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Effects of Lead on the Human Body

            
Permission graciously given by the author to reproduce this paper

THE HARMFUL EFFECTS OF LEAD ON THE HUMAN BODY

Ann Marie Yaros
2003

Abstract:  This paper will give a general overview of lead in the environment and the effects of health.  It examines the scope of lead in the environment, the pervasiveness of the substance, the likely sources of exposure, suggestions for reducing the exposure, and the effects on health.  It looks at lead exposure and its relationship to chronic renal diseases, lead exposure and intellectual impairment in children, lead exposure and possible delayed puberty, lead exposure and possible connections to Alzheimer’s disease, and neuropsychological toxicology as a result of lead exposure.  Assessment techniques and treatment recommendations are also examined.

Discussion of the History, the Mental, Emotional, and Behavioral Effects of Lead

     Lead has long been used in modern industrial society and has also long been known to be highly toxic.  According to the 1980 Council on Environmental Quality report (Congressional Quarterly, 1981), Pliny the Elder, a Roman naturalist and writer in the first century A.D. warned against the poisonous effects of lead fumes.  Charles Dickens (Congressional Quarterly, 1981), referred in 1861 to lead’s acute effects on human health including convulsions, coma, and death.  Greek physicians first recognized the association between exposure to lead and disease over two millennia ago (Marsden, 2003).   Wedeen (as cited in Hartman, 1995) reports that lead beads have been found in Asia Minor dating back to 6500 B.C.  Lead was employed in ancient Egypt in ornaments, glass, and eye paint.  The ancient Romans used it in paint, makeup, and piping and aqueducts (Windebank et al, as cited in Hartman, 1995). 

     Lead is poisonous because it interferes with the body’s basic functions.  The body cannot tell the difference between lead and calcium, which is needed for bone development.  Lead remains in the blood stream for weeks, then is absorbed in the bones, where it can collect for a lifetime (EPA, 1998).  Balch and Balch (2000), state that lead is a cumulative poison that is retained in the body.  Lead that is not excreted through the digestive system accumulates and is absorbed directly from the blood into other tissues.  When lead leaves the blood stream, it is stored in the bones where it continues to build up over a lifetime.  Lead from the bones may then reenter the blood stream at any time as a result of severe biologic stress, such as renal failure, pregnancy, menopause, or prolonged immobilization or illness (Balch & Balch, 2000). 

     Symptoms of chronic exposure include fatigue, headache, poor appetite, clumsiness, diminished mental capacity, central nervous system damage, and damage to the blood forming system and the kidneys (Congressional Quarterly, 1981).  The Congressional Quarterly report (1981) also lists concerns about the effect of lead on the reproductive systems.  Lead has been shown to disrupt the ovarian cycle in women and to produce impotence, impaired libido and decreased number and quality of sperm in men.  A study by Dr. Philip J. Landrigan, director of epidemiology at NIOSH (Congressional Quarterly, 1981) showed that lead is particularly dangerous for young children because their nervous systems are still undergoing development and are thus vulnerable.   According to the September, 1981, issue of the Smithsonian magazine (as reported in the Congressional Quarterly, 1981) Dr. Herbert L. Needleman and a research team at the Children’s Hospital Medical Center in Boston found that the higher the lead concentration in the children’s teeth, the lower their scores on intelligence and functional tests and the lower their ratings on classroom performance.  A study by Lin, Lin-Tan, Hsu, and Yu (2003) concluded that low level environmental lead exposure may accelerate progressive renal insufficiency in patients without diabetes who have chronic renal disease.  A study by Canfield, Henderson, Cory-Siechta, Cox, Jusko, and Lanphear (2003) showed that children’s IQ scores at ages 3 and 5 were inversely associated with blood lead concentrations, even when the lead levels were below the CDC and WHO levels of concern.  A previous meta-analysis (as cited in Rogan and Ware, 2003) reported a 2.6 point decline in IQ for increased lead concentrations from 10 to 20 microgram per deciliter.  Bellinger et al (as cited in Rogan and Ware, 2003), reported a decline of 5.8 points with an increase in blood lead concentration from 10 to 20 micrograms per deciliter.  A report by the EPA (1998) also lists nervous system and kidney damage as well as learning disabilities, attention deficit disorder, decreased intelligence, speech, language, and behavior problems, poor muscle coordination, decreased muscle and bone growth, fetal brain damage, memory and concentration problems, and hearing damage.  The same report also states that high levels of lead can have devastating effects on children, including seizures, unconsciousness, and possibly death.  A study by Selevan, Rice, Hogan, Euling, Hutchens, and Bethel (2003) suggested that blood lead concentrations of 3 micrograms per deciliter were associated with significant delays in breast and pubic hair development in pubertal girls.  Autopsies have revealed excess mercury, aluminum, copper, and lead in the brains of Alzheimer’s and schizophrenia patients (Warren, 1991).  A study by Huel (as cited in Hartman, 1995) found that maternal hair lead level during pregnancy is negatively correlated with cognitive, verbal, qualitative, and memory subscales on the McCarthy Scales of Children’s Abilities.  Needleman et al (as cited in Hartman, 1995) found WISC-R Full Scale IQ’s to be significantly lower by about 45 points between high and low lead groups as measured by lead assays of shed teeth.  This study also reported that high tooth lead children also performed more poorly on all subtests of the Seashore Rhythm Test, which suggests auditory processing dysfunction, and on a reaction time measure, suggesting impaired vigilance or attention.  Bellinger, Hu, Titlebaum, and Needleman (as cited in Hartman, 1995) also show that dentin lead levels continue to correlate with neuropsychological function through the end of adolescence.  Dentin lead levels were inversely related to the number of categories achieved on the Wisconsin Card Sort Test and positively associated with the perseverative responses on this test.  Hoffman, David, Clark, Grad, & Swerd (as cited in Hartman, 1995) have also noted association of hyperactivity with lead.  The overall weight of the literature strongly supports the continued finding that childhood lead exposure is neurotoxic to the developing child (Hartman, 1995).  Schwartz (as cited in Hartman, 1995) suggests that there may be no safe level of childhood lead exposure. 

      Hartman (1995) lists case studies in which performance on a variety of neuropsychological tests are impaired with increased lead toxicity in both children and adults.  Emotional effects are also noted.  Lead induced emotional alterations include depression, confusion, anger, fatigue, and tension (Baker, Feldman, White, & Harley as cited in Hartman, 1995).  These symptoms have been observed both in chronically exposed patients as well as in individuals with lead exposure histories of 2 weeks to 8 months (Bleeker et al as cited in Hartman, 1995). Behavioral observations were also noted.  Hartman (1995) reports the case of a 7 year old lead exposed child who quickly became frustrated with neuropsychological testing, had difficulty remaining in his seat, became continually active, restless, and would constantly manipulate objects on the testing table.  He was easily distractible and difficult to focus on task.  The behaviors could not be controlled with verbal command.  IQ scores showed mild to moderate mental retardation.  He showed global impairment of intellectual functions and school readiness skills.  Neuropsychological impairment also included concentration, fine motor coordination, visuospatial skills, abstract reasoning, planning, memory, and learning.  Prior to his exposure to lead, his development was considered normal (Hartman, 1995).   An article by Bernard Windham entitled Effects of toxic metals on learning ability and behavior (date unknown) also cited several studies discussing the harmful effects of lead, and other toxic metals, of the cognitive behavioral development of children.

     The negative effects of lead exposure are also evident in pets.  Young pets, as well as young children, are especially susceptible.  Anderson and Peiper (1998) report that young animal’s bodies absorb up to 90 percent of the lead to which they are exposed, whereas adult animal’s bodies absorb 10 percent.  Pets suffer from similar neurological and physical symptoms as humans.  Anderson and Peiper (1998) point out that any family whose pet is diagnosed with lead poisoning should have their children tested immediately.  Pets live and eat and drink water in the same environment and may develop identifiable signs of lead poisoning long before symptoms are obvious in children.

Discussion of Known Etiology

     According to the EPA (1998), people are exposed to lead through a variety of means.  Manufacturers used to put lead pigments in paint.  This use was banned in 1978, but many older homes, toys, and furniture still exist containing lead based paint.  Oil companies used to add lead to gasoline to stop engine knock, but lead particles escaped into the air through auto exhaust systems, leading to the EPA reducing the amount of lead allowed in gasoline in 1978, and ultimately banning it altogether.  This lead contamination may still be found in soils near roads.  Household pipes may also be a source of lead.  Homes built prior to 1930 contained lead water pipes.  Newer homes with copper pipes may also be a source of lead due to the solder used on them, which is 50% lead.  Lead solder used to seal food cans may mix with the food in the can.  The U.S. banned the use of lead solder in cans in 1995, but it is still used in other countries.  Therefore, lead solder may be found in cans imported to the U.S.  Some imported, non glossy vinyl miniblinds can also be a lead hazard because sunlight and heat can break down the blinds and may release lead contaminated dust.  Lead glazed ceramic ware, pottery, and leaded crystal can contaminate food and liquids stored in them.  Lead smelters and other industries can release lead into the air and can contaminate workers through dust and air.  Hobbies such as pottery, stained glass, or refinishing furniture can also be sources of lead exposure.  Lead dust from lead painted walls can be released if sanded or scraped.  Folk remedies that contain lead are also advised against by the EPA.  Two examples listed are “Greta” and “Azarcon”, which are used in Hispanic and Asian communities to treat an upset stomach.  Another listed is “Pay loo ah”, which is a red powder used to treat a rash or fever.  Balch and Balch (2000) also list the following additional sources of lead exposure:  lead acid batteries used in automobiles, tobacco, liver, water, some domestic and imported wines, bone meal, insecticides, and porcelain glazed sinks and bathtubs. 

     Lead in its pure form and various compounds continues to be used in many ways, with annual worldwide production estimated at about 5.8 million tons.  Leaded gasoline and paint are no longer used in the U.S., but U.S. consumption of lead has increased since the 1980’s, with 1.3 million tons of lead consumed in 1989 alone (Mushak, as cited in Hartman, 1995).  Lead is used in traditional heavy industry, and has found additional uses in electronic components, home radon barriers, television and CRT screens, medical imaging devices, nuclear shielding, aviation soundproofing, ceramic glazes, batteries, and paint pigments (Hartman, 1995).  OSHA has identified five industries with high risk for significant lead exposure:  lead smelting, battery manufacture, brass/bronze and copper foundries, and pigment manufacture (Froines, Baron, Wegman, and O’Rourke, as cited in Hartman, 1995).  More than 2 million metric tons of lead are emitted into the environment annually (Mushak, as cited in Hartman, 1995).  More than 800,000 U.S. workers are exposed to lead in their jobs, and up to 20% have elevated blood lead levels (Schottenfeld & Cullen, as cited in Hartman, 1995).  In terms of quantity produced and number of workplace exposure victims, lead’s potential effect of human health remains greater than for any other neurotoxin except alcohol (Hartman, 1995). 

Discussion of Possible Causative Agents/Factors Consistent with this Course

     This course deals with the body-mind connection.  As cited above, the toxic effects of lead have been known for years.  The effects of lead on the physical, mental, behavioral, and cognitive functioning have also been well researched.  Some of the studies and the effects of the lead exposure are cited in this paper.  Working with a neuropsychologist for the past 12 years has made me very aware of the effects of metal and chemical exposure on psychological and neuropsychological functioning.  Too often a person’s mental or physical problems are taken at face value and futile attempts are made at treating the condition without ever testing for metal or chemical toxicity.  This is essential, identifying if toxic exposure is causing the symptoms. 

Discussion of Possible Mechanisms of Action of this Causative Agent

     In relation to the study above regarding lead exposure and chronic renal disease, Marsden (2003) states that “divalent lead compounds derived from environmental sources accumulate either rapidly or gradually and target proteins that bind to zinc or calcium at the molecular level.”  He further states that “erythrocytes store more than 99 percent of blood lead bound to the zinc dependent delta aminolevulinic acid dehydratase.  This is an important enzyme in heme synthesis that is potently inhibited by lead, explaining tests that involve the measurement of porphyrin or the determination of heme-synthesizing enzyme activity.”  Marsden (2003) also states that “lead accumulates in the proximal renal tubules, which explains the relationship between kidney disease and lead.  Impaired tubular function in patients with acute toxic effects of lead are aminoaciduria and renal glucosuria due to diminished reabsorption and hyperuricemia due to diminished secretion of urate.”  He also states that “long term exposure to lead results in increases in the body lead burden that are not reflected in blood levels, because the lead content of red cells reflects only recent exposure.  Approximately 90 to 95% of the lead is stored in calcium dependent skeletal pools and with slow turn over, especially in cortical bone.”

     Lead is accumulated via inhalation and ingestion.  It is transported throughout the body by the erythrocytes and is deposited in soft tissue and bone (Wedeen, as cited in Hartman, 1995).  Silbergeld, (as cited in Hartman, 1995) states that several mechanisms of lead related neurotoxic damage have been proposed.  Lead may compete with calcium, sodium, and/or magnesium in neurotransmission.  Direct and indirect effects on nerve cell mitochondria, inhibiting phosphorylation, have been suggested.  He also states that “non neural effects of lead on such processes as membrane transport, oxidative phosphorylation, and heme synthesis may affect neuronal function by depleting supplies of precursors, reducing energy sources or producing neurotoxic intermediates”.  Ronnback and Hansson (as cited in Hartman, 1995) propose that “low dose lead and mercury are neurotoxic to astroglial structures and damage glutamate transmission, leading to secondary decreases in other neurotransmitter systems.  Astrogliosis may be particularly evident in the hippocampus and cerebellum, which are particularly vulnerable to lead toxicity”.  Leggett (as cited in Hartman, 1995) states that distribution of low levels of lead in the brain is significantly correlated with the brain’s potassium concentration, indicating that lead concentrated in areas of high cell density such as the hippocampus.  Lead is taken up by the mitochondria in brain cells and accumulates in areas of calcium localization.  At high levels of lead exposure, the blood brain barrier breaks down and lead gains direct access to neural tissue (Leggett, as cited in Hartman, 1995).  Fullerton (cited in Hartman, 1995) states that there is evidence from animal research and some corroboration in human case studies that lead is a demyelinating agent.  Niklowitz (as cited in Hartman, 1995) has observed neurofibrillary tangles in animals and in an autopsy, indicating a possible relationship of chronic lead exposure and Alzheimer like symptoms. 

     Lead passes through the placenta and penetrates the blood brain barrier, accumulating in both breast milk and brain tissue.  Neurological deficits may be produced both prenatally, and after birth, through breast feeding (Hartman, 1995).  Roelevelt et al, (as cited in Hartman, 1995) states that many studies have linked prenatal lead exposure with mental retardation and impaired cognitive development.  Organic lead is contained in leaded gasoline, solvents or cleaning fluids.  Organic lead exposure exerts its neuropsychological effects by interfering with energy metabolism and possibly damaging the hippocampus, amygdala, and pyriform cortex (Grandjean, as cited in Hartman, 1995).  One form of organic lead, tetraethyl lead, is metabolized into triethyl lead, which can cross the blood brain barrier and disrupt cholinergic and adrenergic central pathways (Bolder, Stanczik, & Long, as cited in Hartman, 1995).

      The causes of lead induced emotional changes are uncertain.  Direct organic brain dysfunction may produce depression via cortical and subcortical tissue damage.  Hypothalamic alterations and changes in catecholamine metabolism have also been suggested (Schottenfeld & Cullen, as cited in Hartman, l995).  Secondary emotional reactions to diminished cognitive functioning may also contribute to affective changes (Hartman, 1995).

Discussion of Assessment Techniques and How They Might Be Used

     Hartman (1995) states that EDTA chelation challenge has been termed the “gold standard” in accurate assessment of lead body burden in adults who are not currently exposed to excessive lead.  Tell et al (as cited in Hartman, 1995) says that chelated lead is not a good indicator of total body burden, but only of more readily mobilized lead in blood, soft tissue, and active exchangeable bone fractions (vertebra, rib, and surface cortical bones).  Wedeen (as cited in Hartman, 1995) says that in vivo tibial x-ray induced x-ray fluorescence is considered a promising alternate procedure.  Bone lead is highly correlated with urinary excretion of lead for 24 hours after i.v. infusion with 1 g of calcium disodium edentate, a chelating agent (Tell, as cited in Hartman, 1995).  Zinc protoporphyrin level, a substance accumulated in red blood cells when lead inhibits the cells’ ability to contain iron, is also an indicator of biologically active lead on the nervous system than blood lead levels (Lilis et al, as cited in Hartman, 1995).  ZPP levels persist for the lifetime of red blood cells (120 days) and may be useful for individuals who have been exposed over this time frame, but whose blood or urinary lead levels have returned to normal (Zhang, as cited in Hartman, 1995).  Blood lead levels may provide only a very preliminary approximation of body and brain lead burden and use of blood lead levels alone might underestimate lead body burden (Erkkila et al, as cited in Hartman, 1995).  Long term exposure to lead results in increases in the body lead burden that are not reflected in blood lead levels because the lead content of red cells reflects only recent exposure. 
Approximately 90 to 95% of the lead is stored in calcium dependent skeletal pools with slow turnover, especially the cortical bone.  More reliable techniques for measuring this bone lead content are x-ray fluorescence studies of bone and infusions of chelating agents followed by measurement of blood or urinary lead levels.  Infusions of EDTA that extract lead from tissue are used both to diagnose and to treat increases in the body lead burden (Marsden, 2003).

     Hair analysis is another assessment technique for detecting lead in the body.  Hair analysis is discussed by Bland (1984) and by Passwater and Cranton (1983) as being a valid technique for detecting lead as well as other metals in the body.   As noted above, blood or urinary levels may have returned to normal but lead may still be present in the body, which will be detected in hair, bone, and teeth. 

      Since lead also accumulates in teeth, analyzing the lead composition of teeth might be an option, especially in baby teeth once they are shed. The analysis of baby teeth has been done to detect levels of strontium 90 to collect epidemiological data showing the risk for cancer associated with point sources of ionizing radiation (Sherman, 2000).  This “tooth fairy” project was conducted in Suffork County, New York, which is surrounded by nuclear power plants.  As of January, 1999, children born in Suffolk zip codes displayed an anomalous rise from below one picocurie per gram of calcium for children born in 1977 to levels as high as 8 picocuries per gram of calcium in 1992 (Sherman, 2000).  A similar “tooth fairy” project might be useful in many areas of the country to detect lead levels in children as well as adults.  Sherman (2000) states that testing baby teeth is a simple, inexpensive, noninvasive, and objective way to obtain necessary clinical evidence to coordinate with epidemiological data.  Since it’s effective for ionizing radiation it seems logical that it could also be effective to detect lead or other toxic chemicals or metals that are retained in the teeth. 

     An aminolevulinic acid (ALA) test is a urine test used to diagnose porphyria, and in the evaluation of subclinical forms of lead poisoning in children (Pagana & Pagana, 2002).  According to Pagana & Pagana (2002), “the basic precursor for the porphyrins, ALA is needed for the normal production of porphobilinogen, which leads to heme synthesis in erythroid cells.  Heme is used in the synthesis of hemoglobin.  In lead intoxication, heme synthesis is similarly diminished by the inhibition of ALA dehydrase.  This enzyme assists in the conversion of ALA to prophobilinogen.  As a result of lead poisoning, ALA accumulates in the blood and urine.”  Lead diminishes the activity of ALA dehydrase which converts ALA to porphobilinogen in the synthesis of heme for hemoglobin within erythroid cells. This test is a 24 hour urine collection test. 

      Pagana and Pagana (2002) also discuss another urine screen that can be used in conjunction with the ALA test.  The porphyrins and porphobilinogens levels can be measured.  It, along with the ALA test identifies various forms of porphyria.  Lead intoxication is associated with increased porphyrins in the urine.  This urine screen is also a 24 hour urine collection test

       A blood smear may also be used to identify lead poisoning.  Pagana & Pagana (2002) state “when examined microscopically by an experienced technologist and pathologist, a smear of peripheral blood is the most informative of all hematologic tests”.  By examining RBC intracellular structure through basophilic strippling, which refers to bodies enclosed or included in the cytoplasm of the RBC, blood lead levels can be detected (Pagana & Pagana, 2002). 

     The Quest Diagnostic web site, which was consulted for an HBM 607 assignment, listed twelve tests for lead toxicity, including blood, urine, hair, and nail analysis.

Treatment

        Lead is a cumulative toxic substance.  Lead that is not excreted through the digestive system accumulates in the body and is absorbed from the blood into other tissues.  As described above, when it leaves the blood stream it is stored in the bones where it continues to build up over a life time.  Some effects of lead poisoning are irreversible.  Therefore, prevention is the key to eliminating the devastating effects of lead toxicity.

     Chelation therapy is one method of treatment for lead toxicity.  Chelation comes from the Greek work chele meaning “to claw” or “to bind.” (Burton Goldberg Group, 1994).  Chelation therapy is used to rid the body of toxic metals.  Alternative medicine:  The definitive guide (1994) states that chelation takes approximately three and a half hours and that twenty to thirty treatments are recommended.  The patient reclines and is given an intravenous solution of EDTA with vitamins and minerals.   Infusions of EDTA that extract lead from tissue are used both to diagnose and to treat increases in the body lead burden.  Lin, Lin-Tan, Hsu, and Yu (2003) found that repeated chelation therapy can improve renal function and retard the progression of renal insufficiency for at least 24 months. 

     Gordon (as cited in Burton Goldberg, 1994) also suggests oral chelation may be useful.  Penicillamine is a drug used to treat heavy metal poisoning and works in a fashion similar to EDTA.  EDTA when taken orally provides chelating activity in the body even though only five percent of it is absorbed.  The chelating effects are therefore less dramatic and slower than when received intravenously.  He also states other substances serve as oral chelators, such as garlic, vitamin C, carrageenan, zinc and cysteine and methionine. 

     Balch and Balch (2000) list several nutrients and herbs which may be useful in treading lead toxicity.  Alpha-lipoic acid helps detoxify the body of pollutants, apple pectin binds metals and removes them from the body, calcium and magnesium prevents lead from being deposited in the body tissues, garlic helps to bind with and excrete lead, kelp removes metal deposits, L-lysine, L-cysteine and L-cystine act as detoxifiers and remove heavy metals, MSM helps detoxify metals, SAME helps chelate heavy metals, Vitamin C with bioflavenoids helps to neutralize the effects of lead, and zinc can displace lead and lower the body burden.  Balch and Balch (2000) also suggest the following nutrients and herbs as being beneficial for detoxifying the body of lead.  Gluthathione, L-methionine, lecithin granules, selenium, vitamin B complex, vitamin B1, vitamin B6, vitamin A, vitamin E, alfalfa, aloe vera juice, and chlorella.  They also suggest a high fiber supplement, a low fat diet, and vegetables such as beans, broccoli, Brussels sprouts, cauliflower, eggs, garlic, kale, legumes, onions, and spinach. 

     Some suggestions for avoiding lead ingestion are as follows:  avoid foods in lead soldered cans; keep painted surfaces in good repair so that older paint is not exposed or chipped; wash hands before eating to avoid possible contamination of hands from soils exposed to lead; replace lead water pipes and soldering; reduce boiling water longer than necessary as boiling concentrates contaminants; avoid ceramics that have lead glazing and lead crystal decanters and glasses; and avoid eating foods from gardens near roadways (Balch & Balch, 2000).  If one works in heavy industry or lives near industrial sites, it may be difficult to avoid exposure.  Shoes and clothes should be changed before entering the house to avoid bringing lead dust into the home. 

     In conclusion, lead is pervasive in the environment and causes numerous physical, behavioral, and mental difficulties.  Once ingested, it stores in the bones of the body for years.  While there is no cure for severe damage due to exposure, chelating agents can be administered to reduce toxicity from short term exposure.  The best treatment is prevention.  This paper has examined various maladies due to lead poisoning, assessment techniques to determine lead levels, treatment options, and prevention tips.  There may be no way to avoid lead contamination totally, but there are ways to eliminate exposure as much as possible. 

References

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