LEAD
POISONING OVERVIEW
World
Health Organization
Summary
This monograph focuses
on the risks to human health associated with exposure to lead and inorganic
lead compounds. Emphasis has been given to data which have become available
since the publication of Environmental Health Criteria 3: Lead (IPCS,
1977). The environmental effects of lead are discussed in Environmental
Health Criteria 83: Lead - Environmental Aspects (IPCS, 1989).
Identity, Physical
and Chemical Properties, and Analytical Methods
Lead is a soft,
silvery gray metal, melting at 327.5 C. It is highly resistant to Corrosion,
but is soluble in nitric and hot sulfuric acids. The usual valence state
in inorganic lead compounds is +2. Solubility in water vary, lead sulfide
and lead oxides being poorly soluble and the nitrate, chlorate and chloride
salts are reasonably soluble in cold water. Lead also forms salts with
such organic acids as lactic and acetic acids, and stable organic compounds
such as tetraethyllead and tetramethyllead.
The most commonly
used methods for the analysis or low concentrations of lead in biological
and environmental materials are flame, graphite furnace and inductively
coupled plasma atomic absorption spectroscopy and anode stripping voltametry.
Depending on sample pretreatment, extraction techniques and analytical
instrumentation, detection limits of 0.12 m moles lead/litre blood
(2.49/m g/dl) can be achieved. However, reliable results are obtained
only when specific procedures are followed to minimize the risk of contamination
during sample collection, storage, processing and analysis.
Sources of Human
Exposure
The level of lead
in the earth's crust is about 20 mg/kg. Lead in the environment may
derive from either natural or anthropogenic sources. Natural sources
of atmospheric lead include geological weathering and volcanic emissions
and have been estimated at 19000 tonnes/year, compared to an estimate
of 126000 tonnes/year emitted to the air from the mining, smelting,
and consumption of over 3 million tonnes of lead per year. Atmospheric
lead concentrations of 50 pg/m3 have been found in remote
areas. Background levels of lead in soil range between 10 and 70 mg/kg
and a mean level near roadways of 138 mg/kg have been reported. Present
levels of lead in water rarely exceed a few micrograms/litre; the natural
concentration of lead in surface water has been estimated to be 0.02
m g/litre.
Lead and its compounds
may enter the environment at any point during mining, smelting, processing,
use, recycling or disposal. Major uses are in batteries, cables, pigments,
petrol (gasoline) additives, solder and steel products. Lead and lead
compounds are also used in solder applied to water distribution pipes
and to seams of cans used to store foods, in some traditional remedies,
in bottle closures for alcoholic beverages and in ceramic glazes and
crystal tableware. In countries where leaded petrol is still used, the
major air emission is from mobile and stationary sources of petrol combustion
(urban centres). Areas in the vicinity of lead mines and smelters are
subject to high levels of air emissions. Airborne lead can be deposited
on soil and water, thus reaching humans through the food chain and in
drinking water. Atmospheric lead is also a major source of lead in household
dust.
Environmental
Transport, Distribution and Transformation
The transport and
distribution of lead from fixed, mobile and natural sources are primarily
via air. Most lead emissions are deposited near the source, although
some particulate matter (< 2 m m in diameter) is transported
over long distances and results in the contamination of remote sites
such as arctic glaciers. Airborne lead can contribute to human exposures
by the contamination of food, water and dust, as well as through direct
inhalation. The removal of airborne lead is influenced by atmospheric
conditions and particulate size. Large amounts of lead may be discharged
to soil and water. However, such material tends to remain localized
because of the poor solubility of lead compounds in water.
Lead deposited in
water, whether from air or through run-off from soils, partitions rapidly
between sediment and aqueous phase, depending upon pH, salt content,
and the presence of organic chelating agents. Above pH 5.4, hard water
may contain about 30 m g lead/litre and soft water about 500 m
g lead/litre. Very little lead deposited on soil is transported to surface
or ground water except through erosion or geochemical weathering; it
is normally quite tightly bound (chelated) to organic matter. Airborne
lead can be transferred to biota directly or through uptake from soil.
Animals can be exposed to lead directly through grazing and soil ingestion
or by inhalation. There is little biomagnification of inorganic lead
through the food chain.
Environmental
Levels and Human Exposure
In the general non-smoking
adult population, the major exposure pathway is from food and water.
Airborne lead may contribute significantly to exposure, depending upon
such factors as use of tobacco, occupation, proximity to motorways,
lead smelters, etc., and leisure activities (e.g., arts and crafts,
firearm target practice). Food, air, water and dust/soil are the major
potential exposure pathways for infants and young children. For infants
up to 4 or 5 months of age, air, milk, formulae and water are the significant
sources of lead exposure.
Levels of lead found
in air, food, water and soil/dust vary widely throughout the world and
depend upon the degree of industrial development, urbanization and lifestyle
factors. Ambient air levels over 10 m g/m3 have been
reported in urban areas near a smelter, whereas lead levels below 0.2
m g/m3 have been found in cities where leaded petrol
is no longer used. Lead intake from air can, therefore, vary from less
than 4 m g/day to more than 200 m g/day.
Levels of lead in
drinking water sampled at the source are usually below 5 m g/litre.
However, water taken from taps: (faucets) in homes where lead is present
in the plumbing can · contain levels in excess of 100 m g/litre,
particularly after the water has been standing in the pipes for some
hours.
The level of dietary
exposure to lead depends upon many lifestyle factors, including foodstuffs
consumed, processing technology, use of lead solder, lead levels in
water, and use of lead-glazed ceramics. For infants and children, lead
in dust and soil often constitutes a major exposure pathway. Lead levels
in dust depend upon such factors as the age and condition of housing,
the use of lead-based paints, lead in petrol and urban density. The
intake of lead will be influenced by the age and behavioral characteristics
of the child and bioavailability of lead in the source material. Inhalation
is the dominant pathway for Lead exposure of workers in industries producing,
refining, using or disposing of lead and lead compounds. During an 8
-h shift, workers can absorb as much as 400 m g lead, in addition
to the 20-30 m g/day absorbed from food, water and ambient air,
significant intake may occur from ingestion of large inhaled particulate
material.
Kinetics and
Metabolism in Laboratory Animals and Humans
Lead is absorbed
in humans and animals following inhalation or ingestion; percutaneous
absorption is minimal
in humans. Depending
upon chemical speciation, particle size, and solubility in body fluids,
up to 50 % of the inhaled lead compound may be absorbed. Some inhaled
particulate matter (larger than 7 m m) is swallowed following mucociliary
clearance from the respiratory tract, in experimental animals and humans,
absorption of lead from the gastrointestinal tract is influenced by
the physico-chemical nature of the ingested material, nutritional status,
and type of diet consumed. In adult humans approximately 10% of the
dietary lead is absorbed; the proportion is higher under fasting conditions.
However, in infants and young children as much as 50% of dietary lead
is absorbed, although absorption rates for lead from dusts/soils and
paint chips can be lower depending upon the bioavailability. Diets that
are deficient in calcium, phosphate, selenium or zinc may result
in increased lead
absorption. Iron and vitamin D also affect absorption of lead.
Blood lead (PbB)
levels are used as a measure of body burden and absorbed {internal}
doses of lead. The relationship between blood lead and the concentration
of lead in exposure sources is curvilinear.
Once it has been
absorbed, lead is not distributed homogeneously throughout the body.
There is rapid uptake into blood and soft tissue, followed by a slower
redistribution to bone. Bone accumulates lead over much of the human
life span and may serve as an endogenous source of lead, The half-life
for lead in blood and other soft tissues is about 25-36 days, but it
is much longer in the various bone compartments. The percentage retention
of lead in body stores is higher in children than adults. Transfer of
lead to the human fetus occurs readily throughout gestation.
Blood lead is the
most commonly used measure of lead exposure. However, techniques are
now available for measuring lead in teeth and bone, although the kinetics
are not fully understood.
Effects on Laboratory
Animals and in vitro Systems
In all species of
experimental animals studied, including nonhuman primates, lead has
been shown to cause adverse effects in several organs and organ systems,
including the haematopoietic, nervous, renal, cardiovascular, reproductive
and immune systems. Lead also affects bone and has been shown to be
carcinogenic in rats and mice.
Despite kinetic
differences between experimental animal species and humans, these studies
provide strong biological support and plausibility for the findings
in humans. Impaired learning/memory abilities have been reported in
rats with PbB levels of 0.72-0.96 m moles/litre (15-20 m g/d1)
and in non-human primates at PbB levels not exceeding 0 .72 m moles/litre
(15 m g/dl). In addition, visual and auditory impairments have
been reported in experimental animal studies.
Renal toxicity in
rats appears to occur at a PbB level in excess of 2.88 m mol/litre
(60 m g/dl), a value similar to that reported to initiate renal
effects in humans. Cardiovascular effects have been seen in rats after
chronic low-level exposures resulting in PbB levels of 0.24-1.92 m
mol/litre {5-40 m g/dl). Tumors have been shown to occur at dose
levels below the maximum tolerated dose of 200 mg lead (as lead acetate)
per litre of drinking-water. This is the maximum dose level not associated
with other morphological or functional changes.
Effects
on Humans
In humans, lead
can result in a wide range of biological effects depending upon the
level and duration of exposure. Effects at the subcellular level, as
well as effects on the overall functioning of the body, have been noted
and range from inhibition of enzymes to the production of marked morphological
changes and death. Such changes occur over a broad range of doses, the
developing human generally being more sensitive than the adult.
Lead has been shown
to have effects on many biochemical processes; in particular, effects
on haem synthesis have been studied extensively in both adults and children.
Increased levels of serum erythrocyte protoporphyrin and increased urinary
excretion of coproporphyrin and à -aminolaevulinic acid are observed
when PbB concentratins are elevated. Inhibition of the enzymes Ã
-aminolaevulinic acid dehydratase and dihydrobiopterin reductase are
observed at lower levels.
The effects of lead
on the haemopoietic system result in decreased haemoglobin synthesis,
and anemia has been observed in children at PbB concentrations above
1.92 m mol/litre (40 m g/dl). For neurological, metabolic
and behavioral reasons, children are more vulnerable to the effects
of lead than adults. Both prospective and cross-sectional epidemiological
studies have been conducted to assess the extent to which environmental
lead exposure affects CNS-based psychological functions. Lead has been
shown to be associated with impaired neurobehavioural functioning in
children.
Impairment of psychological
and neurobehavioural functions has been found after long-term lead exposure
of workers. Electrophysiological parameters have been shown to be useful
indicators of subclinical lead effects in the CNS. Peripheral neuropathy
has long been known to be caused by long-term high-level lead exposure
at the workplace. Slowing of nerve conduction velocity has been found
at lower levels. These effects have often been found to be reversible
after cessation of' exposure, depending on the age and duration of exposure.
The effect of lead
on the heart is indirect and occurs via the autonomic nervous system;
it has no direct effect on the myocardium. The collective evidence from
population studies in adults indicates very weak associations between
PbB concentration and systolic or diastolic blood pressure. Given the
difficulties of allowing for relevant confounding factors, a causal
relationship cannot be established from these studies. There is no evidence
to suggest that any association of PbB concentration with blood pressure
is of major health importance.
Lead is known to
cause proximal renal tubular damage, characterized by generalized aminoaciduria,
hypophosphataemia with relative hyperphosphaturia and glycosuria accompanied
by nuclear inclusion bodies, mitochondrial changes and cytomegaly of
the proximal tubular epithelial cells. Tubular effects are noted after
relatively short-term exposures and are generally reversible, whereas
sclerotic changes and interstitial fibrosis, resulting in decreased
kidney function and possible renal failure, require chronic exposure
to high lead levels. lncreased risk from nephropathy was noted in workers
with a PbB level of over 3. 0 m mol/litre (about 60 m g/dl).
Renal effects have recently been seen among the general population when
more sensitive indicators of function were measured. The reproductive
effects of lead in the male are limited to sperm morphology and count.
In the female, some adverse pregnancy outcomes have been attributed
to lead. Lead does not appear to have deleterious effects on skin, muscle,
or the immune system. Except in the case of the rat, lead does not appear
to be related to the development of tumors.
Evaluation of
Human Health Risks
Lead adversely affects
several organs and organ systems, with subcellular changes and neurodevelopmental
effects appearing to be the most sensitive. An association between PbB
level and hypertension (blood pressure) has been reported. Lead produces
a cascade of effects on the haem body pool and affects haem synthesis.
However, some of these effects are not considered adverse. Calcium homoeostasis
is affected, thus interfering with other cellular processes.
a) The most substantial
evidence from cross-sectional and prospective studies of populations
withPbB levels generally below 1.2 m mol/litre (25 m g/dl)
relates to decrements in intelligence quotient (IQ). It is important
to note that such observational studies cannot provide definitive evidence
of a causal relationship with lead exposure. However, the size of the
apparent IQ effect, as assessed at 4 years and above, is a deficit between
0 and 5 points (on a scale with a standard deviation of 15) for each
0.48 m mol/litre (10 m g/dl) increment in PbB level, with
a likely apparent effect size of between 1 and 3 points. At PbB levels
above 1.2 m mol/litre
(25 m g/dl),
the relationship between PbB and IQ may differ. Estimates of effect
size are group averages and only apply to the individual child in a
probabilistic manner. Existing epidemiological studies do not provide
definitive of a threshold. Below the PbB range of 0.48-0.72 m mol/litre
(10-15 m g/dl), the effects of confounding variables. and limits
in the precision in analytical and psychometric measurements increase
the uncertainty attached to any estimate of effect. However, there is
some evidence of an association below this range.
b) Animal studies
provide support for causal relationship between lead and nervous system
effects, reporting deficits in cognitive functions at PbB levels as
low as 0.53-0.72 m mol/litre (11 -15 m /dl) which can
persist well beyond the termination of lead exposure.
c) Reduction in
human peripheral nerve conduction velocity may occur with PbB levels
as low as 1.44 m mol/litre (30 m g/dl). In addition, sensory
motor function may be impaired with PbB levels as low as about 1.92
m mol/litre (40m g/dl), and autonomic nervous system function
(electrocardiographic R-R interval variability) may be affected at an
average PbB level of approximately 1.6 m mol/litre (35 m g/dl).
The risk of' lead nephropathy is increased in workers with PbB levels
above 2.88 m mol/litre (60 m g/dl). However, recent studies
using more sensitive indicators of renal function suggest renal effects
at lower levels of lend exposure.
d.) Lead exposure
is associated with a small increase in blood pressure. The likely order
of magnitude is that for any twofold increase in PbB level (e.g., from
0.8 to 1.6 m mol/litre, i.e. 16.6 to 33.3 m g/dl), there is
a mean 1 mmHg increase in systolic blood pressure. The association with
diastolic pressure is of a similar but smaller magnitude. However, there
is doubt regarding whether these statistical associations are really
due to an effect of lead exposure or are an artifact due to confounding
factors.
e) Some but not
ell epidemiological studies show a dose-dependent association of pre-term
delivery and some indices of Fetal growth and maturation at PbB levels
of 0.72 m mol/litre (15 m /dl) or more.
f.) The evidence
for carcinogenicity of lead and several inorganic lead compounds in
humans is inadequate.
g) Effects of lead
on a number of enzyme systems and biochemical parameters have been demonstrated.
The PbB levels, above which effects are demonstrable with current techniques
for the parameters that may have clinical significance, are all greater
than 0.96 m mol/litre (20 m g/dl). Some effects on enzymes
are demonstrable at lower PbB levels, but the clinical significance
is uncertain.
