INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
WORLD HEALTH ORGANIZATION
SUMMARY OF TOXICOLOGICAL DATA OF CERTAIN FOOD ADDITIVES
AND CONTAMINANTS
WHO FOOD ADDITIVES SERIES NO. 13
The data contained in this document were examined by the
Joint FAO/WHO Expert Committee on Food Additives*
Rome, 3-12 April 1978
Food and Agriculture Organization of the United Nations
World Health Organization
* Twenty-second Report of the Joint FAO/WHO Expert Committee on Food
Additives, Geneva, 1978, WHO Technical Report Series No. 631
LEAD
Explanation
Lead as a food contaminant was evaluated for provisional
tolerable weekly intake for man (adult) by the Joint FAO/WHO Expert
Committee on Food Additives in 1972. Additional data have become
available and are summarized below.
Absorption and retention by animals
In short-term, 48-hour, feeding studies with groups of six
weanling rats lead absorption from the diet was increased by high fat,
low mineral, low protein, and high protein diets. Low fat, low fibre,
high fibre, low vitamin, and high vitamin diets had no effects on lead
absorption (Barltrop and Khoo, 1975).
The retention and tissue distribution of 210Pb were studied on
10-day-old, 150-day-old, and adult Macaca fascicularis monkeys,
each age-group comprising four animals (Willes et al., 1977). Lead
nitrate, 10 micrograms lead/kg body weight, containing 10
micro-Ci210Pb/microgram Pb was administered by gavage after a 12-hour
fast. The 210pb excreted in urine and faeces was monitored for 96
hours. All monkeys were necropsied 96 hours after dosing and the 210Pb
contents of various tissues was determined. The data demonstrate that
infant monkeys retain significantly more lead than adults.
Blood 210Pb levels 96 hours after dosing did not vary
significantly between age-groups, and of the 210Pb contained in blood
98-99% was found in the cells, and 1-2% in the plasma. In the cells,
5-8% of the 210Pb was bound to the cell membranes. The distribution
between blood components did not vary significantly with age.
The percentage of the lead dose excreted in urine did not vary
significantly between age-groups. Both the tissue Pb concentrations,
and tissue-blood Pb ratios were significantly higher in the bone
structures of the young animals than in the adults. The brain:blood Pb
ratio in the infants was significantly higher than in the older
groups.
Radioactive lead was administered intravenously to beagle dogs
(11-26 micro-Ci/dog), and whole-body gamma-ray counting and
measurement of the excreta was continued for about two years. The
effective half-lives for the slowest time constant component was 815
days, based on the in vivo counting results, and 1940 days, based on
the analysis of the excreta. The longer half-life given by the data
from the counting of the excreta is considered more reliable. In the
whole-body counting system the progressive burying of the radioactive
lead in the bony skeleton would gradually increase the absorption of
the weak gamma-rays simulating a loss of lead. The observed half-life
of 1940 days (equal to 5.3 years), can be extrapolated to man, using a
factor of 4, yielding a figure of 21.2 years (Hursh, 1973). This
compares with the estimate based on stable lead measurements performed
on man indicating a biological half-life of 16.8 years (Holzman et
al., 1968, cited by Hursh, 1973).
Biochemical effects of lead in man
In a recant study Kuhnert et al. (1976, 1977) have determined the
ALAD activity, and the lead level in the blood of 47 urban mothers,
and in the cord blood of their infants. In addition the activated ALAD
activity was also determined: this was done in the presence of a
chelating agent which removes the lead from the enzyme. These were
signs of enzyme inhibition avon at the lowest lead levels, below
20 micrograms/100 mL red blood cells. There was a close correlation
between maternal and infant blood lead levels, and maternal and infant
ALAD activities.
Metabolism of lead - relationship in man of oral intake and blood
levels
In most epidemiological studies, the actual exposure is not
accurately known. In a recent study male volunteers were given known
amounts of lead acetate via the oral route for seven weeks; the doses
were designed to maintain a blood lead level of 400 ppb. Various
biochemical parameters were determined weekly. Increases in blood
lead levels were accompanied by decreases in the activity of
delta-aminolaevulinic acid dehydratase (ALAD) in the blood to levels
of 45-70% of the initial values by the end of exposure. Free
erythrocyte porphyrins (FEP) were increased after a latent period of
0-21 days from the beginning of lead exposure. The rate of increase of
FEP and the latent period were influenced by the percentage absorption
of the lead from the gastrointestinal tract, the distribution of
absorbed lead within the body and the rate of release of new
erythrocytes from the bone marrow into the peripheral blood (Cools et
al., 1976).
Effects on children
The relationship of blood lead and mental development was
investigated by Kotok et al. (1977). The high lead group consisted of
31 children with a mean blood lead level of 79.6 micrograms/100 mL,
range 61-200 micrograms/100 mL. The control group of 36 children
with a mean lead level of 28.3 micrograms/100 mL (range 11-40
micrograms/100 mL). The parameters measured were social maturity,
spatial relationships, spoken vocabulary, comprehension, visual
attention and auditory memory. This study did not reveal significant
differences in the cognitive functions of the lead and control groups.
In another study three groups of children were compared. One
group consisted of 31 mentally-retarded children, in whom the etiology
of their condition was unknown. The second group was composed of 33
mentally retarded, with a known probable etiology. The last group
was a control sample of 30 normal children. The mean lead level
of the mentally retarded unknown etiology group was 25.5 ± 9.1
micrograms/100 mL, whereas in the control groups the mean values were
18.7 ± 6.5 and 18.8 ± 7.3 micrograms/100 mL, a significant difference
(David et al., 1976).
Epidemiology of lead poisoning in infants, young children and adults
The signs of lead poisoning are well documented and there are
many well known sources of contamination such as ceramic glazes,
decorations on cocktail glasses, etc. However, there have been recent
reports of lead poisoning from some unexpected sources. In one case,
powdered horse bone, prescribed for dysmenorrhoea, was found to
contain 190 ppm of lead (Crosby, 1977). In another case, a young child
in Hong Kong showed signs of acute lead poisoning after treatment with
various Chinese herbal medicines (Chan et al., 1977). The risk of lead
poisoning from herbal medications has also been reported in America
where haematological and neurological symptoms ascribed to lead
poisoning resulted from the ingestion of certain herbal pills
(Lightfoote et al., 1977).
There is a well-documented history of lead poisoning in
Queensland, where a high incidence of cerebellar calcification has
been reported to occur. These findings at autopsy are confined to
people born in Queensland, or who have lived there for long periods of
time. There is definite statistical correlation between cerebellar
calcification and raised lead levels in cranial bone and it is also
noted that the lesion occurs in almost all cases of lead nephropathy.
However, the lesion is not present in all cases with raised lead
levels in bone and it is therefore thought that a brief, though
severe, episode of poisoning might result in brain injury whilst a
more sustained exposure might be necessary to produce renal damage
(Tonge et al., 1977).
Blood lead levels in some pre-school children (approximately two
years old), living near a lead battery manufacturing works, were found
to be elevated and especially if the father was employed at the works.
In a follow-up to this study, certain children were re-examined three
years later for developmental and behavioural functions. There were no
significant differences in any of the tests employed between the
"high" lead group (> 35 µg/100 ml) and the "moderate" lead group
(<35 µg/100 ml). Nevertheless, The "high" lead group consistently
did "slightly less well" than the "moderate" lead group. The
difficulties of determining actual lead exposure over several years,
and thus the allocation into "high" or "moderate" lead exposure were
noted (Ratcliffe, 1977).
Effect of lead on chromosomes of man
Chromosome analyses have been carried out on children living in a
town with a lead smelter plant where there were indications of
increased lead exposure (shown by increased blood lead levels,
decreased delta-aminolaevulinic acid dehydratase or increased free
erythrocyte porphyrins). There was no evidence of a higher number of
cells with structural chromosome aberrations or of an increased
aberration yield (Bauchinger et al., 1977).
Lead intake and blood-lead levels
Very few estimates exist in which total lead intakes are
correlated with blood-lead levels. Goyer and Mushak (1977) evaluated
several recent data and deduced that every 100 micrograms of lead
present in the daily diet would contribute about 10 micrograms of lead
per 100 mL blood. They estimated also that with blood levels in the
normal range of 20-30 micrograms/100 mL, environmental air-lead levels
contribute only a small fraction of this blood-lead level. For
children such estimates are more difficult and less well established.
In the United States of America, children of one to three years of age
consume about 100 micrograms of lead per day. Since absorption from
the gastrointestinal tract may be as high as 50%, their diet may
contribute more to the blood-lead level.
Ziegler et al. (quoted by Mahaffey, 1977) conducted metabolic
balance studies in young children from two to 25 months of age,
consuming diets containing "usual" levels of lead. A lead intake of
less than 50 micrograms/day (based on individual balance data) appears
to be accompanied by negative lead balance.
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