1. Sponsor Organization: NIH/NIEHS

2. Project Title: 46004-13 INTERACTION FOR TCDD AND ITS STRUCTURAL ANALOGS--SPECIES COMPARISONS

3. Project Focus:

• Project Primary Focus: Human Health Effects
• Project Secondary Focus:

4. Description:

This project uses isolated cell systems, experimental rodent models, and human samples to address a number of issues that impact on risk assessment of dioxin and its structural analogs: (a) Determine the shape of the dose-response curve for the effects of TCDD in rat liver and lung by quantifying transcriptional activation of dioxin responsive regions and comparing responses to more complex biological effects such as cell proliferation and growth including exposure levels encountered by humans from day to day living, (b) Quantitatively and qualitatively compare human and rodent responses to dioxin. Human samples are obtained from groups exposed to dioxin either occupationally or environmentally, (c) Determine the extent of interindividual variation in human responses to dioxin, (d) Develop biologically-based dose response models for predicting dioxin's effects. This project is addressing key knowledge gaps which have created uncertainty in risk assessments by clarifying the shape of the dose-response curve in the low-dose region, by determining if animal models are appropriate for estimating human risks, and by characterizing the potential importance of interindividual variation in human responses to dioxin and its structural analogs. In order to determine changes in gene expression at levels which approximate human exposures, a reverse transcript PCR method has been developed which can detect less than on mRNA per cell of some dioxin responsive genes. This method is permitting examination of TCDD's biochemical effects in blood samples from humans occupationally or accidentally exposed to dioxin. Dose-response studies have demonstrated that the response to different levels of dioxin exposure cannot be predicted solely on the basis that the response is receptor-mediated. Animal and human data are being used to construct biologically-based models for dioxin?s effects and are an important element in estimation of human risk from exposure.

5. References:

6. Inventory Category:

• Primary: Models
• Secondary:

7. Inventory Subcategory:

• Primary: Exposure and Risk Models
• Secondary:

8. Keywords for Experimental System/Species:

• Species:
  • Mammal
  • Human
• Study Type:
• Fate and Transport:

9. Keywords for Experimental Endpoints:

• Health Effect:
• Hormonal Measures:
• Level Of Study:
  • Gene Expression
  • Molecular
• Chemistry Metabolism:
  • Exposure Monitoring
• Life Stage:
  • Growth
• Risk Assessment:
  • Biologically Based-Dose Response
  • Risk Assessment

10. Chemical Agents:

• Dioxins

11. Performing Institution:

• NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

12. Contact:

Edit (password needed)