In a panel discussion organized by Carnegie Mellon University’s Institute for Green Science and Environmental Health Sciences, independent experts urged the U.S. Food and Drug Administration (FDA) to review their standards on Bisphenol A (BPA) in light of a new report collecting academic studies on the chemical’s toxic effects at low doses.
The report, published today in the journal Reproductive Toxicology, integrates data collected from eight different studies that were part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA), a landmark academic collaboration initiated by U.S. federal regulatory agencies. Notably, the paper uses datasets of BPA’s effects on various organ and body systems in rodent models to show that the safe dose of BPA in humans is thousands of times lower than the standards set by regulatory agencies worldwide.
“The CLARITY-BPA study was an opportunity for scientists to bridge a gap that existed between academic studies and regulatory studies,” said panelist Laura Vandenberg, an associate professor at the University of Massachusetts and expert on endocrine disrupting chemicals (EDCs).
Traditional regulatory toxicology studies use methods developed decades ago to gauge whether a potential toxic agent causes harmful effects. However, these techniques, which include weighing the organs of exposed laboratory animals and observing for immediately visible negative impacts, are outdated and can miss important clues of toxicity, the panelists charged.
Many academic researchers studying toxicants nowadays prefer conducting more detailed studies on their potential effects by looking for things like changes in gene expression or subtler, long-term changes in behavior. Vandenberg related the difference between regulatory and academic studies as similar to the difference between looking at the Moon with a pair of binoculars to looking at the Moon with a telescope. Regulatory studies, like an observer with binoculars, can spot highly visible toxicity issues. But a modern academic study, like a higher resolution telescope, can allow observers to see long-term or smaller, but still harmful, effects.
“CLARITY-BPA offered a new way of looking at data with 21st century analyses,” Vandenberg said.
These modern analyses are also better at dealing with the unique mechanisms and effects of endocrine disrupting chemicals compared to other toxins, said panelist Patricia Hunt, a professor at Washington State University and longtime researcher on the effects of BPA on reproduction.
EDCs like BPA can appear to mimic the natural hormones in the human body and demonstrate some of their most harmful effects at very low doses. Many regulators such as the FDA conduct toxicology studies that assume that the higher the toxin the dose, the worse the negative effects.
Harmful effects seen at very low doses in past regulatory studies on BPA overseen by the FDA have often been dismissed as “spurious” outliers because those effects are not seen at higher doses, Hunt said.
In the eight studies analyzed in this report, however, effects were consistently seen in organ systems including the brain, heart, prostate, urinary tract, mammary glands and ovaries at the lowest dose tested, 2.5 micrograms per kilogram of body weight per day.
“What we should conclude from this is that all of these correlations can provide compelling evidence that the effects we’re seeing at low doses are not spurious,” Vandenberg said. “There are consistent effects across organs and across outcomes.”
Factoring in a margin of safety onto the lowest dose tested in the academic CLARITY-BPA studies, the panelists said that the actual tolerable daily intake of BPA should probably be 0.0025 micrograms per kilogram of body weight per day – 20,000 times lower than the current FDA standard of 50 micrograms per kilogram of body weight per day, and
“The lowest dose elicited the strongest effects across studies,” Hunt said. “We really need to reassess the safety of this chemical.”
Ultimately, Vandenberg concluded, CLARITY-BPA offered a promise. “The promise was to link regulatory outcomes with academic studies,” she said, pointing out that academic researchers have now fulfilled their end of the promise.
“My hope is still that the FDA will fulfill their promise,” she said.
More information about the panel, which was moderated by Pete Myers, founder and chief scientist of Environmental Health Sciences and an adjunct professor of chemistry at Carnegie Mellon, can be found online here.