1. Sponsor Organization: NIH/NIEHS

2. Project Title: 06806-03 AH RECEPTOR INDEPENDENT CNS/REPRODUCTIVE EFFECTS OF PCBS

3. Project Focus:

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

4. Description:

Toxicity of PCB mixtures is generally attributed to their coplanar and mono-ortho- chlorinated congeners that bind to the same (Ah) receptor as does 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and risk of exposure to PCBs is currently measured in terms of how many "TCDD equivalents" are present in the mixtures. However, most PCB congeners do not bind to the Ah receptor; PCB mixtures cause numerous biological responses not mediated by binding to the Ah receptor; and potent Ah receptor agonists constitute only a tiny percentage of all PCBs in environmental samples. The possibility that perinatal exposure to PCB mixtures adversely affects health in adulthood via Ah receptor-independent mechanisms is essentially unexplored. Our hypothesis is that PCB mixtures adversely affect development of the male reproductive, female reproductive, and central nervous systems via at least three Ah receptor-independent mechanisms, and that PCB mixtures do so at occupationally if not environmentally relevant exposure levels. To test this hypothesis, pregnant/lactating rats will be treated daily with prototype congeners that are major constituents of the human PCB body burden: 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), an inducer of phenobarbital-responsive, drug and steroid metabolizing enzymes; 2,2',5,5'-tetrachlorobiphenyl (PCB 52), a congener whose major metabolite is estrogenic; and 2,3,3',4,4'-pentachlorobiphenyl (PCB 105), a congener whose metabolites bind strongly to thyroid hormone-binding proteins. A fourth congener, the Ah receptor agonist 3,3',4,4',5-pentachlorobiphenyl (PCB 126), will serve as a positive control. Effects of these congeners on development of the male reproductive, NIEHS, PO BOX 12233, RESEARCH TRIANGLE PARK, NC 27709, 919-541-0781, HEINDEL_J@NIEHS.NIH.GOV female reproductive, and central nervous systems of offspring of treated dams will be determined.

5. References:

6. Inventory Category:

• Primary: Models
• Secondary:

7. Inventory Subcategory:

• Primary: Basic Research
• Secondary:

8. Keywords for Experimental System/Species:

• Species:
  • Mammal
  • Rat
• Study Type:
  • In Vivo
• Fate and Transport:

9. Keywords for Experimental Endpoints:

• Health Effect:
  • Neurological
  • Reproductive
• Hormonal Measures:
  • Hormone Receptors
  • Thyroid Hormones, Ah Receptor
• Level Of Study:
• Chemistry Metabolism:
• Life Stage:
  • Female
  • Male
• Risk Assessment:

10. Chemical Agents:

• Pcbs

11. Performing Institution:

• UNIVERSITY OF WISCONSIN MADISON

12. Contact:

Edit (password needed)