Omnipresent hazard

Ordinary plastics pose extraordinary health risks

Ana M. Soto and Carlos Sonnenschein didn’t mean to change a paradigm. But after 16 years of researching endocrine disruptors—compounds that interfere with the normal cascade of chemical signals in the body—a new study by the research team shows that prenatal exposure to even minute levels of a common chemical long thought to be safe can significantly impact growth and development during adolescence.

Carlos Sonnenschein and Ana M. Soto © MELODY KO

The culprit is the common plastics additive bisphenol-A (BPA). It’s in our baby bottles, eyeglass lenses, cell phones, water bottles, CDs and DVDs, and household appliances as well as in industrial resins and epoxies.

Soto and Sonnenschein, both professors of anatomy and cellular biology at the School of Medicine, and their colleagues at the Universidad Nacional del Litoral in Santa Fe, Argentina, found that exposing fetal mice to BPA led to abnormal mammary gland development when those mice reached adolescence. Very small doses of the chemical—of the same magnitude people routinely encounter—were responsible for significant morphological changes in the mammary glands. Soto and Sonnenschein’s findings, reported in the journal Endocrinology, refute the conventional—and industry-touted—wisdom that the amount of BPA in the environment is too low to affect human health.

“We used BPA as a model, as a way to demonstrate the effects of the hundreds of compounds that add up,” Sonnenschein says.

In their recent experiment, the researchers fitted pregnant mice with pumps that delivered precise daily doses of BPA. One group of mice received a higher dose of BPA, while another received a relatively low dose. The dosing began on the ninth day of the 20-day gestation period and continued for two weeks, until the mice pups were four days old.

Developmental changes
As the female pups approached puberty, the researchers compared their mammary glands. During puberty—in rodents as in human females—hormones signal the tree-like branching ducts to increase in number and grow through the fatty tissue of the mammary gland. Bulbous structures called terminal end buds (TEBs) are the locus of all this growth and cell division.

Before the onset of puberty, all the mice had similar numbers of TEBs. However, as they officially entered puberty, both groups of BPA-exposed mice showed an increased number of TEBs relative to the ductal area, compared to the control mice, which were not exposed to the compound. Moreover, the effect was more pronounced in the mice exposed to the higher dose of BPA than in those exposed to the lower dose.

The researchers’ other findings suggest that BPA caused the developmental and morphological changes by enhancing the mammary cells’ sensitivity to estrogen. To test that hypothesis, the scientists removed the ovaries from the mice and exposed the animals to estradiol, the most active of the natural estrogens. The total number of TEBs, total TEB area, mean TEB size, TEB number per ductal area and TEB area per ductal area all spiked in the animals exposed to BPA before birth, showing that perinatal exposure to BPA renders the mammary gland more sensitive to estrogen during adolescence.

What might this mean for people? A 2004 study revealed that people ingest a maximum of 0.23 micrograms of bisphenol-A per kilogram of body weight per day. It is now found in 95 percent of Americans’ bodies.

First synthesized in 1905, BPA, a common ingredient in plastics that are see-through and shatter- and heat-resistant, has been commercially produced in the United States and Europe since the 1950s, according to the Bisphenol A Global Industry Group. In 1983, the National Academy of Sciences concluded that BPA “poses no known risk to human health.”

Hormonal activity
But it wasn’t until 1996 that the EPA—influenced by the work of Soto and Sonnenschein and their colleagues—recommended screening industrial chemicals for hormonal activity. Studies by Sonnenschein and Soto and others revealed that BPA and its chemical cousins can, in fact, behave like estrogens in the body.

“There are minimal requirements to be an estrogen, chemically speaking,” says Soto. “Everything that is a phenol has some estrogenic characteristics.”

Soto and Sonnenschein learned this the hard way in 1987, when a routine experiment suddenly went wrong. Believing that cells will divide continually when left to their own devices, the researchers had spent several years attempting to isolate the compounds that inhibit cell growth—a somewhat radical notion at a time when most of their colleagues believed just the opposite: that growth factors nudge cells out of their default state of nonproliferation. In search of their hypothetical inhibitors, Soto and Sonnenschein routinely exposed colonies of breast cancer cells to varying levels of estrogen and other compounds to see which combinations encouraged cell growth and which seemed to arrest it.

Laboratory culprit
But when all the cells suddenly began exhibiting uncontrolled growth, their research was delayed for four months while they searched for the estrogenic contaminant. Eventually, they identified the culprit: The manufacturer of the plastic test tubes they’d long been using had changed the formula. Though the manufacturer would not divulge the compound in the new formula that triggered the cell growth in Soto and Sonnenschein’s lab, two more years of research revealed the culprit to be p-nonylphenol, another plastics additive found in PVC. Soto and Sonnenschein were among the first to report estrogenic effects in plastics long thought to be safe and inert.

Nearly 20 years after their surprising discovery, Soto and Sonnenschein continue to investigate the impact of endocrine disruptors on the environment. Soto is currently designing follow-up experiments to test whether BPA enhances the incidence of cancer in rodents exposed to a known carcinogen. She hypothesizes that it will, given that the area BPA affects—the TEBs and the ducts—are the very tissues in which cancers commonly develop.

“Everything [BPA] does is a risk factor for cancer,” Soto says.

Jacqueline Mitchell is a senior health sciences writer in Tufts’ Office of Publications. She can be reached at