Biochemical laboratory

“Ushering In a New Generation of Chemical Screening”

ToxCast-Robotic-ArmOn the EPA’s “Science” blog, Dr. Richard Judson explains how the agency is using automated chemical screening processes in its Endocrine Disruptor Screening Program:

Ushering In a New Generation of Chemical Screening | Science.




Photo: National Center for Advancing Translational Sciences (NCATS) ultra-high-throughput robotic screening system

alternative toxicity testing EPA Tox21
Tools for PCR amplification of DNA

US government program makes progress in non-animal toxicity testing

In the United States, the process of validating methods that reduce, refine or replace the use of animals in safety testing is coordinated by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). Established by Congress in 2000, the committee consists of representatives from each of the 15 federal regulatory and research agencies that “develops, or employs tests or test data using animals, or regulates on the basis of the use of animals in toxicity testing.”

ICCVAM just released its biennial progress report (covering 2012-2013), which includes summaries of its safety testing activities and its collaborations with other federal and international agencies and organizations.  Among the highlights:

  • The Committee moved two non-animal eye irritation testing methods closer to approval for regulatory use: “OptiSafe” will undergo a formal validation procedure managed by the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) which provides scientific support to ICCVAM; and the Kao Corporation submitted NICEATM’s test results on its Short Time Exposure test (STE) to the Organization for Economic Co-operation and Development (OECD) for formal validation.  (The OECD establishes chemical testing guidelines used by industries in the European Union).
  • Representatives of NICEATM and ICCVAM served on the management team for two EURL ECVAM validation studies: one using HepaRG (a human liver cell line) in an in vitro assay for liver toxicity, and another that validated and formally recommended (to the OECD) the direct peptide reactivity assay, an in vitro skin sensitization test.
  • ICCVAM helped to coordinate two international workshops aimed at reducing or replacing animal tests for vaccine development.
  • ICCVAM scientists collaborated with scientists from Procter & Gamble to develop open source software facilitates an integrated testing strategy that combines existing data from in vitro tests, chemical structure information, and computational models to predict the potency of a skin sensitizer; this information can be used to classify sensitization hazard without additional animal testing.
  • ICCVAM coordinated an international validation study of an in vitro method for detecting estrogenic activity, and began compiling an endocrine disruptor database of “high quality in vivo data” on 52 chemicals selected by the EPA; this can be used for validating in vitro methods.
  • With the FDA, ICCVAM developed industry guidelines on pyrogen testing and photosafety testing that highlight available in vitro methods and strategies for reducing animal use.

The report also summarizes inter-agency activities that support the development of alternative methods, such as “crowd-sourcing” data analysis and modeling through data challenges, and ICCVAM’s participation in international efforts to harmonize test guidelines and regulations.

For more information about ICCVAM and NICEATM, see their web site.

alternative toxicity testing

AOP workshop in Prague

At the 9th World Congress on Alternatives and Animal Use in the Life Sciences, the HTPC – along with Physicians Committee for Responsible Medicine (PCRM) – will co-sponsor an introductory workshop on Adverse Outcome Pathways, “AOPs 101: The How and Why of Development and Use,” on August 24, 2014 from 10 AM to 12 PM at Riverdance + Hibernia Conference Halls, Jurys Inn (next to the WC9 venue).

The curriculum will compliment several presentations on AOPs at the World Congress, and is intended for those scientists who are not yet familiar with the AOP concept but would like to learn to apply it to their own work, or would like to become involved in ongoing projects. An overview of “what, why, and how” will be given according to the latest existing international guidance, and experts will present case studies demonstrating AOP development and application.

A draft agenda is available here.

9th World Congress on Alternatives AOPs Meetings & Events
Rod photoreceptors (in green) within a "mini retina" derived from human iPS cells in the lab.

3D “mini retina” from stem cells

Scientists at Johns Hopkins University School of Medicine have cultivated functional 3-dimensional human retinal tissue in vitro from induced human pluripotent stem cells.  And in a significant technical advance over previous cultured retina studies, the resulting tissue exhibits mature cell differentiation and organization, and is able to detect light.

From the JHU press release:

(Lead investigator M. Valeria Canto-Soler) says that the newly developed system gives them the ability to generate hundreds of mini-retinas at a time directly from a person affected by a particular retinal disease such as retinitis pigmentosa. This provides a unique biological system to study the cause of retinal diseases directly in human tissue, instead of relying on animal models.

The system, she says, also opens an array of possibilities for personalized medicine such as testing drugs to treat these diseases in a patient-specific way. In the long term, the potential is also there to replace diseased or dead retinal tissue with lab-grown material to restore vision.

The study appears in last week’s issue of Nature Communications.

(To learn more about stem cells – especially about their potential in toxicity testing – see this stem cell “primer” on

stem cells toxicity testing alternatives

Unilever’s pathway-based, non-animal approaches to toxicity testing

A new article by scientists at Unilever, a corporate member of the HTPC, describes several areas of safety science in which they are using a pathway-based approach to replace traditional animal tests with a combination of human cell-based in vitro assays and computational models.  The article, “Toxicity testing – non-animal approaches and safety science” (by Fiona Reynolds, Carl Westmoreland and Julia Fentem) is included in the current issue of The Biochemist: “Replacement in Research” (Vol. 36(3), June 2014).

alternative toxicity testing HTPC members in the news pathway-based approaches

New Chemical Lists Information System (CheLIST)

The European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) released a new search tool, the Chemical Lists Information System (CheLIST), to help researchers determine if a chemical has ever been used in a research or validation study.  To develop and validate new non-animal alternative toxicity tests, researchers need to test a method’s performance with “reference” chemicals, or group of chemicals that have already been well-characterized.  The availability of extensive libraries of such reference chemicals – thoroughly characterized and tested – can speed up the development of non-animal toxicity test methods by providing many benchmarks against which the method’s findings can be compared.  There is undoubtedly a wealth of such chemical information scattered throughout published scientific literature and in various public and private databases, but these sources are difficult and time-consuming for researchers to access and interpret.  CheLIST is the EURL ECVAM’s first effort to consolidate chemical information in a central database with a user-friendly interface.  A Joint Research Centre (JRC) announcement describes CheList as being “in its infancy” at present, but notes that it will grow as its developers continue to search for and curate content.  To learn more about CheList, see the JRC’s announcement, or explore the database here.

databases toxicity testing alternatives

HTPC co-sponsors training in non-animal cosmetics testing

HTPC is co-sponsoring an important training program coordinated by the Institute for In Vitro Sciences (IIVS) and Humane Society International (HSI), to introduce Chinese scientists and regulators to non-animal methods for cosmetics testing.  As part of the program, scientists will receive hands-on training in state-of-the-art in vitro methods that replace traditional tests on rabbits and guinea pigs.

Organized through China’s Guangdong Inspection and Quarantine Bureau, HSI and the IIVS’s training aims to help fill this knowledge gap, making the option to move away from animal testing a practical alternative. China’s consumer and science sectors have much to gain from such a transition – animal toxicity tests are some of the least scientifically credible methods still in use. Indeed, when you consider the scale of uncertainty associated with some of these approaches, it’s astonishing that in so many countries and across so many sectors we’re still gambling consumer safety on methods that were devised in the 1940s.

Read more about the program in this article by Troy Seidle (HSI).

HTPC members in the news Meetings & Events