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      An update on toxicology of aluminum phosphide

      research-article
      1 ,
      DARU Journal of Pharmaceutical Sciences
      BioMed Central
      Aluminum phosphide, Phosphine, Management, Poisoning, Suicide

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          Abstract

          Aluminum phosphide (AlP) is a cheap solid fumigant and a highly toxic pesticide which is commonly used for grain preservation. In Iran it is known as the “rice tablet”. AlP has currently aroused interest with increasing number of cases in the past four decades due to increased use in agricultural and non-agricultural purposesand also its easy availability in the markets has increased its misuse to commit suicide. Upon contact with moisture in the environment, AlP undergoes a chemical reaction yielding phosphine gas, which is the active pesticidal component. Phosphine inhibits cellular oxygen utilization and can induce lipid peroxidation. It was reported that AlP has a mortality rate more than 50% of intoxication cases. Poisoning with AlP has usually occurred in attempts to suicide. It is a more common case in adults rather than teen agers. In some eastern countries it is a very common agent with rapid action for suicide. Up to date, there is no effective antidote or treatment for its intoxication. Also, some experimental results suggest that magnesium sulfate, N-acetyl cysteine (NAC), glutathione, vitamin C and E, beta-carotenes, coconut oil and melatonin may play an important role in reducing the oxidative outcomes of phosphine. This article reviews the experimental and clinical features of AlP intoxication and tries to suggest a way to encounter its poisoning.

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          Most cited references70

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          Aluminium and zinc phosphide poisoning.

          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. 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. 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.
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            Induction of mitochondrial permeability transition by auranofin, a gold(I)-phosphine derivative.

            1 Gold(I)-thiolate drugs are compounds that specifically interact with thiol and/or selenol groups and are essentially utilized in the treatment of rheumatoid arthritis. 2 Considering the importance of thiol groups in regulating mitochondrial membrane permeability, the effects of auranofin (S-triethylphosphinegold(I)-2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranoside), a second-generation gold drug, were studied on mitochondria isolated from rat liver. 3 Auranofin, at submicromolar concentrations, was able to induce the mitochondrial membrane permeability transition observed as swelling and loss of membrane potential. Both events are completely inhibited by cyclosporin A, the specific inhibitor of mitochondrial permeability transition. Calcium ions and energization by succinate are required for the occurrence of permeability transition. 4 By interacting with the active site selenol group, auranofin results as an extremely potent inhibitor of mitochondrial thioredoxin reductase, both isolated and in its mitochondrial environment. 5 It is concluded that auranofin, in the presence of calcium ions, is a highly efficient inducer of mitochondrial membrane permeability transition, potentially referable to its inhibition of mitochondrial thioredoxin reductase.
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              Successful treatment of acute aluminium phosphide poisoning: possible benefit of coconut oil.

              Aluminium phosphide is used to control rodents and pests in grain storage facilities. It produces phosphine gas, which is a mitochondrial poison. Unfortunately, there is no known antidote for aluminium phosphide intoxication, but our recent experience with a case showed that rapid prevention of absorption by coconut oil might be helpful. In the present case, we used the same protocol in a 28-year-old man who had ingested a lethal amount (12 g) of aluminium phosphide with suicidal intent and was admitted to hospital approximately 6 hours postingestion. The patient had signs and symptoms of severe toxicity, and his clinical course included metabolic acidosis and liver dysfunction. Treatment consisted of gastric lavage with potassium permanganate solution, oral administration of charcoal and sorbitol suspension, intravenous administration of sodium bicarbonate, magnesium sulphate and calcium gluconate, and oral administration of sodium bicarbonate and coconut oil. Conservative and supportive therapy in the Intensive Care Unit was also provided. The patient survived following rapid treatment and supportive care. It is concluded that coconut oil has a positive clinical significance and can be added to the treatment protocol of acute aluminium phosphide poisoning in humans.
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                Author and article information

                Journal
                Daru
                Daru
                DARU Journal of Pharmaceutical Sciences
                BioMed Central
                1560-8115
                2008-2231
                2012
                3 September 2012
                : 20
                : 1
                : 25
                Affiliations
                [1 ]Department of Pharmacology, Babol University of Medical Sciences, Babol, Iran
                Article
                2008-2231-20-25
                10.1186/2008-2231-20-25
                3555759
                23351193
                e45ca7b1-d4ea-48ef-89ac-5154bab1e4eb
                Copyright ©2012 Moghhadamnia; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 4 May 2012
                : 17 May 2012
                Categories
                Review Article

                Pharmacology & Pharmaceutical medicine
                suicide,poisoning,phosphine,management,aluminum phosphide
                Pharmacology & Pharmaceutical medicine
                suicide, poisoning, phosphine, management, aluminum phosphide

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