The Scientific Advisory Committee on Alternative Toxicological Methods considered a proposed federal research priority ranking for the development of non-animal-based approaches to toxicity testing at a Nov. 30 meeting in Research Triangle Park, N.C.

The ranking is part of a push from the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) and the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) to establish a five-year plan that addresses the research, development, translation and validation of new and revised alternative assays.

The five-year plan was mandated by Congress in appropriations for the National Institutes of Health. Legislators have set a deadline of Nov. 15, 2007.

Tests that assess acute eye irritation and corrosion claim the ranking's top spots, followed by tests for biologics/vaccines, acute skin toxicity, acute systemic toxicity, chronic toxicity/carcinogenicity, reproductive/developmental toxicity, endocrine disruptors, neurotoxicity and immunotoxicity.

The list was developed from the input of federal agencies that were asked to prioritize based on their regulatory needs, said Marilyn Wind, PhD, vice chair of the Consumer Product Safety Commission.

Federal agencies are looking for tests "that are ripe for development and validation that could be an immediate payoff," Wind said. "We also need to [identify] areas where there may be methodologies that are up-and-coming but are going to take longer. ... All have to play into our strategic plan."

Wind noted that the experience of animals subjected to a particular testing method is another consideration. "Ocular came up on the top ... because of the pain and suffering" associated with that type of testing, she explained.

The panel's discussion likewise recognized the need for a research agenda that balances two compelling aims: validating tests that address the most pressing human health issues and reducing, refining or replacing tests that visit the greatest pain and distress on animals.

Questions of cost and availability of resources also emerged as components not to be overlooked.

Better Map Is Needed For Road Ahead - SACATM Rep

In a Dec. 7 interview, Martin Stephens, PhD, VP-Animal Research at the Humane Society, stressed that the government's strategic plan is still in its infancy.

Stephens was a member of SACATM; the Nov. 30 meeting was the last meeting following the expiration of his appointment.

A proposed list of research priorities is not yet a strategic plan, he said. Further discussion and justification of each of the priorities need to be developed going forward.

After acute eye irritation and corrosion, "the [rest of] ICCVAM's list seems to be more or less a laundry list of areas of toxicity. Whether they should all be perused as part of the strategic plan or some of them - that remains to be justified and argued," Stephens said.

"In an era of limited budgets there should be ... some rational basis for [research areas shown favor], whether that's the numbers of animals that would be impacted or the level of animal suffering that would be impacted, or agency priorities."

Up to this point, ICCVAM has been evaluating alternative tests that are submitted, rather than setting the research agenda, according to Stephens.

"We'd like to see ICCVAM have a more proactive role in setting priorities and helping to actually catalyze the research and development that needs to be done, not simply evaluate work that other people have accomplished," he said.

Kevin Renskers, VP-corporate safety & regulatory affairs for Takasago International Corp., maintains that the development of assays for the more complicated endpoints - such as carcinogenicity and reproductive and developmental toxicity - is of utmost importance.

However, the prognosis for these tests in the near-term is "poor," Renskers told "The Rose Sheet" Dec. 6.

"Those are going to be unbelievably complex to try to develop. ... People have been working on it for 15, 20 years," he said.

For example, acute eye irritation is an important test to validate, he noted, but devising an appropriate test is made difficult by the fact that the eye is a sophisticated system consisting of many different tissues.

SACATM member George DeGeorge, PhD, director of toxicology at MB Research Laboratories, contended that immunotoxicity and neurotoxicity represent the greatest challenges.

Stephens said he was pleased to see that vaccines and biologicals made the list of priorities "because that's an area where lots of animals are used and lots of unrelieved pain and distress occur. That area hasn't gotten a lot of attention."

Another factor to bear in mind, according to Stephens, is the extent to which public health is served by existing test methods. "Virtually all" of the toxicity areas are covered to some degree already, "endocrine disrupters being a glaring omission," he said.

The successful development of alternative methods relies heavily on the resources that can be brought to the problem. Industry has invested heavily in alternatives to animal testing, Renskers noted, but success has not come easily.

"When I was at Avon for over 10 years we funded a specific project at Johns Hopkins looking for alternatives for sensitization testing, for contact allergens. And a lot of good work was done. I left Avon almost 10 years ago and we still don't have any validated alternative."

Looming in the future for the cosmetic and fragrance industries is a European ban on animal testing for many of their products - set to go into effect in 2009.

To ensure that industry can comply with the ban by the deadline, the European Commission and industry joined forces in 2005 to form the European Partnership on Alternative Approaches to Animal Testing. The partnership issued an action plan in June 2006 laying out a plan to promote the validation of alternative tests (¹ Also see "EU Path To Alternative Methods: Labeling Guidelines, “3Rs” Plan Issued" - HBW Insight, 26 June, 2006., p. 8).

Industry insiders have suggested that alternative tests may not be developed in time to comply with the ban (² Also see "EU REACH, Seventh Amendment Issues Addressed By Lauder Exec" - HBW Insight, 6 November, 2006., p. 3).

But Stephens says the pace of alternative testing research has accelerated since the ban's announcement. Cooperation with key parties overseas - particularly with ICCVAM's European counterpart, the European Center for the Validation of Alternative Methods - is integral to moving forward, he suggested.

"We would like to see the U.S. play more of a role in the overall global effort to move toward non-animal methods. ICCVAM's strategic planning will become part of that process," Stephens concluded.

- Molly Laas

SACATM Examines Federal Five-Year Plan For Non-Animal Toxicity Research

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