89–010

Calendar No. 946

106TH CONGRESS REPORT

2d Session " ! SENATE 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

REPORT

[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.

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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 animalbased 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

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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.

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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.

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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

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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.

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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.

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