Definitions

Definitions used in this project are built on the definitions and terminology provided in the ECHA RAAF and the OECD Guidance Document (GD) 194. We refer to the ECHA RAAF (ECHA 2017) and the OECD GD 194 (OECD 2014) for additional definitions and explanations of relevant terms.

Grouping approach which aims to fill a data gap for one substance in the group based on information from one or a few source substances.

The ECHA RAAF defines that the term analogue approach is used when read- across is employed between a few, very structurally similar substances for which it is not possible to establish a trend or a regular pattern. As a result of the structural similarity, a given (toxicological or other) property of one substance (the source) is used to predict the same property for another substance (the target), for which this property is not available but is needed to fulfil a REACH information requirement. The outcome of a study conducted with the source substance is read- across for all investigated parameters to the target substance. A worst-case approach may also be used (ECHA 2017).

The OECD GD 194 defines that the term analogue approach is used when the focus is to fill data gaps for one specific chemical, based on empirical data from one or more similar chemicals. The analogue approach is specified to be useful when the target and source chemicals share a known common mode (or mechanism) of action and the adverse effects resulting from this is evaluated (OECD 2014).

The set of inclusion/exclusion rules that identify the ranges of values within which a reliable prediction can be made for category members (ECHA 2017).

A critical scientific aspect of a read-across to be assessed through a number of questions to be answered (ECHA 2017).

In this document used when defining a group of similar substances. Can be used interchangeably with the term grouping, which is the preferred one in this document.

Grouping approach which aims to fill gaps for a given property for multiple substances in the category based on available information from the source category members.

The ECHA RAAF defines that the term category approach is used when read- across is employed between several substances with structural similarities. These substances are grouped together based on defined structural similarities and differences between the substances. As a result of the structural similarity, one or more (toxicological or other) properties are proposed to be similar or to follow a regular pattern. The predictions are made within the group for the target substance(s) based on the observed regular pattern. Alternatively, the prediction is based on a read-across from a category member in a conservative manner (worst case) (ECHA 2017).

The OECD GD 194 defines that the term category approach is used when chemicals whose physico-chemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern due to structural similarity. In this approach, the properties of the individual chemicals within a category are assessed based on evaluating the category as a whole (OECD 2014).

Explanation as to why property(ies) of category members may be predicted from reference substances within the category. This explanation must be based on a relationship between structural similarity and the predicted property(ies) (ECHA 2017).

Reasoning and associated supporting evidence that are provided to verify the scientific validity and robustness of the category hypothesis (ECHA 2017).

Under REACH, substances that are structurally similar with physicochemical, toxicological, ecotoxicological and/or environmental fate properties that are likely to be similar or to follow a regular pattern may be considered as a group of substances. Within a group of substances, a data gap might be filled by read-across, as described below (ECHA 2017).

In this document used when defining a group of similar substances. Can be used interchangeably with categorization, but grouping is preferred in this document.

Mathematical model (often a statistical correlation) relating one or more qualitative and/or quantitative parameters (molecular descriptors) derived from the chemical structure to a qualitative or quantitative measure of a property or activity. QSARs are quantitative models yielding a continuous or categorical result. For regulatory use, QSARs should be validated according to the OECD (Q)SAR Validation Principles, hereunder also associated with a defined applicability domain (AD).

A qualitative relationships that relates a (sub)structure and/or other molecular descriptors to the presence or absence of a property or activity of interest, by expert judgement but most often also by use of statistical considerations. For regulatory use, SARs should be validated according to the OECD (Q)SAR Validation Principles. Often, the SAR expert systems incorporates mechanistic interpretation with literature references into the system.

A combination of SAR and QSAR, as they are very overlapping concepts, both based on the similarity principle, i.e. the hypothesis that substances with similar molecular structure will have similar properties, hereunder biological activities.

Method used to fill data gaps for substances in an analogue or a category approach.

Under REACH, read-across is a technique for predicting endpoint information for one substance (target substance), by using data from the same endpoint from (an)other substance(s), (source substance(s)). Consequently, the read-across is considered as property-specific (ECHA 2017).

Hypothesis on the basis of which property(ies) of target substance(s) may be predicted from source substance(s). This hypothesis must be based on a relationship between structural similarity and the predicted property(ies) and needs to be supported by a read-across justification (ECHA 2017).

The reasoning and associated supporting evidence that are provided to verify the scientific validity and robustness of the read-across hypothesis (ECHA 2017).

In this document used when defining a smaller group of similar substances out of a larger group.