Therapeutic Effect of Smilax glabra Roxb. on Weaning Rats Against Pb-Induced Nephrotoxicity Based on Network Pharmacology.

Lead (Pb) is a major environmental pollutant that can cause nephrotoxicity, hepatotoxicity, encephalopathy, and even death. Smilax glabra Roxb. has been used to treat heavy metal poisoning in China for over 500 years. We hypothesized that the Smilax glabra flavonoid extract (SGF) can ameliorate lead poisoning and investigated the possible mechanisms using network pharmacology. In total, 13 active compounds of Smilax glabra Roxb. and 71 overlapping potential targets were identified. The drug-compound-target-disease network analysis revealed that oxidative stress, inflammation, and apoptosis were mainly involved in the treatment of lead poisoning. Gene Ontology (GO) enrichment analysis showed that the biological processes involved in the therapeutic effect of Smilax glabra Roxb. against lead poisoning included biological processes, cellular components, and molecular functions. Additionally, 112 Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathways were obtained with the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways showing strong associations with lead poisoning by KEGG enrichment. The results of target pathway analysis showed that NF-κB was the most relevant gene involved in the therapeutic effect of Smilax glabra Roxb. against lead poisoning and was closely related to the MAPK signaling pathway. In vivo experiments confirmed that SGF treatment alleviated the pathological damage caused by lead-induced nephrotoxicity in weaning rats. Furthermore, SGF treatment markedly inhibited the expression of key proteins involved in the NF-κB/MAPK signaling pathway, highlighting the strong therapeutic effect of SGF against lead-induced nephrotoxicity. Results from network pharmacology and experimental verification indicated that SGF mitigated Pb-induced nephrotoxicity by downregulating the NF-κB/MAPK signaling pathway.

A Possible Nocebo Effect in Children Following the Flint Water Crisis: Evidence From Schoolteacher Perceptions and Neuropsychological Evaluations.

OBJECTIVE: Special education enrollment increased in Flint following the 2014-2015 Flint Water Crisis, but lead exposure is not plausibly responsible. Labeling Flint children as lead poisoned and/or brain damaged may have contributed to rising special education needs (ie, nocebo effect). To better document this possibility, we surveyed schoolteachers and reviewed neuropsychological assessments of children for indications of negative labeling. METHODS: A survey of Flint and Detroit (control) public schoolteachers using a modified Illness Perception Questionnaire was conducted 5 years post-crisis. We also examined neuropsychological assessments from a recently settled class lawsuit. RESULTS: Relative to Detroit (n = 24), Flint teachers (n = 11) believed that a higher proportion of their students had harmful lead exposure (91.8% Flint vs 46% Detroit; P = 0.00034), were lead poisoned (51.3% vs 24.3%; P = 0.018), or brain damaged (28.8% vs 12.9%; P = 0.1), even though blood lead of Flint children was always less than half of that of Detroit children. Neuropsychological assessments diagnosed lead poisoning and/or brain damage from water lead exposure in all tested children (n = 8), even though none had evidence of elevated blood lead and a majority had prior learning disability diagnoses. CONCLUSION: Teachers' responses and neuropsychological assessments suggest Flint children were harmed by a nocebo effect.

Association between relatively low blood lead levels and urinary δ-aminolevulinic acid concentrations among male workers at a Japanese battery factory.

OBJECTIVES: Whether the known positive association between blood lead (PbB) levels and urinary δ-aminolevulinic acid (ALAU) also exists at relatively low PbB levels (<40 µg/dL) remains unclear. We aimed to investigate this association at lower PbB levels. METHODS: We analyzed data from biannual medical examinations of workers at a Japanese factory from August 2013 to August 2023. We excluded records from female workers and those with missing data, resulting in a dataset consisting of 1396 records from 155 male workers. We employed mixed-effect linear regression models with a random intercept for workers and additional adjustments for age and smoking status. RESULTS: The median PbB level across all the analyzed records was 8 µg/dL (range: 1, 31 µg/dL). Significant positive associations were observed between PbB and ALAU, with a one-unit increase in natural logarithm-transformed PbB corresponding to a 10.0% increase in ALAU (95% CI: 2.7, 17.9%). Categorized PbB analyses showed a 23.8% increase in ALAU (95% CI: 2.7, 49.2%) for PbB levels at 20-24 µg/dL and an 83.1% increase (95% CI: 30.1, 157.7%) for PbB levels ≥25 µg/dL, compared to those <5 µg/dL. The exposure-response curve analysis indicated a plateau followed by an increasing trend. CONCLUSIONS: A positive and non-linear association between PbB and ALAU levels was observed at relatively low PbB levels.

High lead contamination in Mother's breastmilk in Bihar (India): Health risk assessment of the feeding children.

Lead poisoning in the recent times has caused serious health threats in the exposed human population. It is estimated that about 815 million people are exposed to lead poisoning worldwide and in India total 275 million children are exposed to blood lead contamination. The present study was carried outed in 6 districts of Bihar to know the extent of lead exposure in the children through their mother's breastmilk. The biological samples such as breastmilk, mother's urine, child's urine, and mother's blood samples were collected for quantitative lead estimation. Moreover, the selected household water sources (handpump) and the food consumed by the individuals-wheat, rice and potato samples were also collected for lead quantification. The study reveals that the breastmilk had high lead content in 92% of the samples (highest value 1309 µg/L), in blood presence of lead was observed in 87% studied samples (highest value 677.2 µg/L). In mother's urine the highest lead value was 4168 µg/L (62%) and in child's urine the highest value was 875.4 µg/L (62%) respectively of the studied samples. Moreover, in the studied food samples, wheat had lead content in 45% the studied samples (highest value 7910 µg/kg). In rice in 40% of the studied samples (highest value 6972 µg/kg) and in potato 90% of the studied samples (highest value = 13786 µg/kg) were found with elevated lead content respectively. The hazard quotient (HQ) and the cancer risk (CR) for lead contamination was very much higher in mothers followed by their children. The entire study indicated that lead exposure through food (wheat, rice and potato) has reached the mother's breastmilk and from their it has reached their child's body. This could cause serious hazards in the exposed children causing serious neurological damages, low IQ, low memory, and low mental growth in them. Therefore, a strategic action is required to control the present problem.

Applied Informatics Innovation Within a Childhood Blood Lead Poisoning Prevention Program Resulted in Improved Data Management and Demonstrated Client Outcomes.

This poster presentation describes innovative use of the Omaha System, a standardized terminology, into public health nurses' (PHNs) workflow and electronic records within a local health department's Childhood Lead Poisoning Prevention Program. The Omaha System facilitated the tracking of evidence-based interventions and client outcomes, showing a significant improvement in record completeness (from 33% pre-implementation to 84% post-implementation) and client outcomes in health care supervision, growth and development, and nutrition. Outcome data analysis revealed improvement across all post-implementation records from initial assessments to interim assessments for Health care supervision (p<.001), Growth and development (p<.001), and Nutrition (p = .025). This achievement has given program leaders and employees the ability to clearly present their services and results to policymakers, facilitating better assessment of the program's effectiveness. The successful implementation illustrates its potential applicability to other public health projects and areas.

Radiological changes in lead poisoning.

INTRODUCTION: Lead poisoning in childhood remains an important public health concern. We highlight the radiological findings in a patient with a high blood lead concentration. CASE SUMMARY: A 7-year-old girl presented to hospital with abdominal pain, nausea, and asthenia. Laboratory tests showed severe hypochromic microcytic anemia, punctate basophilic stippling of erythrocytes, and a blood lead concentration of 880 µg/L (4.3 µmol/L). IMAGES: Radiographs of the femur, tibia, and fibula demonstrated dense metaphyseal bands ("lead lines"). On cranial computed tomography, we observed multiple speck-like and curvilinear hyperdensities involving subcortical regions, putamen, and left cerebellar hemisphere. CONCLUSION: In patients with lead poisoning, imaging of the brain and bones may show characteristic features. These imaging findings may point to the diagnosis of lead toxicity when these radiographic findings are discovered during the evaluation of vague complaints such as abdominal pain or mental status changes or when a blood lead concentration is not readily available.

One in Four US Households Likely Exceed New Soil Lead Guidance Levels.

Lead exposure has blighted communities across the United States (and the globe), with much of the burden resting on lower income communities, and communities of color. On 17 January 2024, the US Environmental Protection Agency (USEPA) lowered the recommended screening level of lead in residential soils from 400 to 200 parts per million. Our analysis of tens of thousands of citizen-science collected soil samples from cities and communities around the US indicates that nearly one quarter of households may contain soil lead that exceed the new screening level. Extrapolating across the nation, that equates to nearly 30 million households needing to mitigate potential soil lead hazards, at a potential total cost of 290 billion to $1.2 trillion. We do not think this type of mitigation is feasible at the massive scale required and we have instead focused on a more immediate, far cheaper strategy: capping current soils with clean soils and/or mulch. At a fraction of the cost and labor of disruptive conventional soil mitigation, it yields immediate and potentially life-changing benefits for those living in these environments.

Trends in Shortages of Lead Chelators From 2001 to 2022.

OBJECTIVE: The study aims to describe drug shortages affecting lead chelators in the United States from 2001 through 2022. METHODS: Drug shortage data were retrieved from the University of Utah Drug Information Service from January 1, 2001, through December 31, 2022. Shortages of first- and second-line lead chelators were analyzed. Drug class, formulation, administration route, shortage reason, shortage duration, generic status, single-source status, and presence of temporally overlapping shortages were examined. Total shortage months, percentages of study period on shortage, and median shortage durations were calculated. RESULTS: Thirteen lead chelator shortages were reported during the study period. Median duration was 7.4 months and the longest shortage (24.8 months) involved calcium disodium edetate. Calcium disodium edetate and dimercaprol had the greatest number of shortages, 4 each, and 61.5% of shortages involved parenteral medications. Median shortage duration was 14.2 months for parenteral agents and 2.2 months for non-parenteral agents. All shortages involved generic, single-source products. Supply/demand and manufacturing problems were the most common shortage reasons provided. Overlapping shortages occurred for 3.7% of the study period. Median shortage duration increased from 3 to 11 months in the second half of the study period, and 61.5% of shortages occurred in the second half of the study period. CONCLUSIONS: All chelators experienced multiple shortages, which became increasingly frequent and prolonged over time. Concurrent shortages occurred, potentially hampering substitution between different agents. Health care stakeholders must build supply chain resilience and develop guidelines regarding how to modify chelation therapy based on shortage conditions.

Burton's Line on the Gum Seen in Lead Poisoning Among Petroleum Refinery Workers in Kirkuk City, Iraq: A Case Series.

Lead poisoning is a serious occupational health risk, especially for those who work in fields where lead-containing products are frequently exposed, including petroleum refining. Three cases of lead poisoning among employees of the petroleum refinery in Kirkuk City, Iraq, have been presented in this case series, emphasizing the clinical significance of Burton's line (blue-purplish line or gingival pigmentation) on the gums as an indication of lead toxicity. Patients presented with typical gingival margin darkening along with symptoms like fatigue, headaches, abdominal pain, and neurological impairments. Subsequent laboratory analysis confirmed that all three patients had increased blood lead levels, which ranged from 30 to 43 µg/dL (normal range <10 µg/dL). In the process of refining petroleum, lead can be inhaled, ingested, or come into direct touch with lead-containing items. Burton's line identification is essential for prompt diagnosis and intervention. This case series highlights the importance of taking preventative action to lessen the risks of lead exposure and protect the well-being and safety of employees of petroleum refineries. Healthcare providers should be vigilant, and strict safety protocols, worker education, and regular monitoring are all essential.

Co-administration of resveratrol rescued lead-induced toxicity in Drosophila melanogaster.

Lead toxicity poses a significant environmental concern linked to diverse health issues. This study explores the potential mitigating effects of resveratrol on lead-induced toxicity in Drosophila melanogaster. Adult fruit flies, aged three days, were orally exposed to lead (60 mg/L), Succimer (10 mg), and varying concentrations of resveratrol (50, 100, and 150 mg). The investigation encompassed the assessment of selected biological parameters, biochemical markers, oxidative stress indicators, and antioxidant enzymes. Resveratrol exhibited a dose-dependent enhancement of egg-laying, eclosion rate, filial generation output, locomotor activity, and life span in D. melanogaster, significantly to 150 mg of diet. Most of the investigated biochemical parameters were significantly rescued in lead-exposed fruit flies when co-treated with resveratrol (p < 0.05). However, oxidative stress remained unaffected by resveratrol. The findings suggest that resveratrol effectively protects against lead toxicity in Drosophila melanogaster and may hold therapeutic potential as an agent for managing lead poisoning in humans.

Abdominal pain caused by Tibetan medicine: A case report of lead poisoning.

Nowadays, lead poisoning in children commonly occurs, but lead poisoning caused by the administration of Tibetan medicine is rarely reported. This report describes the diagnosis and management of lead poisoning in a 16-year-old girl presented with abdominal pain, vomiting, and anemia with limb numbness, who had a childhood history of epilepsy and took Tibetan medicine intermittently to control the symptoms. After admission into hospital, Computed tomography showed high-density shadows in the gastrointestinal tract. Video-Electroencephalography showed no signs of seizure. Reflux esophagitis was observed in gastroscopy. And no obvious abnormalities in the colonic mucosa through colonoscopy. Bone marrow smear test showed basophilic stippling in the erythrocytes. The blood and urine lead levels of 626 and 75.9 µg/L, respectively. We therefore considered lead poisoning, and the patient improved after chelation therapy. Due to its atypical clinical manifestations, lead poisoning is easily misdiagnosed. Thus, clinicians should pay more attention to this disease. When abdominal pain, anemia, and neurological symptoms are present, the possibility of lead poisoning should be considered.

Peppered with lead: An environmental forensics approach to identify the source of rising blood lead levels.

Despite the phase-out of lead-based products, lead contamination can still present a contemporary risk to public health. In situations where elevated blood lead cannot be attributed to common sources, detailed environmental investigation is needed to identify more elusive sources and manage harmful exposure pathways. We apply a forensics approach to assess common and elusive sources of lead in the home environment of two individuals with fluctuating blood lead levels in Sydney, Australia. Using multiple analytical lines of evidence (portable X-Ray Fluorescence spectrometry (pXRF), inductively coupled-plasma mass spectrometry (ICP-MS), lead isotopic compositional analysis (PbIC) and haematological assessment) a pewter pepper grinder containing lead (>6000 mg/kg; 70% bioavailable) was identified as a potential source. After removing the pepper grinder from the home, the couple's blood lead decreased to below the Australian intervention level of 5 µg/dL within a year (Person A: from 12.5 µg/dL in August 2020 to 4.4 µg/dL in March 2022; and Person B: 15.4 µg/dL in August 2020 to 2.1 µg/dL in July 2021). This case study demonstrates how environmental science investigations can play a crucial role in supporting people to take evidence-based action to improve their health.

Effect of Environmental and Socioeconomic Factors on Increased Early Childhood Blood Lead Levels: A Case Study in Chicago.

This study analyzes the prevalence of elevated blood lead levels (BLLs) in children across Chicagoland zip codes from 2019 to 2021, linking them to socioeconomic, environmental, and racial factors. Wilcoxon tests and generalized additive model (GAM) regressions identified economic hardship, reflected in per capita income and unemployment rates, as a significant contributor to increased lead poisoning (LP) rates. Additionally, LP rates correlate with the average age of buildings, particularly post the 1978 lead paint ban, illustrating policy impacts on health outcomes. The study further explores the novel area of land surface temperature (LST) effects on LP, finding that higher nighttime LST, indicative of urban heat island effects, correlates with increased LP. This finding gains additional significance in the context of anthropogenic climate change. When these factors are combined with the ongoing expansion of urban territories, a significant risk exists of escalating LP rates on a global scale. Racial disparity analysis revealed that Black and Hispanic/Latino populations face higher LP rates, primarily due to unemployment and older housing. The study underscores the necessity for targeted public health strategies to address these disparities, emphasizing the need for interventions that cater to the unique challenges of these at-risk communities.

Mapping Blood Lead Levels in China during 1980-2040 with Machine Learning.

Lead poisoning is globally concerning, yet limited testing hinders effective interventions in most countries. We aimed to create annual maps of county-specific blood lead levels in China from 1980 to 2040 using a machine learning model. Blood lead data from China were sourced from 1180 surveys published between 1980 and 2022. Additionally, regional statistical figures for 15 natural and socioeconomic variables were obtained or estimated as predictors. A machine learning model, using the random forest algorithm and 2973 generated samples, was created to predict county-specific blood lead levels in China from 1980 to 2040. Geometric mean blood lead levels in children (i.e., age 14 and under) decreased significantly from 104.4 µg/L in 1993 to an anticipated 40.3 µg/L by 2040. The number exceeding 100 µg/L declined dramatically, yet South Central China remains a hotspot. Lead exposure is similar among different groups, but overall adults and adolescents (i.e., age over 14), females, and rural residents exhibit slightly lower exposure compared to that of children, males, and urban residents, respectively. Our predictions indicated that despite the general reduction, one-fourth of Chinese counties rebounded during 2015-2020. This slower decline might be due to emerging lead sources like smelting and coal combustion; however, the primary factor driving the decline should be the reduction of a persistent source, legacy gasoline-derived lead. Our approach innovatively maps lead exposure without comprehensive surveys.

Subnormal Serum Liver Enzyme Levels: A Review of Pathophysiology and Clinical Significance.

Subnormal levels of liver enzymes, below the lower limit of normal on local laboratory reports, can be useful diagnostically. For instance, subnormal levels of aminotransferases can be observed in vitamin B6 deficiency and chronic kidney disease. Subnormal alkaline phosphatase levels may indicate the presence of hypophosphatasia, Wilson's disease, deficiencies of divalent ions, or malnutrition. Subnormal levels of gamma glutamyl transferase may be seen in cases of acute intrahepatic cholestasis, the use of certain medications, and in bone disease. Finally, subnormal levels of 5'-nucleotidase have been reported in lead poisoning and nonspherocytic hemolytic anemia. The aim of this review is to bring attention to the fact that subnormal levels of these enzymes should not be ignored as they may indicate pathological conditions and provide a means of early diagnosis.

United States house dust Pb concentrations are influenced by soil, paint, and house age: insights from a national survey.

BACKGROUND: Lead (Pb) in house dust contributes significantly to blood lead levels (BLLs) in children which may result in dire health consequences. Assessment of house dust Pb in the United States, relationships with Pb in soil and paint, and residential factors influencing Pb concentrations are essential to probing drivers of house dust Pb exposure. OBJECTIVE: Pb concentrations in vacuum-collected house dust are characterized across 346 homes participating in the American Health Homes Survey II (AHHS II), a US survey (2018-2019) evaluating residential Pb hazards. Connections between house dust Pb and soil Pb, paint Pb, and other residential factors are evaluated, and dust Pb concentration data are compared to paired loading data to understand Pb hazard standard implications. RESULTS: Mean and median vacuum dust Pb concentrations were 124 µg Pb g-1 and 34 µg Pb g-1, respectively. Vacuum-collected dust concentrations and dust wipe Pb loading rates were significantly correlated within homes (α < 0.001; r ≥ 0.4). At least one wipe sample exceeded current house dust Pb loading hazard standards (10 µg ft-2 or 100 µg Pb ft-2 for floors and windowsills, respectively) in 75 of 346 homes (22%). House dust Pb concentrations were correlated with soil Pb (r = 0.64) and Pb paint (r = 0.57). Soil Pb and paint Pb were also correlated (r = 0.6). IMPACT: The AHHS II provides a window into the current state of Pb in and around residences. We evaluated the relationship between house dust Pb concentrations and two common residential Pb sources: soil and Pb-based paint. Here, we identify relationships between Pb concentrations from vacuum-collected dust and paired Pb wipe loading data, enabling dust Pb concentrations to be evaluated in the context of hazard standards. This relationship, along with direct ties to Pb in soil and interior/exterior paint, provides a comprehensive assessment of dust Pb for US homes, crucial for formulating effective strategies to mitigate Pb exposure risks in households.

Blood lead levels in pregnant women and their newborn infants at an Indian teaching hospital.

Background and Aim: With the growth of the world's economy and industrialization, lead (Pb) contamination in the environment has become a major issue on a global scale. Lead is typically linked to unfavorable pregnancy outcomes such as stillbirth, low birth weight preterm, and spontaneous abortion. In this study, we evaluated the blood lead levels of pregnant women and their birth outcomes attending an Indian tertiary care teaching hospital, those who were not exposed to any lead-associated industry or shops. Methods: A descriptive study was undertaken to evaluate blood lead estimation in pregnant women and umbilical blood lead levels in a community hospital. Blood samples from 104 mothers during the 1st trimester, 90 mothers during 3rd trimester, and from the umbilical cord were collected. Self-administered questionnaires were used to collect information on demographics, medical history, and concerns linked to pregnancy. Following acid digestion, the levels of lead in whole blood were determined by an atomic absorption spectrometer. The DNA damage in high blood lead-concentrated pregnant women was evaluated by comet assay methods. Results: Among 194 blood samples of pregnant women, 31 (15.98%) samples revealed ≥5 µg/dL blood lead levels. High lead concentration (≥5 µg/dL) in 1st trimester pregnant women, end of 3rd trimester and cord blood were detected 20.19%, 11.11% and 1.11% respectively. The mean blood lead levels in 1st trimester, 3rd trimester, and cord blood were 3.88 ± 3.19, 2.66 ± 1.82, and 1.53 ± 1.06 mg/dL, respectively. The blood lead concentrations were significantly higher in the 1st trimester of pregnancy than in the 3rd trimester of pregnancy (P < 0.0017). A positive correlation between maternal and infant blood lead levels was revealed (P < 0.0001). When the comet assay was used to assess the genotoxic consequences of elevated blood lead levels during pregnancy, higher amounts of DNA damage were found in the samples (P < 0.01). Conclusion: In this descriptive study, there was a significant amount of lead transferred from mother to baby through the placenta. All mothers were not exposed to lead-associated industry and most were housewives. This article may be viewed as an eye-opener for understanding the blood lead concentration during pregnancy to avoid abnormal birth outcomes. To minimize exposure to environmental lead, all possible measures should be undertaken.

How Chicago's Past Resulted in Disproportionate Lead Poisoning of Minority Children of the Present: A Narrative Review.

Chicago's lead problem has been shown to disproportionately affect populations of color and lower socioeconomic status (SES). The disproportionate effects on low-income areas and communities of color can be traced back to several key decisions in Chicago's history. A search of the National Library of Medicine's MEDLINE/PubMed as well as Google, and Google Scholar was performed to find all articles relating to lead poisoning in Chicago, lead utilization, Chicago's municipal and political history, and lead physiology between May 2020 and May 2023. Additionally, several studies and textbooks were reviewed regarding the latest advancements in lead poisoning. The study identified several key political moves over the course of Chicago's history that have resulted in disproportionate toxicity in minority populations and those of lower SES. Lead is more readily absorbed in the pediatric population. Additionally, prior regulations had published acceptable blood lead levels (BLLs) in children, but more recent evidence indicates a myriad of detrimental effects in BLLs below that cutoff. There is substantial evidence to suggest that there is no acceptable BLL. Lead toxicity is generally improving nationally but there still exists a considerable need for improvement. Programs should be expanded to ensure that individuals living in communities most at risk of lead exposure have the means to both, replace lead-contaminated infrastructure, and to be able to supply these communities with affordable housing. From a physician and clinician standpoint, knowing the increased risk of lead poisoning in these populations should prompt earlier testing.

IEUBK Modeling of Children's Blood Lead Levels in Homes Served by Private Domestic Wells in Three Illinois Counties.

Lead is known to impair neurocognitive development in children. Drinking water is routinely monitored for lead content in municipal systems, but private well owners are not required to test for lead. The lack of testing poses a risk of lead exposure and resulting health effects to rural children. In three Illinois counties, we conducted a cross-sectional study (n = 151 homes) examining water lead levels (WLLs), water consumption, and water treatment status to assess risk of lead exposure among residents using private water wells. Since blood lead levels (BLLs) were not available, EPA's Integrated Exposure Uptake Biokinetic (IEUBK) modeling was used to estimate the incremental contribution of WLL to BLL, holding all other sources of lead at their default values. Nearly half (48.3%) of stagnant water samples contained measurable lead ranging from 0.79 to 76.2 µg/L (median= 0.537 µg/L). IEUBK modeling showed BLLs rose from 0.3 to 0.4 µg/dL when WLLs rose from 0.54 µg/L (the tenth percentile) to 4.88 µg/L (the 90th percentile). Based on IEUBK modeling, 18% of children with a WLL at the 10th percentile would have a BLL above 3.5 µg/dL compared to 27.4% of those with a WLL at the 90th percentile. These findings suggest that the consumption of unfiltered well water likely results in increased blood lead levels in children.