[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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