**7. Toxicokinetics**

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,

Aluminium Phosphide Poisoning 349

Akkaoui, et al, 2007; Bayazit, et al, 2000; Memis, et al, 2007) but jaundice secondary to liver damage (Chugh, et al, 1998) is much less common. It was present in 12 out of 92 cases (Singh, et al, 1991) and was said to be common in another series of 15 patients (Singh, et al, 1985) but confirmatory laboratory data were not provided. Jaundice was alleged to be present in 16 (52%) members of the crew of a grain freighter who inhaled phosphine after an accidental release (Wilson, et al, 1980) but, in the six tested, serum bilirubin concentrations were normal and transaminase activities only minimally disturbed, casting doubt on the clinical observation. Acute hepatic failure and encephalopathy was considered to be the cause of death in one man (Chittora, et al, 1994), while a 12-yearold girl died from a combination of acute hepatic failure and encephalopathy with renal failure (Bayazit, et al, 2000). Portal edema, congestion of the portal tract and central veins, and vacuolization of

Hypokalemia. metabolic acidosis, mixed metabolic acidosis and respiratory alkalosis, and acute renal failure are reported frequently. Also,Hypoglycemia and hypomagnesemia have been reported in several studies (Chugh, et al, 2000; Dueñas, et al, 1999). Hypokalemia is common soon after ingestion of metal phosphides and is probably secondary to vomiting, though catecholamine release could also contribute. It is thought to be the result of impaired gluconeogenesis and glycogenolysis (Frangides & Pneumatikos, 2002) possibly secondary to adrenal gland damage and low circulating cortisol concentrations (Chugh, et al, 2000). Hyperglycemia (Abder-Rahman, 1999) appears to be rare. The main controversy relates to the existence or otherwise of disturbances of magnesium homeostasis. In 1989, prompted by reports of the empirical use of magnesium sulphate to treat phosphide toxicity, this study (Singh, et al, 1989; Singh & Sharma, 1991) demonstrated that serum magnesium concentrations were increased, possibly secondary to release from damaged cardiac myocytes and hepatocytes, and confirmed the findings in subsequent studies (Singh, et al, 1991; Singh, et al, 1990). Unfortunately, other studies have found the converse, that is serum and erythrocyte concentrations were reduced rather than increased. Chugh, et al, (1991) compared serial serum and erythrocyte magnesium concentrations in four groups of people. One comprised patients poisoned with aluminium phosphide who had resulting shock and cardiotoxicity while the second included those poisoned but without shock or cardiac features. The remaining two groups acted as controls, the first being patients in shock secondary to trauma or hemorrhage but without other features of cardiac toxicity and the second, normal volunteers. The only significant finding in admission samples was that cell and serum concentrations were lower in shocked, cardiotoxic patients (mean serum and RBC concentrations 0.9 and 3.7 mEq/L respectively compared with 1.8 and 5.2 mEq/L in volunteers). Since, first, hypomagnesemia was found in toxic shocked patients but not in those with non-toxic shock and secondly, 75% of those in the toxic/shock group had ECG changes, it was concluded that the evidence supported a causal relationship between hypomagnesemia and phosphide induced shock. Without intervention both serum and cell values returned to normal by about 24 h. The authors confirmed their findings in a later study (Chugh, et al, 1994) and thought the hypomagnesemia secondary to consumption in combating free radical stress (Chugh, et al, 1997). Hypomagnesemia has also been found in a recent single case of phosphine inhalation from aluminium phosphide (Dueñas, et al, 1999). The situation became even more complicated when, in 1994, a study (Siwach, et al, 1994) found themselves unable to agree with either. They found pre-treatment mean serum and

hepatocytes are the most frequent findings at autopsy (Saleki, et al, 2007).

**8.5 Electrolyte and metabolic abnormalities**

these reactions support the involvement of erythrocytes in the biotransformation of phosphine in vivo in humans (Stewart, et al, 2003).
