title: Phosphine toxicity: a story of disrupted mitochondrial metabolism.
abstract: Rodenticides and pesticides pose a significant threat not only to the environment but also directly to humans by way of accidental and/or intentional exposure. Metal phosphides, such as aluminum, magnesium, and zinc phosphides, have gained popularity owing to ease of manufacture and application. These agents and their hydrolysis by-product phosphine gas (PH3 ) are more than adequate for eliminating pests, primarily in the grain storage industry. In addition to the potential for accidental exposures in the manufacture and use of these agents, intentional exposures must also be considered. As examples, ingestion of metal phosphides is a well-known suicide route, especially in Asia; and intentional release of PH3 in a populated area cannot be discounted. Metal phosphides cause a wide array of effects that include cellular poisoning, oxidative stress, cholinesterase inhibition, circulatory failure, cardiotoxicity, gastrointestinal and pulmonary toxicity, hepatic damage, neurological toxicity, electrolyte imbalance, and overall metabolic disturbances. Mortality rates often exceed 70%. There are no specific antidotes against metal phosphide poisoning. Current therapeutic intervention is limited to supportive care. The development of beneficial medical countermeasures will rely on investigative mechanistic toxicology; the ultimate goal will be to identify specific treatments and therapeutic windows for intervention.
authors.affiliation: Medical Toxicology Branch, Analytical Toxicology Division.
authors.forename: Alfred M
authors.initials: AM
authors.lastname: Sciuto
authors.affiliation: Medical Toxicology Branch, Analytical Toxicology Division.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Wong
authors.affiliation: Physiology and Immunology Branch.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Martens
authors.affiliation: Cell and Molecular Biology, Research Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Hoard-Fruchey
authors.affiliation: Medical Toxicology Branch, Analytical Toxicology Division.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Perkins
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects; D010720:Phosphines / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D010720:Phosphines; D017382:Reactive Oxygen Species; C044646:phosphine
keywords: mitochondria; phosphine; reactive oxygen species; rodenticide; systemic poison