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Module 3: Toxicology -
Section 11: Lead |
TOX 11.4: Lecture: Lead
(Occupational
Aspects - Continued)
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INORGANIC LEAD:
Toxicology:
Routes of entry:
- Inhalation (typically dust
or fume)
- Ingestion (occupationally
from smoking, eating while exposed, ?swallowing sputum)
- (Skin - not normally.)
Compartments (complex "4
compartment model"):
- Blood (half life 36 days)
- Soft tissues (half life:
> 40 days)
- Trabecular (surface) bone:
circulating (half life of the order of months)
- Cortical (deep) bone:
non-circulating (half life: 20 yrs plus)
Chemical actions :
- Binds to ligands, (-OH, -SH,
-NH2)
- Enzyme inhibition
- Cell membrane site of action
Rate of exposure in relation
to effects:
- Acute: high dose over
relatively short period
- Delayed post-acute: High
dose, e.g. in childhood, followed by adverse effects many years later
- Chronic: steady dosage -
typical occupational exposure
Clinical effects:
I. Classic syndrome of acute
lead poisoning
- abdominal pain/colic
- constipation
- myalgias, arthralgias
- fatigue
- "lead line" on gums
(historically associated with poor periodontal hygiene)
- anaemia
- wrist drop
- encephalopathy
This textbook syndrome is very
uncommon today.
II. Organ system effects of
chronic exposure (or delayed effects of acute exposure)
1. Haematologic
- Normocytic, normocytic
anaemia
- Reticulocytosis
- Basophilic stippling of red
blood cells (this textbook feature is not a common finding)
Mechanism:
- Reduced red cell survival
- Inhibition of red cell
formation
Reversible?
Yes.
2. Renal (including
hypertension)
Acute:
Fanconi like syndrome - mainly with acute exposures, e.g. in children.
Chronic:
- Chronic nephritis
- Hyperuricaemia / gout
("saturnine gout")
- Hypertension
Mechanisms:
- Proximal tubular damage
- Diffuse tubulo-interstitial
lesion
- ? Increased reabsorption of
urate
- ? Impaired renin-aldosterone
function (hypertension)
Reversible?
No/partly.
3. Neurologic
- Peripheral:
motor neuropathy clinically
(? "Amyotrophic lateral sclerosis"
syndrome - not proven).
Early or mild effect: abnormalities on
nerve conduction studies
Severe: wrist (or ankle) drop.
- Central:
Subjective: irritability, fatigue,
insomnia, headache
Psychiatric
disturbances have been described.
- Objective:
Neuropsychological deficits
Acute encephalopathy/seizures (rare in
adults).
Mechanism:
Axonal degeneration, demyelination, neurotransmitter disturbance.
Reversible:
No/partly.
4. Reproductive:
- Impotence, decreased libido
(part of CNS effect?)
- Infertility - women and men
(altered sperm morphology)
- Foetotoxicity, adverse
pregnancy outcomes
- abortion, stillbirths
- deficits in child (interference with
growth and neuropsychological development)
Mechanisms:
- Defective spermatogenesis
- Central gonadotrophic defect
- Teratogenic, pregnancy
effects?
5. Other endocrine
- Hypothyroidism
- Impaired adrenocortical axis
Reversible:
?
6. Carcinogenic:
IARC 2B: possible human
carcinogen
Biologic monitoring:
See Lead
Regulations 2001 (Open
up the book on Regulations, and then the book on Lead Regulations 2001
1. Blood
lead (µg/dl or mmol/l)
(Be aware of laboratory error or inter laboratory variation)
NB:
distinction between blood lead in those newly exposed (measures recent
exposure) vs those chronically exposed who have high bone stores
(integrates recent and distant exposure).
2. Zinc
protoporphyrin (ZPP) or free
erythrocyte protoporphyrin (FEP)
- Haematofluorometer
(fingerprick) - easier in workplace
- More integrated exposure
over past few months than blood lead in recently exposed.
- May be elevated in iron
deficiency (false positive)
Other:
3. Urinary
lead -not useful for inorganic
lead unless following chelation challenge to determine body load.
4. Urinary
delta ALA (delta
aminolaevulinic acid) - very sensitive, specific; not routine.
Biological effect monitoring
and clinical investigation:
- Blood pressure
- Urinalysis (note:
proteinuria may be absent in chronic renal effects)
- Full blood count (anaemia
not common at lower lead levels)
- Renal function: - urea,
creatinine (insensitive)
- creatinine clearance -
(ensure proper 24 hour urine collection)
- concentrating ability
following overnight fast
- Nerve conduction studies (if
symptomatic)
- Neurobehavioural test
battery for CNS effects
- Semen analysis (after
fertility history)
- Endocrine workup (uncommon)
Dose-effect relationships:
- Complex relationship lead in
air with blood lead.
- Acute vs chronic loading
important because of bone stores.
- Thresholds of effect being
lowered with improved information.
Dose |
Effect |
0-40
µg/dl |
Delta-ALA enzyme
inhibition
Earliest (ulnar) nerve conduction abnormalities
Effects on foetus and children |
40-80
µg/dl |
ZPP elevated
Vague symptoms
Neuropsychological performance impairment
? Hypertension
Subclinical renal effects
Sperm counts or morphology affected |
80
- 120 µg/dl |
Anaemia
Frank symptoms |
>
120 µg/dl |
Risk of encephalopathy |
Treatment:
1. Removal
from exposure (Lead Regulations):
- Blood Pb ³
60 µg/dl
- or ZPP ³
10 µg/g Hb
- or, if symptomatic, or other
clinical indication.
2. Monitor
- Return when blood Pb
< 50 µg/dl, or ZPP < 6 µg/g Hb
3. Chelation:
clinical decision!
- Acute symptoms
- Blood lead > 120
µg/dl?
- Chronic deficits - no
evidence from trials. Empirical.
Never:
- Prophylactic
- While still exposed
Chelating
agents available in SA:
1.
Dimercaprol: IM x 5 days (painful)
2. Pencillamine orally, 600-1100 mg/daily
x 2 months
- Monitor: urine, FBC,
allergic reaction
Chelating
agents unavailable in SA:
3.
Calcium EDTA (Calcium Versenate)
- 5 days IV as inpatient;
monitor output, renal function
- (Also used for diagnostic
body burden challenge: - 1 g. IV or IM - measure urine lead)
4.
Dimercaptosuccinic acid (DMSA)
Reporting/recording:
Excess
absorption: (Pb > 60
µg/dl, ZPP > 10 µg/g Hb)
Should be recordable incident under OHSA
Lead Regulations.
Not compensatable under COIDA.
Occupational
lead poisoning, i.e. clinical disease
Compensatable disease under COIDA
Community
lead poisoning:
Notifiable disease under Health Act, 11177
ORGANIC LEAD:
Very
different from inorganic lead
Tetraethyl lead is more toxic
and less volatile than tetramethyl lead.
Exposure
- Manufacture, transport
(spills!), blending at refinery
- Cleaning and maintenance of
storage tanks:
- highest risk
- skin and respiratory
route
- difficult to predict
Toxicology:
- Highly lipid soluble ®
CNS
- Liver metabolism to water
soluble trialkyl lead
Clinical:
- Nervous instability
(insomnia,agitation)
- Nausea, vomiting
- Normal blood count
- Severe: hyperactivity,
delusions ®
coma
Treatment:
Sedation, hydration.
Prevention:
- Enclosure
- Air supplied full body
protection in tanks
Biological monitoring (See
Lead Regulations, HT notes on lead regulations)
Urine lead: < 150
µg/l
Postgraduate Diploma in Occupational Health (DOH) - Modules 3:
Occupational Medicine & Toxicology (Basic) by Profs Mohamed
Jeebhay and Rodney
Ehrlich,
Health
Sciences UCT is licensed under a
Creative
Commons Attribution-Noncommercial-Share Alike 2.5 South Africa License.
Major contributors: Mohamed Jeebhay, Rodney Ehrlich, Jonny Myers,
Leslie London, Sophie Kisting, Rajen Naidoo, Saloshni Naidoo. Source available
from here.
For any updates to the material, or more permissions beyond the scope
of this license, please email healthoer@uct.ac.za
or visit www.healthedu.uct.ac.za.
Last updated Jan 2007.
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