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

Abstract

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.

Antidiarrhoea and toxicological evaluation of the leaf extract of Dissotis rotundifolia triana (Melastomataceae)

“…The dose is used to calculate the initial dose to be tried in man during the clinical trials. It has been suggested that a simple limit test, aimed at determining the effect on animals, of the largest dose likely to be administered to a human being is often enough [ 27 ].…”

Structural, electronic, intermolecular interaction, reactivity, vibrational spectroscopy, charge transfer, Hirshfeld surface analysis, pharmacological and hydropathy plot on 5-Bromo nicotinic acid – Antiviral study (Hepatitis A, B, and C)

“…Moreover, it does not cause p53 gene (tumour suppressor) mutation along with the inactive Heat shock response. The average lethal dosage (LD50) for 5BNA is predicted to be 3720 mg/kg and it lies in the toxicity class of Class VI which indicates that the compound is non-toxic in nature and can also be proposed as the drug [ 85 ].…”

An Overview of Bacterial Toxigenesis and a Potential Biological Weapon in Warfare

“…The lethal dose (LD50) is amount required to kill 50% of test animals (usually rats or mice). LD50 < 25 mg/kg represents very toxic; LD50 < 25 mg/kg to 200 mg/kg is toxic; LD50 < 200 mg/kg to 2000 mg/kg < LD50 is harmful, while substances of LD50 > 2000 mg/kg are not classified as toxic agents [38]. Human beings have been using biological toxins since long.…”