LD50 - its value for the pharmaceutical industry in safety evaluation of drugs.

Does the pharmaceutical industry perform LD50-determinations in animals just because it is required by the authorities or are there any scientific benefits from counting dead animals and calculating and index of lethal toxicity? This is an important question when discussing LD50 and possible alternatives. We will try to answer this question by presenting data and some views collected during almost ten years at a Swedish pharmaceutical company. We will describe how we have made use of the LD50-values in the safety evaluation process. We will compare LD50-values with the dose levels used in longterm toxicity both after single or repeated administration and with therapeutical dose levels in man for different classes of drugs. These data will enable us to demonstrate the value of the LD50-determinations. As we are of the opinion that the LD50-value itself has a limited value for the total safety evaluation of drugs we will look into the possibility of replacing the LD50-determination with something else as an indication of lethal toxicity. In order to minimize the number of animals used and the number of animals dying because of dosing in studies on lethal toxicity we will try to support a proposal to use the maximal nonlethal dose (MNLD) as an indication of lethal toxicity in small animals.