August 17th, 2009
Albania, Melanie and I were recently asked to contribute an article to a special supplement of Chemisty Today dedicated to REACH. REACH (Registration, Evaluation, Authorisation and Restriction of Chemical substances) is EU legislation with the aim to improve the protection of human health and the environment through the better and earlier identification of the intrinsic properties of chemical substances.
Where there are gaps in a chemical substance’s health or environmental effects dataset, REACH requires Registrants to fill them, initially by considering approaches that do not require animal testing. In the article we describe some of the computational approaches which we regularly use to fill data gaps for clients, discussing their strengths and weaknesses. We also describe approaches to make better use of more plentiful data sets, which are available for some substances. A very brief summary of the article is included below. Access to the full article is available for free from the Chemistry Today website for a limited period.
Filling data gaps
Approaches that can be used to fill data gaps include Quantitative Structure Activity Relationships (QSARs), read-across based on structural similarity, and derivation of Thresholds of Toxicological Concern (TTC) for substances with low exposure concentrations.
Comparison of EPI Suite (5) QSAR estimates and experimental fish acute LC50 values for selected priority substances. The diagonal line is a 1:1 relationship.
Making better use of data
In contrast to situations when Registrants may have too few experimental data, we also describe computational approaches such as the generation of Species Sensitivity Distributions (SSDs) and Probabilistic Risk Assessments (PRAs) which may be of benefit to registrants with reasonably substantial data sets on exposure or effects, potentially enabling the derivation of less conservative PNECs and RCRs than by using standard assessment factors.
Example of an SSD. The HC5 is 2.3 mg l-1 (CI=0.71 – 4.53 mg l-1)
For some registrants, these tools may offer an important benefit, allowing them to demonstrate safe use without the need to introduce expensive and unnecessary risk management measures or undertake additional vertebrate testing.
