Chemical Categories and Read-Across

A chemical category is a group of chemicals whose physicochemical and human health and/or ecotoxicological properties and/or environmental fate properties are likely to be similar or follow a regular pattern, usually as a result of structural similarity.

The similarities may be based on the following:

  • a common functional group (e.g. aldehyde, epoxide, ester, specific metal ion);
  • common constituents or chemical classes, similar carbon range numbers;
  • an incremental and constant change across the category (e.g. a chain-length category);
  • the likelihood of common precursors and/or breakdown products, via physical or biological processes, which result in structurally similar chemicals (e.g. the metabolic pathway approach of examining related chemicals such as acid/ester/salt).

As a result of these similarities, data gap filling in a chemical category can be carried out by applying one or more of the following procedures: read-across, trend analysis, and (external) (Q)SARs.

A chemical category can be represented graphically as a two-dimensional matrix in which different category members occupy different columns, and the different category endpoints occupy different rows, as illustrated in the following figure.

 

chemical categories

Graphical illustration of a chemical category

 

In the read-across approach, endpoint information for one chemical (the source chemical) is used to predict the same endpoint for another chemical (the target chemical), which is considered to be "similar" in some way (usually on the basis of structural similarity). In principle, read-across can be used to assess physicochemical properties, toxicity, environmental fate and ecotoxicity. For any of these endpoints, it may be performed in a qualitative or quantitative manner.

Qualitative read-across is similar to the use of a SAR, and the process involves:

  • the identification of a chemical substructure that is common to two substances (which are considered to be analogues); and
  • the assumption that the presence (or absence) of a property/activity for a substance can be inferred from the presence (or absence) of the same property/activity for the analogous substance.

The main application of qualitative read-across is in hazard identification.

Quantitative read-across involves:

  • the identification of a chemical substructure that is common to two substances (which are considered to be analogues); and
  • the assumption that the known value of a property for one substance can be used to estimate the unknown value of the same property for another substance.

In both cases, expert judgement is needed and some justification should be provided.

Guidance on chemical categories and r­ead-across

As part of the scientific and technical preparations for the implementation of REACH, an activity was set up to develop guidance on categories and read across; specifically how to build and use a category, how to fill data gaps (e.g. by applying read-across), and how to justify the results by documenting "adequate information" in defined reporting formats. The starting point was the guidance published by the OECD in Section 3.2 of the OECD Manual for Investigation of HPV Chemicals (September 2004). This guidance was developed further on the basis of case studies on chemical categories assessed within various programmes under the OECD and the EU, as well as experience from a number of other case studies, some of which were research-based in nature.

The REACH guidance on categories and read-across is included in Chapter R.6 of the Guidance on Information Requirements and Chemical Safety Assessment. All of the finalised Guidance Documents are available on the ECHA website at: http://guidance.echa.europa.eu/guidance_en.htm.

ECHA has also published a practical guide on how to report categories and read-across:

ECHA guide on how to report categories and read-acrosspdf icon
The compendium of case studies, developed by the RIP 3.3 subgroup responsible for drafting the REACH technical guidance on categories, is available for download here:

Compendium of case studies on chemical categories (JRC report EUR 22481 EN)pdf icon
These case studies represent the findings, views and ideas of their individual authors at the time of writing, and do not necessarily represent the positions of the individual organisations with which the authors were affiliated or the consensus view of the group. They are provided solely for the purposes of transparency and completeness and should not be used in place of the technical guidance for REACH.
An additional set of research-based investigations and case studies has been developed by the ECB. Again, these represent the findings, views and ideas of the individual authors and do not necessarily reflect the position of the JRC or the Commission:

JRC report - EUR 22941 EN (October 2007)pdf icon