Prediction of Human Lethality of Psychoactive Drugs From Rodent LD50 Values

The number of deaths from the abuse of psychoactive drugs is increasing year after year, and new designer psychoactive drugs of unknown toxicity frequently appear on the streets. Human lethal drug doses generally do not correlate well with animal LD50 values. In order to investigate whether that holds for psychoactive drugs, human lethal dose values and rat and mouse LD50 values for several routes of administration for eighteen such drugs were collected from the literature. Quantitative toxicity-toxicity relationship (QTTR) regression correlations of human and rodent lethal doses were poor for both rat and mouse oral and intraperitoneal lethal doses, but both rat and mouse intravenous LD50 values correlated very well with human lethal doses (r2 = 0.823 and 0.756, respectively). Rat and mouse intravenous LD50 values predicted from commercial software also correlated reasonably well with human lethal doses (r2 = 0.631 and 0.678, respectively). This means that it should be possible to use these correlations to predict the human lethal doses of new psychoactive drugs.