not-yet-known not-yet-known not-yet-known unknown Nanomaterials Nanomaterials (NM) were an important subject at FDA and especially CDRH. CDRH submissions sometimes claimed that products contained nanomaterials (considered advantageous for marketing) when they didn’t. On the other hand, products might have nanomaterials that were not disclosed. Policy didn’t seem to require authenticity regarding NM. A draft medical device standard calling NM a default carcinogenic risk led to investigations into whether this was true. Much of the data related to this claim was from genotoxicity testing. Characterization of medical device materials as a carcinogenic risk would effectively shut down their use in new products, vastly affecting product development using such materials. Nanomaterials were a bandwagon topic at FDA and elsewhere beginning around 2007. FDA proposed to assess the issue collaboratively among centers. However, the agency representatives (not including me) could not harmonize even on a definition of NM. This was emblematic of the difficulty in categorizing NM chemical composition, physical attributes and biological effects. The subject required collaboration of a diversity of scientists with different expertise, a task that still seems of questionable feasibility. FDA inter-center collaboration was abandoned. After several years of little progress in safety assessment of NMs, it seemed reasonable to address it from the perspective of our expertise, genotoxicity, and leave the physics and chemistry to others. Stefan Pfuhler and I worked on this issue by chairing an EMGS workshop in 2010 on strategic approaches to NM assessment (Pfuhler et al. 2013). A review of some genotoxicity assessments showed that these were not always good studies. Moreover, according to Shareen Doak, most of the standard assays needed methods adjustments or other alterations for assessment of NM, because of lack of exposure (bacterial assays) or interference with the assay (in vitro micronucleus assay). Thereafter, we continued with the Health and Environmental Sciences Institute (HESI) Nanomaterials group, beginning with a critique of the genotoxicity literature that was the basis of the NM characterization. We found much of the literature faulty, i.e. invalid, incorrectly conducted, or uninterpretable, often in non-standard systems (Elespuru et al., 2018). Our experiments on the lack of uptake of silver (Butler et al. 2015) or titanium dioxide (Butler et al. 2014) NM into bacteria contributed to the development of the altered test battery. NM could be seen to associate on the outside of bacteria, but were not internalized; they were uniformly negative in valid bacterial mutagenicity assays.