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Old 05-28-2009, 01:56 PM
Richard Long Richard Long is offline
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Join Date: Oct 2006
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Smile LEAD EXPOSURE INFORMATION (pt. 1)

Background

In the worlds of environmental health and environmental medicine, lead exposure remains one of the most important problems in terms of prevalence of exposure and public health impact. Despite decades of intensive research, lead toxicity also remains one of the most, if not the most, studied subjects of all within the fields of environmental health and environmental medicine. This reflects the large gaps that continue to exist in our understanding of the full implications of lead exposure on health: how lead exposure may impact on chronic diseases; what mechanisms dictate lead’s health effects; how to predict, monitor, and manage lead toxicity; and what factors may modify lead’s effects.

Measurement of Lead Dose
Concepts and overview. In reviewing studies of the health effects of lead, it is critical to understand the available lead biomarkers in terms of how they represent external exposure (in terms of timing, duration, magnitude, and accumulation), how they are influenced by metabolic factors (organ distribution, compartmental dynamics, the influence of physiologic factors), and how the combination of these considerations impacts inferences regarding the health effects of lead.

To determine recent and cumulative lead doses, researchers have incorporated measurements of lead in both blood (whole blood, using standard chemical assays such as graphite furnace atomic absorption spectroscopy) and bone (using noninvasive in vivo K-shell X-ray fluorescence [KXRF] instruments). Blood lead levels are an indicator of circulating lead that captures variation in recent external lead exposure as well as lead that has been mobilized from tissue stores (mostly bone). Lead levels in tibia and patella provide an indication of cumulative dose over decades (particularly cortical tissue in tibia) as well as the largest pool of lead in the body that is available for mobilization into blood. The latter phenomenon is heightened at times of high bone resorption (e.g., during pregnancy, aging, postmenopause).Taken together, blood and bone lead levels have provided recent epidemiologic studies with the best available assessment tools for estimating both recent and cumulative lead.

The blood lead test cannot be assumed to be the best and only metric of lead exposure that matters. A blood lead level reflects, for the most part, recent lead exposure (i.e., over weeks to months) from environmental or occupational sources. Although lead in blood is also in equilibrium with bone lead stores, its variability mostly reflects changes in external exposure. Over the past 10 years or so, epidemiologic studies have generated growing and undeniable evidence that the most important standard for predicting some adverse health outcomes is not recent lead exposure; rather, it is cumulative lead exposure that occurs over many years, with or without the additional dimension of latency (i.e., the passage of time that may be needed for a toxic outcome to be expressed).

The importance of cumulative dose (and latency) has also been supported by longitudinal epidemiologic studies in which, compared with subjects with low lead exposure, individuals with a clear history of high lead exposure in the past have been found to have a higher profile of disease despite having current blood lead levels similar to those without such a history [e.g., rates of hypertension and adverse reproductive outcomes (Hu et al. 1991a, 1991b), respectively].

Lead uptake, distribution, metabolism, and excretion. The principal routes of exposure and absorption of lead are through ingestion and inhalation (White et al. 1998). Absorption in the gut is partial, influenced by physical form, chemical species of lead, and the presence of other nutrients and dietary cations such as iron and zinc. The molecular mechanism for lung absorption is unknown, but it is well known that if the physical form is of respirable size (i.e., < 1 μm, such as lead fume generated by burning lead paint), absorption is efficient (> 90%; Rabinowitz et al. 1977). Lead-containing particles > 2.5 μm in diameter are deposited in the ciliated regions of the nasopharyngeal and tracheobronchial airways, where they are passed to the gastrointestinal tract by the mucociliary lift mechanism and then subject to intestinal absorption.

Once absorbed through either ingestion or inhalation, lead enters the bloodstream where it is predominantly bound to erythrocyte proteins (Barltrop and Smith 1972; Bergdahl et al. 1997; Church et al. 1993; O’Flaherty 1993; Rabinowitz 1991; Rabinowitz et al. 1976; Simons 1984, 1988), with an average clearance half-time after a short-term limited exposure of approximately 35 days from whole blood (Rabinowitz 1991). Clearance occurs through distribution into soft tissues and bone as well as excretion, primarily through kidney filtration and elimination in urine. A small amount of lead is also excreted in feces, sweat, hair, and nails.

Lead circulates widely and is found in all organs and tissues; it also crosses the blood– brain barrier and placenta, making the brain and developing fetus among the targets of concern (Hu 1998). On a molecular level, lead binds to many proteins, especially to thiol and carboxyl groups, and mimics calcium in many biologic pathways (Goldstein and Ar 1983; Kern et al. 2000; Rabinowitz 1991; Rabinowitz et al. 1973).

Bone
If lead exposure is long-term (i.e., with a duration of years), upon cessation the kinetics of clearance of lead from blood is considerably more complicated, with an initial rapid decline in levels reflecting partial clearance from blood and other soft tissues followed by a much slower clearance, reflecting the replenishment of soft tissue pools of lead with lead from long-lived deposits in bone. Thus, as a biological marker of dose, blood lead levels can be a reflection of acute external exposure; internal bone lead stores released into blood, but, most commonly, a steady-state mixture of both external exposure and internal stores with almost no ability to distinguish between either.

With respect to lead and bone, it has been well established from autopsy studies that the skeleton contains 90–95% of lead burden in adults and 80–95% in children (Barry and Mossman 1970; Hu et al. 1989; Schroeder and Tipton 1968). Roughly 15% of circulating lead per day is incorporated into bone (Rabinowitz et al. 1976), where it substitutes for calcium in the hydroxyapatite of bone mineral during the normal and ongoing process of bone deposition. The bulk of lead in bone is contained within long-lived compartments of cortical (clearance half-time of decades) and trabecular (clearance half-times of years to decades) bone, with comparatively small amounts of lead in bone tissue compartments that rapidly exchange with extracellular fluid and plasma.

Bone and age
A combination of decreased “external” lead exposure and normal rates of bone resorption
can result in bone constituting the predominant source of circulating lead in elderly individuals (Hu et al. 1996b) or in individuals with past long-duration high exposure and low current exposure.

In persons whose peak lead exposures were decades in the past, the current tibia lead is not very bioavailable and thus does not contribute much to current blood lead levels (Martin et al. 2006; Schafer et al. 2005). Greater levels of circulating lead may derive from bone during physiologic states accompanied by heightened bone resorption, such as pregnancy and lactation, postmenopausal osteoporosis (Korrick et al. 2002; Webber et al. 1995), and hyperthyroidism (Goldman et al. 1994). When considered in relation to a longterm conceptual model of lead exposure, dose, and the ability to retrospectively estimate dose in individuals, it is clear that bone lead levels provide a cumulative dose metric that is completely distinct from that of blood lead levels, particularly among individuals whose peak lead exposures had occurred in the past (Hu et al. 1998).

When interpreting Cumulative Blood Level Index (CBLI) is that some of tibia lead (and blood lead) may derive from higher past environmental (nonwork) exposures. Older workers may have higher baseline bone lead levels from living at times when environmental exposures were higher. The population mean BLL was 13 μg/dL in the late 1970s (Annest et al. 1983; Pirkle et al. 1994). By the late 1990s, the mean BLL had fallen to < 3 μg/dL (Pirkle et al. 1998). This point is relevant to cumulative dose estimation with both tibia lead and CBLI; that is, if associations are observed, we cannot clearly distinguish early from mid-life from later life exposures using these summary metrics and thus must interpret the critical periods of exposure with caution.


Howard Hu, Regina Shih, Stephen Rothenberg and Brian S. Schwartz. 2007. The Epidemiology of Lead Toxicity in Adults: Measuring Dose and Consideration of Other Methodological Issues. Environmental Health Perspectives. 115;3:455-462.


Problems Remain Despite Early Successes
Recognition of lead as a major toxic hazard was one of the concerns that resulted in the creation of both the US Environmental Protection Agency (EPA) and the Occupational Safety and Health Administration (OSHA) in 1970. The removal of lead from many commercial products—such as gasoline, ceramic glazes, house paint, and solder in plumbing pipes and food cans—dramatically reduced environmental sources of lead exposure. Average blood lead levels in adults were between 10–15 μg/dL in the late 1970s. Now they are 1–2 μg/dL. Despite this progress, research conducted over the past several decades emphasizes that major public health concerns persist.

Legal protections lag current knowledge about lead toxicity. OSHA standards for permissible lead exposure limits were established in the late 1970s. At that time, the primary goal was preventing signs and symptoms of overt lead poisoning, particularly anemia, central nervous system problems, peripheral nerve damage, severe kidney damage, and reproductive problems. To protect against overt lead poisoning, OSHA established permissible exposure limits that were intended to prevent the blood lead level of most workers from exceeding 40 μg/dL. Over the past three decades, extensive research has shown that lead causes significant health problems in adults at much lower levels. Cumulative exposure to low to moderate levels of lead has been associated with an increased risk of hypertension and reduced cognitive and kidney function. Low levels of lead exposure during pregnancy have been associated with an increased risk of miscarriage and impaired fetal growth and neurological development.

Reproductive problems. Low to moderate levels of lead exposure during pregnancy have been associated with an increased risk of spontaneous abortion and with harmful effects on fetal physical growth and brain development. Two prominent studies in which the average maternal blood lead level during pregnancy was approximately 10 μg/dL or less found that prenatal lead exposure was associated with decreased childhood IQ.

Current Lead Standards Do Not Protect Workers
Public health advocates have applauded US successes in reducing environmental levels of lead and protecting children from lead exposure. However, many assert that we are not protecting workers—and their children. Occupational health experts agree that OSHA’s lead standards have serious limitations:

The standards are based on outdated toxicity information. Current standards require removing workers from lead exposure when their blood lead level exceeds 50 or 60 μg/dL. However, a number of studies show that harmful effects can occur at much lower levels. A group of experts (including co-author Kosnett) recently recommended removing
workers from exposure “if a single blood lead concentration exceeds 30 μg/dL . . .[and] if exposure control measures over an extended period do not decrease blood lead concentrations to less than 10 μg/dL.” Women who are or may become pregnant are advised to reduce lead exposure if their blood lead levels (BLLs) exceed 5 μg/dL.

OSHA is not required to update standards.
Environmental health scientists Drs. Ellen Silbergeld and Virginia Weaver of Johns Hopkins University note that environmental protection law requires periodic review of new data “to determine whether existing standards should be revised.” OSHA has no such requirement. OSHA’s failure to update its lead standards ignores medical evidence of harm from lowerlevel, long-term exposures and has likely resulted in preventable disease in many leadexposed workers. In the mid-1970s, when OSHA established a permissible exposure limit and a medical removal requirement, adult blood lead levels from background environmental exposures were considered to be 19 μg/dL. Today it is more feasible to maintain workers’ blood lead levels below 10 μg/dL, in part because current background lead exposures contribute significantly less to their overall blood lead levels.
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