LEAD (EVALUATION OF HEALTH RISK TO INFANTS AND CHILDREN)
Lead was previously evaluated at the sixteenth meeting of the
Joint FAO/WHO Expert Committee on Food Additives (Annex 1, reference
30). The Committee established a provisional tolerable weekly intake
of 3 mg of lead/person, equivalent to 0.05 mg/kg b.w. for adults. This
level does not apply to infants and children. The provisional weekly
tolerable intake established by JECFA at that time related to all
sources of exposure to lead. The Committee indicated that any increase
in the amount of lead derived from drinking water or inhaled from the
atmosphere will reduce the amount that can be tolerated in food. A
toxicological monograph was published (Annex 1, reference 31).
Two other publications of WHO have dealt with effects of lead on
human health (WHO, 1973; WHO, 1977). These publications did not deal
specifically with the health risks for infants and children. However,
JECFA and the other WHO committees recognize that children should be
considered a high-risk group in relation to lead exposure.
JECFA at its twenty-first meeting (Annex 1, reference 44)
discussed the problem of exposure of infants and children to
contaminants in foods. The IPCS (International Program on Chemical
Safety) and CEC (Commission of the European Communities), recognizing
the need for a special approach to evaluating the health risks from
chemicals during infancy and early childhood, have recommended
principles for evaluating these risks (WHO, 1986).
The basis of the special concern for infants and children relates
to certain structural, functional, and behavioural differences between
infants and young children and adults, in particular, the higher
metabolic rate and therefore higher oxygen consumption and air intake
per unit body weight in the young, the large surface area to weight
ratio, the rapid body growth, different body composition, immaturity
of the kidney, liver, nervous system, and immune system, and the rapid
growth and development of organs and tissues such as bone and brain.
The higher energy requirements of infants and children and the higher
fluid, air, and food intake per unit body weight place them in a
special position with regard to intake of chemicals from air, water
and food. The absorption and retention of a number of metals appear to
be greater in the young than in adults, and there are differences in
the distribution, biotransformation, and excretion of chemicals in
infants, children, and adults. Additionally, the dependence of young
infants on milk or infant formula as their sole source of nutrition
may raise special problems. Particular behavioural characteristics of
children, such as heightened hand to mouth activity, may place them at
particular risk from environmental contaminants. The nutritional and
health status of the young may also modify their response to chemical
contaminants and the social and cultural attitudes to child rearing
may influence the degree of exposure to chemicals.
EXPOSURE AND INTAKE
Sources of exposure
It is important to identify sources of exposure, particularly
those that may be of significance to infants and children. This will
provide information for developing strategies for control of exposure,
Although lead is ubiquitous in the environment of industrialized
nations, the contribution of natural sources of lead to concentrations
in the environment is low compared to the contribution from human
activities (Patterson, 1965). Through human activities such as mining,
smelting, refining, manufacturing, and recycling, lead finds its way
into the air, water, and surface soil. Lead-containing manufactured
products (gasoline, paint, printing inks, lead water pipes,
lead-glazed pottery, lead-soldered cans, battery casings, etc.) also
contribute to the lead burden. Lead in contaminated soil and dust can
find its way into the food and water supply.
Food, drinking water, and air
Lead in foods may be derived from the environment in which the
food is grown or from food processing. Agricultural crops grown near
heavily travelled roads or industrial sources of lead can have
significant concentrations because of airborn lead deposited on them
or in the soil. Canned foods are a source of lead which is leached
from the solder in the seams of the cans. However, exposure from this
source can be reduced by the use of seamless cans. Among cases of lead
poisoning cited in the literature, lead from ceramic glazed storage
vessels, leached out by acid foods, is the most frequently-reported
source of high lead concentrations in foods (Mahaffey, 1983). The
major source of lead contamination of drinking water is the
distribution system itself. Where lead water pipes or lead-lined
cisterns are used, lead may contaminate the water supply and
contribute to increased blood levels in children who consume the water
(Elias, 1985). Water used to prepare infant formula is always a
significant source of lead for infants if it contains high lead levels
(Sherlock & Quinn, 1986).
The atmospheric levels of lead depend on geographical location,
with major differences in lead in the atmosphere in urban and remote
areas of the world. The highest concentrations are observed near
sources of lead such as smelters. Levels range from 0.000076 µg/m3
in remote areas to up to 10 µg/m3 in areas near smelters
The domestic environment
The domestic environment, in which infants and children spend the
greater part of their time, is of particular importance as a source of
lead intake. In addition to exposure from general environmental
sources, some infants and young children, as a result of normal,
typical behaviour, can receive high doses of lead through mouthing or
swallowing of non-food items. Pica, the habitual ingestion of non-food
substances, which occurs among many young children, has frequently
been implicated in the etiology of lead toxicity.
Soil and dust in and about the home
The extent of the contribution of inhaled airborne lead to the
lead burden of children is probably small. However, lead-containing
particles that deposit from the air can be responsible for high
concentrations of lead in dust that children ingest (Charney, 1982). A
study of urban and suburban infants (USA) followed from birth to 2
years of age found that the average blood lead levels highly
correlated with amounts of lead in indoor dust, top soil, and paint in
their immediate environment (Rabinowitz et al., 1984). Children
living near high-level sources of lead such as smelters are at high
risk from lead poisoning (Landrigen et al., 1976). Exhaust from
vehicles using leaded gasoline is a common source of atmospheric lead
which contributes to the lead content of dust. Data from the United
States Second National Health and Nutrition Examination Survey
(NHANES II) indicate that leaded gasoline is a more significant source
of lead than previously thought. Annest et al. (1983), using data
from this study, correlated major reductions in the amounts of lead
added to gasoline sold in the United States with significant
reductions in children's blood lead levels. A similar relationship
between leaded gasoline sales and umbilical cord blood lead levels was
shown by Rabinowitz and Needleman (1983). However, other studies have
indicated that the influence of lead from gasoline on blood lead
levels may be relatively low (Quinn, 1985). In general, lead in soil
and dust appears to be responsible for blood lead levels in children
increasing above background levels when the concentration in the soil
or dust exceeds 500-1,000 ppm (Milar & Mushak, 1982).
Lead-based paint in the home
Lead-based paint in the home has been and continues to be the
major source of high-dose lead exposure and symptomatic lead poisoning
for children, in spite of the fact that the use of lead in interior
paints has been restricted in some countries for many years (Lin-Fu,
1982). In the past, some interior paints contained 20-30% lead and
these paints remain in many older homes. Overt lead poisoning, when it
occurs, is usually seen in children under 6 years of age who live in
deteriorated older housing.
Indirect occupational exposure in the home
Lead dust that clings to the skin, hair, and clothing of workers
can be carried from the workplace to the home. In one study
(Baker et al., 1977) it was shown that when a parent worked with
lead, the amount of lead in the blood of children correlated with the
concentration of lead in dust in their homes. Children have been
poisoned by lead-bearing dust brought home on parents' work clothing
Children are more vulnerable to exposure to lead than adults
because of metabolic and behavioural differences. The degree to which
individual sources of lead contribute to the intake of lead by infants
and children varies according to its availability in particular
environmental circumstances. While lead in air, food, and water
generally is at lower levels than lead in paint, soil, and dust, the
former contribute to the background or baseline level which determines
how much extra lead is needed from other sources before toxicity
ensues. It has been estimated that in the United States, an average
two-year old child may receive 44% of his daily lead intake from dust,
40% from food, 14.6% from water and beverages, and 1% from inhaled air
(Elias, 1985). Detailed reviews of intake of lead are available
(WHO, 1977; Elias, 1985; FAO, 1986a).
Among children the higher food intake relative to size and the
higher metabolic levels and greater motor activity compared to adults
leads to higher dietary lead consumption (Mahaffey, 1985). Reported
intakes of lead from food are quite variable (WHO, 1977). However,
developing a reasonable estimate of lead in the diet is a continuing
problem because of (1) methodological weaknesses in the accurate
analysis for lead in foods and (2) the need for good dietary survey
data. Beloian (1985) has proposed a mathematical model for estimating
daily intake. A detailed report of dietary intake of lead by infants
and children has been compiled by FAO (1986a). There has been a
considerable reduction in dietary intake of lead in infants in the 0-5
month age group since the 1970s, probably due to improvements in
packaging and handling of foods during processing and to reduction in
lead solder in cans used for milk and infant food.
Inhaled lead contributes little to the background body burden
compared to intake from food, water, beverages, and dust. Airborne
lead, however, represents an important source of lead exposure in
children when deposited in dust and dirt. However, different studies
reach widely different assessments of the contribution of air lead to
food lead and hence body burden (Royal Commission on Environmental
Dust contributes a greater proportion of lead to the background
body burden of young children than to adults and older children
because of their greater proclivity for ingesting dust due to their
greater hand-to-mouth activity. It has been calculated that dust
contributes only 7 to 11% of the baseline lead in adults, but 44% in
2-year old children (Elias, 1985).
Indices of exposure
For practical reasons, lead exposure in infants and children is
based primarily upon measurements of lead in the blood, sometimes
supplemented by measurement of lead in urine, particularly after
treatment with chelating agents. These measurements correlate
imperfectly with lead levels in the tissue or organ where the toxic
effect may be observed. Furthermore, blood lead levels reflect only
recent exposure to lead, not long-term exposure. Other methods to
determine total body burden involve measurement of lead in hair, bone,
or teeth (Goyer, 1982).
The use of the lead content of teeth as an index of lead exposure
in the general population has been considered an important advance,
particularly in the investigations of the neuropsychological effects
of ordinary levels of lead in the environment, since this reflects
lead exposure over the child's lifetime, not merely recent exposure.
However, considerable variations may occur in tooth lead
concentrations in different teeth from the same child, especially when
teeth are different types or from upper and lower jaws. Also, there is
a marked variation of lead concentration throughout the tooth
(Delves et al., 1982; Smith et al., 1983). Because of these
variations, there is always a need to make suitable adjustments when
using teeth for assessing lead body burden.
The haematopoietic system is considered by many to be the most
reliable and sensitive indicator of lead toxicity. The clinical
endpoint is anaemia, which apparently occurs at lower blood lead
levels in children that in adults (Goyer, 1982). The elevation of
erythrocyte protoporphyrin (EP) has been well studied and can be
reliably measured (U.S. CDC, 1985). Among the biologic markers of lead
toxicity, this method has been the most useful in screening programs
because its measurement is not susceptible to error from lead
contamination and the test can be performed on capillary blood.
However, correlation with blood lead at levels below 30 µg/dl is poor,
and there is a rather high proportion of false negative results
(Meredith et al., 1979; Bush et al., 1982). High EP values in the
absence of elevated blood lead levels may indicate iron deficiency
Blood lead levels in children
In general, blood lead levels of children up to 6-7 years of age
are higher than those of non-occupationally exposed adults. Blood lead
levels are highest in children aged 2-3 years, but they decrease again
in children aged 6-7 years. There are no significant differences in
blood lead levels between males and females less than 7 years of age.
However, males in the 7+ age group generally have higher blood lead
levels than females. In the United States NHANES II found that the
mean blood lead concentration among children under 6 years of age was
about 16 µg/dl, with mean values in about 5% of the population equal
to or greater than 30 µg/dl. After the age of 5, mean blood levels
declined until age 17. Mean blood levels of adult females remained
lower, but blood levels in adult males were similar to those of
younger children (Mahaffey, 1985).
A similar pattern of distribution of blood lead levels with age
in children and infants was reported in the U.K. and European Economic
Community (EEC) Blood Lead Survey, 1979-1981 (Quinn, 1985), with
average blood lead concentrations in the range 9-11.5 µg/dl. In
addition, these studies reported the effect of geographical,
environmental and personal factors on the average blood lead
concentrations (Pollution Report No. 18, 1983).
Blood lead levels of concern in screening programmes
The U.S. Centers for Disease Control (U.S. CDC) has lowered its
definition of an elevated blood lead level from 30 to 25 µg/dl. Lead
toxicity is defined as an elevated blood level with an EP level in
whole blood of 35 µg/dl or greater (U.S. CDC, 1985). The U.S. CDC has
also described a system for grading the severity of lead toxicity
using two distinct scales, one for use in screening and the other for
use in clinical management. For example, at a blood level of 25 µg/dl
or less and an EP of 35 µg/dl or more, the U.S. CDC recommends that
children be retested, with additional assessment of iron studies.
Also, in terms of clinical management, the U.S. CDC points out that
the first priority is for environmental investigation and intervention
and the single most important factor is to reduce exposure to lead.
The EEC directive on the biological screening of the population
and specific groups in the population indicated certain reference
levels for each survey. The reference levels are as follows: no more
than 50% should be above 20 µg/100 ml, no more than 10% above
30 µg/100 ml, and no more than 2% above 35 µg/100 ml. It was also
recommended that if these levels were exceeded, action should be taken
to trace and reduce the source of exposure. Follow-up investigations
should be carried out in individuals over 30 µg/100 ml (EEC, 1977).
In the U.K. it has been recommended that when a blood level over
25 µg/100 ml has been confirmed in a person (particularly a child),
action should be taken to investigate the individual's environment and
steps should be taken to reduce lead exposure (Department of the
Environment and the Welsh Office, 1982).
Absorption and retention
The main route of lead absorption in infants and children is the
gastrointestinal tract. Children absorb lead with greater efficiency
than do adults. It has been estimated that 40-50% of dietary lead is
absorbed in children, whereas in adults normally 5-10% of dietary lead
is absorbed from the gastrointestinal tract. However, absorption in
adults shows considerable variation depending on whether the lead is
present in food or water or if the lead is ingested between meals.
Decreased intake of essential metals such as iron, zinc, and calcium
as well as poor nutritional status increase lead absorption
(Rosen, 1985). In experimental animals there is some evidence that
milk may promote lead absorption (Stephens & Waldron, 1975). The
estimated gastrointestinal absorption rate of lead from soil and dust
has been reported to be somewhat lower than from food, approximately
30% (Lepow et al., 1975).
In a study by Zeigler et al. (1978) faecal excretion of lead in
infants generally exceeded intake when the dietary intake of lead was
less than 4 µg/kg/day. When intake of dietary lead exceeded
5 µg/kg/day, net absorption averaged 42% of intake, and retention
averaged 32% of intake. Absorption and retention of lead expressed as
a percentage of intake increased significantly with increasing lead
intake. Absorption may be higher when nutrition is not optimal.
Correlation between blood lead levels and exposure
In a study with infants Ryu et al. (1983) demonstrated that
with low non-dietary exposure to lead, a mean intake of 3-4 µg
lead/kg b.w. was not associated with an increase in blood lead
concentration. However, increased blood lead levels did occur when the
dietary intakes of lead were 8-9 µg/kg b.w./day.
The Glasgow duplicate diet study (Sherlock & Quinn, 1986)
reported a significant correlation between dietary lead intake and
blood lead concentrations of 13-week old infants. The study involved a
wide range of lead intakes (40 µg to over 3000 µg/week). The high
levels of lead in the diet were derived from water used to prepare the
diet. The blood lead concentrations appeared to have a "non-linear"
(cube root) relationship between water lead concentrations and dietary
intakes of lead, with the greatest increment in blood lead levels
occurring at the lower range of exposure.
Lead intake from air is relatively greater in children than in
adults. In adults without prolonged previous exposure to lead, each
1 µg/m3 increase in ambient air lead increases the mean blood level
by approximately 1 µg/dl, while in children each 1 µg/m3 increase in
ambient air lead exposure causes a mean increase of 2 µg/dl or more in
the blood lead level (US EPA, 1977).
Distribution and excretion
A single dose of lead, orally ingested or inhaled, distributes to
the various organs and systems in the body in relation to the rate of
blood delivery and then redistributes in proportion to affinity of
particular tissues for lead. The concentration of lead in blood
reflects the overall balance between uptake and excretion and the
equilibrium of exchange to and from soft and hard tissues. Lead is not
uniformly distributed in the body but is apportioned among several
physiologically-distinct compartments which differ in size and
accessibility to lead (Rabinowitz et al., 1976; Rabinowitz et al.,
1977). The blood and some components of soft tissue in rapid exchange
with blood contain about 1% of the body lead, of which 90 to 99% is
associated with the red blood cells. This accessible fraction
correlates most closely with recent environmental exposure and to most
toxic effects. Lead in this accessible portion has a mean half-life of
about 36 days. Lead in other soft tissue has a mean half-life of about
40 days; this compartment is slightly smaller than the blood
compartment. The lead in bone and teeth has a long half-life, about
10,000 days, and forms the largest and least accessible depot. There
is variation in the amount of lead stored in various skeletal regions
and in its accessibility (Rabinowitz et al., 1976).
Animal experiments show that the tissue distribution of lead in
the young and in adults differs. In the rat, a greater percent of the
dose accumulates in the immature brain than in the adult brain. In
fact, young animals retain a greater percentage of lead in all organs
than do adults, even when the exposure of young and adults is the same
on a µg lead/kg b.w. basis. When the blood lead level concentration in
rats is plotted against tissue lead levels, the slope of the
regression line for the young is greater than that for adults,
indicating that tissue lead levels rise faster than blood lead levels
in the young animal (Mahaffey, 1983).
Man excretes lead primarily by way of the kidneys (76%) and to a
lesser extent via the gastrointestinal tract (16%) and through the
sweat, bile, hair, and nails (8%) (WHO, 1977). Lead accumulates in
bone due to an inherent affinity for osseus tissue and only slowly
returns to the blood. The longer the period of exposure to lead, the
slower the rate of removal from the body (Hammond, 1982). Although
animal studies suggest that lead is excreted more slowly in the young
than in the adult (Hammond, 1982), metabolic balance studies in normal
infants suggest that infants and young children not only absorb lead
more efficiently but also excrete it more rapidly than do adults
(Rabinowitz et al., 1976).
Transplacental transport of lead and lead in maternal milk
Lead in fetal tissues has been detected by the twelfth week of
gestation (Barltrop, 1972) with highest concentrations in bone,
kidney, and liver, followed by blood, brain, and heart. Cord blood
contains concentrations of lead that correlate with maternal levels.
Lead appears in mothers' milk, but breast milk contains only about
one-tenth of the maternal blood lead concentrations (Moore, 1983).
Lead impairment of normal metabolic pathways
The biochemical basis for lead toxicity is its ability to bind
the biologically-important molecules, thereby interfering with their
function by a number of mechanisms. Lead may compete with essential
metallic cations for binding sites, inhibiting enzyme activity, or
altering the transport of essential cations such as calcium. At the
subcellular level, the mitochondrion appears to be the main target
organelle for toxic effects of lead in many tissues. Lead has been
shown to selectively accumulate in the mitochondria and there is
evidence that it causes structural injury to these organelles and
impairs basic cellular energetics and other mitochondrial functions
(Brierley, 1977; Holtzman et al., 1978).
Lead has been reported to impair normal metabolic pathways in
children at very low blood levels (Farfel, 1985). At least three
enzymes of the haeme biosynthetic pathway are affected by lead and at
high blood lead levels the decreased haeme synthesis which results
leads to decreased synthesis of haemoglobin. (Haeme is also a
prosthetic group of a number of tissue heme proteins such as
myoglobin, the P450 component of the mixed function oxidases, and the
cytochromes.) Blood lead levels as low as 10 µg/dl have been shown to
interfere with one of the enzymes of the haeme pathway, delta-
amino-levulinic acid dehydrase (Hernberg & Nikkanen, 1970). No
threshold for this effect has been established. Alterations in the
activity of the enzymes of the heme synthetic pathway lead to
accumulation of the intermediates of the pathway. There is some
evidence that accumulation of one of the intermediates, delta-
amino-levulinic acid, exerts toxic effects on neural tissues
through interference with the activity of the neurotransmitter
gamma-amino-butyric acid (GABA) (Silbergeld & Lamon, 1980). The
reduction in heme production per se has also been reported to
adversely affect nervous tissue by reducing the activity of tryptophan
pyrollase, a heme-requiring enzyme. This results in greater metabolism
of tryptophan via a second pathway which produces high blood and brain
levels of the neurotransmitter serotonin (Litman & Correia, 1983).
Red cell pyrimidine-5'-nucleotidase activity in children is
inhibited at blood lead concentrations of 10-15 µg/dl and no threshold
was found even below these levels (Angle et al., 1982).
Lead interferes with vitamin D metabolism, since it inhibits
hydroxylation of 25-hydroxy-vitamin D to produce the active form of
vitamin D. The effect has been reported in children at blood levels as
low as 10-15 µg/dl (Mahaffey et al., 1982).
Rosen (1985) and Moore & Goldberg (1985) have published detailed
reviews of the metabolic and cellular effects of lead.
Target organs and systems
Lead is a cumulative poison. It produces a continuum of effects,
primarily on the haematopoietic system, the nervous system, and the
Excessive lead exposure in pediatric groups results in a
microcytic, hypochromic, mildly haemolytic anemia. Increased blood
concentrations and urinary excretion of the metabolic precursers of
haeme, such as protoporphyrins and 6-amino-levulinic acid, occur
before the development of overt anaemia. Blood lead concentrations in
children in excess of 40 µg/100 ml have been associated with an
increased incidence of anaemia (WHO, 1977).
Measurements of the inhibitory effects of lead on haeme synthesis
have been widely used in screening tests to determine whether medical
treatment for lead toxicity is needed for children in high-risk
populations who have not yet developed overt symptoms of lead
poisoning. Piomelli (1980) has reported that an increase of
erythrocyte protoporphyrin could be measured at blood lead levels of
14-17 µg/dl in children and Cavelleri et al. (1981) found an
increase at blood lead levels between 10 and 20 µg/dl, suggesting that
the erythrocyte protoporphyrin "no response" level is lower than
10 µg/dl in children. Specific changes relating to the haematopoietic
system have been reported to occur at the following blood lead
concentrations in children:
5 - 10 µg/100 ml 40% inhibition of erythrocyte
delta-amino-levulinic acid dehydratase
10 - 25 µg/100 ml increased erythrocyte protoporphyrins
20 - 25 µg/100 ml 70% inhibition of delta-amino-levulinic acid
30 - 40 µg/100 ml increased urinary excretion of
delta-amino-levulinic acid (above 5 mg/l)
40 - 50 µg/100 ml decreased haemoglobin level
The biological significance of the effects noted below
40 µg/100 ml are not known, since the degree of impairment is not
sufficiently large to be reflected as a decrease in haemoglobin or
haem synthesis. However there is general agreement that at levels
greater than 40 µg/100 ml, lead exerts a significant effect on the
The haematological changes associated with lead are considered
Effects on the nervous system
Lead causes a continuum of nervous system effects in children
ranging from slowed nerve conduction (Landrigan et al., 1976),
behavioural changes (David et al., 1972; de la Burde et al., 1975;
Landrigan et al., 1975; Winneke et al., 1982, 1983), and possible
small decrements in cognitive ability at about 30-60 µg lead/dl blood,
to mental retardation (80 µg/dl) and acute encephalopathy and death
(80-100 µg/dl) (Needleman et al., 1979; Needleman & Landrigan, 1981;
Needleman, 1983). Encephalopathy and other effects on the nervous
system develop in children at lower blood lead levels than in adults.
Effects on the central nervous system are principally responsible
for the morbidity and mortality due to lead poisoning
Chelation therapy and earlier detection of lead toxicity have led
to a marked decline in death from lead poisoning since the 1950s, but
residual impairment of CNS function due to lead toxicity continues to
occur, even in children treated with chelation therapy. Sequalae can
include mental retardation, seizures, cerebral palsy, and optic
atrophy. In studies with experimental animals, perinatal lead exposure
delayed normal brain development in offspring and was associated with
blood lead levels from 25-89 µg/dl (Reiter, 1982). Indications of
peripheral nerve dysfunction, as indicated by slowed nerve conduction
velocities, have been shown in children at blood lead levels as low as
30 µg/dl (Landrigan et al., 1975).
The neuropsychological effects of low-level lead exposure, below
that causing overt toxic effects, represent a subject of increasing
interest and of continuing controversy. The concern relates to the
possibility that early asymptomatic environmental lead exposure
results in adverse effects on I.Q., perception, and fine motor skills
of children. In the past 12-15 years, both clinical studies of
children and animal research have provided information which bears on
the problem of CNS effects at low-level lead exposure. Data needed to
define dose-response relationships in children come principally from
retrospective epidemiological studies. These have the well-known
methodological problems of controlling for confounding covariants, of
selection bias, of obtaining sufficiently-large population samples to
achieve statistical significance, and of appropriate statistical
analysis. In the case of lead there is also the problem of the
shortcomings of assessing the body lead burden by the most widely used
and practical method, which is measurement of blood lead levels, and
the difficulties with clinical measurements of neuropsychological
function. The interpretation of statistical associations between
raised lead levels and psychological impairment raises another
question, that of the biological mechanism by which low-level lead
exposure could cause the psychological damage.
Observations in animals
Animal studies are available that provide information on the
effects of neonatal low-level lead exposure on locomoter
scheduled-controlled behaviour (Brown, 1975; Bushnell & Bowham,
1979; Rice, 1984). Other studies provide suggestions as to the
biological mechanisms that may underlie the neurophysiological or
neuro-psychological effects of low-level lead exposure. In one recent
study, cynomolgus monkeys were dosed from birth with 0, 50, or
100 µg/kg/day of lead, resulting in steady-state blood lead levels of
3, 11, or 13 µg/dl, respectively. At 3 years of age, the monkeys were
tested on an intermittent schedule for the usual measures of
differential reinforcement of low rate (DRL). The performance of
treated monkeys did not improve as rapidly as controls, and the
treated monkeys showed greater between-session variabilities during
terminal sessions. These results suggest that blood lead levels
comparable to those generally found in the human population may
produce neurophysiological effects (Rice & Gilbert, 1985). Other
studies with experimental animals have shown that lead (a) inhibits
haeme biosynthesis at lead levels below 20-30 µg/dl blood, with
subsequent neurotoxic effects of 6-amino-levulinic acid or one of its
metabolites, (b) interferes with the neuronal system that is
responsive to acetylcholine, catecholamines, and GABA (Sibergeld &
Lamon, 1980), and (c) affects intraneuronal haeme biosynthesis
(Rice & Gilbert, 1985).
Neuropsychological effects of lead in children
Rutter (1980), Yule & Rutter (1983), DHSS (1980), Needleman
(1980), and MRC (1986) have published reviews of studies on the
neuropsychological effects of lead in on-overtly intoxicated children.
Several categories of studies have been reviewed, including
(1) clinical studies of children thought to be at risk because of
high blood levels,
(2) studies of children from general pediatric populations,
(3) studies of children living close to lead-emitting smelters,
(4) studies of mentally-retarded or behaviourally-deviant children,
(5) chelation studies.
Studies prior to 1980 suggested that lead could cause
psychological impairment (lower IQ and behavioural deviance) at levels
below those associated with overt clinical signs of toxicity. However,
most of these studies were carried out with children with blood levels
in the range 40-70 µg/dl. There was little evidence that adverse
neurophysiological effects could occur at much lower blood lead
levels. For the studies to be applicable to the general population,
studies should be carried out with children with blood lead levels
below 35 µg/dl, since the median blood level of the population in nine
Member States of the CEC is 13 µg/dl, with about 2% exceeding the
critical level of 30 µg/dl. Similar blood lead levels have been
reported in the U.S. In addition, a number of major methodological
issues have been identified. These include selection of children,
neuropsychological measurements, estimates of body lead levels, and
adequate statistical analysis to control the effects of possible
Since 1979 a number of studies which have attempted to correct
these design deficiencies have been reported. Studies by Needleman and
his colleagues (Needleman et al., 1979; Needleman, 1983) using
deciduous teeth of first and second grade school children (estimated
age 5.5-7.5 years) indicated a small but possible effect of lead on
several measurements of neuropsychological performance, as well as
reducing the IQ by 1-5 points at tooth lead levels above 20 ppm
(indicative of a level of exposure). The mean blood lead level of the
children was about 30 µg/dl. Similar findings were reported in other
studies using tooth lead as an indicator of exposure in Germany
(Winneke et al., 1982, 1983) and in the U.K. (Smith et al., 1983).
In another series of studies, groups of children with blood lead
levels ranging between less than 10 to 14 µg/ml or greater than
15 µg/100 ml were studied. These studies also included groups from
various socio-economic backgrounds. Although one study indicated an
association between full-scale I.Q. and blood lead levels, a number of
confounding factors, e.g. lack of information on socio-economic
background and parental I.Q., made interpretation of the study
difficult (Yule et al., 1981). However, in another study corrected
for these factors, no significant association between blood lead
levels and various neuropsychological tests was observed
(Yule & Landsdown, 1983; Yule et al., 1984).
The general conclusions relating to these and other studies have
been summarized by Yule & Rutter (1983) and MRC (1986). Briefly, they
indicate that because of the complexity of the situation, it is
impossible from the available evidence to come to a definitive
conclusion on the neurophysiological effect of "ordinary" levels of
lead exposure. However, the possible neurophysiological effects of
lead within the range in the ordinary environment without special
risks (absence of excessive sources of environmental lead), are at
Electrophysiological studies on children with high and low lead
levels, (teeth or blood) have also been carried out. However, the
significance of the variations in EEGs is not understood.
Effects of lead on the kidney
The kidney is the major pathway for lead excretion and is
directly subject to effects of lead toxicity that may lead to
impairment of its multiple functions. The early or reversible effects
of lead toxicity result in proximal renal tubular dysfunction,
evidenced by increased urinary excretion of glucose, amino acids, and
phosphate. These effects have been reported in children with
relatively high blood levels of 150 µg/dl (NAS, 1972). Chronic or
irreversible lead nephropathy is characterized by intense interstitial
fibrosis and tubular atrophy and dilation and results from prolonged
exposure to high levels of lead.
Effects on growth
A recent analysis of 2695 children 7 years of age or younger,
based on U.S. survey data (NHANES II), indicated that blood lead
levels were a statistically-significant predictor of children's
height, weight, and chest circumference. The strongest relationship
was between blood lead and height, with no evident threshold found for
the relationship down to the lowest observed blood lead level of
4 µg/dl (Schwarz et al., 1986). However, other factors need to be
considered in the evaluation of these results, e.g. social factors.
Available information on tolerable levels of lead intake for
infants and young children
Estimates of tolerable exposure to lead have been based on the
maximum intake from all sources that would preclude accumulation of
lead. The data used include (a) levels of lead in the blood of
non-exposed and exposed individuals and of those with frank lead
poisoning, (b) the results of experimental lead ingestion by adults,
(c) measurements of faecal output of lead in exposed and non-exposed
children, (d) the initial effects of increased lead ingestion, (e)
rates of increase in levels of lead in the blood of exposed children,
and (f) sequelae of lead poisoning. Based on the available data the
U.S. Public Health Service established a daily permissible lead intake
from all sources for children of 300 µg/day, which has been considered
a reference base in developing measures for prevention of lead
poisoning in children (DHEW, 1970; King, 1971). At the time this
standard was established, 40 µg/dl of whole blood was considered
evidence of undue absorption of lead; it was assumed that (1) 90% of
the ingested lead was excreted and (2) total lead ingestion of
600 µg/day of lead for an adult or an estimated equivalent dose for a
child 2 to 3 years old, i.e. 300 µg/day, would not result in increased
blood lead levels. In 1972, Barltrop estimated the permissible limits
of intake for children of different ages from birth to 15 years by
scaling down from the level which was not known to cause toxicity in
adults. Since he considered the surface area of the body rather than
body weight to be the major variable in determining metabolic
activity, he calculated the acceptable daily intake, based on the WHO
adult tolerable intake of 600 µg/day (340 µg/square meter), corrected
for the caloric intake of children, and determined the permissible
daily intake to be 72 µg per square meter of body surface for a
newborn and 298 µg per square meter for a three-year old
(Barltrop, 1972). When this value was adjusted for varying body size
of infants between birth and three years of age, and when the newer
information on the increased absorption of lead in infants compared to
that of adults was taken into account, Mahaffey recommended that the
maximum tolerable intake for lead from all sources for infants between
birth and age 6 months should be as low as possible and less than
100 µg/day, and that intake should be no more than 150 µg of lead/day
for children between 6 months and 2 years (Mahaffey, 1977).
In 1983, Ryu measured the relationship between dietary lead
intake and blood lead concentration in infants from birth to 6.4
months and showed that intakes of as little as 61 µg/day resulted in
increased blood levels of lead, an indication of lead accumulation.
The metabolic balance studies reported by Ziegler et al. (1978)
demonstrated that faecal excretion of lead generally exceeded intake
when dietary intake of lead was less than 4 µg/kg/day. The study by
Ryu et al. (1983) showed that with low non-dietary exposure to lead,
a mean dietary intake of 3-4 µg/kg/day is not associated with an
increase in blood lead concentration. Thus, the authors concluded that
it seems reasonable to set the daily permissible intake for lead from
all sources closer to 3 than to 8 µg/kg/day, for infants. In addition,
based on their observations in the Glasgow duplicate diet study,
Sherlock & Quinn (1986) have developed an equation whereby they
calculate that infants having a lead intake of 680 µg/week (about
100 µg/day) will have an average blood lead level of 25 µg/dl. This
blood level is now considered to be one requiring intervention to
determine and reduce sources of exposure. The calculations of DHEW, of
Baltrop and of Mahaffey, were based on extrapolations from data
obtained from adults while those of Ryu and Sherlock & Quinn were
based on measured lead intake and blood lead levels in children and
therefore should be more reliable. Furthermore, at the time the
earlier calculations were made, the level of blood lead considered to
be indicative of toxicity in children was considerably higher than the
Because of special concern for them, the present Committee
evaluated the health risks of lead to infants and children. The
Committee noted that the previous principles governing the
toxicological evaluation of metal contaminants (Annex 1, Reference 30,
section 3.1), as well as the principles contained in the IPCS and CEC
report (WHO, 1986) on the need for a special approach to evaluating
health risks during infancy and early childhood, provide valuable
guidelines for evaluating these risks. The basis of the special
concern for infants and children relates to a number of factors,
including higher metabolic rate, rapid body growth, different body
composition, immaturity of the kidney, liver, nervous system, and
immune system, and development of organs and tissues such as bone and
brain. The higher energy requirements of infants and children and the
higher fluid, air, and water intake per unit body weight results in a
relatively greater intake of contaminants in food, compared to that of
adults. In addition, particular behavioural characteristics of
children such as heightened hand-to-mouth activity, as well as the
ingestion of non-food items (pica), may result in significant exposure
to lead from non-food sources. Social and cultural attitudes of child
rearing may influence exposure to non-food sources. Because the
evaluation of the health effects of lead relates to exposure from all
sources, any increase in lead from non-food sources (e.g. water and
air) will reduce the amount that can be tolerated from food. It is
important to identify sources of exposure that may be of greater
significance to infants and children than adults so that strategies
for control may be developed.
Detailed information on sources of exposure is available
(FAO, 1986a; WHO, 1977). Sources include those from the general
environment, the domestic environment, and food, air, and drinking
water. Exposure in the domestic environment is a particularly
important source of lead exposure for children and infants, and
includes lead in indoor dust, top-soil, and paint in the immediate
Detailed information on levels of lead in food and total intake
for infants and children is available (FAO, 1986a; WHO, 1977).
There is a large amount of information on the toxic effects of
lead. The information used in this evaluation has been largely derived
from studies with infants and children. Children absorb lead from the
diet with greater efficiency than do adults. Lead absorption for
adults is normally in the range of 5-10% of dietary lead. Children
with lead intakes of 5 µg/kg b.w. per day are in positive balance for
The net absorption of dietary lead at this level averages 40% of
the lead intake, and the net retention has been estimated to be about
30% of intake. However, metabolic studies indicate a negative balance
when lead intake is less than 4 µg/kg b.w./day. The relationship
between oral lead intake and blood lead levels is non-linear, with the
greatest increases in blood lead levels occurring at the lower range
The Committee considered the available information, including
correlations between blood lead levels and specific effects, blood
lead levels in children in the general population, and controlled
epidemiology studies. Based on the information that a mean daily
intake of 3-4 µg/kg b.w. of lead by infants and children was not
associated with an increase in blood lead levels, a provisional
tolerable weekly intake (PTWI) of 25 µg/kg b.w. was established. This
level refers to lead from all sources.
The Committee recognizes that in some situations the PTWI may be
exceeded, when blood lead levels may exceed 25 µg/dl. In such
circumstances investigations should be carried out to determine the
major source(s) of exposure, and all possible steps should be taken to
ensure that lead levels in food are as low as possible, and that
contributions from other environmental sources are minimized. The
following are possible strategies for achieving this:
Reducing or eliminating the use of lead solder and other
lead-containing materials in equipment and containers coming into
contact with food during its processing and handling can reduce lead
contamination of foodstuffs.
Lead contamination of foods in tinplate cans with lead-soldered
side-seams originates mainly from the solder used in can manufacture.
Contamination of foodstuffs in soldered cans can be reduced by
operating the can-making equipment in such a way as to minimize
contamination of the inside of the can with solder (FAO, 1986b),
replacing high-lead solder by low-lead or lead-free solder, and
lacquering the cans after soldering. Other ways of reducing lead
contamination of canned foods include using electro-welding or other
techniques instead of soldering to manufacture the can body, using
two-piece cans instead of three-piece cans, limiting the level of lead
permitted in the tin used to manufacture tinplate for food cans, or
replacing tinplate cans by other types of container.
Some glazes used for ceramic foodware contain appreciable levels
of lead. If such foodware is not fired correctly, it may release large
amounts of lead to foods, especially acidic products, that come into
contact with it. Contamination of foods with lead from this source can
be reduced by using lead-free glazes. Foodware can be checked for
levels of leachable lead using one of the standardized methods now
Contamination of drinking water with lead from plumbing systems
can be eliminated by replacing the lead in such systems with other
materials. If this cannot be done, contamination of soft water
(pH 4.5 - 5.5) with lead from plumbing systems can be reduced by
increasing the pH of the water to about pH 8.5 by the addition of lime.
In some circumstances, a major source of environmental lead
pollution is tetraalkyl lead used as a petrol additive. Lead in motor
vehicle exhausts increases lead exposure of infants and young children
in several ways. Elevated lead levels in air result directly in
increased lead exposure via inhalation. Atmospheric deposition of lead
on growing crops or the use of sewage sludge contaminated with lead
from highway runoff as fertiliser on agricultural land can result in
increased lead levels in foodstuffs and animal fodder and thus
indirectly in increased dietary exposure. This type of lead pollution
can be reduced by reducing or eliminating the use of lead compounds as
House paints used in the past sometimes contained high levels of
lead and therefore it is prudent to warn the parents of young children
of the serious health hazards associated with the ingestion of flakes
of such paint. Similar considerations apply to the use of lead in
cosmetics and toys.
The discharge of lead into the environment by industry, e.g. lead
ore mines and primary and secondary lead smelters, and from waste
disposal may give rise to high levels of local pollution. If such
pollution cannot be reduced, careful attention should be given to the
problems inherent in the consumption of heavily lead-contaminated food
produced in areas affected by such pollution.
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of contaminated fingers and mouthing or swallowing of other non-food
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