Lead, organic
| 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 |
| 3.4.1 Shelf-life of the substance |
| 3.4.2 Shelf-life of the locally available formulation |
| 3.4.3 Storage conditions |
| 3.4.4 Bioavailability |
| 3.4.5 Specific properties and composition |
| 4. USES |
| 4.1 Indications |
| 4.2 Therapeutic dosage |
| 4.2.1 Adults |
| 4.2.2 Children |
| 4.3 Contraindications |
| 5. ROUTES OF ENTRY |
| 5.1 Oral |
| 5.2 Inhalation |
| 5.3 Dermal |
| 5.4 Eye |
| 5.5 Parenteral |
| 5.6 Other |
| 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. PHARMACOLOGY AND TOXICOLOGY |
| 7.1 Mode of action |
| 7.1.1 Toxicodynamics |
| 7.1.2 Pharmacodynamics |
| 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 |
| 7.3 Carcinogenicity |
| 7.4 Teratogenicity |
| 7.5 Mutagenicity |
| 7.6 Interactions |
| 7.7 Main adverse effects |
| 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 Other |
| 9.4.7 Endocrine and reproductive systems |
| 9.4.8 Dermatological |
| 9.4.9 Eye, ear, 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 Other |
| 9.6 Summary |
| 10. MANAGEMENT |
| 10.1 General principles |
| 10.2 Relevant laboratory analyses |
| 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/specific 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 ADDRESS(ES) |
1. NAME
1.1 Substance
Tetraethyl lead and Tetramethyl lead
1.2 Group
Lead alkyl compounds
1.3 Synonyms
lead tetraethyl
lead tetramethyl
TEL
Tetraethylplumbane
Tetramethylplumbane
TML
1.4 Identification numbers
1.4.1 CAS number
Tetraethyl lead : 78-00-2
1.4.2 Other numbers
Tetraethyl lead : NIOSH TP4550000
Tetramethyl lead: NIOSH TP4725000
1.5 Brand names, Trade names
No data available
1.6 Manufacturers, Importers
No data available
2. SUMMARY
2.1 Main risks and target organs
The central nervous system is particularly sensitive to
organic compounds of lead.
Poisoning due to organic compounds is a consequence of
industrial exposure. Indirect exposure arises from
environmental contamination. Humans can be exposed to lead
from breathing air, drinking water, and eating foods that
contain lead. A large number of occupations may be associated
with risk of exposure to organic lead compounds, particularly
the cleaning of gasoline tanks.
Some reports have associated the risks of repeated inhalation
of leaded gasoline as a drug of abuse (Edmindster, 1985).
Other possible source of exposure is skin absorption from
gasoline burns.
Subclinical effects have been identified with sensitive
methods used to detect cognitive and behavioral changes,
especially in children. There are subtle neuropsychiatric,
reproductive and renal effects of chronic low-dose lead
exposure, children being particularly susceptible. The effects
of low-dose of lead in adults remains to be cleared.
Hypertension, gout, nephropathies, and neurotoxic
manifestations may be related to lead exposure.
Organic compounds of lead have toxic properties which require
precautions against both their percutaneous and respiratory
absorption.
2.2 Summary of clinical effects
Poisoning by organic lead compounds presents mainly acute
effects on the central nervous system. The chronic form of
this intoxication has been observed following prolonged and
deliberate inhalation of leaded gasoline vapours ("gasoline
sniffing") (Hansen et al, 1978). Poisoning may result from
the absorption of a sufficient quantity of lead, whether
briefly at a high rate or for prolonged periods at a lower
rate. Ingestion is not a significant occupational hazard.
Respiratory and percutaneous absorption are the main routes
of exposure.
Mild manifestations are: insomnia and nervous excitation,
nausea, vomiting, associated with tremor, hyperreflexia,
muscular contractions, bradycardia, arterial hypertension,
and hypothermia.
Most severe cases present episodes of complete disorientation,
mania, ataxia, hallucinations, exaggerated muscular activity,
and violent convulsive seizures, which may terminate in coma
and death.
In severe cases, muscle, hepatic and renal damage may occur.
The clinical picture may persist for days and weeks. A rapid
onset of symptoms after exposure indicates a poor prognosis.
When the onset of symptoms is delayed for many days recovery
is usually complete, but some neurological sequelae have been
reported. Prolonged compulsive sniffing of gasoline has
resulted in encephalopathy and death.
2.3 Diagnosis
Is based on history of exposure to lead alkyl compounds
(occupational in most cases) and occurrence of nausea,
vomiting and CNS symptoms: irritability, anxiety,
restlessness and more severe disorders (tremor, confusion and
seizures).
The laboratory studies to confirm the diagnosis are:
In blood: complete blood-count, whole blood-count lead level
free erythrocyte protoporphyrin red cell delta aminolevulinic
acid dehydratase activity.
In urine: 24-hour urine lead levels delta aminolevulinic acid
and coproporphyrin
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 glassware.
2.4 First aid measures and management principles
- Remove the patient from further exposure, send for
medical assistance.
- Remove and discard contaminated clothing.
- Exposed eyes should be irrigated with copious amounts of
water.
- Wash skin with soap and copious amount of water.
- Control convulsions with appropriate drug regimen.
- In case of ingestion, unless vomiting is extensive,
perform gastric lavage and administer a cathartic. If the
patient is obtunded, convulsing, comatose, insert an oro- or a
naso-gastric tube and lavage after endotracheal intubation.
- Open and maintain at least one intravenous route.
- Administer intravenous fluids.
- Chelation is indicated only if blood levels are high.
Penicillamine and calcium disodium edetate have been used
and the increased urinary excretion of lead does not
correspond with clinical improvement.
- In case of encephalopathy, BAL and edetate calcium
disodium are indicated.
- In cases of inhalation of vapours and fumes, symptomatic
and supportive treatment are indicated. Ensure patient's
airway and ventilation. Supportive measures include
oxygen and artificial respiration.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Organic lead compounds include a number of common high-
pressure lubricants (lead soaps) and the gasoline anti-knock
agents tetraethyl lead (TEL) and tetramethyl lead (TML). TEL
and TML are lipid-soluble liquids of high volatility and are
prepared by chemical synthesis.
3.2 Chemical structure
Chemical name: Tetraethyl lead and Tetramethyl lead
Molecular weight: TEL: 323.45 TML: 267.3
Structural formula: Pb(C2H5)4 Pb (CH3)4
3.3 Physical properties
Boiling point: TEL = 200 C (decomposes) TML =
110 C
Melting point: TEL = -136.8 C TML = -
27.5 C
Flash point: TEL = 93.3 C TML =
37.7 C
Autoignition temperature:
Relevant density (20 C) : TEL = 1.653 TML =
1.99
Relative vapour density: TML =
9.2
Vapour pressure: TEL = 1 mmHg at 38.4 C
TML = 22 mmHG (25 C)
Solubility: TEL = soluble in benzene,
ethyl alcohol petrol ether, gasoline and ethyl
ether; insoluble in water.
TML = slightly soluble in
benzene, ethyl alcohol and ethyl ether;
insoluble in water.
Explosive limits: no data available.
Viscosity: no data available.
Relative molecular mass: no data available.
pH: no data available.
3.4 Other characteristics
3.4.1 Shelf-life of the substance
3.4.2 Shelf-life of the locally available formulation
3.4.3 Storage conditions
3.4.4 Bioavailability
3.4.5 Specific properties and composition
4. USES
4.1 Indications
Organic compounds of lead can be used as solvents for
fatty materials and rubber. TEL and TML are liquid
compounds of lead, which are miscible in all
proportions with gasoline (and other organic solvents)
and are available as "anti-knock" ingredients in
gasoline fuel for the internal combustion engine (WHO,
1977; Budavari, 1989; Sax, 1989).
Alkyl lead compounds, the organic forms of lead, have
been in use as anti-knock additives in gasoline for
almost 60 years. Use of these compounds (almost
exclusively tetraethyl lead and tetramethyl lead)
increased steadily up to 1973. A decline in consumption
was started as more cars fitted with catalysts requiring
lead-free gasoline have come into use (WHO, 1977).
4.2 Therapeutic dosage
4.2.1 Adults
4.2.2 Children
4.3 Contraindications
Workers may be exposed to organic lead compounds in a wide
variety of occupations, including alkyl lead manufacture,
gasoline processing, transportation, tank cleaning, filling
station operators and garage workers. Both TEL and TML are
absorbed through the skin and the respiratory tract. Ingestion
is not a significant occupational hazard (WHO, 1977; ILO,
1983; Gosselin, 1984; Sax, 1989).
5. ROUTES OF ENTRY
5.1 Oral
Accidental or deliberate ingestion of alkyl lead compounds may
occur, but is not frequent.
5.2 Inhalation
Inhalation of vapours of alkyl lead compounds should be
considered as a major route of entry (ILO, 1983). It may
occur in the occupational setting or as a result of "sniffing
gasoline".
5.3 Dermal
Dermal absorption is an efficient route of entry for organic
compounds of lead (ILO, 1983; Sax, 1989).
5.4 Eye
Not relevant.
5.5 Parenteral
Not relevant.
5.6 Other
Not relevant.
6. KINETICS
6.1 Absorption by route of exposure
Accidental or deliberate ingestion of alkyl lead compounds is
not frequent. Inhalation of mists and vapours of alkyl lead
compounds should be considered as the major route of entry.
Dermal absorption is an efficient process: organic compounds
of lead are capable of penetrating the intact skin rapidly
(Gosselin, 1984; Sax, 1989).
6.2 Distribution by route of exposure
Lead is distributed in man according to a three-compartment
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. There is
redistribution by deposition in 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, in which the
concentration of lead is about 16 times greater than in plasma
(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; Garettson, 1990).
6.4 Metabolism
Alkyl lead compounds are transformed in trialkyl derivatives
by dealkylation in the liver. TEL and TML are not the primary
toxins but they are converted to triethyl lead and inorganic
lead (WHO, 1977; Garettson, 1990).
6.5 Elimination by route of exposure
The rate of excretion of lead is low. Renal clearance of
unchanged lead occurs 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).
7. PHARMACOLOGY AND TOXICOLOGY
7.1 Mode of action
7.1.1 Toxicodynamics
7.1.2 Pharmacodynamics
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
7.2.1.1 Adults (volunteer and clinical case
data) The precise doses of the alkyl lead
compounds responsibe for the effects are rarely,
if ever, known. Patients with organic lead
poisoning due to gasoline sniffing have been
shown to have blood lead levels higher than 100
µg/dl (Keenlyside, 1984). A lead urine
concentration of about 350 µg/dl is seen in
severe TEL poisoning (ILO, 1983). The lowest
reported lethal dose in man (LDL0) is 1470
µg/kg (Sax, 1989).
7.2.1.2 Children
No data available.
7.2.2 Relevant animal data
Tetraethyl lead:
Lowest toxic dose oral mouse: 11 mg/kg
LD50 oral rat: 1200 µg/kg
LC50 inhalation rat: 850 mg/m3
LD50 intraperitoneal rat: 850 mg/kg
LD50 intravenous rat: 14400 µg/kg
Lowest lethal dose skin dog: 547 mg/kg
Tetramethyl lead:
Lowest toxic dose oral rat: 112 mg/kg
LD50 oral rat: 105 mg/kg
LD50 intraperitoneal rat: 90 mg/kg
LD50 intravenous rat: 88 mg/kg
LC50 inhalation rat: 8870 mg/m3
Lowest lethal dose oral rabbit: 24 mg/kg
Lowest lethal dose skin rabbit: 3391 mg/kg
Lowest lethal dose intravenous rabbit: 90 mg/kg
There is no qualitative difference between the toxic
effects of TEL and TML. However, the inhalation LC50 for
tetramethyl lead is about 10 times greater than that
for tetraethyl lead (WHO, 1977; Sax, 1989).
7.2.3 Relevant in vitro data
Biochemical studies of the respiration of brain slices
incubated with inorganic lead compared with triethyl
lead (the active metabolite of TEL) have demonstrated a
fundamental difference in the action of alkyl lead
compounds on the brain (WHO, 1977).
7.3 Carcinogenicity
A study of workers manufacturing TEL revealed an excess of
respiratory cancers (15 observed, 11.2 expected) and brain
cancer (3 observed, 1.6 expected) but the evidence for
carcinogenicity in humans is inadequate (IARC, 1987). Alkyl
lead compounds have not been tested adequately: the evidence
for carcinogenicity of organolead compounds in animals is
inadequate (IARC, 1987).
7.4 Teratogenicity
No adequate animal studies exist of the possible teratogenic
effects of lead (WHO, 1977).
7.5 Mutagenicity
TEL and TML did not induce mutation 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).
7.7 Main adverse effects
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
Not available
8.1.1.2 Biomedical analyses
Blood may be collected at any time. It is
essential to avoid contamination: use only lead
free needles, containers and stoppers;
anticoagulant must be lead free. Urine can be
collected at any time. A 24-hour specimen of
urine is preferable to a single specimen.
Avoid lead contamination from containers (ACGIH,
1986).
8.1.1.3 Arterial blood gas analysis
Not relevant.
8.1.1.4 Haematological analyses
Avoid lead contamination of samples
8.1.1.5 Other (unspecified) analyses
No data available
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
Blood and urine samples should be stored in
specially cleaned glassware, and refrigerated as
indicated for the specific method.
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
Transport of samples should be done in
refrigerated containers.
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)
Analysis of lead in blood is done by the wet
chemical dithizone method.
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
Blood concentrations of lead are determined by
atomic absorption spectroscopy. Lead in urine is
analyzed after chelation and extraction by
means of atomic absorption.
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
The concentration of lead in blood varies, in general,
it is slightly elevated but in some cases of poisoning
it is nearly normal. In cases of repeated gasoline
sniffing the content of lead in blood is high. No close
correlation exists between blood lead levels and the
severity of intoxication. The urinary excretion of lead
is increased markedly (Hansen, 1978; ILO, 1983; Gilman,
1990; Garrettson, 1990).
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
Determination of whole-blood lead level.
Determination of red cell delta-aminolevulinic
acid dehydratase activity. Determination of
free erythrocyte protoporphyrin.
8.3.1.2 Urine
24-hour urine lead level. Urinary delta-
aminolevulinic acid. Urinary coprophyrin.
8.3.1.3 Other fluids
Lead in urine after calcium disodium EDTA
mobilization test.
8.3.2 Arterial blood gas analyses
Not relevant.
8.3.3 Haematological analyses
Full blood count (red cells, white cell and platelet
count). Determination of haemoglobin content and
reticulocyte count.
8.3.4 Interpretation of biomedical investigations
In case of recent exposure or poisoning: whole-blood
levels rarely exceeds 500 µg/L. Red cell delta-
aminolevulinic dehydratase activity is inhibited
(normal 30-60 IU). The concentration of protoporphyrin
in erythrocytes may be increased (normal: 600 µg/L),
but the results are inconsistent. In severe organic lead
poisoning the concentration of lead in urine is rarely
less than 3500 µg/L. The urinary delta-aminolevulinic
acid (ALA-U) (normal: 4.5 mg/L) and the urinary
coproporphyrin (CP-U) (normal: 150 µg/L) may be
increased. The urinary lead excretion is increased by
calcium disodium EDTA or D-penicillamine). Anaemia and
basophilic stippling are uncommon. These findings occur
in chronic exposure, as in gasoline sniffing cases, but
the chemical and morphological abnormalities in blood
are absent in acute exposure (Beattie, 1972; ILO, 1983;
Gilman, 1990; Garrettson, 1990).
8.4 Other biomedical (diagnostic) investigations and their
interpretation
Serum creatinine, urinalysis, 24-hour creatinine and protein
(evaluation of renal function). Serum creatine phosphokinase
(CPK), lactic dehydrogenase (LDH) and serum glutamic
oxaloacetic transaminase (SGOT): muscle and hepatic damage.
Peripheral motor nerve conduction velocity (damage to
peripheral nerves) only in cases of chronic exposure.
Intelligence and personality tests: evaluation of
psychological and neurological impairment.
Electroencephalogram: in cases of lead encephalopathy (ILO,
1983; Garrettson, 1990).
8.5 Overall Interpretation of all toxicological analyses and
toxicological investigations
Determination of lead in urine is the most commonly used
indicator of lead organic exposure (ILO, 1983; Garrettson,
1990).
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
Acute poisoning from ingestion is rare. In one case of
massive ingestion of pure tetraethyl lead the initial
signs and symptoms were related to increased
intracranial pressure. The patient died 36 hours later
with pulmonary oedema (Gosselin, 1984).
9.1.2 Inhalation
Inhalation is the most important route of absorption in
the working environment. Inhalation induces sneezing,
irritation of the upper respiratory tract and mild to
severe systemic responses: insomnia, lassitude, nervous
excitation, anxiety states, associated with tremors,
hyperreflexia, spasmodic muscular contractions,
bradycardia, vascular hypotension, and hypothermia. The
most severe responses include complete disorientation
with hallucinations, and facial contortions. Such
episodes may progress to maniacal and violent
convulsive seizures which may terminate in coma and
death (ILO, 1983; Gosselin, 1984; Garrettson, 1990).
9.1.3 Skin exposure
Skin is a very important route of exposure, as alkyl
lead compounds are easily absorbed through the intact
structures. In contact with the skin they induce
itching, burning and transient redness (ILO, 1983). In
one case of massive skin exposure, a patient remained
asymptomatic even though the urinary lead excretion was
very high (Gosselin, 1984).
9.1.4 Eye contact
In contact with the ocular membranes organolead
compounds induce itching, burning, and transient redness
(ILO, 1983).
9.1.5 Parenteral exposure
No available data.
9.1.6 Other
Not relevant.
9.2 Chronic poisoning
9.2.1 Ingestion
Chronic poisoning by ingestion is not described.
9.2.2 Inhalation
No chronic form has been observed in a population
exposed occupationally (ILO, 1983). Chronic
recreational sniffing of leaded gasoline as a drug of
abuse has led to neurological damage: tremors,
exaggerated tendon reflexes, severe encephalopathy, and
death (Hansen et al, 1978; Gosselin, 1984; Garrettson,
1990).
9.2.3 Skin exposure
No data available.
9.2.4 Eye contact
No data available.
9.2.5 Parenteral exposure
Not relevant.
9.2.6 Other
Not relevant.
9.3 Course, prognosis, cause of death
Illness resulting from acute episodes may persist for days or
weeks, with intervals of quietude readily triggered into over-
activity by any type of disturbance. Arterial hypotension and
loss of body weight are common.
When the symptoms occur within in a few hours the exposure, an
early fatal outcome is possible. When the interval is longer,
the prognosis is better. Partial or recurrent disorientation
and depressed circulatory function may persist for weeks.
Residual damage to the nervous system has not been described.
Cause of death is direct damage to the brain (encephalopathy)
involving capillary dysfunction, cerebral oedema, and
interference with cerebral metabolism. In one case pulmonary
oedema was described as terminal event.
Reported long term effects of chronic gasoline inhalation are
body weight loss, muscular weakness, cramps, and neurasthenia.
Recovery is complete and no evidence of neurological sequelae
have been reported (Hansen et al, 1978; ILO, 1983; Keenlyside,
1984; Gosselin, 1984).
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Acute : Arterial hypotension. Bradycardia.
Chronic: Arterial hypotension.
9.4.2 Respiratory
Acute : pulmonary oedema.
Chronic: not relevant.
9.4.3 Neurological
9.4.3.1 CNS
Acute: Insomnia, lassitude, muscle weakness,
nervous excitation, anxiety, tremors,
hyperreflexia. Disorientation, hallucinations,
facial contortions, episodes of mania,
convulsions. Encephalopathy with severe headache,
convulsions, delirium and coma may occur.
Chronic: Disturbed sleep, headache, anxiety,
irritability, intermittent stupor, generalized
myoclonus, ataxia. Suicidal tendencies,
psychosis, mania. Lead encephalopathy includes
vertigo, ataxia, headache, insomnia,
restlessness and irritability; delirium, tonic-
clonic convulsions, coma; increased
intracranial pressure.
9.4.3.2 Peripheral nervous system
Acute and chronic: paraesthesiae, pain, muscle
weakness.
9.4.3.3 Autonomic nervous system
Acute and chronic: not relevant.
9.4.3.4 Skeletal and smooth muscle
Acute and chronic: weakness and tremor; muscle
damage is confirmed by elevated serum creatine
phosphokinase (CPK).
9.4.4 Gastrointestinal
Nausea, vomiting, anorexia.
9.4.5 Hepatic
Transient elevation of transaminases.
9.4.6 Urinary
9.4.6.1 Renal
Proteinuria.
9.4.6.2 Other
Not relevant.
9.4.7 Endocrine and reproductive systems
Not relevant.
9.4.8 Dermatological
Itching, burning and transient redness of skin.
9.4.9 Eye, ear, nose, throat: local effects
Acute: conjunctivitis. Paroxysmal sneezing.
Chronic: not relevant.
9.4.10 Haematological
Acute: not relevant.
Chronic: erythrocytes with basophilic stippling are
described in some cases. Anemia is uncommon and
substrates of the haem synthesis, such as erythrocyte
protoporphyrin may be normal.
9.4.11 Immunological
Not described.
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
Not relevant.
9.4.12.2 Fluid and electrolyte disturbances
Not relevant.
9.4.12.3 Others
Not relevant.
9.4.13 Allergic reactions
Not relevant.
9.4.14 Other clinical effects
Pallor of the face, loss of body weight in chronic
exposure.
9.4.15 Special risks
There are no reliable data on the risk of spontaneous
abortions and still births. Lead crosses the placenta
and the fetal blood concentration at birth
approximates that of the mother. Lead is also excreted
in human milk in concentrations as high as 12 µg/L.
Animal studies demonstrate that low-level exposure to
lead during prenatal or postnatal life results in
retarded growth.
(WHO, 1977; Hansen et al, 1978; ILO, 1983; Gosselin,
1984; Keenlyside, 1984; Ellenhorn, 1988; Garrettson,
1990).
9.5 Other
Not available
9.6 Summary
10. MANAGEMENT
10.1 General principles
Treatment is symptomatic in the acute stages of poisoning
and chelation therapy is indicated only if inorganic lead
levels are high. In case of ingestion of organic lead
compounds or exposure to vapours, it is mandatory to
decontaminate the patient and remove him from further
exposure.
In case of chronic poisoning, prevent further exposure and
treat symptomatically. Individuals with blood lead levels
> 600 µg/L must be removed from the work place.
General supportive treatment is based on: maintenance of
clear airway and respiration, control of convulsions,
reduction of cerebral oedema, and eventually chelation
therapy, if indicated.
The treatment of organic lead poisoning is mainly
symptomatic: in acute phase, the drugs of choice are
diazepam to control convulsive seizures, and mannitol and
steroids to reduce cerebral oedema. In cases of chronic
poisoning, chelation therapy with calcium disodium edetate
(EDTA), penicillamine, dimercaprol (BAL) or succimer will
promote the excretion of the inorganic lead produced from
the metabolism of organic lead. Chelation therapy is
indicated in all symptomatic patients and patients whose
blood lead levels exceed 700 µg/L.
In case of chronic poisoning, prevent further exposure and
treat symptomatically. In adults with blood levels up to
1000 µg/L, combined treatment with intramuscular BAL and
intravenous EDTA for 5 days is indicated. Interrupt
treatment for 2 days and start EDTA if blood lead levels
remain high (>1000 µg/L). Then penicillamine should be
given for 3 - 6 months (20 mg/kg/day oral route). Note
that some problems may arise in the use of chelators (see
10.6)
10.2 Relevant laboratory analyses
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 reticulocyte count).
Electroencephalogram (ILO, 1983; Gosselin, 1984;
Ellenhorn, 1988; Garrettson, 1990).
10.2.3 Toxicological analysis
Not available
10.2.4 Other investigations
Not available
10.3 Life supportive procedures and symptomatic/specific
treatment
In case of severe poisoning, make a proper assessment of
breathing, circulation and neurological status. Maintain a
clear airway and aspirate secretions from airway. Start
artificial respiration at the first sign of respiratory
failure. Administer oxygen if cyanosis is present. Correct
dehydration.
Analgesics may be necessary to control abdominal pain.
If the patient is obtunded, convulsing or comatose, insert
an oro- or nasogastric tube and lavage after endotracheal
intubation.
If the patient is convulsing, administer diazepam 0.1 mg/kg
IV. Coma or convulsions may indicate increased intracranial
pressure; mannitol, steroids and hypothermia, and referral
to a neurosurgical unit, may be necessary.
Administer intravenous fluids. Monitor vital signs. A
successful outcome has been achieved with sustained
supportive therapy in association with persistent, vigorous
sedation (ILO, 1983; Garrettson, 1990).
10.4 Decontamination
In case of ingestion, provided convulsions are not imminent,
induce emesis or perform gastric lavage. In general, emesis
is not induced if the product solvent is a petroleum
distillate.
Gastric lavage may be performed if emesis fails, but bearing
in mind the risk of imminent convulsions.
In cases of inhalation, the management is symptomatic and
supportive: remove from exposure and maintain the airway and
ventilation. Supportive measures include oxygen and
artificial respiration.
Skin - remove all contaminated clothing and wash the skin
and hair.
Eyes - extensive irrigation with water or saline should be
performed.
10.5 Elimination
Chelation therapy will promote the excretion of inorganic
lead produced by the metabolism of organic lead through
urine. A good urinary output is mandatory. Haemodialysis
is indicated in case of impaired renal function.
10.6 Antidote treatment
10.6.1 Adults
There are no antidotes for tetraethyl lead,
tetramethyl lead or triethyl lead (Garrettson, 1990).
Lead chelators may be used only to promote excretion
of inorganic lead produced by the metabolism of
organic lead compounds.
Calcium disodium edetate (CaNa2EDTA): 1 to 2 g daily
(non-convulsing or comatose) patients 2 to 4 g daily
(convulsing or comatose patients), in two divided
doses intramuscularly or IV in saline infusion,
slowly, for 5 days.
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.
Succimer could also be used.
D-penicillamine: 250 mg 4 times daily for 5 days.
Doses in long-term treatment should not exceed 40
mg/kg/day.
Problems with chelators:
- oral chelators may promote lead absorption from
the gastrointestinal tract.
- the chelator-lead complex is nephrotoxic; urine
output must be monitored.
- chronic chelation therapy with EDTA or
penicillamine promotes loss of essential metals.
- intra/muscular injection of EDTA is painful;
multiple sites should be used.
- BAL may cause local pain, nausea, vomiting;
hypertension has been reported after BAL therapy.
Antihistamines may be administered.
- D-penicillamine may cause alteration of taste,
neutropenia, allergic rashes, aplastic anaemia,
nephropathy and hepatitis (Gosselin, 1984; Noji &
Kelen, 1989; Gilman, 1990; Garrettson, 1990).
10.6.2 Children
There are no antidotes for tetraethyl lead,
tetramethyl lead or triethyl lead (Garrettson,
1990). Lead chelators may be used only to promote
excretion of inorganic lead produced by the
metabolism of organic lead compounds.
Calcium disodium edetate (CaNa2EDTA): 50 mg/kg/day in
two divided doses (non-convulsing child) or 75
mg/kg/day in two divided doses (convulsing child)
intramuscularly of IV in saline infusion, slowly,
for 5 days.
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 than 7 days.
Succimer could also be used.
D-penicillamine: 20 to 40 mg/kg/day (maximum 1 g/day)
may be given for 3 to 6 months.
10.7 Management discussion
Chelation therapy is effective in removing only inorganic
lead. The role of chelating agents in acute organic lead
poisoning is controversial.The risks of chelation include
depletion of essential metals due to rapid mobilization and,
after oral administration, impaired absorption from the
gastrointestinal tract. Good therapeutic results with
chelators have been reported in cases of chronic exposure
(gasoline sniffing). The efficacy of chelators in organic
lead encephalopathy has recently been established (Hansen
et al, 1978; Gosselin, 1984; Gilman, 1990; Garrettson,
1990).
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Four men cleaned a tank which had held leaded aviation
gasoline. Exposure was followed shortly by illness in
which mental symptoms were prominent. Blood lead levels
were raised to 645 to 925 µg/L. Lead was found
predominantly in the lipid blood fraction. Urinary
coproporphyrin was slightly raised in one case.
Erythrocyte protoporphyrin was slightly raised in the three
more severe cases. Blood delta aminolevulinic acid
dehydratase activity was markedly reduced. Urinary lead
excretion was increased by D-penicillamine administration.
All men recovered in a few weeks (Beattie et al, 1972).
Several cases of organolead compound poisoning associated
with gasoline sniffing presented with lead blood levels
higher than 1000 µg/L. Signs of organic lead poisoning,
mostly neurological symptoms, have been detected in
children and adolescents who had been sniffing gasoline for
periods ranging from 6 months to 5 years. Blood delta
aminolevulinic acid dehydratase activity was reduced.
Treatment with chelating agents resulted in symptomatic
improvement (Keenlyside, 1984).
Over 3 years, 62 persons burned by gasoline flame were
admitted to a burns unit. Increased mortality associated
with gasoline burns led the authors to question the
influence of lead in this problem. Urinary lead and
coproporphyrins were measured in 18 persons burned by
gasoline. The levels were elevated above the normal or safe
limits in 14 (Wood et al, 1968).
11.2 Internally extracted data on cases
Not available
11.3 Internal cases
12. Additional information
12.1 Availability of antidotes
To be completed locally.
12.2 Specific preventive measures
Occupational exposure:
- use protective clothes (including shoes).
- the protective clothes and shoes must not leave the
plant.
- avoid skin contact with lead vapours.
- 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 on personal hygiene: do not smoke, do not eat,
do
not drink in contaminated environment.
- eating facilities must be separated from working area.
- face and hand coverings should be made of impermeable
material.
- medical surveillance programme for lead: pre-employment
and pre-placement examination, periodical examination,
clinical tests, record-keeping and health education.
- immediate cleaning up of spills. Floors can be wet with
a
fine spray to avoid stirring up dusts.
- storage receptacles should be kept covered to reduce
fumes and dust.
- measurement of lead air levels (ILO, 1983; Glenn,
1987).
Non-occupational exposure:
- avoid gasoline sniffing.
- control of lead emissions in air (ATSDR, 1990).
12.3 Other
In the 1980s it was considered that about 90 percent of
airborne lead was derived from the exhaust gases of motor
vehicles. In many countries a decrease in the use of lead
in petrol has been associated with reductions in the air
lead concentrations of urban areas (UNEP, 1984).
Concern over improving the quality of the environmental by
lowering the lead content in gasoline and the control of the
occupational exposure decreased average blood levels of the
population in the USA by nearly 50% (Goyer, 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. US Public Health Service in
collaboration with US Environmental Protection Agency (EPA).
Beattie AD, Moore MR & Goldberg A (1972) Tetraethyl lead
poisoning. Lancet 2 (7766): 12-15.
Budavari S, ed. (1989) The Merck Index: an encyclopedia of
chemicals, drugs and biologicals, 11th ed. Rahway, New Jersey,
Merck and Co., Inc.
Edminster SC, Bayer MJ (1985) Recreational gasoline sniffing.
Acute gasoline intoxication and latent organolead poisoning. Case
reports and literature review. J. Emerg Med 3: 365.
Ellenhorn MJ & Barceloux DG (1988) Medical Toxicology. Diagnosis
and Treatment of Human Poisoning. New York, Elsevier.
FAO-WHO Expert Committee on Food Additives (1987) Tec Rep Ser WHO
No. 751.
Garrettson LK (1990) Lead. IN. Haddad LM & Winchester JF ed.
Clinical management of poisoning and drug overdose. Philadelphia,
W. Saunders Co. p. 1017-1023.
Gilman AG, Rall TW, Nies AS & Taylor P, eds. (1990) Goodman and
Gilman's The Pharmacological Basis of Therapeutics. 8th ed New
York, Pergamon Press.
Glenn RA (1986) Workplace lead poisoning and Dr Alice Hamilton: a
struggle against indifference. OH&S Canada, 3(2): 20-21.
Gosselin RE, Smith RP & Hodge HC (1984) Clinical Toxicology of
Commercial Products, 5th ed. Baltimore, Williams & Wilkins.
Goyer RA (1990) Lead toxicity: from overt to subclinical to
subtle health effects. Environmental Health Perspectives, 86: 177-
181.
Hansen KS & Sharp FR (1978) Gasoline sniffing, lead poisoning,
and myoclonus. JAMA, 240 (13):1375-1376.
IARC - International Agency for Research on Cancer (1987) IARC
Monographs on Carcinogenic Risks to Humans. Lyon, Suppl.7: 230-
231.
ILO - International Labour Office (1983) Encyclopedia of
Occupational Health and Safety. 3d ed. Geneva, vol 1, 1201-1205
Keenlyside RA (1984) The gasoline-sniffing syndrome. In:
Grandjean P & Grandjean E, eds. Biological effects of organolead
compounds. Boca Raton, Florida, CRC Press, p. 219-225.
Noji EK & Kelen GD (1989) Manual of Toxicologic Emergencies.
Chicago, Year Book Medical Publishers, Inc.
NIOSH - National Institute for Occupational Safety and Health
(1978) Criteria for a recommended Standard Occupational Exposure
to Inorganic Lead - Revised Criteria. Cincinnati, DHEW (NIOSH)
Publication No. 78-158.
Sax NI & Lewis RJ (1989) Dangerous Properties of Industrial
Materials, 7th ed. New York, Van Nostrand Reinhold.
Spencer PS & Schaumburg HH (1980) Experimental and Clinical
Neurotoxicology. Baltimore, Williams & Wilkins, p. 885.
UNEP - United Nations Environment Programme (1984) List of
Environmentally Dangerous Chemical Substances and Processes of
Global Significance. UNEP Report No 2, Geneva, IRPTC.
Volans G, Henry J.A. (1984) Br. Med. J., 289: 742-748.
WHO - World Health Organization (1977) Lead. Environmental Health
Criteria No 3, Geneva, WHO.
Wood MacD, Price WR, Childers D, Cook F (1968) Absorption and
excretion of lead in gasoline burns. Am J Surgey 116 (5): 622-
626.
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)
Author: Alberto Furtado Rahde
Rua Riachuelo 677, app 201
90010 Porto Alegre
Brazil
Telephone: 55.512.275419
Telefax: 55.512.246563
Date: December 1991
Reviewer:
Peer Review: Newcastle-upon-Tyne, United Kingdom, February 1992
Finalized by the IPCS: May 1994