Alternative Testing Strategies for Nanomaterials: State of the Science and Considerations for Risk Analysis

Abstract

The rapid growth of the nanotechnology industry has warranted equal progress in the nanotoxicology and risk assessment fields. In vivo models have traditionally been used to determine human and environmental risk for chemicals; however, the use of these tests has limitations, and there are global appeals to develop reliable alternatives to animal testing. Many have investigated the use of alternative (nonanimal) testing methods and strategies have quickly developed and resulted in the generation of large toxicological data sets for numerous nanomaterials (NMs). Due to the novel physicochemical properties of NMs that are related to surface characteristics, the approach toward toxicity test development has distinct considerations from traditional chemicals, bringing new requirements for adapting these approaches for NMs. The methodical development of strategies that combine multiple alternative tests can be useful for predictive NM risk assessment and help screening-level decision making. This article provides an overview of the main developments in alternative methods and strategies for reducing uncertainty in NM risk assessment, including advantages and disadvantages of in vitro, ex vivo, and in silico methods, and examples of existing comprehensive strategies. In addition, knowledge gaps are identified toward improvements for experimental and strategy design, specifically highlighting the need to represent realistic exposure scenarios and to consider NM-specific concerns such as characterization, assay interferences, and standardization. Overall, this article aims to improve the reliability and utility of alternative testing methods and strategies for risk assessment of manufactured NMs.

Advancing Risk Analysis for Nanoscale Materials: Report from an International Workshop on the Role of Alternative Testing Strategies for Advancement

“…In vivo studies were performed mostly in rats, whereas in vitro experiments were mostly with human cells. More details about this effort are reported in Shatkin and Ong (2016) …”

“…In vivo studies were performed mostly in rats, whereas in vitro experiments were mostly with human cells. More details about this effort are reported in Shatkin and Ong (2016). (11) The relatively large and inestimable number of NM permutations (due to variations in chemical compositions, coating, charge, size, and other features) to be tested, the interference of NM with measurements in some existing standard protocols, (1) and the desire to reduce animal testing have, therefore, led to further ATS development for NM.…”

“…More details about this effort are reported in Shatkin and Ong (2016). (11) The relatively large and inestimable number of NM permutations (due to variations in chemical compositions, coating, charge, size, and other features) to be tested, the interference of NM with measurements in some existing standard protocols, (1) and the desire to reduce animal testing have, therefore, led to further ATS development for NM. Information from "nontesting" analytical methods, such as read-across or computational modeling (in silico), has been recently promoted (12) and there is a strong demand for such approaches.…”

The role of alternative testing strategies in environmental risk assessment of engineered nanomaterials

“…What is different is that in the course of evaluating ENMs, ATS have matured conceptually to incorporate both particulate as well as chemical behaviors, allowing for the generation of data for human health-related hazard assessment of ENMs. 2 At the same time the validity of ERA for ENMs is challenged. 24,29,30 However there is currently a gap in defining what "alternative" means in the ERA of ENMs.…”

“…Meanwhile, alternative testing strategies (ATS) with new organisms, endpoints and a span of variations in the scale and complexity of the tests have increasingly found usage in the nanotoxicological literature. 2,3 This is especially the case with high throughput screening (HTS) methods of in vitro testing and in silico simulation to study the mode of action of ENMs, whereby these methods have grown in popularity as ATS in nanotoxicology. Advocates of using HTS methods point to the staggering number of possible variations of ENMs that can be introduced to the market as well as the possible novel endpoints a test should evaluate.…”