Scientists rebut federal finding on baby safety
By Susanne Rust srust@journalsentinel.com

Scientists furious at conclusions reached by a federal panel charged with assessing the safety of a common household chemical have retaliated. And they're using science as their weapon.

In a paper released online this month in the journal Reproductive Toxicology, a team of researchers at the University of Missouri published a study that strikes at the core of the panel's findings on bisphenol A, a chemical found in baby bottles and the linings of food cans.

The researchers have shown that the panel's decision to disregard dozens of studies in which animals were exposed to the chemical via injections, instead of through the mouth or stomach, was specious. And they are calling on the government to re-evaluate, or dismiss, the panel's conclusions.

In November, the Center for the Evaluation of Risks to Human Reproduction released a report on bisphenol A that minimized concern about the chemical after reviewing more than 700 studies published over the past 30 years.

Hundreds of studies have shown that this chemical can cause a host of maladies, including breast cancer, testicular cancer, diabetes, hyperactivity, obesity, low sperm counts and miscarriage in laboratory animals. The chemical has been detected in 93% of Americans tested.

In December, the Journal Sentinel found that the panel's report, written by 12 scientists appointed by the National Institute of Environment Sciences, gave more weight to industry-funded studies and more leeway to industry-funded researchers. The newspaper found that the panel missed dozens of studies publicly available that the newspaper found online using a medical research Internet search engine.

This latest research exposes one of the major criticisms raised against the panel -- namely, the decision to throw away, or give only marginal weight, to studies in which animals were injected with bisphenol A, as opposed to getting it through the mouth or stomach.

The panel wrote that because people are most likely exposed to bisphenol A by the mouth, when it leaches into canned foods or liquids consumed in clear plastic bottles, it's the only relevant way to expose animals.

It also cited research showing that when adult animals and people ingest bisphenol A, enzymes in the liver make the chemical inactive.

However, when adult animals are injected with the chemical, this route is bypassed, and they show much higher concentrations.

Some studies ignored This decision caused the panel to consider more than 40 government and academic studies as inadequate, or of only limited value.

One of these papers, published in 2003 and funded by the Japanese government, found that bisphenol A could disrupt the development of female reproductive organs in mice that were exposed in utero. The panel considered it of only limited value, because the mother mice were injected with the chemical.

Another study, funded by the National Institutes of Health, showed that mice exposed in utero had a higher propensity to have prostate lesions than animals that were not exposed. Again, this study was considered of only limited value because the animals were not exposed orally.

In response, Frederick vom Saal, a biologist at the University of Missouri-Columbia and a vocal critic of the panel, decided to test the panel's assumption.

"Their decision was absurd," he said.

"First of all, fetuses don't eat," he said. "Anything in maternal blood will freely cross the placenta. And unless the chemical is immediately cleared out of the mother's system, which it isn't, that blood will go immediately to the baby."

In addition, fetuses and newborns lack, or express at low levels, the liver enzyme that deactivates the chemical.

"This is not news," said vom Saal. "Pediatricians will tell you, babies are not little adults. They do not process chemicals the same way adults do."

To demonstrate this, vom Saal and fellow researchers Wade Welshons and Juliet Taylor exposed 3-day-old female mice to bisphenol A. They separated the mice into four groups.

Two groups were exposed to the chemical through the mouth -- one group received a high dose, the other a low dose. Two other groups received injections -- again, one high and one low.

Animals were killed at intervals over the next 24 hours, and concentrations of bisphenol A in the blood were measured.

The team found no difference between animals that had received the chemical orally or via injection.

"It wasn't just that there was no difference," said vom Saal. "It was exactly the same."

Vom Saal said that both people and rodents have this particular enzyme, and in both cases, fetuses and newborns do not express it at the same level as adults.

This new research has the potential to upset the panel's findings, said Gail Prins, a researcher at the University of Illinois at Chicago who has been critical of the panel's report.

The bottom line She said that what really matters in these studies is the concentration of biologically active bisphenol A in the blood, irrespective of how it got there. Animals should have concentrations that are similar to what is found in people, because that is what is relevant in these studies.

However, Robert Chapin, the chairman of the panel, and an executive at Pfizer, said the new research "stands in contrast to a number of other studies that show the opposite." He said it was those other studies that "led us to the logical conclusion we reached."

When asked to supply the citations for those studies, he said he could not remember them offhand. He also said that if other scientists could eplicate vom Saal's work "and provide a rational explanation for the sudden shift," the panel would reconvene and reconsider its position.

Prins said her lab will take up that challenge immediately.

The Journal Sentinel reviewed the panel's report and found several studies that showed differences between oral and non-oral exposures in adult animals, but none that looked at newborns.

When asked to respond to the Missouri study, L. Earl Gray Jr., an Environmental Protection Agency toxicologist and a member of the panel, forwarded a study funded by the American Plastics Society. He said the study, which was reviewed by the panel, suggested that newborn mice have enough of the liver enzyme to deactivate bisphenol A at low doses.

However, the authors of the study, who were from Dow Chemical, reported that 4-day-old mice had a 10- to 18-fold higher concentration of biologically active bisphenol A in their blood than adults -- a finding that vom Saal and Prins say supports their contention.

"They had this information right there," said Prins. "Yet, they ignored it."

Michael Shelby, director of the government agency that selected the panel to evaluate bisphenol A, said his program will take all public comments and new publications into consideration before preparing the National Toxicology Program's final report on the chemical.

The Toxicology Program will use the panel's report, as well as other research, as a guide for its own final report on bisphenol A.

"We recognize that there are concerns about the issue of route of  exposure," he said, "and we will give careful consideration to all the scientific evidence available to us on this issue."