Medical Device Daily National Editor

Health activists attending a Sept. 16 FDA meeting concerning the use of Bisphenol A (BPA) to make consumer plastics products will have some new ammunition and somewhat more persuasive ammunition, at that to fight for a ban on these products.

New research out of the University of Cincinnati (UC) indicates that BPA in humans may become a risk factor for metabolic syndrome and its disease consequences.

The FDA earlier this year issued a statement saying that there is insufficient evidence proving that BPA used in making plastic baby bottles is harmful and that a ban on this use is unnecessary (Medical Device Daily, June 18, 2008). It set the Sept. 16 meeting to provide a close look at the evidence for its view and to collect public input (MDD, Aug. 21, 2008).

The FDA opinion has produced considerable vocal pushback from several health advocate groups, claiming that the FDA has failed to consider the totality of evidence, and alleging undue influence by the American Chemistry Council (ACC; Arlington, Virginia).

Thus far, however, those claiming the harm of BPA in humans have been able to cite only evidence from animal models, easily attacked as insufficient to be generalized to humans.

But the new UC research uses an alternative to the animal model methodology to indicate the connection between BPA and metabolic syndrome.

Nira Ben-Jonathan, PhD, a professor studying cancer and cell biology, and the research team leader, told Medical Device Daily that while the previous research used rats and high levels of BPA, her work employs amounts that reflect the general exposure to humans and that "for the first time, we are using human material" in determining the effects of the chemical.

Metabolic syndrome is the result of a combination of risk factors including reduced responsiveness to insulin and higher blood levels of sugar and lipids with the syndrome thought to increase the risk of Type 2 diabetes, heart disease and stroke. The American Heart Association (Dallas) estimates that about 25% of all Americans have metabolic syndrome.

Whether this new evidence will have much influence on the debate is yet to be known, however, since there is some debate concerning the causative association between it and diabetes and heart disease. Some researchers say that while risk factors for these diseases do come together, they may not add up to causation of these diseases.

However, the UC research appears to take the debate concerning BPA to another level in terms of its methodology.

Using human fat tissues, the research data showed that BPA suppresses a key hormone, adiponectin, responsible for regulating insulin sensitivity in the body, thus putting people at much higher risk for metabolic syndrome. The researchers emphasize that the study mimics "realistic" human exposure (between 0.1 and 10 nanomolar), to establish a direct correlation between human exposure and health effects.

And Ben-Jonathan said the study is the first to provide scientific evidence on the health effects of BPA at environmentally relevant doses equal to "average" human exposure.

"Fresh" fat tissue was collected from patients undergoing several types of breast or abdominal surgery, including three types: breast, subcutaneous and visceral. The tissue was then incubated with different concentrations of BPA or estrogen for six hours to observe how the varied amounts of BPA affected adiponectin levels. The effects of BPA then were compared to those of estradiol, a natural form of human estrogen.

They found that exposing human tissues to BPA levels — within the range of common human exposure — resulted in suppression of a hormone that protects people from metabolic syndrome.

Ben-Jonathan said she began studying the effects of BPA in 1994, published her first paper on it in 1996 and has produced subsequent papers on the issue.

She told MDD that the recent research underlines what she has felt before: that she is "quite concerned" about BPA use in plastics. In a press statement, she said, "As the scientific evidence continues to mount against the chemical, it should be given serious attention to minimize future harm."

Ben-Jonathan said that the use of human tissue "is the closest we can come to testing the effects of BPA in humans" and offers an "exciting breakthrough," given the widespread use of the chemical.

She noted the difficulty of developing a comparator control group, because "most people have already been exposed to" to the chemical, citing data indicating that more than 80% of people tested have measurable BPA in their bloodstream.

"These results are especially powerful because we didn't use a single patient, a single tissue source or a single occurrence," Ben-Jonathan added. "We used different fat tissues from multiple patients and got the same negative response to BPA."

The impact of the research on the debate is likely to be another point for the debate, however, because the clinical value of a diagnosis of metabolic syndrome may not be definitive.

Some researchers assert that different sets of conflicting and incomplete diagnostic criteria exist, and that metabolic syndrome has only a negligible association with the risk, for instance, of heart disease.

But Ben-Jonathan said that she has still other concerns about BPA, based on research she expects to be published later this year.

This research, she said, indicates that BPA suppresses the effects of chemotherapeutic drugs, oncology being her broad area of interest.

In this research, breast cancer cells were used to study the effect of BPA on "three or four different," commonly used cancer therapeutics, she said, with the chemical suppressing the effect of the drugs.

On its web site, the ACC cites FDA's draft assessment concerning BPA, specifically its belief that "an adequate margin of safety exists for BPA at current levels of exposure from food contact uses."

"These conclusions," the ACC says, "are consistent with the findings of many other recent reviews conducted by government agencies worldwide."

The new UC study, reported in the Aug. 14 online edition of the journal Environmental Health Perspectives, was funded by grants from the National Institute of Environmental Health Safety.