Division 1.2 DEFINITIONS

The following definitions are applied within this Test Method:

Accuracy: The closeness of agreement between test method results and accepted reference values. It is a measure of test method performance and one aspect of relevance. The term is often used interchangeably with ‘concordance’ to mean the proportion of correct outcomes of a test method.

Batch control substance: Benchmark substance producing a mid-range cell viability response of the tissue.

Cell viability: Parameter measuring total activity of a cell population e.g. as ability of cellular mitochondrial dehydrogenases to reduce the vital dye MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Thiazolyl blue;), which, depending on the endpoint measured and the test design used, correlates with the total number and/or vitality of living cells.

ET₅₀ : The exposure time required to reduce cell viability by 50 % upon application of the marker substance at a specified, fixed concentration, see also IC₅₀.

False negative rate: The proportion of all positive substances falsely identified by a test method as negative. It is one indicator of test method performance.

False positive rate: The proportion of all negative (non-active) substances that are falsely identified as positive. It is one indicator of test method performance.

Infinite dose: Amount of test substance applied to the skin exceeding the amount required to completely and uniformly cover the skin surface.

GHS (Globally Harmonized System of Classification and Labelling of Chemicals): A system proposing the classification of substances and mixtures according to standardised types and levels of physical, health and environmental hazards, and addressing corresponding communication elements, such as pictograms, signal words, hazard statements, precautionary statements and safety data sheets, so that to convey information on their adverse effects with a view to protect people (including employers, workers, transporters, consumers and emergency responders) and the environment (1) and implemented in the EU in Regulation (EC) No 1272/2008.

IC₅₀ : The concentration at which a marker substance reduces the viability of the tissues by 50 % (IC₅₀) after a fixed exposure time, see also ET₅₀.

Performance standards: Standards, based on a validated reference method, that provide a basis for evaluating the comparability of a proposed test method that is mechanistically and functionally similar. Included are (I) essential test method components; (II) a minimum list of reference substances selected from among the substances used to demonstrate the acceptable performance of the validated reference method; and (III) the comparable levels of accuracy and reliability, based on what was obtained for the validated reference method, that the proposed test method should demonstrate when evaluated using the minimum list of reference substances.

Reliability: Measures of the extent that a test method can be performed reproducibly within and between laboratories over time, when performed using the same protocol. It is assessed by calculating intra- and inter-laboratory reproducibility.

Sensitivity: The proportion of all positive/active substances that are correctly classified by the test. It is a measure of accuracy for a test method that produces categorical results, and is an important consideration in assessing the relevance of a test method.

Specificity: The proportion of all negative/inactive substances that are correctly classified by the test. It is a measure of accuracy for a test method that produces categorical results and is an important consideration in assessing the relevance of a test method.

Skin irritation: The production of reversible damage to the skin following the application of a test substance for up to 4 hours. Skin irritation is a locally arising, non-immunogenic reaction, which appears shortly after stimulation (24). Its main characteristic is its reversible process involving inflammatory reactions and most of the clinical characteristic signs of irritation (erythema, oedema, itching and pain) related to an inflammatory process.