Identification of emerging safety and sustainability issues of advanced materials: Proposal for a systematic approach.

The EU Chemicals Strategy for Sustainability is a first step to achieve the Green Deal ambition for a toxic-free environment, and ensure that chemicals are produced and used in a way that maximises their contribution to society while avoiding harm to our planet and to future generations. Advanced materials are predicted to play a pivotal role in achieving this ambition and the underlying sustainability goals, and considerable efforts are invested in designing new classes of materials. Examples of such materials are metamaterials, artificially architectured materials designed to have material properties beyond those of the individual ingredient materials, or active materials at the boundary between materials and devices (e.g., new biomedical soft materials). Such innovative advanced materials raise concern about possible future safety and sustainability issues and would benefit from appropriate risk governance that promotes innovation, while pushing for safety and sustainability. To balance these aspects, a methodology is proposed for the early-stage identification of emerging safety and sustainability issues of advanced materials. As exemplified by two case studies, the methodology aims to be of use for innovators, risk assessors, and regulators. Extension of the methodology is highlighted, as well as implementation in broader initiatives like the EU's industrial policy approach.

Derivation of point of departure (PoD) estimates in genetic toxicology studies and their potential applications in risk assessment.

Genetic toxicology data have traditionally been employed for qualitative, rather than quantitative evaluations of hazard. As a continuation of our earlier report that analyzed ethyl methanesulfonate (EMS) and methyl methanesulfonate (MMS) dose-response data (Gollapudi et al., 2013), here we present analyses of 1-ethyl-1-nitrosourea (ENU) and 1-methyl-1-nitrosourea (MNU) dose-response data and additional approaches for the determination of genetic toxicity point-of-departure (PoD) metrics. We previously described methods to determine the no-observed-genotoxic-effect-level (NOGEL), the breakpoint-dose (BPD; previously named Td), and the benchmark dose (BMD10 ) for genetic toxicity endpoints. In this study we employed those methods, along with a new approach, to determine the non-linear slope-transition-dose (STD), and alternative methods to determine the BPD and BMD, for the analyses of nine ENU and 22 MNU datasets across a range of in vitro and in vivo endpoints. The NOGEL, BMDL10 and BMDL1SD PoD metrics could be readily calculated for most gene mutation and chromosomal damage studies; however, BPDs and STDs could not always be derived due to data limitations and constraints of the underlying statistical methods. The BMDL10 values were often lower than the other PoDs, and the distribution of BMDL10 values produced the lowest median PoD. Our observations indicate that, among the methods investigated in this study, the BMD approach is the preferred PoD for quantitatively describing genetic toxicology data. Once genetic toxicology PoDs are calculated via this approach, they can be used to derive reference doses and margin of exposure values that may be useful for evaluating human risk and regulatory decision making.