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. Ingestion of metal phosphides is a well-known suicide route, especially in Asia. An 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.

Successful management of zinc phosphide poisoning: possible benefit of virgin olive oil

“…In our case, we used virgin olive oil to induce antioxidant activity. According to an article published in 2016, more aggressive gastrointestinal decontamination is necessary for patients [4]. Different studies in rats [14] and humans [15] have revealed that N-acetylcysteine can help as it replenishes cellular glutathione and magnesium, in addition to its antioxidant properties.…”

“…It progressively converts oxyhaemoglobin to methaemoglobin and hemi chrome species. The reaction of phosphine with oxyhaemoglobin leads to a formation of phosphite and phosphate ions [4]. Phosphine thus reduces the oxyhaemoglobin of blood.…”

Adjuvant potential of selegiline in treating acute toxicity of aluminium phosphide in rats

“…More than 90% of these poisonings are related to suicide . A three‐gram tablet can produce one gram of phosphine (PH 3 ) gas, which is a colourless and odourless toxic gas …”

“…PH 3 is a highly toxic metabolic poison that affects all organs of the body and causes a wide range of effects including cellular poisoning, oxidative stress, cholinesterase inhibition, circulatory failure, cardiac toxicity, pulmonary toxicity and gastrointestinal (GI) tract damage, liver damage, neurotoxicity and electrolyte imbalance. It has been shown that cardiac tissue is one of the main target organs for the toxicity of PH 3 . In this regard, AlP has shown to induce significant deterioration in cardiovascular anatomy and functions.…”

“…8 A three-gram tablet can produce one gram of phosphine (PH 3 ) gas, which is a colourless and odourless toxic gas. 9,10 PH 3 is a highly reactive radical that penetrates freely into the intracellular space and increases the production of H 2 O 2 from mitochondria, which induces oxidant-derived cellular damage, due to the products of H 2 O 2 reduction, 11 such as the very reactive hydroxyl radicals. 12 PH 3 poisoning also increases reactive oxygen species (ROS) and lipid peroxidation in affected subjects.…”