In the wake of the National Toxicology Program’s 2008 report, a team of scientists at the Centers for Disease Control and Prevention (CDC) analyzed more than 2,000 urine samples collected from a statistically representative cross section of the American population. More than 90% of those samples tested positive for BPA; the average concentration was 2.6 parts per billion (ppb), though the top 5% of samples had an average concentration of almost 16 ppb. That’s well past the amount of BPA known to cause harm in rodents. Concentrations seemed to decrease with age, so that children had more BPA in their systems than adolescents, and adolescents had more than adults. “This study really laid to rest any doubts about whether or not BPA was in fact leaching from our food containers into our bodies,” says Vogel. But did that necessarily mean that BPA was dangerous to humans?

Any given toxic substance has several characteristics we must consider when evaluating its safety. One such characteristic is its persistence—how long it takes the substance to break down in the environment. Chemicals with low persistence tend to break down quickly, especially in the presence of sunlight. Chemicals with high persistence tend to linger for a long time and can affect ecosystems well after their initial release.

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Another trait that must be considered is a toxic’s solubility—its ability to dissolve in liquid, particularly water. In some cases, water-soluble chemicals are safe for humans but not so good for the environment. Because we can excrete them in our urine, they don’t linger in our bodies for very long. (Of course, at high enough doses, these chemicals can still prove toxic, and at low but continual doses, they can cause kidney damage.) But because water-soluble chemicals are easily taken up by aquatic organisms, they can wreak slow havoc on aquatic environments and, by extension, on the ecosystems that surround them.

Fat-soluble chemicals present an extra level of complexity. Because they pass easily through cell membranes, our cells can readily absorb these chemicals. Once they’re inside, our bodies have a hard time expelling fat-soluble chemicals. In some cases, the liver can convert a fat-soluble molecule into a water-soluble one, so that it can be broken down and excreted in urine. But when our livers can’t work this magic, fat-soluble chemicals are stored in our fatty tissue, where they can pile up in a process known as bioaccumulation.

Bioaccumulation refers to the buildup of fat-soluble substances in the tissue of an organism over the course of its lifetime. Biomagnification describes a consequence of bioaccumulation; it’s what happens when animals that are higher up on the food chain eat other animals that have bioaccumulated toxic substances: They consume their prey’s entire lifetime dose of those toxics. Biomagnification means that animals higher on the food chain accumulate far more toxics than do those lower on the chain. The best examples in the human diet are tuna and swordfish. These fish are large predators and thus are high up on the ocean food chain. So when we eat them, we consume all the toxic substances—of special concern is mercury— that they have picked up from preying on smaller fish. INFOGRAPHIC 3.2

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BPA has a low persistence, meaning that it breaks down rapidly in the environment. Although it is fat soluble, liver and gut cells can readily convert it to a water-soluble form, so that it’s easily excreted in urine. This means it should not bioaccumulate or biomagnify.

So how then was it present in more than 90% of the 2,000 human urine samples analyzed by the CDC? BPA is so commonplace and people are exposed to it so continuously that it remains ever present in our systems. Even as we are breaking down and excreting some bits of BPA, we are ingesting more. Scientists have spent the past decade trying to determine what such exposure might mean for human health.

Figuring out the cause-and-effect relationships between our bodies and the chemicals that enter them is tricky work. Epidemiologists—the scientists charged with this type of research—can’t just give a test group of humans a toxic substance to see what effects it has. They must do a bit of detective work. They can start by looking for health problems in specific populations and work their way backward to find the culprit. Or they can look at groups that have been exposed to a given toxic and see if any common health problems emerge or have already emerged. This latter approach is the one researchers took with BPA. Epidemiologists looked at the health profiles of hundreds of individuals who had BPA in their urine; in one study of 1,455 such people, they found a correlation between BPA concentrations and cardiovascular disease.

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The task of determining exactly how BPA might go about wreaking havoc inside actual human bodies falls to toxicologists. Toxicologists concern themselves with determining the specific properties of potentially toxic substances and how they affect cells or tissues. They do this by testing lab animals through in vivo (in vivo means “in the body”) studies, or by testing cells in Petri dishes in what scientists call in vitro studies (in vitro means “in glass”). Toxicologists use these data to determine how toxic a substance is and what effects it has on living organisms. INFOGRAPHIC 3.3

Toxicity can be affected by a host of factors. Individual susceptibility varies with genetics, age, and underlying health status. When a person is exposed to a toxic substance, the type and amount of chemicals already in the person’s system are important. Some chemicals in the body might combine to increase overall toxicity (additive effects); other chemicals may reduce toxicity due to interactions between the toxins that “cancel each other out” or at least lessen the effect (antagonistic effects). Still other chemicals may work together to produce an even bigger effect than expected (synergistic effects). Route of exposure (for example, inhalation, injection, or skin contact) and the dose at the time of exposure also play a role. (Large doses can cause immediate effects that differ from those caused by lower doses acquired continually over a longer time period.) INFOGRAPHIC 3.4

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But in general, toxicologists like to say that “the dose makes the poison.” This means that almost anything can be tolerated in low enough doses; conversely, anything—even water—can be toxic if the dose is big enough. And in most cases, as the dose increases, so does the severity of the effect. This idea—that higher doses of something harmful are worse for you than lower doses—makes obvious sense. It guides both regulatory efforts and modern medicine. And it applies to almost every chemical you can think of—except for the class of which BPA is a part: endocrine disruptors.