For nanotechnology to meet its potential as a game-changing and sustainable technology, it is important to ensure that the engineered nanomaterials and nanoenabled products that gain entry to the marketplace are safe and effective. Tools and methods are needed for regulatory purposes to allow rapid material categorization according to human health and environmental risk potential, so that materials of high concern can be targeted for additional scrutiny, while material categories that pose the least risk can receive expedited review. Using carbon nanotubes as an example, we discuss how data from alternative testing strategies can be used to facilitate engineered nanomaterial categorization according to risk potential and how such an approach could facilitate regulatory decision-making in the future.

There has been a conceptual shift in toxicological studies from describing what happens to explaining how the adverse outcome occurs, thereby enabling a deeper and improved understanding of how biomolecular and mechanistic profiling can inform hazard identification and improve risk assessment. Compared to traditional toxicology methods, which have a heavy reliance on animals, new approaches to generate toxicological data are becoming available for the safety assessment of chemicals, including high-throughput and high-content screening (HTS, HCS). With the emergence of nanotechnology, the exponential increase in the total number of engineered nanomaterials (ENMs) in research, development, and commercialization requires a robust scientific approach to screen ENM safety in humans and the environment rapidly and efficiently. Spurred by the developments in chemical testing, a promising new toxicological paradigm for ENMs is to use alternative test strategies (ATS), which reduce reliance on animal testing through the use of in vitro and in silico methods such as HTS, HCS, and computational modeling. Furthermore, this allows for the comparative analysis of large numbers of ENMs simultaneously and for hazard assessment at various stages of the product development process and overall life cycle. Using carbon nanotubes as a case study, a workshop bringing together national and international leaders from government, industry, and academia was convened at the University of California, Los Angeles to discuss the utility of ATS for decision-making analyses of ENMs. After lively discussions, a short list of generally shared viewpoints on this topic was generated, including a general view that ATS approaches for ENMs can significantly benefit chemical safety analysis.

Alternatives analysis (AA) is a method used in regulation and product design to identify, assess, and evaluate the safety and viability of potential substitutes for hazardous chemicals. It requires toxicological data for the existing chemical and potential alternatives. Predictive toxicology uses in silico and in vitro approaches, computational models, and other tools to expedite toxicological data generation in a more cost-effective manner than traditional approaches. The present article briefly reviews the challenges associated with using predictive toxicology in regulatory AA, then presents 4 recommendations for its advancement. It recommends using case studies to advance the integration of predictive toxicology into AA, adopting a stepwise process to employing predictive toxicology in AA beginning with prioritization of chemicals of concern, leveraging existing resources to advance the integration of predictive toxicology into the practice of AA, and supporting transdisciplinary efforts. The further incorporation of predictive toxicology into AA would advance the ability of companies and regulators to select alternatives to harmful ingredients, and potentially increase the use of predictive toxicology in regulation more broadly. Integr Environ Assess Manag 2017;13:915-925. © 2017 SETAC.

Background:Ten years ago, leaders in the field of toxicology called for a transformation of the discipline and a shift from primarily relying on traditional animal testing to incorporating advances in biotechnology and predictive methodologies into alternative testing strategies (ATS). Governmental agencies and academic and industry partners initiated programs to support such a transformation, but a decade later, the outcomes of these efforts are not well understood.Objectives:We aimed to assess the use of ATS and the perceived barriers and drivers to their adoption by toxicologists and by others working in, or closely linked with, the field of toxicology.Methods:We surveyed 1,381 toxicologists and experts in associated fields regarding the viability and use of ATS and the perceived barriers and drivers of ATS for a range of applications. We performed ranking, hierarchical clustering, and correlation analyses of the survey data.Results:Many respondents indicated that they were already using ATS, or believed that ATS were already viable approaches, for toxicological assessment of one or more end points in their primary area of interest or concern (26–86%, depending on the specific ATS/application pair). However, the proportions of respondents reporting use of ATS in the previous 12 mo were smaller (4.5–41%). Concern about regulatory acceptance was the most commonly cited factor inhibiting the adoption of ATS, and a variety of technical concerns were also cited as significant barriers to ATS viability. The factors most often cited as playing a significant role (currently or in the future) in driving the adoption of ATS were the need for expedited toxicology information, the need for reduced toxicity testing costs, demand by regulatory agencies, and ethical or moral concerns.Conclusions:Our findings indicate that the transformation of the field of toxicology is partly implemented, but significant barriers to acceptance and adoption remain. https://doi.org/10.1289/EHP1435

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