Developing OECD test guidelines for regulatory testing of nanomaterials to ensure mutual acceptance of test data

Abstract

The OECD Working Party on Manufactured Nanomaterials (WPMN) provides a global forum for discussion of nano-safety issues. Together with the OECD Test Guidelines Programme (TGP) the WPMN has explored the need for adaptation of some of the existing OECD Test Guidelines (TGs) and Guidance Documents (GDs) as well as developing new TGs and GDs to specifically address NM issues. An overview is provided of progress in the TGP and WPMN, and information on supporting initiatives, regarding the development of TGs for nanomaterials addressing Physical Chemical Properties, Effects on Biotic Systems, Environmental Fate and Behaviour, and Health Effects. Three TGs specifically addressing manufactured nanomaterials have been adopted: a new TG318 ″Dispersion Stability of Nanomaterials in Simulated Environmental Media”, and adaptation of TG412 and TG413 on Subacute Inhalation Toxicity: 28-Day Study/90-day Study. The associated GD39 on Inhalation Toxicity Testing has also been revised. The TGP current develops four new TGs and four GDs. One new TG and six GDs are developed in the WPMN. Six new proposals were submitted to the TGP in 2018. Furthermore, as TGs are accompanied by OECD harmonised templates (OHTs) for data collection, an outline of recently developed OHTs particularly relevant for NMs is also included.

Toxicological assessment of nanoparticle interactions with the pulmonary system

“…in vitro skin absorption test (OECD TG 428), or animals sacrificed for any other cause excluding the need for the experiment, e.g. slaughterhouse (isolated Chicken Eye test; OECD TG 438) (Rasmussen et al 2019). Ex vivo models evaluate NP uptake, distribution, and toxicokinetics.…”

“…They provide conditions that are realistic and mimic the in vivo response, and more control over experimental conditions. For example, ex vivo lung slices from either human or rat or mouse are used to assess the respiratory system for various types of NPs to detect cytotoxicity, oxidative stress, genotoxicity, alteration of protein expression, or inflammation (Rasmussen et al 2019). The use of ex vivo studies is new and some variations are there preventing their standardizations (Wick et al 2015).…”

“…A study by Gupta et al had successfully predicted the in vitro cytotoxici-ty of five different NPs based on their physicochemical characters (Yan et al 2017). In silico models are yet to be validated for the NPs models even though they are validated by the OECD guidance for conventional chemical testing (Suzuki et al 2017;Qiu, Clement, and Haynes 2018;Rasmussen et al 2019). Successful QSAR models are in need for data availability of accurate and consistent grouping of NPs based on physicochemical characters, mechanisms of action, exposure scenarios, standardized in vitro and in vivo testing conditions.…”

“…They provide a set of protocols to assess the safety of nanomedicines (Sainz et al 2015;Accomasso, Cristallini, and Giachino 2018;Siegrist et al 2018). In the UK, organizations like DEFRA, FSA, DH, ISO, OECD, REACH are controlling the handling, use, and assessment of nanomaterials (Rasmussen et al 2019). Detailed and recommended methods for physicochemical characterizations of NPs, for occupational, environmental, and consumer exposure modeling; and for in vitro/in vivo methods of nanotoxicological testing, agreed by a variety of regulatory bodies to assess different nanomaterials, can be found in these sources (Sainz et al 2015;Drasler et al 2017…”

Nanocharacterization, Materials Modeling, and Research Integrity as Enablers of Sound Risk Assessment: Designing Responsible Nanotechnology

“…[ 10 ] As a result, an OECD Test Guidelines Programme is active for producing new and improved characterization methods for the detection of nanomaterials in complex matrices, for properties related to their fate and toxicological activity in the environment, with the contribution of Horizon 2020 funded projects. [ 11–14 ]…”