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. Author manuscript; available in PMC: 2019 Sep 5.
Published in final edited form as: Toxicol Sci. 2018 Nov 1;166(1):163–179. doi: 10.1093/toxsci/kfy190

Figure 1.

Figure 1.

The AOP framework and experimental design. A, An example of a generic neurodevelopmental AOP with TPO inhibition as the molecular initiating event (first box, left). Each subsequent linkage is a key event; quantitative support for key events related to serum TH reductions, brain TH reductions, and gene expression changes are investigated in this study (highlighted). B, In the experimental design, an extensive dose response of PTU was administered to pregnant rats beginning on GD6 (triangle). In experiment I, pregnant rats were euthanized on GD20 and the fetuses analyzed for serum THs, brain THs, and cortical gene expression (circle); in experiment II, pups were euthanized on postnatal day 14 (PN14) for similar comparisons (circle). GD20 and PN14 are developmental stages currently requested and/or recommended for analysis in regulatory studies.