Some Toxic Effects of Dieldrin in Rats.

Dieldrin is a technical product containing 85% of H.E.O.D., the approved name for 1,2,3,4,10,10,hexachloro-exo-6,7-epoxy1,4,4a ,5,6,7,8,8a-octahydro-exo -1,4, endo -5,8,dimethanonaphthalene. The remaining 15% of the technical product consists of active isomeric compounds. Dieldrin is a powerful insecticide that has been extensively used in agriculture, food storage, and public health work. Where men have been exposed to dieldrin over long periods in house spraying programmes many cases of poisoning have been reported (Hayes, 1959). Dieldrin acts as an acute convulsive poison in man and laboratory animals. Although the manifestations of poisoning may be severe and dramatic, there have been very few human fatalities, and no irreversible neurological sequelae have so far been reported. Most cases of occupational poisoning in man have followed fairly long periods of exposure, and in some cases convulsions have recurred some days or weeks after exposure had ceased (Hayes, 1959). Thus dieldrin appears to be a cumulative poison with prolonged effects. Recent work on the metabolism of dieldrin (Heath and Vandekar, 1964) provides a possible explanation for the behaviour of dieldrin as a poison in man. These same observations also provide an explanation for some experiments on laboratory animals carried out about five years ago, which are the subject of this paper. As a single dose given by mouth in a solution in edible oil, dieldrin has been reported to have an LD50 of 87 mg./kg. (Lehmann, 1951), 65 mg./kg. (Klimmer, 1955), and 38 mg./kg. (Treon and Cleveland, 1955). These differences are probably accounted for partly by variations in the quality of the material tested and partly by differences in the strain, sex, and ages of the rats. However, the important feature of dieldrin tested in this way is that, as recorded first by Lehmann (1951), death after a single dose may be delayed up to six days or longer. The experiments to be described here record the influence of the concentration of solution used on the pattern of poisoning and the effect of previous semi-starvation on susceptibility, and also the fact that rats that have survived one dose of dieldrin remain much more sensitive than normal rats to a second dose given up to three weeks later.