RESUMEN
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.
Asunto(s)
Peces , Contaminación de Alimentos , Intoxicación del Sistema Nervioso por Mercurio/etiología , Estado Nutricional/fisiología , Efectos Tardíos de la Exposición Prenatal , Adolescente , Adulto , Animales , Desarrollo Infantil/efectos de los fármacos , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Intercambio Materno-Fetal , Intoxicación del Sistema Nervioso por Mercurio/epidemiología , Embarazo , Estadística como Asunto , Adulto JovenRESUMEN
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.
Asunto(s)
Desarrollo Infantil/efectos de los fármacos , Ácidos Grasos Insaturados/análisis , Compuestos de Metilmercurio/toxicidad , Efectos Tardíos de la Exposición Prenatal , Adolescente , Adulto , Desarrollo Infantil/fisiología , Estudios de Cohortes , Femenino , Contaminación de Alimentos , Humanos , Lactante , Recién Nacido , Masculino , Compuestos de Metilmercurio/sangre , Embarazo , Análisis de Regresión , Seychelles/epidemiología , Factores de Tiempo , Adulto JovenRESUMEN
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.
Asunto(s)
Desarrollo Infantil/efectos de los fármacos , Contaminación de Alimentos , Compuestos de Metilmercurio/efectos adversos , Modelos Estadísticos , Actividad Motora/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Alimentos Marinos , Contaminantes Químicos del Agua/efectos adversos , Niño , Preescolar , Análisis por Conglomerados , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Lactante , Inteligencia , Pruebas de Inteligencia , Pruebas Neuropsicológicas , Embarazo , Análisis de Regresión , Seychelles , Medio Social , Factores Socioeconómicos , Factores de TiempoRESUMEN
Methyl mercury (MeHg) is highly toxic to the developing nervous system. Human exposure is mainly from fish consumption since small amounts are present in all fish. Findings of developmental neurotoxicity following high-level prenatal exposure to MeHg raised the question of whether children whose mothers consumed fish contaminated with background levels during pregnancy are at an increased risk of impaired neurological function. Benchmark doses determined from studies in New Zealand, and the Faroese and Seychelles Islands indicate that a level of 4-25 parts per million (ppm) measured in maternal hair may carry a risk to the infant. However, there are numerous sources of uncertainty that could affect the derivation of benchmark doses, and it is crucial to continue to investigate the most appropriate derivation of safe consumption levels. Earlier, we published the findings from benchmark analyses applied to the data collected on the Seychelles main cohort at the 66-month follow-up period. Here, we expand on the main cohort analyses by determining the benchmark doses (BMD) of MeHg level in maternal hair based on 643 Seychellois children for whom 26 different neurobehavioral endpoints were measured at 9 years of age. Dose-response models applied to these continuous endpoints incorporated a variety of covariates and included the k-power model, the Weibull model, and the logistic model. The average 95% lower confidence limit of the BMD (BMDL) across all 26 endpoints varied from 20.1 ppm (range=17.2-22.5) for the logistic model to 20.4 ppm (range=17.9-23.0) for the k-power model. These estimates are somewhat lower than those obtained after 66 months of follow-up. The Seychelles Child Development Study continues to provide a firm scientific basis for the derivation of safe levels of MeHg consumption.
Asunto(s)
Desarrollo Infantil , Monitoreo del Ambiente/métodos , Concentración Máxima Admisible , Intoxicación del Sistema Nervioso por Mercurio , Compuestos de Metilmercurio/análisis , Animales , Niño , Preescolar , Monitoreo Epidemiológico , Femenino , Peces , Estudios de Seguimiento , Contaminación de Alimentos , Humanos , Masculino , Intercambio Materno-Fetal , Intoxicación del Sistema Nervioso por Mercurio/etiología , Intoxicación del Sistema Nervioso por Mercurio/fisiopatología , Modelos Estadísticos , Pruebas Neuropsicológicas/estadística & datos numéricos , Embarazo , Efectos Tardíos de la Exposición Prenatal , Seychelles/epidemiologíaRESUMEN
BACKGROUND: The Seychelles Child Development Study (SCDS) has been longitudinally following a cohort of over 700 children enrolled in 1989. Their mothers consumed a diet high in fish during pregnancy. Repeated examination of the SCDS cohort at six different ages through age 11 years has shown no pattern of adverse effects. Some early appearing beneficial associations between both prenatal and postnatal hair MeHg and several child development endpoints were noted. We hypothesized these might be related to micronutrients in the fish, but they were not found when the children reached middle school age. These findings suggest that the associations observed between MeHg and developmental outcomes may vary with developmental stage. METHOD: We examined the main cohort of the SCDS to determine if this might be true using a longitudinal multiple regression analysis design that focused on those endpoints that were repeatedly measured at different ages. The primary endpoint analyzed was global cognition, involving a measure of developmental quotient or IQ. Secondary analyses included other domains such as Reading and Mathematics scholastic achievement, social behavior, and memory. Analyses involved two different approaches, one including incorporation of a passage of time variable, the other including a difference of scores across time points. RESULTS: No significant associations were found between prenatal MeHg exposure and any of the repeatedly measured endpoints. CONCLUSIONS: These results suggest that even when individual subject variance is controlled there was no consistent pattern of associations between child development outcomes and prenatal exposures to MeHg from maternal consumption of a diet high in fish. The Seychellois diet contains about 10 times more ocean fish than is typically consumed by US citizens. Our primary focus on IQ should further inform growing scientific interest in the analysis of the risks and benefits of fish consumption on overall cognitive ability.
Asunto(s)
Desarrollo Infantil/efectos de los fármacos , Cognición/efectos de los fármacos , Contaminación de Alimentos/análisis , Compuestos de Metilmercurio/envenenamiento , Alimentos Marinos , Niño , Estudios de Cohortes , Femenino , Cabello/química , Humanos , Masculino , Compuestos de Metilmercurio/análisis , Pruebas Neuropsicológicas , Embarazo , Efectos Tardíos de la Exposición Prenatal , Receptores Nicotínicos/metabolismo , Seychelles , Factores de TiempoRESUMEN
CONTEXT: No randomized trials have been published that address the concern that inhalation of mercury vapor released by amalgam dental restorations causes adverse health effects. OBJECTIVE: To compare the neuropsychological and renal function of children whose dental caries were restored using amalgam or mercury-free materials. DESIGN AND SETTING: The New England Children's Amalgam Trial was a 2-group randomized safety trial involving 5 community health dental clinics in Boston, Mass, and 1 in Farmington, Me, between September 1997 and March 2005. PARTICIPANTS AND INTERVENTION: A total of 534 children aged 6 to 10 years at baseline with no prior amalgam restorations and 2 or more posterior teeth with caries were randomly assigned to receive dental restoration of baseline and incident caries during a 5-year follow-up period using either amalgam (n=267) or resin composite (n =267) materials. MAIN OUTCOME MEASURES: The primary neuropsychological outcome was 5-year change in full-scale IQ scores. Secondary outcomes included tests of memory and visuomotor ability. Renal glomerular function was measured by creatinine-adjusted albumin in urine. RESULTS: Children had a mean of 15 tooth surfaces (median, 14) restored during the 5-year period (range, 0-55). Assignment to the amalgam group was associated with a significantly higher mean urinary mercury level (0.9 vs 0.6 microg/g of creatinine at year 5, P<.001). After adjusting for randomization stratum and other covariates, no statistically significant differences were found between children in the amalgam and composite groups in 5-year change in full-scale IQ score (3.1 vs 2.1, P = .21). The difference in treatment group change scores was 1.0 (95% confidence interval, -0.6 to 2.5) full-scale IQ score point. No statistically significant differences were found for 4-year change in the general memory index (8.1 vs 7.2, P = .34), 4-year change in visuomotor composite (3.8 vs 3.7, P = .93), or year 5 urinary albumin (median, 7.5 vs 7.4 mg/g of creatinine, P = .61). CONCLUSIONS: In this study, there were no statistically significant differences in adverse neuropsychological or renal effects observed over the 5-year period in children whose caries were restored using dental amalgam or composite materials. Although it is possible that very small IQ effects cannot be ruled out, these findings suggest that the health effects of amalgam restorations in children need not be the basis of treatment decisions when choosing restorative dental materials. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00065988.
Asunto(s)
Amalgama Dental , Intoxicación por Mercurio/etiología , Cementos de Resina , Niño , Amalgama Dental/efectos adversos , Amalgama Dental/química , Caries Dental/terapia , Femenino , Humanos , Pruebas de Función Renal , Estudios Longitudinales , Masculino , Mercurio/análisis , Mercurio/farmacocinética , Intoxicación por Mercurio/diagnóstico , Pruebas Neuropsicológicas , Cementos de Resina/efectos adversos , VolatilizaciónRESUMEN
In the midst of research focusing on the neurodevelopmental effects of mercury vapor in rats, we detected significant levels of mercury (30-60 ng/g) in the blood of nonexposed control subjects. We determined that the dominant form of the mercury was organic and that the standard laboratory chow we used in our vivarium was the source of the contamination. The dietary levels were deemed of potential biologic significance, even though they might have fallen below the limits of measurement specified by the supplier. All investigators employing animals in research must assess such potential contamination because dietary agents may alter a) conclusions based on intentionally administered doses, b) outcomes by interacting with other agents that are the primary focus of the research, and c) outcomes of research unrelated to the toxic effects of experimentally administered agents.
Asunto(s)
Alimentación Animal/análisis , Contaminantes Ambientales/análisis , Contaminación de Alimentos , Compuestos de Metilmercurio/análisis , Animales , Animales Recién Nacidos , Factores de Confusión Epidemiológicos , Grupos Control , Dieta , Contaminantes Ambientales/administración & dosificación , Contaminantes Ambientales/sangre , Femenino , Productos Pesqueros , Masculino , Compuestos de Metilmercurio/administración & dosificación , Compuestos de Metilmercurio/sangre , Ratas , Ratas Long-EvansRESUMEN
Thimerosal is a preservative that has been used in manufacturing vaccines since the 1930s. Reports have indicated that infants can receive ethylmercury (in the form of thimerosal) at or above the U.S. Environmental Protection Agency guidelines for methylmercury exposure, depending on the exact vaccinations, schedule, and size of the infant. In this study we compared the systemic disposition and brain distribution of total and inorganic mercury in infant monkeys after thimerosal exposure with those exposed to MeHg. Monkeys were exposed to MeHg (via oral gavage) or vaccines containing thimerosal (via intramuscular injection) at birth and 1, 2, and 3 weeks of age. Total blood Hg levels were determined 2, 4, and 7 days after each exposure. Total and inorganic brain Hg levels were assessed 2, 4, 7, or 28 days after the last exposure. The initial and terminal half-life of Hg in blood after thimerosal exposure was 2.1 and 8.6 days, respectively, which are significantly shorter than the elimination half-life of Hg after MeHg exposure at 21.5 days. Brain concentrations of total Hg were significantly lower by approximately 3-fold for the thimerosal-exposed monkeys when compared with the MeHg infants, whereas the average brain-to-blood concentration ratio was slightly higher for the thimerosal-exposed monkeys (3.5 +/- 0.5 vs. 2.5 +/- 0.3). A higher percentage of the total Hg in the brain was in the form of inorganic Hg for the thimerosal-exposed monkeys (34% vs. 7%). The results indicate that MeHg is not a suitable reference for risk assessment from exposure to thimerosal-derived Hg. Knowledge of the toxicokinetics and developmental toxicity of thimerosal is needed to afford a meaningful assessment of the developmental effects of thimerosal-containing vaccines.
Asunto(s)
Animales Recién Nacidos/metabolismo , Encéfalo/metabolismo , Compuestos de Metilmercurio/farmacocinética , Conservadores Farmacéuticos/farmacocinética , Timerosal/farmacocinética , Animales , Femenino , Macaca fascicularis , Masculino , Mercurio/sangre , Compuestos de Metilmercurio/sangre , Medición de Riesgo , Timerosal/sangre , VacunasRESUMEN
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.
Asunto(s)
Cabello/química , Inteligencia/efectos de los fármacos , Compuestos de Metilmercurio/toxicidad , Leche Humana/química , Envejecimiento , Encéfalo/efectos de los fármacos , Encéfalo/crecimiento & desarrollo , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Masculino , Exposición Materna , Mercurio/análisis , Mercurio/toxicidad , Alimentos Marinos , SeychellesRESUMEN
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.
Asunto(s)
Monitoreo del Ambiente/métodos , Cabello/metabolismo , Compuestos de Metilmercurio/farmacocinética , Cuero Cabelludo/metabolismo , Animales , Autorradiografía , Femenino , Cabello/embriología , Cabello/crecimiento & desarrollo , Cabello/trasplante , Humanos , Bombas de Infusión , Inyecciones Intraperitoneales , Compuestos de Metilmercurio/administración & dosificación , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Modelos Biológicos , Reproducibilidad de los Resultados , Cuero Cabelludo/embriología , Cuero Cabelludo/crecimiento & desarrollo , Cuero Cabelludo/trasplante , Espectrometría por Rayos X , Espectrofotometría AtómicaRESUMEN
OBJECTIVES: Thimerosal is a mercurial preservative that was widely used in multidose vaccine vials in the United States and Europe until 2001 and continues to be used in many countries throughout the world. We conducted a pharmacokinetic study to assess blood levels and elimination of ethyl mercury after vaccination of infants with thimerosal-containing vaccines. METHODS: Blood, stool, and urine samples were obtained before vaccination and 12 hours to 30 days after vaccination from 216 healthy children: 72 newborns (group 1), 72 infants aged 2 months (group 2), and 72 infants aged 6 months (group 3). Total mercury levels were measured by atomic absorption. Blood mercury pharmacokinetics were calculated by pooling the data on the group and were based on a 1-compartment first-order pharmacokinetics model. RESULTS: For groups 1, 2, and 3, respectively, (1) mean +/- SD weights were 3.4 +/- 0.4, 5.1 +/- 0.6, and 7.7 +/- 1.1 kg; (2) maximal mean +/- SD blood mercury levels were 5.0 +/- 1.3, 3.6 +/- 1.5, and 2.8 +/- 0.9 ng/mL occurring at 0.5 to 1 day after vaccination; (3) maximal mean +/- SD stool mercury levels were 19.1 +/- 11.8, 37.0 +/- 27.4, and 44.3 +/- 23.9 ng/g occurring on day 5 after vaccination for all groups; and (4) urine mercury levels were mostly nondetectable. The blood mercury half-life was calculated to be 3.7 days and returned to prevaccination levels by day 30. CONCLUSIONS: The blood half-life of intramuscular ethyl mercury from thimerosal in vaccines in infants is substantially shorter than that of oral methyl mercury in adults. Increased mercury levels were detected in stools after vaccination, suggesting that the gastrointestinal tract is involved in ethyl mercury elimination. Because of the differing pharmacokinetics of ethyl and methyl mercury, exposure guidelines based on oral methyl mercury in adults may not be accurate for risk assessments in children who receive thimerosal-containing vaccines.
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Recién Nacido/sangre , Mercurio/sangre , Conservadores Farmacéuticos/farmacocinética , Timerosal/farmacocinética , Vacunas/farmacocinética , Vacuna BCG/farmacocinética , Vacuna contra Difteria, Tétanos y Tos Ferina/farmacocinética , Compuestos de Etilmercurio/farmacocinética , Heces/química , Femenino , Semivida , Vacunas contra Hepatitis B/farmacocinética , Humanos , Lactante , Recién Nacido/metabolismo , Inyecciones Intramusculares , Masculino , Mercurio/análisis , Mercurio/orina , Vacunas/administración & dosificaciónRESUMEN
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.
Asunto(s)
Compuestos de Metilmercurio/farmacocinética , Timerosal/farmacocinética , Animales , Animales Recién Nacidos , Femenino , Masculino , Ratones , Ratones Endogámicos ICR , Distribución TisularRESUMEN
Studies of the association between prenatal methylmercury exposure from maternal fish consumption and neurodevelopmental test scores in the Seychelles Child Development Study have not found adverse effects through age 9 years. The analysis for the most recent 9-year data (Lancet 361 (2003) 1686) employed conventional linear regression models. In this study we reanalyzed the same Seychelles 9-year data using semiparametric additive models with different degrees of smoothing to explore whether nonlinear effects of prenatal exposure were present. Of 21 endpoints in the linear analysis, we chose only those with a two-tailed P value less than 0.2 for the effect of prenatal exposure. Six endpoints met the criterion. A nonlinear effect was identified with the more smooth model for only one endpoint. The test for an overall effect of prenatal exposure was also significant, with a P value of 0.04, while the corresponding P value in the linear regression analysis was 0.08. The nonlinear curve appeared to be nearly flat when the level was below approximately 12 ppm in maternal hair, with a linear trend above that level, suggesting a possible adverse effect in the uppermost range of prenatal exposure included in this cohort. Because of the descriptive nature of semiparametric additive models, the P values are not precise, and certainly there are fewer data above 12 ppm. We conclude that this reanalysis supports the primary linear analysis, showing little evidence for a prenatal adverse effect.
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Desarrollo Infantil/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Contaminación de Alimentos , Exposición Materna , Compuestos de Metilmercurio/toxicidad , Efectos Tardíos de la Exposición Prenatal , Niño , Femenino , Productos Pesqueros/análisis , Estudios de Seguimiento , Cabello/química , Humanos , Modelos Estadísticos , Embarazo , SeychellesRESUMEN
1. The hermatypic coral, Pocillopora damicornis was incubated in the laboratory and in its reef habitat with Na214CO3 for 1-24 hours. Controls were incubated in darkness. 14C fixation in light exceeded that in darkness. 2. Fractionation of corals labeled on the reef for 24 hours revealed that 35-50% of the total 14C fixed appeared in the animal tissue lipid (as 14C-glycerol) and protein. From a comparison with dark controls it is concluded that photosynthetic products of zooxanthellae are translocated to host coral tissue. The skeletal organic matrix also acquires 14C. 3. Zooxanthehellae isolated from corals and incubated in a homogenate of host coral tissue selectively release glycerol and traces of other organic material including glucose, alanine, and glycolic acid confirming previous observations.
RESUMEN
BACKGROUND: Thiomersal is a preservative containing small amounts of ethylmercury that is used in routine vaccines for infants and children. The effect of vaccines containing thiomersal on concentrations of mercury in infants' blood has not been extensively assessed, and the metabolism of ethylmercury in infants is unknown. We aimed to measure concentrations of mercury in blood, urine, and stools of infants who received such vaccines. METHODS: 40 full-term infants aged 6 months and younger were given vaccines that contained thiomersal (diptheria-tetanus-acellular pertussis vaccine, hepatitis B vaccine, and in some children Haemophilus influenzae type b vaccine). 21 control infants received thiomersal-free vaccines. We obtained samples of blood, urine, and stools 3-28 days after vaccination. Total mercury (organic and inorganic) in the samples was measured by cold vapour atomic absorption. FINDINGS: Mean mercury doses in infants exposed to thiomersal were 45.6 microg (range 37.5-62.5) for 2-month-olds and 111.3 microg (range 87.5-175.0) for 6-month-olds. Blood mercury in thiomersal-exposed 2-month-olds ranged from less than 3.75 to 20.55 nmol/L (parts per billion); in 6-month-olds all values were lower than 7.50 nmol/L. Only one of 15 blood samples from controls contained quantifiable mercury. Concentrations of mercury were low in urine after vaccination but were high in stools of thiomersal-exposed 2-month-olds (mean 82 ng/g dry weight) and in 6-month-olds (mean 58 ng/g dry weight). Estimated blood half-life of ethylmercury was 7 days (95% CI 4-10 days). INTERPRETATION: Administration of vaccines containing thiomersal does not seem to raise blood concentrations of mercury above safe values in infants. Ethylmercury seems to be eliminated from blood rapidly via the stools after parenteral administration of thiomersal in vaccines.
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Mercurio/metabolismo , Conservadores Farmacéuticos/metabolismo , Timerosal/metabolismo , Vacunas , Estudios de Casos y Controles , Cabello/química , Semivida , Humanos , Lactante , Mercurio/sangre , Mercurio/farmacocinética , Conservadores Farmacéuticos/farmacocinética , Timerosal/sangre , Timerosal/farmacocinéticaRESUMEN
Studies of the effects of environmental exposures on human health typically require estimation of both exposure and outcome. Standard methods for the assessment of the association between exposure and outcome include multiple linear regression analysis, which assumes that the outcome variable is observed with error, while the levels of exposure and other explanatory variables are measured with complete accuracy, so that there is no deviation of the measured from the actual value. The term measurement error in this discussion refers to the difference between the actual or true level and the value that is actually observed. In the investigations of the effects of prenatal methylmercury (MeHg) exposure from fish consumption on child development, the only way to obtain a true exposure level (producing the toxic effect) is to ascertain the concentration in fetal brain, which is not possible. As is often the case in studies of environmental exposures, the measured exposure level is a biomarker, such as the average maternal hair level during gestation. Measurement of hair mercury is widely used as a biological indicator for exposure to MeHg and is the only indicator that has been calibrated against the target tissue, the developing brain. Variability between the measured and the true values in explanatory variables in a multiple regression analysis can produce bias, leading to either over or underestimation of regression parameters (slopes). Fortunately, statistical methods known as measurement error models (MEM) are available to account for measurement errors in explanatory variables in multiple regression analysis, and these methods can provide an (either "unbiased" or "bias-corrected") estimate of the unknown outcome/exposure relationship. In this paper, we illustrate MEM analysis by reanalyzing data from the 5.5-year test battery in the Seychelles Child Development Study, a longitudinal study of prenatal exposure to MeHg from maternal consumption of a diet high in fish. The use of the MEM approach was made possible by the existence of independent, calibration data on the magnitude of the variability of the measurement error deviations for the biomarker of prenatal exposure used in this study, the maternal hair level. Our reanalysis indicated that adjustment for measurement errors in explanatory variables had no appreciable effect on the original results.
Asunto(s)
Desarrollo Infantil , Exposición a Riesgos Ambientales , Contaminación de Alimentos , Intercambio Materno-Fetal , Compuestos de Metilmercurio/análisis , Modelos Estadísticos , Adulto , Animales , Niño , Preescolar , Dieta , Femenino , Peces , Cabello/química , Humanos , Lactante , Estudios Longitudinales , Masculino , Embarazo , Reproducibilidad de los Resultados , Proyectos de Investigación , Medición de RiesgoRESUMEN
INTRODUCTION: Exposure to methylmercury (MeHg) before birth can adversely affect children's neurodevelopment. The most common form of prenatal exposure is maternal fish consumption, but whether such exposure harms the fetus is unknown. We aimed to identify adverse neurodevelopmental effects in a fish-consuming population. METHODS: We investigated 779 mother-infant pairs residing in the Republic of Seychelles. Mothers reported consuming fish on average 12 meals per week. Fish in Seychelles contain much the same concentrations of MeHg as commercial ocean fish elsewhere. Prenatal MeHg exposure was determined from maternal hair growing during pregnancy. We assessed neurocognitive, language, memory, motor, perceptual-motor, and behavioural functions in children at age 9 years. The association between prenatal MeHg exposure and the primary endpoints was investigated with multiple linear regression with adjustment for covariates that affect child development. FINDINGS: Mean prenatal MeHg exposure was 6.9 parts per million (SD 4.5 ppm). Only two endpoints were associated with prenatal MeHg exposure. Increased exposure was associated with decreased performance in the grooved pegboard using the non-dominant hand in males and improved scores in the hyperactivity index of the Conner's teacher rating scale. Covariates affecting child development were appropriately associated with endpoints. INTERPRETATION: These data do not support the hypothesis that there is a neurodevelopmental risk from prenatal MeHg exposure resulting solely from ocean fish consumption.
Asunto(s)
Exposición a Riesgos Ambientales/análisis , Contaminación de Alimentos/análisis , Compuestos de Metilmercurio/análisis , Efectos Tardíos de la Exposición Prenatal , Alimentos Marinos , Animales , Niño , Trastornos del Conocimiento/inducido químicamente , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/epidemiología , Estudios de Cohortes , Comorbilidad , Femenino , Peces , Estudios de Seguimiento , Cabello/química , Humanos , Lactante , Intoxicación por Mercurio/epidemiología , Compuestos de Metilmercurio/efectos adversos , Embarazo , Análisis de Regresión , Seychelles/epidemiologíaRESUMEN
A poluiçäo por mercúrio orgânico (MeHg) das cadeias alimentares aquáticas nos ecossistemas amazônicos constitui tema de relevância na saúde ambiental. O MeHg pode chegar às populaçoes humanas mediante o consumo de peixe. Os ribeirinhos do Alto Madeira consomem grandes quantidades de peixe. O cabelo é o melhor biomarcador para exposiçäo ao MegHg; é possível também assumir uma taxa constante de crescimento do cabelo, para verificar o comportamento das exposiçöes no passado recente. Apresenta as concentraçöes de Hg total (máxima de 339 ppm) em segmentos de 3 cm de cabelo de dez pessoas de uma única família. Apresenta também os percentuais de MeHg nas amostras de cabelo de quatro pessoas, dentre as dez em estudo. Nessa família, foi observada uma grande variaçäo na concentraçäo de Hg total (8 a 339 ppm) no cabelo de pessoas que repartiam suas refeiçöes no mesmo domicílio. Foi também observada uma grande variaçäo de Hg total (136 a 274 ppm) nos diversos segmentos de cabelo da mesma pessoa. A especiaçäo de Hg mostrou média e desvio padräo do conteúdo de MeHg de 62 por cento e 6 por cento, respectivamente. As variaçöes das concentraçöes de Hg em cabelo sugerem ser possível prevenir exposiçöes críticas através de recomendaçöes de consumo de peixe.