Toxicity of metals - chronic health hazards, prevention and surveillance

1. Toxicity of metals - chronic health hazards, prevention and surveillance Vesa Riihimäki Unit for toxicological risk assessment Finnish Institute of Occupational Health TYÖTERVEYSLAITOS

2. Metals causing harm in the occupational setting • Aluminium • Cadmium • Chromium(VI), note: chromium(III) is essential to man • Cobolt, note: essential component of B12 vitamin • Lead • Manganese, note: essential trace element • Mercury • Nickel • Vanadium • Zinc, note: essential trace element TYÖTERVEYSLAITOS

3. Metal foundry Flame cutting and welding- stainless steels (Cr, Ni)- special steels (Mn)- cadmium plating- zinc plating- painted steel (Pb)- aluminium Soldering- silver solder (Cd)- lead solder Grinding and polishing (Co, Cr, Ni) Storage batteries- lead- cadmium and nickel- manganese Instrument repair- mercury Furnace cleaning- vanadium Chemicals, catalysts Occupational exposures to metals TYÖTERVEYSLAITOS

4. Common concepts in metal toxicology • Most metals exhibit limited absorption • Metabolism is usually limited to oxidation/reduction, alkylation/dealkylation or complexation • Many have a long residence time in the body due to binding (sequestering) or storage • Toxicokinetics and target organ toxicity are highly dependent on the metal species

5. Species specific metal toxicity • Underlying factors: solubility, uptake (systemic, cellular), tissue distribution, specific biological reactivity • Examples: mercury compounds- metallic mercury- mercuric salts, e.g. chloride- methylmercury- methoxymethylmercury acetate

6. Species specific toxicity, cont'd • Aluminium: oxide versus sulphate • Chromium(VI) versus chromium(III) • Lead dust & salts versus alkyl lead • Nickel: metallic Ni, Ni oxides, Ni subsulfide, Ni carbonyl • Zinc: freshly generated fumes of Zn oxide versus Zn chloride

7. Aluminium Kadmium Chromium(VI) Cobolt Lead Manganese CNS, bone Kidney, lung, carcinogenicity Airways, skin, sensitisation, carcinogenicity, kidney Lung, skin, sensitisation CNS & PNS, blood forming organs, kidney, reproduction CNS (signs of Parkinsonism) Target organs for metals toxicity in humans

8. Mercury- elemental vapour- mercuric salts- alkyls Nickel Vanadium Zinc - CNS, kidney- kidney, skin sensitisation- CNS, developmental toxicity Airway carcinogenicity, skin sensitisation Respiratory system Respiratory system Target organs for metals toxicity in humans, cont'd

9. Tissue distribution and elimination of lead • Central compartment: blood lead- half-time about 30 days- about 4% of the body burden • Soft tissue lead- half-time about 30-40 days- about 2% of the body burden • Lead in bone- half-time up to 30 years- 94% of the body burden

10. Physiologically-based toxicokinetic model for lead

11. Dose-effect and dose-response relationship: lead decreased erythrocyte delta-ALAD activity increased zinc protoporphyrin anemia CNS effects decreased peripheralnerve conductivity Nervous paralysis, lead colics Adapted from Elinder C-G et al., Biologisk monitoring av metaller hos människa. Arbetsmiljöfonden, Uppsala, 1991

12. Prevention and surveillance • Control exposure from all sources that may lead to hazardous accumulation • Perform biological monitoring of body burden U-Cr, U-Co, B-Pb, U-Mn (?), U-Hg, U-Ni, U-V to ensure that accumulation will not reach critical levels • Perform health surveillance for early effects, making note of individual susceptibility

13. Basis for health surveillance among aluminium welders • Indication of increasing body burden with time at exposure • Suspicion of aluminium accumulation in the target organ of toxicity (the brain) • Demonstration of a dose-response between aluminium in serum and urine and CNS effects (symptoms, attention & working memory impairment, EEG abnormality) • Effect threshold: U-Al 4-6 µmol/l, S-Al 0.25-0.35 µmol/l

14. Relationship between aluminium welding months and urinary aluminium concentration