Bisphenol-A Study Adds to Worries over Its Effects on Humans

Chemical found in plastics, canned foods linked to synapse damage in monkeys.

by Jim Schnabel

October 21, 2008

The controversial industrial chemical known as Bisphenol A (BPA), to which most people are routinely exposed, blocks a normal process of synapse formation in the brains of monkeys, even at a dose currently labeled as “safe” by the U.S. Environmental Protection Agency (EPA), report Yale researchers. The study, reported online Sept. 3 in the Proceedings of the National Academy of Sciences, is the first to look at the effects of BPA in primates. It suggests that previous studies showing negative effects of BPA on the brains of rodents are likely to apply to humans as well.

“We found that primates are at least as sensitive to BPA as rats,” says Csaba Leranth, the Yale University neurobiologist who led the study.

BPA is a component of some polycarbonates and epoxy resins used in clear plastic water bottles, the linings of food and beverage cans, dental sealants and other products. Tiny amounts of the chemical are known to leach from these products.

For years researchers have wondered whether these small exposures could be harmful to humans over the long term. BPA is known as an “endocrine disrupter” for its ability to interfere with ordinary hormonal signaling in the body. Such signaling is important to the function of various organs including the reproductive organs and the brain, but it is also crucial for the proper development of those organs.

Since the late 1990s, researchers have performed dozens of studies on BPA in rodents, and have generally found the kinds of effects one would expect from an estrogen signaling disrupter, including abnormalities of the breast, prostate and genitals, especially when BPA exposure occurs during early development.

Estrogen normally works in the brain, too. In 2005, Neil MacLuskey of the Helen Hayes Hospital in New York, together with Yale’s Tibor Hajszan and Leranth, reported that in rodents, BPA exposure at the EPA’s “safe” dose for humans inhibited the estrogen-induced formation of an important class of synapses on neurons in the brain’s hippocampus region, needed for most kinds of memory.

Leranth says that the study was criticized by the chemical industry because it was conducted only in rats; therefore he and his colleagues obtained National Institutes of Health (NIH) funding to do the same set of experiments in monkeys. The research team took young female monkeys whose ovaries had been removed and gave them either estrogen or estrogen-plus-BPA at the EPA’s current “maximum safe dose” of 5 micrograms per kilogram. Comparing the numbers of synapses on the input spines of a major class of neurons in the hippocampus and prefrontal cortex of the monkeys before and after treatment, the researchers found that, as Leranth puts it, “Bisphenol A completely wipes out the normal hormone-induced spine synapse number.”

“The key is that they found profound alterations in a primate model with exposure levels that are considered in the safe range,” says John Morrison, a researcher at Mount Sinai School of Medicine in New York who is an expert on hormonal effects on the brain.

How would BPA affect people?

In their rat and monkey studies, Leranth and his colleagues didn’t examine behavioral effects. But the researchers have found, in a study published in March, that BPA also disrupts the normal synapse-generating effects of testosterone in male rats, suggesting that it can have cognitive effects on animals of both genders.

“It is safe to say that should [synapse] deficits exist, they would be manifested in decreased cognitive performance,” says Morrison, although he notes that the effects could vary depending on the sex of the people exposed, as well as their age and overall neural health.

Researchers have not yet identified the brain-cell receptor or signaling pathway through which BPA exerts its synapse-inhibiting effects. They also don’t yet know how the effects of the chemical vary with the way it enters the body. In their animal experiments so far, Leranth and his colleagues have delivered BPA by subcutaneous injection, whereas humans are exposed to BPA primarily through food and drink. The few studies in which BPA has been administered orally, Leranth notes, have shown “major deterioration in the dopamine and the cholinergic system in the pups.” He and his colleagues are currently applying for funding to make direct comparisons between subcutaneous and oral administration of BPA in monkeys, as well as to study long-term and prenatal effects.

Common in the environment

The average person is frequently exposed to BPA, not only from food products but from dust and other sources. A study published earlier this year by the Centers for Disease Control, based on a recent National Health and Nutrition Examination Survey, suggested that more than 90 percent of people in the United States have detectable amounts of BPA in their urine. Moreover, in 2007, a Tufts University review of epidemiological and metabolic studies concluded that the “reported levels of BPA in human fluids ... appear to be within an order of magnitude of the levels needed to induce effects in animal models.”

Infants, whose rapidly developing bodies are particularly vulnerable to hormonal disruption, may be much more exposed than adults: BPA is commonly found in polycarbonate baby bottles, and it is known to leach into milk much more quickly when it is warmed.

“I usually don’t eat canned foods,” says Leranth, “but I have two grandchildren, and I’ve strictly prevented my daughter from giving them milk or baby food in plastic bottles. Usually these are heated, and that is the danger.”

Environmental studies also suggest that even low exposures to endocrine disrupters can have significant and widespread effects. In the past few years, researchers have reported that several rivers on America’s eastern seaboard have detectable levels of estrogens and other endocrine disrupters from upstream industrial and agricultural sources; in these rivers, biologists have reported a striking prevalence of “intersex” male fish that produce eggs.

A recent observational study in humans also hints at an environmental risk. Epidemiologists from the University of Exeter and their colleagues, using data from the National Health and Nutrition Examination Survey, found that Americans with elevated BPA levels also tended to have slightly higher rates of cardiovascular diagnoses, diabetes, liver function abnormalities and other conditions. Although an observational study such as this has little or no ability to link such conditions to a particular cause, its results are at least consistent with those of some animal studies.

Canada officially banned BPA from use in baby bottles this past April. In the United States and Europe, public awareness of BPA’s possible toxicity has led many bottle manufacturers to avoid using BPA-containing plastics, although it continues to be used in can linings and has not been officially banned. In April, the Food and Drug Administration (FDA) announced that “we believe there is a large body of evidence that indicates that FDA-regulated products containing BPA currently on the market are safe and that exposure levels to BPA from food contact materials, including for infants and children, are below those that may cause health effects.”

The U.S. National Toxicology Program (NTP) is an interagency group whose work often informs decisions made by the EPA, the FDA and other agencies. They recently reviewed existing publications on BPA and issued a report, coincidentally on the same day as the publication of Leranth’s study, that expressed “some concern for effects on the brain, behavior, and prostate gland in fetuses, infants, and children at current human exposures to bisphenol A.” The group expressed less concern that BPA could adversely affect breast tissue and the onset of puberty in girls, and that fetal exposure at the usual levels could cause birth defects.

Leranth says that as far as he knows, the NTP panel wasn’t aware of his group’s results in monkeys, although he was contacted by government scientists after the publication of those results.

“I think they are likely to reconsider the definition of a safe exposure in their next review,” says Morrison.