MONOGRAPH FOR UKPID
LEAD
Grainne Cullen
Alison Dines
Stoyko Kolev
National Poisons Information Service (London Centre)
Medical Toxicology Unit
Guy's & St Thomas' Hospital Trust
Avonley Road
London
SE14 5ER
UK
This monograph has been produced by staff of a National Poisons
Information Service Centre in the United Kingdom. The work was
commissioned and funded by the UK Departments of Health, and was
designed as a source of detailed information for use by poisons
information centres.
Peer review group: Directors of the UK National Poisons Information
Service.
1 SUBSTANCE/PRODUCT NAME
1.1 Origin of substance
Lead rarely occurs in the elemental state. It is present in the
earth's crust at 15 g/ton or 0.002% (depth of crust: 16 km). It occurs
as several ores galena (sulphide ore which is most common), cerussite
(carbonate), mimetite and pyromorphite and anglesite (sulphate). It is
recovered from the ore and purified. Lead also occurs in various
uranium and thorium minerals arising directly from radioactive decay
(Budavari, 1989, Beliles 1994).
1.2 Name
1.2.1 Brand/trade name
1.2.2 Generic name
1.2.3 Synonyms
Metallic lead: lead flake, lead inorganic, lead metal, plumbum.
Lead acetate: dibasic lead acetate, lead (II) acetate, plumbous
acetate, salt of saturn, sugar of lead, lead acetate trihydrate.
Lead chloride: lead dichloride, lead (II) chloride, plumbous
chloride.
Lead chromate: chrome yellow, Cologne yellow, King's yellow, Leipzig
yellow, Paris yellow
Lead dioxide: brown lead, lead peroxide, lead superoxide, lead (IV)
oxide
Lead fluoride: lead difluoride, plumbous fluoride
Lead hydroxide: lead oxide hydrate, basic lead hydroxide
Lead monoxide: lead oxide yellow, plumbous oxide, litharge,
massicot, lead protoxide
Lead tetraoxide: lead oxide, mineral orange, mineral lead, Paris
red, orange lead, red lead, red lead oxide, trilead tetraoxide
Tetraethyl lead: tetraethylplumbane, lead tetraethide
Tetramethyl lead: tetramethylplumbane
1.2.4 Common names/street names
Not applicable.
1.3 Chemical group/family
Lead is a metal atomic weight 207.2, atomic number 82. It has four
naturally occurring isotopes 204 (1.4%), 206 (25.2%), 207 (21.7%) and
208 (51.7%). Valence 2 and 4.
Lead acetate C4H6O4Pb molecular weight 325.28
Lead azide Pb(N3)2 molecular weight 291.26
Lead Borate Pb(BO2)2.H2O
Lead Bromate Br2O6Pb
Lead Bromide Pb Br2 molecular weight 367.04
Lead Butyrate Pb(C4H7O2)2 molecular weight 381.40
Lead chlorate Pb(ClO3)2
Lead chloride PbCl2 molecular weight 278.12. Occurs naturally as the
mineral cotunnite.
Lead chromate (VI) PbCrO4 molecular weight 323.22
Lead dioxide PbO2 molecular weight 239.21
Lead fluoride PbF2 molecular weight 245.21
Lead hydroxide 3PbO.H2O molecular weight 687.59
Lead iodide PbI2 molecular weight 461.05
Lead monoxide PbO molecular weight 223.21
Lead nitrate Pb(NO3)2 molecular weight 331.23
Lead phosphate Pb3(PO4)2 molecular weight 811.54
Lead sulphate PbSO4 molecular weight 303.28. Occurs as the minerals
anglesite and lanarkite.
Lead sulphide PbS molecular weight 239.28. Occurs as the mineral
galena.
Lead tetraoxide Pb3O4 molecular weight 685.63
Tetraethyl lead Pb(C2H5)4 molecular weight 323.45
Tetramethyl lead PbC4H12 molecular weight 267.33
1.4 Substance identifier and/or classification by use
1.5 Reference numbers
Lead CAS 07439/92/1
RTECS OF7525000
EINECS 2311004
Lead acetate CAS 301-04-2
RTECS AI5250000
UN 1616
Lead azide CAS 13424-46-9
RTECS OF8650000
EINECS 2365421
UN 0129
Lead Bromide CAS 10031-22-8
EINECS 2330844
Lead chloride CAS 7758-95-4
RTECS OF9450006
EINECS 2318455
Lead chromate CAS 7758-97-6
RTECS GB2975000
Lead dioxide CAS 1309-60-0
RTECS OG0700000
EINECS 2151745
UN 1872
Lead fluoride CAS 778-34-62
RTECS OG1225000
EINECS 2319988
Lead hydroxide CAS 19783-14-3
EINECS 2433103
Lead iodide CAS 10101-63-0
EINECS 2332569
Lead monoxide CAS 1317-36-8
RTECS OG1750000
EINECS 2152670
Lead nitrate CAS 10099-74-8
RTECS OG2100000
UN 1469
Lead phosphate CAS 7446-27-7
RTECS OG3675000
Lead sulphate CAS 7446-14-2
RTECS OG4375000
Lead sulphide CAS 1314-87-0
RTECS OG4550000
EINECS 2152466
Lead tetraoxide CAS 1314-41-6
RTECS OG5425000
Tetraethyl lead CAS 78-00-2
RTECS TP4550000
Tetramenthyl lead CAS 75-74-1
RTECS TP4725000
UN 1649
1.6 Manufacturer
Name
Address
Telephone
Fax
1.7 Supplier/importer/agent/ licence holder
Name
Address
Telephone
Fax
1.8 Presentation
1.8.1 Form
1.8.2 Formulation details
1.8.3 Pack sizes available
1.8.4 Packaging
1.9 Physico-chemical properties
Physical state
Metallic lead: metal - highly lustrous when freshly cut, tarnishes
upon exposure to air. Very soft and malleable, easily melted, cast,
rolled and extruded
Lead acetate: colourless crystals or white granules or white powder
Lead azide: needles or white powder
Lead borate: white powder
Lead bromate: colourless crystals
Lead butyrate: colourless scales or viscid mass
Lead chlorate: coulourless deliquescent crystals
Lead chloride: white powder
Lead chromate: yellow or orange-yellow powder
Lead dioxide: dark brown powder
Lead fluoride: white to colourless crystals
Lead hydroxide: white powder
Lead iodide: bright yellow powder
Lead monoxide: reddish to reddish-yellow tetragonal crystals or yellow
orthorhombic crystals
Lead nitrate: white or colourless translucent crystals
Lead phosphate: white powder
Lead sulphate: white crystalline powder
Lead sulphide: black powder
Lead tetraoxide: bright red powder
Tetraethyl lead: colourless liquid
Tetramethyl lead: colourless liquid
Colour
Metallic lead: Bluish - white, silvery, grey
Lead acetate: colourless or white
Lead azide: white
Lead borate: white
Lead bromate: colourless
Lead butyrate: colourless
Lead chlorate: colourless
Lead chloride: white
Lead chromate: yellow or orange-yellow
Lead dioxide: dark brown
Lead fluoride: white to colourless
Lead hydroxide: white
Lead iodide: bright yellow
Lead monoxide: reddish to reddish-yellow or yellow
Lead nitrate: white or colourless
Lead phosphate: white
Lead sulphate: white
Lead sulphide: black
Lead tetraoxide: bright red
Tetraethyl lead: colourless
Tetramethyl lead: colourless
Odour
Tetraethyl lead: characteristic fruity odour
Tetramethyl lead: characteristic fruity odour
Viscosity
Metallic lead: of molten lead 3.2 centipoises (cp) at 327°C, 2.32 cp
at 400°C, 1.54 cp at 600°C, 1.23 cp at 800°C.
Solubility in water and organic solvents
Metallic lead: insoluble in hot or cold resistant to tap water,
attacked by pure water, resistant to hydrofluoric acid, brine, organic
solvents. Soluble in nitric acid and hot concentrated sulphuric acid.
Lead acetate: 1 g dissolves in 1.6 ml water, 0.5 ml boiling water, 30
ml alcohol; freely soluble in glycerol
Lead azide: solubility in water 0.023% at 18°: 0.09 at 70° freely
soluble in acetic acid, insoluble in ammonium hydroxide
Lead borate: insoluble in water, soluble in dilute nitric acid
Lead bromate: slightly soluble in cold water, moderately in hot water
Lead butyrate: insoluble in water, soluble in dilute nitric acid
Lead chlorate: soluble in 0.7 part water, freely in alcohol
Lead chloride: soluble in 93 parts cold water, 30 parts boiling water,
readily soluble in solution of ammonium chloride, ammonium nitrate,
alkali hydroxides, slowly in glycerol
Lead chromate: one of the most insoluble salts (0.2 mg/L H2O),
soluble in solutions of fixed alkali hydroxides, soluble in dilute
nitric acid
Lead dioxide: insoluble in water, soluble in hydrochloric acid with
the evolution of chlorine, soluble in dilute nitric acid (in the
presence of hydrogen peroxide, oxalic acid or other reducers), soluble
in alkali iodide solutions with liberation of iodine, soluble in hot
caustic alkali solutions
Lead fluoride: solubility in water 0.057 g/100 ml water at 0°: 0.065
g/100 ml water at 20° - the solubility increases in the presence of
nitric acid or nitrates
Lead hydroxide: insoluble in water, soluble in dilute acids and fixed
alkali hydroxides
Lead iodide: 1 g dissolves in 1350 ml cold water or 230 ml boiling
water, soluble in concentrated solutions of alkali iodides, freely
soluble in solution of sodium thiosulphate, soluble in 200 parts cold
or 90 parts hot aniline, insoluble in alcohol or cold hydrochloric
acid
Lead monoxide: insoluble in water and alcohol, soluble in acetic acid,
soluble in dilute nitric acid, soluble in warm solutions of fixed
alkali hydroxides
Lead nitrate: 1 g dissolves in 200 ml cold or 0.75 ml boiling water,
2500 ml absolute alcohol, 75 ml absolute methanol, insoluble in
concentrated nitric acid
Lead phosphate: insoluble in water and alcohol, soluble in nitric acid
and fixed alkali hydroxides
Lead sulphate: soluble in about 2225 parts water, more soluble in
dilute hydrochloric acid or nitric acid, less in dilute sulphuric
acid, soluble in sodium hydroxide, ammonium acetate or tartrate
solution, soluble in concentrated hydriodic acid, insoluble in alcohol
Lead sulphide: insoluble in water, soluble in nitric acid and hot
dilute hydrochloric acid
Lead tetraoxide: insoluble in water or alcohol, soluble in excess
glacial acetic acid, in hot hydrochloric acid with evolution of
chlorine, soluble in dilute nitric acid in the presence of hydrogen
peroxide
Tetraethyl lead: practically insoluble in water, soluble in benzene,
petroleum ether and gasoline, slightly soluble in alcohol
Important chemical interactions
Metallic lead: reacts with hot concentrated nitric acid, with boiling
concentrated hydrochloric or sulphuric acid. Can react vigorously with
oxidising materials. Forms a violent reaction on ignition with
chloride trifluoride, concentrated hydrogen peroxide and ammonium
nitrate. Ground mixtures of sodium carbide and lead can react
vigorously.
Lead chloride: incompatible with strong oxidisers, hydrogen peroxide,
acids.
lead monoxide: incompatible with chlorinated rubber, chlorine,
ethylene, hydrogen trisulphide, metals, peroxy formic acid, glycerol.
Tetramethyl lead: dangerous when exposed to oxidisers
Major products of combustion/pyrolysis
Many inorganic lead compounds give off toxic lead fumes on combustion
(lead chloride, lead chromate, lead sulphate, lead sulphide).
Explosion limits
Metallic lead is moderately explosive in the form of dust when exposed
to heat or flame.
Tetraethyl lead and tetramethyl lead are dangerous when exposed to
heat or flame.
Flammability
Tetraethyl lead and tetramethyl lead are flammable.
Boiling point
Metallic lead: 1740°C
Lead chloride: 950°C
Lead fluoride: 1293°C
Tetraethyl lead: 198°-202°C
Tetramethyl lead: 110°C
Melting point
Metallic lead: 327.4°C
Lead bromide: 373°C
Lead butyrate: 90°C
Lead chloride 501°C
Lead chromate: 844°C
Lead fluoride: 824°C
Lead monoxide: 888°C
Lead phosphate: 1014°C
Lead sulphate: 1170°C
Tetraethyl lead: 125°-150°C
Tetramethyl lead: 18°C
Density
Metallic lead: 11.34
Lead chromate (VI): 6.3
Lead dioxide: 9.38
Lead formate: 4.63
Lead hydroxide: 7.41
Lead iodide: 6.16
Lead monoxide: 9.53
Lead nitrate: 4.53
Lead oxalate: 5.28
Lead sulphate: 6.2
Tetraethyl lead: 1.653
Flash point
Tetraethyl lead: 200°F
Tetramethyl lead: 100°F
1.10 Hazard/risk classification
1.11 Uses
Used as construction material for tank linings, piping and other
equipment handling corrosive gases and liquids, used in the
manufacture of sulphuric acid, petroleum refining, halogenation,
sulphonation, extraction, condensation; for X-ray and atomic radiation
protection; manufacture of tetraethyl lead, pigments for paints and
other organic and inorganic lead compounds; bearing metal and alloys;
storage batteries; in ceramics, plastics and other lead alloys; in the
metallurgy of steel and other metals (Budavari, 1989).
Lead acetate is used in dyeing and printing cottons, in the
manufacture of lead salts, in varnishes, chrome pigments, manufacture
of insecticides, as a colour additive in hair dyes, in small amounts
in some explosives and as an astringent in some lotions. It was
previously used in medicine in poultices and washes for the treatment
of poison ivy inflammation and in lotions for treatment of bruises.
Lead azide is used as a primer in explosives.
Lead carbonate is used as a white pigment in oil paints and water
colours, as a component of cement, putty and ceramics and in the
manufacture of lead carbonate paper.
Lead chloride is used in the preparation of lead salts and lead
chromate pigments, in solder and fluxes and in some flame retardants.
Lead chromate is used as a pigment in oil and water colours, printing
fabrics, decorating china and porcelain, in chemical analysis or
organic substances and in traffic paints.
Lead dioxide is used as an electrode in batteries, oxidising agent in
manufacture of dyes, manufacture of rubber substances, manufacture of
pigments.
Lead fluoride is used in electronic and optical applications and in
the manufacture of lead compounds, glass and underwater paints.
Lead monoxide is used in ointments and plasters, glazing pottery and
in lead glass. It is also used in oil refining, in the manufacture of
paints and inks.
Lead nitrate is used in the manufacture of matches and special
explosives, in dyeing and printing textiles, in the manufacture of
lead compounds, nylon, polyesters and rodenticides.
Lead phosphate is used as a stabilizer for plastics.
Lead sulphate is used as a pigment, in galvanising batteries, in
lithography, weighting fabrics.
Lead sulphide is used for glazing earthenware.
Inorganic lead compounds - tetraethyl lead and tetramethyl lead are
used as antiknocking additives in petrol.
1.12 Toxicokinetics
1.12.1 Absorption
In adults approximately 5% to 10% of an ingested lead dose is absorbed
in the gut, the remainder appears in the faeces. In children
gastrointestinal absorption of lead is higher and may be as much as
40%. Gastric acid solubilizes lead salts and lead absorption occurs in
the small bowel by both active and passive transport (Ellenhorn and
Barceloux 1988, Tsuchiya 1986). Absorption may be augmented in
individuals with iron, zinc or calcium deficiency (Poisindex 1994).
Heard and Chamberlain (1982) demonstrated that lead absorption
decreases if equivalent doses of calcium and phosphate are added in
human volunteer studies.
Lead may also be absorbed via lungs. Absorption of inorganic lead may
depend on particulate size and physical state of the compound
(Tsuchiya 1986). It is estimated that between 50% and 70% of an
inhaled dose is absorbed if the particle size (less than 1 µm) allows
the material to reach the alveoli (Ellenhorn and Barceloux 1988). This
is the primary route of absorption of organic lead.
There is some evidence to suggest that inorganic lead may be absorbed
via skin (Florence et al 1988). However in this study increases in
lead levels in sweat and saliva were reported but there was no
corresponding increase in blood lead levels or urine lead levels. It
was postulated that inorganic lead absorbed through skin was
transported in plasma and rapidly concentrated into the extracellular
fluid pool of sweat and saliva without significant uptake by the
erythrocytes and with a very low transient concentration in the
plasma. Organic lead however is absorbed via skin in sufficient
quantities to produce toxicity (Ellenhorn and Barceloux 1988).
1.12.2 Distribution
To summarise, absorbed lead is transported by blood and initially
distributed in various organs and tissues. It is then gradually
redistributed to form an exchangeable compartment (blood and soft
tissues) and a storage compartment, essentially bone (Tsyuchi 1986).
With continuing exposure the lead which is at first only loosely
deposited in bone, gradually becomes fixed to bone probably as inert
and insoluble lead phosphate. Lead deposits in the area of the
skeleton which are growing most rapidly. These areas include the
radius, tibia and femur which are the most metabolically active. The
hypermineralisation is reflected in the densities that are seen as
characteristic lead lines observed on X-ray. The width of the lead
lines is related to the duration of the exposure. These lines reflect
"bone growth arrest" not deposition.
In healthy humans the kinetics of lead metabolism fit a
three-compartment model. The first compartment includes the blood.
About 95% of the lead in the circulation exists in the erythrocytes
where it has a half life of 35 days and distributes into the soft
tissues or bone stores. Hence blood lead levels may not reflect the
total body lead burden (Ellenhorn and Barceloux 1988). This first
compartment receives lead absorbed from the gut, delivers some of it
to the urine and communicates with the other two pools.
The second compartment is the soft tissues, i.e. kidney, liver,
nervous tissue, about 10% of the total body lead burden equilibrates
here where the half life is 40 days with distribution of some of it to
hair, nails, sweat, saliva, bile and other digestive secretions.
The third compartment, the skeleton, contains the vast bulk of the
total body burden, here lead has a very long half life although bones
may differ in their rates of lead turnover (Rabinowitz et al 1976).
Bones are the major depository for lead in the body with about 90% of
the total lead body burden existing in the skeleton. The half life of
lead in bone is approximately 20 to 30 years. Some equilibration
between bone and blood lead does occur. Up to 70% of blood lead may
derive from the bone.
The lead content of dense human bone increases steadily with age
whereas in spongy bone lead reaches a plateau or even decreases.
1.12.3 Metabolism
Inorganic lead is not metabolized. Alkyl lead compounds, however, are
oxidized by the hepatic P450 system. Experimental studies have shown
that tetraethyl lead is converted to triethyl lead and inorganic lead.
Triethyl lead is relatively stable and becomes rapidly distributed
between brain, liver, kidney and blood (Reynolds et al 1993).
1.12.4 Elimination
About 90% of ingested lead is eliminated unabsorbed through faeces
(Tepper and Levin, 1972). Absorbed lead is excreted mainly in the
urine (about 76%); other routes are gastrointestinal secretions (about
16%) and hair, nails and sweat (< 8%). The rate of biliary excretion
in man is not known. The mechanism of urinary excretion appears to be
essentially glomerular filtration with some renal tubular resorption.
With elevated blood levels, excretion may be augmented by trans
tubular transport (Reynolds et al 1993).
Lead is also excreted in human milk in concentrations of up to 12 mg/L
(Klaassen, 1980).
1.12.5 Half-life
The total body burden of lead may be divided into at least two kinetic
pools, which have different rates of turnover. The larger and
kinetically slower pool is the skeleton with a half life of more than
20 years, and a much more labile soft tissue and a rapidly
exchangeable bone fraction pool with a half life 19-21 days. Other
studies indicate that mean retention of lead in the blood and soft
tissues is about 3 weeks to one month and in the bone about five years
(Klaassen, 1980).
1.12.6 Special populations
Children appear to be more susceptible than adults to the toxic
effects of lead because of incomplete development of the blood brain
barrier, greater intestinal absorption of lead and a tendency to put
objects or their hands into their mouths thereby increasing ingestion
of contaminated substances. In addition, they have a smaller
proportion of dense bone tissue than adults and this prevents the
transfer of the absorbed lead into bone, it remains in the soft
tissues where it produces toxic effects (Knodel, 1995).
Disproportionate numbers of children from lower socioeconomic
backgrounds have high lead levels. This may be because they live in
older poorly maintained housing where old lead paint and lead water
pipes may remain (Bellinger et al 1989).
It is thought that millions of workers may be exposed to lead in the
United States and Europe (Cullen et al 1983). The highest and most
prolonged lead exposures have been seen among workers in the lead
smelting, refining and manufacturing industries. Potentially high lead
levels may also occur in steel welding or cutting operations,
construction, rubber products and plastics industries, printing
industries and other industries requiring flame soldering of lead
solder (Clement International Corporation 1993).
There have been reported cases of lead toxicity in occupations
including stained glass workers (Baxter et al 1985), mechanics
(Goldman et al 1987), painters (Ennever et al 1995), in the
manufacture of batteries and lead smelting (Williamson and Teo 1986),
manufacture of lead pigments (Davies 1984) and workers on firing
ranges (Chau et al 1995).
There is some evidence to suggest that people with iron-deficiency
anaemia are more prone to lead toxicity and that lead exposure impairs
iron utilization for haem biosysnthesis and therefore exacerbates iron
deficiency. Also calcium deficiency greatly enhances lead absorption
and during periods of low calcium, lead may be mobilised from tissue
stores particularly bone. Lead poisoning may also recur in the
presence of osteoporosis indicating that bone can be a significant
source of lead level elevation in conditions associated with
accelerated resorption (Shannon et al 1988).
Some ethnic groups may be more at risk of lead poisoning because of
the use of traditional remedies (Middleton 1989) or cosmetics.
In some groups the inhalational abuse of leaded petrol can be
relatively common (Burns and Currie 1995).
2 SUMMARY
3 EPIDEMIOLOGY OF POISONING
Lead has been used both industrially and domestically since
pre-historic times. Since lead and lead compounds are utilized in a
wide variety of industrial and domestic situations, many people and
all age groups may potentially be exposed and could be at risk of lead
toxicity.
The general population is exposed to lead in ambient air, many foods,
drinking water and dust. Human exposure to lead above baseline levels
is common. Exposure may occur from living in an urban environment,
particularly in areas with high traffic flow, or near a lead industry
(e.g. lead smelters), consumption of produce from lead contaminated
soil, renovation of homes containing lead paint, pica, contact with
interior lead paint dust, smoking and wine consumption.
Occupational exposure
Since the industrial revolution environmental concentrations of lead
have risen steadily (Landrigan 1983). It is thought that millions of
workers may be exposed to lead in the United States and Europe (Cullen
et al 1983).
The highest and most prolonged lead exposures have been seen among
workers in the lead smelting, refining and manufacturing industries.
Potentially high lead levels may also occur in steel welding or
cutting operations, construction, rubber products and plastics
industries, printing industries and other industries requiring flame
soldering of lead solder (Clement International Corporation 1993).
There have been reported cases of occupational lead toxicity in
stained glass workers (Baxter et al 1985), mechanics (Goldman et al
1987), painters (Ennever et al 1995), and in those involved in the
manufacture of batteries and lead smelting (Williamson and Teo 1986),
manufacture of lead pigments (Davies 1984) and operating firing ranges
(Chan et al 1995).
In work the major routes of lead exposure are inhalation and ingestion
involving both lead dusts and fumes. Airborne dusts settle onto food,
water, clothing and other objects and may therefore be transferred to
the mouth. Workers involved in the production of petrol additives,
tetraethyl lead and tetramethyl lead are exposed to both inorganic and
organic lead. The major potential hazard to these workers appears to
be from dermal exposure since organic lead may be absorbed through the
skin (Clement International Corporation 1993).
There have been many epidemiological studies on blood lead
concentrations in exposed workers and people living in urban and rural
areas. In a large health screening programme within the USA during
1976-80 over 27,000 residents aged 6 months to 74 years were examined.
Blood lead concentrations were examined in a subsample of 9933
individuals and yielded a mean value of 130 µg/L (0.67 µmol/L). In
another study residents in the centre of large urban areas were found
to have blood lead levels of 149 µg/L (0.72 µmol/L), while in rural
areas it was 130 µg/L (0.62 µmol/L). Male workers in occupations with
a high potential for lead exposure had mean blood lead levels of 162
µg/L (0.78 µmol/L) for non-drinkers and non-smokers and 197 µg/L (0.95
µmol/L) for drinkers or smokers. During this study a true decrease of
37% in blood lead levels was seen (WHO 1995).
Non-occupational exposure
Exposure of the general population to lead is most likely to occur
through the ingestion of contaminated food or drinking water and by
the inhalation of lead particulates in ambient air. Direct inhalation
of lead accounts for only a small part of the total human exposure,
mainly from lead that is adsorbed to soil and inhaled as dust. Fruits,
vegetables and grains may contain levels of lead in excess of
background levels as a result of direct deposition of lead onto plant
surfaces or plant uptake of lead from soils (Clement International
Corporation 1993, Carrington at al 1993). Foods may also become
contaminated during processing (Kocak et al 1989) and food in lead
soldered cans (which are uncommon) may contain high lead levels.
A new European safety limit was introduced in 1995 which recommended
that lead levels in tapwater should not exceed 10 µg/L. It is
estimated that as many as 20% households in Great Britain exceed this
safety limit, where a survey in 1994 found that 3.2% of households
failed the old safety margin which was 50 µg/L (Pearce 1995).
Adults and children may be at risk of lead poisoning from the use of
lead utensils (Roberge and Martin 1992), lead glazed ceramics, lead
crystal (Graziano and Blum 1991, Zuckerman 1991), lead foil on wine
bottles (Marks and Taylor 1987) the use of contaminated health foods
(Crosby 1977), traditional remedies (Middleton 1989), aphrodisiacs
(Brearley and Forsythe 1978) or cosmetics (Anon 1985) and crayons
(Wilks et al 1994).
There have also been cases of lead contamination of heroin and lead
toxicity has resulted from the intravenous use of heroin (Montefort et
al 1987, Parras et al 1989) and lead contaminated methamphetamine
(Norton et al 1989).
The abuse of petrol by inhalation is relatively common in some groups
and sniffing leaded petrol can result in lead toxicity (Burns and
Currie 1995).
Pica
Pica (from the Latin for magpie) is the compulsive eating of
non-nutritional substances. It may occur either through deliberate
ingestion or through the mouthing of objects or hands. Pica is common
in young children and it is thought that pica may explain the higher
blood lead levels that occur in young children compared to adults
(Norman and Bordley 1995). House dust is probably the most important
source relevant to pica (Gallacher et al 1984). There may be a variety
of sources for high concentrations of lead in house dust, older houses
may contain a lot of leaded paint (Shannon 1989) and indeed children
may eat flakes or chips of peeling lead paint (Goldfrank et al 1990),
children may live near a lead industry or in an area of heavy traffic
(Gallacher et al 1984) and parents who work in lead industries may
bring home lead dust on their clothing, skin, cars etc (Landrigan
1983). Children may also swallow small lead weights, lead bullets,
toys etc.
Disproportionate numbers of children from lower socioeconomic
backgrounds have high lead levels (Bellinger et al 1989, Guinee 1972).
This may be because they live in older poorly maintained housing where
old lead paint may remain and lead pipes may be used in plumbing or
because of poor nutrition. It has been found that independent of
socioeconomic status, children who live in older housing may be more
at risk of lead toxicity (Paulozzi et al 1995, Rosen 1995).
It is estimated that in the UK 26.9% of children have blood lead
concentrations >100 µg/L (0.48 µmol/L) and 0.5% children have blood
lead concentrations of >250 µg/L (1.22 µmol/L). In London 55.5% of
children are estimated to have blood lead concentrations >100 µg/L
(0.48 µmol/L) and 3.9% with blood lead concentrations >250 µg/L (1.22
µmol/L) (Millstone and Russell 1995).
There were 139 deaths related to lead poisoning in the United States
between 1979 and 1988. The death rate was higher in older age groups,
higher amongst males than females and greatest among blacks and
persons living in the southeastern states. Eleven deaths were reported
in children, 9 of these were younger than 3 years old. Three ingested
leaded paint, one ingested a lead object and one ingested a home
remedy. Of the 25 people in the older age groups in which a lead
source was identified 20 ingested illegally produced alcohol
(moonshine), two inhaled leaded petrol and three had occupational
exposures (Staes et al 1995).
4 MECHANISM OF ACTION/TOXICITY
4.1 Mechanism
Bone marrow
The anaemia caused by lead results from two basic red cell defects,
shortened life-span and impaired haem synthesis. The mechanism by
which synthesis of the red cell pigment haem is inhibited by lead
involves at least two enzymes, a cytoplasmic one (delta-aminoleuvinic
acid dehydrogenase - ALAD) at the beginning of haem synthesis and a
mitochondrial one, ferrochelatase, at the end of synthesis. The
inhibition of ALAD is observed at lead blood concentrations as low as
100 µg/L (0.49 µmol/L). The conversion of ALA to porphobilinogen is
blocked, resulting in plasma concentrations of 0.2 to 1.4 µg/ml
(normally 0.1 µg/ml) and ALA urinary concentrations of 50 µg/L or
more. The inhibition of ferrochelatase which plays a role in the
insertion of Fe 3+ into protoporphyrin during the formation of haem in
bone marrow occurs at a slightly higher lead blood concentration (140-
200 µg /L). This inhibition results in an increase in the free
erythrocyte protoporphyrin (FEP). The increases in ALA and FEP are
earlier indicators of anaemia which is generally not observed until
the blood concentration reaches 40 µg/L. The red blood cell zinc
protoporphyrin blood test measures the effects of lead on bone marrow
occurring in the preceding 120 days and begins to occur in children at
150 µg/L (0.72 µmol/L) in women at 200 µg/L (0.97 µmol/L) and in men
at 300 µg/L (1.45µmol/L).
Indicators of lead exposure relate to the inhibition by lead of the
synthesis of haem. The inhibition of delta-aminoleuvinic acid
dehydrase (ALAD) an enzyme involved in the biosynthesis of cytochromes
and haemoproteins and porphyrins leads to an increase in levels of
delta-aminoleuvinic acid (ALA) in blood and urine. The discovery that
lead forms a specific complex with the substrate ALA indicates this
may be the inhibitory action. The blood and urine levels of
coproporphyrin III and free erythrocyte protoporphyrins (FEP) are also
usually elevated. The FEP combine with zinc in the blood to form zinc
protoporphyrin (ZPP) which is the moiety assayed (Hathaway et al 1991,
Gosselin 1984).
ALAD remains active in the circulating red cell, but the activity of
ferrochelatase disappears as soon as the red cells reach circulation,
along with the disappearance of the mitochondria. From the usual
measurements of ALAD in peripheral blood and the substrate
erythroporphyrin (EP) from changes in ferrochelatase activity, the
direct action of lead on circulating blood is evaluated very early.
However the inhibition of medullary erythroblastic ferrochelatase from
the action of lead in the bone marrow is evidenced only indirectly by
a late and gradual increase in EP corresponding to the gradual
maturation and slow release of mature red cells carrying
protoporphyrin from the marrow to the circulating blood. This is why
EP concentrations may continue to rise after all other biologic
measurements of lead effects have improved or returned to normal and
long after environmental lead exposures have ceased (Beliles 1994).
One study has found a metallothionen-like lead containing protein
within human erythrocytes which may act to sequester lead into a
non-bioavailable form hence protecting the body from lead toxicity. In
this study two lead poisoned patients were examined. One patient who
had a blood lead concentration of 1800 µg/L (8.69 µmol/L) had 70% of
their erythrocyte lead bound to this protein and remained
asymptomatic. The other patient had a blood lead concentration of 1610
µg/L (7.77 µmol/L) with only 20% of erythrocyte lead bound to this
protein and showed signs of lead toxicity. It is not clear if the
second patient had less metallothionen-like protein or a much higher
total lead body burden than the first patient (Church et al 1993).
CNS
The exact nature of the effect on the central nervous system is
unknown but it may involve neurotransmitters. In one study rats of
various ages were fed lead acetate. Lead values in the brains of all
rats were similar. There were decreases in brain levels of
noradrenaline, GABA, and glutamate decarboxylase and increases in
levels of glutamate, glutamine and asparagine, tyrosine and monoamine
oxidase in the brains of rats prenatally or 5 days postnatally exposed
to lead. Brain ammonia, alanine, aspartic acid and dopamine levels
were not affected by the prenatal or 5 day postnatal treatment.
Exposure of 5 week old rats to lead did not affect the brain
catecholamine and amino acid levels. These results suggest that the
brains of young rats are more sensitive to lead exposure than those of
adult rats.
Another study showed alterations in the concentrations of the
transmitters noradrenaline and dopamine in addition to changes in the
activities of the enzyme tyrosine hydroxylase and
phenylethanolamine- N-methyl transferase. The activity of choline
acetyltransferase was also altered.
Segmental demyelination of peripheral nerves causes decreased nerve
conduction velocities in adults. Lead crosses the blood-brain barrier
disrupting mitochondrial function. Other studies have suggested that
the permanent neuropsychological deficits seen after exposure to high
lead concentrations may be due to impairment of astrocyte function
especially in their capacity to regulate the ionic and amino acid
concentrations in the extracelluler milieu, brain energy metabolism
and cell volume. These functions are under monoaminergic control
(Beliles 1994).
Other
In children exposed to lead, elevations in urinary catecholamine
metabolites have been shown (Beliles 1994). Significant increases in
plasma noradrenaline and adrenaline have also been found in children
with chronic lead poisoning which suggests that this may play a part
in the mechanism of hypertension and hyperactivity (de Castro 1990).
Lead may be associated with increased serum lipid levels. High doses
in animal and human studies may have a direct toxic action on the
heart. There may also be evidence to suggest that lead at low doses
may cause altered myocardial contractility. Schwartz (1995) carried
out meta-analysis of epidemiological studies and found a relationship
between blood lead and systolic BP in males in that a decrease of
blood lead from 10 mg/L to 5 mg/L is associated with a decrease in BP
of 1.25 mmHg. Animal data suggests a mechanism i.e. disturbance of
calcium messenger system regulation of blood pressure (there may be
modulation of BP through control of vascular tone).
4.2 Toxic dose/Levels
In children, blood lead concentrations (prior to any treatment or
other action to abate exposure) of:-
a) greater than 250µg/L (1.2µmol/L) may require chelation therapy
although there is no consensus.
b) greater than 400µg/L (1.9µmol/L) require treatment with either
succimer or sodium calciumedetate.
c) greater than 600µg/L (2.9µmol/L) are a medical emergency and
require immediate chelating agent, sodium calciumedetate being the
treatment of choice.
Pharmacological intervention is not needed for blood lead
concentrations of less than 250µg/L (1.2µmol/L).
In adults, blood lead concentrations (prior to any treatment or other
action to abate exposure) of:-
a) greater than 400µg/L (1.92µmol/L) may require treatment with
chelating agents if the patient is symptomatic, although this is
unlikely.
b) greater than 800µg/L (3.86µmol/L) will require treatment with
chelating agents if the patient is symptomatic which is quite likely.
c) greater than 1200µg/L (5.79µmol/L) require treatment with chelating
agents as patients are very likely to have symptoms.
Lead levels in preindustrial humans has been estimated at around 0.16
µg/L (0.8 nmol/L). This estimate is 50-200 fold lower than the lowest
reported lead levels of contemporary humans in remote regions of the
Northern and Southern hemispheres and approximately 600 times lower
than the upper blood lead concentration of 100 µ/L (0.48 µmol/L) that
is currently considered acceptable in children (Flegal and Smith
1992).
5 FEATURES OF POISONING
5.1 Acute
5.1.1 Ingestion
Adults: The most common acute effect is gastrointestinal colic. This
is characterised by nausea, vomiting, anorexia, and diffuse paroxysmal
abdominal pain. Acute exposures have also resulted in malaise,
convulsions, coma, encephalopathy, hepatic and renal damage, anaemia,
hypertension and bradycardia (Carlton et al 1987, Khan et al 1983,
Parras et al 1989).
Children: Ingestion of lead or lead salts may result in a metallic
taste in the mouth, severe abdominal pain or cramping, vomiting and
diarrhoea often with discoloured stools. There may also be anorexia,
irritability, malaise, fatigue, muscle weakness and shock.
Neurological effects include headache, insomnia, drowsiness and more
rarely convulsions.
5.1.2 Inhalation
Lead does not cause any local irritation but may cause the same
effects as for ingestion if enough is inhaled.
Organic lead
Organic lead compounds can cause severe toxicity by inhalation, the
latent period between acute exposure and the onset of symptoms varies
from a few hours in the more severe cases to as much as ten days. The
initial effects are anorexia, vomiting, insomnia, tremor, weakness,
fatigue, nausea, headache, aggression, depression, irritability,
restlessness, hyperactivity, confusion and memory impairment. From the
onset of the initial effects there may be a delay of hours or even
days before acute mania, convulsions, delirium, fever and coma.
Apparent complete recovery can take two to six months to occur and
some effects may persist for some time (Grandjean and Nielsen 1979).
5.1.3 Dermal
Inorganic lead
Inorganic lead salts may cause mild local irritation but systemic
toxicity from this route has not been described.
Organic lead
Acute poisoning may occur from dermal exposure to organic lead
compounds. There is often a latent period between exposure and onset
of symptoms. Effects within 24 hours indicate a severe exposure while
in mild cases it may take up to 14 days before effects are apparent.
Mild effects include anxiety, irritability, insomnia, anorexia,
nausea, vomiting, metallic taste, pallor, mild diarrhoea, dizziness
and lack of coordination.
Moderate effects include disorientation, hyperexcitability, tremor,
twitching, chorea, hyperreflexia, bradycardia, hypotension,
hypothermia and nystagmus.
Severe effects include delusions, hallucinations, mania, decreased
nerve conduction velocity, convulsions, cerebral oedema, coma and
death.
5.1.4 Ocular
Inorganic lead
Lead metal foreign bodies in the eye are unlikely to cause any toxic
effects but may cause mechanical injury.
Lead chloride and lead sulphate placed in the anterior chamber of
rabbits have caused a moderate purulent reaction and general
inflammation of the eye. Lead acetate was formerly applied in aqueous
solutions to the eye for astringent effect but induced opacities and
lead encrustation of the cornea and conjunctiva. Lead sulphide (from
the eye cosmetic surma) has caused minute conjunctival abrasions but
no toxic injury to the eye (Grant and Schuman 1993).
Organic lead
Gasoline containing tetraethyl lead applied to rabbit eyes caused
immediate pain and blepharospasm. When the application is repeated ten
times in the course of 5 minutes under local anaesthesia it produced
conjunctival hyperaemia and moderate flocculent discharge but no
damage to the cornea. Scanning electron microscopy has revealed
changes in the corneal epithelium from exposure to leaded gasoline
(Grant and Schuman, 1993).
5.1.5 Other routes
Inorganic lead
Lead toxicity has occurred by the intravenous route by the use of
contaminated heroin (Montefort et al 1987, Parras et al 1989).
Systemic lead toxicity has also occurred from gunshot wounds and the
presence of lead shot in the synovial fluid. Lead toxicity from this
route may take many years to manifest (Manton 1994). An insoluble lead
phosphate coat is formed around retained pellets and lead poisoning is
a risk if the pellets are in a position where the coating may be
eroded (e.g. a joint).
5.2 Chronic toxicity
5.2.1 Ingestion
Inorganic lead
Adult: effects from chronic exposure include gastrointestinal signs
such as nausea, vomiting, abdominal pain, metallic taste, anorexia and
general feeling of malaise or fatigue. With longer exposures the
patient may also have joint pain, progressive fatigue and anaemia.
There is a strong association between elevated blood lead
concentrations and anaemia which is characterised as hypochromic
monocytic with a decrease in mean corpuscular haemoglobin and
stippling of erythrocytes and reticulocytes. There may also be altered
renal and hepatic function. Motor weakness may progress to paralysis
of the extensor muscles of the wrist (wrist drop) and less often the
ankles (foot drop). Adults may have a bluish gingival "lead-line".
Encephalopathy rarely occurs in adults except from exposure to organic
lead.
Child: clinical effects from chronic exposures include severe
gastrointestinal disturbances with constipation, abdominal pain and
tenderness. Other effects include anaemia, weakness, pallor, anorexia,
insomnia, renal hypertension and mental fatigue. There may be a bluish
"lead line" on the gums although this is not often present. Lead may
also be drawn to areas of the skeleton that grow most rapidly and in
some cases hypermineralisation of the radius, tibia and femur can be
seen on X-ray with the development of metaphyseal lines (Goldfrank et
al 1990).
Children with increased lead body burden may be asymptomatic but it is
likely that they have metabolic effects involving haem synthesis, red
cell nucleotide metabolism, vitamin D and cortisol metabolism and
renal function (Piomelli et al 1984).
Neuromuscular dysfunction may result in signs of motor weakness and
paralysis of the extensor muscles of the wrist and ankles.
Encephalopathy can occur in patients with previously mild symptoms.
Effects include vomiting, confusion, ataxia, apathy, bizarre behaviour
and coma and convulsions due to cerebral oedema.
Nephropathy may occur and is characterised by albuminuria, glycosuria
and renal tubular acidosis.
Chronic low level exposures in children are linked with decreased
intelligence and behavioural and learning disorders. There is evidence
to suggest that growth may be inhibited. Thyroid and adrenal functions
may also be inhibited.
Children with chronically elevated blood lead levels of 600-1000 µg/L
(2.90-4.83 µmol/L) showed squint, foot drop, albuminuria and delayed
growth. An inverse correlation was found between height, weight and
chest circumference with blood lead concentration (Angle et al 1989).
In another study there was evidence of decreased insulin-like growth
factor and diminished 24 hour secretion of growth hormone in children
with lead levels >400 µg/L (1.93 µmol/L). These children also showed
signs of growth retardation. With chelation therapy normal growth
velocity was resumed when the lead levels came down to <250 µg/L
(1.21 µmol/L). Levels of insulin-like growth factor also returned to
normal (Huseman et al 1992).
Pica, pallor and irritability is commonly seen at blood lead
concentrations of 400-600 µg/L (1.93-2.90 µmol/L). Children with these
levels typically have iron-deficient anaemia with basophilic
stippling. "Lead-lines" in the gums and long bones may be seen and
there may be abdominal radiopacities of ingested lead. Glycosuria,
aminoaciduria, abnormal liver function tests and peripheral neuropathy
is common.
Early childhood exposure to environmental lead may result in subtle
deficits in neuropsychological development. One study has found an
inverse relationship between blood lead concentration and visual-motor
performance (Baghurst et al 1995). Other studies have found that
increased blood lead concentrations decrease IQ (Pocock et al 1994).
At chronic low level exposure it may not be apparent that children are
being exposed to lead without determination of blood lead
concentrations (Dowsett and Shannon 1994). It has been suggested that
there may be no threshold for adverse effects of lead in children
(Needleman 1993).
5.2.2 Inhalation
Organic lead
This is the main route for absorption of tetraethyl lead and
tetramethyl lead. The initial symptoms of poisoning are nonspecific
and include asthenia, weakness, fatigue, pallor, headache, nausea,
vomiting, diarrhoea, anorexia and weight loss. Insomnia is usually
present. Ataxia, tremor, hypotonia, bradycardia and hypothermia may
also develop. In more severe poisoning disorientation, hallucinations,
facial contortions and episodes of intense hyperactivity may occur. In
severe cases maniacal behaviour and convulsions may develop which may
lead to coma and death. Recovery may take weeks or months and may be
incomplete (Hathaway et al 1991).
5.2.3 Dermal
Inorganic lead
Inorganic lead and lead compounds may cause mild local irritation and
may be absorbed through the skin, but it is not clear whether this
type of exposure would increase the lead body burden and toxicity from
this route is thought to be unlikely.
Organic lead
Organic lead compounds are mildly irritant and may be absorbed through
the skin. The initial symptoms of poisoning are nonspecific and
include asthenia, weakness, fatigue, pallor, headache, nausea,
vomiting, diarrhoea, anorexia and weight loss. Insomnia is usually
present. Ataxia, tremor, hypotonia, bradycardia and hypothermia may
also develop. In more severe poisoning disorientation, hallucinations,
facial contortions and episodes of intense hyperactivity may occur. In
severe cases maniacal behaviour and convulsions may develop which may
lead to coma and death. Recovery may take weeks or months and may be
incomplete (Hathaway et al 1991).
5.2.4 Ocular
There are no reports of chronic toxicity in the eye and systemic
effects from ocular exposure would not be expected.
5.2.5 Other routes
Inorganic lead
Systemic lead toxicity has also occurred from gunshot wounds and the
presence of lead shot in the synovial fluid. Lead toxicity from this
route may take many years to manifest (Manton 1994). An insoluble lead
phosphate coat is formed around retained pellets and lead poisoning is
a risk if the pellets are in a position where the coating may be
eroded (e.g. a joint).
5.3 Systematic description of clinical effects
5.3.1 Cardiovascular
Inorganic lead
Acute: Hypertension may be seen.
Chronic: Low level exposure to lead can result in hypertension
(Sharp 1990). In a study of 23 severely poisoned adult patients 40%
were mildly hypertensive (Whitfield et al 1972). Increases in blood
pressure have been associated with and increase in the risk of
cardiovascular and cerebrovascular disease in prospective
epidemiological studies.
Organic lead
Bradycardia and hypotension may be observed with organic lead
poisoning.
5.3.2 Respiration
Inorganic lead
Although inorganic lead compounds can be absorbed by inhalation, they
do not cause respiratory effects.
Organic lead
Organic lead compounds can be absorbed by inhalation and may also
cause mild respiratory irritation.
5.3.3 Neurological
Inorganic lead:
Acute exposures have resulted in fatigue, malaise, convulsions and
encephalopathy. Encephalopathy is rare in adults.
Adults:
Chronic exposures in adults may result in fatigue and malaise. There
may also be insomnia, aggressive behaviour.
Seppalainen et al (1983) have shown in a study of workers exposed to
lead in their occupations that nerve conduction velocities especially
in the arm nerves decreased. They also noted that the motor and
sensory conduction velocities decreased. These changes were noted only
in workers whose blood lead levels were between 300 and 500 µg/L
(1.45-2.41 µmol/L). No change in conduction velocity was seen in
workers with blood lead levels of below 300 µg/L (1.45 µmol/L).
A study was carried out on 23 adults (13 men, 10 women) who attended
one hospital (over a ten year period) with lead encephalopthy. All had
been consuming illicit alcohol which had been contaminated with lead.
Only one patient who worked with lead products as a plumber was known
to have additional exposure to lead. 82% (18/23) patients had
recurrent seizures either generalised or focal, 40% (10/23) were
either comatose or semicomatose on admission. The remainder had a
variety of neurological effects including confusion, dizziness,
lethargy, headache, disorientation with bilateral blindness and
fainting (Whitfield et al 1972).
Children:
Developmental defects including learning disabilities, lowered IQ and
behavioural abnormalities can occur in the absence of any other signs
of lead toxicity and at low blood lead levels. It is possible that
neurological injury can occur at levels above 100 µg/L (0.48µmo/L).
High lead levels are associated with encephalopathy with imminent risk
of death or permanent mental retardation and motor deficits.
A study of 160 children who lived near a lead smelting works were
assessed on a battery of psychometric tests. Blood lead concentrations
in this group ranged from 70 to 330 µg/L (0.34-1.59 µmo/L) and the
group performed within the average range on all tests of attainment
and intelligence. There was, however, a significant association
between blood lead concentrations and attainment scores on reading,
spelling and intelligence tests but not on mathematics tests. Analyses
suggested that while only a small proportion of the variance in
intelligence is explained by blood lead concentrations, the
relationship is independent of social class (Yule et al 1981).
The Port Pirie cohort study in Australia found that visual-motor
functions were lead sensitive. Children's VMI scores
(visual-motor-integration) were inversely associated with both
prenatal (i.e. maternal) and postnatal blood lead concentrations
(Baghurst et al 1995). Another study has demonstrated that increased
postnatal blood lead levels have adverse effects on intelligence
(Angle et al 1993).
It is now thought that decreases in the cognitive abilities of
children occurs at blood lead levels >100 µg/L (0.048 µmol/L). Also
there seems to be a consistent link between low-level lead exposure
during early development and later deficits in intellectual and
academic performance (Rosen 1995). In one study 249 children were
studied form birth to 2 years. They were initially divided into three
groups according to blood lead concentrations in the umbilical cord at
birth - high (umbilical cord blood level >100 µg/L (0.48 µmol/L)),
medium (umbilical cord blood level 60-70 µg/L (0.29-0.34 µmol/L)) and
low (umbilical cord blood level 30 µg/L (0.14 µmol/L)). Development
was assessed every six months. It was found that at all ages infants
in the high prenatal exposure group had lower development scores than
infants in the low and medium groups (Bellinger et al 1987). Pocock et
al (1994) found an inverse relationship between body lead burden and
blood lead concentration as low as 100 µg/L (0.48 µmol/L). Another
study measured lead levels in teeth and concluded that children with
high levels were more likely to need special services such as speech
therapy, remedial teaching for reading and behavioural counselling. It
was also thought that even slight elevations of blood lead
concentrations at age 2 years are associated with significant
decrements in intellectual and academic performance at age 10 years
(Needleman, 1993).
Organic lead
These can cause severe toxicity by inhalation, the latent period
between acute exposure and the onset of symptoms varies from a few
hours in the more severe cases to as much as ten days. The initial
effects are anorexia, vomiting, insomnia, tremor, weakness, fatigue,
nausea, headache, aggression, depression, irritability, restlessness,
hyperactivity, confusion and memory impairment. From the onset of the
initial effects there may be a delay of hours or even days before
acute mania, convulsions, delirium, fever and coma. Apparent complete
recovery can take two to six months to occur and some effects may
persist for some time (Grandjean and Nielsen 1979).
5.3.4 Gastrointestinal
Inorganic lead
Nausea, vomiting, abdominal pain or cramping and diarrhoea or
constipation are common features of lead toxicity.
Organic lead
Nausea, vomiting, diarrhoea, anorexia and weight loss may be seen.
5.3.5 Hepatic
Inorganic lead
Abnormal liver function tests and hepatitis are seen in adults and
children.
Organic lead
Elevated LFTs may be observed.
5.3.6 Urinary
Inorganic lead
Renal tubular damage can be characterised by aminoaciduria,
hypophosphataemia and glycosuria sometimes followed by
hyperphosphataemia.
Nephropathy has been associated with chronic lead poisoning in workers
exposed to lead. (Hathaway et al 1991). Most of the excess deaths
occurred before 1970 among men who began work before 1946 suggesting
that current lower levels of exposure may reduce the risk.
Most studies of kidney function involving lead have used levels of
blood urea nitrogen (BUN), serum creatinine or urinary protein as
measurements of renal function. However because the kidney has a great
reserve capacity these measures of excretory function can be normal or
in the normal range despite major unrecognised impairment of kidney
function. BUN and creatinine will be increased only when approximately
two thirds of kidney function is lost. These tests are unlikely
therefore to detect mild or moderate renal impairment due to lead
toxicity and are unlikely to discover a lead nephropathy.
There are thought to be two main stages of lead nephropathy.
1) Stage I involves acute reversible stages with intranuclear
inclusion bodies and alteration of mitochondrial morphology. These
intranuclear inclusion bodies have been extensively studied in
experimental animals and from renal biopsy from exposed workers and
children with acute lead poisoning. The intranuclear inclusion bodies
are reported to be the most characteristic feature of stage one
nephropathy. These occur in the lining cells of the proximal tubules
and are composed of sulphydryl-rich lead protein complex. They are
thought to serve as protective temporary storage mechanisms by which
soft tissue lead is complexed in a non-diffusable form thereby
reducing the concentration of lead available to disrupt essential cell
function.
The renal proximal tubules are rich in mitochondria and in
experimental animals swelling of mitochondria can be observed at
relatively low lead concentrations. In exposed workers distortion of
the proximal tubules have been noted after a couple of months of
exposure.
2) Stage II is defined as a chronic condition characterised by
interstitial fibrosis, tubular atrophy and dilatation and
arteriosclerotic changes. These have been found in lead workers with
excessive lead exposure for more than two years but these workers did
not have to exhibit renal failure until many years later. It has also
been found in workers exposed over ten years.
A relationship between gout and lead nephropathy has been recognised
for centuries and gout (sometimes termed saturnine gout) occurs more
frequently in the presence of chronic lead nephropathy than in any
other type of chronic renal disease. There is some evidence to suggest
that chronic low level environmental lead exposure may affect kidney
function (Bernard and Becker 1988).
Organic lead
Urinary retention has been reported.
5.3.7 Endocrine and reproductive system
In a study of workers exposed to lead there was a high prevalence of
low serum thyroxine concentrations, none had clinical features of
hypothyroidism (Cullen et al 1983).
There may also be reduced vitamin D and cortisol metabolism and
adrenal function. Inhibition of insulin-like growth factor has been
seen in children.
The reproductive effects of lead in the male are limited to sperm
morphology and count.
Most recent information relates to reports of occupational cohorts and
of populations living in polluted areas near industrial plants. There
is a qualitative evidence that lead is toxic to the reproduction
system in both men and women. However, there are insufficient data to
provide the basis for estimation of dose effect relationship in women
(WHO, 1995).
A study of pregnancies in the centre and surroundings areas of lead
smelter town showed that the incidence of miscarriages (22 or 23) and
stillbirths (10 or 11) was higher in women living close to the
smelter. Some studies have also found decreased length of gestation in
women whose lead level were greater than 230 mg/L. Other studies have
not shown a significant association between birth weight and lead
exposure.
5.3.8 Dermatological
Inorganic lead
Inorganic lead and lead compounds are not irritant and may be absorbed
through the skin, but it is not clear whether this type of exposure
would increase the lead body burden and toxicity from this route is
thought to be unlikely.
Organic lead
Organic lead compounds are not irritant but may be absorbed through
the skin.
5.3.9 Eye, ears, nose and throat
Inorganic lead
Hearing impairment has been described in children with elevated lead
levels (Clement International corporation 1993).
Organic lead
Nystagmus may be a feature of organic lead exposure. Limited upward
gaze has also been reported (Poisindex, 1994). Tinnitus has been
reported following the inhalation of tetraethyl lead fumes (Poisindex
1994).
5.3.10 Haematological
Inorganic lead
Lead may cause haemolysis and hypoproliferative anaemia (Cullen et al
1983). This is generally hypochromic monocytic anaemia with a decrease
in mean corpuscular haemoglobin and stippling of erythrocytes and
reticulocytes.
Red blood cell zinc protoporphyrin (known as erythrocyte
protoporphyrin or EP) will be raised.
Organic lead
Anaemia, basophilic stipling and neutrophilia may occur.
5.3.11 Immunological
Inorganic lead
There is some evidence to suggest that lead may cause adverse effects
on the cellular component of the immune system in lead workers with
blood lead levels exceeding 500 µg/L (2.41 µmol/L) but there few human
studies have been carried out (Clement International Corporation 1993,
WHO 1995).
5.3.12 Metabolic
5.3.12.1 Acid-base disturbances
No data.
5.3.12.2 Fluid and electrolyte disturbances
No data.
5.3.12.3 Other
Inorganic lead
ALAD is depressed which leads to an increase in urinary and blood
delta-aminolevulinic acid (ALA) concentrations. Urinary coproporphyrin
is also usually raised.
Blood concentrations of 1,25 dihydroxy vitamin D may be reduced.
Organic lead
Both hypothermia and pyrexia have been reported. ALAD concentrations
may be reduced.
5.3.13 Allergic reactions
No data
5.3.14 Other clinical effects
No data.
5.4 At risk groups
5.4.1 Elderly
No data.
5.4.2 Pregnancy
5.4.3 Children
Children appear to be more susceptible than adults to the toxic
effects of lead because of incomplete development of the blood brain
barrier, greater intestinal absorption of lead, and a tendency to put
objects or their hands into their mouths thereby increasing ingestion
of contaminated substances. In addition, they have a smaller
proportion of dense bone tissue than in adults which reduces the total
transfer of the absorbed lead into bone, so that it remains in the
soft tissues where it produces toxic effects (Knodel, 1995).
Disproportionate numbers of children from lower socioeconomic
backgrounds have high lead levels. This may be because they live in
older poorly maintained housing where old lead paint and lead water
pipes may remain (Bellinger et al 1989).
5.4.4 Enzyme deficiencies
No data.
5.4.5 Enzyme induced
No data.
5.4.6 Occupations
It is thought that millions of workers may be exposed to lead in the
United States and Europe (Cullen et al 1983).
The highest and most prolonged lead exposures have been seen among
workers in the lead smelting, refining and manufacturing industries.
Potentially high lead levels may also occur in steel welding or
cutting operations, construction, rubber and plastics industries,
printing industries and other industries requiring flame soldering of
lead solder (Clement International Corporation 1993).
There have been reported cases of lead toxicity in occupations
including stained glass workers (Baxter et al 1985), mechanics
(Goldman et al 1987), painters (Ennever et al 1995), in the
manufacture of batteries and lead smelting (Williamson and Teo 1986),
manufacture of lead pigments (Davies 1984) and workers on firing
ranges (Chan et al 1995).
5.4.7 Others
There is some evidence to suggest that people with iron-deficiency
anaemia are more prone to lead toxicity, as lead impairs iron
utilization for haem biosysnthesis and thus exacerbates iron
deficiency. Calcium deficiency greatly enhances lead absorption and
during periods of low calcium lead may be mobilised from tissue stores
particularly bone. Lead poisoning may also recur in the presence of
osteoporosis indicating that bone can be a significant source of lead
level elevation in conditions associated with accelerated resorption
(Shannon et al 1988).
Some ethnic groups may be more at risk of lead poisoning because of
the use of traditional remedies (Middleton 1989) or cosmetics.
In some groups the inhalational abuse of leaded petrol can be
relatively common (Burns and Currie 1995).
6. MANAGEMENT
6.1 Decontamination
Inorganic lead:
An X-ray should be performed to confirm the acute ingestion of a lead
weight or similar foreign body. Gastric decontamination is not
indicated, although a mild laxative may be given. A further X-ray
should be done if the foreign body has not been passed in the stools
after 48 hours and surgical removal may be indicated if it has become
lodged in the gastrointestinal tract or the patient develops marked
symptoms.
Gastric lavage is recommended within 2 hours of an acute ingestion of
lead salts and an X-ray will confirm effective removal. Activated
charcoal does not adsorb lead.
In cases of chronic toxicity an abdominal X-ray should be performed to
determine whether lead is present in the gut. Specks or flecks of
highly radio-opaque material will be seen, almost as if the film has
faults. Chelation therapy should not begin until the X-ray is clear so
a mild laxative should be given or whole bowel irrigation performed,
depending on the clinical condition of the patient and the urgency to
start chelation therapy.
In cases of patients who have retained gun shot pellets they do not
have to be removed unless they are in a position where the insoluble
lead phosphate coating will be eroded (e.g. in a joint).
Organic lead
In cases of dermal exposure contaminated clothing should be removed
and the area thoroughly irrigated.
6.2 Supportive care
Inorganic lead:
Management entails identifying and removing the source of the lead,
symptomatic care and using chelating agents if indicated.
GI disturbances and renal impairment should be treated supportively.
Anaemia should be treated with iron supplements.
Convulsions as a result of acute encephalopathy may be treated with
diazepam. Mannitol and corticosteroids should be used for cerebral
oedema.
Organic lead:
Chelating agents are not useful for organic lead poisoning. Treatment
is symptomatic and supportive.
6.3 Monitoring
Inorganic lead:
Blood lead concentration should be determined to confirm the diagnosis
of lead toxicity, the urgency of this analysis will depend on the
clinical condition of the patient. In children ensure blood samples
are obtained by venipuncture only, as finger-puncture or capillary
blood samples may show elevated lead concentrations as a result of
skin contamination.
In children, blood lead concentrations (prior to any treatment or
other action to abate exposure) of:-
a) greater than 250µg/L (1.2µmol/L) may require chelation therapy
although there is no consensus.
b) greater than 400µg/L (1.9µmol/L) require treatment with either DMSA
(succimer) or sodium calciumedetate.
c) greater than 600µg/L (2.9µmol/L) are a medical emergency and
require immediate chelating agent, sodium calciumedetate is the
treatment of choice.
Pharmacological intervention is not needed for blood lead
concentrations of less than 250µg/L (1.2µmol/L), however in all cases
the source of the lead must be identified and removed. The blood lead
concentration should be monitored at least every three months and
ideally every 4-6 weeks.
In adults, blood lead concentrations (prior to any treatment or other
action to abate exposure) of:-
a) greater than 400µg/L (1.92µmol/L) may require treatment with
chelating agents if the patient is symptomatic, although this is
unlikely.
b) greater than 800µg/L (3.86µmol/L) will require treatment with
chelating agents if the patient is symptomatic which is quite likely.
c) greater than 1200µg/L (5.79µmol/L) require treatment with chelating
agents as patients are very likely to have symptoms.
Most standard tests of renal function do not appear to detect early
effects of lead exposure (Winship, 1989). However renal function
should be assessed as renal tubular damage, characterised by
aminoaciduria, hypophosphataemia and glycosuria, sometimes followed by
hyperphosphataemia, has been reported. Increased urinary uric acid and
hyperuricaemia are seen as a consequence of chronic renal damage.
Since several nutritional and dietary deficiencies will increase the
absorption of lead they must be excluded. Assess plasma concentrations
of calcium, phosphorous, iron and zinc as well as total intake of
calories, fat, ascorbic acid, vitamin D and protein.
Chelating agents can be nephrotoxic (sodium calcium edetate),
hepatotoxic (succimer) and deplete systemic copper and zinc. If the
drugs are being used regular monitoring must taken place.
Full blood count and iron studies should be performed as microcytic
hypochromic anaemia is common. Reticulocytosis and punctate basophilia
can occur.
The following tests may be considered but are not considered
essential: red blood cell zinc protoporphyrin (known as erythrocyte
protoporphyrin or EP) is raised, urinary delta-aminolevulinic acid and
coproporphyrin are also raised and the blood concentration of 1,25
dihydroxy vitamin D is reduced.
6.4 Antidotes
There are a number of chelating agents available to treat inorganic
lead toxicity. The aim of chelation therapy is to reduce the lead
concentration to less than 150 µg/L (0.72 µmol/L) and ideally to less
than 100 µg/L (0.48 µmol/L). After therapy there is a period of
re-equilibriation of 10-14 days after which the lead concentration
should be measured in order to determined the need for further courses
of chelation.
Antidotes are of no benefit in organic lead poisoning.
a) SODIUM CALCIUMEDETATE (Ledclair)
This drug forms chelates with metal ions that have a higher affinity
for sodium calciumedetate than calcium. It has to be given
parenterally because of its low bioavailability following ingestion.
It has a high incidence of side effects and should be given with
antihistamine cover, however it is the treatment of choice in serious
lead toxicity. When sodium calciumedetate is given in combination with
dimercaprol there is a more rapid decline in lead concentrations
(Chisholm, 1992) but the rationale for the use of these two agents
together has recently been questioned (O'Connor, 1992).
Dosage: up to 80mg/kg body weight/day in 2 equal divided doses (8-12
hours apart) by slow IV infusion for 5 days. Contents of 5ml ampoule
should be diluted with 250-500ml of normal saline or 5% dextrose and
the dilute solution given over at least an hour. The concentration
should not exceed 3% of the infusate.
The above daily regime can be given by IM. injection divided into 2 or
4 injections with procaine as an anaesthetic.
Therapy is continued for up to 5 days, followed at least 48 hours
later, by a further course for a maximum of 5 days. If further courses
are necessitated there must be an interval of at least 7 days before
recommencing therapy.
Adverse effects: Nausea and cramp, particularly during IV
administration. Can be nephrotoxic so i.v. hydration is required and
U&Es should be checked daily
b) SUCCIMER (MESO-2,3-DIMERCAPTOSUCCINIC ACID, DMSA)
(Chemet - 100mg only)
This is a water-soluble analogue of dimercaprol which is active
orally. It appears to be relatively specific for heavy metals and to
only minimally enhance the excretion of iron, zinc and calcium. It is
not licensed for use in the UK and is available on a named-patient
basis from NPIS (London) as 100mg or 300mg capsules (the 100mg
capsules are also available from McNeil, USA). There are several
reviews on the use of succimer (Mann and Travers 1991, Glotzer 1993).
Dosage: orally 30 mg/kg body weight daily, in three divided doses,
for 5 days, then 20 mg/kg, in two divided doses, for 14 days.
Adverse effects: Gastrointestinal symptoms and rashes may occur.
Mild to moderate neutropenia has been reported and a complete blood
count should be obtained prior to and weekly during treatment with
succimer. Transient mild elevations of serum transaminases have been
reported so serum transaminases should be monitored prior to and
weekly during treatment with succimer.
c) DIMERCAPROL (BAL)
Chelation complexes are formed between the sulphydryl groups of this
drug and metals. It cannot be administered orally and is given as a
deep IM injection in peanut oil. It is contraindicated in patients
sensitive to peanuts. It is available in 2ml ampoules of 50mg/ml.
Dosage: By IM injection 2.5-3 mg/kg every 4 hours for 2 days, 2-4
times on the third day, then 1-2 times daily for 10 days or until
recovery.
Adverse effects: These are relatively frequent but are almost always
reversible. The following have all been reported: hypertension;
tachycardia; nausea and vomiting; a burning sensation of the lips,
mouth, throat and eyes; salivation and lacrimation; conjunctivitis;
rhinorrhoea; muscle pain and spasm; headache; tingling of the hands
and other extremities; a feeling of constriction in the chest and
throat; sweating of the forehead and hands. Local pain and abscess may
occur at the site of the injection and children can develop a fever
after the second or third injection which persists until treatment is
terminated.
d) PENICILLAMINE (Distamine, Pendramine)
Penicillamine is well absorbed from the gastrointestinal tract so is
used orally and is available as 50mg, 125mg and 250mg tablets. There
is a risk that patients allergic to penicillin may have an anaphylatic
reaction to penicillamine but preparations no longer contain traces of
penicillin (Klaassen, 1990). With the introduction of succimer the use
of penicillamine in lead poisoning is declining.
Dosage: Orally, adults 1-2g daily and children 20 mg/kg body weight
per day in divided doses until blood lead level falls below toxic
level.
Adverse effects: Nausea, anorexia, fever and rash. Thrombocytopenia
and less commonly neutropenia can occur, so full blood counts should
be carried out weekly or fortnightly during therapy. Proteinuria and
rarely haematuria and other complications such as Stevenson-Johnson
syndrome have been described.
6.5 Elimination techniques
Elimination is dependent chiefly on the urinary excretion of the
lead-chelate complex and there is no indication for extracorporeal
elimination.
6.6 Investigations
a) Sodium calciumedetate mobilization (challenge) test
This is used to assess the size of the chelatable lead stores. A
single IV dose of 1g (adults) and 500mg/m2 (children, maximum dose of
1g) sodium calciumedetate, diluted in 250-500ml of 5% dextrose or
normal saline is given over 1 hour. Alternatively it can be given IM
undiluted with procaine. The patient's urine is then collected for the
next 24 hours (adults) or 6-8 hours (children). The lead excretion
ratio calculated is the total urinary lead (in µg) excreted per
milligram of sodium calciumedetate administered i.e.
total urinary lead excreted (µg)
total dose of sodium calciumedetate given (mg)
The test is considered positive if the ratio exceeds 1 by some authors
(Markowitz and Rosen 1984) or 0.6 in children (Piomelli et al 1984).
b) Succimer provocation test
Succimer (DMSA) has been used instead of sodium calciumedetate as a
diagnosis of lead poisoning (Bentur et al 1987). 270mg of succimer was
administered orally and the ratio above used, substituting the dose of
sodium calciumedetate with that of succimer.
Other workers (Lee et al 1995) have compared provocation chelation
with succimer and sodium calciumedetate, using an oral dose of
succimer of 10mg/kg in adults. They conclude that using succimer may
provide an estimate of lead in storage sites that is more directly
relevant to the health effects of lead.
c) Radiographic studies
Bone X-rays are used in the diagnosis of lead poisoning as increased
density is an indication of exposure to lead of several months
duration.
X-ray fluorescence can be used to non-invasively quantify bone lead
stores. A superficial bone, such as the tibia, is exposed to a low
energy X-ray beam and the fluorescence photons are counted. This count
can be converted into a bone lead concentration. The technique has
been used evaluate sodium calciumedetate chelation therapy on the bone
lead levels (Rosen and Markowitz 1993).
d) Identifying the source of the lead
The most important aspect in the successful treatment of lead
poisoning is the identification and elimination of the source of the
lead.
In adults this is usually occupational, although it may result from
contaminated food or water or through the use of traditional
medicines. In children it is often as a result of behavourial
disturbances such as pica.
A comparison of the isotopes of lead in samples of suspected sources
(e.g. water, air, soil, food, cooking utensils, paint or jewellery) to
the lead isotopes found in the blood can be used to confirm the source
of lead. The blood lead concentrations of patient's immediate family
should also be determined.
6.7 Management controversies
Children, and especially young children, are much more susceptible
than adults to the effects of lead poisoning. However, despite the
fact that gross effects on health were well recognised, a survey of
paediatric departments in the United States found no common approach
for the treatment of lead toxicity (Glotzer and Bauchner 1992).
Factors contributing to this are the concerns about neurotoxicity with
blood lead concentrations of 100 µg/L and the availability of a safer
orally acting antidote, succimer. The decision as to when to begin
chelation therapy is not clear-cut, especially at blood lead
concentrations of between 250µg/L and 400µg/L. The controversies and
suggested protocols are well reviewed in two recent papers (Commitee
on Drugs 1995, Mortensen and Walson 1993).
Although chelation therapy has been used for many years in the
treatment of lead poisoning, there is a lack of data regarding its
efficacy in terms of clinical outcome (Kosnett, 1992). Chelation
increases the urinary excretion of lead, but does excretion equal
efficacy? The Food and Drug Administration in the United States has
approved succimer for use in childhood lead poisoning with little
published data on its pharmacokinetics in children. Pharmacokinetics,
proper dosing and efficacy are particularly important because of the
potential that the drug will be widely used in children with low-level
asymptomatic lead poisoning (Mortensen, 1994).
There is no evidence that available chelation agents have significant
access to lead stored in the brain. A study in rats found that brain
lead content increased following a single dose of sodium
calciumedetate (Cory-Slechta et al 1987) which raises concerns that
chelating agents redistribute lead from less to more vulnerable body
tissues (e.g. bone to brain).
7 CASE DATA
Cases 1, 2 and 3: Chronic ingestion in children
A 2 year 6 month old boy presented to the casualty department
convulsing. Phenobarbital failed to control the fitting which
eventually abated after diazepam was administered. The child's mother
stated that the boy had a 2 week history of irritable behaviour and
difficulty sleeping. He appeared thin, pale and malnourished with
blood pressure 100/80 mm Hg, pulse 120 beats/min, temperature 38.5°C
and respiration 32 breaths/min. Hard faeces were found on rectal
examination. Neurological examination revealed diffuse hypotonia with
symmetrically depressed deep-tendon reflexes and bilateral plantar
extension. The neck was supple and there was no papilloedema. A lumbar
puncture was performed but because the opening pressure was
unexpectedly high (230 mm Hg) only a small amount of fluid was
collected. A mannitol infusion was started immediately. Blood analysis
showed normal values for glucose, BUN, electrolytes and LFTs. The CBC
showed Hb 9.8 g/100ml, Hct 33% and WBC count 14,000/mm3. The
differential was normal except for the presence of RBCs with
basophilic stippling. The reticulocyte count was 3.9%. The CSF protein
was 70 mg/100ml, glucose 55 mg/dL, with 12 WBCs (all lymphocytes).
Gram stain India ink prep for cryptococcus, and AFB stains of the CSF
sediment failed to reveal any organisms. The ECG showed sinus
tachycardia with normal axis for the patient's age, and T wave
inversions in V5 and V6. A urine sample obtained after treatment
had 2+ glucose and 1+ protein but no ketones or cells.
The mother noted that her other two sons (aged 4 and 6 years) had also
been irritable, listless and apathetic and on occasion had refused to
eat over a period of several weeks, but both had recently had a
flu-like illness. When questioned further she stated that the symptoms
were vomiting, headache, and diffuse aches and pains. The 6 year old
was physically examined and no abnormalities were found. The 4 year
old was found to be ataxic, with bilateral wrist-drop and a blue line
at the base of the gums.
Abdominal X-ray of the 2´ and 4 year old showed characteristic
opacities suggesting recent ingestion of lead containing particles.
Lead poisoning was confirmed by the presence of 3+ qualitative urinary
coproporphyrins and elevated erythrocyte protoporphyrin. Both children
were admitted and given a magnesium sulphate cathartic, a cleansing
enema and chelation therapy. X-rays of the wrists and knees revealed
lead lines in all three children (Goldfrank et al 1990)
Case 4: Chronic ingestion - confusion in diagnosis
Symptoms such as abdominal pain, anorexia, joint pain and anaemia can
be confused with other disorders. In this case lead poisoning was
mistaken for sickle cell crisis in a 12 year old boy known to have
sickle cell anaemia.
The patient presented to hospital complaining of severe abdominal and
bilateral knee pain with intermittent vomiting. His last sickle cell
crisis had occurred five months earlier and gave rise to abdominal
pain. Physical examination revealed enlarged tonsils and erythematous
oropharynx. Blood pressure was 100/70 mmHg; pulse 100, respirations 16
and temperature 37.1°C rectally. Laboratory analysis revealed normal
urinanalysis, haemocrit 16.3%, WBC 13,000 cells/mm2 (with 39 bands,
33 neutrophils, 16 lymphocytes, 12 monocytes and reticulocytes 14.1%).
A diagnosis of vasooclusive crisis was made and the patient discharged
home on codeine 15 to 30 mg by mouth every three to four hours as
needed.
The patient returned three days later complaining of continued
abdominal pain as well as a convulsion that lasted two to three
minutes and resolved spontaneously. The patient's mother described it
as a generalized tonic-clonic convulsion. The patient had no history
of convulsions and denied any drug ingestion. Blood pressure was 95/70
mmHg, pulse 110, respirations 18 and temperature 37.2°C rectally.
Physical examination revealed dried blood in the right nostril,
diffuse abdominal tenderness and a normal neurological examination.
Laboratory data included haemocrit 18.3%, WBC 19,600 cells/mm2 (with
a normal differential and reticulocytes 23.8%). The impression was of
vasooclusive crisis and the patient was again discharged home with
codeine.
The patient returned again 24 hours later complaining of anorexia,
constipation, persistent vomiting as well as abdominal and knee pain.
He became increasingly lethargic and obtunded. Vital signs were as
follows: blood pressure 90/60 mmHg, pulse 125, respirations 22 and
temperature 38.5°C rectally. The abdomen was soft with diffuse
tenderness and decreased bowel sounds. On neurological examination the
patient occasionally responded to vocal commands. Cranial nerves were
intact although a right gaze preference was noted. The patient was
hyperreflexic and hypertonic. He moved all limbs appropriately in
response to pain. Initial laboratory results were as follows:
haemocrit 19.6%, WBC 24,500 cells/mm2 (with two myolocytes, 23 bands,
48 neutrophils, 10 lymphocytes, 14 monocytes and 3 atypical
lymphocytes), normal electrolytes and ammonia. A blood urine and urine
toxicology screen which did not include heavy metals was negative. The
patient was admitted to the paediatric intensive care unit for further
investigation. Lumbar puncture, computed tomography scan with contrast
and EEG were normal. A chest X-ray showed mild cardiomegaly. Knee
X-rays showed bilateral bands of increased density at the metaphyseal
plate. During the next few days the patient became increasingly
obtunded with occasional periods of agitation. His lead level was 1001
mg/L. Treatment with dimercaprol 500 mg/m2/day and calcium edetate
1,500 mg/m2/day was started immediately. After three days of
chelation therapy his lead level had fallen to 500 mg/L and one week
after chelation therapy started he had begun to respond to verbal
commands. The patient was eventually discharged from a chronic care
facility after two months. During a routine follow up investigation
one year later the patient was found to have a less severe case of
clinical lead poisoning but further chelation therapy was not
necessary. The source of the lead was thought to be house paint
(Nelson and Chisholm 1986).
Case 5: Child - ingestion of traditional remedy
A 2´ year old boy was admitted to hospital with a temperature of
37.8°C. The diagnosis was dehydration and severe electrolyte imbalance
following prolonged diarrhoea syndrome which lasted for seven days and
hypochromic anaemia. The patient died within a few hours of
hospitilization. The child had been given a teaspoonful of a yellow
powder three times a day for 3 days prior to admission. One sister of
the patient had died in similar circumstances. A postmortem was not
performed but the yellow powder was identified as lead oxide by
analysis (Cueto et al 1989).
Case 6: Chronic in a child - reversible acute renal
failure
A 26 month old girl was admitted to hospital with a one week history
of anorexia, vomiting, lethargy and pallor. She had been routinely
screened at another healthcare facility three weeks earlier and had an
elevated blood lead level of 970 µg/L. She had been hospitalised and
given calcium disodium edetate 150 mg and dimercaprol (BAL) 48 mg
intramuscularly every four hours for seven days. Blood urea nitrogen
level was 22 mg/100ml before and after therapy. Serum creatinine
concentrations had not been measured. Follow up had revealed a blood
lead level of 320 µg/L.
Physical examination of the patient showed a pale, mildly dehydrated
child with normal pulse, respiration and temperature. Her blood
pressure was 92/64 mmHg. She was admitted to hospital and blood
analysis revealed a haemocrit of 22.1%, reticulocytes 0.3%, platelets
340,000/mm3 and leucocytes 20,400/mm3 with a normal differential.
The red blood cell indices indicated iron deficiency anaemia. There
was no basophilic stippling. Bleeding and coagulation profiles were
normal except for glucose-6-phosphate dehydrogenase deficiency.
Urinanalysis revealed proteinuria, BUN 113 mg/100ml and serum
creatinine 13.4 mg/100ml. The urine was not examined for amino acids.
Her serum cholesterol was elevated. In view of this severe renal
failure further management included complete restriction of protein
and appropriate intravenous fluid administration. Her blood lead level
on admission was 210 µg/L. The patient was discharged after 17 days
and two weeks later urinanalysis was normal. Twenty months after
admission the patient was in excellent health. This severe acute renal
failure could have been associated with either chelation therapy or
preexisting lead nephropathy or both and was further complicated by
glucose-6-phosphate dehydrogenase deficiency (Khan et al 1983).
Case 7: Child - ingestion of metallic lead
A nine year old girl complaining of abdominal cramping presented to an
emergency department two days after ingesting a lead muzzle ball. An
abdominal X-ray confirmed the presence of the ball in the right upper
quadrant of the small intestine. A baseline blood lead level was 150
µg/L. She was given magnesium citrate cathartic and discharged home.
She returned to hospital six days later having had normal bowel
movements but had not passed the ball. She had experienced
intermittent abdominal cramping and the day before returning to
hospital she had felt lethargic, with a decreased appetite, headache
and dysuria. At the time of presentation her temperature was 39.5°C,
pulse 128 beats per minute, respiration 28 per minute and blood
pressure 128/72 mmHg. Her abdomen was soft with normal bowel sounds.
She had diffuse abdominal tenderness with no rebound or guarding.
Laboratory analysis revealed a white blood cell count of 3.3x103/mm3
with 62% segmented neutrophils, 6% band neutrophils and 31%
lymphocytes. The remainder of the complete blood count, serum
electrolytes, urinanalysis and erythrocyte sedimentation rate were all
normal. Serial abdominal X-rays during her stay in hospital showed
gradual movement of the ball through the bowel. A 24 hour urine
collection for lead excretion revealed a lead concentration of <100
µg/L. On the second and third days in hospital her blood lead levels
were 80 µg/L and 70 µg/L respectively. The rest of her stay in
hospital was uneventful apart from mild diffuse abdominal cramps. On
the fourth day in hospital (11 days post ingestion) the lead ball was
passed in the stools completely intact with no evidence of corrosion.
The blood lead level after the ball had been passed was found to be 50
µg/L. Analysis of the muzzle ball revealed that it was 95% lead and 5%
antimony with traces of titanium, manganese, iron, nickel and copper
also detected (Durback et al 1989).
Case 8: Fatal in a child - ingestion of metallic lead
A 23 month old female presented with a two week history of flu-like
symptoms and an episode of vomiting on the day of admission. The child
had shown normal growth and development following a premature birth
and surgical repair for gastroschisis. Physical examination showed the
child to be rather pale. She was crying but was easily consolable and
was alert and cooperative. Her temperature was 37.2°C (oral), blood
pressure 112/70, pulse 110 beats per minute and a respiratory rate of
16 per minute. Her abdomen was soft with no guarding, rebounding or
tenderness. Neurological examination was normal. Blood tests showed
haemoglobin of 8.0 g/100ml with a mild hypochromic microcytic smear.
White blood cell count was 16,700 per mm3 with 25% bands. A
diagnosis was made of probable gastroenteritis and anaemia of unknown
etiology. The patient's mother was told to continue giving clear oral
fluids and to return if symptoms worsened. Later that day the
patient's mother contacted the surgeon who had performed the
gastroschisis repair and the patient was admitted to the surgical unit
for evaluation of possible intermittent intestinal obstruction. At the
time of admission the physical examination was unchanged. Repeat
laboratory analysis showed haemoglobin 8.2 g/100ml and haemocrit 24%.
White blood cell count was 15,700 per mm3 with 29% bands. Platelet
count was 338,000. SGOT was 43 units per ml. Total bilirubin was 1.2
mg/100ml. Serum ammonia was 22 µg/100ml. Serum osmolality was 279
milliosmoles. Sodium was 140 mEq/L, potassium 4.6 mEq/L, chloride 106
mEq/L total CO2 was 16.1 mEq/L, creatinine 1.6 mg/100ml. Repeat
urinanalysis was normal. An abdominal X-ray was taken to rule out the
possibility of obstruction. This revealed a small radiopaque object in
the left upper quadrant but no evidence of obstruction. The
significance of the presence of a foreign body was not appreciated and
the initial impression was that of a probable viral syndrome; and the
patient was rehydrated intravenously. Approximately ten hours after
admission the patient had a grand mal tonic clonic convulsion and was
found unresponsive in respiratory arrest. Her pupils were fixed and
dilated with the eyes deviating to the right. Phenobarbitone was
administered. She was transferred to the intensive care unit where
over the next couple of hours she became comatose with response to
painful stimuli only. Convulsions continued which were treated with
phenobarbitone and the patient was ventilated. Despite aggressive
supportive therapy the patients condition continued to worsen becoming
decerebrate, completely unresponsive with fixed dilated pupils and 18
hours after admission the patient was pronounced dead. Shortly after
her death the abdominal X-ray films were reexamined and because of her
overall clinical course and the presence of the radiopaque body in her
stomach the possibility of lead poisoning was considered. Her
premortem blood lead level was 2830 µg/L. Postmortem findings included
diffuse cerebral oedema and hyperaemia of the lungs, liver and spleen.
A 2 cm x 3 cm metallic body was found in the stomach which was later
identified as a lead curtain weight. The object was bile stained with
some local mucosal irritation which suggested that it had been in the
stomach for some time. The patient's mother estimated that the child
must have ingested it approximately one month prior to admission
(Hugelmeyer et al 1988).
Case 9: Chronic ingestion in an adult - illegally distilled
alcohol (moonshine)
A 28 year old chronic alcoholic male presented to the casualty
department with a history of twelve convulsions over the previous four
days. He appeared lethargic and disorientated. His vital signs were
normal apart from a raised temperature. Physical examination revealed
purulent conjunctivitis. A preliminary diagnosis of diffuse metabolic
encephalopathy of unknown etiology and possible lead poisoning was
made.
Blood tests showed white blood cell count of 13,000/mm3 with 91%
neutrophils. There was marked basophilic stippling of the red cells in
the peripheral blood. His convulsions continued. On the fifth day of
admission lead encephalopathy was suspected and intravenous Ca EDTA
therapy was started. Over the next two days the convulsions abated and
the patient was able to give appropriate responses to simple
questions. The lead levels determined in 24 hour urine collection on
the first two days of therapy were 6.6 and 5.2 mg/L respectively.
Three separate five day courses of CaEDTA therapy were given over the
next three weeks. The patient was left with a chronic brain syndrome
thought to be due to lead encephalopathy (Whitfield et al 1972).
Case 10 Acute ingestion in an adult - traditional
remedy
A 50 year old man complaining of impotence for several months
consulted his general practitioner after developing progressive
general malaise, anorexia, vague abdominal discomfort and impaired
taste. A blood count was arranged as part of his investigations. This
showed mild anaemia with a haemoglobin concentration of 11.9 g/100ml
and a normal white cell and platelet count. His peripheral blood film
showed coarse basophilic stippling and occasional circulating
nucleated red cells. His physical examination was normal. His blood
lead level was 960 µg/L and erythrocyte (zinc) levels were high at 89
µg/100ml. Analysis of urinary porphyrins showed total porphyrins 1446
µg/100ml (normal <150), urinary delta aminolaevulinic acid levels
raised at 319 µg/100ml (normal <34) and normal urinary
porphobilinogen of 5.8 mol/L. His bone marrow showed erythoid
hyperplasia with prominent siderotic granules and ringed sideroblasts
consistent with lead toxicity. He had no history of occupational
exposure to lead and his wife's lead level was 20 µg/L. He admitted
taking three preparations given to him by an traditional Asian
practitioner for the treatment of impotence. These consisted of a
brown paste, some brown pellets and a yellow-white powder. He had been
taking these orally for five weeks before presentation. Samples of
these preparations were analysed for lead and the yellow-white powder
was shown to have a very high lead content. It contained lead oxide,
lead nitrate, and lead sulphate with a total of 84% elemental lead by
weight. Since he had no major clinical problems after consultation,
chelation therapy was deemed unnecessary and after four weeks his
blood lead levels had decreased to 550 µg/L (Dolan et al 1991).
Case 11: Lead poisoning from retained bullet
A 73-year old man complained of suffering from increasing weakness,
progressive difficulty in carrying out routine tasks and shortness of
breath over a period of 2 weeks. He also complained of accentuation of
longstanding bilateral leg pain that resulted from a gunshot wound to
his right hip 52 years earlier. For several months he had suffered
from decreased appetite and chronic epigastric pain. He had a previous
history of hypertension, cholecystectomy and left hernia repair.
Physical and neurological examinations were normal. He had a
haemoglobin of 6.9 g/100ml and a haemocrit of 21.7%. His white blood
cell count was 6000 cells/100ml, platelet count 234000/100ml and his
reticulocyte count was elevated at 5.7%. A peripheral blood smear
showed marked polychromasia with occasional target cells, histocytes
and ovalocytes. The patient was investigated for haemolytic anaemia
and an autoimmine process was excluded. A bone marrow biopsy showed
features of refractory anaemia with ring sideroblasts. The patient's
serum lead level was found to be elevated at 4600 µg/L (normal <250
µg/L). X-rays showed a bullet partially imbedded in the medial portion
of the right acetabulum and partially protruding into the joint space.
There were several tiny metallic fragments within the joint cavity.
The right hip joints had changes of severe osteoarthritis with
osteophytes, joint space narrowing, subchondral cysts and sclerosis.
The left hip joint was normal. The patient was given three units of
packed red blood cells and underwent removal of the intra-articular
bullet fragments together with a total hip replacement. He made a
satisfactory recovery with symptomatic improvement (Peh et al 1995).
Case 12: Lead poisoning from sniffing petrol
A 14 year old boy was admitted with a six day history of chorea and
increasing mental confusion. He was known to have sniffed petrol for
several hours a day for four or five years and was in the habit of
falling asleep beside an open petrol can. He appeared mute and unable
to follow simple commands. He had upward gaze limitation and rotary
nystagmus on lateral gaze. Deep tendon reflexes were absent and both
plantar responses were extensor. His haemoglobin was 14.2 g/100ml with
moderate basophilic stippling, BUN 44 mg/100ml, serum creatinine
phosphokinase (CPK) 38,193 iu/L (normal 5-98 iu/L), SGOT 163 iu/L
(normal 4-20 iu/L), blood ammonia 143 µg/L (normal 20-120 µg/L) and
blood lead 1690 µg/L. X-rays of his distal radius showed no lead
lines. His EEG showed generalised 1 to 6/s, 10 µV waves but no
cortical activity. His conduction velocities were slowed to 60% of
normal. He passed a small amount of blood stained urine and his BUN
and plasma potassium rose rapidly. Peritoneal dialysis was started as
was disodium calcium edetate therapy. During the following week his
signs of hepatocellular and muscle damage regressed and he passed
increasing amounts of isothenuric urine. Despite chelation therapy his
blood lead level remained elevated at 1490 µg/L and there was no
change in his level of consciousness or his movement disorder. He
suffered a cardiorespiratory arrest associated with the introduction
of 500 ml of diasylate into the peritoneal cavity. Despite rapid
restoration of cerebral perfusion his chorea was replaced by
decerebrate posturing and he died two weeks later. By the 22nd day he
had received eight 500 mg doses of disodium calcium edetate and his
blood lead level had fallen to 390 µg/L.
At postmortem the brain was found to be oedematous and there was
hypoxic changes with necrosis of hippocampal nerve cells and a focus
of demyelination in the ventral aspect of the pons. The cut surface of
the liver showed small foci of yellowish discolouration due to
centrilobular necrosis compatible with hypoxic damage. The left kidney
contained several abscesses and the right kidney had an oedematous
stroma and diffuse changes of acute and chronic inflammation but
preservation of glomerular and tubular architecture (Robinson 1978).
Case 13: Probable intentional lead poisoning
A 27 year old female painter presented to a hospital in Germany
complaining of general malaise, nausea and vomiting, colicky abdominal
pain and constipation. The appendix was removed at laparotomy and was
found to be normal. Her abdominal pain persisted. She was noticed to
have a blue line on her upper gingival margin and lead poisoning was
suspected. Her haemoglobin was 7.4 g/100ml with no basophilic
stippling, blood lead level 3.7 µmol/L, delta-aminolaevulinic acid
excretion was 83.9 µmol/24 h and her bone marrow was sideroblastic.
Oral penicillamine improved her symptoms but no source of lead could
be found in her home.
One year later she presented to a UK hospital again complaining of
general malaise and intermittent colicky abdominal pain. Subacute
bowel obstruction was diagnosed. Her haemoglobin was 12.0 g/100ml, her
blood lead level 1.9 µmol/L with basophilic stippling and her 24 hour
urinary delta-aminolaevulinic acid excretion was normal. Her symptoms
resolved but one month later she returned with similar symptoms as
well as bilateral wrist drop and muscle pains. On this occasion her
blood lead level was 4.3 µmol/L, urinary 15,300 nmol/24h (normal
<300) and her faecal excretion was 313,066 µg/24 h (normal 200-500)
which indicated further exposure.
The patient used an Indian eye-liner which was found to contain 69%
lead. She stopped using this and was treated with intravenous calcium
edetate and oral penicillamine. However her symptoms continued and her
blood lead level remained at 4-5 µmol/L. She was admitted to hospital
several times with exacerbations of her symptoms and found to have
raised urinary lead levels. She persistently denied deliberate
ingestion of lead. Her home and art studio were searched for the lead
source. The patient had bought a large sack of what she believed to be
"titaniun white" powder in Germany several years before. This was
found to contain 47% lead by weight and was probably "lead white" i.e.
basic lead carbonate. The patient denied the common practice of
painters licking their paintbrushes to achieve a fine point but
admitted that she often mixed the powder to form a paste and applied
it to the canvas with her hands. Also when she scooped powder out of
the sack some would be blown up as dust and inhaled. This source of
exposure was removed and her blood lead levels fell rapidly to normal
(Graham et al 1981).
It was later reported that the same patient was admitted about a year
after these events to another hospital again with the symptoms of lead
toxicity and a blood lead level of 3.7 µmol/L. It was learnt that she
had been admitted to at least two other hospitals in different parts
of the country where lead poisoning was also diagnosed without the
patient giving any history that this had been investigated for before.
Again her home and studio were searched for a possible lead source and
a canister of a white powder which contained 80% by weight of lead
(probably basic lead carbonate) was discovered. Although there was no
irrefutable evidence that this patient was deliberately ingesting lead
her behaviour and length of intermittent exposure over five years
suggest such a conclusion (Taylor et al 1985, Bass 1985).
8 ANALYSIS
8.1 Agent/toxin/metabolite
8.2 Sample containers to be used
Blood: 2ml plastic container with EDTA anticoagulant.
Urine: 20ml in sterile universal container.
8.3 Optimum storage conditions
8.4 Transport of samples
8.5 Interpretation of data
8.6 Conversion factors
To convert µg/L to µmol/L multiply by 0.004826
To convert µmol/L to µg/L divide by 0.00486
To convert µg/100ml to µmol/L multiply by 0.0486
To convert µmol/L to µg/100ml divide by 0.0486
8.7 Other recommendations
9 OTHER TOXICOLOGICAL DATA
9.1 Carcinogenicity
Although there is no evidence that lead is carcinogenic in humans,
there are several reports in which benign and malignant tumours were
produced in experimental animals. In most of the studies malignant and
benign neoplasms were induced in mice and rats by oral or parenteral
administration of various types of lead compounds in high doses. A few
clinical studies have found increased chromosomal defects in workers
with blood lead concentration above 600 mg/L (WHO, 1995). A
epidemiological study (Klaassen, 1980) of causes of mortality in 7000
lead workers in the US, showed a slight increase of deaths from cancer
but the statistical significance of these findings have been debated.
Lead chromate is a suspected human carcinogen of the lung (Hathaway et
al 1991) but a study of 1152 workers at a pigment factory did not find
any relationship between exposure to lead chromate and lung cancer
(Davies 1984).
9.2 Genotoxicity
No data.
9.3 Mutagenicity
Lead induced gene mutations in cultures of mammalian cells have only
been observed at concentrations toxic to the cells. Studies for point
mutations in bacterial systems have also yielded negative results.
Insoluble lead sulphide and soluble lead nitrate were found to be
mutagenic when added to Chinese hamster V79 cells. A 6 fold increase
in mutation frequency was noted at a lead nitrate level of 500 mmol/L
medium. However, the authors concluded that these effects may not have
been the result of direct damage to DNA but may have occurred via
indirect mechanisms including disturbances in enzyme functions
important in DNA synthesis or repair. Studies on the production of
chromosome aberrations, sister chromatin exchange and micronuclei by
lead, whether in in vitro or in vivo, have given mixed results.
9.4 Reprotoxicity
The reproductive effects of lead in the male are limited to sperm
morphology and count (Assennato et al 1986).
It is not known if exposure to organic lead can cause similar problems
(Barlow and Sullivan 1982).
Lead is thought to represent a significant environmental hazard to
pregnant women and their offspring (Angle and McIntire 1964, Palmisano
et al 1969). Exposure to high environmental levels of lead has been
associated with spontaneous abortion, premature rupture of foetal
membranes and preterm delivery. There may also be obstetric
complications at chronic low lead levels (Angell and Lavery 1982).
Most recent information relates to reports of occupational cohorts and
of populations living in polluted areas near industrial plants. There
is a qualitative evidence that lead is toxic to the reproduction
system in both men and women. However, there are insufficient data to
provide the basis for estimation of dose effect relationship in women
(WHO 1995).
9.5 Teratogenicity
A study of pregnancies in the centre and surroundings areas of lead
smelter town showed that the incidence of miscarriages (22 or 23) and
stillbirths (10 or 11) was higher in women living close to the
smelter. Some studies have also found decreased length of gestation in
women whose lead level were greater than 230 mg/L. Other studies have
not shown a significant association between birth weight and lead
exposure.
9.6 ADI
Provisional maximum tolerable weekly intake:
Adults: 3 mg per person or 50 mg/kg body weight; children and infants:
25 mg/kg body weight (Reynolds et al 1993).
Amount of lead in food:
In the UK is restricted to a maximum of 1 ppm with the exception of
foods specially prepared for infants and children, where the limit is
0.2 ppm (Reynolds et al 1993).
Maximum exposure limit:
In the UK the maximum exposure limit of lead and lead compounds
(except tetraethyl lead) is 0.15 mg (as Pb) per m3 (long term) and
for tetraethyl lead is 0.10 mg (as Pb) per m3
In the US the permitted and recommended exposure limit of inorganic
lead is 0.10 mg/m3 (long term) and for organic lead is less than
0.10 mg/m3, so that blood concentrations are 0.6 mg/ml or less
(Reynolds et al 1993).
9.7 MRL
9.8 AOEL
9.9 TLV
9.10 Relevant animal data
In all species of experimental animals studied lead has been shown to
cause adverse effects in several organ systems, including the
haemopoetic, nervous, renal, cardiovascular, reproductive and immune
systems. Lead also affects bone and has been shown to be carcinogenic
in rats and mice.
Despite kinetic differences between experimental species and humans,
these studies provide strong biological support and plausibility for
the findings in humans. Impaired learning and memory abilities have
been reported in rats with lead concentrations of 150-200 mg/L and in
non-human primates at lead levels not exceeding 150 mg/L. In addition,
visual and auditory impairment has been reported in experimental
studies.
Renal toxicity in rats appears to occur at lead levels of 600 mg/L, a
value similar to that reported to initiate renal effects in humans.
Cardiovascular effects have been seen in rats after chronic low levels
exposure resulting in lead concentrations of 50-400 mg /L. Tumours
have been shown to occur at dose levels below the maximum tolerated
dose of 200 mg lead (as lead acetate) per litre of drinking water.
This is the maximum level not associated with other morphological or
functional abnormalities (WHO 1995).
9.11 Relevant in vitro data
10 ENVIRONMENTAL DATA
10.1 Ecotoxicological data
Solubility in water
Metallic lead is insoluble in water.
Tetraethyl and tetramethyl lead are poorly soluble.
Trialkyl lead compounds are more soluble in water (WHO 1989).
10.2 Behaviour
Adsorption onto soil
Lead is strongly adsorbed onto sediment and soil particles (WHO 1989).
If released or deposited onto soil lead will be retained in the upper
2 - 5 cm of soil especially in soils with at least 5% organic matter
or pH 5 or above. Leaching is not important under normal conditions
although there is some evidence to suggest that lead is taken up by
some plants. Generally the uptake of lead by plants is not
significant. It is expected to slowly undergo speciation to the more
insoluble sulphate, sulphide, oxide and phosphate salts.
10.3 Biodegradation
Environmental fate
Lead released into the atmosphere partitions to surface water, soil
and sediment. Lead is transported in the atmosphere and in surface
water.
Photolysis
Organic lead compounds are transformed in surface waters by
photolysis.
Hydrolysis
Organic lead compounds are transformed in surface waters by
hydrolysis.
10.4 Environmentally important metabolites
No data.
10.5 Hazard warnings
10.5.1 Aquatic life
Aquatic plants: There is little evidence for toxicity of lead on
aquatic plants at concentrations below 1 to 15 mg/L. Concentrations of
more than 15 mg/L may be toxic.
Aquatic invertebrates: The results of toxicity studies on aquatic
invertebrates is difficult to interpret because of the variation in
experimental conditions. Also organisms in some lead polluted waters
may be more lead sensitive than others. Studies have shown that the
larvae of the oyster Crassostrea gigas had inhibited growth when
incubated in water with a lead nitrate at a concentration of 0.01 or
0.02 mg/L.
Fish: The toxicity of lead-contaminated water in fish varies according
to a number of conditions including pH and organic matter
concentration. Uptake is also affected by the presence of other
cations and the oxygen concentration. Organic lead is taken up more
readily than inorganic lead and may be 10 to 100 times more toxic than
inorganic lead. Long-term exposure of adult fish to inorganic lead
induces sub-lethal effects on morphology as well as enzyme activities
(e.g. delta-aminolevulinic acid dehydratase) and avoidance behaviour
at available lead concentrations of 10-100 mg/L. Juvenile stages are
generally more sensitive than adults. However eggs are thought to be
less at risk of lead toxicity because lead is adsorbed onto the
surface of the egg and excluded from the developing embryo. Generally
lead does not appear to bioconcentrate significantly in fish (WHO
1989).
Amphibia: There is evidence that frog and toad eggs are sensitive to
lead concentrations of <1 mg/L in standing water and 0.04 mg/L in
flow-through systems. Lead at these concentrations may cause arrested
development and delayed hatching. There are no significant effects in
adult frogs at levels <5 mg/L in aqueous solutions but lead in the
diet at a concentration of 10 mg/kg food may cause some biochemical
abnormalities. (WHO 85 1993)
10.5.2 Bees
No data.
10.5.3 Birds
High dietary doses of lead salts (>100 mg/kg) are toxic to birds. A
variety of effects have been reported at high doses but the most
common effects are diarrhoea, lack of appetite and consequent anorexia
and weight loss. Lethal and sublethal effects have not been reported
at concentrations likely to occur in the wild.
Metallic lead is toxic at high doses when fed as a powder. It is
highly toxic however when given as lead shot. Ingestion of a single
lead pellet can be fatal for some birds, however there is variable
interspecies sensitvity and toxicity can be dependent on the diet.
Birds have commonly been found in the wild with as many as 20 lead
shot in the gizzard (WHO 1985). Clinical signs include ataxia, leg
weakness, paralysis, emaciation and diarrhoea (Fahy 1987).
There is limited information on the toxicity of organolead compounds
in birds. When starlings were fed trialkyl lead compounds a dose of 2
mg/day was fatal. There have been recurring incidents of bird deaths
in estuaries near to industrial plants manufacturing leaded antiknock
compounds. The total lead content of the livers was sufficiently high
to cause mortalities: lead was mainly present in the alkyl form (WHO
1993).
10.5.4 Mammals
Dogs: There is a high prevalence of lead toxicity in dogs. Usually
gastrointestinal effects precede neurological signs by several days.
The most common signs are vomiting, abdominal pain and anorexia. The
abdominal pain or "lead colic" is manifest by whining, restlessness,
tense abdomen and crying when the abdomen is palpated. Neurological
signs include convulsions, hysteria (barking and crying continuously,
running in all directions and biting at animate and inanimate
objects), ataxia, blindness and chomping of the jaws.
Cattle and sheep: in cattle the first signs are usually depression
and anorexia. Gastrointestinal signs include constipation and
diarrhoea. Abdominal pain may be evident and cattle may grind their
teeth and appear to be chewing. Neurological signs include twitching
of the ears, fine muscle tremor, eye blinking, head bobbing, circling
and pushing against objects. There may be marked excitement and
convulsions prior to death. Terminal excitement and death may be the
only signs observed. Death may occur a few hours to several days after
the onset of clinical signs. Lead intoxication in sheep is similar and
characterised by depressed rumen motility, lethargy and coarse body
tremors immediately prior to death. Chronic lead exposure in lambs may
result in osteoporosis and hydronephrosis.
Horses: Acute lead poisoning is rare because of their selective
eating habits but horses seem to be quite susceptible to chronic
low-level poisoning. Generally affected horses live near lead
industries and chronic poisoning occurs from lead contaminated
pasture. Horses show more peripheral nerve involvement than other
domestic animals. This is characterised by muscle weakness and
"roaring" resulting from paralysis of the recurrent laryngeal nerve.
Aspiration pneumonia may also result as a consequence of this
paralysis. Sudden death may occur from anoxia precipitated by
laryngeal paralysis. Other signs include progressive loss of weight,
anorexia, muscle weakness, stiffness of joints and progressive arching
of the back (Fahy 1987).
Other species: Three fruit bats and 34 simian primates died in
Washington Zoo after lead paint was used to paint their cages (WHO
1989).
10.5.5 Plants
In terrestrial plants the availability of lead is limited since lead
tends to form highly insoluble salts and complexes with various anions
and lead compounds tend to be bound to soil. Translocation of the lead
ion is limited and most bound lead stays at root or leaf surfaces.
Most studies on lead toxicity to plants have shown that very high soil
lead levels are needed (100-1000 mg/kg) to cause inhibition of
photosynthetic rate and growth (WHO 1989).
10.5.6 Protected species
No data.
10.6 Waste disposal data
Authors
Grainne Cullen
Alison Dines
Stoyko Kolev
National Poisons Information Service (London Centre)
Medical Toxicology Unit
Guy's & St Thomas' Hospital Trust
Avonley Road
London
SE14 5ER
UK
This monograph was produced by the staff of the London Centre of the
National Poisons Information Service in the United Kingdom. The work
was commissioned and funded by the UK Departments of Health, and was
designed as a source of detailed information for use by poisons
information centres.
Peer review was undertaken by the Directors of the UK National Poisons
Information Service.
March 1996
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See Also:
Toxicological Abbreviations
Lead (EHC 3, 1977)
Lead (ICSC)
Lead (WHO Food Additives Series 4)
Lead (WHO Food Additives Series 13)
Lead (WHO Food Additives Series 21)
Lead (WHO Food Additives Series 44)
LEAD (JECFA Evaluation)