A study claiming that low doses of bisphenol A (BPA) and bisphenol S (BPS) increased brain-cell growth in embryonic zebrafish—which later exhibited hyperactive behaviors as larvae—has urged health authorities to reconsider the use of linear dose-response relationships to set tolerable daily intake levels. Cassandra Kinch, et al., “Low-dose exposure to bisphenol A and replacement bisphenol S induces precocious hypothalamic neurogenesis in embryonic zebrafish,” Proceedings of the National Academy of Sciences, January 2015.

After exposing embryonic zebrafish to the two substances at levels (0.0068 μM) similar to those found in rivers that supply two major urban centers, University of Calgary researchers reported that BPA and BPS caused “180% and 240% increases, respectively, in neuronal birth (neurogenesis) within the hypothalamus, a highly conserved brain region involved in hyperactivity.” This increased neurogenesis apparently relied not on estrogen receptors as predicted, but on “androgen receptor-mediated up-regulation of aromatase.”

Based on these results, the study’s authors concluded that BPA/BPS “can alter the normal developmental timing of this critical neuroendrocrine center, the consequences of which can lead to early synaptogenesis and improper fine-turning of the brain later in development.” As one author explained in a January 13, 2015, press release, “These findings are important because they support that the prenatal period is a particularly sensitive stage, and reveals previously unexplored avenues of research into how early exposure to chemicals may alter brain development.”

In particular, the study warns that many endocrine-disruptors follow “U-shaped dose-response curves, whereby exposure to midrange concentrations activates physiological defense mechanisms against the compounds, but at low-range concentrations, the compound mimics endogenous hormones. Thus, our finding that BPA at a very low dose (0.0068 μM) alters neurogenesis and that a moderate BPA (1 μM) dose did not affect neurogenesis significantly calls for change in government-sanctioned methods of assessing human tolerable intake levels.”