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.