1 Aluminium phosphide - draft revised Poisons Information 2 Monograph for peer review 3 4 5 CHEMICAL SUBSTANCES 6 7 1. NAME 8 9 1.1 Substance 10 11 Aluminium Phosphide 12 13 1.2 Group 14 15 1.3 Synonyms 16 17 Celphos, Quickphos, Alphos, Synfume, Chemfume, Phostoxin, Phostek, 18 Delicia 19 20 1.4 Identification numbers 21 22 1.4.1 CAS number 23 20859-73-8 24 25 1.4.2 Other numbers 26 27 vi 867(I)ALP(F)11 28 29 2. SUMMARY 30 31 2.1 Main risks and target organs 32 33 Cardiovascular system is the major system affected and severe hypotension is 34 a major risk. 35 36 2.2 Summary of clinical effects 37 38 Vomiting, abdominal pain, loose motions, restlessness are seen. Cardiovascular 39 complications include thready pulse, tachycardia, tachypnoea, acidosis, marked 40 hypotension. 41 42 Other common complications of aluminium phosphide poisoning include 43 haemorrhage, acute renal failure, disseminated intravascular coagulation and 44 arrhythmias 45 46 Patients remain mentally clear till cerebral anoxia due to shock supervenes 47 resulting in drowsiness, delirium and coma. 48 49 Several ECG changes ranging from ST segment elevation/depression, PR and 50 QRS interval prolongation, complete heart block to ectopics and fibrillation have 51 been observed. Reversible myocardial injury has also been reported. 52 1 1 2.3 Diagnosis 2 3 The following factors alone or in combination would help in the diagnosis. 4 1. Positive history of ingestion 5 2. Symptoms compatible with aluminium phosphide ingestion 6 3. Chemical test for phosphine positive in gastric aspirate and breath 7 The breath of patients who have ingested aluminium phosphide has a 8 characteristic garlic-like odour. Conformation of diagnosis is based on the 9 patient’s history and a positive result (blackening) on tests of the patient's breath 10 with paper moistened with fresh silver nitrate solution or by chemical analysis of 11 blood or gastric acid for phosphine. 12 13 2.4 First-aid measures and management principles 14 15 Gastric lavage is important in the initial stage. 16 The management principles aim to sustain life with appropriate resuscitation 17 measures until phosphine is excreted from the body. 18 The main principles are – 19 1. Carry out methods to absorb phosphine through GI tract. 20 2. Steps to reduce organ toxicity 21 3. Steps to enhance phosphine excretion 22 4. Supportive measures 23 24 3. PHYSICO-CHEMICAL PROPERTIES 25 26 3.1 Origin of the substance 27 This is a synthetic substance. 28 29 3.2 Chemical structure 30 31 AIP (aluminium phosphide) 32 33 3.3 Physical properties 34 35 3.3.1 Colour 36 Dark grey or dark yellow crystals. 37 38 3.3.2 State/Form 39 Solid - crystalline 40 41 3.3.3 Description 42 43 Formulated as a greenish grey tablet of 3 gm which in presence of 44 moisture or HC1 releases phosphine: 45 46 AlP+3H20 = Al(OH)3+PH3 47 AlP+3HC1 = AlC13+PH3 48 49 The residue, Al (OH)3 is non-toxic 50 51 3.4 Hazardous characteristics 52 53 The tablet has typical odour of garlic. 2 1 2 3 4. USES/CIRCUMSTANCES OF POISONING 4 5 4.1 Uses 6 7 4.1.1 Uses 8 9 4.1.2 Description 10 11 Grain fumigant 12 13 4.2 High risk circumstance of poisoning 14 15 Self poisoning is common. Rarely accidental poisoning is seen in grain freight 16 trades. 17 18 4.3 Occupationally exposed populations 19 20 Farmers while using the fumigant, but poisoning is rare. 21 22 23 5. ROUTES OF ENTRY 24 25 5.1 Oral 26 27 Common route 28 29 5.2 Inhalation 30 31 Rare route 32 33 5.3 Dermal 34 Not relevant 35 36 5.4 Eye 37 Not relevant 38 39 5.5 Parenteral 40 Not relevant 41 42 5.6 Others 43 Not relevant 44 45 6. KINETICS 46 47 6.1 Absorption by route of exposure 48 49 In the stomach phosphine is released which is responsible for toxicity. 50 51 6.2 Distribution by route of exposure 52 53 6.3 Biological half-life by route of exposure 3 1 2 6.4 Metabolism 3 4 6.5 Elimination by route of exposure 5 6 7. TOXICOLOGY 7 8 7.1 Mode of Action 9 10 The exact mechanism is not known. It is suggested to produce non-competitive 11 inhibition of the cytochrome oxidase of mitochondria, blocking the electron 12 transfer chain and oxidative phosphorylation producing an energy crisis in the 13 cells. (Cherfuka W et al.1976) 14 15 Recently Chugh et al. found inhibiton of catalase and induction of SOD in 16 humans leading to free radicals stress brought out lipid peroxidation and 17 protein denaturation of cell membrane leading to hypoxic cell damage 18 19 7.2 Toxicity 20 21 7.2.1 Human data 22 23 7.2.1.1 Adults 24 25 1/4th tablet is lethal. 26 Cardiotoxicity (Toxic chemical myocarditis is manifested as depressed 27 left ventricular ejection fraction, ECG changes varying from ST segment 28 elevation/depression, PR prolongation, broad QRS complexes, and right 29 or left bundle branch block, supraventricular ectopics or fibrillation. 30 (Mathur A, et al. 1999) 31 32 Biochemical changes include rise in AST, CPK-MB and LDH. 33 Histopathology shows myocytolysis, multiple areas of necrosis, 34 congestion. 35 (Karanth S & Nayyar V. 2005) 36 37 7.2.1.2 Children 38 Toxicity, biochemical changes and histopathological changes are similar 39 to adults. 40 41 7.2.2 Relevant animal data 42 43 LD50 mice (Inhalation of fumes) 44 Rat: 0.68gm/m3 - 65-75 min. exposure. 45 1.47gm/m3 - 35-50 min. exposure 46 Cat: 25ppm (2-4hrs daily during 3 days) 47 48 7.2.3 Relevant in vitro data 49 Data not available 50 51 7.2.4 Workplace standards 52 Data not available for aluminium phosphide. 53 4 1 For phosphine: TLV: 0.3 ppm as TWA; 1 ppm as STEL. EU OEL: 0.1 ppm 2 and 0.14 mg/m³ as TWA; 0.2 ppm and 0.28 mg/m³ as STEL (WHO/ICSC 3 2006) 4 5 7.2.5 Acceptable daily intake (ADI) and other guideline levels 6 Data not available 7 8 7.3 Carcinogenicity 9 10 Not known 11 12 7.4 Teratogenicity 13 14 Not known 15 16 7.5 Mutagenicity 17 18 Not known 19 20 7.6 Interactions 21 Not known 22 23 8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS 24 8.1 Material sampling plan 25 8.1.1 Sampling and specimen collection 26 8.1.1.1 Toxicological analyses 27 Gastric lavage - test for phosphine. 28 8.1.1.2 Biomedical analyses 29 8.1.1.3 Arterial blood gas analysis 30 8.1.1.4 Haematological analyses 31 8.1.1.5 Other (unspecified) analyses 32 8.1.2 Storage of laboratory samples and specimens 33 8.1.2.1 Toxicological analyses 34 Send immediately to laboratory after properly covering the sample. 35 8.1.2.2 Biomedical analyses 36 8.1.2.3 Arterial blood gas analysis 37 8.1.2.4 Haematological analyses 38 8.1.2.5 Other (unspecified) analyses 39 8.1.3 Transport of laboratory samples and specimens 40 8.1.3.1 Toxicological analyses 41 8.1.3.2 Biomedical analyses 42 8.1.3.3 Arterial blood gas analysis 43 8.1.3.4 Haematological analyses 44 8.1.3.5 Other (unspecified) analyses 45 8.2 Toxicological analyses and Their Interpretation 46 8.2.1 Tests on toxic ingredient(s) of material 47 8.2.1.1 Simple Qualitative Test(s) 48 Determine the phosphine liberated by acid treatment, measure by GLC. 49 8.2.1.2 Advanced Qualitative Confirmation Test(s) 50 Determine the phosphine liberated by acid treatment, measure by GLC. 51 8.2.1.3 Simple Quantitative method(s) 52 8.2.1.4 Advanced Quantitative method(s) 53 8.2.2 Tests for biological specimens 5 1 8.2.2.1 Simple Qualitative test(s) 2 Heat the lavage at 50 degree C for 15-20 minutes and place a silver nitrate 3 impregnated filter paper (0.1M) on the mouth of flask. On drying the paper 4 turns black indicating the presence of phosphine. 5 6 8.2.2.2 Advanced Qualitative confirmation Test(s) 7 8.2.2.3 Simple Quantitative Method(s) 8 8.2.2.4 Advanced Quantitative Method(s) 9 8.2.2.5 Other Dedicated Method(s) 10 8.2.3 Interpretation of toxicological analyses 11 8.3 Biomedical investigations and their interpretation 12 8.3.1 Biochemical analysis 13 8.3.1.1 Blood, plasma or serum 14 8.3.1.2 Urine 15 8.3.1.3 Other fluids 16 8.3.2 Arterial blood gas analyses 17 8.3.3 Haematological analyses 18 8.3.4 Interpretation of biomedical investigations 19 8.4 Other biomedical (diagnostic) investigations and their interpretation 20 8.5 Overall Interpretation of all toxicological analyses and toxicological 21 investigations 22 8.6 References 23 24 9. CLINICAL EFFECTS 25 26 9.1 Acute poisoning 27 28 9.1.1 Ingestion 29 30 This is the most common mode of poisoning. 31 32 Vomiting, abdominal pain, loose motions, restlessness are seen. 33 Cardiovascular complications include thready pulse, tachycardia, 34 tachypnoea, acidosis, marked hypotension. ECG changes can be seen. 35 Other common complications of aluminium phosphide poisoning 36 include haemorrhage, acute renal failure, disseminated intravascular 37 coagulation and arrhythmias.