1 GAO/RCED-00-246R National Toxicology Program

B-285796

July 28, 2000

The Honorable George P. Radanovich

House of Representatives

The Honorable Mike Thompson

House of Representatives

Subject: National Toxicology Program: Procedures Were Followed in Listing Alcoholic

Beverage Consumption as a Known Carcinogen

Each year, Americans consume significant quantities of alcoholic beverages, including beer,

spirits, and wine. In 1997, sales of these beverages amounted to about $70 billion. While light

to moderate use of alcoholic beverages could offer potential health benefits, such as possible

cardiovascular benefits, high levels of consumption could create a number of health

problems, such as liver damage and a variety of cancers.

In 1978, the Secretary of Health and Human Services established the National Toxicology

Program (NTP) to provide information to health regulatory and research agencies, scientific

and medical communities, and the public about potentially toxic substances. NTP is required

to issue a biennial report listing all substances that are either known to be carcinogens in

humans or may reasonably be anticipated to be human carcinogens and to which a significant

number of people residing in the United States are exposed. In this regard, NTP recently

concluded that alcoholic beverage consumption is a known human carcinogen, particularly at

the highest levels of consumption1 and when used in conjunction with smoking.2

Concerned about whether NTP, in deciding to list alcoholic beverage consumption as a

known carcinogen, adequately considered all available scientific studies, provided

opportunities for public comment, and followed its standard voting procedures of straight

majority rule, you asked us to examine NTP’s listing procedures, including whether they were

consistently applied to the review of alcoholic beverages. Specifically, you asked us to

• identify the procedures NTP uses to list a substance as either a known or a

reasonably anticipated human carcinogen and

• determine whether NTP followed its procedures in determining to list alcoholic

beverage consumption as a known human carcinogen.

1

The report did not define the highest levels of consumption.

2

9

th

Report on Carcinogens, May 2000.

United States General Accounting Office

Washington, DC 20548

Resources, Community, and

Economic Development Division
B-285796

2 GAO/RCED-00-246R National Toxicology Program

As agreed with your offices, we reviewed NTP’s listing procedures, as well as specific

documentation applicable to the listing of alcoholic beverages. We also discussed the listing

procedures with program officials responsible for making listing decisions. In addition, we

interviewed officials representing the alcoholic beverage industry regarding their concerns

about the listing procedures, as well as any specific concerns they had about the application

of these procedures to the review of alcoholic beverage consumption. Furthermore, we

reviewed documentation related to their concerns provided by these officials. This report

summarizes our answers to your questions. Enclosure I documents the information we

provided to your staff on June 19, 2000.

In brief, we found the following:

• The procedures used by NTP to make listing decisions constitute a comprehensive,

multistep process. Among other things, these procedures provide for the careful

consideration of relevant scientific literature, input from leading scientists representing a

variety of disciplines, and repeated opportunities for industry and public comment.

• NTP consistently applied its listing procedures in deciding to list alcoholic beverage

consumption as a known human carcinogen.

National Toxicology Program’s Listing Procedures

NTP’s review process starts when a substance, mixture, or exposure circumstance is

nominated for review.3

Such groups as federal or state agencies, international scientific

organizations, industry, labor, academia, and the public can make a nomination. The

nomination, generally supported by numerous scientific studies, is then sequentially reviewed

by a series of four committees consisting of scientists from government, academia, and

industry who represent a wide variety of disciplines. Each committee conducts its own

independent analysis of the carcinogenicity of each nomination and votes whether to list it as

either a known human carcinogen or reasonably anticipated to be a human carcinogen.

During this phase of the review process, there are three opportunities for public comment on

the nomination, including an open public forum for discussing why a substance should or

should not be listed. Once the committees complete their review, the nomination is

compiled, along with other nominations, into the Report on Carcinogens and forwarded to

the Director, National Toxicology Program, for a final independent review. The Director then

forwards the report to the Secretary of Health and Human Services and provides a briefing

and recommendation on how each substance or mixture should be listed in the final Report

on Carcinogens. The process, generally about 2 years in length, is completed when the

Secretary approves the report for publication and submits it to the Congress.

Procedures Consistently Applied

We found that NTP consistently applied its prescribed procedures in deciding to list alcoholic

beverage consumption as a known human carcinogen. Nominated for review in February

1997, and supported by a large number of scientific studies cited as references for review, it

was listed in the 9

th

Edition of the Report on Carcinogens. As the nomination went through

the review process, each committee conducted its own independent analysis of the available

scientific data and voted in the majority to list alcoholic beverage consumption as a known

human carcinogen. A minority of the committee members voted against the listing because

3

A mixture relates to such consumer products as smokeless tobacco and alcoholic beverages, while an exposure circumstance

relates to the use of such products as sunlamps.
B-285796

3 GAO/RCED-00-246R National Toxicology Program

of the high level of consumption needed to cause cancer, the potential cardiovascular

benefits of low to moderate consumption, and the impact of confounding factors, such as

smoking and alcoholic lifestyle. During the review process, public comments—both for and

against the listing—were also received. According to NTP officials and relevant

documentation, both the dissenting opinions from committee members and related public

comments were addressed to the satisfaction of the various committee members and

incorporated into the report as appropriate. As a result of this process, the Director, National

Toxicology Program, recommended that alcoholic beverage consumption be listed as a

known human carcinogen. The Secretary of Health and Human Services approved this

recommendation in May 2000 for listing in the 9

th

Edition of the Report on Carcinogens.

We provided a draft of this report to NTP officials for their review and comment. We

discussed their comments during a teleconference with the Acting Director, Environmental

Toxicology Program, and other NTP officials. They generally agreed with the report’s

contents and provided us with some technical comments, which have been incorporated

where appropriate.

We conducted our review from May 2000 through July 2000 in accordance with generally

accepted government auditing standards.

As agreed with your office, we will make copies of this report available to others upon

request. If you have any questions or need additional information, please contact me or Jim

Jones at (202) 512-5138. Key contributors to this report include Paul Bollea and Sheldon

Wood.

Robert E. Robertson

Associate Director

Food and Agriculture Issues

Enclosure
Enclosure I

4 GAO/RCED-00-246R National Toxicology Program

National Toxicology Program

Listing of Alcoholic Beverage Consumption as a

Known Human Carcinogen
Enclosure I

5 GAO/RCED-00-246R National Toxicology Program

Objectives of Review

• Identify the procedures used by the National Toxicology

Program (NTP) to identify substances that are either known

or reasonably anticipated to be human carcinogens.

• Determine whether NTP followed these procedures in

deciding to list alcoholic beverage consumption as a known

human carcinogen.
Enclosure I

6 GAO/RCED-00-246R National Toxicology Program

Results in Brief

• NTP’s procedures include a comprehensive seven-step

process that incorporates independent reviews of scientific

literature by various committees and provides opportunities

for public comment. Committees consist of scientists from

government, academia, and industry who represent a

variety of disciplines.

• NTP followed its established procedures in determining to

list alcoholic beverage consumption as a known human

carcinogen.
Enclosure I

7 GAO/RCED-00-246R National Toxicology Program

Objective 1: Procedures NTP uses to

identify known or suspected carcinogens.

Seven Steps in NTP’s Review Process

• Nomination

• National Institute of Environmental Health Sciences Review

Group (RG1)

• Interagency Working Group (RG2)

• NTP Board of Scientific Counselors, Report on Carcinogens

Subcommittee

• NTP Executive Committee

• NTP Director

• Secretary, Health and Human Services
Enclosure I

8 GAO/RCED-00-246R National Toxicology Program

Objective 1: Procedures NTP uses to

identify known or suspected carcinogens.

Nomination of Substance for Review

• Nominations, supported by scientific studies, can be

submitted by federal or state agencies, industry, labor,

academia, and the public.

• NTP officials estimate that 85 to 90 percent of the

nominations are based on (1) reviews prepared by the

International Agency for Research on Cancer (part of the

United Nations World Health Organization) and (2) the

results of NTP’s Bioassay Program.
Enclosure I

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Objective 1: Procedures NTP uses to

identify known or suspected carcinogens.

National Institute for Environmental Health Sciences

Review Group (RG1)

• Prioritize nominations and decide what substances can be

reviewed for the next Report on Carcinogens.

• Solicit public comment via the Federal Register on the

carcinogenicity of the substance.

• Have a contractor perform a literature search and prepare

the first draft of a background document summarizing the

search results.

• Identify primary reviewers to prepare the first draft of a

summary statement on the carcinogenicity of the substance.

• Vote to list or delist the substance, as appropriate.
Enclosure I

10 GAO/RCED-00-246R National Toxicology Program

Objective 1: Procedures NTP uses to

identify known or suspected carcinogens.

Interagency Working Group (RG2)

• Identify new primary reviewers to review the background

document and summary statement provided by RG1 and

make changes as necessary.

• Vote to list or delist the substance after independent review

of all relevant documentation.

• Finalize the background document, which becomes the

document of record.

• Issue a notice in the Federal Register announcing the next

review meeting and solicit comments on the listing decision.
Enclosure I

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Objective 1: Procedures NTP uses to

identify known or suspected carcinogens.

NTP Board of Scientific Counselors’

Report on Carcinogens Subcommittee

• Hold a 2-day meeting, open to the public (first used for the

8th Edition of the Report on Carcinogens).

• Identify new primary reviewers to lead the discussion as the

group performs an independent review of all relevant

documentation.

• Vote to list or delist the substance.

• Issue a notice in the Federal Register to solicit final public

comments on the listing decision (period of 60 days

allowed). The notice includes the results of the RG1, RG2,

and Board of Scientific Counselors’ Report on Carcinogens

Subcommittee meetings.
Enclosure I

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Objective 1: Procedures NTP uses to

identify known or suspected carcinogens.

NTP Executive Committee

• Perform an independent review of the background

document, summary statement, results of prior three votes,

and all public comments.

• Vote to list or delist the substance (vote not publicized).
Enclosure I

13 GAO/RCED-00-246R National Toxicology Program

Objective 1: Procedures NTP uses to

identify known or suspected carcinogens.

NTP Director

• Is briefed by the Head, Report on Carcinogens, and other

NTP staff; receives all documentation for review.

• Makes final recommendation on listing or delisting the

substance.
Enclosure I

14 GAO/RCED-00-246R National Toxicology Program

Objective 1: Procedures NTP uses to

identify known or suspected carcinogens.

Secretary, Health and Human Services

• Is briefed by NTP staff; all documentation is made available

for review.

• Gives final approval to list or delist the substance.

• Sends the Report on Carcinogens to the Congress and

publishes a notice in the Federal Register.
Enclosure I

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Objective 2: Did NTP follow its procedures

in listing alcoholic beverage consumption?

Alcoholic Beverage Consumption

Nominated in February 1997

• NTP accepts nomination from recommendation made by the

International Agency for Research on Cancer.

• Nomination is supported by a large number of scientific

studies that NTP needed to assess.

• For the first time, NTP reviews “mixtures” and “exposure

circumstances” (i.e., consumer products, such as alcoholic

beverage consumption, smokeless tobacco, sunlamps) in

addition to individual substances.
Enclosure I

16 GAO/RCED-00-246R National Toxicology Program

Objective 2: Did NTP follow its procedures

in listing alcoholic beverage consumption?

National Institute for Environmental Health Sciences

Review Group (RG1)

• Identified over 800 references in the literature search.

• Voted 6-1 to list alcoholic beverage consumption as a

known human carcinogen.

• Dissenting vote related to a member’s desire to have “heavy

consumption” in the first paragraph of the summary

statement.

• Added paragraph on potential benefits of alcoholic beverage

consumption to the summary statement.
Enclosure I

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Objective 2: Did NTP follow its procedures

in listing alcoholic beverage consumption?

Interagency Working Group (RG2)

• Voted 7-0 to list alcoholic beverage consumption as a

known human carcinogen.

• Voted 4-3 to remove the paragraph on potential benefits,

stating that the Report on Carcinogens is a cancer

document and not a cardiovascular document.
Enclosure I

18 GAO/RCED-00-246R National Toxicology Program

Objective 2: Did NTP follow its procedures

in listing alcoholic beverage consumption?

NTP Board of Scientific Counselors’

Report on Carcinogens Subcommittee

• Voted 9-3-1 to list alcoholic beverage consumption as a

known human carcinogen.

• Three dissenting voters noted the possible impact of

confounding factors (i.e., smoking and lifestyle).

• One abstaining voter was not comfortable with the

discussion on synergy between alcohol and smoking.

• Added confounding effect of smoking to the summary

statement.
Enclosure I

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Objective 2: Did NTP follow its procedures

in listing alcoholic beverage consumption?

Final deliberations

• NTP Executive Committee voted 7-0 to list alcoholic

beverage consumption as a known human carcinogen.

• NTP Director recommended the listing.

• Secretary of Health and Human Services approved the

listing.

• Alcoholic beverage consumption was listed in the 9th

Edition of the Report on Carcinogens, May 2000, as a

known human carcinogen based on sufficient evidence of

carcinogenicity from human studies.
Enclosure I

20 GAO/RCED-00-246R National Toxicology Program

(150183)

Objective 2: Did NTP follow its procedures

in listing alcoholic beverage consumption?

Conclusion

• NTP followed its established procedures in determining to

list alcoholic beverage consumption as a known human

carcinogen.
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