[Federal Register Volume 73, Number 84 (Wednesday, April 30, 2008)]
[Notices]
[Pages 23463-23465]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-9379]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES


National Toxicology Program (NTP); Report on Carcinogens (RoC); 
Request for Public Comments on the RoC Expert Panel's Recommendations 
on Listing Status for Aristolochic Acids and Riddelliine in the 12th 
RoC and the Scientific Justifications for the Recommendations

AGENCY: National Institute of Environmental Health Sciences (NIEHS); 
National Institutes of Health (NIH).

ACTION: Request for public comments.

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SUMMARY: The RoC Office invites public comments on the recommendations 
from an expert panel on listing status for aristolochic acids and 
riddelliine in the 12th RoC and the scientific justifications for the 
recommendations. The recommendation and scientific justification for 
each candidate substance are available electronically in Part B of the 
Expert Panel Report (http://ntp.niehs.nih.gov/go/29682, see Expert 
Panel Report Part B) or in printed text from the RoC Office (see FOR 
FURTHER INFORMATION CONTACT below). The RoC Office convened an eight-
member expert panel of scientists from the public and private sectors 
on January 24-25, 2008, to review aristolochic acid related exposures 
and riddelliine. The panel was asked (1) to apply the RoC listing 
criteria to the relevant scientific evidence and make recommendations 
regarding listing status (i.e., known to be a human carcinogen, 
reasonably anticipated to be a human carcinogen, or not to list) for

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aristolochic acids and for riddelliine in the 12th RoC and (2) to 
provide the scientific justifications for the recommendations.

DATES: The Expert Panel Report (Part B) for aristolochic acids and for 
riddelliine will be available for public comment by April 23, 2008. 
Written comments should be submitted by June 16, 2008.

ADDRESSES: Comments should be sent to Dr. Ruth Lunn, RoC Office [NIEHS, 
P.O. Box 12233, MD EC-14, Research Triangle Park, NC 27709, FAX: (919) 
541-0144, or [email protected]. Courier address: RoC Office, 79 T.W. 
Alexander Drive, Building 4401, Room 3118, Research Triangle Park, NC 
27709].

FOR FURTHER INFORMATION CONTACT: Dr. Ruth Lunn, RoC Office, (919) 316-
4637 or [email protected].

SUPPLEMENTARY INFORMATION: 

Background

    Aristolochic acid related exposures (which includes ``aristolochic 
acid'' and ``botanical plants containing aristolochic acid'') and 
riddelliine are among the candidate substances under review for 
possible listing in the 12th RoC (see complete list at http://ntp.niehs.nih.gov/go/10091). Aristolochic acid is a generic name for a 
family of nitrophenanthrene carboxylic acids that occurs naturally in 
plants in the Aristolochiaceae family, primarily of the genera 
Aristolochia and Asarum. Botanical products from plants containing 
aristolochic acid are used in traditional folk medicines to treat 
arthritis, gout, rheumatism, and festering wounds, and have been used 
inadvertently as part of a weight-loss regimen. Exposure to 
aristolochic acid has been reported for many countries, including the 
United States. In 2001, the Food and Drug Administration issued 
warnings to consumers, health care professionals, and industry 
associations concerning herbal products containing aristolochic acid. 
Other countries, including the United Kingdom, Germany, Canada, and 
Australia, have banned these herbs. Nevertheless, botanical products 
potentially containing aristolochic acid are still available legally in 
other countries and can be bought via the Internet.
    Riddelliine is a pyrrolizidine alkaloid (PA) of the macrocyclic 
diester class. Riddelliine and riddelliine N-oxide (a metabolite of 
riddelliine that can be converted back to riddelliine) occur in plants 
of the genus Senecio that are found in sandy desert areas of the 
western United States and other parts of the world. At least 15 Senecio 
species have been identified that are used in herbal medicines or 
possibly as food worldwide. Exposure to humans could result from direct 
contamination of foodstuffs by parts of Senecio plants or from indirect 
introduction of the alkaloid through products derived from animals that 
have fed on the plants. PAs have been found in eggs, honey, bee pollen, 
and milk.
    As part of the RoC review process (available at http://ntp.niehs.nih.gov/go/15208), the NTP announced the availability of the 
draft background documents for aristolochic acid related exposures and 
riddelliine in the Federal Register (72 FR 63900, November 13, 2007), 
invited public comments on the draft background documents, and 
announced the expert panel meeting for aristolochic acid related 
exposures and riddelliine. The RoC Office convened an eight-member 
expert panel of scientists from the public and private sectors to 
evaluate these two substances. The expert panel met on January 24-25, 
2008, in a public forum at the Chapel Hill Sheraton Hotel in North 
Carolina. The panel first addressed aristolochic acid related exposures 
and then riddelliine in its deliberations. The panel was charged to 
peer review the draft background document for the candidate substance, 
and then to make a recommendation on its listing status in the 12th RoC 
and to provide a scientific justification for that recommendation. 
Details about the meeting, including public comments received and the 
expert panel reports, are available on the RoC Web site (http://ntp.niehs.nih.gov/go/29682). The expert panel report for each candidate 
substance contains two parts: Part A has the peer-review comments on 
the draft background document and Part B is the recommendation on 
listing status and its scientific justification. The expert panel 
recommended redefining the two proposed candidate substances: (1) 
``Aristolochic acid'' and (2) ``botanical plants containing 
aristolochic acid'' into a single candidate substance, ``aristolochic 
acids.'' They concluded that aristolochic acids, the nitrophenanthrene 
carboxylic acids found primarily in the Aristolochiaceae family of 
plants, are responsible for the carcinogenic effects observed in humans 
who consume Aristolochia or herbal remedies prepared from these plants. 
The expert panel recommended that (1) aristolochic acids be listed in 
the 12th RoC as known to be human carcinogens and (2) riddelliine be 
listed in the 12th RoC as reasonably anticipated to be a human 
carcinogen. The panel's recommendation on listing status and its 
scientific justification are now being released for public comment.

Next Steps

    The RoC Office is in the process of finalizing the background 
document for each candidate substance based upon the expert panel's 
peer-review comments and the public comments received (72 FR 63900). 
Persons can register free-of-charge with the NTP listserve (http://ntp.niehs.nih.gov/go/231) to receive notification when the final 
background documents are posted on the RoC Web site (http://ntp.niehs.nih.gov/go/10091).
    As part of the RoC review process, two government groups will also 
conduct reviews of aristolochic acids and riddelliine; these meeting 
are not open to the public. Upon completion of these reviews, the NTP 
will (1) draft a substance profile for each candidate substance that 
contains its listing recommendation for the 12th RoC and the scientific 
information supporting that recommendation, (2) solicit public comments 
on the draft substance profiles, and (3) convene a meeting of the Board 
of Scientific Counselors to peer review the draft substance profiles.

Request for Comments

    The RoC Office invites written public comments on the expert 
panel's recommendations on listing status for aristolochic acids and 
riddelliine and the scientific justifications for the recommendations. 
All comments received will be posted on the RoC Web site. Persons 
submitting written comments are asked to include their name and contact 
information (affiliation, mailing address, telephone and facsimile 
numbers, e-mail, and sponsoring organization, if any) and send them to 
Dr. Lunn (see ADDRESSES above). The deadline for submission of written 
comments is June 16, 2008.

Background Information on the RoC

    The RoC is a Congressionally mandated document that identifies and 
discusses agents, substances, mixtures, or exposure circumstances 
(collectively referred to as ``substances'') that may pose a hazard to 
human health by virtue of their carcinogenicity. The RoC follows a 
formal, multi-step process for review and evaluation of selected 
chemicals. Substances are listed in the report as either known or 
reasonably anticipated to be human carcinogens. The NTP prepares the 
RoC on behalf of the Secretary of Health and Human Services. 
Information about the RoC and the review process are available on its 
Web site (http://ntp.niehs.nih.gov/go/

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roc) or by contacting Dr. Lunn (see FOR FURTHER INFORMATION CONTACT 
above).

    Dated: April 21, 2008.
Samuel H. Wilson,
Acting Director, National Institute of Environmental Health Sciences 
and National Toxicology Program.
 [FR Doc. E8-9379 Filed 4-29-08; 8:45 am]
BILLING CODE 4140-01-P