohort study, no consistent pattern of associations emerged to support a causal relationship.

The assessment of the contribution of hair to methyl mercury excretion.

Due to its ability to avidly accumulate methyl mercury from blood, scalp hair has been widely used as a biological monitor for human exposure. The question arises that hair may also be an important route of elimination of methyl mercury from the body. Taking original publications and reviews on the physiology of hair (including growth by weigh and density) and on the deposition parameters for methyl mercury in the body (including the hair to blood concentration ratio of methyl mercury), one can calculate the rate of elimination of methyl mercury in hair. The result indicates that hair accounts for only a small fraction, less than 10%, of the total elimination of methyl mercury from the body. This relationship is expected to be maintained at every level when the dominant form of mercury is methyl. Other species of mercury I eliminated by hair even at a lower rate.

Neurodevelopmental effects of maternal nutritional status and exposure to methylmercury from eating fish during pregnancy.

Fish contain nutrients that promote optimal brain growth and development but also contain methylmercury (MeHg) that can have toxic effects. The present study tested the hypothesis that the intake of selected nutrients in fish or measures of maternal nutritional status may represent important confounders when estimating the effects of prenatal methylmercury exposure on child development. The study took place in the Republic of Seychelles, an Indian Ocean archipelago where fish consumption is high. A longitudinal cohort study design was used. A total of 300 mothers were enrolled early in pregnancy. Nutrients considered to be important for brain development were measured during pregnancy along with prenatal MeHg exposure. The children were evaluated periodically to age 30 months. There were 229 children with complete outcome and covariate data for analysis. The primary endpoint was the Bayley Scales of Infant Development-II (BSID-II), administered at 9 and 30 months of age. Combinations of four secondary measures of infant cognition and memory were also given at 5, 9 and 25 months. Cohort mothers consumed an average of 537 g of fish (nine meals containing fish) per week. The average prenatal MeHg exposure was 5.9 ppm in maternal hair. The primary analysis examined the associations between MeHg, maternal nutritional measures and children's scores on the BSID-II and showed an adverse association between MeHg and the mean Psychomotor Developmental Index (PDI) score at 30 months. Secondary analyses of the association between the PDI and only MeHg alone or nutritional factors alone showed only a borderline significant association between MeHg and the PDI at 30 months and no associations with nutritional factors. One experimental measure at 5 months of age was positively associated with iodine status, but not prenatal MeHg exposure. These findings suggest a possible confounding role of maternal nutrition in studies examining associations between prenatal MeHg exposures and developmental outcomes in children.

Associations of maternal long-chain polyunsaturated fatty acids, methyl mercury, and infant development in the Seychelles Child Development Nutrition Study.

Fish consumption during gestation can provide the fetus with long-chain polyunsaturated fatty acids (LCPUFA) and other nutrients essential for growth and development of the brain. However, fish consumption also exposes the fetus to the neurotoxicant, methyl mercury (MeHg). We studied the association between these fetal exposures and early child development in the Seychelles Child Development Nutrition Study (SCDNS). Specifically, we examined a priori models of Omega-3 and Omega-6 LCPUFA measures in maternal serum to test the hypothesis that these LCPUFA families before or after adjusting for prenatal MeHg exposure would reveal associations with child development assessed by the BSID-II at ages 9 and 30 months. There were 229 children with complete outcome and covariate data available for analysis. At 9 months, the PDI was positively associated with total Omega-3 LCPUFA and negatively associated with the ratio of Omega-6/Omega-3 LCPUFA. These associations were stronger in models adjusted for prenatal MeHg exposure. Secondary models suggested that the MeHg effect at 9 months varied by the ratio of Omega-6/Omega-3 LCPUFA. There were no significant associations between LCPUFA measures and the PDI at 30 months. There were significant adverse associations, however, between prenatal MeHg and the 30-month PDI when the LCPUFA measures were included in the regression analysis. The BSID-II mental developmental index (MDI) was not associated with any exposure variable. These data support the potential importance to child development of prenatal availability of Omega-3 LCPUFA present in fish and of LCPUFA in the overall diet. Furthermore, they indicate that the beneficial effects of LCPUFA can obscure the determination of adverse effects of prenatal MeHg exposure in longitudinal observational studies.

Association between prenatal exposure to methylmercury and visuospatial ability at 10.7 years in the seychelles child development study.

The Seychelles Child Development Study was designed to test the hypothesis that prenatal exposure to MeHg from maternal consumption of a diet high in fish is detrimental to child neurodevelopment. To date, no consistent pattern of adverse associations between prenatal exposure and children's development has appeared. In a comprehensive review of developmental studies involving MeHg, a panel of experts recommended a more consistent use of the same endpoints across studies to facilitate comparisons. Both the SCDS and the Faeroe Islands studies administered the Bender Visual Motor Gestalt Test. However, the method of test administration and scoring used was different. We repeated the test on the SCDS Main Study children (mean age 10.7 years) using the same testing and scoring procedure reported by the Faeroe studies to obtain Copying Task and Reproduction Task scores. We found no association between prenatal MeHg exposure and Copying Task scores which was reported from the Faeroese study. However, our analysis did show a significant adverse association between MeHg and Reproduction Task scores with all the data (p=0.04), but not when the single outlier was removed (p=0.07). In a population whose exposure to MeHg is from fish consumption, we continue to find no consistent adverse association between MeHg and visual motor coordination.

Validity of methyl mercury hair analysis: mercury monitoring in human scalp/nude mouse model.

OBJECTIVE: The grafting of human scalp hair was used as a new application of this method to explore methyl mercury incorporation into human hair and to validate this model for mercury monitoring in hair. METHODS: Human scalp grafts were transplanted to athymic BALB/c nude mice. The animals were exposed to methyl mercury either as a single dose i.p. or continuously for 4 months, using ALZET osmotic pumps. The mercury concentration in hair was determined using x-ray fluorescence (XRF) spectrometry by segmental (2 mm) analysis of a single strand, and tissue concentrations were measured by cold vapor atomic absorption analysis. RESULTS: Human scalp hair grown in nude mice showed long-term persistence of human features including the expression of histocompatibility antigens (KAB 3, W 6/32, SF 1-1.1.1) and normal hair morphometry. The disposition of methyl mercury in nude mice followed a one-compartment model with a whole body elimination half-life of 6.7 days (elimination constant, k = 0.1/day). Autoradiographic studies revealed that methyl mercury was rapidly incorporated into areas of the hair follicle undergoing active keratinization. Methyl mercury concentrations in human hair transplanted onto nude mice were two orders of magnitude higher than in blood and attained a mean hair: blood ratio of 217 : 1, similar to ratios reported only in human studies. CONCLUSIONS: This study demonstrated that human hair grown on nude mice can record the level of exposure to methyl mercury and can serve as a valuable research tool to study mercury incorporation into human hair.

Is susceptibility to prenatal methylmercury exposure from fish consumption non-homogeneous? Tree-structured analysis for the Seychelles Child Development Study.

Studies of the association between prenatal methylmercury exposure from maternal fish consumption during pregnancy and neurodevelopmental test scores in the Seychelles Child Development Study have found no consistent pattern of associations through age 9 years. The analyses for the most recent 9-year data examined the population effects of prenatal exposure, but did not address the possibility of non-homogeneous susceptibility. This paper presents a regression tree approach: covariate effects are treated non-linearly and non-additively and non-homogeneous effects of prenatal methylmercury exposure are permitted among the covariate clusters identified by the regression tree. The approach allows us to address whether children in the lower or higher ends of the developmental spectrum differ in susceptibility to subtle exposure effects. Of 21 endpoints available at age 9 years, we chose the Weschler Full Scale IQ and its associated covariates to construct the regression tree. The prenatal mercury effect in each of the nine resulting clusters was assessed linearly and non-homogeneously. In addition we reanalyzed five other 9-year endpoints that in the linear analysis had a two-tailed p-value <0.2 for the effect of prenatal exposure. In this analysis, motor proficiency and activity level improved significantly with increasing MeHg for 53% of the children who had an average home environment. Motor proficiency significantly decreased with increasing prenatal MeHg exposure in 7% of the children whose home environment was below average. The regression tree results support previous analyses of outcomes in this cohort. However, this analysis raises the intriguing possibility that an effect may be non-homogeneous among children with different backgrounds and IQ levels.

Does prenatal methylmercury exposure from fish consumption affect blood pressure in childhood?

INTRODUCTION: Prenatal exposure to organic methylmercury (MeHg) from seafood consumption has been reported to increase children's blood pressure (BP). A report from the Faroe Islands noted significantly increased diastolic and systolic BP in 7-year-old children as prenatal MeHg exposure increased. The Faroese diet includes sea mammals that contain MeHg, cadmium, and other pollutants. We examined this relationship in the Seychelles Islands to determine if it was present in a society exposed primarily to MeHg from consuming ocean fish. METHODS: We obtained BP at ages 12 and 15 years on children with known prenatal MeHg exposure enrolled in the Seychelles Child Development Study (SCDS). We examined the association between prenatal MeHg exposure and BP using longitudinal models and linear regression adjusted for relevant covariates. RESULTS: Blood pressure at both ages was associated with BMI, height and maternal hypertension during pregnancy as expected. No association between prenatal MeHg exposure and BP was present in girls at either age or in either sex at age 12 years. At age 15 years diastolic BP in boys increased with increasing prenatal MeHg exposure, while systolic BP was unaffected. SUMMARY: It is unclear whether the association between prenatal MeHg exposure and diastolic BP seen in 15-year-old boys is of biological significance or if it is a chance finding. However, the finding is intriguing and deserves further study.

Thimerosal distribution and metabolism in neonatal mice: comparison with methyl mercury.

Thimerosal, which releases the ethyl mercury radical as the active species, has been used as a preservative in many currently marketed vaccines throughout the world. Because of concerns that its toxicity could be similar to that of methyl mercury, it is no longer incorporated in many vaccines in the United States. There are reasons to believe, however, that the disposition and toxicity of ethyl mercury compounds, including thimerosal, may differ substantially from those of the methyl form. The current study sought to compare, in neonatal mice, the tissue concentrations, disposition and metabolism of thimerosal with that of methyl mercury. ICR mice were given single intramuscular injections of thimerosal or methyl mercury (1.4 mg Hg kg(-1)) on postnatal day 10 (PND 10). Tissue samples were collected daily on PND 11-14. Most analysed tissues demonstrated different patterns of tissue distribution and a different rate of mercury decomposition. The mean organic mercury in the brain and kidneys was significantly lower in mice treated with thimerosal than in the methyl mercury-treated group. In the brain, thimerosal-exposed mice showed a steady decrease of organic mercury levels following the initial peak, whereas in the methyl mercury-exposed mice, concentrations peaked on day 2 after exposure. In the kidneys, thimerosal-exposed mice retained significantly higher inorganic mercury levels than methyl mercury-treated mice. In the liver both organic and inorganic mercury concentrations were significantly higher in thimerosal-exposed mice than in the methyl mercury group. Ethyl mercury was incorporated into growing hair in a similar manner to methyl mercury. The data showing significant kinetic differences in tissue distribution and metabolism of mercury species challenge the assumption that ethyl mercury is toxicologically identical to methyl mercury.

Mechanisms of mercury disposition in the body.

Today the most widespread human exposures to mercury are to mercury vapor emitted from amalgam tooth fillings, to ethylmercury as a preservative in vaccines, and to methylmercury in edible tissues of fish. This review will focus on the mechanisms of transport of these three species of mercury. All three species are freely moveable throughout the body. Inhaled vapor in view of its physical properties as an uncharged atomic gas is believed to be transported by passive diffusion. Methylmercury and ethylmercury also move freely in the body. Methylmercury, and presumably its closely related chemical cousin ethylmercury, cross cell membranes as complexes with small molecular weight thiol compounds, entering the cell in part as a cysteine complex on the large neutral amino acid carriers and exiting the cell in part as a complex with reduced glutathione on endogenous carriers. The implications of these mechanisms with regard to biological monitoring are discussed.