Figure 1 shows a heat map of the entire in vitro data set, providing an overview of the data. Generally, the biochemical HTS assays (indicated by red in the top band) had fewer hits than did the cell-based assays, as evident from the increasing density of hits progressing from left to right in the heat map. On the left side of this plot are 87 assays that had no AC 50 /LEC values identified for any of the chemicals at levels below the highest concentration tested (see Table 1 for concentration ranges tested). In Figure 1 , all hits are shown, up to where the AC 50 /LEC occurred at the highest tested concentration. However, some of these values may not be physiologically relevant because in vitro systems can be exposed to concentrations higher than can occur in vivo in relevant tissues under conditions of a bioassay. Supplemental Material, Figure 1 (doi:/) shows the number of hits per chemical as a function of the threshold AC 50 /LEC values used to define a hit. At the comparatively low threshold of 1 µM, there were relatively few hits per chemical. There were 828 chemical–assay pairs (% of pairs tested) with an AC 50 /LEC < 1 µM (listed in Supplemental Table 2), many of which were related to nuclear-receptor–mediated xenobiotic metabolism. Of the chemicals that had AC 50 /LEC values < 1 µM in multiple assays, some showed cytotoxicity in one or more of the cell-based assays, which suggests cytotoxicity pathway activation, although in many cases we do not have a specific (cell-free) assay that would indicate which pathway that was. Cytotoxicity may comprise a relevant end point of specific biological process(es) leading to cellular demise (., apoptosis), or it may comprise nonspecific collapse of cellular homeostasis (., necrosis). Both are considered in phase I, and the former may be the result of targeted pathways engaged by specific molecular lesions, whereas the latter may generally follow from nonspecific cell injury. In other chemicals, we only saw specific targeted activities at these low concentrations, without any accompanying cytotoxicity.
When the breasts start to grow, this is normally the first sign of puberty that can be seen on the outside of a girl's body. This usually happens when girls are about the age of years. A lump that is a bit hard appears in each breast under the areola, which is the dark ring around the nipple. The lump in one breast may grow before the other one.  This is called breast budding.  Within six to 12 months, both breasts will have started growing. The swelling can be felt and seen outside the edges of the areolae. About one and a half to two years after the breasts first start growing, they are close to the shape and size of an adult woman's breasts. The nipple and areola may be on a smaller mound on each breast. This small mound usually goes away when each breast is fully grown.  Whether the breasts are small or large depends on how much fat there is in the body.