THE
IMPACT OF LEAD POISONING ON THE
WORKFORCE
AND SOCIETY
Dr
Yasmin von Schirnding
Lead is a ubiquitous
and versatile metal which has been used by mankind for over 6000 years,
and is today one of the most widely distributed toxins in the environment.
We probably know more about the toxicity of lead than about any other
toxic substance. Lead is associated with a continuum of health effects
at both high levels of exposure (resulting in damage to virtually all
organs and organ systems, culminating ultimately in death at excessive
levels of exposure) to effects at low levels, including effects on hem
synthesis and other biochemical processes, impairment of psychological
and neurobehavioral functions, and a range of other effects.
The toxic nature
of lead was well documented by the second century BC and there is a
long history of public exposure to lead in food and drink. Lead poisoning
was common in Roman times due to the wide use of lead in lining water
pipes, earthenware containers and in storing wine. It then became common
among industrial workers in the 19 and early 20th centuries when workers
were exposed to lead in numerous occupations such as painting, plumbing,
printing and many others. They were assumed to absorb lead from contamination
of food eaten at the workplace, by inhalation of fine lead dust and
by absorption through the skin.
Amongst adults today,
exposure is normally greatest for those who come into closest contact
with the production process. Workers are exposed to lead in numerous
occupations, including motor vehicle assembly, panel beating, battery
manufacture and recovery, soldering, lead smelting and lead mining,
lead alloy production, and in the glass, plastics, printing, ceramics
and paint industries. In most highly industrialised countries, stricter
controls and improvements in industrial methods have helped ensure that
occupational lead poisoning is no longer as prevalent as before, however
in developing countries occupational lead poisoning remains a problem
of potentially huge dimensions.
In many countries
of the world, occupational exposure to lead which results in poisoning,
both moderate and clinically symptomatic, is still common. Occupational
lead exposure is frequently entirely unregulated in many developing
countries and little monitoring of exposures is conducted. The potential
for hazardous exposures to lead during lead smelting and refining is
well recognised, for both primary new metal and secondary (lead scrap)
smelters and refineries. Small domestic versions of secondary smelters
exist in a large number of countries, which are typically located within
close proximity to homes. The lead fumes and dust generated from such
operations can pose an exceptional health hazard to children and adults
living near these operations.
Other occupations
where workers have been shown to be at particular risk include battery
manufacturing, demolition, welding, pottery and ceramic ware production,
which is often a home-based occupation involving women and children,
small businesses repairing automobile radiators and artisans producing
jewellery and decorative wares. This latter industry is of particular
concern since it is predominantly carried out at home or in non-regulated
shops, often by women and children. In one Indian study conducted, silver
jewellery makers were found to have a blood lead level of 121 m
g/dl, compared to non-exposed controls with a blood lead level of 27
m g/dl.
Whilst concern in
the occupational setting tended previously to focus mainly on the identification
of late stage, highly symptomatic cases of lead poisoning (ex. encephalopathy),
there is now concern for much lower exposures to lead in the workplace.
Although adults are mainly involved, in many countries, especially in
those with developing industries, and small home-based industries, the
distinction between home and the workplace is virtually non-existent
and children are exposed to workplace lead. In addition, because of
transfer of lead to the fetus (in utero) and the transport to the home
of lead on clothing, thereby exposing the young child in the home, problems
of occupational exposures become community ones.
I’d like now to
say a few words about lead poisoning in children specifically, about
whom we now have a wealth of data on exposures and health effects, derived
mainly from the US and Europe. Lead poisoning in children was first
reported in Australia in 1892, although it was not until twelve years
later that the source (lead based peeling paint) was identified in this
case series of ten children with lead colic. In 1924, several cases
of lead poisoning were reported in the USA, and it was proposed that
pica, a perverted appetite for non-food items such as paint, was an
important etiologic factor. Other sources of lead such as lead food
containers, lead chromate in food colouring and lead medicinal ointments
were also recognised. In the USA around the same time, there were many
cases of lead poisoning amongst poor families during the depression
years, mostly caused by burning discarded storage battery casings for
fuel. Lead poisoning at that time was in fact referred to as the "Depression
Disease".
In many parts of
the world between 1930 and 1960, increased awareness among health workers
was associated with an increase in the reported cases of lead poisoning.
It was mainly caused by the repeated ingestion of flaking lead paint
in dilapidated housing and was particularly prevalent among socially
deprived inner city slum children. Mass screening studies were conducted
to detect such children at high risk.
In the late sixties
and seventies in countries such as the US, cases of clinical lead poisoning
had become less frequent, and focus turned to children with moderately
raised blood lead levels associated with environmental exposure. Reports
also began to suggest at this time that lead even at lower levels might
cause behavioural and psychological disorders in children. Attention
also turned to the issue of increased lead exposure among urban dwellers,
and those living next to point sources such as smelters, or to heavily
travelled roads.
Whilst in the past
two decades the incidence of clinical lead poisoning in children has
substantially declined in developed countries, the presence of lead
in blood at lower levels has been linked to a broad range of adverse
health effects. The safety or action level for lead in young children
has consequently been progressively lowered over the years, more recently
from 25 to 10 m g/dl in the US. Before moving on to discuss briefly
the problem of low level lead exposure, I would like to draw your attention
to the fact that in developed countries like the US, overt lead poisoning
in children went unrecognised for years. It was only with increased
awareness and active case-finding efforts, that the full extent of the
problem was realised. Of particular relevance to us here, is that in
addition to leaded paint, other sources of poisoning identified included
for example the migration of lead from food containers, and the use
of lead in cosmetics and medicines. In respect of the former, one study
reported the re-coating of the inner surface of brass utensils with
a mixture of lead and tin, ("tinning"). This is widely practised
by artisans in India in at least three southern states. The tin-lead
alloy contained 55 to 70% lead levels, and water-containing tamarind
contained 400-500 m g lead/litre after 5 minutes of boiling.
Another example
of the use of lead as a medicinal or cosmetic product is that of surma
or kohl used as an eye cosmetic or as an astringent on the umbilical
cord stump. A US study (1995) reported Indian and Pakistani children
using an imported leaded eye cosmetics to have a mean blood lead level
of 13m g/dl compared to 4.3 m g/dl for those not using such
cosmetics. I would like now to return to the issue of low level environmental
exposure.
Whilst children
in general are particularly vulnerable to the ill health effects of
lead due to various reasons, elevated lead levels continue to be a particular
problem among those socially and economically deprived. The poor are
more likely to live near industry and heavy traffic, to live in poor
housing, to be exposed to lead dust brought home by lead workers, and
to be nutritionally deprived, causing them to be more susceptible. Over
the last two decades, controversy has raged over the issue of the significance,
in health terms, of moderately elevated blood lead levels, i.e. those
under 25 m g/dl.
One reason for the
uncertainty regarding the health effects of lead at these lower levels
has been the methodological pitfalls that beset many of the earlier
cross-sectional studies (studies where exposures and outcomes are measured
at the same time) led to conflicting and inconclusive results. The newer
and more recently conducted studies (for example by Dietrich et al,
Bellinger and Needleman in the US, others in Australia), have included
highly sophisticated longitudinal prospective studies on the effects
of blood lead levels on prenatal and postnatal development, which have
used common and more sensitive measures of exposure and developmental
outcomes than previously, have considered numerous co-variates and confounding
variables and have used meticulous quality control measures. Children
have been followed up from birth in a prospective manner at regular
intervals, and the true nature of the relationship between exposure
and outcome has in this manner been more readily determinable. Despite
the methodological problems associated with the earlier cross-sectional
studies, in many instances the associations suggested by these studies
have been confirmed by the subsequent prospective studies.
We now know that
exposure to lead during the early stages of a child’s development is
linked to deficits in later neurobehavioral performance. In particular,
low level prenatal exposure has been found to be associated with subsequent
impaired mental development in young children. It would appear that
the size of the IQ effect, as assessed at four years and above, is most
likely between one and three points for each 10 m g/dl increment
in blood lead levels, at levels below 25 m g/dl, with no definitive
evidence of a threshold. In addition to neurobehavioral effects, heme
synthesis effects, and effects on a number of enzymes and biochemical
parameters, as well as reduced gestational age have been documented.
No socio-economic or ethnic group is exempt from risk. Adults too may
not be spared, and there is some evidence that low levels of lead exposure
may contribute to increased blood pressure.
Where does the lead
come from? Unlike overt lead toxicity, where there is usually one identifiable
source, low level environmental exposure is multifactorial. Multiple
sources (lead in gasoline, industrial processes, paint, solder in canned
foods, water pipes) and pathways (air, household dust, street dirt,
soil, water, food) all play a role. The evaluation of the relative contribution
of sources is therefore extraordinarily complex, and is likely to differ
from one area to the next, and in different population groups.
Much controversy
has existed about the extent to which gasoline-derived lead (the major
constituent of atmospheric lead) is a contributor to the body lead burden.
While it is the most widely distributed source in the environment, elucidating
its influence on blood lead levels has proved elusive for a variety
of reasons. As far as children are concerned, we do know that atmospheric
lead that is deposited into the soil and dust, and which may be ingested
by children via hand-to-mouth activities, is of great significance,
and may contribute substantially to raising blood lead levels in many
circumstances. For the population at large, who is not occupationally
exposed, food and water are important sources of baseline exposure to
lead, as well as the inhalation of atmospheric lead, although this is
of lesser significance usually.
Some of the early
and very convincing data on the relationship between gasoline lead and
blood lead levels came from the United States Second National Health
and Nutrition Examination Survey carried out during 1976 to 1980. A
37% decrease in national blood lead levels occurred, which correlated
closely with decreases in gasoline lead and air lead. The association
held after controlling for numerous factors such as race, age, season,
income, region, and exposure to other sources of environmental lead.
With the introduction of lead-free fuels, many countries have turned
their attention to other sources. Nevertheless even in countries where
control of lead has been vigilant vast reservoirs of lead still exist
in soil, dust and house paint, and these sources will continue to contribute
to the population for many years to come.
The general trend
observed in all countries engaged in risk reduction programmes over
the last 15 to 20 years, is a fall in blood lead levels. Whilst it is
always difficult to obtain comparative data for various countries due
to the differences in the designs of studies and the population groups
assessed (there have been very few national blood lead surveys conducted)
during the period 1978 - 1988 marked decreases (30-40%) in the average
blood lead levels of adults were noted in Belgium, Germany, New Zealand,
Sweden, UK and the USA. Decreases of 25 to 45 % in average blood lead
levels in children between 1978 and 1988 were reported in Belgium, Canada,
Germany, New Zealand, Sweden and the UK.
Whilst the problem
is now much less of a public health issue in many industrialised countries,
it is also clear that it is only just becoming recognised as a potential
problem in many developing countries, with studies now appearing in
the literature from all corners of the globe - in Africa, Asia, South
America. It would indeed be tragic if the rest of the world were not
in a position to benefit from the wealth of knowledge already accumulated
on lead - its sources and pathways of exposure, its effects at high
and low levels, and the control measures necessary to reduce the risks
in both the occupational and environmental settings.
Many international
conventions have indeed acknowledged the importance of exposure to lead
as a key public health issue - for example the 1989 Convention of the
Rights of the Child, Agenda 21 adopted by the UN Conference on Environment
and Development in 1992, the 1997 Declaration of the Environment Leaders
of the Eight (on Children's’ Environmental Health), the OECD Declaration
on Lead Risk Reduction, and so on.
What can be done?
The decreases in blood lead levels observed in many parts of the world
must be attributed in part to the better control of sources such as
petrol, paint, canned foods, and drinking water. Public health measures
must continue to be directed to the reduction and prevention of exposure
to lead by reducing the use of lead and lead compounds, and by minimising
lead containing emissions that result in human exposures. This can be
achieved in various ways -
- Phasing out lead
additives in fuels
- Reducing and
phasing out lead-based paints
- Eliminating use
of lead in food containers
- Identifying,
reducing, eliminating lead used in traditional medicines and cosmetics
- Minimising plumbosolvency
in water treatment and water distribution systems
- Better control
over exposure to lead in the workplace
- Better identification
of populations at high risk of exposure on the basis of monitoring
systems
- Improved procedures
of health risk assessment
- Better promotion
of understanding and awareness of the problem
- Better emphasis
placed on adequate nutrition, health care, and attention to socio-economic
conditions which may exacerbate the effects of lead
- Development of
international analytical quality control programmes
Many international
bodies are well equipped to provide assistance in addressing the various
dimensions of the problem, and have been active in the field over many
years. WHO and IPCS for example have been involved in addressing the
health and environmental effects of lead over the past 20 years. Various
evaluations have been done, for example of health risks from food-borne
lead, the derivation of health-based guidance values for lead in water,
air, the workplace; the publication of environmental health criteria
documents - for example one on inorganic lead published in 1995, the
publication of air quality guidelines (shortly to be revised based on
updated reviews), guidelines for drinking water quality, guidelines
for poisons control, and so on. Health and safety guides and International
Chemical Safety cards aimed mainly at the occupational sector have also
been published. These have all proved of importance in providing the
basis for national and international authorities to make their risk
assessment and risk management decisions. The IPCS has also prepared
a Poisons Information Package for Developing Countries (INTOX), training
material for the health sector, and programmes for the evaluation of
antidotes and guidelines for prevention of toxic exposures. All of these
activities refer to, or include the consideration of lead exposure as
one of the most serious health hazards. Thus, WHO, through awareness-raising
activities, promotion of regulatory measures, dissemination of advice
on clinical and analytical matters, promotion of prevention and toxico-vigilance,
plays an important role in primary, secondary as well as tertiary prevention
of lead poisoning and lead exposure.
We hope, together
with other international agencies and institutions, to work together
with governments and communities to continue to address this all pervasive,
and sometimes still "hidden" epidemic, in order that the long-term
impact of lead on society is ultimately eliminated.
The following
paper is submitted by WHO as a supplement to this presentation.
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.
TOP
