INFORMATICA

A basic introduction to QSAR

Introduction to QSAR

View more presentations or Upload your own.

The methods called quantitative structure-activity relationship (QSAR) are based on the assumption that the activity of a certain chemical compound is related to its structure. More precisely, this approach says that the activity, or the property, for instance the toxic effect, is related to the chemical structure through a certain mathematical algorithm, or rule.

The activity of a certain chemical compound is related to its structure.

QSAR models are also called in silico methods, which actually refer to a somehow broader set of methods. Human experts can identified links between structure and toxicity in two ways:

1. by considering the presence of a particular characteristic in the chemical compound, which is present or not in the structure. For instance, it is well known that if in the chemical compound there are certain groups, like an aromatic amine, or an epoxide, there is a higher probability that the chemical compound is genotoxic.
2. by a statistical analisys on toxic effect of chemical within a series of very similar compounds.

There are at least seven advantages offered by using QSAR models. REACH, since its first article, promotes innovation, and mentions that new, alternative methods should be searched to improve the evaluation of the chemicals. QSAR methods are included in the alternative methods.

7 reasons to use QSAR

Sometimes it is said that QSAR models represent a way for industry to spend less for toxicological research, or can be used to save animals to be used for experiments. It is also added that the real target of REACH is the protection of health and environment, and for this purpose other methods are more reliable.

Actually this position is in disagreement with what indicated by REACH. As we have seen, innovation is a milestone for REACH, and REACH states to use all pieces of information, in order to get a more reliable evaluation. The real challenge is not to identify the best method to protect human beings and environment. The challenge is to take advantage of all the contributions that each approach, in vivo, in vitro, and in silico, offer.

For this reason it is important to understand the multiple advantages offered by QSAR models. There are at least seven reasons to use QSAR.

1. Innovation. We already discussed this. Very soon a huge amount of data, on 100,000 chemicals, will become available, through USA initiatives, like Tox21 and ToxCast. To analyse manually such a huge amount of data is obviously impossible, and thus computer, in silico methods, will represent a privileged way to explore these new values.

2. The time necessary for the experiments, in particular for the chronic endpoints, would be very long. QSAR methods are very fast.

3. The number of laboratory in Europe to make all the necessary studies may be insufficient. For instance, a recent evaluation done within ANTARES identified this lack of suitable laboratories in Italy.

4. The cost to perform all in vivo experiments would be very high, billions of euros. QSAR methods are often free.

5. Millions of animals should be used to get the necessary data. This raises ethical issues.

6. The regulators have to identify the most risky compounds, and check the dossier submitted by industries. Many tens of thousands of chemicals will be submitted to ECHA, the Agency responsible for the registration process. However, only a limited number of dossiers will be evaluated by regulators, about 5%. It means that the toxicity properties submitted by industries will not be checked for 19 substances, out of 20 chemicals registered. QSAR methods may offer tools to screen all registered chemicals, and identify in this way the chemicals which are predicted more toxic.

7. So far chemical industry addressed the development of new chemicals only on the basis of the target properties for the candidate new products. Critical issues, such as toxicity, have been analysed in a second stage, to comply to regulations. QSAR methods offer tools to incorporate the process of the evaluation of the toxic properties since the beginning of the planning of new compounds, within a pro-active strategy, minimizing the impact of chemicals on the environment and human beings, and reducing the economic resources due to the development of chemicals without the knowledge on their toxicological and environmental properties.