TOXICVB

Toxicity of metals - chronic health hazards, prevention and surveillance: 

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

Metals causing harm in the occupational setting: 

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

Occupational exposures to metals: 

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

Common concepts in metal toxicology: 

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

Species specific metal toxicity: 

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

Species specific toxicity, cont'd: 

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

Target organs for metals toxicity in humans: 

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)

Target organs for metals toxicity in humans, cont'd: 

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 Respiratory system

Tissue distribution and elimination of lead: 

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

Physiologically-based toxicokinetic model for lead: 

Physiologically-based toxicokinetic model for lead

Slide11: 

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

Prevention and surveillance: 

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

Basis for health surveillance among aluminium welders: 

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

Relationship between aluminium welding months and urinary aluminium concentration: 

Relationship between aluminium welding months and urinary aluminium concentration