Virtual Tissue Models: Predicting How Chemicals Impact Development
Virtual tissue models use new computational methods to construct advanced computer models capable of simulating how chemicals may affect human development. Virtual tissue models are some of the most advanced methods being developed today. The models will help reduce dependence on animal study data and provide much faster chemical risk assessments.
Virtual Embryo Models
EPA’s Virtual Embryo (v-Embryo™) research is developing prediction models to improve our understanding of how chemical exposure may affect unborn children. Researchers are integrating new types of in vitroin vitroExperiments or tests done under controlled experimental conditions outside of the body, such as in a test tube or laboratory dish. These tests tend to focus on organs, tissues, cells, cellular components, proteins, and/or biomolecules., in vivoin vivoTests or evaluations performed within an intact, living organism such as a laboratory animal or humans., and in silicoin silicoA general term used to mean "performed on computer or via computer simulation." models that simulate critical steps in fetal development.
Virtual Embryo models simulate biological interactions observed during development and predict when chemicals disrupt key biological events in pathways that are thought to lead to adverse effects.
- Blood Vessel Development Model
EPA researchers used the ToxCast high-throughput screening data to develop a model for predicting the potential for chemical disruption of blood vessel formation. The model was tested using compounds known to be detrimental to vascular development. There was a strong correlation between animal developmental toxicity data and ToxCast data used in positively identifying Vascular Disruptor Compounds (VDCs).
- Developmental Toxicity Model
EPA researchers used traditional animal toxicity data and high-throughput screening data from ToxCast to study the toxic effects of chemicals on prenatal development. ToxCast data could distinguish between chemicals that affect rat versus rabbit development effects. Key biological signaling associated with developmental toxicity identified by ToxCast assays included those regulating cellular growth and differentiation as well as inflammatory signaling.
Virtual Thyroid Models
The thyroid gland regulates hormones critical for human nervous system development. Disruption of thyroid function during development leads to reduced IQ in children. The goal of the Virtual Thyroid is to model the potential impact of chemical disruption of thyroid function and subsequent adverse impacts on brain development.
The Virtual Thyroid are models of the human fetal physiological state and the developing nerves and blood vessel unit (neurovascular unit - NVU). These models represent the complex relationships among fetal organs that regulate thyroid function during brain-liver-thyroid development, and among cell-cell interactions in organotypic culture models (OCMs). OCMs are representative models of various organ systems. For example, EPA researchers are developing an in vitro assay for human brain effects or ‘minibrains’. The minibrains may be used to critically evaluate patterns of neural growth, differentiation and migration in response to varying thyroid hormone levels. Another OCM application is modeling the dynamics of local thyroid hormone transport, metabolism, and signaling in the NVU.
Toxicological Tipping Points (Point of No Return)
A key question in modeling the effects of chemical exposure is distinguishing between adaptive responses and those that result in adverse health and environmental outcomes. Biological systems have compensatory processes that protect organisms from stressors like chemical exposure. EPA researchers are figuring out how to determine the “Tipping Point”, the point when biological systems are unable to recover from or adapt to chemical exposure. EPA researchers are developing mathematical models that will predict perturbation of biological systems and determine when cellular systems are no longer able to recover. When cellular systems are unable to recover, chemical exposures could lead to adverse outcomes such as cancer.