Module 3: Toxicology - Section 10: Other Heavy Metals

TOX 10.3: Arsenic

ARSENIC:

Uses and high risk exposures:

• produced as byproduct of mining/smelting of copper and other non-ferrous metal ores viz. Pb, Zn, gold from which arsenic is removed as an impurity;

• various arsenic compounds produced, the most common being inorganic arsenic trioxide (As₂O₃);

• other arsenic compounds include inorganic eg. arsenic pentoxide (As₂O₅), arsine (AsH₃) and organoarsenicals eg. arsenobetaine present in seafood;

• mainly used for agricultural purposes (insecticides, herbicides) but also used in wood preservatives, pharmaceutical, chemical, smelting, mining and microelectronic industries.

Metabolism:

a) Absorption:

• arsenic compounds are mainly absorbed by ingestion, skin or inhalation;
• inhalation is the principle route of occupational exposure to inorganic arsenic (trivalent) and ingestion becomes important in domestic setting (dietary arsenic in seafood or contaminated water from industrial or natural processes).

b) Distribution:

• arsenic is immediately bound to RBC and rapidly redistributed to liver, lungs, GIT and spleen (t_½ in blood = 60 hours);
• slowly redistributed to skin, hair, bone and nails (over few weeks);
• inorganic arsenic metabolised in liver to less toxic monomethylarsonic acid and cacodylic acid.

c) Excretion:

• renal major means of elimination and is rapid (30% excreted within 24 hrs);
• presence of inorganic arsenic compounds and their metabolites in urine can differentiate between occupational exposure and non-occupational arsenic present usually in the diet.

Health effects:

• toxic effects depend on the type of arsenic exposure. The trivalent compounds viz. arsenic trioxide and arsine are regarded as more toxic than the pentavalent form;

• all arsenic compounds (except arsine) act by inhibiting sulfhydryl enzyme systems required for cell metabolism.

INORGANIC ARSENIC (ARSENIC TRIOXIDE):

a) Acute effects:

• follows ingestion of contaminated food or water but can also be caused by massive industrial exposure;
• major symptoms are due to inflammation of the bowel presenting with abdominal pain, diarrhoea and bleeding which may lead to kidney failure, coma, fits and death.

b) Chronic effects:

1. Skin: most common:

1. Eczematous dermatitis:

   • red, itchy and painful swelling of the skin;

   • usually irritant in nature;
   • commonly occurs among workers cleaning dust collectors or loading the flue dust;
   • fine dust collects in the clothing and under the rubber facepieces of respirators, mixes with sweat and may cause marked dermatitis.

      

2. Follicular dermatitis:

   • lesions consist of perifolicular erythema accompanied by burning and itching;
   • late reactions include papular and vesicular lesions sometimes leading to widespread pustular folliculitis;
   • lesions localised chiefly to areas of greatest exposure such as face, neck, forearms, wrist and hands.

      

3. Patchy hyperpigmentation pronounced around the eyelids, neck, armpits and groin.

4. Hyperkeratosis (thickening) of palms and soles of feet.

5. Transverse white lines (Mees' lines) on the nails.

6. Skin cancer: Bowen's disease, basal cell carcinoma and squamous cell carcinoma.

2. Eyes:

Conjunctivitis (red, itchy and painful eyes).

3. Nose:

• Erosions of the respiratory mucosa and perforation of the nasal septum.
• Symptoms: excessive secretions from the nose, irritation or blocked noses, epistaxis (complication).

4. Peripheral Nerves:

• Symmetric distal polyneuropathy involving both sensory and motor fibres within 1-2 weeks after acute exposure.
• Symptoms: loss of sensation and muscle weakness mainly in the lower limbs, but also upper limbs.
• Neuropathy is partially reversible on removal from exposure.

5. Liver:

• Reversible liver enlargement and liver cirrhosis.
• Some case reports have linked arsenic exposure to hepatic angiosarcoma.

6. Lung:

• Excess risk of lung cancer and excessive death rates from lung cancer (arsenic trioxide): 8-fold increase in lung cancer deaths.
• Occupational arsenic exposure and smoking appear to have independent, multiplicative effects on lung cancer deaths.

ARSINE (ASH₃):

• Colourless gas (garlic smell).
• Produced when inorganic acids used to etch metals in the presence of arsenic.
• Exposure common when metal storage tanks are cleaned and in semi-conductor manufacturing.
• Produces intravascular haemolysis (jaundice, fever, bloody urine, hepatomegaly etc.) within 6 - 36 hours of exposure and possible renal failure - fatal.

Risk management:

a) Limiting exposure:

• Engineering controls.
• Administrative controls.
• Personal protective equipment.
• Personal hygiene.
• Education and training.

b) Industrial hygiene monitoring:

The occupational exposure limit (OEL) according to the Regulations for Hazardous Chemical Substances:

• Arsenic and compounds: TWA - 0.1 mg/m³ (control limit).
• Arsine gas: TWA - 0.2 mg/m³ (recommended limit).

ACGIH:

• Arsenic and compounds: TWA - 0.01 mg/m³.
• Arsine gas: TWA - 0.16 mg/m³.

c) Biological monitoring:

• Urine arsenic is a good indicator of current exposure (1-2 days).

• Due to the presence of organic arsenic present in diet (seafood), measurement of inorganic arsenic acid and its metabolites viz. cacodylic acid, monomethylarsonic acid better indicators of occupational arsenic absorption.

• While hair arsenic determinations are a good indicator of past exposure to arsenic it does not distinguish between ingested/inhaled arsenic and that deposited on the hair due to bathing or working in arsenic-contaminated environments. Their use is therefore limited.

• Biological exposure indices (BEI) for arsenic and arsine metabolitites according to the Regulations for Hazardous Chemical Substances and ACGIH is an end of workweek urine specimen with arsenic metabolites not exceeding 50 µg/g creatinine (includes background levels - important to abstain from seafood for 2 days).

d) Medical surveillance:

• Skin and nasal examination (speculum).
• Liver function tests, chest x-rays (?).

e) Treatment:

• Dimercaprol (IM) in acute arsenic and arsine poisoning or D-penicilamine (arsenic poisoning).
• Exchange transfusion (arsine poisoning).
• Haemodialysis (renal failure).

f) Compensation:

Any disease or pathological manifestation due to arsenic is compensable under COIDA as it is listed as one of the substances in schedule 3 of the Act.

g) Notify the case to the Chief Inspector in DOL:

• Medical practitioners are required by the OHSA to notify all cases of suspected occupational disease to the Chief Inspector, Department of Labour.
• form WCl 22 (First Medical Report in respect of an Occupational Disease).

Postgraduate Diploma in Occupational Health (DOH) - Modules 3: Occupational Medicine & Toxicology (Basic) by Profs Mohamed Jeebhay and Rodney Ehrlich, Health Sciences UCT is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 2.5 South Africa License. Major contributors: Mohamed Jeebhay, Rodney Ehrlich, Jonny Myers, Leslie London, Sophie Kisting, Rajen Naidoo, Saloshni Naidoo. Source available from here. For any updates to the material, or more permissions beyond the scope of this license, please email healthoer@uct.ac.za or visit www.healthedu.uct.ac.za. Last updated Jan 2007.
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