Aluminium and zinc phosphide poisoning.
BACKGROUND
Aluminium and zinc phosphides are highly effective insecticides and rodenticides and are used widely to protect grain in stores and during its transportation. Acute poisoning with these compounds may be direct due to ingestion of the salts or indirect from accidental inhalation of phosphine generated during their approved use.
Both forms of poisoning are mediated by phosphine which has been thought to be toxic because it inhibits cytochrome c oxidase. While phosphine does inhibit cytochrome C oxidase in vitro, the inhibition is much less in vivo. It has been shown recently in nematodes that phosphine rapidly perturbs mitochondrial morphology, inhibits oxidative respiration by 70%, and causes a severe drop in mitochondrial membrane potential. This failure of cellular respiration is likely to be due to a mechanism other than inhibition of cytochrome C oxidase. In addition, phosphine and hydrogen peroxide can interact to form the highly reactive hydroxyl radical and phosphine also inhibits catalase and peroxidase; both mechanisms result in hydroxyl radical associated damage such as lipid peroxidation. The major lethal consequence of phosphide ingestion, profound circulatory collapse, is secondary to factors including direct effects on cardiac myocytes, fluid loss, and adrenal gland damage. In addition, phosphine and phosphides have corrosive actions.


METHODS
There is usually only a short interval between ingestion of phosphides and the appearance of systemic toxicity. Phosphine-induced impairment of myocardial contractility and fluid loss leads to circulatory failure, and critically, pulmonary edema supervenes, though whether this is a cardiogenic or non-cardiogenic is not always clear. Metabolic acidosis, or mixed metabolic acidosis and respiratory alkalosis, and acute renal failure are frequent. Other features include disseminated intravascular coagulation, hepatic necrosis and renal failure. There is conflicting evidence on the occurrence of magnesium disturbances.


RESULTS
There is no antidote to phosphine or metal phosphide poisoning and many patients die despite intensive care. Supportive measures are all that can be offered and should be implemented as required.
Proudfoot
Alex T
AT
National Poisons Information Service, City Hospital, Birmingham, UK. alexproudfoot@mortonhall.demon.co.uk
D017607:Aluminum Compounds / Q000493:pharmacokinetics / Q000506:poisoning*; D000818:Animals; D001711:Biotransformation; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000628:therapy; D019069:Cell Respiration / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D004781:Environmental Exposure; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000628:therapy; D006801:Humans; D007306:Insecticides / Q000493:pharmacokinetics / Q000506:poisoning*; D015227:Lipid Peroxidation / Q000187:drug effects; D008107:Liver Diseases / Q000628:therapy; D008171:Lung Diseases / Q000139:chemically induced / Q000628:therapy; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016273:Occupational Exposure; D010720:Phosphines / Q000378:metabolism / Q000493:pharmacokinetics / Q000506:poisoning*; D018570:Risk Assessment; D012378:Rodenticides / Q000493:pharmacokinetics / Q000506:poisoning*; D014882:Water-Electrolyte Balance / Q000187:drug effects; D017967:Zinc Compounds / Q000493:pharmacokinetics / Q000506:poisoning*
D017607:Aluminum Compounds; D007306:Insecticides; D010720:Phosphines; D012378:Rodenticides; D017967:Zinc Compounds; C009701:zinc phosphide; C001864:aluminum phosphide; C044646:phosphine