Early chronic low-level lead exposure reduced C-C chemokine receptor 7 in hippocampal microglia.

Chronic low-level lead exposure alters cognitive function in young children however the mechanisms mediating these deficits in the brain are not known. Previous studies in our laboratory showed that early lead exposure reduced the number of microglial cells in hippocampus/dentate gyrus of C57BL/6 J mice. In the current study, C-C chemokine receptor 7 (CCR7) and major histocompatibility complex II (MHC II) were examined to investigate whether these neuroimmune factors which are known to trigger cell migration and antigen presentation, were altered by early chronic lead exposure. Thirty-six C57BL/6 J male mice were exposed to 0 ppm (controls, n = 12), 30 ppm (low-dose, n = 12), or 430 ppm (higher-dose, n = 12) of lead acetate via dams' milk from postnatal day (PND) 0 to 28. Flow cytometry was used to quantify cell types and cell surface expression of MHC II and CCR7 in hippocampal and whole brain microglia. Non-parametric independent samples median tests were used to test for statistically significant differences between groups. As compared to controls, CCR7 in hippocampal microglia was decreased in the low-dose group, measured as geometric mean fluorescence intensity (GMFI); in the higher-dose group CCR7+MHC II- hippocampal microglia were decreased. Further analyses revealed that the higher-dose group had decreased percentage of CCR7+MHC II- hippocampal macrophages as compared to controls but increased MHC II levels in CCR7+MHC II+ hippocampal macrophages as compared to controls. It was also noted that lead exposure disrupted the balance of MHC II and/or CCR7 in lead exposed animals. Reduced CCR7 in hippocampal microglia might alter the neuroimmune environment in hippocampi of lead exposed animals. Additional studies are needed to test this possibility.

Latent subgroups of cognitive performance in lead- and manganese-exposed Uruguayan children: Examining behavioral signatures.

OBJECTIVES: Lead (Pb) and manganese (Mn) are confirmed neurotoxins but it is unclear to what extent low-level exposure produces a unique behavioral signature. The objective of this study was to investigate latent cognitive profiles among children (6-8 years) from Montevideo, Uruguay co-exposed to these metals. METHOD: Among 345 children, blood Pb and hair Mn were measured using atomic absorption spectroscopy and ICP-MS, respectively. Sixteen measures, reflecting multiple domains of cognitive functioning were gathered: (1) three tests from Cambridge Neuropsychological Test Automated Battery (CANTAB): Intra-Extra Dimensional Shift (IED), Spatial Span (SSP) and Stockings of Cambridge (SOC), (2) ten tasks from Woodcock-Muñoz Achievement Battery, Revised (WM): Visual-Motor Integration, Verbal Comprehension (Vocabulary, Synonyms, Antonyms, Analogies), Visual-Auditory Comprehension, Concept Formation, Visual Spatial Thinking, Number Inversion and Spatial Relations, (3) Bender Gestalt task, and (4) Weschler block design task. Scores were modeled using latent profile analysis (LPA). Association between blood Pb and hair Mn on performance profiles was assessed using ordinal regression, controlling for confounders. An interaction between Pb and Mn was tested. RESULTS: Mean ± SD of blood Pb was 4.1 ± 2.1 µg/dL and 35% of children had blood Pb ≥ 5 µg/dL. Median [5%, 95%] hair Mn level was 0.8 [0.3, 4.1] ppb. Three latent cognitive performance profiles were identified: high (n = 46, 13%), average (n = 209, 61%) and low (n = 90, 26%). Each one-unit increase in blood Pb was associated with a 28% greater likelihood of belonging to a poorer-performing profile. The association was non-linear, with the effect of Pb on profile membership strongest at lower levels of exposure. There was no meaningful interaction between Pb and Mn. CONCLUSIONS: A behavioral signature for low-level Pb & Mn exposure was not identified, but the likelihood of membership in low-performing profile was higher at lowest levels of blood Pb. There was no effect measure modification between Pb and Mn. Future research should address how complex environments created by chemical exposures and the social context relate to cognitive performance in young children.

Elevated lead levels from e-waste exposure are linked to sensory integration difficulties in preschool children.

Exposure to lead is associated with adverse effects on neurodevelopment. However, studies of the effects of lead on sensory integration are few. The purpose of this research is to investigate the effect of lead exposure on child sensory integration by correlating the blood lead levels of children with sensory processing measures. A total of 574 children, from 3 to 6 years of age, 358 from an electronic waste (e-waste) recycling town named Guiyu, and 216 from Haojiang, a nearby town with no e-waste recycling activity, were recruited in this study. The median blood lead level in Guiyu children was 4.88 µg/dL, higher than the 3.47 µg/dL blood lead level in Haojiang children (P < 0.001). 47.2% of Guiyu children had blood lead levels exceeding 5 µg/dL. The median concentration of serum cortisol, an HPA-axis biomarker, in Guiyu children was significantly lower than in Haojiang, and was negatively correlated with blood lead levels. All subscale scores and the total score of the Sensory Processing Measure (Hong Kong Chinese version, SPM-HKC) in Guiyu children were higher than Haojiang children, indicating greater difficulties, especially for touch, body awareness, balance and motion, and total sensory systems. Sensory processing scores were positively correlated with blood lead, except for touch, which was negatively correlated with serum cortisol levels. Simultaneously, all subscale scores and the total SPM-HKC scores for children with high blood lead levels (blood lead > 5 µg/dL) were higher than those in the low blood lead level group (blood lead < 5 µg/dL), especially for hearing, touch, body awareness, balance and motion, and total sensory systems. Our findings suggest that lead exposure in e-waste recycling areas may result in a decrease in serum cortisol levels and an increase in child sensory integration difficulties. Cortisol may be involved in touch-related sensory integration difficulties.

Early chronic exposure to low-level lead alters total hippocampal microglia in pre-adolescent mice.

Developmental lead (Pb) exposure alters brain function through mechanisms that are not yet understood. A previous study showed that early lead exposure reduced microglia number in the dentate gyrus region of the hippocampus. Given the critical role of microglia in brain development, it is important to determine whether these differences are unique to the dentate gyrus, or occur throughout the hippocampus. Unbiased stereology was used to quantify microglia mean cell body number in total hippocampus, and compare the proportion of microglia in the ventral vs. dorsal regions. Total hippocampal volume was also measured and compared. The study included brain tissue from 30 pre-adolescent C57BL/6 J mice, exposed to 30 ppm Pb acetate (n = 10, mean BLL 3.4 µg/dL at sacrifice), 330 ppm Pb acetate (n = 10, mean BLL 14.1 µg/dL at sacrifice), or 0 ppm Pb acetate (n = 10, negative controls). In lead exposed animals, microglia mean cell body number was reduced in total hippocampus; total hippocampal volume was reduced. Importantly, effects in low- and high-dose exposure groups did not differ. Contrary to study hypotheses, the distribution of hippocampal microglia in the ventral vs. dorsal hippocampal regions did not differ. Overall, lowest and higher levels of lead exposure during development had strikingly similar disruptive effects in the neuroimmune system. Studies are needed to determine the immune and other mechanisms responsible for these effects. Future studies would benefit from larger samples to determine whether in fact there is a group by sex interaction driving the effects of early lead exposure on microglia.

The effects of lead on GABAergic interneurons in rodents.

Lead is a heavy metal that affects various systems and organs in the body, especially the nervous system. In this study, the in vivo and in vitro effects of lead on neurons were analyzed. We divided mouse pups into three groups based on the concentration of lead exposure: the control group, the low-dose group, and the high-dose group. Changes in behavior (measured by an open-field test and a tail suspension test), blood lead levels (measured by atomic absorption spectrophotometry), the number of GABAergic interneurons (measured by immunohistochemistry), gene expression (measured by qRT-PCR), and DNA methylation (measured by pyrosequencing) were determined in the three groups. The lead-exposed pups showed significantly higher blood lead levels ( p < 0.001). Lead exposure caused hyperactivity and reduced the body weight of the exposed mice compared with that of the controls. The lead-exposed groups showed significantly lower numbers of parvalbumin and neuropeptide Y interneurons and lower expression levels of distal-less homeobox ( Dlx) 1, 2, 5, and 6 genes in the cerebral cortex. To further clarify the mechanism of Dlx gene downregulation, we selected the GE6 cell line, which can differentiate into various subtypes of GABAergic interneurons, for in vitro experiments. We found that high levels of lead also inhibited the expression of Dlx 1/ 2/ 5/ 6 in vitro, but DNA methylation levels were not changed in the GE6 cell line. Furthermore, lead exposure significantly decreased the expression of Olig1 and Ki67 and increased that of Tubb3 in vitro. The present study revealed that lead exposure can alter behaviors, reduce the number of GABAergic interneurons, and change the expression of some important genes in neuronal cells.

Glycogen metabolism in brain and neurons - astrocytes metabolic cooperation can be altered by pre- and neonatal lead (Pb) exposure.

Lead (Pb) is an environmental neurotoxin which particularly affects the developing brain but the molecular mechanism of its neurotoxicity still needs clarification. The aim of this paper was to examine whether pre- and neonatal exposure to Pb (concentration of Pb in rat offspring blood below the "threshold level") may affect the brain's energy metabolism in neurons and astrocytes via the amount of available glycogen. We investigated the glycogen concentration in the brain, as well as the expression of the key enzymes involved in glycogen metabolism in brain: glycogen synthase 1 (Gys1), glycogen phosphorylase (PYGM, an isoform active in astrocytes; and PYGB, an isoform active in neurons) and phosphorylase kinase ß (PHKB). Moreover, the expression of connexin 43 (Cx43) was evaluated to analyze whether Pb poisoning during the early phase of life may affect the neuron-astrocytes' metabolic cooperation. This work shows for the first time that exposure to Pb in early life can impair brain energy metabolism by reducing the amount of glycogen and decreasing the rate of its metabolism. This reduction in brain glycogen level was accompanied by a decrease in Gys1 expression. We noted a reduction in the immunoreactivity and the gene expression of both PYGB and PYGM isoform, as well as an increase in the expression of PHKB in Pb-treated rats. Moreover, exposure to Pb induced decrease in connexin 43 immunoexpression in all the brain structures analyzed, both in astrocytes as well as in neurons. Our data suggests that exposure to Pb in the pre- and neonatal periods results in a decrease in the level of brain glycogen and a reduction in the rate of its metabolism, thereby reducing glucose availability, which as a further consequence may lead to the impairment of brain energy metabolism and the metabolic cooperation between neurons and astrocytes.

[Intelligence quotient loss in Mexican pottery artisan's children]. / Pérdida de coeficiente intelectual en hijos de alfareros mexicanos.

BACKGROUND: In Mexico, artisans frequently use lead oxide or greta in order to produce utensils, which are destined to preparation and storage of food and drinks. Additionally, the risk of lead poisoning of artisans and their families is greater than in general population, and within these families, children are the most susceptible to lead poisoning. The aim of this study was to estimate IQ loss in Mexican children from potter families exposed to lead. METHODS: Lead concentrations in soil were determined in 19 potter's homes that functioned as pottery workshops in seven Mexican states between 2009 and 2012. This information was used to estimate blood lead levels through the integrated exposure uptake biokinetic (IEUBK) model. The loss of IQ points was then estimated according to the Lanphear and Schwartz models. RESULTS: The mean lead concentration found in the workshops' soil was 1098.4 ppm. Blood lead levels estimated in children under 8 years old were 26.4 µg/dL and the loss of IQ points comprised from 7.13 to 8.84 points depending on the model. CONCLUSIONS: It is possible that 11 children from families of artisans in Mexico may be losing between 7.13 to 8.84 IQ points, due to lead exposure in their houses-workshops. This loss in IQ points could have important health, economic and social impacts.

Introducción: en México, los alfareros continúan usando frecuentemente el óxido de plomo o greta para producir utensilios, los cuales se destinan a la preparación y almacenamiento de alimentos y bebidas. Adicionalmente, el riesgo de intoxicación por plomo de los alfareros y sus familias es mayor que en la población general, y en tales familias, los niños son los más susceptibles a la intoxicación por plomo. El objetivo del estudio fue estimar la pérdida de puntos de coeficiente intelectual (CI) en hijos de alfareros mexicanos expuestos al plomo. Métodos: durante el periodo de 2009 a 2012 se determinaron las concentraciones de plomo en suelo de 19 casas-talleres de alfareros en siete estados mexicanos. Esta información se utilizó para estimar el nivel de plomo en sangre, por medio del modelo biocinético integrado de absorción por exposición (IEUBK, por sus siglas en inglés). Posteriormente, se calcularon los puntos perdidos de CI según los modelos de Schwartz y Lanphear. Resultados: la concentración promedio de plomo en suelo fue de 1098.4 ppm. Se estimó un nivel de plomo en sangre de 26.4 µg/dL para menores de 8 años. La pérdida de puntos de CI estimada fue 7.13 y 8.84, según el modelo utilizado. Conclusión: es posible que al menos 11 niños de familias alfareras mexicanas estén perdiendo entre 7.13 y 8.84 puntos de CI, debido a la exposición al plomo en sus casas-talleres, lo que supone importantes impactos económicos, sociales y de salud.

Environmental and Occupational Lead Exposure Among Children in Cairo, Egypt: A Community-Based Cross-Sectional Study.

The aim of this study was to assess childhood lead exposure in a representative sample of Cairo, and to investigate the possible risk factors and sources of exposure. This cross-sectional study was conducted from November 2014 through April 2015. The target population was children aged 6 to 18 years, recruited into 4 groups, garbage city, moderate-living standard area, urban and suburban schools, and workshops in the city of Cairo. Blood lead levels (BLLs) and hemoglobin (Hb) concentrations were measured. Also, potential local environmental sources were assessed for hazardous lead contamination. Analysis on 400 participants has been carried out. A total of 113 children had BLLs in the range 10 to 20 µg/dL. Smoking fathers, housing conditions, playing outdoors, and exposure to lead in residential areas were significantly correlated with high BLLs. The mean values of hemoglobin were inversely correlated with BLLs. Children involved in pottery workshops had the highest BLLs and the lowest Hb values with a mean of (43.3 µg/dL and 8.6 g/dL, respectively). The mean value of environmental lead in workshop areas exceeded the recommended levels. Also, those values measured in dust and paint samples of garbage city were significantly high. Moreover, the mean lead levels in the soil samples were significantly higher in urban schools (P = 0.03) than the suburban ones. Childhood lead poisoning accounts for a substantial burden in Egypt, which could be preventable. Development of national prevention programs including universal screening program should be designed to reduce incidence of lead toxicity among children.

Low Levels of Awareness of Lead Hazards among Pregnant Women in a High Risk--Johannesburg Neighbourhood.

BACKGROUND: The widespread use of lead and elevated risk of lead exposure in South African children justifies a need for high levels of awareness of the sources, exposure pathways, and measures to reduce this risk in children. This study aimed to determine the levels of knowledge of lead hazards among pregnant women in an area where children had already been established to be at a high risk of lead exposure and poisoning. METHODS: Following informed consent, a structured questionnaire was administered to 119 pregnant women attending antenatal clinic services at Rahima Moosa Mother and Child Hospital, west of central Johannesburg. Questions were asked about social, demographic and residential characteristics, as well as knowledge, perceptions, behaviours and practices in relation to child lead hazards. CONCLUSION: Overall awareness of the dangers of lead in pregnancy was low (11%). Amongst those who had heard of it, only 15% thought that lead could cause detrimental health effects. A consequence of this low level of awareness of lead hazards is a high potential for the participants and their children to unwittingly be exposed to environmental lead from various sources, thereby undermining preventative approaches.

Occupational and environmental lead exposure to adolescent workers in battery recycling workshops.

Lead (Pb), as other environmental neurotoxicant substances, has the capability to interfere with many biochemical events present in cells throughout the body. In the present study, the environmental and occupational exposure to Pb has been assessed by analyzing the scalp hair samples of male adolescents aged 12-15 years, who have worked for the last 12-36 months in Pb battery recycling workshops (BRWs). For comparative purposes, gender and age-matched subjects living in the vicinity of recycling workshops as well as in areas without industrial activity were used as controls. The scalp hair samples were oxidized by acid in a microwave oven prior to determination of Pb by electrothermal atomic absorption spectrometry. The results indicated that both workers and nonworking exposed subjects had higher levels of Pb than nonexposed controls. The contents of Pb in scalp hair of adolescent workers in the present study were compared with those reported in other studies.

Effects of lead exposure on D-serine metabolism in the hippocampus of mice at the early developmental stages.

The aim of this study was to explore the mechanisms of lead neurotoxicity by focusing on the alteration of D-serine metabolism in the hippocampus of mice at the early life. Mother mice and their offspring were exposed to 0, 0.5, 1.0 and 2.0 g/L lead in lead acetate via drinking water from the first day of gestation until the postnatal day (PND) 40. Morris water maze was used to measure the spatial learning and memory ability of PND 40 mice. Expressions of serine racemase (SR), D-amino acid oxidase (DAAO), alanine-serine- cysteine transporter-1 (asc-1) and subunits of N-methyl-D-aspartate receptor (NMDAR) in the hippocampus of PND 10, 20 and 40 mice were examined by western blot and real time RT-PCR. Findings from this study disclosed that the spatial learning ability of mice tested by place trial could be significantly impaired by 0.5 g/L lead exposure, and the spatial memory ability tested by probe trail could be impaired by 1.0 g/L lead exposure. Exposure to 2.0 g/L lead in the water could significantly inhibit the protein and mRNA expression of SR; conversely enhance the expression of DAAO protein and mRNA in the hippocampus during the early developmental stages. However, the protein expressions of DAAO and asc-1 in the hippocampus were significantly enhanced by 0.5 g/L lead exposure at different developmental stages. On the other hand, the protein and mRNA expressions of both NR1 and NR2A were inhibited significantly by 1.0 g/L lead exposure since PND 10, and by 0.5 g/L lead exposure since PND 20. Noteworthy, the protein expression of NR2B was inhibited significantly by 0.5 g/L lead exposure in PND 10 mice, and by 1.0 g/L lead exposure in PND 20 mice, but there was no significant group difference in PND 40 mice. Meanwhile, expressions of asc-1 and NR2B mRNA were not affected obviously by lead exposure. In conclusion, chronic lead exposure during brain development might affect D-serine metabolism by enhancing its degradation, which might be related to the inhibited expression of NMDAR subunits, and furthermore contribute to deficits in learning and memory ability in mice.

Unknown risk: co-exposure to lead and other heavy metals among children living in small-scale mining communities in Zamfara State, Nigeria.

The lead poisoning crisis in Zamfara State, Northern Nigeria has been called the worst such case in modern history and it presents unique challenges for risk assessment and management of co-exposure to multiple heavy metals. More than 400 children have died in Zamfara as a result of ongoing lead intoxication since early in 2010. A review of the common toxic endpoints of the major heavy metals advances analysis of co-exposures and their common pathologies. Environmental contamination in Bagega village, examined by X-ray fluorescence of soils, includes lead, mercury, cadmium, arsenic and manganese. Co-exposure risk is explored by scoring common toxic endpoints and hazard indices to calculate a common pathology hazard risk ranking of Pb > As > Hg >> Cd > Mn. Zamfara presents an extreme picture of both lead and multiple heavy metal mortality and morbidity, but similar situations have become increasingly prevalent worldwide.

Epigenetic histone modification regulates developmental lead exposure induced hyperactivity in rats.

Lead (Pb) exposure was commonly considered as a high environmental risk factor for the development of attention-deficit/hyperactivity disorder (ADHD). However, the molecular basis of this pathological process still remains elusive. In light of the role of epigenetics in modulating the neurological disease and the causative environment, the alterations of histone modifications in the hippocampus of rats exposed by various doses of lead, along with concomitant behavioral deficits, were investigated in this study. According to the free and forced open field test, there showed that in a dosage-dependent manner, lead exposure could result in the increased locomotor activity of rats, that is, hyperactivity: a subtype of ADHD. Western blotting assays revealed that the levels of histone acetylation increased significantly in the hippocampus by chronic lead exposure, while no dramatic changes were detected in terms of expression yields of ADHD-related dopaminergic proteins, indicating that histone acetylation plays essential roles in this toxicant-involved pathogenesis. In addition, the increased level of histone acetylation might be attributed to the enzymatic activity of p300, a typical histone acetyltransferase, as the transcriptional level of p300 was significantly increased upon higher-dose Pb exposure. In summary, this study first discovered the epigenetic mechanism bridging the environmental influence (Pb) and the disease itself (ADHD) in the histone modification level, paving the way for the comprehensive understanding of ADHD's etiology and in further steps, establishing the therapy strategy of this widespread neurological disorder.

Role of chelation in the treatment of lead poisoning: discussion of the Treatment of Lead-Exposed Children Trial (TLC).

Lead exposure in children is one component leading to cognitive impairment. The Treatment of Lead-Exposed Children Trial (1994-2004) studied the effect of succimer in treating low levels of lead exposure (20-44 mcg/dL) in children 12 to 33 months old. While succimer was effective in reducing blood lead concentrations in the short term, treatment of blood lead levels did not result in any detectable improvement in a wide variety of measurements of cognitive or behavioral function. Furthermore, blood lead concentrations were not distinguishable between chelated and non-chelated individuals at 1 year. The most important treatment strategy is identification and termination of major sources of lead exposure.

Primary prevention of pediatric lead exposure requires new approaches to transfusion screening.

OBJECTIVE: To facilitate further assessment of transfusion-associated lead exposure by designing a procedure to test packed red blood cells (pRBCs) prepared for transfusion. STUDY DESIGN: The relationship between pRBCs and whole blood lead concentration was investigated in 27 samples using a modified clinical assay. Lead concentrations were measured in 100 pRBC units. RESULTS: Our sample preparation method demonstrated a correlation between whole blood lead and pRBC lead concentrations (R(2) = 0.82). In addition, all 100 pRBC units tested had detectable lead levels. The median pRBC lead concentration was 0.8 µg/dL, with an SD of 0.8 µg/dL and a range of 0.2-4.1 µg/dL. In addition, after only a few days of storage, approximately 25% of whole blood lead was found in the supernatant plasma. CONCLUSION: Transfusion of pRBCs is a source of lead exposure. Here we report the quantification of lead concentration in pRBCs. We found a >20-fold range of lead concentrations in the samples tested. Pretransfusion testing of pRBC units according to our proposed approach or donor screening of whole blood lead and selection of below-average units for transfusion to children would diminish an easily overlooked source of pediatric lead exposure.

The conjoint influence of home enriched environment and lead exposure on children's cognition and behaviour in a Mexican lead smelter community.

A range of studies has been conducted on the detrimental effects of lead in mining and smelting communities. The neurocognitive and behavioural health effects of lead on children are well known. This research characterized the conjoint influence of lead exposure and home enriched environment on neurocognitive function and behaviour for first-grade children living in a Mexican lead smelter community. Structural equation models were used for this analysis with latent outcome variables, Cognition and Behaviour, constructed based on a battery of assessments administered to the first-grade children, their parents, and teachers. Structural equation modelling was used to describe complex relationships of exposure and health outcomes in a manner that permitted partition of both direct and indirect effects of the factors being measured. Home Environment (a latent variable constructed from information on mother's education and support of school work and extracurricular activities), and child blood lead concentration each had a main significant effect on cognition and behaviour. However, there were no statistically significant moderation relationships between lead and Home Environment on these latent outcomes. Home Environment had a significant indirect mediation effect between lead and both Cognition and Behaviour (p-value<0.001). The mediation model had a good fit with Root Mean Square Error of Approximation <0.0001 and a Weighted Root Mean Square Residual of 0.895. These results were highly significant and suggest that Home Environment has a moderate mediation effect with respect to lead effects on Behaviour (ß=0.305) and a lower mediation effect on Cognition (ß=0.184). The extent of home enrichment in this study was most highly related to the mother's support of schoolwork and slightly less by the mother's support of extracurricular activities or mother's education. Further research may be able to develop approaches to support families to make changes within their home and child rearing practices, or advocate for different approaches to support their child's behaviour to reduce the impact of lead exposure on children's cognitive and behavioural outcomes.

Prenatal lead and cadmium co-exposure and infant neurodevelopment at 6 months of age: the Mothers and Children's Environmental Health (MOCEH) study.

BACKGROUND: This study aimed to explore the developmental effects of prenatal exposure to Pb and Cd on infant cognitive development at 6 months of age. METHODS: Between 2006 and 2010, the blood levels of Pb and Cd were measured in 884 mothers during their early and late pregnancy. The mental (MDI) and psychomotor (PDI) development index scores of the infants were assessed using the Bayley Scales of Infant Development. The development index scores were adjusted for birth weight, maternal age, maternal education level, family income, breastfeeding status, and residential area. RESULTS: The geometric mean of the maternal blood concentration was 1.36µg/dL (10th percentile=0.83; 90th percentile=2.13; range=0.26-9.10) for Pb and 1.42µg/L (10th percentile=1.01; 90th percentile=2.16; range=0.03-9.87) for Cd during the early pregnancy period and 1.27µg/dL (10th percentile=0.77; 90th percentile=2.10; range=0.12-4.28) for Pb and 1.52µg/L for Cd (10 percentile=1.07; 90th percentile=2.10; range=0.43-3.73) during the late pregnancy period. The prenatal Pb and Cd concentrations during the early pregnancy period showed no association with the adjusted MDI or PDI scores. The antagonistic interaction between the prenatal Pb and Cd levels during the early pregnancy period had a significant effect on the MDI score (B=-4.64, 95% CI=-8.17 to -1.12, p=0.01), but the effect of this interaction did not reach statistical significance for the PDI score (B=-3.69, 95% CI=-7.94 to 0.56, p=0.09). The Pb levels during the late pregnancy period were inversely associated with the MDI score (B=-1.94, 95% CI=-3.60 to -0.29, p=0.02) but not with the PDI score (B=-1.69, 95% CI=-3.65 to 0.27, p=0.09). The prenatal Cd levels during the late pregnancy period showed no association with the MDI or PDI score. However, the MDI score (B=-3.20, 95% CI=-5.35 to -1.06, p<0.01) and the PDI score (B=-2.86, 95% CI=-5.55 to -0.16, p=0.04) of infants with Cd levels >1.51µg/L were significantly associated with the Pb level, whereas there were no such associations for infants with Cd levels <1.51µg/L. These results suggest that there is a synergistic effect modification between Pb and Cd during the late pregnancy period. CONCLUSIONS: These findings suggest that there is dose-dependent interaction between prenatal exposure to Pb and prenatal exposure to Cd. The results further demonstrate the biological complexities of examining the neurodevelopmental effects of co-exposure to multiple toxicants.

Effects of chronic lead exposure on functions of nervous system in Chinese children and developmental rats.

Lead pollution is a very serious problem in China with the rapid economic development. A large amount of lead has been released into the environment due to mineral processing activities and has impacted water resources, soils, vegetables, and crops. The gasoline with lead has been banned in China since July 1, 2000. Though a noticeable decrease of lead poisoning rates has been evidenced, the children's blood lead levels are still significantly higher than those in developed countries. Therefore, lowering the lead exposure in childhood continues to be an important public health objective in China. There is also a lot that remains to be done to reduce children's exposure to lead. In this section, five scientists from China presented latest research results regarding the current situation of lead poisoning in China, the mechanisms involved in lead-induced neurotoxicity, and the new advances related to the potential therapy methods. Their researches may pave new way not only for the prevention of lead poisoning but also for the treatment of affected children in China and other countries.

Association between lead exposure from electronic waste recycling and child temperament alterations.

We aimed to evaluate the dose-dependent effects of lead exposure on temperament alterations in children from a primitive e-waste (obsolete electrical and electronic devices) recycling area in Guiyu of China and a control area (Chendian, China). Blood lead levels (BLL) might be correlated with temperament, health, and relevant factors that were evaluated through Parent Temperament Questionnaire (PTQ), physical examination, and residential questionnaires. We collected venipuncture blood samples from 303 children (aged 3-7 years old) between January and February 2008. Child BLL were higher in Guiyu than in Chendian (median 13.2 µg/dL, range 4.0-48.5 µg/dL vs. 8.2 µg/dL, 0-21.3 µg/dL) (P<0.01). Significant differences of mean scores in activity level (4.53±0.83 vs. 4.18±0.81), approach-withdrawal (4.62±0.85 vs. 4.31±0.89), and adaptability (4.96±0.73 vs. 4.67±0.83) were found between Guiyu and Chendian children (all P<0.01). High BLL (BLL≥10µg/dL) child had higher mean scores of approach-withdrawal when compared with those children with low BLL (BLL<10 µg/dL) (4.61±0.87 vs. 4.30±0.88, P<0.01). Location of child residence in Guiyu, and parents engagement in work related to e-waste were the risk factors related to child BLL, activity level, approach-withdrawal, adaptability, and mood. Child hand washing prior to food consumption was a protected factor for BLL and several dimensions. There are close relationships between BLL elevation, temperament alteration and the e-waste recycling activities in Guiyu. Primitive e-waste recycling may threaten the health of children by increasing BLL and altering children temperament, although the exposure to other toxicants needs to be examined in future studies.