Mortality of lead smelter workers: A follow-up study with exposure assessment.

BACKGROUND: Lead exposure has been linked to impaired renal function and kidney failure. High lead exposures have been associated with increased mortality from certain cancers, hypertension, cardiovascular disease, and amyotrophic lateral sclerosis (ALS). METHODS: We extended vital status follow-up on a cohort of 1,990 lead smelter workers by 25 years and computed standardized mortality ratios and rate ratios (RR) stratified by cumulative lead exposure. RESULTS: The update added 13,823 person-years at risk and 721 deaths. Increased risk of mortality was observed for the a priori outcomes of lung cancer, cardiovascular disease (including cerebrovascular disease), chronic kidney disease, and ALS. However, of these outcomes, only cardiovascular, cerebrovascular, and chronic kidney diseases were associated with a positive exposure-response in RR analyses. CONCLUSIONS: This study reaffirms the association of lead exposure with cardiovascular and kidney diseases; however, increased mortality observed for certain cancers is not likely to be due to lead exposure. Am. J. Ind. Med. 59:979-986, 2016. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Putting the genie back in the bottle: protecting children from lead exposure in the 21st century. A report from the field.

This paper highlights progress on an important public health issue which, despite significant progress, has now stalled and is in need of renewed investment. The objective is to describe the effectiveness of efforts to reduce childhood lead exposure in Broken Hill - a historic mining town in western NSW - and what is required to further reduce exposure. Lead has no known function in the human body, and emerging evidence suggests that no level of exposure is without health effects. A 1991 blood lead survey of 1-4-year-old children identified lead exposure as a significant public health issue in Broken Hill. A major NSW Government-funded program to reduce lead exposure began in 1994, and, by 2001, blood lead levels had reduced by two-thirds. The program was then integrated into other services and funding significantly reduced; blood lead levels have remained relatively unchanged since 2005. At present, 53% of children in Broken Hill have blood lead levels above the recently released National Health and Medical Research Council draft reference value for lead. Participation in annual blood lead screening declined from 52% to 38% after project funding decreased, but recent changes have doubled participation rates. A comprehensive abatement program is required to further reduce lead exposure in this community, and further research is required into how to maintain low blood lead levels and how best to engage the community about reducing individual lead risks. Findings from such studies would be relevant to the broader Australian community.

Altered myelination and axonal integrity in adults with childhood lead exposure: a diffusion tensor imaging study.

Childhood lead exposure is associated with adverse cognitive, neurobehavioral and motor outcomes, suggesting altered brain structure and function. The purpose of this work was to assess the long-term impact of childhood lead exposure on white matter integrity in young adults. We hypothesized that childhood lead exposure would alter adult white matter architecture via deficits in axonal integrity and myelin organization. Adults (22.9+/-1.5 years, range 20.0-26.1 years) from the Cincinnati Lead Study were recruited to undergo a study employing diffusion tensor imaging (DTI). The anatomic regions of association between water diffusion characteristics in white matter and mean childhood blood lead level were determined for 91 participants (52 female). Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured on an exploratory voxel-wise basis. In adjusted analyses, mean childhood blood lead levels were associated with decreased FA throughout white matter. Regions of the corona radiata demonstrated highly significant lead-associated decreases in FA and AD and increases in MD and RD. The genu, body, and splenium of the corpus callosum demonstrated highly significant lead-associated decreases in RD, smaller and less significant decreases in MD, and small areas with increases in AD. The results of this analysis suggest multiple insults appear as distinct patterns of white matter diffusion abnormalities in the adult brain. Neurotoxic insults from the significant lead burden the participants experienced throughout childhood affect neural elements differently and may be related to the developmental stage of myelination at periods of exposure. This study indicates that childhood lead exposure is associated with a significant and persistent impact on white matter microstructure as quantified with diffusivity changes suggestive of altered myelination and axonal integrity.

Lead neurotoxicity and socioeconomic status: conceptual and analytical issues.

Socioeconomic status (SES) is usually considered to be a potential confounder of the association between lead exposure and children's neurodevelopment, but experimental and epidemiological data suggest that SES might also modify lead neurotoxicity. The basis of this effect modification is uncertain, but might include differences among SES strata in co-exposures to other neurotoxicants, genetic susceptibilities, environmental enrichment, and stress. The role of SES in the causal nexus is likely to include other dimensions, however. It conveys information about lead exposure opportunities as well as about predictors of child outcome that are correlated with but causally independent of lead. Failure to distinguish these aspects of SES will lead to an underestimate of lead's contribution, and might even result in attributing to SES health effects that should be attributed to lead. Conventional models, which treat SES and SES-related factors solely as potential confounders, do not capture the possibility that a child's early lead exposure alters the behaviors that the child elicits from others. Failure to model lead's contribution to such time-varying covariates will also tend to bias estimates of lead neurotoxicity toward the null. On a trans-generational level, low SES might be a proxy for vulnerability to lead. To estimate the burden of lead-associated neurotoxicity on a population level, we need to apply analytical approaches that model a child's development and its context as a complex system of interdependent relationships that change over time.

Update on the clinical management of childhood lead poisoning.

Childhood lead poisoning is still an enormous public health issue in the United States, affecting thousands of children and their families. New evidence suggests that even very low blood lead levels, less than 10 microg/dL, can be associated with neurologic injury. This article discusses characteristics of children at high risk for lead poisoning, unusual sources of lead contamination, and new aspects of lead's pathophysiology. It includes current thinking on the clinical management and prevention of childhood lead poisoning.

Childhood lead poisoning: the torturous path from science to policy.

The long history of lead poisoning provides many lessons about the process by which scientific knowledge is translated into public health policy. In the United States, lead was added to paint and to gasoline in enormous quantities long after medical evidence clearly showed that excessive lead exposure caused considerable morbidity in the population. This article discusses some of the factors that contributed to the slow pace of efforts to address this problem, including the ubiquity and magnitude of lead exposure during much of the twentieth century, which produced a distorted notion about the blood lead level that can be considered "normal"; the prevailing model of disease during this period, notably the novelty of the concept of subclinical disease; the fact that childhood lead poisoning affected mostly families that were politically and economically disenfranchised, fostering a "blame the victim" attitude; and that controlling lead exposure would have impeded efforts to achieve other desirable goals, illustrating the role that value trade-offs often play in policy decisions.

Cost of child lead poisoning to taxpayers in Mahoning County, Ohio.

Lead poisoning in children imposes both immediate and long-term financial burdens on taxpayers. The District Board of Health of Mahoning County, Ohio, quantified some of the direct costs to taxpayers of providing medical care and public health services to the 279 children diagnosed with lead poisoning in the county in 2002, using methods described by Katrina Korfmacher at the University of Rochester. The Board of Health also attempted to quantify the longer-term costs of special education and juvenile justice services attributable to lead exposure. The realization that lead poisoning costs local government on the order of 0.5 million dollars each year has mobilized community leaders in education and juvenile justice to demand more aggressive action against rental property owners who fail to remediate lead hazards.

Disparities in cognitive functioning by race/ethnicity in the Baltimore Memory Study.

The Baltimore Memory Study is a cohort study of the multilevel determinants of cognitive decline in 50-70-year-old randomly selected residents of specific city neighborhoods. Prior studies have demonstrated that cognitive function differs by race/ethnicity, with lower scores in minorities than in whites, but the underlying basis for these differences is not understood. Studies have differed in the rigor with which they evaluated and controlled for such important confounding variables as socioeconomic status (SES), health-related behaviors, comorbid illnesses, and factors in the physical environment. The goal of this study was to describe differences in neurobehavioral test scores by race/ethnicity, before and after control for a four-dimensional measure of SES and health-related behaviors and health conditions, in a cross-sectional analysis of first visit data. Random samples of households in the study area were selected until enrollment goals were reached. Among the 2,351 persons on whom eligibility was determined, 60.8% were scheduled for an enrollment visit; of these, 1,140 (81.3%) were enrolled and tested. These study participants were 34.3% male and 65.7% female and were from 65 Baltimore, Maryland, neighborhoods. After adjustment for age, sex, and testing technician, there were large and statistically significant differences in neurobehavioral test scores by race/ethnicity, with African-American scores lower than those for whites, for both men and women. After adjustment for individual SES (educational status, household income, household assets, and occupational status), the average difference declined by 25.8%. After additional adjustment for SES, health-related behaviors and health conditions, and blood lead, the average difference declined another 10%, but large differences persisted; African Americans had test scores that averaged 0.43 standard deviation lower than those for whites across all neurobehavioral tests. These differences were present in all cognitive domains, including tests that would not be characterized as susceptible to differential item functioning by race/ethnicity, suggesting that the results are not due to race/ethnicity-associated measurement error.

Estimating the global burden of disease of mild mental retardation and cardiovascular diseases from environmental lead exposure.

The disease burden from exposure to lead resulting in mild mental retardation (due to IQ point decreases) and cardiovascular outcomes (due to increases in blood pressure) was estimated at a global level. Blood lead levels were compiled from the literature for 14 geographical regions defined by the World Health Organization according to location and adult and child mortality rates. Adjustments were applied to these levels, where appropriate, to account for recent changes relating to the implementation of lead-reduction programs and the lower levels seen in rural populations. It is estimated that mild mental retardation and cardiovascular outcomes resulting from exposure to lead amount to almost 1% of the global burden of disease, with the highest burden in developing regions. This estimate can be used to assess the magnitude of the benefits that could be accrued by increasing the global coverage of lead-reduction programs.

A community-based assessment of learning disabilities using environmental and contextual risk factors.

Childhood placement in learning disability (LD) programs in the USA has tripled over the last few decades to 6% of all children enrolled in the public schools today. The revision of educational laws to improve LD testing and reporting guidelines has been credited for these trends. However, some researchers also believe that the increase in LD incidence may be due, in part, to chronic low level exposure to toxicants such as lead, heavy metals, solvents and others chemicals in the physical environment. This study employs the use of geo-statistical methods to explore the potential linkages between these pollution sources and the prevalence rates of LD within an urbanized environment, in the USA. The role of contextual factors such as housing quality, poverty, low parental educational achievement, and other disadvantages are also examined. Using primary data on childhood disabilities for 1997, the LD cases were queried and analyzed to identify the spatial clusters within the community. The neighborhoods within the LD clusters were then compared to other areas in the community on the basis of the environmental and contextual risk factors. The results confirmed that areas of high risk for LD were strongly associated with historically significant sources of lead toxicity and air pollution facilities. Among the socio-economic indicators, the high-risk neighborhoods were characterized by multiple/subdivided housing units, poverty, higher percentage of residents on public assistance and lower adult educational attainment. Taken together, these results suggest the need for a more inclusive multi-disciplinary research on LD that extends beyond the classroom context to the neighborhoods and communities in which these children reside.

Association between iron deficiency and blood lead level in a longitudinal analysis of children followed in an urban primary care clinic.

OBJECTIVE: To determine if iron deficiency (ID) is longitudinally associated with lead poisoning. STUDY DESIGN: Blood lead levels, hemoglobin, mean corpuscular volume (MCV), red cell distribution width (RDW), insurance status, and age were determined for 1,275 children. ID was defined as MCV <70 fl and RDW >14.5 if age was <2 years and MCV <73 fl and RDW >14.5 if age was >/=2 years. Logistic regression models were constructed by using the second-visit blood lead levels dichotomized at >/=0.48 microm/L (10 microg/dL) as the outcome. RESULTS: The odds ratio (OR) for baseline ID predicting lead poisoning at the second visit was 4.12 (95% CI, 1.96-8.65). In the second model, using children who were iron-replete at both visits as the referent group, for children with ID at both visits, the OR for predicting lead poisoning at the second visit was 5.54 (95% CI, 2.25-13.62). For children with ID at the first visit and iron-replete at the second visit, the OR was 2.73 (95% CI, 0.90-8.27), and for children iron-replete at the first visit and ID at the second visit, the OR was 0.81 (95% CI, 0.10-6.30). CONCLUSIONS: ID is associated with subsequent lead poisoning. These data are consistent with a biological mechanism of increased lead absorption among iron deficient children.

A risk assessment for lead in birds.

Ecotoxicologists and ecologists have examined the effects of pollutants on individuals and populations largely in terms of one or only a few effects. Yet the recent trend toward a holistic approach to ecological risk assessment suggests that a rigorous paradigm should be applied to toxicants, from hazard identification to risk characterization. Recent discussions have recognized that an up-front problem formulation phase is more critical in ecological risk assessment than it is for human health risk assessment. In this article a modified environmental health risk assessment paradigm is used to examine the risk of lead to birds. This risk analysis is largely conceptual, based on laboratory and field data, and incorporates information currently available. The model expands the hazard identification phase to create a target identification phase that includes the identification of receptors, endpoints, relationships, spatial and temporal scales, and indicators. The target identification phase is unique to the particular hazard, species, population, or community being examined. Lead can cause mortality, or can indirectly affect populations through effects on the food base, avian behavior, reproductive success, and recruitment. Lead can (1) decrease the abundance and availability of prey, (2) bioaccumulate in prey causing increased lead toxicosis in predators, or (3) increase prey availability by interfering with its hiding or escape behavior. Moreover, lower abundance of prey can lead to starvation or nutrient deficiencies, which amplify the absorption and retention of lead. Lead also causes decreases in clutch and egg size, mortality of embryos and nestlings, depression of growth, and deficits in behavior that affect survival. Lead decreases migratory behavior, and increases vulnerability to cold stress, hunters, and other predators. Research needs for evaluating the risk of lead in birds include obtaining data on (1) metal dynamics within various tissues as a function of dose and time since initial exposure, (2) low-level effects on embryos, (3) effects on chicks following fledging and in the period prior to recruitment, (4) effects on adult foraging skills and reproductive behavior, and (5) the relationship between effects from exposure in the laboratory and those from exposure in the wild. This latter point is extremely important, particularly if wild birds have other means of ridding the body of lead not available or less apparent to laboratory birds.

Management of childhood lead poisoning: clinical impact and cost-effectiveness.

OBJECTIVES: No consensus exists regarding the preferred treatment of childhood lead poisoning. The authors used decision analysis to compare the clinical impacts and cost-effectiveness of four management strategies for childhood lead poisoning, and to investigate how effective chelation therapy must be in reducing neuropsychologic sequelae to warrant its use. METHODS: The model was based on a 2-year-old child with moderate lead poisoning [blood lead level 1.21 to 1.88 mumol/L (25 to 39 micrograms/dL)]. The following strategies were compared: 1) no treatment; 2) EDTA provocation testing, followed by chelation if testing is positive (PROV); 3) penicillamine chelation with crossover to EDTA provocation testing if toxicity occurs (PCA); 4) EDTA provocation testing with crossover to penicillamine chelation if testing is negative (EDTA). RESULTS: The EDTA and PCA strategies prevented 22.5% of the cases of reading disability and resulted in an increase of 1.02 quality-adjusted life years compared with no treatment. When the costs of outpatient EDTA testing and chelation are considered, the EDTA strategy is more cost-effective than the PCA strategy; when inpatient costs are considered, the PCA strategy becomes more cost-effective. When costs of remedial education are considered, all strategies are cost-saving compared with no treatment if chelation reduces the risk of lead-induced reading disability by more than 20%. CONCLUSIONS: Treatment strategies for childhood lead poisoning vary in clinical impact, cost, and cost-effectiveness. Chelation of the 1.4% of United States preschoolers whose blood lead levels are 2.21 mumol/L (25 micrograms/dL) or higher could prevent more than 45,000 cases of reading disability, and save more than $900 million per year in overall costs when the costs of remedial education are considered.

Preventing childhood lead poisoning.

Of all the neurotoxins, lead is the longest known and best understood. Because we know so much about what it does, where it is, and what is required to remove it from the presence of children, lead poisoning should also be one of the easiest diseases to eradicate. Despite this, progress in the primary prevention of childhood lead poisoning has been halting and erratic. In this paper, I outline the rapidly advancing state of knowledge on the epidemiology and toxicology of lead, examine some of the reasons for the gap between what is known and what has been accomplished, and outline the steps toward authentic primary prevention. Eradication of childhood lead poisoning is a realizable goal. Its importance is unquestioned; former Secretary of the Department of Health and Human Services Louis Sullivan declared in 1991 that it is the most serious environmental disease of North American children.

Risk assessment of the developmental neurotoxicity of lead.

Lead has long been recognized as a developmental neurotoxicant. Although no reasonable doubt exists about this qualitative characterization, quantitative aspects of the developmental neurotoxicity of lead have been more difficult to resolve. This paper focuses on two key issues in a risk assessment of lead: the blood lead level of concern, i.e., the lowest level of exposure associated with neurotoxic effects in children, and the magnitude and implications of such effects. The distinction between a threshold and a level of concern is also discussed, along with the issue of whether a threshold exists for lead-induced health effects.