Adeela has been controlled up to a

Adeela abbas (15 arid 3122), Dur-e-najaf Bodla (15arid 3135), Maria
Saleem (15 arid 3164), Ayesha siddiqa (15 arid 3134), Mubashir Saleem (15 arid
317 )


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symptoms, types, history and exposure of lead toxicity.

Pages 1-17


Lead toxicity is important disease and its effects on the human body
are devastating. There is almost no function in the human body which is not
affected by lead toxicity. Though in countries like US and Canada the use of
lead has been controlled up to a certain extent, it is still used vehemently in
the developing countries. This is primarily because lead bears unique physical
and chemical properties that make it suitable for a large number of
applications for which humans have exploited its benefits from historical times
and thus it has become a common environmental pollutant. Lead is highly
persistent in the environment and because of its continuous use its levels rise
in almost every country, posing serious threats. This article reviews the works
listed in the literature with recent updates regarding the toxicity of lead.
Focus is also on toxic effects of lead on the renal, reproductive and nervous
system. Finally the technique.

Key words: adverse effects, toxicity, lead poisoning, premature
birth, environmental exposure, occupational exposure, neurological and
nephrological diseases, hematological studies, doses responses, child exposure.


Lead is the most common element
found and can dangerously harm our bodies. Our body cannot synthesize lead from
the other minerals that we need like calcium and iron, and it is absorbed into
our bloodstream if it is breathed in or swallowed. Once absorbed into our
bloodstream, lead is then deposited into our brain and bones where it can cause
serious damage. Children and pregnant
women are at the greatest risk for lead poisoning!

is the most abundant element found in the earth’s crust. It has been used since
early times, and has become widely-distributed in the environment. Lead
poisoning is of two types i.e. acute and chronic poisoning.( Rubin &
Strayer, 2008)



poisoning was common in Roman times because of the use of lead in water pipes
and earthenware containers, and in wine storage. Lead poisoning associated with
occupational exposure was first reported in 370 BC. It became common among
industrial workers in the 19th and early 20th centuries, when workers were
exposed to lead in smelting, painting, plumbing, printing and many other
industrial activities. (Nriagu
JO, Pacnya JM.1988.)



Data for CBCs, plasma biochemical profiles
(total protein, albumin, glucose, cholesterol, total bilirubin, calcium,
phosphorus, gamma-glutamyltransferase GGT, aspartate aminotransferase,
lactate dehydrogenase, glutamate dehydrogenase, creatine kinase, amylase, and
lipase), and whole blood lead concentrations were retrospectively analyzed for
69 trumpeter swans and 52 Canada geese. Laboratory data obtained prospectively
from an additional 20 trumpeter swans also were included. RBC morphology was
semiquantitated in blood smears from 70 of the birds. Data were analyzed
initially by ANOVA and covariance. A statistical model then was constructed to
determine the relationship between each parameter and lead concentration.

Risk factors associated with Lead

-Increase chance
of miscarriage, low birth weight, premature birth, and stillbirth

-May cause
learning and behavior problems for the baby/child.

May cause birth defects.( Rubin, et al, 2008)


1-Sources of lead exposure

Drinking water

Water contamination is the major problem in world especially
in developing countries. Contamination of lead in water causes detrimental
health effects on organ systems e.g. renal, reproductive, endocrine, nervous,
and hematopoietic and in children.

The routes for absorption of lead are through inhalation and
ingestion. Around 35-50% of lead is absorbed during drinking in adults and in
children it raises to 60%. The water which is contaminated of pollution,
industrial waste, tap-water pollutants etc are also contaminated with lead. (N.
Ul-Haq, et a, 2008)

2-Herbal medicines

Lead poisoning can be also occurs by the consumption of
herbal medicines. As the folk medicines used for the treatment of colic problems,
gastrointestinal issues, teething, fever and skin rashes. Lead is the major
constituent in ayurvedic/herbal medicines used in treatment of discomforts. Azarcon
aka: used for intestinal illness

a yellow powder used for intestinal illness.(Breeher L, et al,  2015.)

3-Dust and soil

Children who used
to eat dust and soil are susceptible of lead toxicity, known as Plumbism.
Usually 87% infants and toddlers swallow dust, soil, lead chips, and paints. Lead can be found in the paint in homes built before 1978. The paint can
flake and peel resulting in dust contaminated with lead. Also, plumbing pipes
and fixtures made with lead can contaminate the water that is used for drinking
and cooking. (Nriagu JO, Pacnya JM. 1988)


Lead contamination in food occurs through the utensils and other
food preparatory methods through which lead became part of food. Lead through
utensils is added by the lead enamel pots, during cooking enamel gets off and
became part of food. (Fischbein A, Wallace J, et al,1992.)

5-Fruit juices

Earthenware metal containers are used for the storage of
fruit juices and this is the leading cause of toxicity of lead in juices.

Glazed ceramic pitchers

Ceramic pitchers are also the source of lead poisoning in
infants as well as mothers.

Uses of pitchers for water storage cause lead poisoning and
during pregnancy or breastfeeding it also became part of neonatal. It is also
present in workers who make glazed ceramic pitchers.

(Fischbein A, Wallace J, et al,1992.)

6-Environmental exposure

Low level of environmental exposure of lead is associated
with multiple sources (petrol, industrial processes, paint, water pipes, and
solder in canned foods) and pathways (air, household dust, street dirt, soil,
water, food).Exposure to environmental lead is clearly a major public health hazard
of globally dimensions.

(Yu CC, et al,2004)

7-Occupational exposure

Although the occurrence of severe
lead poisoning has largely receded in many countries, occupational exposure to
lead resulting in moderate and clinically symptomatic poisoning is still
common. Among adults, exposure is normally greatest for those who come into
closest contact with lead in production processes. Workers are exposed to lead
in many occupations, including motor vehicle assembly, panel beating, battery
manufacture and recovery, soldering, lead mining and smelting, lead alloy
production, and in the glass, plastics, printing, ceramics and paint
industries. In most highly industrialized countries, stricter controls and
improvements in industrial methods have helped to ensure that occupational lead
poisoning is less prevalent than formerly. In developing countries, however, it
remains a problem of potentially huge dimensions. (Watts J,


Effects on children

Pregnant women who have elevated blood lead levels are at
risk of premature birth or babies with low birth rate. The fetus may be
adversely affected at blood lead conc. Well below 25 ?g/dl.

Children who have been repeatedly reported to be at higher
risk for lead poisoning because their bodies are in a state of growth and
development. Children due to their childish behavior are more prone to ingest
and inhale dust contaminated with lead.

( Shannon, 2003; Bellinger, 2005)

Dose effect relationship

Elevated lead levels are participated to be specific problem
among socially and economically deprived children. Intake of lead per unit
body weight is higher for children than for adults. Young children often place objects in their
mouths, resulting in dust and soil being ingested possibly, an increased intake of lead.

(- Needleman H, et al,1987 )


Symptoms of lead
poisoning are varied. They may affect many parts of the body. Most of the time,
lead poisoning builds up slowly. It follows repeated exposures to small
quantities of lead.

Lead toxicity is
rare after a single exposure or ingestion of lead.

Signs of repeated
lead exposure include:

       abdominal cramps

       abdominal pain






       loss of developmental in children


of appetite

blood pressure numbness or
tingling in the extremities



       kidney dysfunction

Since a child’s
brain is still developing, lead can lead to intellectual disability. Symptoms
may include:


Behavior problems,
low IQ.

       poor grades at school

       problems with hearing

       short- and long-term learning

       Growth delays.

       A high,
toxic dose of lead        poisoning may
result in emergency symptoms. These include:

       severe abdominal pain and cramping

       muscle weakness



       stumbling when walking




If someone has
symptoms of severe lead exposure, call emergency medical services. Be sure to
have the following information ready to tell the emergency operator:

       the person’s age

       their weight

       the source of the poisoning

       the amount swallowed

       the time the poisoning occurred

non-emergency situations, call poison control to discuss lead poisoning
symptoms. They will let you speak with an expert.( Timbrell JA, 2008.)


Metabolism and biochemistry of lead

Children are more susceptible to lead poisoning
because of the difference of metabolism between children and adults in several
aspects. These include intestinal absorption, bone metabolism and rapid
development of nervous system in young children.


Effect of lead on haem
protein and enzyme

In vitro studies show that many enzymes in haem synthesis
pathways are affected by the presence of lead. Cytosolic enzyme,
?-aminolevulinic acid dehydratase is inhibited by lead, that form
porphobilinogen from g-aminolevulinic acid.

Heam deficiency in lead poisoning results from failure to
reduce ferric iron to ferrous, the form required for haem incorporation. (Tomokuni K et al, 1990)

Effect on mitochondria and calcium

Lead is powerful inactivator of enzymes and reduces
mitochondrial oxidative phosphrylayion in kidney, brain, and the hematopoietic
system. It can inhibit transportation of sodium, potassium, and calcium ATPases
through transmembrane.

Calcium and lead interaction can cause impairment of calcium
metabolism. (Goyer RA,1990)

Inclusion bodies

Lead exposure can stimulate formation of inclusion bodies in
kidney, liver, brain, and bone. The inclusion bodies act to sequester lead in
the same way as zinc is sequestered by metallothionein. Lead can also be
translocated by the inclusion bodies into cell nuclei and thus alter gene
expression. Both nuclear and cytoplasmic inclusion bodies, consisting of lead
bound to a protein rich in aspartic and glutamic amino acids, are found in the
lead exposed kidneys. (Fowler BA,1992)

Systemic effects of lead

Hematological Toxicity

In the red blood cells anemia is the clinical manifestation
of lead toxicity. The severity and prevalence are correlated directly with
conc. of lead in blood.


1.    Impairment of haem biosynthesis

2.    Acceleration of red blood cell

Anemia usually is apparent when blood lead is greater than
1.92 ~mol/L. Coexisting iron deficiency may significantly increase the severity
of the anemia. In both iron deficiency and lead poisoning, there is decreased
incorporation of ferrous iron into protoporphyrin IX to form Heine and
replacement of iron by zinc with formation of zinc protoporphyrin. In lead
poisoning, erythrocyte Heine decreases and zinc protoporphyrin increases.
Erythrocyte protoporphyrin begins to rise at a blood lead of 0.96 tLmol/L. (Lahbe
RF, 1990.)

Renal toxicity

A number of studies found low level environmental lead
exposure to be associated with accelerated deterioration of chronic renal
insufficiency. Chronic nephropathy which may progress to kidney failure is the
classic renal manifestation of lead toxicity. High dose exposure to lead
results in renal toxicity. Clinical manifestations of impairment consisting of
rising in blood urea, nitrogen or serum creatinine to not ordinarily become
evident until 50 – 75 % of nephrons have been destroyed. Even at levels far below
the limits of normal ranges in the general population, both blood lead level
and blood lead burden were found to be increased, predicting accelerated
progression of chronic renal disease. Studies show the effects of occupational
lead hazards on patients. They observed tubular dysfunctions in patients who
underwent biopsy. Such studies suggest that lead nephropathy may be an
important occupational hazard. Excretion of the waste product urate was
reported in lead poisoning, suggesting gout, in which urate builds up in the
body. (Rubin R et al,2008)

Lead and Hypertension

Recent work suggests that even low levels of lead in the
blood may raise blood pressure, but this finding has not been consistent.
Positive correlations were found between blood lead concentrations and
diastolic blood pressure over a range of blood lead levels between 0.24-3.86
~mol/L and between 0.096-0.72 ~mol/L. This supported an earlier finding that
both systolic and diastolic blood pressure showed a statistically significant
relationship to blood lead without threshold for the lead effect. The
relationship of hypertension to chronic lead nephropathy is complex. Both
hypertension and nephropathy are recognized hazards of occupationally exposed
workers with high lead burdens. Diastolic blood pressure is positively
associated with increased risk for myocardial infarction and stroke, even a
small effect of lead on blood pressure would increase the risk of these
cardiovascular events.

(Sharp DS et al,1988.)

Reproductive Toxicity

The reproductive system of both males and females is affected
by lead. In males sperm count is reduced and other changes occur in the volume
of sperm when blood lead levels exceed 40 ?g/dL. Activities like motility and
the general morphology of sperm are also affected at this level. The problems
with the reproductivity of females due to lead exposure are more severe. Toxic
levels of lead can lead to miscarriages, prematurity, low birth weight, and
problems with development during childhood. Blood lead levels in mothers and
infants are usually similar as the lead present in mother blood passes into the
foetus through the placenta and also through breast milk). As bones store the
highest content of lead, if metabolic changes mobilize the lead from bones into
the blood due to pregnancy, the lead toxic risks increase. However increased
calcium intake during pregnancy can help mitigate this phenomenon. In neonates
with maternal umbilical cord-blood lead concentrations of 1.69 ~mol/L or less,
a number of minor malformations (angiomas, hemangiomas, skin tags, syndactyly,
polydactyly, accessory nipples, undescended testicles, and hydrocele) were
found. When the infants were grouped by cord-blood lead concentration, compared
with the group with the lowest mean blood lead of 0.17 ~mol/L, the relative
risk for a minor malformation was increased by 2.7 in the group with a mean
blood lead of 1.15 ~mol/L.

Toxicol. 2015 .)


Lead interacts with calcium-dependent systems in several
different ways. Lead may utilize calcium transport systems to enter cells,
block voltage-sensitive calcium channels on the plasma membrane of presynaptic
nerve endings, or increase spontaneous neurotransmitter re- lease from
synaptosomes. The precise effect of lead on the brain is not clear. Acute lead
encephalopathy occurs with failure of blood-brain barrier function. High lead
concentrations appear to disrupt cellular calcium metabolism and
second-messenger signals. Widening of the normally tight junctions between
brain endothelial cells allows plasma to flow into the brain and cerebral edema
develops. Low-level lead toxicity may result from alteration in the fluid
composition of the brain causing edema or from direct effects on neurons and
synaptic junctions. Chronic exposure of the developing brain to lead may
disrupt structural and functional development during the most vulnerable phase
of synaptic formation and remodeling, between 8 months and 11 years of age. A
selective effect of remodeling of synapses may partially explain the effect of
early low-level lead toxicity on attention, memory, and behavior. Peripheral
neuropathy is a well known effect of severe lead toxicity. High levels of lead
exposure result in a motor neuropathy that manifests as weakness or paralysis
of the wrist and ankle extensor muscles (wrist and ankle drop). Histopathology
shows segmental axonal demyelination and degeneration. Exposure to levels of
blood lead as low as 0.96 ~mol/L in children has been associated with
subclinically impaired peripheral nerve function, shown by slowing of motor
nerve conduction. The effect of prenatal and infantile exposure to low levels
of lead on intelligence remains a contentious issue. The proponents of universal
childhood lead screening believe that there is probably no safe threshold blood
lead value. Longitudinal prospective studies in the United States, Australia,
Mexico and elsewhere associate higher perinatal and postnatal blood lead with
ad- verse neurobehavioral outcome although the relationships are often weak or

(oldstein GW, 1992.)


Lead poisoning causes severe effects and is a matter of
serious concern, yet importantly, it is preventable. The best approach is to
avoid exposure to lead. It is recommended to frequently wash the children´s
hands and also to increase their intake of calcium and iron. It is also
recommended to discourage children from putting their hands, which can be
contaminated, in their mouth habitually, thus increasing the chances of getting
poisoned by lead. Vacuuming frequently and eliminating the use and or presence
of lead containing objects like blinds and jewellery in the house can also help
to prevent exposures. House pipes containing lead or plumbing solder fitted in
old houses should be replaced to avoid lead contamination through drinking
water. It is believed that hot water contains higher lead levels than does cold
water, so it is recommended that for household uses cold water should be
preferred to hot water. (Baselt & Randall, 2008)


The treatment for lead poisoning consists of dimercaprol and
succimer. Due to the persistent findings on cognitive deficits caused by lead
poisoning particularly in children, widespread reduction of exposure should be

Lead poisoning is generally treated by using chelating salt
disodium calcium edentate, which is the calcium chelate of the disodium salt of
ethylene-diaminetetracetic acid (EDTA). Such chelating agents have a great
affinity to the removing agent. The chelating agent for lead has a greater
affinity to lead than calcium and so the lead chelate is formed by exchange.
This is then excreted in urine, leaving behind harmless calcium. Blood lead
levels were shown to be lowered by treatment with succimer used as chelation therapy
in children exposed to lead to improve their neuropsychological development.
And yet, though succimer was observed to help in reducing blood lead levels. (Kasperczyk S, et al,2015)



Environmental lead exposure is clearly a major
public health hazard of global dimensions. As measures are taken to control the
transfer of lead to the environment are implemented in most developed countries
through, for example, the phasing out of lead in fuel, paints and other
consumer products, and tighter control of industrial emissions, environmental
exposure to lead can, in general, be expected to continue to decline. However,
because of rapid industrialization and the persistence of lead in the
environment, exposure is likely to remain a significant public health problem
in most developing countries for many years. Much work needs to be done to
identify and treat children with elevated blood lead levels and reduce lead
exposure in the community. Screening, monitoring, intervention and evaluation
are critical for the development of rational, cost-effective and science-based
public health policies aimed at achieving these goals.


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