The study started as an accident. Geneticist Patricia Hunt of Washington State University and her team were investigating the reproductive effects of BPA in mice. Housed in BPA-free plastic cages, the test group got doses of BPA through a dropper; the control group didn't.

Everything seemed rosy—until it wasn't.

“Our control data just started to get really wonky,” Hunt says. The differences between it and the test group vanished, and many control mice started showing genetic issues. Though initially confused, the team discovered that some of the plastic caging was damaged and was leaching bisphenol S, or BPS—an alternative to the now infamous plastic component BPA.

It was like déjà vu, Hunt says. Twenty years ago, she’d had the same issue with BPA in polycarbonate mouse cages. Now her study of the effects of several BPA alternatives, prompted by the latest accidental findings, suggests that these replacements impact reproduction in mice in much the same way.

Of course, it's hard to draw conclusions between the effects in these tiny furry critters and those in our comparatively massive fleshy forms, but the latest work adds to a growing body of evidence that suggests all is not safe in the world of BPA-free plastics. What's more, the study underlines a broader issue in commercial compound development: When chemicals are removed from the market, they're often replaced by others that not only look similar—but act similarly in our bodies.

“We have to play catch up as disease detectives,” says Leonardo Trasande, director of the division of environmental pediatrics at NYU Langone Health, who was not involved in the research. But this detective work is a losing proposition, he says likening it to a game of “chemical whack-a-mole.”

What Is BPA?

Bisphenol A, or BPA, is a common building block in resins and some types of plastic. It's what's known as an endocrine disrupting compound. In the body, these chemicals can act like hormones or disrupt normal hormone functions.

“What's kind of disturbing about this is hormones regulate almost everything in our bodies,” says Johanna Rochester, senior scientist with the nonprofit The Endocrine Disruption Exchange, who was not involved in the work. In the case of BPA, concerns surround its estrogen-mimicking effects.

In the past couple decades, research on BPA has exploded. A slew of studies document negative reproductive, developmental, and metabolic effects in a menagerie of wildlife— rhesus monkeys, zebrafish, nematodes, and mice. Even human studies have linked BPA to a range of health issues.

In the 1950s, BPA was used in the first epoxy resins. Soon after, Bayer and General Electric discovered the molecules had a nifty trick: They could link together with a small connector compound to form a shiny, hard plastic known as polycarbonate.

Soon, BPA was everywhere: reusable water bottles, plastic plates, the liners in canned foods, sippy cups, grocery receipts, and even some dental sealants. But as people drank from their water bottles and ate their microwaved dinners, they were unknowingly dosing themselves with small amounts of BPA that leached from the plastic containers into their food and drink.

The compound has since become so ubiquitous that of the 2,517 people tested in the Centers for Disease Control and Prevention's 2003-2004 National Health and Nutrition Examination Survey, 93 percent had detectable levels of BPA in their urine.

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Mounting public pressure pushed companies to move away from BPA, leading to an influx of products touting their “BPA-free” status. But the FDA only officially bans the compound from use in baby bottles, sippy cups, and infant formula packaging. According to the FDA website: "Studies pursued by FDA's National Center for Toxicological Research (NCTR) have shown no effects of BPA from low-dose exposure."

Different, But Not Necessarily Better

Since BPA-free became trendy, manufacturers went on a plastic-developing spree, creating more variations than scientists can keep track of: BPS, BPF, BPAF, BPZ, BPP, BHPF, and the list goes on. They all have “BP” in their names because they share the same basic chemical structure of a bisphenol. Each new version has only slight differences, as if swapping a blue Lego block for a red one.

The latest study adds to the mounting research that suggests consumers aren't off the hook buying BPA-free plastic. The results show that common BPA replacements—BPS, BPF, BPAF and diphenyl sulphone—can interfere with what Hunt characterizes as “the very, very, very, very earliest part of making eggs and sperm.”

Mice—and humans—normally get one copy of genetic material from each parent and then splice together bits of each to form the chromosome they pass on to the next generation. Hunt and her team found that BPA and its alternatives disrupt this process in a way that could eventually cause a decrease in sperm counts in males and a reduction in egg quality in females. What’s more, the changes can be passed down to subsequent generations.

Though gaps remain in understanding how the range of BPA alternatives affect humans, researchers are concerned. “They look a lot like BPA,” says Hunt. “It stands to reason that they're going to behave a lot like BPA.” Rochester agrees, saying that such a conclusion “is not a huge leap.” And this is hardly the only study suggesting negative effects from BPA alternatives. Dozens have been published in the past year alone.

“It speaks to the reality we need to regulate chemicals, not one by one, but in a class—in a way that allows us to tackle compounds that function with similar structure,” Trasande says.

How Did This Happen?

Scientists have a term to describe this analogous chemical swapping: regrettable substitutes. And the issue isn't limited to BPA. Many groups of compounds are suffering from the problem of too-similar replacements, including flame retardants (used in furniture, vehicles, and electronics), phthalates (used in cosmetics, personal care products, adhesives, plastics, and pharmaceuticals), and polyfluoroalkyl substances (used in nonstick products like teflon).

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There are startlingly few regulations to keep this from happening. And many of the tests to identify endocrine disruptors such as BPA are outdated. “The old standard toxicology testing methods were devised decades ago,” says Hunt. “And they're pretty crude techniques.”

While many government studies only show effects of BPA at high doses, numerous independent academic researchers have demonstrated BPA's low-dose negative effects as well. To reconcile these differences, three government bodies—the National Institute of Environmental Health Sciences (NIEHS), the National Toxicology Program (NTP), and the Food and Drug Administration (FDA)—recently teamed up with a group of independent researchers to undertake a massive multimillion-dollar study called CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity). Each team looked at different effects, but all used the same basic experimental framework. Ultimately this type of work could lead to better toxicology testing, says Hunt.

The final results of their tests will be released Thursday, after this story is published. But scientists are already perturbed by the draft report released last February that details the regulatory side of the results. Overall, the results of the draft study again conclude BPA has “minimal effects” at low doses. The FDA did not reply to a request for comment.

“It's a great idea; it was really what we need to improve toxicology testing,” says Hunt, but she adds, “there's a lot of problems with the CLARITY.” From issues with controls to selection of study animals to contamination of the system—much like what inspired Hunt’s latest study—outside scientists argue that many factors futzed with the final result.

The Bright Side

There’s a small glimmer of hope at the end of the plastic rainbow. “The good news is, if you can eliminate all of these things from the face of the world, we could go back,” says Hunt. The latest study found that if the researchers stopped dosing the mice with BPA alternatives, the males returned to normal in just four generations.

Consumers can also take steps to avoid BPA alternatives entirely, notes Trasande. He suggests steering clear of plastics with the recycling numbers 3, 6, and 7, which all contain compounds of concern. Don’t put plastics in dishwashers or the microwave, which can damage them and cause them to leach more BPA or its alternatives. Throw away plastic when it looks aged or scratched. And opt for glass or steel containers rather than lined aluminum cans whenever possible.