FDA's Animal Data on BPA Exposure Mixed

The jury's still out on the effects of early and chronic exposure to bisphenol A (BPA), according to a draft report by the National Toxicology Program.

In a pre-peer review report of the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) core study, exposure to BPA seemed to produce minimal and varied outcomes among female and male rodents.

"Although a comprehensive review of this report, along with future data from other CLARITY-BPA research, will be conducted as part of our continued assessment of BPA safety, our initial review supports our determination that currently authorized uses of BPA continue to be safe for consumers," said Stephen Ostroff, MD, FDA deputy commissioner for Foods and Veterinary Medicine, in a statement.

"The report also builds upon the already extensive data collected in the FDA's 2014 assessment of the safety of BPA," he added.

Two groups were assessed in the study -- a continuous-dose BPA group who were exposed to BPA throughout gestation and in the first 1 to 2 years of life and a stop-dose study arm who were only exposed to BPA from gestation through postnatal day 21. The level of exposure to BPA ranged from 2.5 to 25 to 250 to 2,500, to 25,000 μg/kg body weight per day. In the continuous-dose arm, a subgroup exposure to orally active estrogen ethinyl estradiol (EE₂) (0.05 and 0.5 μg/kg dw/day) was also included.

Many of the outcomes associated with BPA exposure were varied, without "a clear pattern of consistent responses in the stop-dose and continuous-dose study arms," the group wrote.

Of the few outcomes that reached significance, most were seen in female rodents. In the continuous-dose group at the 250 μg/kg bw/day exposure to BPA, female body weights were significantly greater than controls later on in the study, although this was not seen among other doses nor at other points of the analysis. There was some variance seen among specific organ weights in the female rats, although the researchers noted that it was not clear that these were treatment-related.

Some of the most apparent outcomes seen in female rats exposed to BPA included the increase in both neoplastic and non-neoplastic lesions over time. In the stop-dose group exposure to 2.5 μg/kg bw/day, there was a significant increase in female mammary gland adenocarcinoma (22% versus 6%, P=0.016) and the combination of adenoma and adenocarcinoma incidence (24% versus 8%, P=0.018) after 2 years. Similarly in the continuous-dose arms, exposure to 2.5 μg/kg bw/day, there were significant increases in the incidence of female mammary gland atypical foci, as well as a trend toward uterine stromal polyps.

For male rats, there were also several trends toward increases in non-neoplastic lesions, although most were seen in higher levels of BPA exposure and nearly all were seen only after 2 years after exposure.

Most notable, however, the researchers said, were the outcomes in the EE₂ reference group -- most of which were seen among females. More than 90% of the females' exposure to the higher dose of EE2 showed prolonged estrus, along with higher mean weights of adrenal glands, heart, liver, kidney, and pituitary glands, along with lower ovary weights.

With the varying degree of outcomes seen through the various BPA doses, "the significance of these findings will be assessed through the peer review process," said Ostroff, adding, however, that this "initial review supports our determination that currently authorized uses of BPA continue to be safe for consumers."

Currently, several organizations recognize BPA as an endocrine-disrupting chemical, including The Endocrine Society, which has suggested that "the BPA substitute, BPS [bisphenol S], is now shown to have endocrine-disrupting activity on par with BPA in experimental studies discussed in [The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals]."

"It is premature to draw conclusions based on the release of one component of a two-part report," commented Endocrine Society spokesperson Laura N. Vandenberg, PhD, in a statement. "The National Toxicology Program draft report released Friday included the results of one government study with a partial data set and has yet to undergo peer review."

"The endpoints studied here do not encompass the full effects of endocrine-disrupting chemicals, especially because the whole point of this study was to compare the [National Center for Toxicological Research]'s endpoints with more sensitive effects evaluated by endocrinologists. Furthermore, the NCTR's data does not provide assurance of BPA's safety. They found certain BPA doses are linked to a higher rate of mammary gland tumors, which is concerning," she added.

The study will go through external peer review in April, and public comments are currently being accepted on the National Toxicology Program's website. The final findings of the CLARITY-BPA consortium are expected in 2019.

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