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Isopropanol
POISONOUS SUBSTANCES
Isopropanol
Lead
Allister Vale
Sally Bradberry Allister Vale
Isopropanol is found in aftershave lotions, disinfectants and window-cleaning solutions, and is used as a sterilizing agent and ‘rubbing’ alcohol.
Lead has widespread applications. It is still used extensively in battery manufacture, solders, pigments (usually for outdoor paints, which require greater resilience to weather), radiation shielding, copper smelting, lead shot for firearms, and rubber and plastic manufacturing. Its use as an additive in household paint has ceased because of concerns about toxicity. Lead tetroxide (red lead) is used as a rust-proofing agent on steel structures such as monuments and bridges. In the UK in 2000–2001, 16,100 workers were occupationally exposed to clinically significant amounts of lead. Inhalation is the predominant route; workers are most likely to be exposed to lead dust when sanding, blasting or abrading lead or lead-coated surfaces, when burning off lead paint, and when reclaiming lead from scrap metal by flame-cutting. Occupational exposure by ingestion results from non-adherence to basic hygiene measures in the workplace. These should prevent eating, drinking, smoking and chewing of gum where contamination may occur. Poisoning has occurred as a consequence of leaching from leadglazed mugs and use of lead-containing cosmetics and ‘medicines’, and when children with pica chew on lead-painted railings or eat contaminated soil. Rarely, lead acetate has been injected intravenously with suicidal intent. Tetraethyl lead, which is used as an antiknock agent in leaded petrol, can be absorbed systemically by inhalation and ingestion and through the skin.
Mechanism of toxicity: following ingestion or absorption through the skin, isopropanol is oxidized to acetone by hepatic alcohol dehydrogenase. The effects of isopropanol on the nervous system are similar to those of ethanol, but are probably more severe and more persistent. Clinical features: coma and respiratory depression are the major sequelae, but gastritis, haematemesis, hypotension, hypothermia, renal tubular necrosis, acute myopathy and haemolytic anaemia have been reported. The odour of acetone may be detected on the breath. Development of hypotension is a poor prognostic feature and may herald cardiac arrest. Management: although gastric lavage is usually advocated in patients with isopropanol poisoning, there is no evidence that it is of value in reducing absorption. In severe cases, haemodialysis should be used to remove isopropanol and reduce the duration of coma; peritoneal dialysis is less effective. No advantage is gained by administering ethanol or fomepizole to block alcohol dehydrogenase, because the toxicity of isopropanol is caused principally by the parent compound and not by acetone.
Toxicokinetics: once lead is absorbed via ingestion (about 10–15% absorbed) or inhalation (up to 80% absorbed), it enters the bloodstream, where it is mainly (> 99%) found in RBCs. Recent studies suggest that it is D-aminolaevulinic acid dehydratase rather than haemoglobin that is the principal lead-binding protein. Bone contains about 90% of the total body lead content. Lead is excreted mainly through the kidneys (75%); other routes of excretion are the bile, gastrointestinal secretions, hair, nails and sweat. Mechanism of toxicity: lead is an electropositive metal with a high affinity for negatively charged sulphydryl groups. It also inhibits zinc-dependent enzyme systems. Conversion of D-aminolaevulinic acid dehydratase (a sulphydryldependent cytoplasmic enzyme) to porphobilinogen is blocked by inhibition of the former, leading to increased D-aminolaevulinic acid in the blood and urine. Aminolaevulinic acid resembles γaminobutyric acid (GABA) and can stimulate GABA receptors in the nervous system; this is thought to be a primary mechanism of lead-induced neurotoxicity. Lead inhibits coproporphyrinogen oxidase, resulting in increased coproporphyrinogen III activity. Inhibition by lead of the
FURTHER READING Pappas A A, Ackerman B H, Olsen K M et al. Isopropanol Ingestion: A Report of Six Episodes with Isopropanol and Acetone Serum Concentration Time Data. Clin Toxicol 1991; 29: 11–21.
MEDICINE
56
© 2003 The Medicine Publishing Company Ltd
Isopropanol
Lead
Allister Vale
Sally Bradberry Allister Vale
Isopropanol is found in aftershave lotions, disinfectants and window-cleaning solutions, and is used as a sterilizing agent and ‘rubbing’ alcohol.
Lead has widespread applications. It is still used extensively in battery manufacture, solders, pigments (usually for outdoor paints, which require greater resilience to weather), radiation shielding, copper smelting, lead shot for firearms, and rubber and plastic manufacturing. Its use as an additive in household paint has ceased because of concerns about toxicity. Lead tetroxide (red lead) is used as a rust-proofing agent on steel structures such as monuments and bridges. In the UK in 2000–2001, 16,100 workers were occupationally exposed to clinically significant amounts of lead. Inhalation is the predominant route; workers are most likely to be exposed to lead dust when sanding, blasting or abrading lead or lead-coated surfaces, when burning off lead paint, and when reclaiming lead from scrap metal by flame-cutting. Occupational exposure by ingestion results from non-adherence to basic hygiene measures in the workplace. These should prevent eating, drinking, smoking and chewing of gum where contamination may occur. Poisoning has occurred as a consequence of leaching from leadglazed mugs and use of lead-containing cosmetics and ‘medicines’, and when children with pica chew on lead-painted railings or eat contaminated soil. Rarely, lead acetate has been injected intravenously with suicidal intent. Tetraethyl lead, which is used as an antiknock agent in leaded petrol, can be absorbed systemically by inhalation and ingestion and through the skin.
Mechanism of toxicity: following ingestion or absorption through the skin, isopropanol is oxidized to acetone by hepatic alcohol dehydrogenase. The effects of isopropanol on the nervous system are similar to those of ethanol, but are probably more severe and more persistent. Clinical features: coma and respiratory depression are the major sequelae, but gastritis, haematemesis, hypotension, hypothermia, renal tubular necrosis, acute myopathy and haemolytic anaemia have been reported. The odour of acetone may be detected on the breath. Development of hypotension is a poor prognostic feature and may herald cardiac arrest. Management: although gastric lavage is usually advocated in patients with isopropanol poisoning, there is no evidence that it is of value in reducing absorption. In severe cases, haemodialysis should be used to remove isopropanol and reduce the duration of coma; peritoneal dialysis is less effective. No advantage is gained by administering ethanol or fomepizole to block alcohol dehydrogenase, because the toxicity of isopropanol is caused principally by the parent compound and not by acetone.
Toxicokinetics: once lead is absorbed via ingestion (about 10–15% absorbed) or inhalation (up to 80% absorbed), it enters the bloodstream, where it is mainly (> 99%) found in RBCs. Recent studies suggest that it is D-aminolaevulinic acid dehydratase rather than haemoglobin that is the principal lead-binding protein. Bone contains about 90% of the total body lead content. Lead is excreted mainly through the kidneys (75%); other routes of excretion are the bile, gastrointestinal secretions, hair, nails and sweat. Mechanism of toxicity: lead is an electropositive metal with a high affinity for negatively charged sulphydryl groups. It also inhibits zinc-dependent enzyme systems. Conversion of D-aminolaevulinic acid dehydratase (a sulphydryldependent cytoplasmic enzyme) to porphobilinogen is blocked by inhibition of the former, leading to increased D-aminolaevulinic acid in the blood and urine. Aminolaevulinic acid resembles γaminobutyric acid (GABA) and can stimulate GABA receptors in the nervous system; this is thought to be a primary mechanism of lead-induced neurotoxicity. Lead inhibits coproporphyrinogen oxidase, resulting in increased coproporphyrinogen III activity. Inhibition by lead of the
FURTHER READING Pappas A A, Ackerman B H, Olsen K M et al. Isopropanol Ingestion: A Report of Six Episodes with Isopropanol and Acetone Serum Concentration Time Data. Clin Toxicol 1991; 29: 11–21.
MEDICINE
56
© 2003 The Medicine Publishing Company Ltd