The animal protection community questions the "genuine commitment" of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) in a June 7 response to the committee's draft five-year plan for reducing, refining and replacing the use of animals in toxicology testing.

In their comments, the stakeholders express concern about "the abbreviated number of methods reviewed by ICCVAM and accepted by federal agencies in recent years" and "the lack of direction, lack of specificity and apparent lack of commitment to a coherent process to achieve its stated goals."

The letter, addressed to William S. Stokes, DVM, director of the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), is signed by the Humane Society Legislative Fund, People for the Ethical Treatment of Animals, Physicians Committee for Responsible Medicine, Alternatives Research & Development Foundation and American Anti-Vivisection Society.

The groups' beef relates primarily to ICCVAM's perceived failure to observe its own principles as outlined in its draft five-year plan released in May (¹ Also see "ICCVAM Plans Next Steps Toward Reducing Animal Use In Toxicity Testing" - HBW Insight, 14 May, 2007., p. 5).

In particular, the stakeholders suggest that ICCVAM has not followed through on its objective "to make best use of existing resources and scientific expertise, maximize the efficiency of test method validation efforts and evaluations, minimize the duplication of effort and ensure an early exchange of information concerning test method validation."

The groups point to the fact that although the scientific committee of the European Center for the Validation of Alternative Methods (ECVAM) has "promptly" reviewed and endorsed multiple alternative methods based on ICCVAM's precedent, "ICCVAM has yet to even consider the great majority of alternative methods and/or testing strategies pioneered in the EU and endorsed by [ECVAM]."

For example, the local lymph node assay for skin allergy and Corrositex test for skin corrosion - for which ICCVAM issued final recommendations in March 1999 and December 2000 - were evaluated by its European counterpart in October 1999 and December 2000, respectively.

The Up-and-Down Procedure for acute oral toxicity, which received ICCVAM's final recommendation in March 2000, needed no statement from ECVAM, the stakeholders note, as the method has been accepted internationally since September 1998.

On the other hand, at least 13 tests endorsed by the European alternative methods center as far back as 1997 are still awaiting ICCVAM's review, the signatories indicate.

They claim that in numerous cases - when it has undertaken the review of an ECVAM-endorsed method - ICCVAM either has adopted a more conservative position on the method allowing for "only a modest reduction in animal use" or called for "substantial" additional work and information - in some cases a second peer review altogether.

"To increase the efficiency and effectiveness of ICCVAM," according to the animal protection community, "it is therefore imperative that ICCVAM establish formal bilateral/multilateral reciprocity agreements with ECVAM and other international validation authorities that require immediate and abbreviated reviews of alternatives that have been validated by other authorities."

The stakeholders also assert that "the draft plan provides no overview or systematic analysis of priority-setting for either methods under development or for planned activities."

Instead, it contains "virtually the same laundry list of methods under consideration" that emerged from a November 2006 meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (² Also see "SACATM Examines Federal Five-Year Plan For Non-Animal Toxicity Research" - HBW Insight, 11 December, 2006., p. 4).

The groups say they provided suggestions for establishing criteria and identifying needs in December 2006 after NICEATM/ICCVAM solicited public comment the month before on priority areas for the development and validation of alternative test methods. However, none of their suggestions have been incorporated into the draft plan, they say.

Priority Endpoints

The animal protection community says it is "gravely dissatisfied with NICEATM/ICCVAM's past and proposed future activities" in the area of acute toxicity.

The European Union, through its AcuteTox project, has brought together 35 regulatory, corporate, academic and other partners from 13 countries to develop an in vitro test strategy "sufficiently robust and powerful to completely replace in vivo testing of acute toxicity," the groups point out.

ICCVAM has lagged behind in its efforts, focusing more on the use of in vitro data to estimate in vivo starting doses and therefore minimize - rather than replace - the use of animals, the stakeholders say.

"ICCVAM and its member agencies must do more than organize workshops on 'humane endpoints,' further validate the same two in vitro assays as a dose-setting tool for mixtures and continue to trumpet the Up-and-Down Procedure to be regarded as a constructive participant in this important area."

Regarding dermal irritation, the stakeholders note ECVAM's recent endorsement of the Episkin skin irrtation test and suggest that "ICCVAM's review of this method should be both prompt and supportive - unlike its previous review of this method for corrosivity testing - and harmonized testing requirements should be forwarded to U.S. agencies before year-end."

The groups take issue with ICCVAM's position that the development and validation of alternative test methods for reproductive toxicity "will likely take longer than the five-year timeframe for [its] strategic plan," holding that the projection is no excuse for passivity, particularly as more animals are consumed in reproductive and developmental toxicity testing than for any other endpoint.

Recommendations also are offered in the areas of ocular irritation, biologics/vaccines, immunotoxicity, endocrine disruption, pyrogenicity and chronic toxicity/carcinogenicity.

The letter's signatories request that ICCVAM member agencies convene an annual meeting of senior science and program office staff, representatives from ECVAM and key U.S. stakeholders to revisit the research agenda for reducing, refining and replacing animal tests.

- Ryan Nelson (r.nelson@elsevier.com)

Federal Commitment To Reducing Animal Testing Called Into Question

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