Lead (inorganic)
Updated: December 2015
...........................................................................................................................
Symbol: Pb
Atomic number: 82
Atomic weight: 207.2
Lead is one of the first metals that man learned to use. It was known and used
in Eastern Asia Minor as early as 4000 B.C. Because of the ubiquitous
distribution of lead, no lead-free environment existed. Thus, man is and
always has been submitted to a "background" exposure from ambient air,
food, and beverages [1]. From the 1960s onwards it was recognized
increasingly as a public health hazard.
It exists in nature as a mixture of three isotopes: Pb 206, Pb 207, Pb 208.
It forms compounds with a valence state of +2, +4. Lead melts at a
temperature of 3270C and boils at 16200 C. Because of its low melting point,
it was one of the first metals smelted and used by ancient humans [2].
Lead is a bluish-white lustrous metal. It is very soft, highly malleable, ductile,
and a relatively poor conductor of electricity. It is very resistant to corrosion
but tarnishes upon exposure to air. Lead pipes with the insignia of Roman
emperors, were used as drains from the baths, and are still in service.
Lead is exploited commercially from a variety of ores, the most abundant of
which is galena – PbS. It is extracted from the ore by a mechanical separation
process involving flotation and the enriched ore is then smelted.
Usage and exposure

Sites and industries with lead exposure:

lead smelters;

battery manufactures;

welding and cutting operations;

construction and demolition;

rubber industry;

plastics industry;

printing industry;

firing ranges;

radiator repair;

soldering of lead products;

production of gasoline additives;

zinc smelting;

solid waste combustion;

organic lead production;

copper smelting;

ore crushing and grinding;

paint and pigment manufacture.
Lead exposure is generally well controlled in the major lead-using industries,
such as smelting and battery manufacture. However, significant exposure can
occur in occupations that are not normally considered to be at risk [ 3]. For
example, significant blood levels were seen in scaffolders involved in erecting
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and dismantling access structures during the renovation of previously leadpainted structures.
The general population could be significantly exposed owing to poorly glazed
ceramic ware, the use of lead solder in the food canning industry, high levels
of lead in drinking water, the use of lead compounds in paint and cosmetics
and by deposition on crops and dust from industrial and motor vehicle sources
[4].
Routes of exposure
The respiratory route is more important in occupational exposure.
The gastrointestinal route is the main route of exposure for the general
population.
Cutaneous absorption of inorganic lead is negligible.
Metabolism
As a fume or fine particles, lead is absorbed through the lungs. Absorption
from the lungs is dependent on the size of the particles and solubility.
Particles in the 0.5-5.0 micron range are most likely to be deposited in the
alveoli and absorbed. Approximately 40% of inhaled lead oxide fumes are
absorbed through the respiratory tract. Larger particles, which are entrapped
in the larger airways, may be swallowed and may lead to gastrointestinal
absorption. Roughly 5-10% of ingested lead compounds are absorbed from
the gastrointestinal tract [5].
Lead is relatively less well-absorbed from the gastrointestinal tract in adults
(20-30%), children absorb as much as 50% of dietary lead.
Inorganic lead is not absorbed through intact skin [Sullivan].
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After absorption into the blood stream, lead is bound to the red cell. It is
distributed extensively throughout tissues, with the highest concentration in
bone, teeth, liver, lung, kidney, brain, and spleen. Bone constitutes the major
site of deposition of absorbed lead, where it is incorporated into the bony
matrix similar to calcium. The lead in dense bone is only slowly mobilized and
gradually increases with time [LaDou, 1997].
Lead has a great affinity to erythrocytes and at least 95% of the circulating
fraction is bound to these cells. The total content of lead in the organism is
called the body burden. In a steady state about 90% of the body burden is
bound to the bone. Long bones contain more lead than do flat bones. Teeth
contain more lead than do any of the bones. The lead deposits in bone
consist of at least two compartments. One is firmly bound and partly located in
the bone matrix. Another fraction ("new lead") is more exchangeable, although
it may persist for months and years after exposure [Zenz].
Lead binds to mitochondrial membranes and interferes with proteins and
nucleic acid synthesis. Excretion is slow, primarily through the kidney. The
half-life of lead is long, estimated to be from 5 to 10 years. Bone disease
(osteoporosis, fractures), pregnancy, and hyperthyroidism may lead to
increased release of stored lead and elevated blood lead levels [LaDou, 1997].
Target organs
Central and peripheral nervous system,
hematologic system,
reproductive system,
skeletomuscular system,
kidneys,
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cardiovascular system.
Health effects
Acute
Extremely high respiratory or gastrointestinal exposure of lead results in acute
poisoning. Acute symptomatic lead intoxication now a rare occurrence, and
usually requires several days or weeks of intense exposure [6]. Symptoms are
usually gastrointestinal. Cramping, colicky abdominal pain, and constipation
are present early. Nausea, vomiting, and black, tarry stool may also
accompany the acute presentation. In the acute stages of lead poisoning, and
particularly if the patient has colic, the blood pressure often is elevated. The
mechanism of colic lies in spasmodic contraction of the smooth muscles of the
arterioles, resulting in pallor of the face, transient elevation of the blood
pressure, and decreased glomerular filtration. With large enough doses, an
acute encephalopathy can develop, accompanied by renal failure. Acute
encephalopathy, characterized by diffuse pathologic changes and cerebral
edema, is usually associated with high blood lead levels (over 150 µg/dL)
[Zenz, Sullivan, LaDou 1997, Gidlow].
Chronic
In most cases lead is absorbed more slowly over weeks to months, and the
clinical course is chronic.
Central nervous system
Chronic encephalopathy affecting both cognitive function and mood is seen
more commonly. Symptoms are headache, lassitude, sleep disturbances, loss
of libido.
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Changes
in
neuropsychological
function
are
seen
in
visual/motor
performance, memory, attention and verbal comprehension. There are
consistent associations of blood lead levels with test scores in executive
abilities, manual dexterity and peripheral motor strength at blood lead levels
as low as18 µg/dL [7].
Progression to franc lead encephalopathy with
seizures and coma is rare in adults [LaDou, 1997].
A study carried out in Taiwan shows significantly impaired neurobehavioral
functions which include slow performance of psychomotor tasks, impaired
processing of visual-spatial information, reduced memory and learning
functions, low performance accuracy, slow execution of responses, and poor
attentional control [8].
One adverse neurophysiological effect that has been reported to be
associated with Pb intoxication is auditory impairment, as revealed by
sensory-neural hearing loss and abnormal neural transmission in the tracts
and nuclei of the auditory brainstem of animals and humans. It is reported that
Pb exposure, even in low levels, impairs the inner ear receptor cells and
neuronal function in the ascending auditory brainstem tracts. The Ecuador
study has reported a relationship between decreased hearing and long-term
ambient Pb exposure but no effects on hearing after short-term exposure [9].
Peripheral nervous system
In the peripheral nervous system lead causes a neuropathy which primarily
affects the motor nerves and which appears to be principally axonal.
Neuropathy is more severe in the upper rather than lower extremity. The
classic wrist drop has become rare [Sullivan, Gidlow].
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Studies have shown a slowing of sensory motor reaction time in male lead
workers with blood lead levels > 40 µg/dL. Peripheral motor neuropathy is
seen as a result of chronic high-level lead exposure. However, there is
conflicting evidence of a reduction in peripheral nerve conduction velocity at
lower blood lead levels. Some studies have not seen effects below a blood
lead level of 70µg/dL [Gidlow].
Hematologic system
Anemia is a frequent manifestation of lead intoxication in children but is
unusual in adults. The anemia is usually normochromic and normocytic.
The hematologic abnormalities of lead poisoning can be attributed to:
1. Inhibition of hemoglobin synthesis
Intracellularly, lead binds to sulfhydryl groups and interferes with numerous
cellular enzymes, particularly zinc-dependent enzymes. Two enzymes are
affected by lead:
ALA-D (aminolevulinic dehydratase), a cytoplasmic enzyme,
ferrochelatase, a mitochondrial enzyme.
Interference with ALA-D is dose- related and occurs at blood lead
concentration between 10 and 20 µg/dL. It is complete at blood lead
concentration of 70-90 µg/dL. As a result of inhibition of ALA-D the levels of
ALA (δ- aminolevulinic acid), coproporphyrin III, porphobilinogen, and
protoporphyrin IX in the blood become elevated [Zenz].
Of all known biologic effects of lead, hematologic or otherwise, inhibition of
ALA-dehydratase is earliest [Zenz].
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Ferrochelatase catalyzes the transfer of iron from ferritin to protoporphyrin to
form heme (Sullivan). As a result of inhibition of ferrochelatase the level of ZPP
(zinc protoporphyrin) in erythrocytes becomes elevated.
2. Shortened life span of circulating erythrocytes
Increased red cell turnover and frank hemolysis may be present, with
basophilic stippling of the red blood cells and reticulocytosis (LaDou, 1997).
Toxic porphyria
Lead intoxication (blood lead level in adults > 60 µg/dL) causes symptoms
and signs similar to acute intermittent porphyria. The excess of δaminolevulinic acid and porphobilinogen represents the neurotoxic effect:
abdominal pain, constipation and vomiting [LaDou, 1997].
Reproductive system
Lead can cross the placental barrier, which means pregnant women who are
exposed to lead also expose their unborn child [10].
At very high blood lead levels, lead is a powerful abortifacient. At lower levels,
it has been associated with miscarriages and low birth weights in infants [11,
Gidlow].
In females, occupational exposure resulting in blood lead levels >10 μg/100
ml is associated with an increased risk of spontaneous abortion, premature
delivery, low birth weight and may be associated with an increased risk of
minor developmental abnormalities [Gidlow].
Some studies have shown reduced sperm count and motility, but there are
few data showing an effect on the reproductive capability of male lead
workers. Current thinking is that significant effects on reproductive capacity
are not seen below a blood lead level of > 50 µg/dL, but blood lead
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concentrations of > 40 µg/dL may affect sperm morphology and function
[Gidlow, IARC].
Recent studies have shown that blood lead levels in men >40 μg/100 ml may
be linked to low libido, low semen volume and sperm counts, increased
abnormal sperm morphology and decreased sperm motility leading to
impairment of reproductive function [Gidlow].
Immunology
There is some evidence for suggesting that workers with increased lead blood
levels may have an increased susceptibility to colds; an increased percentage
and increased absolute count of B lymphocytes may be seen [Gidlow].
Kidneys
Heavy and prolonged exposure to lead may cause progressive and
irreversible renal disease. Lead nephropathy is characterized by a progressive
impairment of renal function and is often accompanied by hypertension. The
functional impairments in lead nephropathy are compatible with damage of the
proximal tubuli and are manifested by decreased reabsorption of amino acids,
glucose, phosphate, and citric acid. In severe cases the whole Fanconi triad
may occur [Zenz].
Exposure to high lead levels can produce renal tubular damage with
glucosuria and aminoaciduria (saturnine gout). Gouty arthritis was noted in
approximately 50% of patients. The possible mechanisms of saturnine gout
include decrease renal clearance of uric acid, crystallization of low urate
concentrations, and lead-induced formation of guanine crystals [LaDou, 1997].
Some studies have found increased levels of N-acetyl-β-d-glucosaminidase
and β2 microglobulin in the urine [Gidlow].
Cardiovascular system
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The studies have not shown the clear association between blood pressure,
development of hypertension, and cardiovascular or cerebrovascular damage
in lead poisoning [Gidlow].
Skeletal system
Lead may perturb calcium-mediated functions, affect bone turnover, and
decrease growth and stature in young children. The high levels of lead in
bones and blood resulting from occupational exposures exacerbated bone
loss in postmenopausal women. The study in Idaho shows that spine bone
mineral density decreased with increasing blood levels among female former
smelter workers [12].
Gastrointestinal system
One of the manifestations of lead exposure is a bluish line on the gums
(Burtonian line). It is formed by precipitated lead sulfide, and it only indicates
that the patient has been exposed to lead [Zenz].
Carcinogenicity
Lead is well defined animal carcinogen with increased tumors reported in both
kidney and brain. Many of the mechanisms that can be proposed for
carcinogenic activity of lead suggest that its role in carcinogenesis is
permissive rather than causative. That is, lead may be able to increase the
risk of cancer by reducing the ability of the cell to protect or repair DNA
damaged by other exposures rather than by causing alterations in DNA
directly [13]. The international Agency for Research on Cancer has concluded
that there is limited evidence for the carcinogenicity to humans of exposure to
inorganic
lead
compounds.
The
available
epidemiological
data
on
occupational exposure to organic lead compounds were considered to provide
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inadequate
evidence
for
carcinogenicity
to
humans.
Inorganic
lead
compounds are probably carcinogenic to humans (Group 2A) [14, IARC,
Gidlow].
References
1. Zenz C.: Occupational Medicine, 3rd ed., pp. 506-541. Mosby, 1994.
2. Sullivan J.B., Krieger G.R., eds.: Hazardous Materials Toxicology : Clinical
Principles of Environmental Health, p 834-844. Williams & Wilkins, 1992.
3. Gidlow DA: Lead toxicity. Occup Med (Lond) 65: 348-356, 2015.
4. Sen D., Wolfson H., Dilworth M.: Lead exposure in scaffolders during
refurbishment construction activity-an observational study. Occup Med (Lond) 52:
49-54, 2002.
5. LaDou J.: Occupational and Environmental Medicine, 2nd ed., Appleton & Lange,
Stamford, 1997. pp 416-420.
6. LaDou J.: Current Occupational and Environmental Medicine, 5th ed., McGraw
Hill Education, 2014. pp 471-474.
7. Gidlow D.A.: Lead toxicity. Occup Med (Lond) 54: 76-81, 2004.
8. Shun-Sheng C., Tsan-Ju C., Chuang-Hao L., et al.: Neurobehavioral Changes in
Taiwanese Lead-Exposed Workers. J Occup Environ Med 47(9):902-908, 2005.
9. Counter S.A., Buchanan L.H., Ortega F.: Neurocognitive impairment in leadexposed children of Andean lead-glazing workers.
J Occup Environ Med
47(3):306-12, 2005.
10. CDC. NIOSH. Information for Workers. Health Problems Caused by Lead
<http://www.cdc.gov/niosh/topics/lead/health.html>
11. IARC. VOL. 87 February 2006.
12. Potula V., Kleinbaum D., Kaye W.: Lead Exposure and Spine Bone Mineral
Density. J Occup Env Med 48(6):556-564, 2006,
13. Silbergeld E.K., Waalkes M., Rice J.M.: Lead as a carcinogen: Experimental
evidence and mechanisms of action. Am J Ind Med 38:316-323, 2000.
14. OSHA. Lead. Health Effects.
<https://www.osha.gov/SLTC/lead/healtheffects.html>
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