Grantee Research Project Results
Final Report: Metal Mixtures and Children’s Health
EPA Grant Number: R831725Center: Health Effects Institute (2015 - 2020)
Center Director: Greenbaum, Daniel S.
Title: Metal Mixtures and Children’s Health
Investigators: Hu, Howard , Brain, Joseph D. , Wright, Robert , Adams, Jeff , Cohen, Amy , Schaider, Laurel , Weisskopf, Marc , Bellinger, David , Hatley, Earl , Wright, Rosalind , Peterson, Karen E. , Shine, James P. , Wessling-Resnick, Marianne , Molina, Ramon , Maher, Tim , Spengler, John D. , Schwartz, Joel , Backus, Ann
Institution: Harvard University
EPA Project Officer: Callan, Richard
Project Period: June 1, 2004 through May 31, 2009 (Extended to May 31, 2011)
Project Amount: $7,894,185
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
Project 1: Metals, Nutrition, and Stress in Child Development
Project 1 is a community-based participatory epidemiologic study that examines biological markers of fetal and early childhood exposure to metals (lead, manganese, cadmium, and iron), their impact on measures of mental development, and their response to a quasi-experimental randomized trial of nutritional and behavioral interventions. This overall objective was pursued through multiple specific aims. For example, we wanted to know whether participation in a multi-component intervention program would result in lower blood levels in children two years of age. Other specific aims dealt with prenatal and infant exposures and their effect on mental development. We also explored the role of maternal stress during pregnancy, as well as the iron status of mothers and infants at birth. We were also interested in cadmium exposures and their impact. Finally, we explored the extent to which hair, serum, and plasma were reliable biomarkers of exposure and outcome.
Project 2: Exposure Assessment of Children and Metals in Mining Waste: Composition, Environmental Transport and Exposure Patterns
This project seeks to characterize children’s exposure to metals originating from mine wastes, especially with respect to the relative amounts of different metals and their bioavailability. We pay specific attention to mixtures of metals to which children are exposed. A second specific aim is to prepare and characterize exposure material, such as chat, soil, dust, and atmospheric particles for use in the animal exposure studies (Projects 3 and 4). Embedded in these specific aims are multiple hypotheses. For example, we wish to test the hypothesis that metal mixtures and primary, secondary, and tertiary exposure media are significantly different from the parent chat material due to differential partitioning, weathering, and transport phenomena. Similarly, we wish to link to Project 1 by testing the hypothesis that differences in lead and manganese in children’s blood can be explained by differences in measurements of the concentration and the bioavailability of these metals in soil, dust, food, and water collected from each home.
Project 3: Exposure Dose Relationship of Toxic Metals
This project seeks to understand the bioavailability of various metals in different forms when mammals are exposed by different routes of administration. How do the physical and chemical properties of particles, such as their size and solubility, influence their pharmacokinetics? If particles are breathed or ingested, what are the relative bioavailabilities? We have exposed animals to a variety of relevant metals which are radioactive via the nose, lungs, GI tract, or by intravenous administration. We have also examined the transplacental transfer of various metals.
Project 4: Behavioral and Neurochemical Changes Resulting from Metal Exposures
Project 4 is examining the effect of pre- and neo-natal exposure to metals on neurochemical changes and neurobehavioral outcomes in rats. The effect of simple mixtures of metals is being compared with the effect of "homogenized chat" in both Projects 3 and 4.
Summary/Accomplishments (Outputs/Outcomes):
Project 1: Metals, Nutrition, and Stress in Child Development
A major accomplishment was a solid foundation for this community-based study resulting in a birth cohort which continues to this day. We now have nearly 800 mother-infant pairs, which are being used to study neurodevelopmental effects from exposures to metal mixtures. We produced the first data on blood manganese collected on one and two year old children. We found blood manganese levels that were higher than non-pregnant adult populations in Tar Creek. We also produced a variety of publications which quantified the impact of mine waste on mothers and children. These studies connected us to the community, and resulted in a significant decrease in metal exposures and associated improvements in health outcomes.
Project 2: Exposure Assessment of Children and Metals in Mining Waste: Composition, Environmental Transport and Exposure Patterns
Project 2 has assessed the utility of size fractionation and sequential extraction studies for characterizing chat, conducting a nested case-control study of the determinants of high versus low burdens of metals amongst children participating in Project 1, and producing standardized "homogenized chat" for Projects 3 and 4.
Project 3: Exposure Dose Relationship of Toxic Metals
Project 3 has employed a pregnant rat model to better understand metal exposures of children and their mothers in contaminated settings like Tar Creek by (1) utilizing exposures during and after pregnancy and lactation, (2) using metal ions as well as complex environmental samples from Tar Creek, and (3) comparing different routes of entry from the environment into the body. Rats were exposed during gestation, lactation, and after weaning by intratracheal instillation, by gavage, via intranasal administration, or by intravenous injection.
Our data clearly shows that the absorbed dose of metals in critical organs such as the brain depends on route of entry and duration of exposure. They also indicate that uptake from the nose and the lungs may be underappreciated in contrast to ingestion. Analyses of these data can be used to help estimate the relative risks of metals from different exposures, e.g. eating contaminated food and water, inhaling airborne chat particles, or children playing in contaminated playgrounds.
Adjacent studies have helped us understand molecular mechanisms of metal transport in both normal and mutant rats, and to elucidate mechanistic differences between manganese and iron absorption. We also describe the expression of binding and transporter molecules for metal transport and the corresponding pharmacokinetics of metals from the lung and gut to the blood, CNS and other organs as they relate to pregnant rats and their weanlings.
As mentioned earlier, a family of zinc minerals was characterized in cooperation with Project 2. Our studies with neutron-activated particles demonstrated a good correlation between the surface area of particles, as determined by nitrogen adsorption and in vivo bioavailability results. The greater the surface area per gram, the greater the zinc bioavailability. We also continued our studies on chat particles and employed elemental analysis by neutron-activation to examine the transport and retention of specific chat-associated metals – primarily 59Fe or 65Zn. We continue to be interested in mechanisms of manganese and iron absorption from the lungs and nose and the influence of iron status on iron absorptive kinetics. We studied olfactory absorption of 54Mn in Belgrade rats, an animal model of DMT1 deficiency, and established that transport of intranasally instilled metal from the nasal cavity to the blood was impaired. Moreover, this pathway of manganese absorption was enhanced in anemic rats relative to iron-sufficient controls. These findings are significant because they suggest that neurotoxicity of inhaled manganese may be modified by iron status.
A final series of experiments, carried out in collaboration with Project 4, studied exposure to manganese (Mn) and lead (Pb) during early development. We showed that exposures during this time may be related to impaired learning and cognitive functions, as well as higher distractibility and impulsiveness, including attention deficit hyperactivity disorder. Manganese exposed pups (but not lead exposed) were more impulsive than control pups. Both manganese and lead exposed pups displayed lower overall velocities of movement when compared with control pups. We also observed that pups from dams given manganese (Mn) or lead (Pb) had significantly lower body weight and higher blood and brain concentrations of the respective metal. These data will be useful in assessing the relative risks for metal toxicity of various exposures to metals. The pharmacokinetic results from chat studies show differences in absorption, vascular kinetics and tissue retention of 59Fe or 65Zn from irradiated chat administered via different routes in rats. Significant differences were also observed as a function of particle size. Smaller, respirable chat had higher metal bioavailability when inhaled or ingested. Data from these studies will be used to assist in estimating the relative risks of metals from different exposures, e.g., eating contaminated food and water, inhaling airborne chat particles, or children playing in contaminated playgrounds.
Project 4: Behavioral and Neurochemical Changes Resulting from Metal Exposures
Project 4 has utilized exposures to metals, especially by ingestion, and has focused on behavioral and neurochemical outcomes. Changes in body weight and other health and disease indicators have also been described. This project utilizes exposures via drinking water. Project 4 emphasizes the long term consequences of perinatal exposure to different concentrations of manganese and lead. Emphasized are behavioral changes and changes in neurochemistry. Project 4 worked closely with Core B (Analytical Chemistry) to quantify levels of heavy metals in the blood and brain of the offspring of exposed mothers. Increases in brain levels of lead and manganese was dose related and was demonstrable in multiple brain tissues, including cortex, hippocampus, and brain stem.
The Morris Water Maze and the elevated-plus maze (EPM) were performed in rats to assess impulsivity and hyperactivity. These results provide evidence that exposure to manganese chloride and lead acetate during gestation and lactation cause subtle neurobehavioral and neurochemical changes resulting from a wide range of exposure levels. These results provide the evidence that exposure to MnCl2 and Pb acetate during gestation and lactation causes subtle neurobehavioral and neurochemical changes resulting from a wide range of the exposure levels.
The data also emphasize the significance of the low doses of MnCl2 and Pb acetate exposures, as impulsivity and hyperactivity were observed from both male and female rats with Pb acetate 2.5-25 mg/ml (blood Pb level lower than 10 mg/dL). In contrast, these neurobehavioral deficits were not shown from high concentration of Pb acetate (2500-4000 mg/ml) that produced very high Pb level in blood and brain tissues. Additionally, low doses of MnCl2 of 1.25 and 5 mg/ml, but not 10 mg/ml produced hyperactivity. However, we can not conclude that these neurobehavioral deficits did not occur with the high levels of MnCl2 and Pb acetate, as other toxic effects resulting from high level exposures can obscure the impulsivity and hyperactivity. Learning and memory were also affected from MnCl2 and Pb acetate exposures. Learning and memory impairment was shown from the medium to high level exposures of Pb acetate (Pb acetate of 100-250 mg/ml and 2500-4000 mg/ml), and MnCl2 of each level (MnCl2 1.25, 5 and 10 mg/ml).
In addition to the neurobehaviors, the results from the microdialysis experiments demonstrate the neurochemical changes from the exposure to these metals. Both dopaminergic and glutamatergic neurotransmissions were affected from MnCl2 exposure, although a gender effect was apparent. Exposure to MnCl2 10 mg/ml in male and female rats had a smaller increase of K+ evoked glutamate levels than controls. This deficit might relate to the learning and memory impairment observed in male and female rats exposed to higher MnCl2 levels. In contrast, there was a gender effect of MnCl2 exposure on the basal and K+ evoked DA levels. The deficit was found only in female rats as evidenced by higher basal DA and decreased K+ evoked DA levels. That the deficit in dopaminergic neurotransmission was found only in female rats might be related to the hyperactivity found from MnCl2 1.25 and 5 mg/ml in female rats.
Conclusions:
Project 1: Metals, Nutrition, and Stress in Child Development
Project 1 exemplifies a major theme of our Center. Research revolves around a “real word” environmental health threat to children at the Tar Creek superfund site. Miami County in Oklahoma is an area well documented to be highly contaminated by metals from mining waste (“chat”) and largely populated by residents of Native American decent. We build upon evidence that the metals in chat at the Tar Creek Superfund site are bioavailable. Our interest in this geographical area also flows from the express concern of community residents about the potential impact of the metals in chat on the ability to learn and other behaviors of their children. We also believe that previous risk assessments did not adequately take into account multiple routes of exposure, especially the respiratory route. Throughout this grant, our major approach has been to carry out a community based participatory epidemiologic study and to create a cohort of mothers and children with documented exposures to mining wastes. We have searched for an found biological markers of fetal and early childhood exposure to metals, especially lead, manganese, and cadmium. These have been related to an ongoing study of IQ and other developmental assessments.
Project 2: Exposure Assessment of Children and Metals in Mining Waste: Composition, Environmental Transport and Exposure Patterns
Project 2 investigators have well established programs on the health effects of these metals. All told, metal investigators are conducting ground breaking research not only on the main effects of metal exposure, but also on mixed exposures and the host factors which modify metal toxicity. Such work is expanding how we think about toxicity, taking us from reductionist principles of a single weighted average dose response to considering how other factors- genetics, social environment, nutrition and mixed chemical exposures- interact with metals, bringing us closer to the real world exposure scenarios. We are confident that our program has the infrastructure, expertise, creativity and energy to continue these lines of research and ultimately improve our ability to prevent and mitigate the toxicity of metals.
Project 3: Exposure Dose Relationship of Toxic Metals
In Project 3, we seek to better understand metal exposures of children and their mothers in settings like Tar Creek by (1) utilizing exposures during and after pregnancy in a rat model, (2) using metal ions as well as complex environmental samples from Tar Creek, and (3) comparing different routes of entry from the environment into the body. As described below, we also performed a collaborative experiment with Project 2, where we examined the solubility and bioavailability of different mineral forms of zinc-containing materials.
Finally we explored the transport of zinc and arsenic, in addition to iron, manganese and cadmium. We also studied the effects of exposure to high levels of lead or manganese as they interact with iron transport, fate and metabolism. Studies on mechanisms of metal transport through the gut, lungs, and nose were major components of this project.
Project 4: Behavioral and Neurochemical Changes Resulting from Metal Exposures
In project 4, we focused on the long term effect of perinatal exposure to different concentrations of manganese (as MnCl2) and lead (as Pb acetate) individually on neurochemistry and behavior in male and female Sprague-Dawley rats. Three different concentration of MnCl2 (1.25, 5 and 10 mg/ml) were chosen, with the highest dose selected based on the maximal tolerated concentration that the rats would consume and the lowest concentration based on the exposure that would increase metal level in the blood or brain tissues.
For Pb acetate, we have completed a wide range of Pb acetate concentrations in order to obtain blood Pb levels that were lower than 10 µg/dL (level that was previously suggested not to produce neurotoxicity). These were grouped as low, medium and high: (1) the low concentration, Pb acetate 2.5-25 µg/ml (blood Pb level < 10 µg/dL); (2) the medium concentration, Pb acetate 100-250 µg/ml (blood Pb level 10-40 µg/dL); and (3) the highest concentration, Pb acetate 2500-4000 µg/ml (blood Pb level > 40 µg/dL). All exposures to the metal occurred via the drinking water to the dams during gestation and lactation.
Journal Articles: 45 Displayed | Download in RIS Format
| Other center views: | All 63 publications | 46 publications in selected types | All 45 journal articles |
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Afeiche M, Peterson KE, Sanchez BN, Schnaas L, Cantonwine D, Ettinger AS, Solano-Gonzalez M, Hernandez-Avila M, Hu H, Tellez-Rojo MM. Windows of lead exposure sensitivity, attained height, and body mass index at 48 months. The Journal of Pediatrics 2012;160(6):1044-1049. |
R831725 (Final) R834800 (2012) R834800 (2013) |
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Arora M, Weuve J, Schwartz J, Wright RO. Association of environmental cadmium exposure with pediatric dental caries. Environmental Health Perspectives 2008;116(6):821-825. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C001 (2008) R831725C003 (2007) R831725C004 (2007) |
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Brain JD, Heilig E, Donaghey TC, Knutson MD, Wessling-Resnick M, Molina RM. Effects of iron status on transpulmonary transport and tissue distribution of Mn and Fe. American Journal of Respiratory Cell and Molecular Biology 2006;34(3):330-337. |
R831725 (2005) R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2005) R831725C003 (2007) R831725C003 (2008) R831725C004 (2007) |
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Cantonwine D, Meeker JD, Hu H, Sanchez BN, Lamadrid-Figueroa H, Mercado-Garcia A, Fortenberry GZ, Calafat AM, Tellez-Rojo MM. Bisphenol A exposure in Mexico City and risk of prematurity:a pilot nested case control study. Environmental Health 2010;9:62. |
R831725 (Final) R834800 (2011) R834800 (2012) |
Exit Exit Exit |
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Chou K, Wright RO. Phthalates in food and medical devices. Journal of Medical Toxicology 2006;2(3):126-135. |
R831725 (Final) |
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Heilig EA, Thompson KJ, Molina RM, Ivanov AR, Brain JD, Wessling-Resnick M. Manganese and iron transport across pulmonary epithelium. American Journal of Physiology–Lung Cellular and Molecular Physiology 2006;290(6):L1247-L1259. |
R831725 (2005) R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2005) R831725C003 (2007) R831725C003 (2008) R831725C004 (2007) |
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Heilig E, Molina R, Donaghey T, Brain JD, Wessling-Resnick M. Pharmacokinetics of pulmonary manganese absorption: evidence for increased susceptibility to manganese loading in iron-deficient rats. American Journal of Physiology–Lung Cellular and Molecular Physiology 2005;288(5):L887-L893. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2005) R831725C003 (2007) R831725C004 (2007) |
Exit Exit |
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Hopkins MR, Ettinger AS, Hernandez-Avila M, Schwartz J, Tellez-Rojo MM, Lamadrid-Figueroa H, Bellinger D, Hu H, Wright RO. Variants in iron metabolism genes predict higher blood lead levels in young children. Environmental Health Perspectives 2008;116(9):1261-1266. |
R831725 (2009) R831725 (Final) R831725C001 (2008) |
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Hu H, Tellez-Rojo MM, Bellinger D, Smith D, Ettinger AS, Lamadrid-Figueroa H, Schwartz J, Schnaas L, Mercado-Garcia A, Hernandez-Avila M. Fetal lead exposure at each stage of pregnancy as a predictor of infant mental development. Environmental Health Perspectives 2006;114(11):1730-1735. |
R831725 (2007) R831725 (2009) R831725 (Final) |
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Hu H, Shine J, Wright RO. The challenge posed to children’s health by mixtures of toxic waste: the Tar Creek Superfund Site as a case-study. Pediatric Clinics of North America 2007;54(1):155-175. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2007) R831725C004 (2007) |
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Lanphear BP, Wright RO, Dietrich KN. Environmental neurotoxins. Pediatrics in Review 2005;26(6):191-198. |
R831725 (2009) R831725 (Final) R831725C001 (2005) R829389 (2003) R829389 (2004) R829389 (2005) R829389 (Final) |
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Oken E, Wright RO, Kleinman KP, Bellinger D, Amarasiriwardena CJ, Hu H, Rich-Edwards JW, Gillman MW. Maternal fish consumption, hair mercury, and infant cognition in a U.S. cohort. Environmental Health Perspectives 2005;113(10):1376-1380. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2005) |
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Ortega Garcia JA, Carrizo Gallardo D, Ferris i Tortajada J, Garcia MM, Grimalt JO. Meconium and neurotoxicants: searching for a prenatal exposure timing. Archives of Disease in Childhood 2006;91(8):642-646. |
R831725 (2009) |
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Ostrea Jr EM, Morales V, Ngoumgna E, Prescilla R, Tan E, Hernandez E, Ramirez GB, Cifra HL, Manlapaz ML. Prevalence of fetal exposure to environmental toxins as determined by meconium analysis. NeuroToxicology 2002;23(3):329-339. |
R831725 (2009) |
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Schaider LA, Senn DB, Brabander DJ, McCarthy KD, Shine JP. Characterization of zinc, lead, and cadmium in mine waste: implications for transport, exposure, and bioavailability. Environmental Science and Technology 2007;41(11):4164-4171. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2007) R831725C004 (2007) |
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Surkan PJ, Schnaas L, Wright RJ, Tellez-Rojo MM, Lamadrid-Figueroa H, Hu H, Hernandez-Avila EM, Bellinger DC, Schwartz J, Perroni E, Wright RO. Maternal self-esteem, exposure to lead, and child neurodevelopment. NeuroToxicology 2008;29(2):278-285. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C001 (2008) R831725C003 (2007) R831725C004 (2007) |
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Tellez-Rojo MM, Bellinger DC, Arroyo-Quiroz C, Lamadrid-Figueroa H, Mercado-Garcia A, Schnaas-Arrieta L, Wright RO, Hernandez-Avila M, Hu H. Longitudinal associations between blood lead concentrations lower than 10 μg/dL and neurobehavioral development in environmentally exposed children in Mexico City. Pediatrics 2006;118(2):e323-e330. |
R831725 (2007) R831725 (2009) R831725 (Final) R835441 (2017) |
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Thompson K, Molina RM, Brain JD, Wessling-Resnick M. Belgrade rats display liver iron loading. Journal of Nutrition 2006;136(12):3010-3014. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2007) R831725C003 (2008) R831725C004 (2007) |
Exit Exit |
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Thompson K, Molina R, Donaghey T, Brain JD, Wessling-Resnick M. The influence of high iron diet on rat lung manganese absorption. Toxicology and Applied Pharmacology 2006;210(1-2):17-23. |
R831725 (2005) R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2005) R831725C003 (2007) R831725C003 (2008) R831725C004 (2007) |
Exit Exit |
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Thompson K, Molina RM, Donaghey T, Schwob JE, Brain JD, Wessling-Resnick M. Olfactory uptake of manganese requires DMT1 and is enhanced by anemia. FASEB Journal 2007;21(1):223-230. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2007) R831725C003 (2008) R831725C004 (2007) |
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Thompson K, Molina RM, Donaghey T, Brain JD, Wessling-Resnick M. Iron absorption by Belgrade rat pups during lactation. American Journal of Physiology-Gastrointestinal and Liver Physiology 2007;293(3):G640-G644. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2007) R831725C003 (2008) R831725C004 (2007) |
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Turker G, Ergen K, Karakoc Y, Arisoy AE, Barutcu UB. Concentrations of toxic metals and trace elements in the meconium of newborns from an industrial city. Biology of the Neonate 2006;89(4):244-250. |
R831725 (2009) |
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Wright RO, Amarasiriwardena C, Woolf AD, Jim R, Bellinger DC. Neuropsychological correlates of hair arsenic, manganese, and cadmium levels in school-age children residing near a hazardous waste site. NeuroToxicology 2006;27(2):210-216. |
R831725 (2005) R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2005) |
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Wright RO, Baccarelli A. Metals and neurotoxicology. The Journal of Nutrition 2007;137(12):2809-2813. |
R831725 (2007) R831725 (2009) R831725 (Final) R831725C001 (2007) R831725C003 (2007) R831725C004 (2007) |
Exit Exit |
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Wright RO, Fields N. Therapeutics and toxicology. Current Opinion in Pediatrics 2008;20(2):171. |
R831725 (2009) R831725 (Final) R831725C001 (2008) |
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Wright RO. Neurotoxicology: what can context teach us? Journal of Pediatrics 2008;152(2):155-157. |
R831725 (2009) R831725 (Final) R831725C001 (2008) |
Exit Exit |
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Wright RO. New morbidities: new challenges. Current Opinion in Pediatrics 2009;21(2):220-221. |
R831725 (2009) R831725 (Final) R831725C001 (2008) |
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Zota AR, Ettinger AS, Bouchard M, Amarasiriwardena CJ, Schwartz J, Hu H, Wright RO. Maternal blood manganese levels and infant birth weight. Epidemiology 2009;20(3):367-373. |
R831725 (2009) R831725 (Final) R831725C001 (2008) |
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Collins JF, Wessling-Resnick M, Knutson MD. Hepcidin regulation of iron transport. The Journal of Nutrition 2008;138(11):2284-2288. |
R831725 (Final) |
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Zota AR, Willis R, Jim R, Norris GA, Shine JP, Duvall RM, Schaider LA, Spengler JD. Impact of mine waste on airborne respirable particulates in northeastern Oklahoma, United States. Journal of the Air & Waste Management Association 2009;59(11):1347-1357. |
R831725 (Final) |
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Pilsner R, Hu H, Ettinger A, Sanchez B, Wright R, Cantonwine D, Lazarus A, Lamadrid-Figueroa H, Mercado-García A, Téllez-Rojo MM, Hernández-Avila M. Influence of prenatal lead exposure on genomic methylation of cord blood DNA. Epidemiology 2009;20(6):S84. |
R831725 (Final) |
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Ettinger AS, Zota AR, Amarasiriwardena CJ, Hopkins MR, Schwartz J, Hu H, Wright RO. Maternal arsenic exposure and impaired glucose tolerance during pregnancy. Environmental Health Perspectives 2009;117(7):1059-1064. |
R831725 (Final) |
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Deb S, Johnson EE, Robalinho-Teixeira RL, Wessling-Resnick M. Modulation of intracellular iron levels by oxidative stress implicates a novel role for iron in signal transduction. Biometals 2009;22:855-862. |
R831725 (Final) |
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Sánchez BN, Hu H, Litman HJ, Téllez-Rojo MM. Statistical methods to study timing of vulnerability with sparsely sampled data on environmental toxicants. Environmental Health Perspectives 201;119(3):409-415. |
R831725 (Final) |
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Cantonwine D, Hu H, Sánchez BN, Lamadrid-Figueroa H, Smith D, Ettinger AS, Mercado-García A, Hernández-Avila M, Wright RO, Téllez-Rojo MM. Critical windows of fetal lead exposure:adverse impacts on length of gestation and risk of premature delivery. Journal of Occupational and Environmental Medicine 2010;52(11):1106-1111. |
R831725 (Final) |
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Cantonwine D, Hu H, Téllez-Rojo MM, Sánchez BN, Lamadrid-Figueroa H, Ettinger AS, Mercado-García A, Hernández-Avila M, Wright RO. HFE gene variants modify the association between maternal lead burden and infant birthweight:a prospective birth cohort study in Mexico City, Mexico. Environmental Health 2010;9:1-9. |
R831725 (Final) |
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Wessling-Resnick M. Iron homeostasis and the inflammatory response. Annual Review of Nutrition 2010;30(1):105-122. |
R831725 (Final) |
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Pilsner JR, Hu H, Wright RO, Kordas K, Ettinger AS, Sanchez BN, Cantonwine D, Lazarus AL, Cantoral A, Schnaas L, Tellez-Rojo MM. Maternal MTHFR genotype and haplotype predict deficits in early cognitive development in a lead-exposed birth cohort in Mexico City. The American Journal of Clinical Nutrition 2010;92(1):226-234. |
R831725 (Final) |
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Molina RM, Phattanarudee S, Kim J, Thompson K, Wessling-Resnick M, Maher TJ, Brain JD. Ingestion of Mn and Pb by rats during and after pregnancy alters iron metabolism and behavior in offspring. Neurotoxicology 2011;32(4):413-422. |
R831725 (Final) |
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Thompson KJ, Molina RM, Donaghey T, Savaliya S, Schwob JE, Brain JD. Manganese uptake and distribution in the brain after methyl bromide-induced lesions in the olfactory epithelia. Toxicological Sciences 2011;120(1):163-172. |
R831725 (Final) |
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Zota AR, Schaider LA, Ettinger AS, Wright RO, Shine JP, Spengler JD. Metal sources and exposures in the homes of young children living near a mining-impacted Superfund site. Journal of Exposure Science & Environmental Epidemiology 2011;21(5):495-505. |
R831725 (Final) |
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Adamkiewicz G, Zota AR, Fabian MP, Chahine T, Julien R, Spengler JD, Levy JI. Moving environmental justice indoors:understanding structural influences on residential exposure patterns in low-income communities. American Journal of Public Health 2011;101(S1):S238-245. |
R831725 (Final) |
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Afeiche M, Peterson KE, Sánchez BN, Cantonwine D, Lamadrid-Figueroa H, Schnaas L, Ettinger AS, Hernández-Avila M, Hu H, Téllez-Rojo MM. Prenatal lead exposure and weight of 0-to 5-year-old children in Mexico City. Environmental Health Perspectives 2011;119(10):1436-1441. |
R831725 (Final) |
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Sánchez BN, Kang S, Mukherjee B. A latent variable approach to study gene–environment interactions in the presence of multiple correlated exposures. Biometrics 2012;68(2):466-476. |
R831725 (Final) |
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Zhang A, Hu H, Sánchez BN, Ettinger AS, Park SK, Cantonwine D, Schnaas L, Wright RO, Lamadrid-Figueroa H, Tellez-Rojo MM. Association between prenatal lead exposure and blood pressure in children. Environmental Health Perspectives 2012;120(3):445-450. |
R831725 (Final) |
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Supplemental Keywords:
Arsenic, behavioral changes, bioavailability, cadmium, gestation, iron, lactation, manganese, metal binding proteins, metal ions, metal transport, mining wastes, neurochemistry, zinc, children, neurobehavioral outcomes, intelligence tests, lead, IQ, ICP-MS, solubility, bioaccessibility, neutron activation, pharmacokinetics, placental transport,, RFA, Health, Scientific Discipline, ENVIRONMENTAL MANAGEMENT, Environmental Chemistry, Health Risk Assessment, Epidemiology, Arsenic, Biochemistry, Children's Health, Immunology, Risk Assessment, community-based intervention, developmental toxicity, Human Health Risk Assessment, neurodevelopmental toxicity, children's environmental health, biological markers, mining wasteRelevant Websites:
Harvard Chan NIEHS Center for Environmental Health Exit
Progress and Final Reports:
Original Abstract Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R831725C001 Metals, Nutrition, and Stress in Child Development
R831725C002 Exposure Assessment of Children and Metals in Mining Waste: Composition, Environmental Transport, and Exposure Patterns
R831725C003 Manganese, Iron, Cadmium, and Lead Transport from the Environment to Critical Organs During Gestation and Early Development in a Rat Model
R831725C004 Metals Neurotoxicity Research Project
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
- 2009 Progress Report
- 2008
- 2007 Progress Report
- 2006
- 2005 Progress Report
- 2004 Progress Report
- Original Abstract
45 journal articles for this center