Daniel Lubetzky

The deleterious estrogen-​mimicking compound, bisphenol A, first came under inspection when peopled noticed that the compound is found on baby bottles and food cans.  Now, the compound has shown up in materials beyond those that make up bottles and cans, and has been exposed as existing on cash register receipts.   Although the BPA on receipts is in miniscule quantities, “When you grab the receipt, your fingertips can get coated with BPA,” says John C. Warner of the Warner Babcock Institute for Green Chemistry (WBI).    The article which delineates these facts goes on to explain the variety of harmful forms and substances that can seep in through the skin that one should be aware of.

Exposure Routes Confound BPA Debate

Beyond bisphenol A in food and drink containers, people face many sources of endocrine disrupters in everyday life

Stephen K. Ritter

John Warner

ON CONTACT Cash register receipts are one source of human exposure to bisphenol A, shown in its off-white crystalline form.

June 16, 2011

Concern over potentially harmful health effects from exposure to the estrogen-​mimicking compound bisphenol A initially leveled a spotlight on baby bottles and food cans. But that focus has left several other potentially important sources of estrogen mimics in the environment largely in the dark.

In fact, sources of these so-called endocrine disrupters go well beyond bottles and cans. Key among them are credit card and cash register receipts that use BPA in the printing process, natural estrogenic compounds found in foods, and estrogenic compounds that leach from a wide range of plastics, not just those that contain BPA.

“When it comes to BPA in the environment, the biggest exposure, in my opinion, is from cash register receipts,” says John C. Warner of the Warner Babcock Institute for Green Chemistry (WBI), in Wilmington, Mass. “Once on the fingers, BPA can be transferred to the mouth, onto food, and likely absorbed through the skin.”

The BPA-receipt connection is something Warner has been thinking about for years, based on knowledge of thermal-imaging printing technology he gained as a researcher at Polaroid in the 1980s and ’90s.

In polycarbonate plastic bottles and epoxy resin food-can liners, BPA exists as a monomer unit bound in a polymer—nanograms of residual BPA might leach out, Warner explains. “But for thermal imaging,” he emphasizes, “receipt-paper manufacturers put a powdery layer containing BPA and an invisible ink on one side of the paper. In this case, BPA is a free substance coated on the paper in milligram quantities.

“When pressure or heat is applied, the chemicals meld together to form an imprint,” he continues. “When you grab the receipt, your fingertips can get coated with BPA.”

In the early 2000s, when he was a chemistry professor at the University of Massachusetts, Boston, Warner had students go to different retail and grocery store chains to gather receipts, bring them into the lab, and then analyze samples by mass spectrometry to quantify the amount of BPA present. With the recent upwelling of interest in BPA exposure, Warner and his team at WBI repeated the experiments last year (Green Chem. Lett. Rev., DOI: 10.1080/17518253.​2010.​502908).

The results in both studies indicate that in the Boston area about 70% of the stores had BPA in their receipts. “But more important, 30% didn’t,” Warner says. “That means there’s already a cost-effective alternative technology in the marketplace, so we don’t need to invent a new technology to solve this problem.”

One “disheartening” detail about almost all of the BPA-free thermal-imaging papers, Warner cautions, is that they employ ­bisphenol S compounds in which an SO₂ unit occupies the spot of BPA’s isopropylidene group. “From what I understand, BPS displays the same estrogenic activity as BPA,” Warner says.

Warner is now helping retailers determine whether their receipts contain BPA and the best way to avoid the issue if they do, either by switching thermal-imaging paper or going to a different printing ­system.

“When you grab the receipt, your fingertips can get coated with BPA.”

Last year, a pair of research studies helped confirm Warner’s speculation that BPA can be readily absorbed through the skin and that people who constantly handle receipts are at risk for higher exposure (C&EN, Nov. 15, 2010, page 36).

Daniel Zalko of the French National Institute for Agricultural Research, in Paris, led a team that measured significant diffusion of ¹⁴C-labeled BPA through samples of pig and human skin. Separately, Harvard University’sJoseph M. Braun and coworkers monitored the diets and analyzed BPA in urine samples of nearly 400 pregnant women, finding that cashiers had the highest BPA levels and that teachers and industrial workers had significantly lower levels.

Actually, people can be exposed to BPA without directly handling receipts: A study released last December by Erika Schreder of the Washington Toxics Coalition, a nonprofit environmental advocacy organization, found that most paper currency is contaminated with small amounts of the chemical, likely originating from contact with receipts.

In addition to food and drink packaging, the food and drink itself is another important route by which humans are exposed to endocrine disrupters. People regularly ingest dozens of natural compounds in foods and beverages that are stronger estrogen mimics than BPA. One letter to the editor sent to C&EN last year by Donald R. Kelsey of Guerneville, Calif., pointed out that exposures to these so-called phytoestrogens typically far exceed the exposure levels of man-made BPA, but they have received little publicity (C&EN, April 19, 2010, page 5). One explanation for this lack of attention, Kelsey writes, “is the common but false assumption that synthetic chemicals such as BPA are suspect, but ‘natural’ chemicals are harmless.”

Phytoestrogens include isoflavones, coumestans, and lignans found in beans, olive oil, some fruits and vegetables, cereal grains, tea and coffee, wine and beer, and chocolate. Their phenolic structures are similar to the structures of estrogens, generally more so than BPA’s structure.

Researchers have observed a mixed bag of effects with phytoestrogens. Some compounds have been shown in lab studies to act as beneficial antioxidants by trapping singlet oxygen, a reactive species that can cause cellular damage. But others exhibit adverse effects in animals and humans. For example, coumestrol and the isoflavone genistein, found in soy products such as tofu, can negatively affect fertility, pituitary function, birth weight, and puberty onset in rats. Soy protein, however, is associated with lower rates of breast cancer and other types of cancers.

BPA manufacturers suggest that, given the level of exposure to phytoestrogens in the daily diet, the tiny amounts of BPA that leach from polycarbonate plastics and ­epoxy resins may not really matter.

The counterargument is that natural estrogenics have been around for millions of years and humans have evolved with them, Warner points out. “The issue with man-made things is that we did not coevolve with them, and thus we likely lack any compensatory biochemistry,” he says.

In fact, studies by Duke University epigeneticist Randy L. Jirtle and coworkers have found that some phytoestrogens can counteract BPA’s adverse effects. The researchers suggest that genistein, for example, might be useful as a dietary supplement for women during pregnancy to protect their unborn children from BPA exposure (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.0703739104).

Other plastics—even BPA-free ones—may also be a source of endocrine disrupters. A recent analysis of more than 450 everyday plastic products, from plastic bags to water bottles, found that about 95% of the items tested leached chemicals that triggered a bioassay for estrogenic activity, including most of the products labeled as BPA-free (C&EN, March 14, page 48).

The plastics analysis didn’t attempt to identify the individual estrogenic compounds responsible in each case. Instead it focused on quantifying estrogenic activity, irrespective of the chemical causes, explains neurobiologistGeorge D. Bittner of the University of Texas, Austin, who led the study. “Although BPA is the most notorious chemical with estrogenic activity used in plastics, it is not the only one, nor does it have the highest biological effect,” Bittner says.

Bittner believes compounds with phenolic moieties such as BPA or that are converted to or degrade to phenolic compounds during product use are the most common causes of estrogenic activity in plastics.

Not all chemicals that show estrogen-like activity are necessarily toxic, he adds. But Bittner is concerned that ingesting these chemicals from plastics contributes to people’s daily load of estrogenic compounds, and he suggests that it makes sense to seek out estrogenic-activity-free plastics, especially when the additional production cost “can often be as little as a fraction of a cent per pound.”

For now, manufacturers that have gone BPA-free have switched from polycarbonate to different base polymer systems, notably Eastman Chemical’s Tritan copolyester, glycol-modified polyethylene terephthalate (also a copolyester), and clarified polypropylene, Bittner notes. “But as our data show, the switch to some new materials has not ameliorated the estrogenic activity: BPA-free does not mean estrogenic-activity-free,” he says. (See also cenm.ag/4.)

Scientists involved in the BPA issue are quick to point out that the estrogenic assay study of plastics needs to be verified, in particular because Bittner has a conflict of interest in the results.

The research was carried out at CertiChem and PlastiPure, a pair of contract firms cofounded by Bittner. CertiChem uses its estrogenic activity assays to test plastics, foods, chemicals, and packaging. PlastiPure designs plastic formulations so that products can be certified to be free of endocrine-disrupting activity. Bittner stands by his results, noting that the study was funded by the National Science Foundation and by the National Institute of Environmental Health Sciences, and it was published in NIEHS’s peer-reviewed journal, Environmental Health Perspectives.

“Before we jump to the conclusion that all plastics are bad, some important details need to be filled in,” observes Daniel F. Schmidt, a polymeric materials chemist at the University of Massachusetts, Lowell, who reviewed the Bittner study for C&EN. “While the compositions of specific plastics formulations often are not publicly released, we know which compounds are used as additives in the plastics industry. What we don’t know is which compounds are being extracted in the Bittner research and trigger the assays, or the extent to which they constitute an important source of human exposure.”

Schmidt argues that rapid progress is needed on the question of human exposure to endocrine disrupters, and that better screening of plastics under actual-use conditions will be an important part of any answer. For additional context, the significance of other sources of possible estrogenic phenolic compounds, such as paper products and phytoestrogens, should also be studied, Schmidt says, “to give ourselves a reality check and make sure we’re not missing the forest for the trees.”