## 2 Accuracy of Predictive Methods and What Is Required
### Organic Molecules: the Virtue of Group Contribution Methods
The boiling points of the lower cycloalkanes show a slight deviation for cyclohexane as shown in Figure 5. These are typically features known and understood by the chemist as particular structures, like six-membered rings, sometimes slightly deviating properties compared to extrapolation between the two neighbouring members of the family. Straightforward method development might require the need for highly non-linear models to cope with this. The more appropriate way of dealing with this is to introduce such a species as a group by itself with its individual property. Upon requesting the property value from the model, the software tool will simply return the experimental value that was provided along with the definition of the group. By introducing one specific experimental value associated with one specific chemical group (molecule in this case), we arrive at a very good method without further complexity of the method. Such an approach may also very well apply to the prediction of toxicological end-points. If the mode of action of a toxic molecule is through very specific interactions of that particular molecule, something that is not an a priori exceptional as it is similar to the action of drug molecules that need a combination of very specific function for being active and molecules with a slightly different composition or structure having no or hardly any activity, the introduction of such species as groups by themselves is a very appropriate and effective action. In fact, in this way one effectively combines a method that was based on parameter optimization with the knowledge of the expert, an example is the so-called Read-Across knowledge of the toxicologist which is further elucidated in [[http://www.ecetoc.org/wp-content/uploads/2014/08/ECETOC-TR-116-Category-approaches-Read-across-QSAR.pdf](http://www.ecetoc.org/wp-content/uploads/2014/08/ECETOC-TR-116-Category-approaches-Read-across-QSAR.pdf)]([http://www.ecetoc.org/wp-content/uploads/2014/08/ECETOC-TR-116-Category-approaches-Read-across-QSAR.pdf](http://www.ecetoc.org/wp-content/uploads/2014/08/ECETOC-TR-116-Category-approaches-Read-across-QSAR.pdf)). Whereas various GC methods have been developed and applied over time, the [PERSON] group has probably made the more important _recent_ advances for a wide variety of properties [32; 33; 44]. These works show and in particular the recent one on heats of formation in which the methodology was adapted to obtain the most accurate results and few outliers, that indeed the Group Contribution methods can do the job in a very appropriate and reliable manner with a standard deviation of less than 3 kJ/mole and a maximum deviation of 10 kJ/mole for a widely varying set of almost 900 organic molecules. Other properties can be modelled in a similar way, leading to better predictive methods. In summary, the GC method seems, for organic molecules, to be a method requiring a minimum of parameters to uniquely describe a molecule and its physicochemical properties by a QSPR. There is no risk of overfitting (see next section) and there are clear ways within the methodology to increase accuracy and scope of predictions. Earlier in this review we have indicated how one can achieve the desired accuracy.