Introduction
This topic covers occupational poisoning by inorganic arsenic compounds: where workers meet arsenic, how the toxic forms act in the body, how acute and chronic poisoning present, how exposure and effect are confirmed, how poisoning is treated, and how occupational medicine assesses such cases for expertise purposes.
Etiology and sources of exposure
Arsenic is a naturally occurring metalloid. Most occupational cases involve inorganic arsenic compounds, which are far more toxic than organic forms. Exposure occurs mainly by inhalation of dust or fumes and by ingestion of contaminated material.
- Non-ferrous metal mining and smelting (copper, lead, zinc, gold ores), where arsenic is a companion element
- Production of wood preservatives, glass, pigments, semiconductors and some alloys
- Agriculture: arsenical pesticides, herbicides and wood preservatives, with contamination of soil and crops
- Natural exposure through contaminated groundwater and, in some regions, through rice and food; seafood contains mainly organic arsenic, which is of low toxicity
Pathogenesis
The trivalent form (As III) is the most toxic, because it binds strongly to sulfhydryl groups of enzymes and proteins. Pentavalent arsenic (As V) is less toxic and must be reduced in the body before it acts. The key mechanisms are:
- Inhibition of pyruvate dehydrogenase and other lipoate-dependent enzymes (including alpha-ketoglutarate dehydrogenase), which blocks entry of pyruvate into the citric acid cycle
- Reduced ATP production, because the cycle and oxidative phosphorylation are impaired; cells dependent on energy, such as neurons, myocardium and the gastrointestinal epithelium, are affected first
- Impaired glucose uptake and utilisation, with compensatory activation of gluconeogenesis and fatty acid oxidation
- Depletion of glutathione, which increases oxidative stress
- Binding of arsenic to erythrocyte membrane and haemoglobin components, causing haemolysis in significant poisoning