LATE POISONING WITH CHLOROFORM AND OTHER ALKYL HALIDES IN RELATIONSHIP TO THE HALOGEN ACIDS FORMED BY THEIR CHEMICAL DISSOCIATION.
The central lobular necrosis in the liver, which has been regarded by some writers as characteristic of late chloroform poisoning, has been produced experimentally with a number of other drugs. It is, therefore, in no sense peculiar to chloroform poisoning. Substances which have been shown to produce a morphological picture indistinguishable from that of late chloroform poisoning are: (a) dichlor- and tetrachlormethane, (b) tribrom- and triiodomethane, (c) monochlor-, monobrom-, and monoiodoethane, also the dibromethane; that is, in general, the halogen substituted aliphatic hydrocarbons containing one or two carbon atoms. Presumably similar results might be obtained with the higher members of the same series. The mechanism by which chloroform produces its characteristic tissue changes must accordingly be considered as a group reaction. Outside the body the similarities between the chemical behavior of different members of this group have been correlated by Nef on the basis of the type of dissociation which these substances undergo and the differences in their behavior on the basis of the differences of the degree to which such dissociations occur. According to the work of Nef, the group of substances under discussion has the property of dissociating to yield a halogen acid and an unsaturated alkylidene rest. Thus with chloroform the type of dissociation may be expressed thus: See PDF for Equation In this paper the view is developed that the changes characteristic of late poisonings with the above named group, namely edema, multiple hemorrhages, fat infiltration, and necrosis are ascribable (1) to acids and (2) to the fact that the amount of acid formed parallels the chemical dissociability of the drug outside of the body. Favoring the view that acid is responsible for the changes are the following observations. 1. All the characteristic features of late chloroform poisoning have been produced merely by the administration of hydrochloric acid, except, however, for a different distribution of the liver necrosis. 2. The areas of central necrosis produced in the liver by the various substances under discussion give an acid reaction to neutral red. 3. Sodium carbonate in a hypertonic sodium chloride solution markedly inhibits the production of the lesions.
Graham
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Otho S. A. Sprague Memorial Institute Laboratory of Clinical Research and the Department of Surgery, Rush Medical College, Chicago.