The Honorable Carol Browner
Administrator
U.S. Environmental Protection Agency
401 M Street, SW
Washington, DC 20460

May 10, 1999

Dear Administrator Browner:

We write with regard to certain substantive, procedural, and research issues relating to the High Production Volume (HPV) Chemical Challenge Initiative, as outlined below.

By way of background, though our organizations come to this issue with different perspectives, we agree on three central points. First, we believe that the Initiative's objective - assuring the existence and public availability of basic safety information on widely used chemicals - is important. Second, we agree that it is also important to assure that any use of animals in toxicity testing is minimized to the extent feasible (and that any animal testing that does occur is conducted as humanely as possible). Third, we are convinced that the heightened attention being paid to toxicity testing issues as a result of the Initiative represents an unusual opportunity to increase the pace of progress in developing and validating non-animal alternatives.

1. Issues Relating to Generation of Additional Test Data. We recognize that the Initiative relies upon procedures and protocols developed for the Screening Information Data Set (SIDS) program of the Organisation for Economic Co-operation and Development (OECD). Some aspects of the SIDS program go beyond the scope of the US HPV Challenge Initiative, and are likewise beyond the scope of this letter (as are issues of post-Challenge activities). However, for many aspects of the Initiative, there are multiple OECD protocols and/or test-design options within existing OECD protocols. Careful selection among these protocols or options can significantly reduce animal use.

Accordingly, we request that EPA clearly state its expectations about which particular OECD protocols and test-design options are to be employed in any new testing conducted under the Initiative, particularly with regard to the issues identified below. Although the HPV Challenge Initiative is a voluntary program, it is clear that EPA's recommendations on how to proceed carry significant weight with the chemical producers who have made, or are considering, sponsorship commitments.

In each instance, these expectations would apply where existing data and available non-animal alternatives such as structure/activity relationship analysis are not adequate, so that additional test data will be generated under the HPV Challenge Initiative.

Category-based approaches and structure-activity analyses are likely to become more and more important in risk assessment as our knowledge of chemical hazards increases. EPA should not miss the opportunity to strongly encourage and support the use of category-based approaches and structure-activity relationship analysis as far as possible and practicable. In addition, EPA should encourage the use of existing data and should work with other regulatory agencies in the Federal Government to identify and make use of existing data bases.

i. Acute Toxicity. Under the Challenge Initiative, the classic LD-50 test (OECD protocol 401) will not be used in the generation of new data for the HPV initiative. Any test data on acute toxicity deemed necessary are to be generated using the up-and-down test (OECD protocol 425).

ii. Combined Protocols. Under the Challenge Initiative, any test data deemed necessary on repeat-dose/reproductive/developmental toxicity are to be generated using the combined protocol (OECD protocol 422), rather than the separate repeat dose, reproductive, and developmental toxicity protocols (OECD protocols 407, 414, and 415 respectively). Under the Challenge Initiative, any test data deemed necessary on reproductive and/or developmental toxicity are to be generated using the combined protocol (OECD protocol 421), rather than the separate reproductive and/or developmental toxicity protocols (OECD protocols 414 and 415 respectively).

iii. Genetic Toxicity. Under the Challenge Initiative, any test data deemed necessary on genetic toxicity are to be generated using in vitro methods (e.g. OECD protocol 473) rather than in vivo methods (e.g. OECD protocol 474).

iv. Test Species. Under the Challenge Initiative, rabbits, guinea pigs, birds, and other animals are not to be used in additional testing (though existing data on these species may be used in lieu of new testing on other species).

v. Terrestrial Ecotoxicity. Under the Challenge Initiative, no data on terrestrial toxicity (including effects on birds) are to be generated; evaluation of possible need for such data are to be deferred until exposure information subsequently becomes available.

vi. Route of Administration. Under the Challenge Initiative, dermal testing is not to be conducted.

We also strongly urge that the Agency affirmatively distribute these explicit recommendations to the 190 companies and consortia that have registered as sponsors so far, and to others as they sign up.

2. Issues Relating to Test Plan Publication and Opportunity for Public Feedback. As you know, the Framework for the Initiative provides that test plans for specific chemicals (or categories) will be made publicly available via the Internet, prior to initiation of testing. We ask that EPA state its expectation that test plans will be posted at least 90 days in advance of the scheduled initiation of any new testing (with the public requested to post comments within 30 days of posting of the plan) (120 days and 60 days for posting and public comment, respectively, for test plans involving categories). This clarification of the Framework is needed to ensure adequate time for the public to review plans and to draw attention to any previously overlooked data that might reduce the need for further testing.

3. Research into Non-Animal Test Methods. Finally, as noted above, we believe that the heightened attention being paid to toxicity testing issues as a result of the Initiative represents an unusual opportunity to increase the pace of developing and validating non-animal alternatives over the longer term. We strongly urge EPA to redirect funds in the Office of Research and Development's budget toward alternatives to animal testing that may be relevant during or after the HPV Initiative. Specifically, we would suggest that funds be provided for two areas affecting animal welfare. The first would be an in vitro program aimed at replacing whole animal methods currently required for legislative mandates affecting the EPA and the SIDS program. Since information from non-lethal experiments is clearly preferable from a humanitarian perspective and is of considerable scientific value, the second research program would address the development of appropriate humane endpoints for regulatory toxicology that would eliminate animal pain and distress.

We appreciate your attention to these issues, and would be happy to meet with you or members of your staff to discuss them.

Very truly yours,