[Federal Register Volume 63, Number 62 (Wednesday, April 1, 1998)]
[Notices]
[Pages 15842-15843]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-8527]
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ENVIRONMENTAL PROTECTION AGENCY
[FRL-5989-5]
Risk Assessment Forum Report on Assessment of Thyroid Follicular
Cell Tumors
AGENCY: Environmental Protection Agency.
ACTION: Notice of availability of Risk Assessment Forum report.
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SUMMARY: The Environmental Protection Agency (EPA) is today announcing
the availability of an EPA Risk Assessment Forum report entitled,
Assessment of Thyroid Follicular Cell Tumors (hereafter ``Forum
Report''). The Forum Report presents science policy guidance that
describes the procedures the Agency will use in the evaluation of
potential human cancer hazard and dose-response assessments from
chemicals that are animal thyroid carcinogens. The Forum Report
describes when, under clearly specified conditions, chemical
carcinogenesis in thyroid follicular cells can be analyzed as a
nonlinear phenomenon, rather than assuming low dose linearity as EPA
customarily does for carcinogenic compounds. Four hypothetical case
studies are summarized which illustrate how to evaluate toxicological
data and make hazard and dose-response estimation choices. The
procedures and considerations developed in the Forum Report embody
current scientific knowledge of thyroid carcinogenesis and evolving
science policy. Should significant new information become available,
the Agency will update its guidance accordingly.
ADDRESSES: An electronic version of the Forum Report is accessible from
EPA's National Center for Environmental Assessment Internet home page
at http://www.epa.gov/ncea. Interested parties can obtain a single copy
of the report by contacting ORD Publications, Technology Transfer and
Support Division, National Risk Management Research Laboratory,
Cincinnati, Ohio by calling 513-569-7562, or by sending facsimile to
513-569-7566. Please provide your name and mailing address, and request
the document by title and the EPA document number (EPA/630/R-97/002)
when ordering. There will be
[[Page 15843]]
a limited number of paper copies available from the above source.
Requests will be filled on a first-come-first-served basis as print
copies become available. After the supply is exhausted, copies of the
report can be purchased by contacting the National Technical
Information Service (NTIS), by calling 703-487-4650, or by sending a
facsimile to 703-321-8547.
FOR FURTHER INFORMATION CONTACT: Dr. William P. Wood, Risk Assessment
Forum (8601-D), 401 M Street, S.W., Washington, DC, 20460, telephone
(202) 564-3361.
SUPPLEMENTARY INFORMATION: In 1986 EPA published cancer risk assessment
guidelines (51 FR 33996) and recently proposed revisions to these
guidelines (61 FR 17960). From time to time scientific developments
prompt the Agency to reexamine its risk assessment guidance (e.g., the
assessment of male rat kidney tumors, 57 FR 8123). The National
Research Council (NRC) in their 1994 report Science and Judgment in
Risk Assessment emphasized that well designed guidelines should permit
acceptance of new evidence that differs from what was previously
perceived as the general case, when scientifically justifiable. In
keeping with this principle, the NRC recommended that EPA be more
precise in describing the kind and strength of evidence that it will
require to depart from a default option and which procedures will be
applied in such situations. That is the case with the review of some
chemicals that have produced thyroid follicular cell tumors in
experimental animals.
EPA's Guidelines for Carcinogen Risk Assessment provide direction
for performing hazard and dose-response assessments for carcinogenic
substances. The guidelines generally operate on the premise that
findings of chemically induced cancer in laboratory animals signal
potential hazards in humans. Likewise, for dose-response analyses, the
guidelines first call for use of the most biologically appropriate
means for dose extrapolation. In the absence of such knowledge,
assessors are directed toward the use of a default science policy
position, a low-dose linear procedure.
Thyroid gland follicular cell tumors are fairly common in chronic
studies of chemicals in rodents. Experimental evidence indicates that
the mode of action for these rodent thyroid tumors involves (a) changes
in the DNA of thyroid cells with the generation of mutations, (b)
disruption of thyroid-pituitary functioning, or (c) a combination of
the two. The only verified cause of human thyroid cancer is ionizing
radiation, a mutagenic insult to which children are more sensitive than
adults.
In 1988, the Agency organized a review of the existing science on
thyroid follicular cell carcinogenesis and a draft science policy
position covering the evaluation of chemicals that have induced thyroid
tumors in experimental animals (53 FR 20685). The EPA Science Advisory
Board (SAB) approved the science review and tentatively embraced the
policy position that in clearly specified circumstances some thyroid
tumors could be assessed using nonlinear considerations. However, they
recommended that the Agency (a) articulate more clearly the steps that
lead to the use of nonlinear considerations in assessments and (b)
illustrate, using case studies, the ways EPA would evaluate data on
animal thyroid carcinogens and make projections of anticipated human
risk from chemicals that are animal thyroid carcinogens. The Agency
revised the Forum Report accordingly, incorporating an update of the
scientific literature, and on July 19, 1996 the SAB reviewed and
approved the revised Forum Report (61 FR 32796).
The scientific analysis and science policy statement in this Forum
Report apply only to tumors involving follicular cells of the thyroid
gland. The Forum Report does not analyze or address comparable issues
for other endocrine organs.
Dated: March 18, 1998.
William H. Farland,
Director, National Center for Environmental Assessment.
[FR Doc. 98-8527 Filed 3-31-98; 8:45 am]
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