WHO Food Additives Series, 1972, No. 4


    The evaluations contained in this publication were prepared by the
    Joint FAO/WHO Expert Committee on Food Additives which met in Geneva,
    4-12 April 19721

    World Health Organization


    1 Sixteenth Report of the Joint FAO/WHO Expert Committee on Food
    Additives, Wld Hlth Org. techn. Rep. Ser., 1972, No. 505; FAO
    Nutrition Meetings Report Series, 1972, No. 51.


    Consideration of lead intake by man must take into account other
    routes in addition to ingestion in food.  Air contains concentrations
    of lead that vary with the degree of urbanization and industrial
    pollution.  Therefore, in the course of respiration lead is inhaled
    and some of it is then absorbed into the body.  Similarly, drinking
    water may contain concentrations of lead which differ according to
    geographical location.  Thus food, water and air contribute to the
    total intake of lead, and their relative importance with respect to
    the resulting body burden of lead depends on the proportion of lead
    retained in the body from each source.

    The same general considerations with respect to sources, levels and
    methods of analysis considered for mercury apply also for lead.


    (a) Environmental sources

    Soil.  Lead is ubiquitous in soil. Levels of 8-20 mg/kg found in
    non-cultivated soils indicate that it has always been present in man's
    environment, although not necessarily at such high levels.  In
    cultivated soils levels up to 360 mg/kg have been reported.  Near
    industrial sources lead may reach 10 000 mg/kg or more.

    Proximity to roads with high traffic density may contribute
    substantially to soil levels (for example, 403 mg/kg in the top 5 cm
    layer of soil).  In addition, high levels of lead may occur in dust
    settling in urban areas, and may result in direct contamination of
    food.  Surface contamination in situ of plants growing near highways
    does occur.  Lead is absorbed by edible and nonedible vegetation, so
    that grasses, for instance in highly contaminated areas, may attain
    levels of 20-60 mg/kg (Chow, 1970).  The chemical forms of lead and
    the various factors limiting their availability for uptake by plants,
    e.g. type of soil, pH, etc., are other important considerations.  Lead
    enters the food chain through plants or through accidental ingestion
    of soil.  However, not all plants take up lead to an equal extent so
    that the soil content of lead may remain high in spite of cultivation.
    Lead accumulates similarly in food of animal origin from absorption
    and retention of plant lead by farm animals.

    Air.  In rural areas levels of lead in air of 0.1 g/m3 or less are
    found.  However, depending upon the degree of pollution due to
    urbanization, the amounts of lead in city air range from 1-3 g/m3,
    and will occasionally be much higher under peak traffic conditions
    (Ludwig et al., 1965; Miettinen, 1972).

    On the basis of the information available, and depending upon the
    degree of urbanization of the area concerned, its topographical
    situation, weather conditions, and habitat, it may be assumed that the

    intake of lead by inhalation in cities could on occasion be 100
    g/day.  Lead-containing dusts are present in many manufacturing
    processes and may add to the lead content in all foods to a small
    degree (Shy et al., 1971).  Infants and children may be exposed to
    proportionally higher levels than adults because the higher metabolic
    rate would entail the inhalation of two to three times the amount of a
    given air pollutant (Shibko, 1972).

    Some unconfirmed reports have suggested that a very small proportion
    of the total lead in urban air might be in organic form.  This is a
    separate problem that needs to be considered by experts in air
    pollution.  The contribution of lead from air to the total intake can
    be estimated solely from the total body burden.

    Also contributing to the atmospheric level of lead are industrial lead
    smelters, disposal of discarded batteries and other lead-containing
    materials, burning of garbage and old painted wood, weathering of old
    lead-containing paints on buildings, as well as the burning of coal
    and fuel oil.

    A source of lead that calls for particular consideration is the lead
    tetra-alkyls used as petrol (gasoline) additives.  The lead derived
    from petrol additives contributes not only to the intake through
    inhalation but also to the intake through ingestion as a result of
    fallout from vehicle exhausts on nearby food crops.  An increased lead
    content may be found in crops at distances up to 50 m from highways,
    depending on weather conditions and traffic volume (Motto et al.,
    1970). Although formerly significant, in many countries the
    atmospheric contributions to total lead levels derived from fossil
    fuels is now less important compared with that from lead-containing
    petrol additives.  The very low atmospheric levels of alkyl lead
    compounds in city air do not contribute significantly to the lead

    Tobacco smoking may also contribute to lead intake by man (FAO/WHO,
    1967).  While atmospheric lead is present in relatively small
    concentrations, this source assumes considerable importance because a
    greater proportion of load is likely to be absorbed after inhalation
    than after ingestion.

    Water.  Sea-water contains lead (0.003-0.20 mg/litre).  Natural
    water probably contains no more than 0.005 mg/litre but in the
    presence of nitrate, ammonium salts or dissolved carbon dioxide the
    water becomes plumbosolvent.  This occurs in soft, slightly acid water
    in older properties where lead piping is still in use (Schroeder &
    Balassa, 1961).  Levels of lead as high as 25 mg/litre have been
    reported (Egan, 1972).  Hard waters normally lay down a protective
    coat of calcium salts which avoids this hazard, but even this form of
    protection may not apply if naturally hard water also has a high
    organic and nitrate content.

    The levels of lead encountered in water supplies are probably about
    0.01 mg/litre.  However, the International standards for drinking
    water (WHO, 1971) suggest a tentative limit for lead of 0.1 g litre.
    Assuming a consumption of 2.5 litres of water per day the maximum lead
    intake from this source would be 250 g; this would contribute
    significantly to the total amount of lead taken in by man.

    Another possible source of contamination that has aroused concern is
    lead present in food containers, in the widest sense, including lead
    water-piping.  Depending on pH, mineralization and other factors,
    traces of lead may leach into food or drink from such containers.  It
    is recognized that the use of lead plumbing for drinking-water
    supplies and especially for soft or softened water is not advisable.

    There is little information on the ability of fish and shellfish to
    accumulate lead from contaminated waters.  Wettenberg (1966) reported
    concentrations of 1.4 ppm in muscle of fish from a lake near a lead
    mine.  High values have been reported by FDA in 1971 of lead in
    shellfish (up to 10 ppm), in certain contaminated areas in the United

    (b) Industrial Sources

    Lead is used in a large number of industrial processes.  In people
    exposed occupationally to lead fumes or dust the intake of lead by
    inhalation and by ingestion will be increased.  Therefore, part of the
    body burden of lead in particular individuals may be contributed by
    industrial exposure.  As mentioned below, industrial emissions near
    smelting works may frequently add lead dust contamination to other
    environmental sources.

    Lead-containing dusts are present throughout all manufacturing
    processes and gradually add to the lead content of all foods to a
    small degree (Miettinen, 1972; Shy et al., 1971).  In the past, lead
    impurities in food additives were another source of lead.  Modern
    legislation and trade practice, and the adoption, in food additive
    specifications, of limits for lead recommended in previous reports of
    the Committee, have virtually eliminated this hazard.  Lead smelters
    and dumps where lead-containing material such as old batteries has
    been discarded or burnt may contribute to localized environmental
    contamination of the food supply.

    (c) Agricultural sources

    The use of lead arsenate in agriculture has diminished.  Where its use
    is still permitted on orchard crops, it contributes only a small
    proportion of the total intake of lead by man.  The use of
    lead-containing pesticides in tobacco has likewise diminished although
    it might have contributed significantly to the lead intake by smokers.
    More recent analytical data however are required.

    (d) Other sources

    Consideration of lead in food and water must take into account lead
    contamination of the domestic environment.  Old lead paint on walls
    and woodwork, and paints on toys may be important sources of excessive
    lead intake in children (Chisolm, 1971; Chisolm & Kaplan, 1968).

    Lead glazes are used on ceramic kitchenware, earthenware and stoneware
    vessels because they allow more flexibility in the kiln temperatures
    for firing pottery.  Lead may also occur in decorative glazes on some
    pottery.  The leaching of lead from inadequately fired glazes has been
    investigated and it is known to present serious health hazards in
    vessels used as containers for acidic foods and beverages.  Lead
    glazes for decorative purposes should not be placed in contact with
    food.  Pewter containers and tinned copperware, in which the use of
    impure tin was a frequent source of lead, have now largely been
    replaced by aluminium and stainless steel containers.

    Tinplate cans with soldered seams have been investigated as possible
    sources of lead contamination for a variety of foods.  In a survey
    carried out in the United Kingdom the mean lead concentration for
    canned baby food was about 0.24 mg/kg compared with a level of 0.04
    mg/kg for baby food in jars (U.K. Report, 1972).  The tin coating
    itself contains little lead, if any, but the solder used for the seam
    may contain up to 98% lead.

    Methods of analysis

    In the basic method for the estimation of traces of lead in biological
    material, the sample is ashed or wet oxidized under controlled
    conditions.  Lead is removed from the digest and concentrated by
    extraction as dithiocarbamate complex.  The amount of lead present is
    estimated by atomic absorption spectrophotometry using the 283.3 nm
    line, due regard being given to the recovery of lead in control
    experiments.  The method given by the International Union of Pure and
    Applied Chemistry for traces of lead in food is currently under
    revision to include atomic absorption spectrephotometry (IUPAC, 1965).

    Biological data

    Intake, retention and absorption

    Lead is a non-essential element for man, with a toxic potention for
    all biological systems.  It accumulates in human tissues particularly
    in the bones, liver and kidneys.  There is an unavoidable total
    daily intake from inhalation and ingestion of various forms of lead
    in the human environment, which is considerably greater than the 
    total actually absorbed.

    Food and water are the major sources of ingestion of lead. In
    addition, some of the inhaled lead is cleared from the respiratory
    tract and swallowed. Lead in food may be added to by a number of
    possible sources of environmental contamination, mentioned previously.

    When results of total diet studies for lead in industrialized
    communities are examined, traces of lead are found to be generally
    distributed over all food groups, including water; and the intake is
    of the order of 200-300 g per person per day.  Certain foods such as
    kidneys and liver tend to have higher than average levels (Cheftel,
    1950).  Total diet surveys in the United Kingdom suggest a mean daily
    intake of 0.22 mg lead although individual results show considerable
    and as yet unexplained variations.  Canadian reports suggest a rather
    lower intake of 0.15 mg lead per day while United States reports
    indicate levels of 0.25-0.30 mg lead per day (Kehoe, 1964).  Romanian
    sources quote 0.7-1.0 mg lead per day (Fleming, 1964).  An estimate of
    lead ingested by children between one and three years of age was given
    as 0.112-0.165 mg lead per day (King, 1971).  Further reports suggest
    that most food in North America reaches a level of less than 0.5 mg/kg
    lead in individual items (Schroeder & Balassa, 1961; Kehoe et al.,
    1940).  Levels of lead in milk seem to have risen slightly over the
    past 20-30 years (Lewis, 1966) but there is no evidence of any real
    increase in dietary lead during recent decades (United Kingdom report,
    1972).  Recent comparisons of lead in food in North America with those
    obtained over 20 years earlier also do not suggest any increase in
    lead intake by man from this source.

    The major routes of entry of lead into the body are the
    gastrointestinal tract and the lungs.  Under conditions of normal
    dietary intake of lead, absorption from the gut is estimated to be
    6-7% (Kehoe, 1961).  The United Kingdom estimate is 5-10% (United
    Kingdom report, 1972).  Individuals given daily doses of 3 or 6 mg
    lead absorbed 20-30% (Imamura, 1957).  These different figures may
    reflect the effects of higher loads and also nutritional differences,
    since calcium, phosphorus and other substances, e.g. phytic acid, can
    affect the absorption of dietary lead (Monier-Willims, 1949).  There
    is some experimental evidence in animals that suggests the possibility
    that very young infants may absorb considerably more lead from the
    diet than adults (Kostial et al., 1971).

    As the lead concentration in ambient air has been shown to vary from
    less than 0.1 g/m3 to more than 30 g/m3 in different localities,
    estimates of the total lead inhaled must necessarily cover a wide
    range.  Figures for inhaled lead have been quoted for an urban
    population to be between 0.01 and 0.10 mg per day. (United States
    public Health Service, 1965), the amount being dependent on the total
    ventilation of the subject as well as on the lead level in ambient
    air.  It is likely that once lead is deposited in the nonciliated
    peripheral part of the lung it is completely absorbed, whilst lead
    deposited on ciliary surfaces will be mostly translocated to the
    gastrointestinal tract and handled subsequently in the same way as
    ingested lead.  A study utilizing a 212Pb labelled aerosol of mass
    median diameter of 0.2 m showed a deposition of 14-45% of the mount
    inhaled, less than 8% of which was deposited in the tracheo bronchial
    tree (Hursh et al., 1969).  However, the pulmonary deposition of
    inhaled particles is dependent on their physical characteristics as
    well as on the respiratory pattern.  Because of the variability of

    these factors it is not possible to arrive at a precise estimate of
    the degree of absorption of inhaled lead.

    Estimates for absorption have mostly ranged from 25-50% of inhaled
    lead (Kehoe, 1964).  On this basis the estimated daily absorption from
    the ambient air in Cincinnati was 0.01-0.02 mg (Goldsmith & Hexter,
    1967).  A study of some of the physical characteristics of particles
    from vehicle exhausts suggests that the estimate of 25-50% absorption
    of inhaled lead may be too high (Lawther at al., 1972).

    Lead is transported mainly on the surface of the red blood cells, and
    is distributed throughout the body, undergoing cumulative storage in
    all tissues and organs.  The largest amounts are stored in bone where
    lead is first deposited as a colloidal compound, and later as
    crystalline material.  Much lower quantities of lead are found in the
    liver and kidneys.  The deposition and removal of lead from bone is
    governed by the same factors that control the movement of calcium. 
    The total body burden of an adult is estimated to be 100-400 mg, but
    it is not certain whether this burden of lead is close to the toxic

    Various ranges may be cited for whole blood levels of lead: 100-500
    ng/ml (mean 300 ng/ml); 110-210 ng/ml or 250-400 ng/ml (Anon., 1966).
    Kehoe (1961) gave upper limits of 400 and 800 ng/ml for children and
    adults respectively, but these values far exceed what would be
    regarded as the upper range of normal today.  A WHO survey of 15
    countries gave 150-330 ng/mi (WHO, 1965).  Lead enters mother's milk;
    it may not cross the placental barrier, nevertheless the foetus is
    known to retain lead (Anon., 1966).  Levels of lead in the blood of
    newborn babies show a direct relationship to the levels present in the
    maternal blood. (Hass, T. H. et al., 1972).

    Most of the ingested lead is excreted in the faeces and these contain
    usually 0.22-0.25 mg lead per day.  Usually lead is excreted in
    inorganic form in the urine of normal subjects but in exposed
    individuals it is excreted in inorganic and lipid extractable form
    (50% or more of total urinary lead) (Dinischiotu et al., 1960).  The
    average total urinary lead excretion amounts to 0.05 mg per day (0.03
    mg/litre) but as much as 0.2 mg has been found in symptomless people
    (Monier-Willlams, 1949).  Very small amounts are excreted in the sweat
    and hair.  Radioactive lead balance studies have shown intakes of 0.41
    mg per day from food and fluids and 0.01 mg from air against a hair
    output of 0.088 mg.  About 0.001 mg per day was retained (Howells,
    1967).  In mother estimate, intake from food was 0.26 mg lead per day,
    water 0.02 mg against an output of 0.175 mg in faeces, 0.03 mg in
    urine, 0.09 mg in sweat and hair, 0.007 mg having been stored in bone
    (Schroeder & Tipton, 1968).

    While under ordinary circumstances absorption of lead exceeds
    excretion, at very low intakes, faecal excretion keeps pace with
    absorption so that little accumulation occurs in tissues.  A rise in
    blood and urine lead levels is therefore evidence of increased

    absorption without necessarily being associated with any detectable
    biological change.

    Lead toxicity

    The lead absorbed from lungs and gastrointestinal tract eventually
    distributes throughout all tissues and at least 95% of the total body
    burden tends to accumulate in the bones.  The amount of lead in bone
    will depend upon the level of past exposure and is found to vary
    between individuals, whereas soft-tissue concentrations remain
    relatively constant.  It is not possible to maintain a clear
    distinction between lead absorption compatible with normal body
    function and subclinical lead intoxication, when the evidence
    available shows only that interference with some metabolic process of
    unknown significance in the body has occurred.  The pattern of lead
    absorption, metabolism and body storage seems to be similar in all
    animal species examined.  The kidneys, the liver, the bone marrow and
    the brain are the target organs of toxic effects.

    At any given time the blood level of lead represents an expression of
    a balance between absorption from environmental sources and excretion
    in urine, faeces, sweat, hair, soft tissues, bone marrow and bone, but
    bears no direct relationship to the threshold for overt poisoning. 
    The majority of occupationally unexposed people have blood lead levels
    lying between 150-250 ng/ml for adults and children.  Blood levels of
    above 360 ng/ml in children and above 600-800 ng/ml in adults are
    usually regarded as excessive and indicative of undue lead absorption
    even if no symptoms are detected.  Urinary lead levels of 150 g/litre
    are considered acceptable but higher levels indicate excessive
    absorption.  For other parameters the limits are haemoglobin 13 g for
    men, urinary coproporphyrin 500 g/iitre and urinary o-aminolevulonic
    acid (ALA) 20 mg/litre (Gibson et al., 1968; British Medical Journal,

    Lead significantly inhibits the enzymatic conversion of ALA to
    prophobilinogen by ALA dehydrase and the final formation of heme by
    the incorporation of iron into protoporphyrin IX.  The inhibitory
    actions result in increased urinary excretion of home precursors,
    including porphobilinogen and coproporphyrin III.  Erythrocyte
    coproporphyrin and non-haemoglobin iron stores are increased.
    Extracellular iron metabolism is not affected by lead, iron clearance
    from adult plasma is normal, but in children it may be prolonged
    (Waldron, 1966).  Iron passes normally to bone marrow but utilization
    for haemoglobin formation is decreased (Simpson et al., 1964).  The
    presence of basophilic stippling in erythrocytes is a feature of frank
    lead poisoning and does not correlate with lead exposure; most
    stippled cells are present in the bone marrow.  The granules are
    altered ribosomes (Waldron, 1966).  Other cells have iron-positive
    non-basophil granules and both granule types occur in some cells,
    megaloblasts appear as well as arrests at metaphase of erythroblastic
    nuclei (Beritic & Vandekar, 1956).

    Mild lead poisoning is associated with slight reduction in nerve
    conduction velocity.  Peripheral nerve damage in lead exposed workers
    was shown to be related to the degree of anaemia (Catton et al.,
    1970).  Lead palsy is probably due to direct action of lead on the
    muscle as well as damage to nerve.  Excessive ingestion of lead causes
    inflammation of the gastrointestinal tract.

    Renal damage which is rare in adults with plumbism but frequent in
    children, results from direct cellular toxic action as shown by
    intranuclear inclusion, aminoaciduria, glycosuria and other features
    of the Falconi syndrome due to renal tubular damage have been
    described in children with lead poisoning (Chisolm, 1962).  In a
    series of cases reported from Australia, 50% of cases of chronic
    plumbism with lead nephropathy were also associated with gout and with
    low urinary uric acid excretion (Emmerson, 1965; Morgan et al., 1966).

    A correlation between childhood plumbism and the development of
    nephropathy 10-40 years later has been noted in Australia.  The
    excessive initial absorption caused no symptoms.  Bone lead of persons
    dying from chronic nephritis was significantly higher than bone lead
    of people dying from non-renal causes (Radosevic et al., 1961; Tepper,
    1963).  Heavy lead exposure with episodes of clinical plumbism
    extending over 10 years caused nephropathy with renal failure in 15%
    of 102 individuals affected, and hypertension developed later (Lilis
    et al., 1968). In another study of 20-year exposure, 4% of the 53
    cases had organic nephropathy.

    In the course of a study carried out in mice given 25 ppm lead acetate
    in drinking water, Schroeder et al., (1970) noted that the mean
    lifespan of male animals was curtailed by 100 days compared with
    controls maintained on leadfree diets. The lead concentration in
    heart, lung, kidney, liver and spleen approached that found in human


    (a) Sources

    Water standing in lead pipes overnight has given rise to lead
    intoxication.  Children have been poisoned by home-grown vegetables
    from gardens whose soil had a high content of lead; cabbage, for
    example, contained 5 mg/kg lead (Moncrieff et al., 1964); frying pans
    with a tin coating with 29-58% of lead (British standard
    specifications, 1964 = 25%) contaminated cooked food with 4-6 mg lead
    per portion.  Home-made wine and liquor has caused intoxication
    through lead dissolved from pottery glaze (Klein et al., 1970) and car
    radiators used in illegal distillation.  "Devonshire colic" has been
    caused by lead dissolved from base trays to give a concentration in
    cider of 6 mg/litre (Walls, 1969).  Gurkha soldiers fell ill following
    ingestion of chilli powder adulterated with 10 800 ppm lead chromate
    (Power et al., 1969).  Many other accidental food contaminations have
    been reported.  Lead from solder used in canning processes is usually
    not an important source of acute lead poisoning.

    (b) Diagnosis

    Of the diagnostic criteria, the most sensitive tests relate to the
    interference with normal heme synthesis, as shown by the development
    of anaemia, risein, urinary coproporphyrin level, urinary ALA
    excretion and fall in red cell ALA dehydrase activity.  Blood and
    urine lead levels do not distinguish between toxicity and exposure.
    Risein urinary ALA levels agree most closely with clinical evidence of
    intoxication and may provide an earlier sign of lead absorption than
    urinary coproporphyrin levels.  Reduced ALA dehydrase activity is
    probably the most sensitive indicator of exposure (Cramer & Selander,
    1965; Bruin 9, Hoolboom, 1967).  Basophil stippling is a poor
    indicator of excess absorption.  Hair concentrates lead and there is
    some evidence that it may be a good indicator of excessive exposure.
    Normal levels are about 24 mg/kg and in chronic poisoning may reach
    280 mg/kg (Kopito et al., 1967).  Urinary ALA levels and lead levels
    in hair might provide suitable parameters in mass screening for
    subclinical lead poisoning (Blanksma et al., 1969; Lin-Fu, 1970).

    Lead intoxication is accompanied by effects on thyroid function at
    various points of the pituitary-thyroid axis, but without change in
    the level of protein bound iodine in the serum (Sandstead et al.,

    An association has been shown between prolonged exposure to lead and
    mortality from cerebrovascular accidents not associated with
    hypertension (Hunt, 1970; Dingwall-Fordyce & Lane, 1963; Cramer &
    Dahlberg, 1966).  It has also been suggested that lead exposure may
    aggravate liver cirrhosis (Butt, 1960).

    The working group of the International Agency for Research on Cancer,
    commenting on the evaluation of carcinogenic risk of chemicals to man
    (IARC, 1972), concluded that there was no evidence to suggest that
    exposure to lead compounds caused cancer of any site in man.
    Dingwall-Fordyee & Lane (1963) in reporting the results of a follow-up
    study of 425 persons who had previously been exposed to lead in an
    accumulator factory, found no evidence to suggest that malignant
    disease was associated with lead absorption.  However, this is only
    one epidemiological study of the possible relationship between
    exposure to lead and the occurrence of human cancer.  In animal
    experiments a carcinogenic effect has been demonstrated but the levels
    of lead acetate, which produced renal tumours in rats, exceed by far
    the maximum tolerated dose for man (van Each et al., 1962).

    Massive exposure to lead has caused reproductive and teratogenic
    effects in animals.  In man lead in high dosage has long been used as
    an abortifacient but there is no evidence that it has any teratogenic
    effects.  A higher incidence of mitoses with secondary chromosomal
    aberrations was seen in workers exposed to lead oxide compared with an
    unexposed control group.  In vitro studies with lead acetate
    produced similar chromosomal abnormalities (Schwanitz et al., 1970). 
    A study of chromosomal changes in the lymphocytes of persons suffering
    from chronic lead poisoning showed a modest percentage of aneuploidy

    of the cells (Biscaldi et al., 1969).  Earlier literature has
    suggested mutagenic effects in chronic lead poisoning.  Plumbism in
    fathers seems to have an adverse effect on reproductive performance
    and the survival of the offspring (Weller, 1915).

    There is experimental evidence that the absorption of lead is high in
    newborn rats and it has been suggested that this may also be the case
    with very young human infants (Kostial et al., 1971).  The suggestion
    of a causal relationship between excessive lead absorption and mental
    retardation in children was not borne out by investigation of blood
    levels of lead in mentally-handicapped and normal control children
    (Gordon et al., 1967).

    (c) Clinical manifestations

    Chronic lead poisoning is usually associated with anaemia, basophil
    stippling of RBC, an elevated reticulocyte count, faulty maturation
    and haemoglobinisation of RBC in bone marrow with, sometimes, an
    additional haemolytic element.  Adults usually have a normocytic and
    normochromic or hypochromic anaemia which rarely falls below 9 g Hb.
    Children may have a microcytic, hypochromic anaemia which may be more
    severe (Waldron, 1966).  A lead line may be seen in the gums in adults
    but rarely in children.  Renal tubular cell abnormalities may give
    rise to a Falconi syndrome.  There is some doubt whether chronic
    exposure to low levels of lead can produce permanent renal damage.
    Mild symptoms of tiredness, lassitude, abdominal discomfort, insomnia,
    constipation or diarrhoea and nausea have been claimed to be
    associated with continuous low dose exposure.  The USSR includes also
    broader subliminal effects associated with changes in conditioned
    reflexes which may appear at levels of 250-300 ng/ml lead in blood
    (Gusev, 1960).

    Investigations on lead exposure

    (a) Short-term studies

    One experimental subject consumed 0.32 mg lead/day in his diet and in
    addition, 3 mg/day lead chloride for 18 weeks.  There was a
    progressive increase in the output and concentration of lead in urine,
    in the lead level in blood and in the amount of lead retained in the
    body (Kehoe, 1965).

    Three groups of men in (a) presymptomatic state, (b) with mild toxic
    symptoms, (c) with severe poisoning, were examined for various
    parameters.  The urinary lead excretion was similar in all three
    groups.  Blood lead levels were poorly correlated with symptoms.
    Haemoglobin, urinary coproporphyrin levels and urinary ALA levels
    correlated well with clinical symptoms.  Porphobilinogen in urine was
    raised only in frank poisoning (Gibson et al., 1968).

    (b) Long-term studies

    Three experimental subjects consumed 0.32 mg lead/day in their diet
    and in addition 2 mg lead chloride/day for two years, 1 mg lead
    chloride/day for four years or 0.3 mg lead chloride/day for 60 weeks.
    Those receiving 1 and 2 mg additional lead showed progressive rise in
    urinary lead output and concentration and progressive rise in blood
    lead level as well as in the quantity of lead retained in the body.
    The urinary output and lead concentration increased slightly at 0.3 mg
    lead/day and by 15 months it was calculated that 12 mg had accumulated
    in the body.  Blood lead levels were not raised.  It was concluded
    that a total dietary intake of 0.62 mg lead/day could not, within the
    human lifetime, reach potentially dangerous blood levels and body
    burden (Kehoe, 1965).

    A group of 14 human volunteers underwent continuous exposure to
    inhaled lead particulates for 23 hours a day over a period of five
    months, under carefully controlled conditions providing a low
    background of lead in food and water, and in the air inhaled which was
    confirmed by a control group of six subjects.  As a result of exposure
    to a mean level of 10.9 g lead/m3 of air, the level of blood lead
    was virtually doubled while the o-aminolevulinic acid dehydrase (ALAD)
    activity in red cells fell concomitantly.  Measurements of urinary
    porphobilinogen, ALA and coproporphyrin III revealed no increase from
    pre-exposure levels.  Follow-up of the subjects for several months
    after the cessation of exposure revealed a return of ALAD and lead to
    pre-exposure levels in blood.  A further study along similar lines,
    but with a mean atmospheric concentration of 3.5 g lead/m3, revealed
    only a very slight and delayed rise in blood lead and simultaneous
    fall in ALAD.  It is thus likely that 2-2.5 g lead/m3 represents a
    level below which no evidence of exposure is manifest, as judged by
    the most sensitive indices considered to be applicable at the present
    time (Golberg, 1972).

    The human studies just described were preceded by continuous
    inhalation exposure of rats and monkeys (M. mulatta) for one year to
    levels of about 20 g lead/m3.  The resulting rise in blood lead
    followed different patterns in the two species.  The level of ALAD in
    red cells fell in rats but was initially so low in monkeys that any
    reduction in activity could not be measured.  (ALAD is a vestigial
    enzyme with no known function in the mature erythrocyte.)

    Epidemiological evidence suggests that ALA dehydrase inhibition is
    demonstrable at blood lead levels considered to be within normal
    limits, i.e. 300-400 ng/ml (Members & Nikkanen, 1970).  The
    significance of these findings for man in terms of a health hazard is
    at present unknown.  It is believed that man can cope with the limited
    effects of low or moderate lead exposure in the short term for there
    is at present no evidence that such specific metabolic interference as
    is demonstrated by a fall in red cell ALA dehydrase is associated with
    any effects on the health of the individual.  Uncertainty exists over
    the long-term consequences of a persistent intake of lead at levels
    not toxic in the short term, and the relation of such effects, if any,

    alone or in combination with other factors, to the development of
    chronic degenerative conditions (Shibko, 1972).  The very low
    atmospheric levels of alkyl lead compounds in city air do not
    contribute significantly to the lead problem.


    It is evident that with present environmental exposures lead
    accumulates in man with age but people differ in the effectiveness
    with which they absorb and eliminate lead.  The environmental
    exposures to lead now existing in industrialized communities are
    sufficient to cause tissue accumulation estimated to reach about 230
    mg at age 60 years (Schroeder & Tipton, 1968).  United Kingdom
    post-mortem studies have revealed mean total body burdens of 162 mg in
    males and 113 mg in females.  Studies in the United States of America
    have revealed that soft tissue levels also gradually increase with age
    in contrast to India, the Far East and Africa, indicating that the
    absorption of lead was greater than the capacity of the body to
    excrete it.  There is no direct evidence that the existing levels of
    total body burden from food and air are harmful, but the Committee
    felt that this body burden should not be allowed to increase further.

    It is virtually impossible to effect a significant reduction in the
    total dietary intake arising from naturally occurring lead in food.
    The Committee made estimates of the lead intake and body burden from
    this source and related this estimate to the total lead intake for 
    rural and urban environments.  This total intake was thought not to
    exceed a maximum of 0.45 mg lead per day.

    The Committee recognized that for any environmental situation the
    hazard to infants and children may be proportionally higher than that
    for an adult, because (a) the higher metabolic rate would entail the
    inhalation of two to three times the amount of given air pollutant, on
    the basis of body-weight; (0 the average dietary lead intake, based on
    a dose per kilogram body-weight, would be considerably higher (400 g
    lead per day for a 60 kg adult, versus 130 g lead per day for a 10 kg
    child), and (c) possibly greater absorption from the gastrointestinal
    tract would lead to a higher body burden of lead, although definitive
    human evidence on this point is lacking.

    The Comittee was also aware that nutritional deficiencies could
    possibly increase lead absorption rates and under these circumstances
    a special assessment would be required.

    The Comittee decided that in arriving at a provisional tolerable
    weekly intake, use could be made of an estimated level of absorption
    from all sources of 1 g/kg body-weight/day.  This would result in the
    average adult in a total absorbed amount of lead of about 60-70 g, of
    which the fraction absorbed from air could reach 20 g, leaving up to
    10 g to be contributed by water and up to 40 g by food.  The
    Committee established in adults, on the assumption that only 10% of
    lead ingested from food and water is absorbed, a provisional tolerable
    weekly intake of 3 mg of lead per person, equivalent to 0.05 mg/kg

    body-weight.  This level does not apply to infants and children.  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.  The lead in air is probably the contribution that is most
    accessible to action for reducing the total body burden of lead,
    especially where this fraction is large compared with that absorbed
    from food.

    The Committee recognized the provisional nature of this estimate, and
    that for some populations the levels suggested might be exceeded in
    practice, because of local conditions.  They felt that this
    represented no hazard in the short term, but the body load of lead
    should be reduced in the long term.


    Anon., (1966) Lancet, i, 1307

    Beritic, T. & Vandekar, M. (1956) Blood, 2, 114

    Biscaldi, G. P., Robustelli della Cuna, C. & Pollini, G. (1969) Lavoro
    Umano, 21, 385, (abstract 363, "The Kettering Abstracts")

    Blanksma, L. A., Sachs, H. K., Murray, E. F. & O'Connell, M. J. (1969)
    ASCP Meeting, Los Angeles 28 February 1969

    Brit. med. J.,  (1968) Statement 23 November 1968, p. 501

    Brit. std. Spec. (1964) 3788, Tin Coated Finish for Colinary Utensils

    Bruin, A. (de) & Hoolboom, H. (1967) Brit. J. industr. Med., 24, 203

    Butt, E. M. (1960) Metalbinding in Medicine, Martin, J. S., ed.,
    Lippincott Co., Philadelphia

    Catton, M. J., Harrison, M. J. G., Fullerton, P. M. & Kazantzis, G.
    (1970) Brit. mod. J., 2, 80

    Cheftel, H. (1950) Ann. Fals. Fraud., 43, 230

    Chisolm, J. J. jr (1971) Sci. Amer., 224 (2), 15 (February)

    Chisolm, J. J. jr & Kaplan, E. (1968) J. Pediat., 73, 942

    Chow, T. J. & Earl, J. L. (1970) Science, 169, 557

    Cramr, K. & Dahlberg, L. (1966) Brit. J. industr. Med., 23, 101

    Cramr, K. & Selander, S. (1965) Brit. J. industr. Med., 22, 311

    Dingwall-Fordyce, I. & Lane, R. E. (1963) Brit. J. industr. Med., 20,

    Dinischiotu, G. T., Nestorescu, B., Radulescu, I. G., Ioneseu, G.,
    Preda, N. & Ilutza, G. (1960) Brit, J. industr. Med., 17, 141

    Egan,  H. (1972) Conference on lead in the Environment, London
    27 January 1972

    Emmerson. B. T., (1965) Aust. Ann. Med., 14, 295

    FAO/WHO FAO/WHO (1967) Specifications for the Identity and Purity of
    Food Additives and their Toxicological Evaluation: Some Emulsifiers
    and Stabilizers and Certain Other Substances: Tenth Report, FAO
    Nutrition Meetings Report Series, 1967, No. 43; Wld Hlth Org. techn.
    Rep. Ser., 1967, No. 373

    Fleming, A. J. (1964) Arch. Environ. Hlth., 8, 265

    Gibson, Gibson, L. M., Mackenzie, J. G. & Goldberg, A. (1968) Brit. J.
    industr. Med., 25, 40

    Goldberg, L. (1972) Personal communication to WHO

    Goldsmith, J. R, & Hexter, A. C. (1967) Science, 158, 132

    Gordon, N., King. E. & MacKay, R. I. (1967) Brit.med. J., 2, 480

    Greenfield, I. (1957) N.Y. State J. Med., 57, 4032

    Gusev, I. M. (1960) Limits of Concentrations. Book No. 4

    Haas, T.Haas, T., Wiech, A. G., Schaller, K. H., Mache, K. & Valentin,
    H. (1972) Zbl. Bakt. Hyg., I. Abt. Orig. B 155, 341

    Haley, T. J. (1966) Arch. Environ. Hlth., 12, 781

    Hernberg, S. & Nikkanen, J. (1970) Lancet, i, 63

    Howells, G. P. (1967) Int. Cmttee on Radiol. Protection, draft report

    Hunt, W. F. (1970) Chem. Eng. News. June 29, p. 37
    Hursh, J. B., Schraub, A., Sattler, E. L. & Hofmann, H. P. (1969) Hlth
    Phys., 16, 257

    IARC (1972) Monograph on the Evaluation of Carcinogenic Risk of
    Chemicals to Man, Vol. 1.

    Imamura, Y. (1957) Osaka City Mod. J., 3, 167

    IUPAC Inform. Bull. Append. (1965) 10, 71

    Kehoe, R. A. (1964) Arch. Environ. Hlth, 8, 232

    Kehoe, R. A. (1965) USPHS, Public. No. 1440, 51, Washington

    Kehoe, R. A. (1961) Roy. Inst. Publ. Hlth Hyg. J., 24, 101

    Kehoe, R. A., Cholak, J. & Story, R. V. (1940) J. Nutr., 12, 579

    King, B. G. (1971) Amer. J. His. Child., 122, 337

    Klein, M., Namer, R., Harpur, E. & Corbin, R. (1970) New Engl. J.
    Med., 283, 669

    Kospito, L., Byers, R. K, & Shwachman, H. (1967) New Engl. J. Med.,
    276, 949

    Kostial, K., Simonovic, I. & Pisonic, M. (1971) Envir. Res., 4, 360

    Lawther, P. J., Commins, B. T., Ellison, J. M. & Biles, B. (1972)
    Conference on lead in the environment

    Lewis, H. K. (1966) USPHS, Public. No. 1441, 18, Washington

    Lilis, P., Gavrileseu, N., Nestorescu, B., Dumitriu, C. & Roventa, A.,
    (1968) Brit. J. Industr. Med., 25, 196

    Lin-Fu, J. S. (1970) Pediatrics, 45, 720

    Ludwig, J. H., Diggs, D. R., Hesselberg, H. E. & Maga J. A. (1965)
    Amer. industr. Hyg. Ass. J., 26, 270

    Mehani, S. (1966) Brit. J. industr. Med., 23, 112

    Miettinen, J, K. (1972) Unpublished report to WHO

    Moncrieff, A. A., Koumides, O. P., Clayton, B. E., Patrick A. D.,
    Renwick, A. G. C. & Roberts, G. E. (1964) Arch. Dis. Childh., 39, 1

    Monier-Williams, G. M. (1949) Trace Elements in Foods, Chapman & Hall,

    Morgan, J. M., Marshall, W. H. & Miller, R. E. (1966) Arch. Intern.
    Med., 118, 17

    Motto, H. L., Daines, R. N., Chilko, D. M. & Motto, C. K. (1970)
    Environm. Sci. Technol., 4, 231

    Palmisano, P. A., Sneed, R. C. & Cassady, G. (1969) J. Pediat., 75,

    Power, J. G. P., Barnes, R. M., Nash, W. N. C. & Robinson, J. D.
    (1969) Brit. med. J., 3, 336

    Radosevic, Z., Saric, M., Beritic, T. & Knezevic, J. (1961) Brit. J.
    Industr, Med., 18, 222

    Sandstead, H. H., Brill, A. B., Arias, L., Terry, R. T. & Tinnell, L.
    E. (1966) Fed. Proc., 25, 688 (Abstr. No. 2820)

    Schroeder, H. A. & Balassa, J. J. (1961) J. Chron. Dis., 14, 408

    Schroeder, H. A. & Tipton, I. H. (1968) Arch. Environ. Hlth., 17, 965

    Schroeder, H. A., Mitchener, M. & Nason, A. P. (1970) J. Nutr., 100,

    Schwanitz, G., Lehnert, G. & Gebhart E. (1970) Dtsch. med. Wschr., 95,

    Shibko, S. 1. (1972) Personal communication to WHO

    Shy, C. M., Hammer, D. I., Newill, V. A. & Nelson, W. C. (1971)
    Health Hazards of environmental lead, US Environmental Protection
    Agency, Bureau of Air Pollution Sciences, Community Research Branch

    Simpson, J. A., Seaton, D. A. & Adams, J. F. (1964) J. Neurol.
    Neurosurg. Psychiat., 27, 536

    Tepper, L. B. (1963) Arch. Environ. Hlth., 7, 76

    United Kingdom Report (1972) Survey of lead in food, Ministry of
    Agriculture, Fisheries and Food, H.M.S.O. 1972

    United States Public Health Service (1965) Publication No. 999-AP-12
    Survey of lead in the Atmosphere of 3 unknown communities

    Van Esch, G. J., Van Genderen, H. & Vink, H. H. (1962) Brit. J.
    Cancer, 16, 289

    Waldron, H. A. (1966) Brit. J. industr. Med., 23, 83

    Waller, R. E., Commins, B, T. & Lawther, P. J. (1965) Brit. J.
    industr. Med., 22, 128

    Walls, A. D. F. (1969) Brit. med. J., 1, 98

    Weller, C. V. (1915) J. Med, Res. 33, 271

    Wettenberg, L. (1966) Lancet, 1, 498

    WHO (1965) Occup. Hlth Report No. 66

    WHO (1971) International standards for drinking-water, 3rd ed.

    See Also:
       Toxicological Abbreviations
       Lead (EHC 3, 1977)
       Lead (ICSC)
       Lead (WHO Food Additives Series 13)
       Lead (WHO Food Additives Series 21)
       Lead (WHO Food Additives Series 44)
       LEAD (JECFA Evaluation)
       Lead (UKPID)