Using TiPED with Known EDCs, a Verification of methodology
To verify TiPED, we identified six known EDCs (chemicals or classes of chemicals) that work through different hormonal mechanisms and are known to have widely different effects.
We “tested” these six chemicals in the EDC literature and identified published studies that determined whether the TiPED assays we have identified as necessary were successful in identifying these six chemicals as EDCs. In short: these system works (see a table summing up these results here).
The details: some of these EDCs could be identified by computational tools in Tier 1. BPA and phthalates, for example, have been tested with both Q/SAR and molecular docking assays, and both of these methods indicate that these chemicals bind to nuclear hormone receptors.
Other EDCs, however, such as perchlorate and atrazine, would likely “pass” the first tier. BPA would be identified as an EDC in Tiers 2, 3, 4 and 5. Thus, a chemical like BPA, with mechanisms that span several NRs, would be easily identified by this tiered screening protocol. In contrast, perchlorate and atrazine might make it to Tiers 3 or 4 before they are identified as EDCs.
Overall, the proposed TiPED system is clearly robust enough that it would have stopped any one of these chemicals before it went to it to market, thus providing supportive evidence that the TiPED screens will be sufficient to identify putative EDCs.
See how these six well-known endocrine disrupting chemicals would have been caught at various stages in the TiPED System.
Examples of Chemists Using Assays in the TiPED System:
Many assays in the TiPED system are already in use, providing chemists information about the materials they are making:
1. Designing Green Oxidation Catalysts for Purifying Environmental Waters. Journal of the American Chemical Society. 2010, 132, 9774–9781. Chadwick Ellis, Camly T. Tran, Riddhi Roy, Marte Rusten, Andreas Fischer, Alexander D. Ryabov, Bruce Blumberg and Terrence J. Collins. Collins’ research group at Carnegie Mellon University tested their cohort of catalysts used for water purification using tier 3 cell-based assays.
2. In vivo biodistribution and toxicity depends on nanomaterial composition, size, surface functionalisation and route of exposure. Journal of Experimental Nanoscience. 2008, 3 (3). pp. 195-206. S. Harperab, C. Usenkoc, J.E. Hutchisonbd, B.L.S. Madduxb & R.L. Tanguayab.
3. Proactively designing nanomaterials to enhance performance and minimise hazard. International Journal of Nanotechnology. 2008, 1, pp. 124-142. Stacey L. Harper, Jennifer A. Dahl, Bettye L.S. Maddux, Robert L. Tanguay, James E. Hutchison. Using a rapid in vivo system (embryonic zebrafish) to assess the biological activity and toxic potential of nanomaterials. The anticipated growth of the nanotechnology industry motivated the development of rapid, relevant and efficient testing strategies to evaluate the biological activity and toxic potential of the growing number of novel nanoparticles.
4. Systematic Evaluation of Nanomaterial Toxicity: Utility of Standardized Materials and Rapid Assays. ACS Nano. 2011, 5 (6), pp 4688–4697. Stacey L. Harper, Jason Lee Carriere, John M. Miller, James Evan Hutchison, Bettye L. S. Maddux, and Robert L. Tanguay. To investigate the relative influence of core size, surface chemistry, and charge on nanomaterial toxicity, the team tested the biological response of zebra fish exposed to a matrix of nine structurally diverse, precision-engineered gold nanoparticles.