**1. Introduction**

344 Toxicity and Drug Testing

Tuomela, M., Malm, M., Wallen, M., Stanescu, I., Krohn, K. & Peterson, P. (2005).

Wang, Z., Troilo, P.J., Wang, X., Griffiths, T.G., Pacchione, S.J., Barnum, A.B., Harper, L.B.,

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Acute aluminium phosphide poisoning is an extremely lethal poisoning. Ingestion is usually suicidal in intent, uncommonly accidental and rarely homicidal. Unfortunately the absence of a specific antidote results in very high mortality and the key to treatment lies in rapid decontamination and institution of resuscitative measures.Aluminium phosphide is a solid fumigant which has been in extensive use since the 1940s. It has rapidly become one of the most commonly used grain fumigants because of its properties which are considered to be near ideal; it is toxic to all stages of insects, highly potent, does not affect seed viability, is free from toxic residues and leaves little residue on food grains(Hackenberg, 1972).

They are formulated as compressed discs, tablets or pellets that commonly weigh 3 g and contain variable amounts of a single phosphide in combination with other substances such as ammonium carbonate. Tablets are dark brown or grayish in colour. It is freely available in the markets with the major virtues of being cheap and not leaving toxic residues. The specified fatal dose in human is 0.15-0.5 gm. Phosphides are used widely to protect grain held in stores, the holds of ships and in wagons transporting it by rail and are admixed with the grain at a predetermined rate as it is put into storage. Moisture in the air between the grains mixes with phosphide and release phosphine (hydrogen phosphide, phosphorus trihydride, PH3) which is the active pesticide. After contact with an acid, phosphine is released even more vigorous. Two kinds of acute poisoning with these substances are reported: indirect inhalation of the phosphine generated during their approved use or direct ingestion of the salts.

Pure phosphine is colorless and odorless up to toxic concentrations (200 ppm), a view accepted by the International Programme on Chemical Safety and others (Pepelko, et al, 2004; Chaudhry, 1997; IPCS, 1988; Dumas & Bond, 1974), it has an odor of garlicky or decaying fish due to the presence of substituted phosphines and diphosphines .If the former view is accepted the smell emanating from phosphide poisoned patients is probably due to contaminants in the pesticide formulations and not phosphine itself. It has been suggested that these volatile contaminants may be alkylphosphines (Fluck, 1976). For "phosphine" liberated from one pesticidal formulation of aluminium phosphide, the odor threshold was 0.01–0.02 ppm, ten times lower than that derived from the technical salt alone (Fluck, 1976).The usefulness of phosphide pesticides is now threatened by the development of resistance to them.

#### **2. Methods**

To complete this review, the terms aluminum and aluminum phosphide and phosphine were searched using the TUMS (Tehran University of Medical Science) digital library,

Aluminium Phosphide Poisoning 347

Occupational exposures to phosphine are uncommon and rarely severe (Sudakin, 2005) but accidental inhalation is a particular risk to those in close proximity to grain that has had a metal phosphide mixed in with it. Recurring locations include ships holds (Gregorakos, et al, 2002, Hansen & Pedersen, 2001, Vohra, et al, 2006), rail wagons (Perotta, et al 1994, Vohra, et al, 2006), grain elevators (Abder-Rahman, et al, 2000), grain stores (Brautbar & Howard, 2002, Misra, et al, 1988), and even stores in homes (Abder-Rahman, et al, 2000). Potentially lethal concentrations of the gas may develop in the head-spaces of unventilated

Phosphine may be released during the illicit manufacture of methamphetamine (Burgess, 2001, Willers-Russo, 1999); deaths have resulted (Willers-Russo, 1999). In another incident, a packet of aluminium phosphide in a container from abroad burst open and the sweepings placed in water causing immediate fizzing and liberation of phosphine (Kamanyire & Murray, 2003). Close proximity to a source of phosphine is not required to be at risk of toxicity as phosphine gas can travel some distance as it is heavier than air (vapor density 1.2:1). Many years ago 12 individuals in a house adjacent to a warehouse used to store aluminium phosphide developed vomiting and one died. The illnesses were attributed to phosphine (Glass, 1959). More recently exposures have been alleged after use of metal

The exact mechanism of action of aluminum phosphide poisoning is still unknown, however an initial survey on different animals showed non-competitive cytochrome oxidase binding by phosphine, changes valences of haeme component of haemoglobin.Other than later articles, distinguished significant inhibition of catalase goes to hydrogen peroxide agglomeration (Price, et al, 1982), Extra-mitochondrial release of hydrogen peroxide and oxygen free radicals (Bolter & Chertuka, 1989), leading to lipid peroxidation and protein denaturation of cell membrane are reported in more recent studies (Chug, et al, 1969). Also, aluminum and phosphine (Potter, et al, 1993; Al-Azzawi, et al, 1990), inhibit cholinesterases activity . Al-Azzawi showed in vitro exposure to phosphine lead to reducing human serum cholinesterase activity; in addition he showed the amount of the inhibition is related to the duration and concentration of phosphine (Al-Azzawi, et al, 1990). On the other hand, other studies declared there is no erythrocyte cholinesterase activity reduction in humans after

Phosphine must be quickly and easily absorbed because of the short interval between ingestion and the appearance of systemic toxicity features. Noticeably, phosphides possibly absorbed as microscopic particles of unhydrolysed salt (Stewart, et al, 2003, Chan, et al, 1983) and permanently, in vitro, interact with free hemoglobin and hemoglobin in intact erythrocytes (rat and human) to produce a hemichrome (a methemoglobin derivative resulting from distorted protein conformation) (Chin, et al, 1992, Potter, et al, 1991). Also Heinz bodies (denatured hemoglobin aggregates) are formed when phosphide concentration in vitro increases to 1.25 ppm (Potter, et al, 1991). Few cases of phosphide poisoning showed intravascular complications as hemolysis and methemoglobinaemia,

accidental phosphine inhalation (Heyndrickx, et al, 1976; Wilson, et al, 1980).

or poorly ventilated storage containers and domestic premises (Memis, et al, 2007).

**5. Occupational and environmental phosphine exposure** 

phosphides to control pests in adjacent buildings (Popp, 2002).

**6. Mechanism of action** 

**7. Toxicokinetics** 

Medline, pubmed and Google Scholar databases. All applicable articles in English were attained. Many isolated case reports and small case series do not appear in the citation list. The ability to highlight important aspects is the only criterion for inclusion in this review.

The criteria used in the current review include below criteria: Articles were selected based on the impact of lifestyle, stress, and/or environmental factor/s predisposing aluminium phosphide poisoning exposure. Criteria for selection of the literature used included yes-no responses to the appropriateness of methodology; adequacy of subject numbers; specificity of sex and/or age of subjects, and statistically significant response rates to survey questionnaires. The time frame used was principally 1990-2011 inclusive, although articles of extreme importance from earlier decades were used where appropriate. A multifactorial overview of the factors eschewed concerning aluminium phosphide poisoning exposure was elucidated. It was supposed that collective articles detailing known factors of usage were not necessarily correlated with functionality and health. Collection of materials for the review started with the published literature or easily available academic research.
