Table 2.
Definition of reference terms for integrated approachesa,b,c
| Term | Definition | Comment |
|---|---|---|
| Test battery no consensus definition |
A series of tests, independent of each other, generally designed to complement each other and/or to measure a different component of a multi-factorial toxic effect, and which are usually performed at the same time or in close sequence. Test batteries typically tend to complement each other but are not integrated into a strategy A group of assays conducted together for a specific purpose, usually to provide a prediction for a toxicity endpoint. The results of each individual assay could be equally weighted, or a statistical weight could be used as an attempt to better model the in vivo response |
“which are usually performed at the same time or in close sequence.” not needed Weighing would make it an ITS |
| Tiered test scheme | Testing approaches based on sequential assessments, where a result at one tier is used to determine the next step, if any. It is usually a decision-tree type of testing; after each step, the information is assessed to determine whether a prediction for the toxicity endpoint can be made or whether further testing/analysis needs to be done. A tiered approach usually progresses from a review of existing literature and data to a review of data for related chemicals or formulations, to perhaps a SAR/(Q)SAR analysis, to simple in vitro screening assays, to the use of more complex in vitro three-dimensional models, to testing in lower species, to the traditional animal test | OECD |
| Integrated testing starategy [ITS] no consensus definition |
A methodology, which integrates information for toxicological evaluation from more than one source, thus facilitating decision-making Strategies to gather and analyze a broad range of data coming from different sources (epidemiological studies, animal data, in vitro data, read-across methodologies, etc.) and used to draw conclusions based on weight-of-evidence approaches Testing strategies composed of, e.g., a number of in vitro and in silico methods that, combined and weighted in a fixed way, would serve to replace some or all in vivo experimentation for a given toxicity endpoint Approaches that integrate different types of data and information into the decision-making process. In addition to the information from individual assays, test batteries, and/or tiered test schemes, integrated testing strategies may incorporate approaches such as weight-of-evidence and exposure/population data into the final risk assessment for a substance |
Definition describes evidence integration not necessarily through testing Weight-of-evidence too narrow Focus on replacement too narrow, not necessarily fixed DIP Definition describes evidence integration not necessarily through testing |
| Defined approach to testing and assessment | A defined approach consists of a fixed data interpretation procedure (DIP) (e.g., statistical, mathematical models) applied to data (e.g., in silico predictions, in chemico, in vitro data) generated with a defined set of information sources to derive a prediction. In contrast to the assessment process within IATA, that necessarily involves some degree of expert judgment, predictions generated with defined approaches are rule-based and can either be used on their own if they are deemed to fit-for-purpose or considered together with other sources of information in the context of IATA | OECD |
| Integrated approach to testing and assessment (IATA) | Approach based on multiple information sources that integrates and weights all relevant existing evidence and guides the targeted generation of new data, where required, to inform regulatory decision-making regarding potential hazard and/or risk. An IATA necessarily includes a degree of expert judgement, for example, in the choice of information sources and their weighting. Nevertheless, some of the IATA components, such as defined approaches to testing and assessment, can be standardised (i.e., rule-based) | OECD |
| Data interpretation procedure (DIP) | Any fixed algorithm for interpreting data from one or typically several information sources. The output of a DIP is typically a prediction of a biological effect of interest. A DIP is rule-based in the sense that is based for example on a formula or an algorithm (e.g. decision criteria, rule or set of rules) that do not involve expert judgment. This definition has been taken and adapted from OECD guidance document 34 | OECD |
| Information source in the context of IATA | Physicochemical properties (e.g., molecular weight, pKa, Log Kow etc.), testing methods (i.e. in chemico, in vitro, in vivo methods), non-testing methods (e.g. QSARs predictions, extrapolation from chemical grouping approaches), and any other source that can generate relevant information for the purpose of the assessment within a defined approach or IATA | OECD |
DIP data interpretation procedure, IATA integrated approaches to testing and assessment, ITS integrated testing strategy, Log KOW decadic logarithm of the n-Octanol/water partition coefficient, i.e., a measure of lipophilicity, OECD the organisation for economic co-operation and development, pKa the negative log base ten of acid dissociation constant, i.e., a quantitative measure of the strength of an acid in solution, (Q)SAR (quatitative) structure activity relationship, SAR structure activity relationship sources
bhttp://alttox.org/mapp/emerging-technologies/integrated-testing-strategies-risk-assessment/
cFerrario D. et al. ALTEX 31, 2014