Approaches to Develop Alternative Testing Strategies to Inform Human Health Risk Assessment of Nanomaterials

Abstract

The development of alternative testing strategies (ATS) for hazard assessment of new and emerging materials is high on the agenda of scientists, funders, and regulators. The relatively large number of nanomaterials on the market and under development means that an increasing emphasis will be placed on the use of reliable, predictive ATS when assessing their safety. We have provided recommendations as to how ATS development for assessment of nanomaterial hazard may be accelerated. Predefined search terms were used to identify the quantity and distribution of peer-reviewed publications for nanomaterial hazard assessment following inhalation, ingestion, or dermal absorption. A summary of knowledge gaps relating to nanomaterial hazard is provided to identify future research priorities and areas in which a rich data set might exist to allow ATS identification. Consultation with stakeholders (e.g., academia, industry, regulators) was critical to ensure that current expert opinion was reflected. The gap analysis revealed an abundance of studies that assessed the local and systemic impacts of inhaled particles, and so ATS are available for immediate use. Development of ATS for assessment of the dermal toxicity of chemicals is already relatively advanced, and these models should be applied to nanomaterials as relatively few studies have assessed the dermal toxicity of nanomaterials to date. Limited studies have investigated the local and systemic impacts of ingested nanomaterials. If the recommendations for research prioritization proposed are adopted, it is envisioned that a comprehensive battery of ATS can be developed to support the risk assessment process for nanomaterials. Some alternative models are available for immediate implementation, while others require more developmental work to become widely adopted. Case studies are included that can be used to inform the selection of alternative models and end points when assessing the pathogenicity of fibers and mode of action of nanomaterial toxicity.

Nano-Inclusions Applied in Cement-Matrix Composites: A Review

“…To this end, many researchers have remarked the convenience of standardising the nanomaterial itself [214,217], as well as the protocols of both the experiments and long-term studies [218,219]. …”

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

“…Including data mining as part of an integrated testing system can help screen and identify NM, pathways, endpoints, and data gaps of particular concern. A recent review of published studies on NM revealed that most toxicity experiments have focused on pulmonary effects, particularly inflammation, oxidative stress, cytotoxicity, and uptake and distribution, with relatively few studies on fibrosis, genotoxicity, and carcinogenicity (Stone et al, 2016). (19) That analysis also revealed information gaps for ingestion and dermal NM exposures.…”

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

“…In human nanotoxicology, ATS is a move towards anticipatory, generic and predictive hazard assessment without the reliance on assessing ENMs through whole organism animal testing. 3 However, for ATS in nanoecotoxicology, testing is diverging into both more predictive, anticipatory testing and more complex, realistic assessments. This divergence is occurring without clearly delineating the various approaches or overtly comparing across them.…”

“…This was discussed at a Society for Risk Analysis (SRA) workshop entitled "Nano Risk Analysis II" in Washington, D. C. (U.S.) in September 2014, with the overarching theme of how to advance risk analysis of ENMs, 3,10 and such discussion serves as the point of departure for this paper. Here we aim to describe and define the use of ATS for ENMs, and to discuss the future role of ATS in environmental risk science as applied to 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.…”