Phosgene rabbits

As was the case with guinea pigs, the few acute lethality studies of phosgene in rabbits do not contain experimental details such as strain or gender, number of animals exposed, or analytical methodology. These less than adequate studies are summarized in Table 1-9. 

Cameron et al. (1942) exposed ten rabbits to phosgene at an average concentration of 0.86 ppm for 5 h. All survived an apparent 24-h postexposure period. 

Sciuto, A.M., Strickland, P.T., Kennedy, T.P., Gurtner, G.H. (1995). Protective effects of N-acetylcysteine treatment after phosgene exposure in rabbits. Am. J. Respir. Crit. Care Med. 151 768-72. 

Ibuprofen studies in rats, mice, and rabbits revealed that parenteral or intraperito-neal adminishation of ibuprofen during the asymptomatic phase following phosgene exposure was effective in preventing pulmonary edema. However, there is no evidence of its effectiveness in human victims and the FDA has not approved its use for this purpose. In addition, a dose comparable to those used in the animal smdies, would require giving patients at least 25-50mg kg orally (34). 

Phosgene has been tested as a rabbit fumigant [768] and was found to be very toxic, not only because of its direct effects, but also because it induces secondary infection. 

Guo et al. (1990) working with an in vivo rabbit model showed that pre- or posttreatment with indomethacin, an inhibitor of thromboxane and prostacyclin production but not of leukotriene production, partially blocked phosgene-induced pulmonary oedema. The leukotriene receptor blockers FPL 55712 and LY 171883 dramatically reduced the oedema when given post-exposure to phosgene. 

Sciuto et al. (1995) showed that postexposure treatment of rabbits with NAC prevented a reduction in GSH induced by phosgene. Production of leukotrienes LTC4, D4 and E4 was also reduced. 

Sciuto et al. (1997) showed that postexposure treatment with aminophylline (known to increase intracellular cAMP levels) protected rabbits against phosgene-... 

Toxicology LD50 (oral, mouse) 110 mg/kg, (IP, mouse) 130 mg/kg, (skin, rabbit) 64 mg/kg LCLo (inh., rat, 4 h) 100 ppm poison by ing., inh., skin contact, IP routes TSCA listed Precaution Combustible exposed to heat or flame can react with oxidizers Hazardous Decomp. Prods. Heated to decomp., emits very toxic fumes of Cr, NOx, and phosgene... 

Halomethyl compounds are subdivided into monohalomethyls, which are alkylating agents, and polyhalomethyls, which must be metabolized to an ultimate species. Reductive dechlorination of carbon tetrachloride 353) to chloroform by rabbit liver microsomes parallels the concentration of cytochrome P-450 in the microsomes but requires anaerobic conditions and NADPH. The identification of hexachloroethane after incubation of NADPH-reduced microsomes with carbon tetrachloride is indicative of homolytic formation of the free radicals of chlorine and trichloromethyl and supports the hypothesis that such species initiate an autocatalytic peroxidation of lipid membranes that results in the observed hepatotoxicity. A similar scheme for radical formation and lipid destruction has been described by Reynolds and Moslen for halothane. In contrast to the reductive dechlorination of carbon tetrachloride, the metabolism of chloroform to carbon dioxide in vitro requires oxygen and produces carbonyl chloride (phosgene) as an intermediate. That this also... 

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