Tag Archives: U.S. ToxCast program

An upcoming alternate testing strategies (ATS) for nanomaterials workshop and the quest to reduce animal testing

It’s too late to announce a call for poster abstracts or travel awards but that still leaves the possibility of attending a September 15-16, 2014 Workshop to Explore How a Multiple Models Approach can Advance Risk Analysis of Nanoscale Materials in Washington, DC. In a July 9, 2014 Nanowerk Spotlight article,, Jo Anne Shatkin (President, Vireo Advisors) and Lorraine Sheremeta (Assistant Director, Ingenuity Lab, University of Alberta) tout the workshop in the context of describing new approaches to nanotoxicology research (Note: A link has been removed),

Engineered nanoscale materials (ENM or ‘nanomaterials’) offer the potential to create safer and more effective products through the use of smaller quantities of improved performance materials. Currently nanomaterials are used to improve the performance of life-saving drugs and medical technologies, to make renewable energy more efficient, to make value added products from industrial waste streams, to improve food, packaging, to lightweight materials used in transportation systems, and to improve many of the personal care products that we use every day. Nanomaterial manufacture and use is expected to increase over the coming years and despite the widespread use of nanomaterials in a variety of consumer products, we are only beginning to understand the impacts of these emerging materials on our health and the environment. To this end, the University of Alberta’s Ingenuity Lab is collaborating with the Society for Risk Analysis to evaluate the potential to use alternative test strategies (ATS) to improve our ability to assess nanomaterial toxicity and environmental impact.

Shatkin and Sheremeta describe toxicology tests and explain the importance of refining and improving these tests (from the article),

Standard in vivo toxicology test methods that depend heavily on the use of animals have long been used to assess chemical safety. [emphasis mine*] Existing and novel in vitro and in silico test methods provide important alternatives to in vivo animal testing for chemicals and potentially for ENM. Genotoxicity tests, for example, are used to assess the mutagenic potential of chemicals or nanomaterials in the replication of DNA in cells. Driven in part by increasing market and regulatory requirements for safer and more sustainable products, large international infrastructure has developed for creating, testing and validating in vitro test methods, and its use is expanding to chemical and nanomaterial assessment (NSF, 2007). The goals of reducing, refining and replacing animal testing (the commonly cited ‘three Rs’) – resonate with key and diverse stakeholders including animal rights groups, the bioethics community, the pharmaceutical industry, regulatory agencies and the broader public. [emphasis mine*]

Despite nearly a decade of effort in the conduct toxicology and exposure research to inform the assessment of health and environmental risks of nanomaterials, major gaps remain in the ability to understand and quantify risks. While there is now a large body of published data on carbon nanotubes and metal oxide nanoparticles, concern has been raised that speculation about nanomaterial risk has hardened into an assumption that there are ‘as-yet-to-be-discovered risks’ that we must identify and manage (Maynard, 2014) that demands extensive testing.

The authors describe ATS (alternative test strategies) in greater detail,

ATS approaches are regarded by many to have the potential for rapid screening of large numbers and types of materials. They can include a breadth of techniques including high throughput screening methods (HTS), high content screening, computational approaches, toxicogenomics, cell-based methods, in vitro assays and non-mammalian whole animal models. The emergence of ATS raises questions about how the results of these methods may be used for assessing the potential risks of ENM. For instance, ATS could be used in combination in a multiple models approach to evaluate new ENM in a number of rapid assays and compare with well-studied substances using in vivo testing; thereby identifying ENM for additional testing in a more strategic fashion than is possible through conventional testing approaches.

They also describe the current state of affairs with ATS,

In the United States, the U.S. ToxCast program has, as part of their 21st century toxicity screening program (NRC, 2007), tested 29 NMs with 62 in vitro test methods (Wang et al. 2013). Many researchers, including several from the University of Alberta, have proposed and developed ATS to include a variety of methods, some which are standardized for chemicals, and others which take advantage of developments including advanced biological mechanistic understanding, genomics, metabolomics, automation and informatics. However, these existing as well as emerging ATS have a short history with nanomaterials, and have not yet proven to be reliable for quantitative estimation of ENM risk. Still, several international efforts have developed ATS that have potential to be used for screening purposes, and to guide further testing priorities for regulatory decision making. The goal of the September [2014] workshop by the Society for Risk Analysis is to explore ways in which distinct ATS may be used for screening and prioritizing the need for more extensive testing of novel ENM.

The parties (including the authors of the article) involved in developing this risk workshop are listed, also mentioned are members of the international testing scene,

Lori Sheremeta, the Assistant Director of Ingenuity Lab in Edmonton Alberta and past Chair of the Society for Risk Analysis (SRA) Emerging Nanoscale Materials Specialty Group (ENMSG), is collaborating with U.S.-based nanomaterials risk expert Jo Anne Shatkin (an SRA Councilor and co-founder of the SRA ENMSG), Environment Canada, Health Canada, the SRA ENMSG and others on a Pilot Project with the Organization for Economic Co-operation and Development (OECD) Working Party on Manufactured Nanomaterials (WPMN) to develop a report on the State of the Science for ATS for nanomaterials, catalogue of existing and emerging ATS methods in a database; and develop a case study to inform workshop deliberations and expert recommendations.

There are many international efforts to develop, as well as to validate and standardize, these methods for chemicals, including organizations such as the US National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (ICCVAM), the European Union Reference Laboratory European Centre for the Validation of Alternative Methods (EURL ECVAM), the Japanese Center for the Validation of Alternative Methods (JacVAM), the Korean Centre for the Validation of Alternative Methods (KoCVAM) and the OECD. There is wide recognition that the diversity of NMs renders it impractical to use traditional animal testing to evaluate safety, hence there is significant interest in assessing the performance of both existing and emerging alternative testing strategies for NMs. Further, the EU directive REACH (Directive 2006/121/EC) requires replacing in vivo testing, and there is widespread popular agreement about the desire to limit animal testing. Finally, there is a need for more biologically informative toxicology methods (Hartung, 2010; Silbergeld et al, 2011; Landsiedel et al, 2009).

A list of the workshop objectives is offered  in the article,

The main objectives of the workshop are to:

assess the state of the science on HTS and ATS from a ‘multiple models’ perspective to identify areas of common findings from differing approaches, areas of greatest uncertainty, and priorities for follow up in applied research toward risk assessment of ENM;
evaluate the ability to use data from ATS/HTS methods for screening purposes – combining suites of assays and comparing well-studied substances to novel ones;

assess the ability to use a suite of ATS methods to amplify the Weight of Evidence;

characterize uncertainty associated with predictive relationships and propose strategies to address uncertainties;

elicit the perspectives of diverse stakeholders about the use of HTS/ATS for screening purposes in risk analysis of ENM; and

develop a set of recommendations for these alternative approaches to become more widely adopted for environmental, health and safety decision making about ENM across the product life cycle. The output of the workshop holds potential for transformation through risk screening approaches that promote safer and more sustainable material and technology development.

You can find more about the September 15-16, 2014 Workshop to Explore How a Multiple Models Approach can Advance Risk Analysis of Nanoscale Materials in Washington, DC here.

The text in the article is a bit rough. Some of the ideas and topics don’t follow each other logically. So, be prepared to spend a little time reading, Happily, there are references included with the article.

I last mentioned Jo Anne Shatkin here in the context of a 2013 paper on alternative test strategies (ATS) in an Aug. 22, 2013 posting. I think the most recent mention of Lorraine Sheremeta here is in a Jan. 11, 2010 posting about Canada, nanotechnology, and food.

Final note, I am hoping to get some more information about the workshop and ATS scene from Lorraine Sheremeta to be published in a subsequent posting.

* I added the emphases at 0830 hours PDT July 10, 2014.