246 1. lODOACETATE AND lODOACETAMIDE 



may be due to uptake by the tissues and the later plateau to labeled iodide 

 released from the iodoacetamide. The liver contains about 3% of the blood 

 level originally and this disappears by 7 hr. Chronic feeding of bromoacetate 

 to pigs (around 50 mg/kg for 39 days with a total dose of 31 g) leads even- 

 tually to death, at which time the tissues were analyzed for organic Br by 

 Dalgaard-Mikkelsen et al. (1955). The results are shown in the accompanying 

 tabulation. Lower dosage (15-20 mg/kg) over 425-460 days gave roughly 



Tissue Organic Br (mg/kg) 



the same or somewhat higher levels. One problem is the form of this organic 

 Br. Bromoacetate reacts with SH groups in the tissues and bromide is 

 released, so that reacted bromoacetate would not be expected to contribute 

 directly to these values. Incorporation of bromide into organic compounds 

 in significant amounts seems unlikely. 



Acute Toxic Reactions 



The first adequate description of iodoacetate poisoning was made by Hall 

 and Field (1932) at Stanford. They injected unanesthetized starved rats 

 intraperitoneally with varying doses of iodoacetate and found, as many 

 others have confirmed, that the chronological sequence of reactions to iodo- 

 acetate depends markedly on the dose; i.e., not only the survival time but 

 also the pattern of the toxic response is altered by dosage level. They de- 

 lineated two response patterns, one from high doses where death is rapid 

 and one from lower doses where the animals survive for several hours. Ani- 

 mals receiving 120 mg/kg or over die within 20 min and symptoms begin 

 in 8 min. The effects may be summarized in the order in which they occur. 



(1) The first sign is a marked hypoactivity, punctuated by attacks of 

 hyperactivity (running, climbing, biting), which soon becomes ataxic and 

 occasionally takes the form of circus movements. 



(2) Distinct hyperpnea which progresses to inspiratory dyspnea. 



(3) Animals become prostrate on one side and cannot right themselves, 

 the hind legs paralyzed in abduction. 



(4) Occasional mild tremors or clonic convulsions appear and the animal 

 is hyperexcitable. 



