-------------------------Indexing Terms------------------------- 
REPORTNUM:   RCED-00-246R						        

TITLE:     National Toxicology Program: Procedures Were Followed in Listing
Alcoholic Beverage Consumption as a Known Carcinogen

DATE:   07/28/2000 
				                                                                         
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GAO/RCED-00-246R

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 consumption 1
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
Carcinogensand 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 9 GAO/ RCED- 00- 246R National Toxicology Program

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 Registeron 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 Registerannouncing the next review meeting and
solicit comments on the listing decision.

Enclosure I 11 GAO/ RCED- 00- 246R National Toxicology Program

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 Registerto 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 12 GAO/ RCED- 00- 246R National Toxicology Program

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
Carcinogensto the Congress and

publishes a notice in the Federal Register.

Enclosure I 15 GAO/ RCED- 00- 246R National Toxicology Program

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

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 Carcinogensis 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 19 GAO/ RCED- 00- 246R National Toxicology Program

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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