Paul Mushak

Chapter 11 – Lead Toxicity in Humans: A Brief Historical Perspective and Public Health Context

Publisher Summary This chapter summarizes the historical record for lead (Pb) toxicity in human populations. This health history of toxic impacts in humans focuses on leads temporal reach and attempts a systematized look at the evolution of lead toxicology and epidemiology as a public health issue. The chapter tabulates some illustrative fragmented descriptions of Pb toxicity that appeared over the period from the Greco-Roman era to about the seventeenth century and cites some scattered and illustrative poisoning reports in the seventeenth and eighteenth centuries. It presents some illustrations of the intersection in the nineteenth century of lead poisoning as a health issue and the industrial development of societies that produced greatly expanded exposures of diverse human populations to lead as a consequence. The first several decades of the twentieth century produced clear evidence of experimental lead poisoning. A table is given depicting illustrative scientific and public health milestones in the second half of the twentieth century to the present that began to frame lead poisoning as a contemporary public health issue.Publisher Summary This chapter summarizes the historical record for lead (Pb) toxicity in human populations. This health history of toxic impacts in humans focuses on leads temporal reach and attempts a systematized look at the evolution of lead toxicology and epidemiology as a public health issue. The chapter tabulates some illustrative fragmented descriptions of Pb toxicity that appeared over the period from the Greco-Roman era to about the seventeenth century and cites some scattered and illustrative poisoning reports in the seventeenth and eighteenth centuries. It presents some illustrations of the intersection in the nineteenth century of lead poisoning as a health issue and the industrial development of societies that produced greatly expanded exposures of diverse human populations to lead as a consequence. The first several decades of the twentieth century produced clear evidence of experimental lead poisoning. A table is given depicting illustrative scientific and public health milestones in the second half of the twentieth century to the present that began to frame lead poisoning as a contemporary public health issue.

Chapter 19 - Effects of Lead on Other Organs and Systems in Human Populations

Publisher Summary This chapter highlights toxicological and epidemiological information regarding a cluster of adverse effects on organs and systems in human populations. It summarizes data for the thyroid endocrine effects of lead (Pb), and presents effects on reproductive hormone functions of Pb exposures in humans and animals. The main effects of Pb on the gastrointestinal tract (GI) and hepatic systems are also presented. The chapter mentions that toxic effects on thyroid hormonal function due to Pb exposure typically occur at relatively high Pb exposure levels usually associated with lead workers. Sex hormone levels and functions are affected by Pb at multiple sites in males and females within a hypothalamic–pituitary–gonadal axis, with Pb exerting potential impacts on testosterone (TES), estradiol (E 2 ), luteinizing hormone (LH), insulin growth factor 1 (IGF 1 ), follicle-stimulating hormone (FSH), prolactin (PRL), and gonadotropin-releasing hormone (GnRH). The chapter discusses Pb effects on the hypothalamic–pituitary–adrenal (HPA) axis in humans and experimental systems. It reports persistent effect of maternal Pb dosing on corticosteroid concentrations in offspring reaching adulthood.

Chapter 8 – Lead Exposure in Human Populations: Lead Toxicokinetics and Biomarkers of Lead Exposure

Publisher Summary This chapter focuses on lead (Pb) toxicokinetics and biomarkers of lead exposure. Toxicokinetics describes the biokinetics of toxic substances. It includes the kinetic processes for toxic substances which govern the movement into, within, and from the bodies of human populations. The overall lead toxicokinetic process includes: (1) the uptake of lead into the bloodstream from various body compartments, (2) movement within the bloodstream followed by transport internally to target tissues and their cellular components, (3) retention within one or more tissues, and (4) excretion from the body by various systemic pathways. The chapter discusses two critical roles in the delineation of lead toxicity: (1) it provides the kinetic underpinnings for expressions of lead intoxication in humans and other species and (2) leads kinetic behavior in vivo provides the means by which biomarkers of toxic lead exposures can be identified and exploited and the dose portion of critical dose–toxic response relationships for lead poisoning can be determined.

Chapter 26 - Lead Regulation and Regulatory Policies: Lead in Paint

Publisher Summary Lead (Pb) paint, as it enters the human environment and in its subsequent environmental behavior, is an illustrative model for regulation considerably different from other lead-containing media or pathways to human exposures. Lead paint applied to a myriad of structural surfaces began environmental life as a marketed commodity for the specific purpose of applications to those structural surfaces. There are two parts to lead paint as a public health issue: (1) occupational health issues arising from Pb exposures of workers producing, using, maintaining, or removing lead paint, and (2) pediatric health concerns from Pb exposures of young children once the substance is applied to surfaces in residential or other surroundings. The exposure and toxic injury consequences resulting from lead paint as a public and child health problem first elicited highly fragmented and relatively localized regulatory responses. This reflected in part the perception that the lead paint problem was confined to certain U.S. communities and states and therefore was best dealt with by local initiatives. The chapter also provides information on some local, state, and Federal regulations for U.S. lead paint control efforts.

Dose–Response Relationships for Toxic Effects of Lead in Human Populations

Publisher Summary This chapter summarizes the dose or exposure component of dose–toxic responses for lead (Pb), presenting the empirical evidence for comparative advantages and limits of various Pb exposure biomarkers. It presents the dose–toxic response relationships for Pb for risk group-specific lead exposures. These relationships are stratified on the basis of affected human risk population subsets, for example, young children, adults, lead workers, and older adults. In addition, individuals within these larger risk categories may be at added differential risk owing to intrinsic factors, such as genetic susceptibilities. The dose–toxic response relationships for environmental lead in humans, taken collectively, produce a picture in which there is not a readily apparent threshold in dose–response terms for the most sensitive toxic endpoints. Dose–toxic response relationships differ with respect to which segments of human populations are affected. Some segments of human populations are much more sensitive to lead contact than others, and these are termed as risk “increased risk,” and “subpopulations.” Given qualitative and quantitative differences across risk populations in terms of dose–responses, these segments are discussed. Each factor defining higher risk is discussed because the basis of differential dose–response relationships in these populations is both exposure driven and toxicology/biology driven.

Chapter 20 - Human Health Risk Assessment for Lead: Introduction, Context, Rationale

Publisher Summary This chapter provides quantification of the health risks of lead (Pb) exposure in segments of human populations at significant risk of adverse health effects from such exposures. It presents and quantifies risk expressions using a reasonable and generally acceptable model of human health risk assessment for those contaminants, such as environmental lead that have already been emitted into the human environment. Such a risk assessment model proceeds through explains how much of a threat to human health lead exposures pose. The elements of human health risk assessment for Pb are presented. Lead is one of those environmental contaminants and human toxicants that produce (1) actual or expressed toxicity as medically diagnosed in Pb-intoxicated individuals or in groups of individuals; and (2) probable risk of toxicity in those mainly Pb-exposed groups. Leads toxic effects are expressed relatively early in certain subsets of human populations, and these subsets can be defined in terms of certain particular Pb exposure sensitivities arising from biological or physiological vulnerabilities. The lead worker defines a risk population on the basis of greater intensities and durations of Pb exposure arising from their employment. Pb worker cohorts with employment histories of longer duration and demonstrates the healthy worker effect, with actual toxicological hyporesponsiveness to workplace Pb contact.

Chapter 2 - A Brief Early History of Lead as an Evolving Global Pollutant and Toxicant

Publisher Summary This chapter provides a brief early history of lead (Pb) as an evolving global pollutant and toxicant. The earliest reported use of lead as the metal itself, based on a surviving artifact of early civilizations, is that of a lead statue unearthed in Turkey and dated to 6500 Before the Common Era (BCE). This age estimate pushes back the introduction and early adoption of the metallurgical process of cupellation for ore smelting. The available records indicate that early lead metallurgy included the use of crude smelting processes to liberate lead but was mainly used to separate lead from more desired metals, particularly silver, well before the Common Era (CE). By the time of the Greco-Roman era, cupellation smelting of lead ores to recover both their lead and silver contents apparently was a widely exploited process. It is mentioned that the early smelting technology was crude and inefficient, so only ores of relatively high lead content like those in Britain were of interest or value. The chapter further describes how lead contamination of the early human environment produces lead exposures at toxic levels. It provides a historical overview of lead uses and exposure sources that were widespread in Greco-Roman times and that continued through recent times.

Chapter 23 – Exposure Characterizations for Lead in Specific Human Populations

Publisher Summary This chapter presents three case studies of site-based lead (Pb) exposure characterizations for subsequent risk assessment purposes. The case studies are based on research where environmental media-specific levels of Pb were determined as part of the epidemiological and statistical designs. The first case study summarizes exposure characterizations of individuals living in a well-known and studied, geographically broad locale impacted by a Pb point source in Idaho that had long released Pb to the environment. The second case study examines a series of site-specific exposure assessments pooled to produce predictive relationships of PbB in children three years of age or younger to such lead sources as dusts and soils. This second illustration presents exposure characterizations for specific locations that were of two general site types: urban lead exposure settings in old city neighborhoods with lead paint and industrial emission histories, and Pb exposure endpoints reported for mining and other extractive industry sites. The third case study presents results of case studies of U.S. populations selected by the U.S. Environmental Protection Agency (EPA) as part of regulatory action for air Pb.

Chapter 14 - Reproductive and Developmental Toxicity of Lead in Human Populations

Publisher Summary This chapter presents the toxicological evidence for lead (Pb) as a potent reproductive and intrauterine developmental toxicant. The principal adverse outcomes for fetal health and development are presented in three categories: spontaneous abortions, stillbirths, and first-year survival rates. Discussion of these outcomes is followed by a treatment of somewhat less severe effects: premature delivery and impaired fetal growth rates. The evidence for lead-associated congenital effects of an anatomical/structural nature, although limited for human populations, is also presented. The role of Pb as a male reproductive toxin, especially in those individuals having elevated occupational Pb exposures, is discussed. Three approaches to evaluating reproductive competence in Pb-exposed men, largely workplace exposures, have been elucidated: (1) direct gametotoxicity through impaired spermatogenesis and quality, (2) assessment of altered time to pregnancy, and (3) reproductive history. The chapter tabulates the various early studies of Pb effects on experimental animal reproduction and development, and summarizes illustrative results, mainly done on rats and mice. It also summarizes the effects of Pb exposure on reproduction and development in three species of monkeys.

Chapter 12 - Neurotoxicity of Lead in Human Populations

Publisher Summary This chapter presents the scientific and medical evidence documenting environmental lead (Pb) as a particularly potent neurotoxin for injuring the developing brain in very young children and the fetal brain during elevated Pb exposures of the mother. It mentions that Pb produces neurotoxic harm across a wide range of Pb exposures, the nature of the harm ranging from fatal outcomes at the highest exposures to demonstrable reduction in normal neurocognitive and neurobehavioral function in very young children at very low exposures. The chapter uses and merges two conceptual approaches: criticality and weight-of-evidence. The criticality concept is useful in elucidating leads dose–toxic response relationships for an array of organ and tissue-specific toxicological data on effects which are simultaneously highly significant and occur at or among the lowest doses. Weight-of-evidence quantifies multiple lines of evidence for lead toxicity. The chapter makes distinction between Pb toxicity observed in young children qualitatively and quantitatively, and explains what comprises the typical case for older children and adults.