aluminium phosphide: toxicity mechanism and credible

www.wjpps.com Vol 4, Issue 10, 2015.

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Kumud et al. World Journal of Pharmacy and Pharmaceutical Sciences

ALUMINIUM PHOSPHIDE: TOXICITY MECHANISM AND

CREDIBLE TREATMENTS

Arshia Berry1, Garima Singh

2, Simran Jeet Kaur

3 and Kumud Bala

4*

1,2,3,4

*J 3 Block, 3rd Floor, Amity Institute of Biotechnology, Amity University, Sector-125,

Noida-201303, Uttar Pradesh, India.

ABSTRACT

Suicides and deaths by "accidental" ingestion or inhalation of

Aluminium Phosphide poisoning are rising at an alarming rate year

after year. Ascribing to the lack of an effective and safe antidote and

with almost a 100% mortality rate, it becomes next to impossible to

save the victim of this particular poisoning. In order to do the same, it

is imperative to fully comprehend the mechanism and action of AlP on

various organs, once it enters the body. Thus, this review explains the

mode of action of phosphine gas produced by AlP inside the human

body, with a special emphasis on the nucleophilic nature of phosphine

and its role in inducing cytochrome c - mediated oxidative stress,

giving way to metabolic acidosis and multiple organ failure. The

predicted treatments will include moieties capable of inhibiting the

cytochrome c pathway and neutralizing the serum acid content along with already established

agents combating various aspects of AlP poisoning.

KEYWORDS: Aluminium Phosphide, Phosphine, poisioning, fumigant.

INTRODUCTION

A highly toxic fumigant with the chemical formula of AlP, aluminium phosphide continues to

kill millions around the globe, with an astonishing mortality rate of 40%-100%

(Moghadamnia, 2002). The lack of a proper antidote is regarded as the underlying reason that

accentuates the mortality rate associated with acute aluminium phosphide poisoning. The

lethal dose (LD50) is 11.5 mg/kg and the estimated time intervals beginning from the

ingestion of its tablet to death has approximately been reported as 3 hours, or on an average,

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 5.210

Volume 4, Issue 10, 2276-2293 Review Article ISSN 2278 – 4357

Article Received on

24 Aug 2015,

Revised on 16 Sep 2015,

Accepted on 04 Oct 2015

*Correspondence for

Author

Kumud Bala

J 3 Block, 3rd Floor,

Amity Institute of

Biotechnology, Amity

University, Sector-125,

Noida-201303, Uttar

Pradesh, India.


2277


between 1-48 hours, with the most common cause of death being cardiac arrhythmias. 95% of

the patients die within 24 hours of ingestion of AlP (Chugh et al, 1993). Also, in a 25-year-

long study reported by Singh et al (2003), a total of 5933 unnatural deaths by poisoning

reported in north-west India, aluminium phosphide was found out to be a major cause.

The pesticidal activity of AlP is attributed to its property of releasing phosphine gas, also

known as hydrogen phosphide (PH3), first discovered by a German company named Degesch.

Later, the Hollywood Termite Control Company, Inc in the United States of America

registered it as a pesticide in 1958. The gas, if inhaled or if produced inside the human body

after ingestion of AlP, affects a number of organs, like: kidneys, lungs, liver, gastrointestinal

tract as well as the central nervous system (Chemistry learner).

Physically, it has a solid, colourless appearance and is sold in the market as yellow or grey

crystals (3gm tablet) or as a grey-green powder (Kirk-Othmer Encyclopedia of Chemical

Technology, 1982). The colour imparted is a result of residing impurities form hydrolysis or

oxidation process. The smell usually resembles that of garlic or rotten fish (Ellenhorn et

al, Medical Toxicology - Diagnosis and Treatment of Human Poisoning, 1988).The crystals

or tablets, which are more commonly available in the markets have a zincblende crystal

structure (Van Zeghbroeck, 1997) and are stable thermodynamically up to a 1000˚C or 1830˚

F with the substance density of 2.85 gm/cm3.

The molar mass and the melting point of

aluminium phsophide is 57.9552 g/mol and 2530˚ C or 4590˚ F respectively. Aluminium

phosphide is readily soluble in water and reacts both, with water as well as moisture present

in the air, to yield the highly toxic phosphine gas. The reaction takes place as follows, where

the water molecule breaks down to produce H+

and OH- ion (Holleman, 2001): AlP + 3 H2O

→ Al(OH)3 + PH3; AlP + 3 H+ → Al

3+ + PH3

Similarly, for the production of aluminium phoshide in laboratories, the mixture of red

phosphorous (P) and powdered aluminium (Al) is made to react with each other and

subjected to ignition in order to yield AlP (White et al, 1953). The reaction takes place as

follows: 4Al + P4 → 4AlP

AlP has a wide number of applications in agricultural industry, namely, as a fumigant,

rodenticide, pesticide, insecticide as well as semiconductor material, as in aluminium gallium

indium phosphide, when alloyed with different binary materials in order to be used in light-

emitting diodes (Corbridge et al, 1995). As a fumigant, it is used to preserve a wide variety of


2278


food products before they are sold in the market for human consumption. The products

include various grains, like wheat, and many dry fruits and cereals (Chemistry learner).

Commonly known as the ―wheat pill‖, it is used to kill several varieties of verminous

mammals, such as, rodents or moles. The phosphine gas, responsible for the killings is highly

toxic and flammable, hence, in order to control its spontaneous and sudden ignition leading to

explosion and development of toxic gas, aluminium phosphide preparations are commonly

mixed with stabilizers such as ammonium carbamate (White et al, 1944). Commercially, it is

supplied by the following companies worldwide: Pestcon (United States), Shanghai Kima

Chemical Co. Ltd. (China), Sandhya Organic Chemicals P. Ltd. (India), Chemcolour (New

Zealand), Excel Industries (Australia), Taiwan Chemicals (Taiwan) ,Globe Chemicals GmbH

(Germany), Agrosynth (India), Penglai Chemical Inc. (China), Central & Western Chemicals

(India).

The compound, AlP, is also available under the following most common brand names, like,

Quick Phos, Phostoxin, Celphos, Talunex and Fumitoxin (White et al, 1944).

EPIDEMIOLOGY

An extremely toxic pesticide and a notably cheap fumigant since 1940, aluminium phosphide

(Moghadamnia, 2012) causes approximately 68% of the total poisoning causalities reported

in the Indian sub-continent. Most of the cases reported in India are, however, associated with

the ingestion of phosphides, mainly among the agricultural workers (Mostafazadeh, 2012).

This, in turn results from the improper storage facility for these fumigants. In India, AlP

poisoning is most prevalent in the age group of 11-30 years, in rural areas (Moghadamnia,

2012). From 1979 to 2004, approximately, 895 patients have been admitted in PGIMER,

Chandigarh, with acute AlP poisoning (Singh, unpublished data). Similarly, a year-round

study conducted in Allahabad managed to record 301 suspicious cases of poisoning, out of

which 11.7% were reported due to AlP. The affected male to female ratio in this study was

2:1 (Moghadamnia, 2012).

Other than in India, a few cases annually are reported from Iran and Jordan, mainly in an

attempt to commit suicide from aluminium phosphide, commonly called as the ―rice tablet‖

there. In Iran, a four-year study was conducted from 1997-2001, which was successful in

recording about 1571 poisoning cases, of which, approximately, 2.1% or 33 cases had their

underlying cause as aluminium phosphide (Moghadamnia, 2012).


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Fatal dose in all the cases has been reported for a healthy adult of 70 kg as 150-500 mg

(Chugh, 1988). Except for in India, Iran and Jordan, a few cases annually are reported from

United Kingdom (Bogle, 2006), Australia (Nocera, 2000), Germany (Alter, 2001), Canada

and the United States (Ragone, 2002), to name a few.

MECHANISM OF TOXICITY

The exact mechanism by which aluminum phosphide causes poisoning is still not known.

Systemic complications and multi-organ failure are involved in acute aluminum phosphide

poisoning (Abedini et al, 2014). Phosphine gas is generally released when aluminum

phosphide is ingested (Moghadamnia, 2012). Phosphine molecule has three hydrogen atoms

and a phosphorus atom i.e. PH3. Phosphorus in turn, has 5 valence electrons, with 2 paired

electrons in s-orbital and 3 unpaired electrons in its p-orbital. Three molecular bonds can

easily be formed by these three unpaired electrons in the p-orbital (Kutzelnigg, 1984). Also,

s-orbital electrons can participate in bond formation with oxygen. This happens in case of

sufficient oxygen, where oxiderivatives of phosphine like H3PO are formed with imbalances

between blood phosphorous and oxygen.

Phosphine is cytotoxic and is mainly involved in free radical mediated injury. It is a

nucleophile and a strong reducing agent and hence is capable enough of holding back many

cellular enzymes in various metabolic processes (Mathai and Bhanu, 2010). PH3 is fully

reduced form of phosphorus in contrast to phosphate which is fully oxidized form and is

thermodynamically favoured in biological tissues (Price and Sadler, 1988). It oxidizes slowly

in weak acids and forms unstable H3PO only if sufficient oxygen is available. This H3PO is

an intermediate and extremely unstable product and had not been observed either in vivo or

experimental procedures (Robinson and Bond, 1970). In H3PO, O2 carries a partial negative

charge and phosphorus carries a partial positive charge. Phosphorus acts as an electrophile

due to polarity of the molecule which also contributes to the reactivity of the whole structure

(Nath et al, 2011). But mechanism by which this transient H3PO causes phosphine toxicity is

yet to be fully discovered.

There are evidences that phosphine inhibits respiration in rat liver mitochondria (Nakakita et

al, 1971) and insect mitochondria (Chefurka et al, 1976). This inhibition is significant when

there is addition of precursors to ATP synthesis or any chemical uncoupler. It is also

suggested that inner membrane of mitochondria, being highly impermeable, is a major hurdle

in PH3 uptake. But usually, it is overcome by activation of transport across mitochondrial


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inner membrane (Nath et al, 2011). It is gradually absorbed by gastro-intestinal tract

following a simple diffusion method wherein phosphine released inhibits cytochrome c

oxidase in the mitochondria, which in turn inhibits cellular utilization. In an experimental

procedure it was revealed that Complex IV, also known as cytochrome c oxidase, is a

primary site for electron transport chain (ETC) and PH3 interaction (Chefurka et al, 1976).

Kashi and Chefurka later suggested that oxidation state of cytochrome a was highly reduced

on treatment with phosphine. Also, PH3 can form complex with metal ion cofactors at active

site of enzymes which is basis of cytochrome c oxidase inhibition (Chaudhry and Price,

1990). Due to this, around 70% of oxidative respiration which occurs in mitochondria is

inhibited. Various harmful cellular radicals like superoxides and peroxides are generated as a

result of lipid peroxidation which is a result of reduction in oxidative respiration

(Moghadamnia, 2012). Furthermore, it promotes protein denaturation that results in

breakdown of integrity of cell (Mehrpour et al, 2012). Cellular oxidative stress, hence, is a

result of this suppression of oxidative respiration and ETC-PH3 interaction (Nath et al, 2011).

Fig. 1: pictorial representation shows the interaction of PH3 with various enzymes

involved in metabolic processes in mitochondria and synapse.


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Phosphine is shown in light blue, NO in orange, and ROS in red. The cross symbol behind

enzymes indicate that they are inhibited. ROS generated at various sites in mitochondria leads

to inhibition of various metabolic processes. The potassium and calcium currents are

regulated by acetylcholine via NO. Ca2+

triggers the release of acetylcholine in cytoplasm into

the neuronal synapse. The acetylcholinesterase degrades acetylcholine, reducing the strength

of neurotransmission. [FAD/FADH2 (Flavin adenine dinucleotide oxidized/ reduced),

NAD+/NADH (Nicotinamide adenine dinucleotide oxidized/ reduced), ADP/ ATP (adenosine

di/ tri nucleotide), NO (nitric oxide), ROS (reactive oxygen species) and TCA (tricarboxylic

acid)].

A study conducted in 1996 by Chugh et al, stated that levels of serum superoxide dismutase

(SOD) and malonyldialdehyde (MDA) were high and serum catalase levels were low which

resulted in peroxide load in patients within first day of the poisoning. It confirmed the

phosphine release. It was observed that indicators of oxidative stress reached their peak levels

within 48 hours of exposure. Autopsy results in non survivors confirmed high levels of SOD

and MDA indicating their direct relation with mortality and low catalase levels indicating the

inverse relationship. However, patients who survived till fifth day of poisoning showed

normal levels of SOD, MDA and catalase which suggested that phosphine was eliminated

and there was a significant drop in levels of oxidative stress indicators.

Phosphine is mainly metabolized and excreted by kidneys, although, it has been studied that

some amount of aluminum phosphide is slowly absorbed and later metabolized by liver. This

results in release of phosphine at a very slow rate which is responsible for delayed onset of

toxicity of aluminum phosphide (Wahab et al, 2008). In the same study it was revealed that,

focal myocardial necrosis is also one of the signs observed in aluminum phosphide poisoning.

This is due to alteration in the ionic permeability of ions such as sodium, magnesium and

calcium. This is evident in a patient as cardiac arrhythmias and ECG anomalies. Also, adrenal

gland damage, fluid loss (Mathai and Bhanu, 2010), hypoxemia with severe metabolic

acidosis are some of the other abnormalities which are observed in aluminum phosphide

poisoning (Anger et al, 2000).

Certain evidences of agitation followed by convulsions in humans and twitching after

hyperactivity in non-human animals have been reported post ingestion of aluminium

phosphide. Lethargy is also observed in a few individuals (Potter et al, 1993). Phosphine also

contributes in increasing acetylcholine neurotransmission by suppressing acetylcholine


2282


esterase (Mittra et al, 2001). This activation in acetylcholine signaling increases metabolic

demand which can also cause hypersensitivity towards phosophine (Valmas et al, 2008).

Patients usually die within 24 hours due to cardiac toxicity. But if a person survives more

than a day, acute respiratory distress syndrome (ARDS) is a major manifestation. There are

also evidences of diffuse alveolar damage (DAD) which appear as alveolar edema and

hemorrhages at times of autopsy, thereby confirming ARDS (Hugar et al, 2015). Also, it has

been reported that ulcerations, gastro-intestinal disorders, liver failure and metabolic

disorders were observed within 24 hours of poisoning.

Ischemic stroke can be considered as one of the delayed responses of aluminum phosphide

poisoning as studied in case report of a 30 year old right-handed man in Iran (Abedini et al,

2014). It was revealed that the stroke was a result of sudden onset of left side hemiplegia

(total or partial paralysis of one side of the body that results from disease of or injury to the

motor centers of the brain) which occurred 11 days after the ingestion of aluminum

phosphide. MRI (Magnetic Resonance Imaging) and MRA (Magnetic Resonance

Angiogram) confirmed ischemic lesions and stenosis in the middle cerebral artery of brain

respectively.


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Fig. 2: phosphine toxicity pathways: Inhalation and Ingestion

During inhalation, aluminum phosphide reacts with water whereas during ingestion, it reacts

with HCl in stomach. Phosphine is formed via both processes. Phosphine follows same


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pathway in both the cases and leads to mitochondrial damage by inhibiting Cytocohrome c

oxidase. Hydroxyl radicals, thus, produced cause lipid peroxidation and protein denaturation.

This mitochondrial damage in gastro-intestinal tract cause ulcers and hemorrhages and

eventually renal and hepatic failure whereas it causes diffused alveolar damage in lungs

leading to alveolar edema, hemorrhages and in many cases Ischemic stroke.

SYMPTOMS AND DIAGNOSIS

Signs and Symptoms

The general signs and symptoms of aluminium phosphide poisoning (AlPP) are: metabolic

acidosis, which may occur due to the accumulation of lactic acid caused by blockage of

oxidative phosphorylation and poor tissue perfusion (Agarwal et al, 2014), gastrointestinal

hemorrhage and ulcerations (Hugar et al, 2015), abdominal pain, vomiting, abnormality in

Glasgow coma scale, systolic blood pressure, and central venous pressure (Louriz et al,

2009). Major complications observed in the course of severe aluminium poisoning are

cardiac dysrhythmias, shock, respiratory distress, hypomagnesemia and lack of vomiting

(leading to retention of AlP in body).

Some studies have reported that aluminium poisoning causes neurological toxicity which, in

turn, can cause clinical effects like headache, stupor (a state of near-unconsciousness),

restlessness, agitation, anxiety, ataxia (loss of full control on body), paresthesia (an abnormal

sensation, typically tingling or pricking) and central nervous system depression leading to

coma and seizures ( Goel and Aggarwal, 2007).

Diagnosis

The diagnosis of AlPP ingestion can be confirmed by detecting phosphine in exhaled air or in

GI aspirate. In stomach, phosphine gas can be detected by the silver nitrate test. To perform

this test, gastric contents are diluted with of water in a flask and the flask is heated at 50oC for

15-20 minutes. Then, two round pieces of filter paper, one impregnated with 0.1 N silver

nitrate and other with 0.1 N lead acetate are placed alternately on the mouth of the flask, if

phosphine gas is present in the gastric contents, then due to conversion silver nitrate to

metallic silver, the silver nitrate paper turns black while the lead acetate paper does not

change color. If hydrogen sulphide is present, both the papers turn black. The reaction takes

place as follows: 8AgNO3 +PH3 +4H2O → 8Ag +H3PO4 + 8HNO3


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A variant of silver nitrate test to detect phosphine gas is the breath test. The patient is asked

to breathe through a filter paper impregnated with 0.1N silver nitrate for 15 minutes. Due to

the presence of phosphine in the breath, the filter paper turns black. The test on gastric

aspirate is much more sensitive than the breath test (Louriz et al, 2009).

The breath test is not reliable. A false negative result may occur in patients being given

oxygen as phosphine may get converted to phosphorus pentoxide. A false positive result may

also occur due to the presence of hydrogen sulfide in the air (Mehrpour et al, 2012). Gas

chromatography is the most specific and sensitive method for detecting the presence of

phosphine in blood/ air and can detect even minute amounts of phosphine in the air (Anand et

al, 2011).

LABORATORY ASSESSMENT AND PROGNOSIS

Laboratory assessment is generally done to obtain the prognosis. In case of AlP toxicity

general prognostic factors are : elevated serum creatinine, low APACHE II (Acute

Physiology and Chronic Health Evaluation II) score, low pH value (< 7.2), low serum bio

carbonate value (<15mmol/L). Louriz et al have also reported that, the prognostic factors

associated with mortality from acute AlP poisoning, includes a low APACHE II score, low

Glasgow coma scale score, shock, electrocardiogram abnormalities, the presence of acute

renal failure, low prothrombin rate, hyperleukocytosis (an unusual large increase in number

and proportion of white blood cells in blood or tissues), use of vasoactive drugs and use of

mechanical ventilation. Recently in 2008, Wahab, et al, reported that the development of

refractory shock, ARDS, aspiration pneumonitis, anaemia, metabolic acidosis, electrolyte

imbalance, coma, severe hypoxia, gastrointestinal bleeding, and pericarditis are the factors

associated with poor prognosis (Mathai and Bhanu, 2010; Louriz et al, 2009; Wahab et al,

2008). Simplified Acute Physiology Score II (SAPSII) was proposed for better estimating the

outcome of patients with acute AlP poisoning requiring ICU admission. SAPSII calculated

within the first 24 hours was recognized as a good prognostic indicator (Moghadamnia,

2012).

Leukopenia (decrease in the number of white blood cells in blood) indicates severe AlP

toxicity. Increased amount of glutamic oxaloacetic transaminase (SGOT) or glutamic pyruvic

transaminase (SGPT) in serum and induced metabolic acidosis signifies moderate to severe

AlP toxicity. Analysis of body electrolytes show decreased magnesium level while level of

potassium may be increased or decreased (Chugh et al, 1990). Analysis of plasma renin is


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significant as its level in blood carries a direct relationship with mortality and is raised in

direct proportion with the dose of pesticide. In case of severe poisoning, the level of cortisol

in serum is usually found to be decreased. Chest X-ray may reveal hilar or perihilar

congestion if ARDS develops (Chugh et al, 1989).

Changes in cardiovascular and respiratory system can also result in death. In myocardial

tissue, AlP induces congestion, necrosis and leucocytes infiltration. ECG shows various

manifestations such as arrhythmias (Sinus tachycardia, bradycardia), supraventricular

ectopics, ventricular ectopics, atrial fibrillation, ventriclar fibrillation conduction defects

(Wide QRS complex, A-V conduction defects), bundle branch block, complete heart block,

ST depression, ST elevation, T wave changes (Singh and Bhalla, 2015).

TREATMENT AND MANAGEMENT OF ALP

Table 1: Various treatment strategies for managing Aluminum phosphide poisoning

Treatment option Type of Study Effects Conclusion Reference

Digoxin (0.5 mg initially

followed by 0.5 mg

at 6 h intervals)

Case Report

Resolved cardiogenic

shock due to left ventricle

failure

Administration of digoxin as

an adjustment therapy can

improve the outcome

Mehrpour

et al, 2011

Hyperbaric

Oxygen

Experimental

(Rats)

Increasing survival

Time

Administration of hyperbaric

oxygen may also be effective

in humans

Saidi et al,

2011

25Mg 2 + carrying

nanoparticle

Experimental

(Rats)

Increased blood pressure

and heart rate; increase in

antioxidant power, Mg

level in the plasma and

the heart; reduction in

lipid peroxidation and

ADP/ATP ratio

25Mg PMC16 at 0.025 LD50 +

Nabicarbonate was the most

effective

combination

Baeeri et

al, 2011

Intragastric

irrigation with

Sweet Almond oil

Experimental

(Rats)

Protective role for plasma

cholinesterase

inhibition in AlP

poisoning, decreased

mortality rate

Significant reduction

of mortality

Saidi and

Shojaie,

2011

Vitamin C

(1 g at 6 h intervals,

i.v.) +

methylene blue

(1 mg/kg of 1 %

solution)

Case Report

Twelve hours after

treatment with vitamin C,

the methaemoglobin

concentration decreased

from 46 % to 33 %. high

doses of methylene blue,

the methaemoglobin

concentration decreased

to 23 %

Administration of

vitamin C followed by

methylene blue may have a

role in successful treatment of

methaemoglobinaemia

and haemolysis following

phosphine poisoning

Soltaninejad

et al, 2011

Extensive gastric Case Series Survival rate 42 % Recommendation to Bajwa et


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lavage

with aliquots of 50

mL of

Coconut oil+ 50

mL of

Sodium

bicarbonate

Solution with

simultaneous

aspiration

(33 patients) intensivists and physicians to

use this

particular regimen of gastric

decontamination

al, 2010

Intra-aortic

Balloon Pump

(IABP)

Case Report

IABP was used for

cardiovascular support

until the effects of AlP

resolved

IABP used for treatment of

cardiogenic shock due

to AlP poisoning can

improve the outcome

Siddaiah et

al, 2009

N-Acetylcysteine

(NAC)

(6.25 mg/kg/min, i.

v. for

30 min)

Experimental

(Rats)

Significantly increased

survival time, stabilization

of blood pressure and

heart rate, decreased

Malonyldialdehyde level

and increased Glutathione

peroxidase

Levels

NAC increased the survival

time by reducing myocardial

oxidative injury

Azad et al,

2011

N-omega-nitro-L-

arginine methyl

ester (L-NAME)

(1 mg/kg/min,, i. v.

for 60 min)

Experimental

(Rats)

Significant rise in

blood pressure but

precipitated ECG

abnormalities. Pre and

post-treatment of L-

NAME with AlP

neither improved the

survival time nor the

biochemical parameters

despite significant rise in

blood pressure

L-NAME showed no

protective effects in

rats exposed to AlP

Azad et al,

2011

Atropine

(1 mg kg-1,

intraperitoneal) +

Pralidoxime

(5 mg/kg,

intraperitoneal)

administered five

minutes

after AlP exposure

Experimental

(Rats)

Increased survival

time. Plasma

cholinesterase levels were

inhibited in rats

poisoned with AlP as

compared to controls

Atropine and pralidoxime can

increase survival time

Mittra et al,

2001

Oral dose of 20 mg

Trimetazidine

twice daily

Case Report

Resolved dysrhythmia

due to AlP poisoning after

48 h [ventricular

premature complexes

(>600 per h) with periods

of bigeminy]

Ventricular dysrhythmias were

treated solely with

oral trimetazidine resulting in

rapid disappearance of all

electrocardiographic

abnormalities

Duenas et

al, 1999


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OTHER POSSIBLE TREATMENTS

Patients suffering from AlP poisoning, toxicity occurs basically due to three reasons, i.e.

inhibition of cytochrome c oxydase, increased pH of body and production of reactive oxygen

species (ROS) so we need a treatment which could counter and restore all the three changes.

Phosphine produced by AlP inhibits the cytochrome c oxidase. Phosphine is a reducing agent

having potential of -1.18, it forms a complex with the metal ion cofactor at the active site of

enzyme cytochrome c oxidase inside mitochondria. Inhibition of cytochrome c oxidase

causes oxidative stress.

It is well known that metal phosphides having lower reduction potential are strong electron

donors and therefore considered as strong poisons. Phosphine donates electron to cytochrome

c oxidase (E = +0.29) that leads to disruption of electron transport chain. Therefore,

according to the electrochemical law, if a receiver with a reducing potential of more than

+0.29 is given to the patient, then it will strongly interact with phosphine and in turn,

cytochrome c oxidase will be left vacant and undisrupted.

Table 2: metal ions having reduction potential more than cytochrome c oxidase

Metal ions Reduction potential

Re 3+

+0.30

Bi3+

+0.308

Cu2+

+0.337

Fc+ +0.4

Cu+ +0.520

Fe3+

+0.77

Ag+ +0.7996

Depending upon the severity of patients these metals can be given to patients either as food

supplements (in case of acute AlPP) or as recombinant biotech drug (in case of sever AlPP).

Supportive treatments to reduce pH and degrade ROS should also be given. To maintain the

pH of body as normal, various minerals can be used. Magnesium is an alkali forming mineral

which can give best result when administered transdermally (via skin). Oral supplementation

of magnesium alone is not enough since most of it is excreted without being processed in

body. Antioxidants like polyphenols and ascorbic acid (vitamin C) can enhance the process of

inhibition of oxidation and prevent the formation of ROS.

Another hope in the treatment for AlPP could come through the phosphine resistant gene

found in Rhyzopertha dominica which requires further intensive studies and manipulations

before it can be regarded as a plausible method to treat human patients.


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CONCLUSION

Phosphine released from AlP has been identified as the primary culprit accentuating the

morbidity and mortality associated with the acute poisoning cases. Owing to the rapidly

increasing number of deaths and suicides due to ingestion or inhalation of aluminium

phosphide, the need of the hour is the generation and development of a specific antidote

capable of countering the action of PH3 molecules, thus preventing the free radical mediated

cellular and mitochondrial injury: the factors associated with the high mortality rate. We have

suggested a number of possible treatments to combat the acute cases of poisoning, however,

fumigants and compounds containing high levels of aluminium phopshide need to be phased

out of the country as soon as possible or number of organic alternatives could also be

employed to be used as fumigants for example, neem oil fumigation, chrysanthemum flower

tea spray or using eucalyptus oil emulsion as fumigant, to name a few. In addition to this,

public awareness and easy availability of AlP become the two most important issues. Strict

measures, both at the administrative as well as the legislative levels are required to

strategically modify and restrict the supply of AlP in India.

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