Methods and data for regulatory risk assessment of nanomaterials: Questions for an expert consultation

- It has been very challenging to obtain a detailed list of nanomaterial regulatory questions, which would inform both the ability of current research products to address regulatory needs and assist in future research needs in this area.
- This article provides such a detailed question set, a process for using these questions to identify the best methods and data sets for current use, and a mechanism to obtain regulatory acceptance of these methods and data sets.

While the general risk assessment paradigm, and associated endpoints for regulatory review and approval of conventional chemicals in essence apply to nanomaterials, two problems have arisen that must be addressed. Due to the physicochemical properties of nanomaterials, additional parameters, in addition to their chemical composition, are needed to identify a manufactured nanomaterial for regulatory purposes. Second, new methods for material characterization, hazard, exposure, fate, and risk assessment are needed to supplement those that exist for the regulatory risk assessment of conventional chemicals. While this area has received extensive funding in the EU, the US and other countries, the resulting range of research results are broad, and it remains unclear how well these current research efforts have answered detailed regulatory needs for nanomaterials. These needs for are driven by applicable statutes such as REACH, and are aimed at questions that must be answered in an efficient and cost-effective manner through the use of reliable protocols and methods. The direct applicability of that research to these regulatory needs has not been comprehensively assessed. In part this is due to the fact that a detailed set of regulatory questions for nanomaterials has not been presented in the open literature. In addition, regulatory questions for emerging areas of science take time to formulate in detail.One purpose for this paper is to provide the context for nanomaterial regulatory risk assessment questions. Second, we present, in detail and for the first time, what these prominent regulatory questions are for all relevant risk assessment endpoints. These detailed regulatory questions were derived in part from the EU FP 7 research programme NANoREG, and then augmented by additional questions that have been raised by regulatory authorities. These questions address the following areas: (1) physicochemical characterization, (2) exposure through the lifecycle, (3) fate - persistence - bioaccumulation, (4) modeling of environmental fate and exposure, (5) ecological effects and biokinetics, (6) human health effects and biokinetics in vivo, (7) human health effects and biokinetics in vitro, (8) in silico strategies - (Q)SAR modeling, and (9) risk assessment. Answers to these questions were provided by an expert solicitation in the EU H2020 coordination activity ProSafe, were presented and discussed at a scientific conference at OECD in November 2016, and are now published separately in this special issue of NanoImpact.The methods deemed acceptable for regulatory use, and targeted regulatory gaps, will be incorporated into a 2017 draft white paper. This white paper will mesh EU regulatory policy with new available and proposed methods, and other future-oriented needs, aimed at streamlining the assessment of nanomaterial risks. The white paper will then receive comments from Member States, industry, and others via an interactive process, resulting in a final white paper in the September 2017 timeframe.