Toxicology studies are used to characterize the possible toxicity profile of a drug. This includes identification of any impact on organ structure and/or function. Tox study is an essential part of the drug development process and provides necessary characteristics of therapeutic benefits, safe doses, and risks. 

GLP toxicology studies FDA is generally completed before the drug can move to clinical trials. Using good laboratory practices (GLP) and following FDA guidelines ensures that the study data is robust and safe. Following GLP guidelines is mandatory for the FDA to accept the No Observed Adverse Effect Level (NOAEL).

Establishing NOAEL also helps in managing the correct dose levels for clinical trials. Thus, toxicology screening helps keep the drug dose within therapeutic levels and keeps it safe for use on humans. 

Determining the Therapeutic Index (TI) of a Drug

The toxicity of a substance is often studied through two methods.

1. Using in vitro samples to study toxicity using cells or cell lines
2. Using in vivo data gathered from animals during a preclinical study

In some cases, in silico methods are also employed. Studying toxicity also includes using TK assays to better understand the toxicokinetic profile of a drug. Understanding toxicokinetics (TK) through the process of ADME (Absorption, Distribution, Metabolism, Elimination) helps in understanding mechanism and dosage.

The Therapeutic Index of a drug compares its therapeutically effective dose to a toxic dose. Simply put, a high dose that produces toxicity is compared to a lower dose that produces therapeutic benefits. This involves using 50% dose-response points, including the toxic and effective dose. Given the dose-response points, the therapeutic dose is represented by ED50 and toxic dose by TD50.

TI = TD50/ED50 = Toxic Dose/Dose for Therapeutic Response

Once the Tox study has defined the TI of a drug, it can be used as a guideline in determining the safe dose and prescription of the said drug. The greater the TI, the less toxic will be the drug. 

Using the Margin of Safety (MOS)

Useful as TI is, its use of a single point on the dose-response curve may be misleading on the relative safety of the drug. Therefore, toxicology studies often make use of another criterion, which is the Margin of Safety. Simply put, the MOS is useful for playing it safe and finding a dosage that is effective with reduced chances of toxicity.
Using MOS means a reduced risk of overdosing or using a dose that is uncomfortably close to toxic levels. This largely depends on the data collected during the Tox study and uses relevant information. Dose-response is non-linear, and on a graph, the difference between toxic dose and effective dose becomes very clear. Also, this response may vary with the person and the intensity of treatment.

MOS is calculated as the ratio of dose-response that is toxic to 1% of the population, versus the dose-response that shows therapeutic benefits in 99% of the population (ED99).
MOS = TD01/ED99

In some cases, more patients may benefit from a higher dosage. At the same time, this may also represent a higher probability of toxicity. MOS may thus also be used to have the drug available in different doses for prescription, leaving room for various treatment options.