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In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse
Published on: October 6, 2023
Predicting chemical impacts on vertebrate endocrine systems
John W Nichols1, Miyuki Breen, Robert J Denver
1U.S. Environmental Protection Agency, Duluth, Minnesota, USA. nichols.john@epa.gov
Environmental Toxicology and Chemistry
|October 22, 2010
Summary
Animals possess protective mechanisms against toxic chemicals, complicating exposure level regulations. Understanding endocrine system (HPT, HPG, HPA axes) responses is key for risk assessment and developing predictive models.
Area of Science:
- Environmental toxicology
- Endocrinology
- Risk assessment
Background:
- Animals have evolved diverse protective mechanisms against toxic chemicals.
- Governmental regulation of chemical exposure is complicated by these adaptive responses.
- Vertebrate endocrine systems (HPT, HPG, HPA axes) are potential targets for environmental contaminants.
Purpose of the Study:
- To identify features of vertebrate endocrine systems that allow accommodation and recovery from chemical insults.
- To distinguish between effects on adult and developing organisms, as early-life disruption can cause permanent changes.
- To explore the use of mechanistically based mathematical models for understanding endocrine disruption.
Main Methods:
- Examined vertebrate hypothalamic-pituitary-thyroid (HPT), hypothalamic-pituitary-gonad (HPG), and hypothalamic-pituitary-adrenal (HPA) axes.
- Differentiated between effects on adult and developing organisms.
- Proposed the use of mechanistically based mathematical models and modified Tier 2 assays for assessment.
Main Results:
- Vertebrate endocrine systems exhibit features enabling accommodation and recovery from chemical insults.
- Endocrine disruption during early development can lead to permanent phenotypic changes.
- Mechanistic models offer a way to understand accommodation and recovery dynamics.
Conclusions:
- Risk assessments must consider endocrine system dynamics and the potential for fitness costs associated with toxic insult accommodation.
- Mechanistically based mathematical models can improve the understanding and prediction of endocrine disruption.
- Validated models could enable extrapolation of testing data to diverse chemicals, species, and exposures.
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