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

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

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

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

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

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

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

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

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

Dose-effect and dose-response relationship: lead decreased erythrocyte delta-ALAD activityincreased zinc protoporphyrin

anemia

CNS effectsdecreased peripheral nerve conductivityNervous paralysis, lead colics

Adapted from Elinder C-G et al., Biologisk monitoring av metallerhos människa. Arbetsmiljöfonden, Uppsala, 1991

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

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