Safety assessment of nanomaterials using an advanced decision-making framework, the DF4nanoGrouping

Abstract

As presented at the 2016 TechConnect World Innovation Conference on 22–25 May 2016 in Washington DC, USA, the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) ‘Nano Task Force’ proposes a Decision-making framework for the grouping and testing of nanomaterials (DF4nanoGrouping) consisting of three tiers to assign nanomaterials to four main groups with possible further subgrouping to refine specific information needs. The DF4nanoGrouping covers all relevant aspects of a nanomaterial’s life cycle and biological pathways: intrinsic material properties and system-dependent properties (that depend upon the nanomaterial’s respective surroundings), biopersistence, uptake and biodistribution, and cellular and apical toxic effects. Use, release, and exposure route may be applied as ‘qualifiers’ to determine if, e.g., nanomaterials cannot be released from products, which may justify waiving of testing. The four main groups encompass (1) soluble, (2) biopersistent high aspect ratio, (3) passive, and (4) active nanomaterials. The DF4nanoGrouping foresees a stepwise evaluation of nanomaterial properties and effects with increasing biological complexity. In case studies covering carbonaceous nanomaterials, metal oxide, and metal sulfate nanomaterials, amorphous silica and organic pigments (all nanomaterials having primary particle sizes below 100 nm), the usefulness of the DF4nanoGrouping for nanomaterial hazard assessment was confirmed. The DF4nanoGrouping facilitates grouping and targeted testing of nanomaterials. It ensures that sufficient data for the risk assessment of a nanomaterial are available, and it fosters the use of non-animal methods. No studies are performed that do not provide crucial data. Thereby, the DF4nanoGrouping serves to save both animals and resources.

Nanoparticles in Daily Life: Applications, Toxicity and Regulations

“…79,81 The DF4nanoGrouping ensures that sufficient data are available to assess the risk of a nanomaterial, and it fosters the use of nonanimal methods to save both animals and resources. 82 …”

In Vitro and In Vivo Short-Term Pulmonary Toxicity of Differently Sized Colloidal Amorphous SiO2

“…An abundance of nanoforms that differ, such as in primary particle size (PPS), shape, or surface function, can be produced for any given nanomaterial [ 1 , 2 ]. While an increasing number of scientific publications address safety assessments of engineered nanomaterials [ 3 , 4 , 5 , 6 , 7 ], it is widely acknowledged that toxicity testing to meet full regulatory information requirements, e.g., in accordance with Regulation (EC) No 1907/2006 on the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH [ 8 ]), for every variant of a given nanomaterial would lead to an insurmountable amount of testing [ 9 ]. This would further stand in contradiction to the ethical and legal requirement to replace, reduce, and refine animal testing (3Rs principle) [ 10 , 11 ].…”

“…A rat short-term inhalation study (STIS) is available that allows reducing and refining the use of animals as compared to the traditional Organisation for Economic Cooperation and Development (OECD) test guideline (TG) 412, Sub-acute inhalation toxicity: 28-day study [ 12 , 13 , 14 , 15 ]. By comparison, standardized in vitro assays to assess the cellular effects of nanomaterials continue to be unavailable [ 6 , 7 , 16 , 17 , 18 ]. Only a few of the numerous published in vitro studies investigating the cellular effects of nanomaterials were aimed at predicting in vivo toxicity potential [ 1 , 6 , 7 , 19 , 20 , 21 , 22 ].…”

“…By comparison, standardized in vitro assays to assess the cellular effects of nanomaterials continue to be unavailable [ 6 , 7 , 16 , 17 , 18 ]. Only a few of the numerous published in vitro studies investigating the cellular effects of nanomaterials were aimed at predicting in vivo toxicity potential [ 1 , 6 , 7 , 19 , 20 , 21 , 22 ].…”

Workshop on the validation and regulatory acceptance of innovative 3R approaches in regulatory toxicology – Evolution versus revolution

“…In vitro methods to test for skin and eye irritation were developed relatively early and are in regulatory use -albeit not quite on equal footage with the animal studies (Sauer et al, 2016). The new approaches to skin sensitization testing (Gabbert et al, 2017) (Burden et al, 2017), (Landsiedel et al, 2017). Methods which are termed 'non-testing methods' (methods using existing data rather than generating new data from experiments) such as grouping and read-across are widely used to fulfil REACH information requirements and are continuously improved and refined (Teubner and Landsiedel, 2015) including the use of computational toxicology (Luechtefeld et al, 2018), (Myatt et al, 2018).…”