Feasibility and challenges of human health risk assessment for engineered nanoparticles (chapter 21)

Field: Pharmacology, Toxicology and Pharmaceutics (Life Sciences)

Nanomaterials are currently regulated essentially under the chemicals legislations in the different OECD countries, possibly with additional data required in specific areas of legislation within a country. The OECD concluded, based on the findings of the OECD Working Party on Manufactured Nanomaterials, that the methods and approaches developed for managing the safety of chemicals can by and large be applied to nanomaterials, though paying special attention to a number of issues, for example, sample preparation.\nNanomaterials, due to their specific properties which may change during their life cycle from cradle-to-grave, pose specific challenges to the risk assessment. A systematic testing of all different forms of NMs in all use/release scenarios is impossible as it would be too time consuming and costly. In addition, modern toxicology requires the reduction and optimization of in vivo tests (especially in higher vertebrates) and recommends in vitro and in silico models in integrated (intelligent) testing approaches. As the development and validation of in vitro and in silico assays for NMs still lags behind conventional chemicals, currently the scaling, grouping, and read-across approach to existing information from different forms (bulk or other nanoforms) seem to be the most promising approach and frameworks have been proposed by some stakeholders. Any hypothesis for grouping and read-across needs to be supported and confirmed by data, for which some testing (in a tiered testing strategy) may still be required.\n(Occupational) inhalation of NMs appears to be the main focus area in relation to the risk (and thereby hazard and exposure) of NMs. Test guidelines for inhalation toxicity are thus attracting specific attention and considerations are made in relation to increasing the number of endpoints to be examined in such guideline studies. At the same time, several efforts are made to model exposure to NMs via different routes by in vitro assays as realistically as possible by testing them in different and more complex cell models and exposure types. Also sample preparation and dosimetry, including characterization of the NMs during the study, is of outmost importance.\nSimilarly, for exposure estimation, most attention is given to the potential for inhaling airborne NMs. Exposure models are not yet validated for NMs, and models for inhalation exposure seem in particular to need further re-development before being applicable to NM. Additional efforts are needed if other metrics than mass are relevant and should be predicted.\nIn relation to measurements, a suite of techniques are available, from relatively cheap particle counters giving quick, but rough and not specific results, to expensive off-line analysis of samples, which can provide insight into elemental composition and particle characteristics. Thus, as for hazards, intelligent exposure assessment strategies are needed. Further, the overall exposure database is very scarce compared to hazard investigations and most exposure data relate to upstream NM’s manufacturing and laboratory work.\nRisk assessment needs to address the challenges of handling data from alternative methods and the potentially higher uncertainty associated, due to fewer data or lower reliability. In principle, current risk assessment frameworks provide sufficient flexibility to use data from alternative methods; however, further experience and consensus building is needed in relation to NMs. Weight of evidence approaches based on expert judgment are being suggested in risk assessment at different levels and could be extended with an increased level of confidence and validation.\nWhile appropriate methods for hazard/exposure and risk characterization are still under development and approval, it is important to consider and manage the potential risk of NMs already in their development phase. Control banding is one such ways to manage risk of nanomaterials, “safety by design” can contribute to a lower risk from both the hazard side by considering those properties that most likely contribute to biological effects, and from the exposure side by minimizing or excluding exposure.