Lead Toxicity:
Low-Level Environmental Exposure

Lead Poisoning Effects Neurobehavioral Changes,
Hypertension, Brain Dysfunction

By Nachman Brautbar, M.D.

Introduction
Lead poisoning is as ancient as Roman history, and indeed lead has been used extensively by the Romans and described by the Romans. The purpose of the manuscript is not to discuss classic lead toxicity and lead poisoning effects, but to address the concept of low-level environmental lead toxicity and poisoning.

Low-Level Environmental Exposure
In developed countries lead poisoning is not prevalent; however, in developing countries lead poisoning is extremely common, to such an extent that world-wide lead toxicity and lead poisoning remain the most common of occupational poisoning. The most common occupational and environmental exposures to lead are encountered in the manufacturing of lead batteries, paints and colors; lead compounds; rubber products and glass; grinding, dicing and cutting by power tools, products containing lead; sanding down from the application of lead paints and glazes; inhalation of lead oxide fumes in the demolition of old industrial buildings and cutting lead pipes with gas powered burning torches; firearm instructors; and law enforcement agents in the process of firearm instruction. The most common environmental nonindustrial exposure to lead is via the drinking water and in communities residing around incinerators, toxic dumps, and manufacturing industries utilizing lead and releasing lead into the environment. Organic lead compounds have been added to petrol as anti knock agents for over half a century, and exposure may result from handling of these compounds in refineries or during cleaning out of tanks which contained leaded petrol.

In the last 10 years, studies by the Environmental Protection Agency, as well as other international regulatory agencies, have shown that chronic low-level exposure to lead is associated with societal problems, such as brain dysfunction in children exposed to lead in drinking water, neurobehavioral changes in adults, hypertension and chronic kidney disease. As a result, the Environmental Protection Agency has moved to reduce the lead concentration in drinking water to very low levels. This notion of low level toxicological exposure to lead is changing the presenting picture of lead toxicity. While in the past the classic presentation would be the patient who has been exposed to high levels of lead and developed abdominal pain, anemia and neurological changes, the picture now becomes more subtle, as a result of prolonged low-level exposure which affects mainly the central nervous system and causes neurobehavioral changes. Also, the issue of prolonged lead exposure and hypertension has recently been recognized as a societal problem and a cause for hypertension and kidney disease.

1. Lead Exposure, Blood Lead Levels And High Blood Pressure
Intense and prolonged lead exposure have been shown as a cause of hypertension. Indeed, observations of lead poisoning effects secondary to exposure to high levels showed increased incidence of strokes, kidney disease and hypertension. An increased incidence of hypertension was also described in communities exposed to lead-containing moonshine. More recent studies have shown that there are harmful effects of low level exposure to lead which is commonly found in the general population. Potential effects on adult blood pressure have been described in populations encountering common environmental concentrations. (New England Journal of Medicine, 1979, Volume 300, Page 689: Lancet, 1976, Volume 2, Pages 1-3.) Other published studies (New England Journal of Medicine, 1982, Volume 307, Pages 573-579; New England Journal of Medicine, 1983, Volume 308, Pages 1373-1377) have shown that blood lead levels were related to ambient environmental exposures. These studies showed a direct relationship between blood pressure elevation and low level toxicological exposure to lead, without the classic presentation of lead toxicity. (New England Journal of Medicine, 1983, Volume 309, Page 17-21) A recent study in the United States looked at the relationship between blood lead levels and high blood pressure and found direct relationship between blood lead levels and systolic and diastolic blood pressure for men and women, and that blood levels of lead were significantly higher in younger men and women with high blood pressure. (JAMA, 1985, Volume 253, Pages 530 to 534) It is of importance to note that in all of these studies the blood pressure was correlated with slightly elevated lead levels which have been considered to be "safe", and are the result of low-level cumulative exposure to lead. This study indicates very clearly that blood lead levels were found to contribute independently to the elevation of systolic and diastolic hypertension. Multiple sources of exposure exist including occupational ambient environmental and consumption of water from lead piping which all contribute to elevation of blood lead levels.

Most thinking about lead exposure and hypertension has usually been directed towards excessive occupational exposure and effects of lead on kidney function and kidney compromise and, in turn, effects on high blood pressure. There is more and more evidence that chronic low-level toxicological exposure to lead has both direct and indirect effects on the blood vessel and the smooth muscle of the blood vessel contractility, and thereby affecting blood pressure.

We have recently studied the effects of lead on various mechanisms of high blood pressure. These studies (Tox Ind Health, 1992, Volume 8(1/2), Pages 89-102) clearly indicated a direct effect of lead administration in the drinking water on the development of hypertension.

Are We Missing These Hypertensive Patients When We Evaluate The Low-Level Industrial or Environmental Exposure to Lead?
I personally believe that since these patients are not seen by trained clinical toxicologists but rather come in "industrial" clinics, the diagnosis is missed. Those of us who practice toxicology and occupational medicine have been trained that lead poisoning is the "classic lead poisoning" with exposure to high levels, and the classic presentation of lead toxicity. However, more and more studies in the last 10 years published in the peer reviewed literature show clearly that chronic environmental and industrial exposure to low levels of lead can be and are associated with toxicity that affected only some systems, among them the cardiovascular system in the form of hypertension.

2. Central Nervous System And Neurobehavioral Changes
Studies published in the scientific literature indicated very clearly that lead poisoning is associated with significant neurobehavioral changes. If lead affects the central nervous system in the same way as other toxic substances, it is reasonable to expect that a dose response relationship exists and that individuals with low to moderate blood levels will manifest neurobehavioral disorders that are qualitatively similar to, although less severe, than those found in lead-toxicated adults with higher levels. This, however, is not the case. Recent studies examined blood lead levels in non exposed individuals with an average of 7.2 mcg per 100 cc as compared to blood levels of exposed individuals to 40.1 mcg per 100 cc. These investigators found that contrary to previous reports, subjects with blood levels in the low to moderate range differ from controls in the measure of psychomotor speed and manual dexterity, the investigators concluded that it is likely that these results are secondary to lead-mediated neuromuscular damage. Most recent studies (British Journal of Industrial Medicine, 1989, Volume 46, Page 698-707) showed that workers with blood levels of lead from 41 to 80 showed definite impairment of neuropsycho logical functioning and reduction in the neuropsycho logical performance of patients with low-level toxicological exposure to lead, with lower blood lead levels.

Studies in children exposed to low-level concentrations of lead (New England Journal of Medicine, 1990, Volume 322, Pages 83-88) showed that exposure to lead in children is associated with deficits in central nervous system functioning that persists into young adulthood. These were exposures to levels which are "not toxic" and were considered as "safe" by the majority of regulatory agencies. Now the Environmental Protection Agency has come out with strong recommendations to reduce this potential hazardous exposure to very minimal or close to zero levels.

Lead is a well-known neurotoxic agent that can cause severe impairment of nerve tissue, particularly in developing brain specifically newborns and children (Harrison's Principles of Internal Medicine, 1987, 11th Edition, Pages 2463-2464). This scientific concept has recently been reported in the peer-reviewed scientific literature. Effects of such environmental exposure on the early cognitive development of brain of children was studied and published in the peer-reviewed literature by Bellinger, et al. (New England Journal of Medicine, 1995, Volume 316, Pages 1037 to 1043) and Harary, R., et al. (Environmental Research, 1995, Volume 50, Page 393), and clearly show that childrens brain and development is extremely sensitive to low-level exposures to lead.

Conclusion
The available scientific peer-reviewed data, described above, show that environmental exposure to low levels of lead on a repetitive basis in some populations and in some patients can be associated with high blood pressure, neurobehavioral abnormalities and kidney disease.

These issues of high blood pressure and neurobehavioral changes in relation to lead exposure are commonly missed, not looked for in patients who present with low-level toxicological exposure to lead. The majority of the doctors look for the "classic" presentation of lead toxicity when patients are exposed to high levels, but forget the concept of low-level toxicological exposure to lead. The prudent physician has to take these into account when evaluating the lead-exposed patient.

The practicing and evaluating physician who has to address the issue of environmental lead exposure and disease process, must go through the process of 1) differential diagnosis, 2) review of the medical records, 3) ruling out other conditions, 4) review of the environmental data and 5) material safety data sheets, and 6) then utilize sound scientific aspects as described by Bradford-Hill. (President's Address. Proc Royal Soc Med, 1965, Volume 9, Pages 295-300).

[Updated Manuscript in preparation]


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