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Lead, inorganic

1. NAME
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Brand names, Trade names
   1.6 Manufacturers, Importers
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First-aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physical properties
   3.4 Other characteristics
4. USES/CIRCUMSTANCES OF POISONING
   4.1 Uses
   4.2 High risk circumstance of poisoning
   4.3 Occupationally exposed populations
5. ROUTES OF ENTRY
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Others
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination by route of exposure
7. TOXICOLOGY
   7.1 Mode of Action
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
      7.2.4 Workplace standards
      7.2.5 Acceptable daily intake (ADI) and other guideline levels
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection
         8.1.1.1 Toxicological analyses
         8.1.1.2 Biomedical analyses
         8.1.1.3 Arterial blood gas analysis
         8.1.1.4 Haematological analyses
         8.1.1.5 Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens
         8.1.2.1 Toxicological analyses
         8.1.2.2 Biomedical analyses
         8.1.2.3 Arterial blood gas analysis
         8.1.2.4 Haematological analyses
         8.1.2.5 Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens
         8.1.3.1 Toxicological analyses
         8.1.3.2 Biomedical analyses
         8.1.3.3 Arterial blood gas analysis
         8.1.3.4 Haematological analyses
         8.1.3.5 Other (unspecified) analyses
   8.2 Toxicological Analyses and Their Interpretation
      8.2.1 Tests on toxic ingredient(s) of material
         8.2.1.1 Simple Qualitative Test(s)
         8.2.1.2 Advanced Qualitative Confirmation Test(s)
         8.2.1.3 Simple Quantitative Method(s)
         8.2.1.4 Advanced Quantitative Method(s)
      8.2.2 Tests for biological specimens
         8.2.2.1 Simple Qualitative Test(s)
         8.2.2.2 Advanced Qualitative Confirmation Test(s)
         8.2.2.3 Simple Quantitative Method(s)
         8.2.2.4 Advanced Quantitative Method(s)
         8.2.2.5 Other Dedicated Method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis
         8.3.1.1 Blood, plasma or serum
         8.3.1.2 Urine
         8.3.1.3 Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
      8.3.4 Interpretation of biomedical investigations
   8.4 Other biomedical (diagnostic) investigations and their interpretation
   8.5 Overall Interpretation of all toxicological analyses and toxicological investigations
   8.6 References
9. CLINICAL EFFECTS
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological
         9.4.3.1 CNS
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Others
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ears, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic
         9.4.12.1 Acid-base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Others
   9.6 Summary
10. MANAGEMENT
   10.1 General principles
   10.2 Relevant laboratory analyses and other investigations
      10.2.1 Sample collection
      10.2.2 Biomedical analysis
      10.2.3 Toxicological analysis
      10.2.4 Other investigations
   10.3 Life supportive procedures and symptomatic treatment
   10.4 Decontamination
   10.5 Elimination
   10.6 Antidote treatment
      10.6.1 Adults
      10.6.2 Children
   10.7 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from literature
   11.2 Internally extracted data on cases
   11.3 Internal cases
12. ADDITIONAL INFORMATION
   12.1 Availability of antidotes
   12.2 Specific preventive measures
   12.3 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESSES
    1. NAME
     1.1 Substance
       Inorganic lead
     1.2 Group
       Non-ferrous metal
     1.3 Synonyms
       C.I. 77575
       C.I. pigment metal
       KS-4
       lead flake
       lead S2
       Plumbum (Pb)
     1.4 Identification numbers
       1.4.1 CAS number
             7439-92-1
       1.4.2 Other numbers
             DOT       1794
             RTECS     OF7525000
     1.5 Brand names, Trade names
       Not applicable.
     1.6 Manufacturers, Importers
       Not applicable.
       (NIOSH, 1978; Budavari, 1989; Sax, 1989)
    2. SUMMARY
     2.1 Main risks and target organs
       Exposure occurs from breathing air, drinking water, and eating 
       foods that contain lead. Inhalation of lead fumes or of fine 
       lead particles is the most important route of absorption in 
       the working environment and general atmosphere.  Chronic low-
       dose lead exposure exerts subtle neuropsychiatric, 
       reproductive and renal effects and children are particularly 
       susceptible.  
       
       Acute poisoning may follow ingestion of lead-containing paint 
       by children (pica). The possible effects of low-dose of lead 
       in adults is still unclear. Hypertension, gout, nephropathy, 
       and neurotoxic symptoms may be related to lead exposure.
       
       Target organs
       
       Lead interferes with the haem biosynthetic pathway, producing 
       haematological effects, and competes at the molecular level 
       with calcium. The central nervous system and kidneys are 
       particularly sensitive to lead. The central and peripheral 
       nervous systems are affected; gastrointestinal structures are 
       also damaged; and there is strong evidence of effects on the 
       reproductive system.  Lead also may have a role as a cofactor 
       in carcinogenesis (Putnam, 1986; Sax, 1989; ATSDR, 1990; Goyer,
        1990).
     2.2 Summary of clinical effects
       Poisoning by inorganic lead compounds presents as three main 
       clinical pictures: chronic poisoning; acute poisoning; and 
       asymptomatic poisoning, occurring during childhood.
       
       Acute poisoning from a single exposure is rare but may result 
       from the ingestion of solutions of soluble lead salts (lead 
       acetate, lead carbonate). The primary symptoms are related to 
       local irritation of the gastrointestinal tract and include: 
       vomiting and abdominal colic.  Pain in the legs, cramps and 
       paresthesiae may follow, with shock, haemolytic anaemia and 
       renal dysfunction.  Depression, coma and death occur within 1 
       to 2 days.
       
       Lead is a cumulative poison and the acute symptoms are 
       commonly a manifestation of chronic poisoning. Chronic 
       symptomatic poisoning (plumbism) causes abdominal colicky 
       pains, anorexia, nausea, vomiting, metallic taste, blue line 
       on the gum margins, anaemia, peripheral neuropathy (wrist 
       drop), convulsions and encephalopathy.
       
       In childhood, lead poisoning may be asymptomatic. There may be 
       elevated levels of lead in the blood but symptoms are delayed. 
       The so-called developmental syndrome, with cognitive and 
       behavioural changes, is the consequence of the absorption of 
       lead, mainly from pica.  Anaemia is often a common
       manifestation.  It is very important to implement chelation 
       therapy soon after diagnosis (Prerovska, 1974; Gilman, 1990; 
       Garrettson, 1990).
     2.3 Diagnosis
       Diagnosis of poisoning is based on history of exposure and the 
       clinical signs and symptoms described above.  Chronic 
       poisoning may be asymptomatic for some time.  Many laboratory 
       tests are used for the diagnosis of lead poisoning. Many 
       laboratory tests are used for the diagnosis of lead poisoning.
       
       Blood: complete blood count (basophilic stippling of red 
       cells); whole-blood lead levels; red cell delta-aminolevulinic 
       acid dehydratase activity; free erythrocyte protoporphyrin.
       
       Urine: 24-hour urine lead levels; Urinary delta-aminolevulinic 
       acid; Urinary coproporphyrin; Lead in urine after calcium 
       disodium EDTA mobilization test.
       
       Hair:     determination of lead levels.
       
       Sample collection: a 24-hour specimen of urine is preferable 
       to a single specimen; the blood sample should be taken and 
       stored in specially cleaned glass-ware; samples of hair should 
       be properly washed. 
     2.4 First-aid measures and management principles
       The main emphasis of management is on symptomatic treatment of 
       life-threatening effects and chelation therapy with EDTA, BAL, 
       DMSA or pencillamine depending on the particular case and 
       antidote availability.
       
       If acute poisoning by inorganic lead occurs, remove patient 
       from further exposure, send for medical assistance, remove and 
       discard contaminated clothing, wash skin with soap and copious 
       amounts of water.  If the patient has seizures, control 

       convulsions with appropriate drug regimen, and treat 
       symptomatically.
       
       After oral ingestion and unless vomiting is extensive, if the 
       patient is obtunded, convulsing, comatose, insert an oro- or a 
       naso-gastric tube and lavage after endotracheal intubation.
       
       In the case of lead encephalopathy, calcium disodium may be 
       indicated, as well as in cases of acute poisoning by ingestion,
        or in acute episodes during chronic poisoning. 
       
       Chronic poisoning: combined treatment BAL and edetate calcium 
       disodium is indicated in adults with blood lead levels up to 
       1000 g/L.  Interrupt treatment for 2 days and, if the blood 
       lead level remains high, restart edetate; subsequently, d-
       penicillamine may be given for 3 to 6 months.
       
       Children with blood lead levels up to 700 ug/L should be 
       treated with combined BAL and edetate calcium disodium; BAL 
       may be discontinued after 3 days if the blood lead is < 500 
       ug/L but edetate should be continued for 5 days.  Long term 
       chelation with penicillamine in children should be limited to 
       2 months.
    3. PHYSICO-CHEMICAL PROPERTIES
     3.1 Origin of the substance
       Lead is a naturally occurring metal in the earth's crust.  Its 
       compounds can be found in all parts of the environment. It 
       occurs in the earth's  crust chiefly as minerals such as 
       galena, anglesite, cerussite, mimetite and pyromorphite.  A 
       large number of inorganic lead compounds is represented by 
       acetate, antimonate, arsenate, arsenite, azide, bromate, 
       bromide, butyrate, chlorate, chloride, chromate, dioxide, 
       fluoride, formate, hexafluorosilicate, hydroxide, 
       hypophosphite, iodide, lactate, molybdate, monoxide, nitrate, 
       oxalate, phosphate, selenate, selenite, sesquioxide, sodium 
       thiosulphate, subacetate, sulfate, sulfide, telluride, 
       tetraacetate, tetrafluoride, tetroxide, thiocyanate, tungstate 
       and vanadate.
     3.2 Chemical structure
       Chemical name:      Lead
       
       Molecular weight:        207.2
       
       Structural formula: not applicable
     3.3 Physical properties
       Boiling point:      1740  C (at 760 mmHg)
       
       Melting point:      327.4  C
       
       Flash point:        not applicable
       
       Autoignition temperature:  Lead is combustible in powder 
       form
       
       Relevant density:        11.34 at 20  C
       
       Vapour pressure:         1.77 mmHg at 1000  C
            
       Solubility:              Lead nitrate, chlorate and, to a lesser
                                degree, chloride are soluble in water. 
                                Other salts are poorly soluble in water,
                                but many are dissolved by acids
            
       Explosive limits:        Lead azide explodes at 350 C
       
       Viscosity:               (Molten lead at 327.4  C) 3.2   
                              centipoises
       
       
                          Molecular  Structural
       Name   CAS Number    Weight    Formula   Solubility  Other
       ----   ----------  ---------  ---------- ----------  -----
       
       Lead   301-04-2     325.28    C4H6O4Pb    Alcohol    pH of
       Acetate                                   Water      water
                                                 Glycerol   sol=5.5-
                                                            6.5
       Lead                          Pb3(SbO4)2  Insoluble
       Antimonate                                in water
       
       Lead   7784-40-9              PbHAsO4     Insoluble
       Arsenate                                  in water;
                                                 soluble in
                                                 HNO3
       
       Lead   10031-13-7             Pb(ASO2)2   Insoluble  Explosive
       Arsenite                                  in water;
                                                 soluble in 
                                                 HNO3 
       
       Lead   13424-46-9   291.26    Pb(N3)2     Soluble in
       Azide                                     water and
                                                 acetic acid
       
       Lead                          Pb(BrO3)2   Soluble in
       Borate                                    water;
                                                 soluble in
                                                 HNO3
       
       Lead   34018-28-5   463.01    Pb(BrO3)2
       Bromate
       
       Lead                367.04    Br2Pb
       Bromide

     3.4 Other characteristics
       Normal state at room temperature: solid, heavy, ductile metal.
       Colour: blueish-white, silvery, grey metal.
       
       Dangers associated with vapours: vapours form at 550-600  C 
       and combine with oxygen in air to form lead oxide.
       
       Present in work atmosphere as fumes, mists (for instance, 
       produced by spray painting) and dusts.
       
       Lead reacts vigorously with oxidizing materials.  Contact with 
       hydrogen peroxide or active metals such as sodium or potassium 
       may cause fire or explosion.  Toxic fumes may be released in a 
       fire involving inorganic lead.  Attacked by pure water or weak 
       organic acids in the presence of oxygen.
       
       Pollution of the environment occurs through the smelting and 
       refining of lead, the burning of fuels containing lead 
       additives, and the smelting of other metals and the burning of 
       coal and oil.
       
       The transport and distribution of lead is mainly via air.  The 
       fraction that remains airborne (about 20%) is widely 
       dispersed.  The concentration of lead in air varies from 2-4 
       g/m3 in large cities to less than 0.2 g/m3 in suburban and 
       rural areas (WHO, 1972; WHO, 1977; ACGIH, 1986; Budavari, 
       1989).
    4. USES/CIRCUMSTANCES OF POISONING
     4.1 Uses
       Lead can be used in its pure form or combined with other 
       elements to form a variety of organic and inorganic 
       compounds. Metallic lead is used in storage batteries, 
       solders, ammunition, shielding systems for protection 
       from X-rays and radiation, lining tanks, and pipes.  It 
       is a major component of many alloys such solders, type 
       metals, and bronzes.  Lead inorganic salts are used in 
       insecticides, pigments, paints, enamels, glazes, glass, 
       plastics, rubber compounds (WHO, 1977; Glenn, 1986; 
       Putnam, 1986; Sax, 1989).
     4.2 High risk circumstance of poisoning
       Non-occupationally exposed individuals are exposed to 
       inorganic lead compounds primarily from ingestion of food and 
       water.  Inhalation of airborne lead originating in dusts and 
       fumes is still a very important environmental source.  Leaded 
       gasoline is an important cause of contamination and is 
       reviewed in the monograph on organic lead.
       
       Domestic sources include contamination of food and beverages 
       from contact with utensils as earth-glazed pottery; ingestion 
       of lead-containing paint by children (pica); and use of herbal 
       medicines contaminated with lead (WHO, 1977; Glenn, 1986; Sax, 
       1989).
     4.3 Occupationally exposed populations
       Lead is the most widely used non-ferrous metal and a large 
       number of occupations may be associated with risk of exposure.

       Workers may be exposed to metallic and inorganic lead 
       compounds in a wide variety of occupations, including mining, 
       smelting and refining operations; high-temperature lead 
       applications such as steel welding and spray coating; lead 
       grinding, cutting or discing; battery manufacturing and 
       recycling; radiator repair shops; production of paints, 
       ceramics and glazes, enamels and rubbers; car refinishing or 
       paint removal associated with building renovation; plumbing 
       and tank cleaning, etc..
       
       The Occupational Safety and Health Administration has 
       identified over 120 occupations in which workers may be 
       exposed to lead (Federal Register, 1978).  Lead poisoning is 
       one of the commonest occupational diseases, specially when 
       preventative measures are not established (WHO, 1977; Glenn, 
       1986; Sax, 1989).
    5. ROUTES OF ENTRY
     5.1 Oral
       Accidental or deliberate ingestion of lead compounds may 
       occur.  Lead may be ingested on contaminated food, drinks and 
       cigarettes, or lead particles trapped in the upper respiratory 
       tract may be swallowed.  5-15% of ingested inorganic lead is 
       absorbed from the gastrointestinal tract; the rest passes 
       through the body unabsorbed, and is eliminated in the faeces. 
       Absorption can increase to as much as 45% under fasting 
       conditions (Putnam, 1986) and 53% in infants and young 
       children (WHO, 1977).  Decreased calcium and zinc levels 
       increase lead absorption, and iron appears to enhance it.  
       Naphthenate, acetate and some oxides of lead are rapidly and 
       more completely absorbed (Garrettson, 1990).  Gastrointestinal 
       absorption of lead occurs by acid solubilization (Ellenhorn, 
       1988) and it seems that lead transport across the digestive 
       mucosa is similar to that of calcium (Gilman, 1990).
     5.2 Inhalation
       Inhalation of fumes, dusts, mists, and vapours of lead should 
       be considered as a major route of entry - from 50 to 70% of 
       the particles that reach the respiratory tract are absorbed, 
       depending on the particles (less than 1 m), their 
       concentration and the ventilation rate (Putnam, 1986; Budavari,
        1989; Gilman, 1990).
     5.3 Dermal
       Dermal absorption is not an efficient process, for inorganic 
       compounds of lead (Sax, 1989).
     5.4 Eye
       Not relevant.
     5.5 Parenteral
       One case of self-injection of lead acetate has been reported 
       (Sixel-Dietrick, 1985).
     5.6 Others
       Not relevant.
    6. KINETICS
     6.1 Absorption by route of exposure
       Accidental or deliberate ingestion of lead compounds may 
       occur.  Lead may be ingested on contaminated food, drinks and 
       cigarettes, or lead particles trapped in the upper respiratory 

       tract may be swallowed.  Between 5-15% of ingested inorganic 
       lead is absorbed through the gastrointestinal tract.  The rest 
       passes through the body unabsorbed, and is eliminated in the 
       faeces.  Absorption can increase to as much as 45% under 
       fasting condition (Putnam, 1986) or 53% in infants and young 
       children (53%) (WHO, 1977). Decreased calcium and zinc levels 
       increase lead absorption, and iron appears to enhance it.  
       Naphthenate, acetate and some oxides of lead are rapidly and 
       more completely absorbed (Garrettson, 1990).  Gastrointestinal 
       absorption of lead occurs by acid solubilization (Ellenhorn, 
       1988) and it seems that lead transport across the digestive 
       mucosa is similar to that of calcium (Gilman, 1990).
       
       Inhalation of fumes, dusts, mists, and vapours of lead should 
       be considered as a major route of entry - from 50 to 70% of 
       the particles that reach the respiratory tract are absorbed, 
       depending in large part of the size of the particles (less 
       than 1 m), their concentration and the ventilation rate 
       (Putnam, 1986; Gilman, 1990).  Dermal absorption is not an 
       efficient process for inorganic compounds of lead (Sax, 1989).
     6.2 Distribution by route of exposure
       Lead is distributed according to a three-compartmental 
       pharmacokinetic model. Blood and soft tissues represent the 
       active pool and bones the storage pool. Lead is distributed to 
       kidney tubular epithelium and to liver, and redistributed to 
       bone, teeth, and hair; the long bones contain more lead and 
       about 95% of the body load is stored in the skeleton.  The 
       largest part of circulating lead is bound to haemoglobin in 
       erythrocytes and the concentration of lead in erythrocytes is 
       about 16 times greater than in plasma (WHO, 1977).
       
       Factors affecting the distribution of calcium, such as 
       phosphate intake, also affect the distribution of lead in 
       bones (a high intake of phosphate favours the storage in the 
       skeleton while a low intake promotes the redistribution from 
       bones to soft tissues) (Ellenhorn, 1988; Gilman, 1990; 
       Garrettson, 1990).
       
       Lead has an affinity for the organic osteoid substance of bone 
       rather than its mineral components (Flood et al., 1988).  In 
       certain circumstances (infection, wasting disease, pregnancy) 
       lead may be mobilized from storage sites in bone. Under 
       conditions of continuous  intake over long periods of time, a 
       near-steady state is achieved with respect to 
       intercompartmental distribution (WHO, 1977).
     6.3 Biological half-life by route of exposure
       The biological half-life of lead is extremely difficult to 
       estimate (WHO, 1977).  The half-life of lead in erythrocytes 
       is 35 days; in soft tissues (kidney, liver, and nervous 
       tissue) the half-life is 40 days; the half-life in bone is 20 
       to 30 years (Ellenhorn, 1988: Garrettson, 1990).
       
       The half-life in blood reaches a steady state in about 6 
       months.  The time required for accumulation of toxic 
       concentrations is inversely proportional to lead intake: a 

       daily intake of 2.5 mg will achieve a toxic level after 4 
       years whereas daily ingestion of 3.5 mg achieves similar 
       levels in only a few months (Gilman, 1990).
     6.4 Metabolism
       Inorganic lead compounds and elemental lead are not modified 
       by organic biochemical processes.
     6.5 Elimination by route of exposure
       The rate of excretion of lead is low. Renal clearance of 
       unchanged lead is essentially by glomerular filtration but at 
       high levels some active tubular transport occurs.  Urinary 
       excretion accounts for 76% of daily losses, while 
       gastrointestinal secretions for 16% and hair, nails, sweat and 
       other routes for 8% (WHO, 1977; Ellenhorn, 1988).
       
       When calcium disodium EDTA is administered the lead normally 
       excreted in the faeces is not transferred to the renal route. 
       Instead, the urinary lead arises from the removal of lead 
       deposited in organic tissue (Prerovska et al., 1974).
    7. TOXICOLOGY
     7.1 Mode of Action
       Lead combines with sulfhydryl groups on proteins and 
       interferes with some biochemical processes. The enzymes 
       involved in the pathways of haem, myoglobin, cytochromes, and 
       catalases, are inhibited by lead. In the blood very low 
       concentrations of lead inhibit the synthesis of haem and 
       reduces the life span of erythrocytes.  In the nervous system, 
       lead disrupts mitochondrial function.  In the kidney, lead 
       produces lesions of the proximal tubules and the loop of Henle 
       (WHO, 1977; Hodgson et al., 1987; Ellenhorn, 1988; Gilman, 
       1990).
     7.2 Toxicity
       7.2.1 Human data
             7.2.1.1 Adults
                     The dose of lead required to cause adverse 
                     effects is rarely, if ever, known.  The lead 
                     blood level confirms a causal link between 
                     likely exposure and an effect (WHO, 1977).
                     
                     Fatal poisoning occurs with lead acetate and 
                     lead carbonate in doses exceeding 30 g (Gosselin,
                      1984).  Accumulation and toxicity occur if > 
                     0.5 mg/day is absorbed.  The fatal  dose is 
                     estimated at 500 mg of absorbed lead (Noji & 
                     Kelen, 1989).
                     
                     The lowest observed adverse effect level (LOAEL) 
                     in human volunteers exposed to particulate lead 
                     (inhalation) is 3.2 g/m3.  The LOAEL in human 
                     volunteers is 20 g/kg/day of lead acetate daily 
                     for 21 days (0.2 mg/kg/day) (ATSDR, 1990).
                     
                     Inhalation:  Lowest toxic concentration in 
                     humans - 10 g/m3.

             7.2.1.2 Children
                     Death from lead poisoning has occurred in 
                     children at blood lead levels of 1250 g/L or 
                     higher.  The LOAEL for children (causing 
                     developmental toxicity) is 100 g/L in blood. 
                     This level is associated with diminishing IQ 
                     score in children (Sax, 1989; ATSDR, 1990).
       7.2.2 Relevant animal data
             The lowest lethal dose for the dog is 191 mg/kg Pb; for 
             the guinea-pig is 313 mg/kg Pb (Sax, 1989).
             
             Lowest Toxic Dose oral rats: 790 mg/kg
             Lowest Toxic Dose oral rats: 1100 mg/kg (over 14 days)
             Lowest Toxic Dose inhalation rats: 10 mg/m3/24 h
             Lowest Lethal Dose intraperitoneal (rat): 1000 mg/kg   
             Lowest Lethal Dose oral (pigeon): 160 mg/kg  (Sax, 1989)
       7.2.3 Relevant in vitro data
             Lead salts did not induce chromosomal aberrations in 
             human lymphocytes in vitro (IARC, 1987).
       7.2.4 Workplace standards
             Permissible Exposure Limit (PEL): 50 g/m3 (NIOSH, 
             1978).
             
             Recommended Exposure Limit (REL) Time Weighted Average 
             (TWA): 100 g/m3 (NIOSH, 1978).
             
             TLV-TWA (Threshold Limit Values-Time Weighted Average) 
             inorganic dusts and fumes, as Pb: 150 g/m3 (ACGIH, 
             1990).
       7.2.5 Acceptable daily intake (ADI) and other guideline levels
             Provisional maximum tolerable weekly intake of lead: 
             adults, 3 mg per person or 50 g/kg body weight; 
             children 25 g/kg body weight (FAO/WHO, 1987).
             
             In Great Britain, the amount of lead in food is 
             generally restricted to a maximum of 1 ppm with the 
             exception of food specially prepared for infants and 
             children, where the limit is 0.2 ppm (Ministry Agric. 
             Fish & Food, 1982).
     7.3 Carcinogenicity
       At very high concentrations, lead displays some carcinogenic 
       activity in experimental animals. The evidence for 
       carcinogenicity in humans is inadequate (IARC, 1987).
     7.4 Teratogenicity
       There have not been any adequate animal studies to provide 
       evidence to support the suggestion that lead may have a 
       teratogenic effect.  In humans, one case has been reported of 
       neuromuscular abnormalities and failure to grow in one child; 
       this was attributed to lead poisoning as a result of the 
       consumption of lead by the pregnant mother (WHO, 1977).
     7.5 Mutagenicity
       Studies of chromosomal aberrations in people exposed to lead 
       have given conflicting results: positive results have been 
       published concerning workers in lead battery industries and 
       lead smelters but other studies have given negative results.  

       Lead salts do not induce chromosomal aberration in human 
       lymphocytes in vitro.  They do not cause aneuploidy in 
       Drosophila, mutation or gene conversion in yeast or mutation 
       or DNA damage in bacteria (IARC, 1987).
     7.6 Interactions
       Interactions between lead and other environmental pollutants 
       occur.  Lead forms lead sulfate in both water and air in the 
       presence of the sulfate ion (ATSDR, 1990).
       
       Lead and disulfiram increase brain lead concentrations, and 
       depress Purkinje neuron function in the rat (Oskarsson et al., 
       1986).  Lead brain levels are increased after long-term 
       treatment with lead and dithiocarbamate or thiuram derivatives 
       in rats (Oskarsson & Lind, 1985).
    8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
     8.1 Material sampling plan
       8.1.1 Sampling and specimen collection
             8.1.1.1 Toxicological analyses
             8.1.1.2 Biomedical analyses
             8.1.1.3 Arterial blood gas analysis
             8.1.1.4 Haematological analyses
             8.1.1.5 Other (unspecified) analyses
       8.1.2 Storage of laboratory samples and specimens
             8.1.2.1 Toxicological analyses
             8.1.2.2 Biomedical analyses
             8.1.2.3 Arterial blood gas analysis
             8.1.2.4 Haematological analyses
             8.1.2.5 Other (unspecified) analyses
       8.1.3 Transport of laboratory samples and specimens
             8.1.3.1 Toxicological analyses
             8.1.3.2 Biomedical analyses
             8.1.3.3 Arterial blood gas analysis
             8.1.3.4 Haematological analyses
             8.1.3.5 Other (unspecified) analyses
     8.2 Toxicological Analyses and Their Interpretation
       8.2.1 Tests on toxic ingredient(s) of material
             8.2.1.1 Simple Qualitative Test(s)
             8.2.1.2 Advanced Qualitative Confirmation Test(s)
             8.2.1.3 Simple Quantitative Method(s)
             8.2.1.4 Advanced Quantitative Method(s)
       8.2.2 Tests for biological specimens
             8.2.2.1 Simple Qualitative Test(s)
             8.2.2.2 Advanced Qualitative Confirmation Test(s)
             8.2.2.3 Simple Quantitative Method(s)
             8.2.2.4 Advanced Quantitative Method(s)
             8.2.2.5 Other Dedicated Method(s)
       8.2.3 Interpretation of toxicological analyses
     8.3 Biomedical investigations and their interpretation
       8.3.1 Biochemical analysis
             8.3.1.1 Blood, plasma or serum
             8.3.1.2 Urine
             8.3.1.3 Other fluids
       8.3.2 Arterial blood gas analyses
       8.3.3 Haematological analyses
       8.3.4 Interpretation of biomedical investigations

     8.4 Other biomedical (diagnostic) investigations and their 
       interpretation
     8.5 Overall Interpretation of all toxicological analyses and 
       toxicological investigations
     8.6 References
    9. CLINICAL EFFECTS
     9.1 Acute poisoning
       9.1.1 Ingestion
             Acute poisoning from a single exposure is rare and may 
             result from the ingestion of soluble lead salts.  Acute 
             episodes are frequently a manifestation of chronic 
             poisoning.  Primary symptoms are related to 
             gastrointestinal irritation and include anorexia, 
             vomiting, abdominal colic.  Pain in the legs, cramps and 
             paresthesiae may follow.  Shock, haemolytic anaemia and 
             renal dysfunction are observed.  Headache and 
             hypertension have been reported in adults (Gosselin, 
             1984; Ellenhorn, 1988; Noji & Kelen, 1989; Garrettson; 
             1990).
       9.1.2 Inhalation
             Inhalation of lead oxides, fumes or of fine lead 
             particles is the most important route of absorption in 
             the working environment (Fischbein, 1983).  However, 
             acute episodes with systemic symptoms are exceptional.
       9.1.3 Skin exposure
             Not relevant.
       9.1.4 Eye contact
             Not relevant.
       9.1.5 Parenteral exposure
             One case of lead acetate intravenously injected has been 
             described (Sixel-Dietrick et al., 1985).
       9.1.6 Other
             Not relevant.
     9.2 Chronic poisoning
       9.2.1 Ingestion
             Chronic poisoning by ingestion causes a number of 
             symptoms: abdominal colicky pains, anorexia, nausea, 
             vomiting, metallic taste,  blue line on the gum margins, 
             anaemia, peripheral neuropathy, irritability, lethargy, 
             convulsions, encephalopathy conditions.  Chronic 
             nephritis and hypertension have been described.  Two 
             groups are particularly affected: adults exposed 
             occupationally, and children.  The symptoms are not 
             specific to lead poisoning and should be considered as 
             signs of poisoning if exposure and working conditions 
             indicate the possibility of increased lead absorption.
             
             Three major clinical syndromes of chronic poisoning are 
             described: the gastrointestinal type, the neuromuscular 
             type and the cerebral type.  The cerebral syndrome is 
             most often seen in childhood and is associated with 
             encephalopathy.  However, many of the signs and symptoms 
             described are features common to all types (ILO, 1983; 
             Gosselin, 1984; Ellenhorn, 1988; Garrettson, 1990).

       9.2.2 Inhalation
             The main route of entry in industrial exposure is the 
             respiratory tract.  However, bad conditions of hygiene 
             and living in the neighbourhood of small industries 
             which use lead can affect general population, especially 
             children.
             
             The clinical picture of chronic plumbism by inhalation 
             is similar to that described after chronic ingestion: 
             fall-off in physical fitness, fatigue, sleep disturbance,
              headache, aching bones and muscles, vomiting, abdominal 
             colic, obstipation, decreased appetite.  Anaemia, 
             peripheral nerve disturbances and acute encephalopathy 
             may develop in children (ILO, 1983; Gosselin, 1984; 
             Ellenhorn, 1988; Garrettson, 1990).
       9.2.3 Skin exposure
             Not relevant.
       9.2.4 Eye contact
             Not relevant.
       9.2.5 Parenteral exposure
             An unusual case of lead poisoning due to intravenous 
             injection has been reported (Sixel-Dietrick et al., 
             1985).
       9.2.6 Other
             Unusual cases of lead chronic poisoning have been 
             reported after liberation into the circulation, over 
             periods of many years, of lead from retained bullets, 
             (Gosselin, 1984).
     9.3 Course, prognosis, cause of death
       After chelation therapy, complete recovery may take up to 1 
       year.  Long-term effects include neurological deficits, 
       chronic nephritis, nephrotic syndrome and saturnine gout.
       
       In children, subtle behavioural, cognitive and neurological 
       deficits (developmental syndrome) become evident many years 
       after the exposure to lead and mortality in lead 
       encephalopathy is as high as 25%.  A large number of patients 
       surviving lead encephalopathy have neurological sequelae, 
       mental retardation, EEG abnormalities, seizures, cerebral 
       palsy, optical atrophy, or dystonia musculorum deformans 
       (Chisolm & Barltrop, 1979).  Death is caused by a multitude of 
       factors as anaemia, infection, immunologic impairment, 
       bleeding from gastrointestinal tract, kidney failure, 
       hypertension and central nervous system effects.  Malignant 
       neoplasms are statistically more common among battery plant 
       workers (Gosselin, 1984; Putnam, 1986; Ellenhorn, 1988; Noji & 
       Kelen, 1989; Goyer, 1990).
     9.4 Systematic description of clinical effects
       9.4.1 Cardiovascular
             Acute: arterial hypertension may be present.  Shock 
             syndrome due to massive gastrointestinal loss of fluids.
             
             Chronic: arterial hypertension.  Peripheral 
             vascoconstriction.

       9.4.2 Respiratory
             Acute: not relevant.
             
             Chronic: not relevant.
       9.4.3 Neurological
             9.4.3.1 CNS
                     Acute: Paresthesiae, pain, muscle weakness.  
                     Encephalopathy (rare): severe headache, 
                     convulsions, delirium, coma.
                     
                     Chronic:  Fatigue, sleep disturbance, headache, 
                     irritability, lethargy. Slurred speech, stupor, 
                     ataxia, convulsions.  Hyperkinetic and 
                     aggressive behaviour disorders. Also in 
                     children: refusal to play and learning 
                     regression.
                     
                     Lead encephalopathy (more common in children): 
                     vertigo, ataxia, headache, insomnia, 
                     restlessness and irritability.  Delirium, tonic-
                     clonic convulsions, coma.  Increased 
                     intracranial pressure.
             9.4.3.2 Peripheral nervous system
                     Acute: Paresthesiae, pain, muscle weakness.
                     
                     Chronic: Paresthesiae, pain, muscle weakness; 
                     lead palsy involves the most active muscles, 
                     including paralysis of the radial nerve with 
                     "wrist drop".  The afferent nerves are not 
                     affected: there is no loss of sensation and no 
                     pain.  Slowing of nerve conduction by segmental 
                     demyelination.
             9.4.3.3 Autonomic nervous system
                     Acute and chronic:  Lead affects cholinergic, 
                     dopaminergic, and noradrenergic functions in 
                     brain.
             9.4.3.4 Skeletal and smooth muscle
                     Acute and chronic:  Smooth muscles of the gut 
                     are affected, producing intestinal colic.
                     
                     Effects on skeletal muscles, especially in the 
                     limbs, cause weakness, tremors and paralysis.
       9.4.4 Gastrointestinal
             Metallic taste, thirst.  The lead line (Burton or blue 
             line) consists of a deposit of dark blue-grey lead 
             sulfide in the gums about 1 mm from the margins.  It 
             does not occur in edentulous gums.  Nausea, vomiting, 
             anorexia, constipation.  Vomitus with milky appearance 
             (indicating the presence of lead chloride). Sometimes 
             black stools due to lead sulfide.  Lead colic (very 
             intense intermittent abdominal cramps) is associated 
             with severe obstipation and vomiting.  Many cases are 
             wrongly diagnosed as acute disease.
       9.4.5 Hepatic
             Transient elevation of transaminases.

       9.4.6 Urinary
             9.4.6.1 Renal
                     Swelling of proximal tubular cells with 
                     correspondent impairment of function.  Amino-
                     aciduria, glycosuria, and phosphaturia (Fanconi 
                     syndrome).  Retention of uric acid.  Chronic 
                     nephritis.  Nephrotic syndrome may occur.
             9.4.6.2 Others
                     Not relevant.
       9.4.7 Endocrine and reproductive systems
             Animal studies demonstrate irregular oestrous cycles in 
             female rats and testicular damage in male rats.  Some 
             data suggest that high-level exposure to lead may cause 
             abortion and stillbirth among pregnant women.  Lead may 
             induce decreased sperm counts.  There is currently no 
             reliable information concerning the risk of adverse 
             effects on the offspring following lead exposure in men.
       9.4.8 Dermatological
             Not relevant.
       9.4.9 Eye, ears, nose, throat: local effects
             Acute:  Not relevant.
             
             Chronic:  Retinal stippling.
       9.4.10 Haematological
              Basophilic stippling occurs in erythrocytes by 
              aggregation of ribonucleic acid.  Anaemia in chronic 
              lead poisoning results from decreased life span of red 
              cells and from inhibition of haem synthesis.  Lead 
              inhibits haem formation at several points, mainly at 
              the steps involving dependent sulfhydryl enzymes such 
              as delta-aminolevulinate, dehydratase and 
              ferrochelatase. This causes hypochromic microcytic 
              anaemia, which is more frequently observed in children.
       9.4.11 Immunological
              Immune effects have been observed in animals but not in 
              humans.
       9.4.12 Metabolic
              9.4.12.1 Acid-base disturbances
                       Not relevant.
              9.4.12.2 Fluid and electrolyte disturbances
                       After massive ingestion of soluble lead 
                       products there is a large gastrointestinal 
                       loss of fluids, with fluid and electrolyte 
                       disturbances.
              9.4.12.3 Others
                       Saturnine gout is a consequence of 
                       hyperuricaemia, due to renal dysfunction. 
                       Inhibition of guanine aminohydrolase (guanase) 
                       by lead may also be responsible for saturnine 
                       gout.
       9.4.13 Allergic reactions
              Not relevant.
       9.4.14 Other clinical effects
              Pallor of the face; retinal stippling; appearance of 
              premature aging.

       9.4.15 Special risks
              Pregnancy, breast-feeding, enzyme deficiencies:  there 
              is no reliable evidence of a risk of spontaneous 
              abortion and still-birth.  Lead crosses the placenta 
              and fetal blood concentrations at birth approximate to 
              those of the mother. Lead is also excreted in human 
              milk. In animals, low-level exposure to lead during 
              prenatal or postnatal life results in retarded growth. 
              Inhibition of gama-glutamyl transpeptidase and adenyl 
              cyclase activity has been demonstrated in rats (WHO, 
              1977; ILO, 1983).
     9.5 Others
       Not relevant.
     9.6 Summary
    10. MANAGEMENT
      10.1 General principles
         -    Acute poisoning
         
         Poisoning by inorganic lead compounds is rare, but in case 
         of ingestion of large quantities of soluble compounds, or 
         exposure to fumes or vapours, it is mandatory to remove the 
         patient from further exposure.  Remove and discard 
         contaminated clothing.  Gastric lavage is preferred to 
         emesis (Noji & Kelen, 1989); administer a cathartic 
         (magnesium sulphate).  Administer atropine for abdominal 
         pain but an opioid may sometimes be necessary.  Treat lead 
         colic with calcium gluconate 10% IV.  If the patient is 
         obtunded, convulsing or comatose, insert an oro- or a naso-
         gastric tube and lavage after endotracheal intubation.
         
         If the patient is convulsing, administer diazepam, 0.1 mg/kg 
         IV, to a maximum dose of 10 mg.  A comatose or convulsive 
         state indicates increased intracranial pressure.  Use of 
         mannitol, steroids and hypothermia, and referral to a 
         neurosurgical unit may then be necessary.
         
         Administer intravenous fluids.  Monitor vital signs.
         
         -    Chronic poisoning: remove the patient from further 
         exposure and treat symptomatically.  Individuals with blood 
         lead levels > 600 g/L must be removed from the work place.
         
         General supportive treatment is to maintain airway and 
         respiration.  Start artificial respiration at the first sign 
         of respiratory failure.  Administer oxygen if cyanosis is 
         present.  Correct dehydration.
         
         The specific pharmacological treatment is chelation therapy 
         using calcium disodium edetate (EDTA), penicillamine, and 
         dimercaprol (BAL).
         
         Chelation therapy is indicated in all symptomatic patients 
         and patients whose blood lead levels exceed 700 g/L.  EDTA 
         is administered in doses of 50 to 75 mg/kg/day in two 

         divided doses of IM or in saline infusion IV slowly, for 5 
         days. 
         
         In case of lead encephalopathy: BAL should be used in doses 
         of 2.5-4 mg/kg IM every 4 hours.  EDTA is started 4 hours 
         after the first dose of BAL, in intravenous continuous 
         infusion.  This therapy should be continued for 5 days. 
         Gosselin, 1984; Putman, 1986; ACHIH, 1986; Ellenhorn, 1988; 
         Noji & Kelen,
         1989; Gilman, 1990; ATSDR, 1990; Goyer, 1990; Garrettson, 
         1990.
         
         Acute poisoning by ingestion or acute episodes during 
         chronic poisoning: EDTA by slow intravenous drip or in 
         divided doses IV.  Continue for 5 days.
         
         In adults with blood levels up to 1000 g/L give combined 
         treatment with intramuscular BAL and intravenous EDTA for 5 
         days.  Interrupt treatment for 2 days and restart EDTA if 
         blood lead levels remain high (> 1000 g/L); penicillamine 
         should then be given for 3-6 months (20 mg/kg/day oral 
         route). In children with blood levels up to 700 g/L, use 
         combined treatment with BAL plus EDTA.  Therapy with BAL may 
         be discontinued after 3 days if blood lead level is < 50 
         g/dl.  EDTA should be continued for 5 days.  Long-term 
         chelation with penicillamine in children should be limited 
         to 2 months.
         
         Problems with chelators are:
         
         -    oral chelators may promote lead absorption from the 
         gastrointestinal tract.
         
         -    the chelator-lead complex is nephrotoxic.  Urine output 
         must be monitored and chelation should be stopped if renal 
         impairment.
         
         -    chronic chelation therapy with EDTA or penicillamine 
         promotes loss of essential metals.
         
         -    intramuscular injection of EDTA is painful.  Multiples 
         sites should be used.
         
         -    BAL may cause local pain, nausea, vomiting.  
         Hypertension is described after BAL therapy.  Antihistamines 
         may be administered.
         
         -    d-penicillamine causes alteration of taste, neutropenia,
          allergic rashes, aplastic anaemia, nephropathy, hepatitis 
         (Gosselin, 1984; Noji & Kelen, 1989; Gilman, 1990;      
         Garrettson, 1990; Volans & Henry, 1984). 
      10.2 Relevant laboratory analyses and other investigations
         10.2.1 Sample collection
                Blood and urine should be collected at any time.  It 
                is essential to avoid contamination: needles, 

                containers, and anticoagulants must be lead-free.  A 
                24-hour urine specimen is preferable.
         10.2.2 Biomedical analysis
                Lead in blood and urine.
                Red cell delta-aminolevulinic acid dehydratase  
                activity.
                Free erythrocyte protoporphyrin.
                Urinary delta-aminolevulinic acid.
                Urinary coproporphyrin.
                Full blood count (red cells, white cells, platelets; 
                haemoglobin and reticulocytes count).
                Radiographs of bones (children).
                
                Abdominal X-rays after ingestion.
                Electroencephalogram.
                Determination of lead in hair.
                (Kopito et al., 1967; ILO, 1983; Gosselin, 1984; 
                Ellenhorn, 1988; Noji & Kelen, 1989; Garrettson, 
                1990).
         10.2.3 Toxicological analysis
                No data available.
         10.2.4 Other investigations
      10.3 Life supportive procedures and symptomatic treatment
         Make a proper assessment of airway, breathing, circulation 
         and neurological status of the patient.
         Maintain a clear airway.  Aspirate secretions from airway.
         Control convulsions with diazepam 0.1 mg/kg.
         Open and maintain at least one intravenous route.  
         Administer intravenous fluids.  Monitor vital signs.
         Increased intracranial pressure in encephalopathy may 
         require mannitol, steroids (dexamethasone), and 
         neurosurgical assistance.
      10.4 Decontamination
         After ingestion, if convulsions are not imminent, induce 
         emesis or perform gastric lavage.  Do not induce emesis if 
         the vehicle of the product is a petroleum distillate.  
         
         To induce emesis use syrup of ipecac. Gastric lavage may be 
         performed if emesis fails, bearing in mind the possible risk 
         of imminent convulsions.  The decision to induce emesis 
         depends on a knowledge of the constituents of the product.
         
         Gastric lavage may be preferred in case of soluble inorganic 
         lead compounds.
         
         Administer a saline cathartic (magnesium sulphate, 15 to 30 
         g in water).
         
         After inhalation, management is symptomatic and supportive:  
         Remove from exposure and ensure the airway and ventilation.  
         Supportive measures include oxygen and artificial 
         respiration.
         
         Skin - remove of all contaminated clothes and wash the skin 
         and hair. 
         
         Eyes - extensive eye irrigation with water or saline should 
         also be performed.
      10.5 Elimination
         Chelation therapy will promote the excretion of inorganic 
         lead through urine.  A good urinary output is mandatory.  
         Haemodialysis is indicated in cases of impaired renal 
         function.
      10.6 Antidote treatment
         10.6.1 Adults
                The antidotes which may be used are:
                
                -  Calcium disodium edetate (CaNa2EDTA): 1 to 2 g 
                daily (non-convulsing or comatose) 2 to 4 g daily 
                (convulsing or comatose) in two divided doses 
                intramuscularly or IV in saline infusion, slowly for 
                5 days.
                
                -  Succimer (DMSA): 10 mg per kg body weight per os, 
                every 8 hours for 5 days, then every 12 hours for an 
                additional 14 days.  The course of treatment may be 
                repeated if necessary, after an interval of two weeks 
                (Reynolds, 1993).
                
                -  Dimercaprol (BAL): 2.5 to 4 mg/kg/dose 
                intramuscularly every 4 hours, for 48 hours; then, 
                every 6 hours, for 48 hours; and every 6 to 12 hours 
                for more 7 days.
                
                -  d-penicillamine: 250 mg 4 times daily for 5 days.  
                Doses in long-term treatment should not exceed 40 
                mg/kg/day.
         10.6.2 Children
                Children with blood lead levels up to 700 ug/L should 
                be treated with combined BAL and edetate calcium 
                disodium; BAL may be discontinued after 3 days if the 
                blood lead is < 500 ug/L but edetate should be 
                continued for 5 days.  Long term chelation with 
                penicillamine in children should be limited to 2 
                months.  (Gosselin, 1984; Ellenhorn, 1988; Noji & 
                Kelen, 1988; Garrettson, 1990; Gilman, 1990; Volans & 
                Henry, 1984).
                
                -  Calcium disodium edetate (CaNa2EDTA):
                   50 mg/kg/day in two divided doses (non-convulsing 
                child) 75    mg/kg/day in two divided doses 
                (convulsing child)    intramuscularly or IV in saline 
                infusion, slowly for 5 days.
                
                -  Dimercaprol (BAL): 2.5-4 mg/kg/dose 
                intramuscularly every 4    hours, for 48 hours; then, 
                every 6 hours, for 48 hours; and    every 6 to 12 
                hours for more 7 days.
                
                -  Succimer (DMSA): to be completed. 
                
                -  d-penicillamine: 20-40 mg/kg/day (maximum 1 g/dat) 
                may be    given for 3-6 months.
      10.7 Management discussion
         Alternatives, controversies and research needs: chelation 
         therapy is effective in removing lead from soft tissues but 
         not from bone.  Significant quantities of lead are present 
         in bone and intercurrent illness may mobilise toxic 
         quantities of lead into soft tissue, thereby exacerbating 
         the symptoms of poisoning.  When chelating agents are given 
         orally, the risks include depletion of essential metals due 
         to rapid mobilization and impaired absorption from the 
         digestive system.
         
         Lead poisoning in childhood is a chronic disease and 
         currently it is accepted that even very low blood levels of 
         lead may induce developmental deficits.  Screening programs 
         to detect these cases are required. (Gosselin, 1984; Noji & 
         Kelen, 1989; Gilman, 1990; Garrettson, 1990).
    11. ILLUSTRATIVE CASES
      11.1 Case reports from literature
         Lead poisoning from cocktail glasses: a man and his wife 
         acquired plumbism by drinking repeatedly from cocktail 
         glasses decorated with lead-based paint (Natelson & Fred, 
         1976).
         
         Lead poisoning in children of lead workers: 38 in 91 
         children (41.8%) presented lead blood levels up to 300 g/L 
         and 10 with lead blood levels higher than 800 g/L.  The 
         source of contamination was lead dust carried home on 
         parents contaminated work clothing (Baker et al., 1977).
         
         Lead intoxication in an adult caused by chinese herbal 
         medication: a patient was diagnosed severe lead poisoning 
         caused by ingestion of herbal medication from Hong Kong 
         (Lightfoote et al., 1977).
      11.2 Internally extracted data on cases
         A man was admitted to hospital with severe epigastric pain.  
         An abdominal explorative surgery was performed.  No elements 
         corroborated the presumptive diagnosis of perforated peptic 
         ulcer.  As he was a worker in a smeltery, lead poisoning was 
         suspected after the detection of basophil stippling in 
         erythrocytes and a blue line in the gums.  Blood lead levels 
         were 124 g/L.  Chelation therapy was instituted with 
         calcium disodium EDTA 2 g a day IV, during 5 days.  He 
         recovered from the acute crisis, but manifested sequels of 
         impaired muscular strength in the right forearm.  The 
         measurement of peripheral motor nerve conduction radial 
         velocity was reduced.
      11.3 Internal cases
    12. ADDITIONAL INFORMATION
      12.1 Availability of antidotes
      12.2 Specific preventive measures
         Use protective clothes (including shoes).
         
         The protective clothes and shoes must not leave plant.
         
         Avoid skin contact with lead dust and fume.
         
         Avoid contact of lead with oxidizers (such as perchlorates, 
         peroxides, permanganates, chlorates and nitrates) and 
         chemically active metals (such as potassium, sodium, 
         magnesium and zinc) since violent reactions occur.
         
         Insist in personal hygiene: do not smoke, do not eat, do not 
         drink in contaminated environment.
         
         Eating facilities must be separated from working areas.
         
         Face and hand coverings should be made of impermeable 
         material.
         
         Medical surveillance program for lead: pre-employment and 
         pre-placement examination, periodical examination, clinical 
         tests, record-keeping and health education.
         
         Immediate cleaning up of spills.  Floors should be wetted 
         with a fine spray to avoid stirring up dust.
         
         Storage receptacles should be kept covered to reduce fumes 
         and dust.
         
         Measurement of lead air levels (ILO, 1983; Glenn, 1987).
         
         -  Non-occupational exposure:
         
         Avoid non-industrial ceramics for foodstuff.
         
         Do not allow small children to swallow chips of deteriorated 
         paint.
         
         Measures of prevention involving Public Health must concern:
         
         -  Control of lead in drinking water.
         -  Treatment of public water systems to decrease 
         contamination from    plumbing.
         -  Control of lead emissions in air.
         (ATSDR, 1990).
      12.3 Other
         The hazards of lead exposure are reported to have been well 
         known as early as the second century BC, when exposure 
         occurred due to the use of lead in plumbing, cooking 
         utensils, and as a "sweetener" of wines. The overt symptoms 
         of poisoning, including colic, encephalopathy, anaemia, and 
         renal disease, were well known. 
         
         Lead poisoning remains a serious problem.  It is often 
         associated with poverty, misuse, ignorance, and bad working 
         conditions. Lead poisoning is one of the commonest 
         occupational diseases.
         
         Over the last 20 years subclinical effects have been 
         described following the development of sensitive methods to 
         detect cognitive and behavioural changes, especially in 
         children. 
         
         Concern about environmental contamination has led to a 
         reduction in the lead content of gasoline and control of 
         occupational exposure; the average blood level of lead in 
         the population in the USA has now declined by nearly 50%.
         
         -  First aid summary
         
         Induce vomiting, if spontaneous vomit is not prompt and 
         profuse.  Ipecac syrup may be administered by mouth.
         Dose of ipecac syrup:
         Children:   6-18 months               10 ml
                     18 months to 12 years     15 ml
                     Adolescents and adults:   30 ml
         
         The decision to induce emesis depends on knowledge of the 
         constituents of the product: emesis is not recommended if 
         the vehicle is a petroleum distillate.  Do not induce emesis 
         if the patient's conscious level is imparied or if fits are 
         likely.  A sample of vomitus should be collected in a clean 
         bottle.
         
         Gastric lavage may be performed if emesis is not induced 
         even when the product contains kerosene or a related 
         petroleum distillate.
         
         A purgative may be given to remove the ingested compound.
         
         Inhalation of vapours and fumes: Treatment is symptomatic 
         and supportive.  Maintain an airway and ventilation; 
         supportive measures include oxygen and artifical respiration 
         (Gosselin, 1984; Noji & Kelen, 1989; Garrettson, 1990).
    13. REFERENCES
    ACGIH - American Conference of Governmental Industrial Hygienists 
    (1986).  Documentation of the threshold limit values and 
    biological exposures indices. 5th ed. Cincinnati, p. 343-345, BEI-
    19 to BEI-23.
    
    ACGIH - American Conference of Governmental Industrial Hygienists 
    (1990).  TLVs Threshold Limit Values and biological exposures for 
    1990-1991, Cincinnati.
    
    ATSDR - Agency for Toxic Substances and Disease Registry (1990). 
    Toxicological profile for lead.  U.S. Public Health Service in 
    collaboration with U.S. Environmental Protection Agency (EPA).
    
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    14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE 
    ADDRESSES
    Author:  Alberto Furtado Rahde
             Rua Riachuelo 677 ap. 201
             90010 Porto Alegre
             Brazil
    
    Telephone:     55-512-275419
    
    Facsimile:     55-512-246563
    
    Date:     December 1991
    
    Reviewer:
    
    Peer Review:  Newcastle-upon-Tyne, United Kingdom, February 1992
    
    
    Finalized at the IPCS: May 1994




    See Also:
       Toxicological Abbreviations