Module 3: Toxicology - Section 11: Lead
TOX 11.4: Lecture: Lead (Occupational Aspects - Continued)

INORGANIC LEAD:

Toxicology:

Routes of entry:
  1. Inhalation (typically dust or fume)
  2. Ingestion (occupationally from smoking, eating while exposed, ?swallowing sputum)
  3. (Skin - not normally.)
Compartments (complex "4 compartment model"):
  1. Blood (half life 36 days)
  2. Soft tissues (half life: > 40 days)
  3. Trabecular (surface) bone: circulating (half life of the order of months)
  4. Cortical (deep) bone: non-circulating (half life: 20 yrs plus)
Chemical actions :
  1. Binds to ligands, (-OH, -SH, -NH2)
  2. Enzyme inhibition
  3. Cell membrane site of action
Rate of exposure in relation to effects:
  1. Acute: high dose over relatively short period
  2. Delayed post-acute: High dose, e.g. in childhood, followed by adverse effects many years later
  3. Chronic: steady dosage - typical occupational exposure

Clinical effects:

I. Classic syndrome of acute lead poisoning

This textbook syndrome is very uncommon today.


II. Organ system effects of chronic exposure (or delayed effects of acute exposure)
1. Haematologic

Mechanism:

  1. Reduced red cell survival
  2. Inhibition of red cell formation

Reversible? Yes.


2. Renal (including hypertension)

Acute: Fanconi like syndrome - mainly with acute exposures, e.g. in children.

Chronic:

Mechanisms:

  1. Proximal tubular damage
  2. Diffuse tubulo-interstitial lesion
  3. ? Increased reabsorption of urate
  4. ? Impaired renin-aldosterone function (hypertension)

Reversible? No/partly.


3. Neurologic

Mechanism: Axonal degeneration, demyelination, neurotransmitter disturbance.

Reversible: No/partly.


4. Reproductive:

Mechanisms:

  1. Defective spermatogenesis
  2. Central gonadotrophic defect
  3. Teratogenic, pregnancy effects?
5. Other endocrine
  1. Hypothyroidism
  2. 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)

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:

  1. Blood pressure
  2. Urinalysis (note: proteinuria may be absent in chronic renal effects)
  3. Full blood count (anaemia not common at lower lead levels)
  4. Renal function: - urea, creatinine (insensitive)
  5. Nerve conduction studies (if symptomatic)
  6. Neurobehavioural test battery for CNS effects
  7. Semen analysis (after fertility history)
  8. Endocrine workup (uncommon)

Dose-effect relationships:

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):

2. Monitor

3. Chelation: clinical decision!

Never:

Chelating agents available in SA:

   1. Dimercaprol: IM x 5 days (painful)
   2. Pencillamine orally, 600-1100 mg/daily x 2 months

Chelating agents unavailable in SA:

   3. Calcium EDTA (Calcium Versenate)

   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
  1. Manufacture, transport (spills!), blending at refinery
  2. Cleaning and maintenance of storage tanks:
Toxicology:
  1. Highly lipid soluble ® CNS
  2. Liver metabolism to water soluble trialkyl lead
Clinical:
  1. Nervous instability (insomnia,agitation)
  2. Nausea, vomiting
  3. Normal blood count
  4. Severe: hyperactivity, delusions ® coma
Treatment:

Sedation, hydration.

Prevention:
  1. Enclosure
  2. Air supplied full body protection in tanks
Biological monitoring (See Lead Regulations, HT notes on lead regulations)

Urine lead: < 150 µg/l



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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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