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 TYÖTERVEYSLAITOS 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

3. TYÖTERVEYSLAITOS Occupational exposures to metals 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

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. Target organs for metals toxicity in humans 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)

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

9. T issue 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 peripheral nerve 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