Canadian researchers have found in animal studies that low-level exposure to either Bisphenol A (BPA) or Bisphenol S (BPS) during the equivalent to a human fetus’ second trimester altered the timetable and rate at which neurons inside the brain’s hypothalamus developed. Such perturbations, they warned, can lead the developing brain to wire itself incorrectly, with potentially subtle but wide-ranging downstream behavioral results.



The findings could shed light on the physiological mechanisms that link the growing use of endocrine-disrupting chemicals, such as BPA, in consumer products to increases in such childhood disorders as clinical anxiety and hyperactivity.



The latest study was conducted on larval zebrafish, an animal whose brain development proceeds similarly to that of human fetuses. Newly hatched zebrafish exposed to very low levels of the neuroendocrine-disrupting chemical BPA displayed bursts in activity — an anxietylike behavior — that were nearly threefold the level seen in normally developing zebrafish larvae.



While low-level exposure to BPA prompted a 180 percent increase in the production of neurons in the hypothalamus of zebrafish, exposure to BPS boosted neurogenesis during a key window by 240 percent.

Pregnant mothers 'should limit exposure'

The new research and nearly a dozen studies of BPA’s physiological and behavioral effects in humans “begin to point to the prenatal period as a period of BPA vulnerability” and “suggest that pregnant mothers limit exposure to plastics and receipts” — two classes of products in which BPA continues to be widely used.



It may be most important to avoid exposure to such industrial chemicals in the second trimester of pregnancy, a formative period for the brain in which neurons are born, specialized brain regions emerge, and synapses begin to lash together the resulting community of cells. Hormones play key roles in all of those processes, and the signals they provide often dictate the duration and sequence of neuronal development.



The study, published online Monday in the journal Proceedings of the National Academy of Sciences, also calls into serious question the safety of the chemical most widely used in products labeled “BPA-free,” and therefore marketed as a safer alternative to BPA. A recent analysis of Americans’ and Asians’ urine samples confirmed previous work in finding that, while 93 percent had detectable levels of BPA, 81 percent had detectable levels of BPS.

Societal push to remove bisphenol 'justified'

Despite a paucity of toxicology testing, BPS appears to have become the “primary replacement” for BPA, the authors wrote. But Bisphenol S “equally affects neurodevelopment,” they concluded, adding that “a societal push to remove all bisphenols from our consumer goods is justified.” Both chemicals appeared to act not just on estrogen receptors in the brain, but to androgen receptors as well, the researchers found.



In the latest research, scientists at University of Calgary in Canada tested exposure levels that were equal to the concentrations of BPA present in the waters of the Oldman River, which runs through southern Alberta and supplies water to two major urban centers. The exposure levels at which changes in zebrafish neurodevelopment and behavior were seen were 100-fold lower than levels that have been measured by other researchers in circulating fetal blood.



That such low concentrations of BPA could perturb the timing of fetal brain-cell development suggests that existing regulatory practices might miss some of the effects of endocrine-disrupting chemicals such as BPA, the authors said. As a result, government regulators may be miscalculating safe levels of exposure.



Mounting research suggests that exposure to BPA at middling levels activates protective mechanisms in humans and other mammals. Exposure to very high levels will overwhelm such defenses and cause damage. But exposure to very low concentrations of BPA may cause more subtle damage: At low doses, the chemicals appear to sneak in under the body’s radar and mimic the effects of hormones found naturally in the body. That could lead to high cancer rates, infertility, brain changes and other endocrine disorders.



Testing by the U.S. Environmental Protection Agency and by Canadian regulators often overlooks the “U-shaped” pattern of damaging exposure: Government scientists determine safe exposure limits by starting at high levels of exposure to a given chemical and lowering the dose progressively. They often stop when the physiological effects of exposure can no longer be detected.



“Our finding that BPA at a very low dose alters neurogenesis and that a moderate dose did not affect neurogenesis significantly calls for a change in government-sanctioned methods of assessing human tolerable daily intake levels,” the authors wrote.

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