[Senate Report 106-496]
[From the U.S. Government Publishing Office]



                                                       Calendar No. 946
106th Congress                                                   Report
                                 SENATE
 2d Session                                                     106-496

======================================================================



 
                    ICCVAM AUTHORIZATION ACT OF 1999

                                _______
                                

   October 11 (legislative day, September 22), 2000.--Ordered to be 
                                printed

                                _______
                                

   Mr. Jeffords, from the Committee on Health, Education, Labor, and 
                    Pensons, submitted the following

                              R E P O R T

                         [To accompany S. 1495]

    The Committee on Health, Education, Labor, and Pensions, to 
which was referred the bill (S. 1495) to establish, wherever 
feasible, guidelines, recommendations, and regulations that 
promote the regulatory acceptance of new and revised 
toxicological tests that protect human and animal health and 
the environment while reducing, refining, or replacing animal 
tests and ensuring human safety and product effectiveness, 
having considered the same, reports favorably thereon with an 
amendment in the nature of a substitute and recommends that the 
bill (as amended) do pass.

                                CONTENTS

                                                                   Page
  I. Background and need for the legislation..........................1
 II. Legislative history and committee action.........................4
III. Cost estimate....................................................5
 IV. Application of law to the legislative branch.....................5
  V. Regulatory impact statement......................................5
 VI. Section-by-section analysis......................................5

          I. BACKGROUND AND NEED FOR THE LEGISLATION OVERVIEW

    Toxicological testing to assess the safety substantiation 
and/or efficacy of products and chemical components of products 
has undergone substantial change in the past two decades. Many 
toxicity tests were developed more than fifty years ago and 
rely heavily on the use of animals. However, members of the 
regulated industries and the nonprofit sector have invested in 
research and development of more predictive methods that 
replace, refine or reduce the use of animals, while providing 
sound scientific results.
    A section of the 1993 NIH Revitalization Act (Public Law 
No. 103-43) created a new mandate for the National Institute of 
Environmental Health Sciences specifically as follows:

SEC. 1301. APPLIED TOXICOLOGICAL RESEARCH AND TESTING PROGRAM.

           applied toxicological research and testing program
    SEC. 463A. (a) There is established within the Institute a program 
for conducting applied research and testing regarding toxicology, which 
program shall be known as the Applied Toxicological Research and 
Testing Program.
    (b) In carrying out the program established under subsection (a), 
the Director of the Institute shall, with respect to toxicology, carry 
out activities--
          (1) to expand knowledge of the health effects of 
        environmental agents:
          (2) to broaden the spectrum of toxicology information that is 
        obtained on selected chemicals;
          (3) to develop and validate assays and protocols, including 
        alternative methods that can reduce or eliminate the use of 
        animals in acute or chronic safety testing;
          (4) to establish criteria for the validation and regulatory 
        acceptance of alternative testing and to recommend a process 
        through which scientifically validated alternative methods can 
        be accepted for regulatory use.

    To fulfill the mandate, in 1994 the National Institute of 
Environmental Health Sciences (NIEHS) established the ad hoc 
Interagency Coordinating Committee for the Validation of 
Alternative Methods (ICCVAM). The initial goal of the ICCVAM 
was to draft to report (NIH Publication No. 97-3981) to 
recommend criteria and processes for validation and regulatory 
acceptance of toxicological testing methods, that would be 
useful to the regulatory agencies, scientific community, 
regulated industry, animal protection advocates and other 
stakeholders.
    The following federal regulatory or research agencies, with 
input through public meetings and comments, drafted the 
``Validation and Regulatory Acceptance of Toxicological 
Methods--A Report of the ad hoc Interagency Coordinating 
Committee for the Validation of Alternative Methods'': Agency 
for Toxic Substances and Disease Registry; Consumer Product 
Safety Commission; Department of Agriculture; Department of 
Defense; Department of Energy; Department of the Interior; 
Department of Transportation; Environmental Protection Agency; 
Food and Drug Administration; National Institute for 
Occupational Safety and Health; National Institutes of Health; 
National Cancer Institute; National Institute of Environmental 
Health Sciences; National Library of Medicine; and Occupational 
Safety and Health Administration.
    After publication of the report, the ad hoc ICCVAM moved to 
standing status under the NIEHS of the NIH under the National 
Toxicology Program Interagency Center for the Evaluation of 
Alternative Toxicological Methods. Fifteen Federal regulatory 
and research agencies have continued to meet, with advice from 
a Scientific Advisory Committee, to assess the validation of 
new, revised and alternative toxicological methods. Since then, 
two methods have undergone rigorous assessment and are deemed 
scientifically valid and acceptable. One, Corrositex, is a 
replacement for animal-based dermal corrosivity for some 
chemicals. The other, the Local Lymph Node Assay, is a 
reduction and refinement of animal use method for the skin 
irritation endpoint. The open public process for comment, input 
by interested stakeholders and the continued commitment by the 
Federal agencies has led to the ICCVAM's success. It has set a 
new coordinated review process for rigorous scientific 
assessment of the validation of new, revised, and alternative 
toxicological test methods that duly considers reducing, 
refining or replacing the use of animals.
    However, the ICCVAM is not a permanent standing committee. 
It could be dismantled by a new director of the National 
Toxicology Program at NIEHS or by the administration. Millions 
of dollars are used for research, development and validation 
studies for new and revised and alternative toxicological 
methods. ICCVAM provides a coordinated entity for streamlining 
a process that would otherwise require a developer or 
manufacturer of a toxicological test method to attempt to 
obtain acceptance on an agency by agency basis. ICCVAM also 
provides due consideration of good science that can reduce, 
refine or replace the use of animals in toxicological testing. 
It is imperative that this standing committee become a 
permanent standing committee.

                summary of the iccvam authorization act

Section 3. Interagency Coordinating Committee for the Validation of 
        Alternative Methods

    Section 3 of the legislation details the program and branch 
within the Government where the ICCVAM will reside. It also 
details the purposes of the ICCVAM; to facilitate crossagency 
reviews of test methods; provide a forum to discuss individual 
agency efforts; cultivate scientific expertise from outside of 
the Federal Government; ensure that new and revised 
toxicological test methods are scientifically validated; and 
provide strong consideration for the reduction, refinement and 
replacement of animals, wherever feasible, in toxicological 
test methods.
    Section 3 details the composition of the ICCVAM, providing 
some flexibility to ensure that Federal regulatory or research 
agencies not explicitly named in the legislation may 
participate on the ICCVAM in the future.
    Section 3 also details the composition of a Scientific 
Advisory Committee, under the National Institute of 
Environmental Health Sciences of the National Institute of 
Health under the National Toxicology Program Interagency Center 
for the Evaluation of Alternative Toxicological Methods. The 
Scientific Advisory Committee will be subject to the Federal 
Advisory Committee Act. Its membership, selected by the 
Secretary of Health and Human Services, shall consist of 
representatives from various regulated industries and national 
animal protection organizations. It may also include 
representation from academic institutions, state government 
agencies, international regulatory bodies, or corporations 
developing or marketing new or alternative test methods.
    Section 3 delineates the responsibilities of the ICCVAM. 
The ICCVAM will review and evaluate new, existing and 
alternative test methods, including coordinating the technical 
review of such methods, of interagency interest. It will also 
facilitate interagency and international harmonization of test 
protocols that encourage the reduction, refinement or 
replacement of animal tests, as appropriate.

Section 4. Federal Agency Action

    Section 4 sets a deadline of not later than 180 days for 
the individual Federal agencies to provide a detailed response 
to the ICCVAM regarding its recommendation. This agency 
response will identify and forward to the ICCVAM appropriate 
regulations or guidelines encouraging animal-based toxicity 
testing for which the ICCVAM recommendation may be added or 
substituted. The Federal agencies would also be required to 
actively promote the development and use of alternative to 
animal test methods, where appropriate, if such test methods 
are effective for generating data in an amount and of a 
scientific value that is at least as equivalent as the data 
generated from its existing tests. Each Federal agency also 
must ensure that any new or revised or alternative test method 
(including animal test) and tests that refine, reduce or 
replace animal tests, must be validated prior to encouraging, 
recommending, or requiring the use of the test methods. This 
requirement ensures that the same standard of scientific 
validity is applied to all new, revised, and alternative test 
methods. Each Federal agency or its specific regulatory unit 
must adopt the ICCVAM recommendation, unless the agency 
determines that one of the four criteria listed in the act 
exists for rejection of the test method by that agency.

Section 5. Application

    Section 5 provides a clear exemption for research, 
including medical research and research using biotechnology 
techniques. The bill covers toxicological test methods used to 
meet regulatory requirements, regulations, recommendations or 
statutes. Toxicological test methods generate information 
regarding the ability of a chemical or agent to produce a 
specified biological effect under specified conditions. (NIH 
Report No. 97-3981)
    Section 5 also provides explicit assurance that each 
Federal agency and regulatory body has final authority for 
incorporating the ICCVAM recommended test method, in the manner 
determined to be appropriate by such agency or body, into their 
recommendations, requirements, regulations and for addressing 
methods mandated by congressional statute, when testing has 
already transpired to meet regulatory needs.
    Section 5 ensures that nothing in this act requires that a 
manufacturer that is not required to perform animal 
toxicological testing to perform such tests. Finally, section 5 
clarifies that as new, revised, or alternative test methods 
become approved, this act does not require that regulated 
industries generate new data for that same endpoint.

              ii. legislative history and committee action

    On September 20, 2000, the committee held an executive 
session to consider S. 1495. Senators DeWine and Kennedy 
offered an amendment in the nature of a substitute that was 
accepted without objection. Senate bill 1495, as amended, was 
adopted by voice vote.

                           iii. cost estimate

    Due to time constraints the Congressional Budget Office 
estimate was not included in the report. When received by the 
committee, it will appear in the Congressional Record at a 
later time.

            iv. application of law to the legislative branch

    Section 102(b)(3) of Public Law 104-1, the Congressional 
Accountability Act (CAA), requires a description of the 
application of this bill to the legislative branch. This bill 
does not amend Federal laws, and therefore does not impact the 
legislative branch.

                     V. REGULATORY IMPACT STATEMENT

    The committee has determined that there will be minimal 
increases in the regulatory burden imposed by this bill.

                    VI. SECTION-BY-SECTION ANALYSIS

Section 1. Short title

    This Act may be cited as the ``ICCVAM Authorization Act of 
2000.''

Section 2. Definition

    This section defines an ``alternative test method'' to 
include new and revised methods that reduce, refine or replace 
the use of animals in toxicological testing. This section also 
defines an ``ICCVAM test recommendation'' as a summary report 
characterizing the results of a scientific expert peer review 
of a test method.

Section 3. Interagency Coordinating Committee on the Validation of 
        Alternative Methods

    Subsection (a). In General. ICCVAM would become a permanent 
standing committee under the National Toxicology Program 
Interagency Center for the Evaluation of Alternative 
Toxicological Methods under the National Institute of 
Environmental Health Sciences of the National Institutes of 
Health.
    Subsection (b). Purposes. ICCVAM will streamline Federal 
agency consideration of test method review; utilize scientific 
expertise from outside the Federal Government; ensure that new 
and revised and alternative test methods are validated; and, 
wherever feasible, reduce, refine, or replace the use of 
animals.
    Subsection (c). Composition. ICCVAM will be comprised of 
representatives from 15 Federal regulatory and/or research 
agencies and any other Federal agency not currently part of the 
existing entity that meets the criteria--namely, that the 
agency develops or employs tests or test data using animals or 
regulates on the basis of the use of animals in toxicity 
testing.
    Subsection (d). Scientific Advisory Committee. ICCVAM will 
receive advice from a Scientific Advisory Committee (SAC) 
selected under the National Toxicology Program Interagency 
Center for the Evaluation of Alternative Toxicological Methods 
under the National Institute of Environmental Health Sciences 
of the National Institutes of Health. The SAC will be a Federal 
Advisory Committee, subject to the provisions of the Federal 
Advisory Committee Act. It will include representatives with 
expertise in the development or evaluation of new, revised, or 
alternative test methods from various sectors of the regulated 
industries, national animal protection organizations, and other 
representatives chosen by the National Institute of 
Environmental Health Sciences from academia, State government 
agencies, international regulatory bodies, or corporations 
developing or marketing new or revised or alternative test 
methods.
    Subsection (e). Duties. ICCVAM will review and evaluate new 
and revised and alternative test methods. ICCVAM will 
coordinate the necessary technical reviews for these proposed 
methods. ICCVAM will facilitate communication regarding 
interagency and international harmonization of test methods 
that reduce, refine or replace animal tests. ICCVAM will 
facilitate and provide guidance on the development of 
validation criteria, studies and processes for new and revised 
and alternative test methods and will help promote the 
acceptance and awareness of such scientifically validated test 
methods by Federal agencies and other stakeholders. ICCVAM will 
submit its test recommendations to each appropriate Federal 
agency providing specific identification of the guidelines, 
recommendations, or regulations for each test, battery of 
tests, test screen or endpoint reviewed by the ICCVAM that may 
be appropriate for scientific improvements, while seeking 
(where feasible) to reduce, refine or replace the use of 
animals for a test currently required or recommended by the 
agency. The ICCVAM will actively review and evaluate petitions 
from the public that recommend alternatives and provide valid 
scientific evidence that the alternative works for carrying out 
the regulatory mandate and identify a specific regulation, 
recommendation or guideline for integrating the alternative. 
The ICCVAM recommendations and the agency's responses will be 
made available to the public. The entity will prepare an annual 
report to be made available to the public on its progress in 
promoting and assessing the validation of new, revised and 
alternative toxicological test methods.

Section 4. Federal agency action

    Subsection (a). Identification of Tests. Each Federal 
agency with programs requiring toxicological testing, within 
180 days of receiving an ICCVAM recommendation, will provide a 
response to ICCVAM. The response will include identifying test 
requirements in regulations or guidelines that currently 
require, recommend or encourage animal tests that could be 
changed by the ICCVAM recommendation. The agency will forward 
the identification of these tests to the ICCVAM.
    Subsection (b). Alternatives. Each Federal agency shall 
actively promote and encourage the development of test methods 
that reduce, refine, or replace animal tests. The alternative 
test methods shall provide data that is of at least equal 
scientific value to the animal tests.
    Subsection (c). Test Validation. Each Federal agency shall 
ensure that any new or revised animal or alternative test 
method must be validated--deemed reliable, relevant and 
reproducible--prior to requiring, recommending or encouraging 
use of the test.
    Subsection (d). Review. Each Federal agency must respond, 
in writing within 180 days, to the ICCVAM regarding its 
recommendation.
    Subsection (e). Recommendation Adoption. Each Federal 
agency or its regulatory unit or units, shall adopt the ICCVAM 
recommendation unless it can substantiate refusal of the method 
by the following criteria. These criteria include: lack of 
biological relevance to the agency's regulatory goal; the data 
is not of a scientific value at least equivalent to data 
generated by current test methods; the agency does not regulate 
the specific endpoint or class of chemical recommended by the 
ICCVAM for the test method; or the agency deems the method 
unacceptable specific to its congressional mandate.

Section 5. Application

    Subsection (a). Application. This Act applies only to 
toxicological testing. It does not apply to research, including 
medical research or research using biotechnology techniques.
    Subsection (b). Use of Test Methods. Federal agencies shall 
retain final authority for incorporating the recommended test 
method in the manner determined to be appropriate by the 
Federal agency or regulatory body.
    Subsection (c). Limitation. This act does not require 
animal testing by a manufacturer not required by other laws or 
regulations to perform animal testing. It also does not require 
a manufacturer to retest specific endpoints.