Publications & Documents

This Test Guideline proposes defined approaches (DA) combining data generated in vitro methods, with information sources such as physicochemical properties. The prediction from a DA may be used alone to determine eye hazard potential according to the hazard classes of the UN GHS (Categories 1, 2, or not classified). A DA consists of a fixed data interpretation procedure (DIP) (i.e. a mathematical model, a rule-based approach) 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 without the need for expert judgment. The DAs use method combinations intended to overcome some of the limitations of the individual, stand-alone methods in order to provide increased confidence in the overall obtained result.

This Test Guideline describes an in vitro procedure the identification on its own of chemicals (substances and mixtures) not requiring classification (No Cat), requiring classification for eye irritation (Cat 2) and requiring classification for serious eye damage (Cat 1) according to the UN GHS ocular hazard categories. It makes use of reconstructed human cornea-like epithelium (RhCE) which closely mimics the histological, morphological, biochemical and physiological properties of the human corneal epithelium. The test evaluates the ability of a test chemical to induce cytotoxicity in a RhCE tissue construct, as measured by the MTT assay. RhCE tissue viability following exposure to a test chemical is measured by enzymatic conversion of the vital dye MTT by the viable cells of the tissue into a blue MTT formazan salt that is quantitatively measured after extraction from tissues. Cytotoxicity is measured at different time points of exposure; this is one of the methodological differences with the original TG 492.

The Rapid Androgen Disruption Activity Reporter (RADAR) Test Guideline describes an aquatic assay that utilizes transgenic Oryzias latipes (O. latipes, Japanese medaka) eleutheroembryos at day post hatch zero, in a multi-well format to detect chemicals active on the androgen axis. The RADAR assay was designed as a screening tool to provide a short-term assay to measure the response of eleutheroembryos to chemicals potentially active on the androgen axis. Test organisms are exposed for 72 hours in six-well plates in the presence and absence of a co-treatment with 17-methyl testosterone. The assay comprises five concentrations of the test chemical. At the end of the exposure, fluorescence imaging is measured and transformed into a numerical format; the statistical analysis and data interpretation procdure enable to determine whether the test chemical is considered active or not active.

The present Test Guideline addresses the human health hazard endpoint skin sensitisation, following exposure to a test chemical. Skin sensitisation refers to an allergic response following skin contact with the tested chemical, as defined by the United Nations Globally Harmonized System of Classification and Labelling of Chemicals (UN GHS). This Test Guideline (TG) provides an in vitro procedure (the ARE-Nrf2 luciferase test method) used for supporting the discrimination between skin sensitisers and non-sensitisers in accordance with the UN GHS. The second key event on the adverse outcome pathway leading to skin sensitisation takes place in the keratinocytes and includes inflammatory responses as well as gene expression associated with specific cell signalling pathways such as the antioxidant/electrophile response element (ARE)-dependent pathways. The test method described in this Test Guideline (ARE-Nrf2 luciferase test method) is proposed to address this second key event. The cell line contains the luciferase gene under the transcriptional control of a constitutive promoter fused with an ARE element from a gene that is known to be up-regulated by contact sensitisers. The luciferase signal reflects the activation by sensitisers of endogenous Nrf2 dependent genes. This allows quantitative measurement (by luminescence detection) of luciferase gene induction, using well established light producing luciferase substrates, as an indicator of the activity of the Nrf2 transcription factor in cells following exposure to electrophilic test substances. There are currently two in vitro ARE-Nrf2 luciferase test method covered by this Test Guideline: the KeratinoSensTM test method and the LuSens test method. Performance standards have been developed to enable the validation of similar test methods.

The method permits estimation of an LD50 with a confidence interval and the results allow a substance to be classified for acute toxicity according to the Globally Harmonised System of classification and labelling of chemicals. It is easiest to apply to materials that produce death within couple of days. This Test Guideline is intended for use with rodents (rat female preferably). There are a limit test and a main test. The limit test can be used efficiently to identify chemicals that are likely to have low toxicity. The test substance is administered generally in a single dose by gavage to animals fasted prior to dosing. Single animals are dosed in sequence usually at 48h intervals. The first animal is dosed a step below the best preliminary estimates of the LD50. The second animal receives a lower dose (if the first animal dies) or a higher dose (if the first animal survives). Animals are observed with a special attention given during the first 4 hours and daily thereafter, for a total of 14 days generally. Weights Animals should be determined at least weekly. All the animals should be subjected to gross necropsy. Globally the LD50 is calculated using the maximum likelihood method. Following this, it may be possible to compute interval estimates for the LD50; most narrow is the interval and better is LD50 estimation. Software to be used with TG 425, 432, 455. Click here. Software not part of the Mutual Acceptance of Data.

Volume 9 of the Series compiles the biosafety consensus documents developed by the OECD Working Party on the Harmonisation of Regulatory Oversight in Biotechnology from 2019 to 2021. It deals with the biology of APPLE, SAFFLOWER and RICE, three important crops for agriculture and consumption worldwide. For each plant species, the book includes elements of taxonomy, morphology, centres of origin, life cycle, reproductive biology, genetics, outcrossing, crop production and cultivation practices, interaction with other organisms, main pests and pathogens, and biotechnological developments. The science-based information collated here is available for use during the risk assessment of transgenic varieties intended for release in the environment. Prepared by authorities from OECD Members and other economies associated with the work, this publication should be of value to crop breeders, applicants for agricultural production of new varieties of apple, safflower and rice, national regulators and risk assessors when conducting biosafety assessments on these varieties obtained from modern biotechnology, as well as the wider scientific community. More information is found at BioTrack Online.

The development of plastic products does not systematically take sustainability, particularly from a chemicals perspective, into account. This report seeks to enable the creation of inherently sustainable plastic products by integrating sustainable chemistry thinking in the design process. By applying a chemicals lens during the plastic material selection process, designers and engineers can make informed decisions to incorporate sustainable plastic during the conceptualisation phase of their products. The report provides an integrated approach to sustainable plastic selection from a chemicals perspective, and identifies a set of generalisable sustainable design goals, life cycle considerations and trade-offs. At a more granular level, considerations are identified for each life-cycle phase, which are brought together as a whole-product assessment and optimisation taking the full life cycle into account. The report also considers trade-offs that will need to be carefully balanced in the design phase and reflection on implications of design choices. Ultimately, the report helps to equip designers and engineers with knowledge of relevant chemical considerations when selecting sustainable plastic, supporting better outcomes and a more transparent process.