Toxicity of Lead in Human Populations

Lead has long been known to produce toxic effects on the heart and blood vessels in human populations and to show links to cardiovascular morbidity and mortality. A number of pubhc agency expert consensus documents have discussed the topic, including lARC (2006), NAS/NRC (1993), U.S. EPA (1977, 1986, 2006), U.S. ATSDR (2007), and WHO (1995). In addition, individual critical reviews have appeared (Navas-Acien et al., 2008, 2007 Vaziri, 2008). This chapter presents some of the more salient toxicological, epidemiological, and mechanistic aspects of these effects and a contexmal comparison with other key toxic endpoints of lead exposure. 

Cardiovascular effects differ in a number of ways from other toxic endpoints associated with human Pb exposures, particularly with respect to Pb neurotoxicity. The focus of attention for neurotoxic effects epidemiologi-cally, medically, and societally has invariably been the very young child, infants and toddlers, and on parallel concerns about prenatal exposures to lead. Lead neurotoxicity in adult humans, by contrast, has had a less voluminous and comprehensive hterature for reasons explained in Chapter 12. By contrast, cardiovascular effects in humans have almost always been evaluated in adult human populations. Data are limited and significant risk analysis attention has not been given to cardiovascular effects in children. 

This difference in attention to risk populations for lead neurotoxicity versus cardiovascular and cerebrovascular toxicity traces in part to what available data currently permit one to conclude comparatively about these serious adverse effects. Childhood Pb neurotoxicity is expressed through a myriad of developmental neurocognitive and neurobehavioral mechanisms centered on the developing brain for which adult neural analogs have not been as well conceptualized. 

Cardiovascular toxicity, by contrast, most commonly employs blood pressure changes as the sentinel effect marker across adult groups. That endpoint 

Trace Metals and other Contaminants in the Environment, Vcriume 10 

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Chapter I 13 Cardiovascular Toxicity of Lead in Human Populations 505 ... 

Dose—Response Relationships for Toxic Effects of Lead in Human Populations... 

C) The evaluation of information on the toxic properties of chemicals, the conditions under which these properties manifest themselves, and the underlying biological processes leading to toxicity, to assess the likelihood that those chemicals might produce their adverse effects in human populations that are or could be exposed to them. 

Part 4 continues with lead-specific discussions of the four components of a human health risk assessment as structurally articulated in 1983 by the NAS/NRC (1983) Chapter 21, human health hazard characterization for lead and diverse human populations Chapter 22, dose—toxic response relationships for lead in humans Chapter 23, illustrative uses of case- or setting-specific lead exposure characterizations and. Chapter 24, the last part of health risk assessment, the overall final and most quantitative step in actualizing (in a relative sense) the estimates of risk outcomes. 

Noted earlier in passing, lead is different from many toxic substances subjected to human health risk assessment methods in that the toxicant not only poses risk of disease but causes actual disease as well. What is more, this disease-producing substance works to do so in human populations as well as in experimental animals. This propensity of lead is amply characterized in a huge database that permits us to discover this duality and to integrate each form with the other. There are many hundreds and thousands of environmental contaminants which are not well characterized, so that we are left with quantifying hazards to human health in the form of calculated probabilities for harm using formulaic methodologies. 

Hematology in human populations has a number of genetic determinants, and the genetic polymorphism for various components of human blood compartments has the potential to affect the binding of lead in blood, the subsequent dose—toxic response relationships for lead from such alterations, and to enhance the variability between subjects with the same overall external lead contact. 

Lead is now known to affect both forms of immunological expression in human populations and experimental systems humoral and cell-mediated immunology. It does so in complex ways that make for adverse responses identified at increasingly lower exposures. One critical aspect of Pb immiino-toxicity in terms of this robust set of dose—response relationships is that it does not impart direct toxic effects which can be discerned histochemically or ultrastructuraUy but produces effects by disrupting the regular function of immunological components. 

The previous parts of this monograph have already provided some quantitative looks at lead and public health within more specific topics. Part 1 presented a measure of the entirety of lead contamination in the human environment, while Part 2 offered descriptions of the nature and extent of lead exposures in the United States and internationally. Part 3, in providing the range of Pb toxic effects in human populations, also referred to various expressions of Pb exposures reported as linked to these various effects epide-miologically. The need to translate those earlier parts and chapters into a coherent expression of threat of harm to human health remains. 

The role of bone as the principal body depository for Pb makes it the principal biomarker of body lead burden. By comparison, the total Pb content of whole blood is considerably less (Rabinowitz et al., 1976). Given current evidence, however, the kinetic and metabolic mobility of bone Pb is sufficient to qualify this Pb reservoir as a biomarker of Pb exposure and a biomarker relevant for much longer periods than PbB. Some recent epidemiological studies, like those for toxic effects described in the toxicity chapters of this book, indicate associations of bone Pb with long-term chronic adverse effects in human populations while PbB provided negative results. 

Lead-contaminated environments have resulted in comparable increases in organism and human lead burdens, as indicated by a recent estimate of the natural level of lead in blood of preindustrial humans (0.016 fxg/dL or 0.8 nM). This estimate has important public health implications because it suggests that blood lead levels that are now considered acceptable in children (i.e., < 10 ug/dL or <480 nM) are nearly 600-fold greater than estimated natural levels, while they are only 10-fold lower than levels ( 100 fig.dL or 4800 n that may cause encephalopathy and death in many individuals of a population. Understanding of the extent of sublethal lead toxicity in humans may benefit from studies that consider control populations possessing natural (i.e., preindustrial) lead burdens. 

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