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An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma
Published on: April 17, 2013
Risk assessment of thyroid follicular cell tumors
R N Hill1, T M Crisp, P M Hurley
1Office of Prevention, Pesticides and Toxic Substances, U.S. Environmental Protection Agency, Washington, DC 20460 USA.
Environmental Health Perspectives
|July 29, 1998
Summary
Chemicals affecting thyroid cell growth can cause rodent thyroid tumors, presumed relevant to humans. Risk assessments require detailed data on chemical mechanisms, thyroid effects, and dose-response relationships for accurate human health evaluations.
Area of Science:
- Toxicology
- Endocrinology
- Carcinogenesis
Background:
- Thyroid follicular cell tumors in rodents are linked to hormone imbalances and growth stimulation by thyroid-stimulating hormone (TSH).
- Ionizing radiation is the only established human thyroid carcinogen; the link between chemical exposure and human thyroid cancer remains uncertain.
- The U.S. Environmental Protection Agency (EPA) has established science policy positions for evaluating chemically induced rodent thyroid tumors for human relevance.
Purpose of the Study:
- To outline the EPA's science policy positions regarding the extrapolation of rodent thyroid tumor data to humans.
- To identify the necessary data for robust risk assessments of thyroid toxicants.
- To clarify the application of linear versus nonlinear dose-response models in thyroid cancer risk assessment.
Main Methods:
- Review of existing scientific literature and regulatory policy positions.
- Analysis of factors influencing thyroid follicular cell growth and tumor development.
- Examination of interspecies extrapolation principles and dose-response assessment strategies.
Main Results:
- Chemically induced rodent thyroid tumors are presumed relevant to humans, with default assumptions of comparable sensitivity when data is lacking.
- Adverse noncancer thyroid effects in rodents due to thyroid-pituitary disruption are also presumed relevant to humans.
- Specific criteria guide the application of linear or nonlinear dose-response models based on a chemical's mode of action, including mutagenicity and effects on thyroid hormones and cell proliferation.
Conclusions:
- Accurate human risk assessment for thyroid toxicants requires comprehensive data on mutagenicity, thyroid cell growth, gland weight, hormone levels, and dose-response relationships.
- The EPA's science policy provides a framework for evaluating thyroid cancer risks, emphasizing the importance of mode of action data.
- Case-by-case assessments are necessary for chemicals that disrupt the thyroid-pituitary axis and exhibit some mutagenic activity.
