Experiments on metabolic activity of phosgene

Several groups have investigated the metabolic activity of phosgene [248,442,443,693, 849aa,1597,1882], particularly in relation to enzyme-controlled energy metabolism and the relationship between these metabolic pathways and the development of observable pulmonary oedema [442]. The results of some of these investigations are summarized in Table 2.4. 

All workers, with one exception [248], found that enzymes and related substances were affected by phosgene, and in vitro studies have shown it to react with a number of tissue-specific amino acids and with some hormones e.g. insulin), as well as with enzymes [731]. It has been speculated [443] that it is the decrease in available energy (via ATP) for maintaining pulmonary ionic and fluid homeostasis which contributes to the formation of oedema fluid [731]. Further work on this topic is needed for clarification. 

Work relating to immune suppression in rats exposed to phosgene has been reviewed [1348a] suppression of natural killer cells by phosgene may compromise the body s ability to protect itself from subsequent disease. The significance of this type of immune damage to the health of an individual has yet to be determined. 

It has long been speculated, since the pioneering work of Muller in 1911 [1459], that phosgene may be an important intermediate in the toxicity of trichloromethane and tetrachloromethane. Experiments on rat liver microsomes have demonstrated that phosgene is generated when CHClj is metabolized both in vitro [1316,1631,1635,1636,1846] and in vivo 

The proposed mechanism for phosgene formation from CHCI3 is illustrated in Fig. 2.3 [1316,1631,1635] and this has been confirmed by isotope labelling techniques [1631]. Similarly, mechanisms for the formation of phosgene from CCl have also been described [1317,1637,1846], and these are summarized in Fig. 2.4. 

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