Effects on Organisms in the Environment: The antimicrobial activity of phosphine varies depending on the microbial species, and the type and moisture content of the product being fumigated. Many microorganisms survive fumigation at exposures (concentration-time) that are effective against arthropods. The few studies available indicate that phosphine has little effect on growing plants (e.g., sugar cane and lettuce) at effective pesticidal doses. Germination of seeds was unaffected by their fumigation with phosphine or by prior fumigation of the soil in which they were planted, except when the moisture content of the seed exceeded 20%. Lettuce sustained substantially less damage after fumigation with phosphine than with 5 other fumigants. (The NOEL of phosphine in air was 3-8 mg/m3). The few data available on the effects of phosphine and phosphides on aquatic organisms suggest that, despite its low solubility, phosphine in solution can be acutely toxic. An aluminium formulation was reported to be highly toxic for the bluegill sunfish, 96-h LC50 = 0.178 mg/m3. A 30-min LC50 for phosphine for frog was 0.56 mg/l. Generally, insects, a principal target, are susceptible, though the susceptibility at different stages of the life-cycle varies and diapausing larvae are particularly tolerant. The threshold for adverse effects of phosphine to Drosophila melanogaster is about 1.4 mg/m3 (1 ppm), which is similar to the threshold for acute inhalation effects in mammals. Resistant strains of insects exist and are sometimes difficult to control. The mechanism of resistance may have a metabolic basis that persists throughout all stages of metamorphosis, and in some cases has been shown to be a process of active exclusion of phosphine by energy-dependent processes. In general, mites are less sensitive than insects. Wild birds and mammals are similarly susceptible to both phosphine and phosphides. An oral LD50 of 35 mg zink phosphide/kg bw was reported for the quail. The acute oral LD50 for the kit fox and the black tail prairie dog was 93 and 18 mg zink phosphide/kg b.w., respectively. Zinc phosphide formulations vary in acceptability as baits, and the relative efficacy of different commercial preparations may be a function of this. Aversion to zinc phosphide at 0.05% in the diet was demonstrated in Indian gerbils. Census studies have shown that, with appropriate use of bait or the application of aluminium phosphide to the entrance of active burrows, elimination of most or nearly all target species can be achieved with a single application. Ingested zinc phosphide is detectable in the intestine and liver of poisoned animals, but not in the muscle tissue. Poisoned animals are not toxic to carrion eaters. Effects on Animals: In mammals, phosphine is readily absorbed by inhalation. Aluminium or magnesium phosphide powder, if inhaled, releases phosphine for absorption on contact with the moist respiratory epithelium. Zinc phosphide would not hydrolyse rapidly in the respiratory tract but might be absorbed as such and hydrolyse in the tissues. The acute dermal LD50 for zinc phosphide in rabbits is in the range of 2000 - 5000 mg/kg body weight, suggesting little dermal absorption. Gastrointestinal absorption of phosphine produced by the hydrolysis of ingested phosphide is likely and the absorption of zinc phosphide itself and its transport to the liver, where it can be detected for many hours, has been demonstrated in the rat and in a case of fatal human poisoning. Information regarding the distribution of phosphine in the body has been derived from the clinical syndromes of poisoning, which indicate that it reaches the central nervous system, liver, and kidney. Absorbed phosphide is hydrolysed to phosphine or oxidized to the salts of the oxyacids of phosphorus. Phosphine is both slowly oxidized to oxyacids and excreted unchanged in the expired air. Hypophosphite is the principal urinary excretion product. Following an oral dose of zinc phosphide, phosphine in the expired air had disappeared after 12 h and clinical symptoms lasted only a few hours. This suggests that phosphine is eliminated fairly rapidly. On the other hand, the phosphide contents of the liver were higher after daily dosing with zinc phosphide than after a single dose, suggesting that liver phosphide is not completely eliminated within 24 h. Studies by the inhalation route indicate that both the concentration and duration of exposure are important determinants of acute lethality and that different mammalian species are essentially similar in susceptibility. The 4-h LC50 of phosphine in rats is about 15 mg/m3. The oral LD50 value of zinc phosphide in wild Norwegian rats is 40.5 mg/kg body weight. Results of short-term administration indicate that the effects of phosphine exposure cumulate with daily exposure so that after 6 days pretreatment, the survival time at a concentration of 681 mg/m3 was reduced to one-third of its value in animals without previous exposure. Clinical features of liver and kidney dysfunction were observed and all the parenchymatous organs were affected by congestion and oedema. Neurohistological changes were seen in rats and less markedly in guinea- pigs and cats, Changes in various serum enzyme levels at very low levels of exposure over a period of 1.5 months have been reported. Short-term feeding studies on female rats administered zinc phosphide resulted in mortality at concentrations of 200 and 500 mg/kg diet, but biological effects, qualitatively similar to those at higher doses, were seen at the lowest dietary concentration of 50 mg/kg. There are no studies relating to long-term effects, carcinogenicity, or mutagenicity. There is no information regarding factors modifying toxicity in vertebrates or the toxicity of any metabolites. Information on biochemical effects is insufficient to explain the mechanisms of toxicity, in either animals or plants. 1.4 Effects on Man Because the odour of phosphine depends on impurities which may be removed by purification or adsorption, odour cannot be relied on for warning of toxic concentrations. Ingestion of phosphides may cause nausea, vomiting, diarrhoea, retrosternal and abdominal pain, tightness in the chest and coughing, headache and dizziness. In more severe cases this may progress to cardiovascular collapse, pulmonary oedema, cyanosis and respiratory failure. Pericarditis, renal failure, and hepatic damage including jaundice, may develop later. Symptoms may be delayed and death may occur up to one week after poisoning. Pathological findings include fatty degeneration and necrosis of the liver and pulmonary hyperaemia and oedema. Inhalation of phosphine or phosphide may cause severe pulmonary irritation. Mild exposure may cause only mucous membrane irritation, with initial symptoms mimicking an upper respiratory tract infection. Other symptoms may include nausea, vomiting, diarrhoea, headache, fatigue, and coughing, whilst more severe symptoms may include ataxia, paraesthesia, intention tremor, diplopia, and jaundice. Very severe cases may progress to acute pulmonary oedema, cardiac arrhythmias, convulsions, and coma. Renal damage and leukopenia may also occur. Exposure to 1400 mg/m3 (1000 ppm) for 30 min may be fatal. Death, which may be sudden, usually occurs within four days but may be delayed for one to two weeks. Post-mortem examinations have revealed focal myocardial infiltration and necrosis, pulmonary oedema and widespread small vessel injury. There is no evidence for cumulative effects from intermittent low-level exposure averaging 14 mg/m3 (10 ppm) or less. Chronic poisoning from inhalation or ingestion may cause toothache, swelling of the jaw, necrosis of the mandible (phossy jaw), weight loss, weakness, anaemia, and spontaneous fractures. Laboratory findings may include abnormal liver function tests, acidosis, increased blood urea and bilirubin, haematuria, and proteinuria. Other diagnostic studies should include electrocardiogram, sputum, and differential white blood cell count. Occasional cases of accidental exposure of the general population to phosphine have occurred in the region of fumigation operations and on board ships carrying cargoes capable of releasing phosphine. There have been many cases of accidental or suicidal ingestion of phosphide pesticides. Lethal doses vary, but most fatal cases have ingested more than 20 g zinc phosphide, and most of those who recovered had ingested less than 20 g phosphide. Pulmonary oedema and congestion and necrosis of the liver and kidneys are the principal pathological features in fatal cases. There have been occasional cases of fatal occupational exposure to phosphine, some of which have involved repeated exposures. Various reports of adverse effects of occupational exposure at normal operational levels have been published, but in no case has the description of exposure or the control group been adequate to draw definite conclusions regarding the possibility of the adverse effects of phosphine at the higher current occupational exposure limits.