Needs and Strategies for Nanomaterial Safety Assessments

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Needs and Strategies for Nanomaterial Safety Assessments

Three recent papers address some of the challenges regulatory agencies and manufacturers face when it comes to nanomaterials and nanomaterial-containing products: one outlines the specific kinds of information most needed for risk assessment and management, and two describe approaches that could be standardized to make those assessments.

In Biological responses to engineered nanomaterials: Needs for the next decade, Murphy and co-authors briefly outline the growing uses and promise of nanomaterials for applications such as in medicine and clean energy, but they acknowledge that concerns about the environmental and health effects of release into the environment “need to be taken seriously, given our past history and experience with introducing supposedly benign materials into the environment.”

They ask, “what will we need to know about new nanomaterials that are to be produced on a large scale if we wish to avoid negative outcomes…,” and identify four overarching needs: (1) mechanistic information about the chemical and physical processes that occur within nanomaterials as they interact with other substances in the environment…, (2) real-time spatial and chemical information about the interaction of nanomaterials with living cells and organisms (the ‘nano-bio interface’), (3) mechanistic pathway studies that describe responses of various cell types and organisms, as they interface with nanomaterials, and (4) computational models of the nano-bio interface.

In Linking exposures of articles released from nano-enabled products to toxicology: An integrated methodology for particle sampling, extraction, dispersion, and dosing, authors Pal, et al. note that “Both risk assessors and industry are struggling with the limited population exposure data across the [life cycle] of [nano-enabled products] and the fact that most of the current data focus on pristine… nanomaterials rather than impacts associated with real world exposures…” They assert that a “standardized integrated methodology that can be used for sampling, extraction, dispersion, and dosing” is essential.

They illustrate one such approach in this paper using two case studies of ‘real world’ nanomaterials: printer toner powder, and aerosolized byproducts from incinerated polyurethane nanocomposites. Their process begins with extensive physico-chemical characterizations that include particle counting and sizing, thermophoretic and electrostatic precipitation, scanning electron microscopy, infrared spectroscopy, and mass spectrometry. The next step involves optimizing methods for particle extraction and quantification. Samples are then prepared and extensively characterized specifically for use in in vitro cellular toxicity tests. Next, the effective doses delivered to the cell in vitro are determined. The samples are now well characterized and standardized, and ready for testing in a variety of assays to assess cellular toxicity.

Comprehensive in vitro toxicity testing of a panel of representative oxide nanomaterials: First steps towards an intelligent testing strategy, is a study produced by scientists working for the European Commission’s Project MARINA, a program to develop and validate risk assessment and risk management methods for nanomaterials (NMs). As the authors note, currently “there are no standardized in vitro tests and experimental protocols suitable for NMs toxicity testing nor any guidelines for the extrapolation of the in vitro results to human health effects.” Furthermore, no one standard testing procedure would be adequate for the task. To account for the varieties and conditions of exposure, as well as the many physico-chemical properties (size, shape, surface area, etc.) and life cycle changes that occur with NMs, a battery of test methods is necessary.

The team assembled and evaluated one such battery, consisting of ten in vitro assays selected to assess cytotoxicity, embryotoxicity, epithelial integrity, cytokine secretion, and oxidative stress across 12 cell models representing 6 different organ systems (immune system, respiratory system, reproductive organs, kidney, and embryonic tissues). To validate the battery, the investigators selected two forms each of three commercially-relevant NMs: zinc, silicon, and titanium oxides.

The battery of tests revealed that:

  • macrophages were the most sensitive cell type after short-term exposures,
  • epithelial integrity was most significantly affected by zinc oxide, but not by silicon or titanium oxides, after longer term exposures,
  • titanium oxides were classified as weakly embryotoxic by the embryonic stem cell test, but zinc and silicon tested as non-embryotoxic, and
  • results made it possible to construct a hazard ranking: zinc oxides>silicon oxides>titanium oxides.

The results support an intelligent testing strategy (ITS) approach for assessing nanotoxicity that includes: (1) biologically relevant cell systems representing multiple target organs, (2) reliable and relevant assays, including complex methods such as the embryonic stem cell test, and (3) thorough physico-chemical characterization of NMs for structure-activity modeling.

Articles cited:
Murphy, C.J., Vartianian, A.M., Geiger, F.M., et al. (2015). Biological responses to engineered nanomaterials: Needs for the next decade. ACS Central Sci. 1, 117-123.

Pal, A.K., Watson, C.Y., Pirela, S.V., et al. (2015). Linking exposures of particles released from nano-enabled products to toxicology: An integrated methodology for particle sampling, extraction, dispersion, and dosing. Toxicol. Sci. 146, 321-333.

Farcal, L., Andon, F.T., Di Cristo, L., et al. (2015). Comprehensive in vitro toxicity testing of a panel of representative oxide nanomaterials: First steps towards an intelligent testing strategy. PLOS One: DOI:10.1371/journal.pone.0127174

Posted: October 23, 2015

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