Plastic and the Developing Brain

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When I was pregnant with my daughter, I had enough on my mind. I didn’t have much time to think much about plastic. I knew vaguely that plastics can release estrogen-mimicking substances like bisphenol A (BPA) into our food and I’d heard that they might cause genital defects in male fetuses. But once my husband and I had the 20-week ultrasound and knew we were having a girl, I thought I could stop searching for products in cardboard or glass. It was just too hard. Everything is packaged in plastic these days.

Apparently I jumped the gun.

Scientific papers warning about the hazards of prenatal exposure to BPA have been coming out in a steady stream, with a string of particularly damning ones appearing over the last 18 months in the Proceedings of the National Academy of Sciences. Last month one in particular caught my eye: a study of how prenatal BPA exposure changes the brain. The results were enough to make this neuroscientist pause.

While we tend to think of estrogens as the sex hormones that manage ovulation and pregnancy, these molecules also have powerful and direct effects on the brain. Many types of neurons have estrogen receptors on their outer surface. While there are several kinds of estrogen receptors in the brain, all bind to estrogens (and other molecules that resemble estrogens) and all trigger changes within their neurons as a result. These small changes can potentially add up to alter how entire neural circuits function. In fact, estrogens influence a wide range of skills and behaviors – from cognitive function to mood regulation and even fine motor control. While we don’t yet know why estrogens have such a broad and powerful influence on the brain, it does appear that we should think twice before mucking around with estrogen levels, particularly in the developing brain.

BPA and other compounds found in plastics resemble estrogens. The similarity is close enough to fool estrogen receptors, which bind to these foreign molecules and interpret them as additional estrogen. Although BPA has been used commercially as a dental sealant and liner for food containers (among many other uses) since the 1960s, the health consequences of this case of mistaken identity are just beginning to be understood.

In the PNAS paper published last month, a group of scientists headed by Dr. Frances Champagne at Columbia report the effect of prenatal BPA exposure on mice. They fed pregnant laboratory mice one of three daily doses of BPA (2, 20, or 200 μg/kg) or a control product without BPA. These are not high doses of BPA. Based on the amount of BPA found in humans, scientists estimate that we are exposed to about 400 μg/kg per day. The U.S. Food and Drug Administration reached their own estimate by testing the amount of BPA in various foods and then approximating how much of these people consume daily. Their calculations put the figure at around 0.19 μg/kg daily for adults. This discrepancy (400 versus 0.19) is one of many points of contention between the FDA, the packaging industry, and the scientific community on the subject of BPA.

Champagne and her colleagues fed their mice BPA on each of the twenty days of mouse gestation. (That’s right, ladies: mouse pregnancies last less than three weeks.) After each mouse pup was born, the scientists either studied its behavior or sacrificed it and examined its brain.

What did they find? Prenatal BPA exposure had a noticeable impact on mouse brains, even at the lowest dose. They found BPA-induced changes in the number of new estrogen receptors being made in all three brain areas they examined: the prefrontal cortex, hypothalamus, and hippocampus. These effects were complex and differed depending on the gender of the animal, the brain area, the BPA dose, and the type of estrogen receptor. Still, in several cases the researchers found a surprising pattern. Without BPA-exposure, female mice typically made more new estrogen receptors than their male counterparts. The same was true for mice given the highest BPA dose. But among pups exposed to the two lowest BPA doses, male mice made more estrogen receptors than females! This sex-difference reversal stemmed from changes in both genders; male mice made more estrogen receptors than normal at these doses while female mice made fewer than their norm.

Champagne and colleagues also observed and recorded several behaviors of the mice in different circumstances. For most behaviors, males and females were naturally different from one another.  Just as human boys tend to chase each other more than girls do, male mouse pups chased more than females. Unexposed male mice sniffed a new mouse more than unexposed females did. They showed more anxiety-like behavior in an open space and were less active in their home cages. Prenatal BPA treatment reversed these natural sex differences. Exposed female mice did more sniffing, acted more anxious, and ran around less than their exposed male counterparts. And at the highest prenatal BPA dose, the male mice chased each other as rarely as the females did. In one case, BPA treatment affected the two genders similarly; both sexes were less aggressive than normal at the two lower doses and more aggressive than normal at the highest dose.

Overall, the results of the study are complex and it might be easy to ignore them because they don’t seem to tell a straightforward tale. Yet their findings can be summed up in a single sentence: BPA exposure in utero has diverse effects on the mouse brain and later behavior. Not only does the BPA ingested by the mom manage to affect the growing fetus, but those effects persist beyond the womb and past the end of the exposure to BPA.

Some will dismiss these results because they come from mice. After all, how much do we really resemble mice? Yet studies in monkeys have also found that BPA affects fetal development. And while mice and monkeys excrete BPA differently, they clear it at a similar rate — to each other and to human women. Results from correlational studies in humans also suggest that BPA exposure during development affects mood, anxiety and aggressiveness to varying degrees (depending on the child’s gender).

Still, there’s a lot we don’t know about the relevance of this study for humans. At the end of the day, mice aren’t humans and no one has agreed on how much BPA pregnant women ingest. Moreover, Champagne and colleagues examined only a small subset of the neural markers and behaviors that BPA might affect in mice. Perhaps the changes they describe are the worst of BPA’s effects, or perhaps they are only the tip of the iceberg. We don’t yet know.

What’s the upshot of all this? You may want to err on the side of caution, particularly if you’re pregnant. Avoid plastics when possible. Be aware of other sources of BPA like canned foods (which have plastic liners) and thermal receipts. Do what you can do and then try not to let it stress you out. If you’re pregnant, you already have enough on your mind.

As for my daughter, she seems to be fine despite her plasticized third trimester. While she doesn’t do much sniffing, she does occasionally slap my husband or me in the face. It could be the BPA making her aggressive. I choose to blame it on her sassy genes instead.

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Photo credit: .imelda on Flickr

ResearchBlogging.org

Kundakovic M, Gudsnuk K, Franks B, Madrid J, Miller RL, Perera FP, & Champagne FA (2013). Sex-specific epigenetic disruption and behavioral changes following low-dose in utero bisphenol A exposure. Proceedings of the National Academy of Sciences of the United States of America, 110 (24), 9956-61 PMID: 23716699

Pb on the Brain

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I’ve got lead on my mind. Lead the element, not the verb; the toxic metal that used to grace every gas tank and paint can in this grand country of ours. For the most part we’ve stopped spewing lead into our environment, but the lead of prior generations doesn’t go away. It lingers on the walls and windows of older buildings, on floors as dust, and in the soil. These days it lingers in my thoughts as well.

I started worrying about lead when my daughter became a toddler and began putting everything in her mouth. I fretted more when I learned that lead is far more damaging to young children than was previously thought. Even a tiny amount of it can irreversibly harm a child’s developing brain, leading to lower IQs, attention problems and behavioral disorders. You may never even see the culprit; lead can sit around as microscopic dust, waiting to be inhaled or sucked off of an infant’s fingers.

Public health programs use blood lead levels (BLLs) to evaluate the amount of lead in a child’s system and decide whether to take preventative or medical action. In the 1960s, only BLLs above 60 μg/dL were considered toxic in children. That number has been creeping downward ever since. In 1985 the CDC’s stated blood lead level of concern became 25 μg/dL and in 1991 it went down to 10. But last year the CDC moved the cutoff down to 5 μg/dL and got rid of the term “level of concern.” That’s because scientists now believe that any amount of lead is toxic. In fact, it seems as if lead’s neurotoxic effects are most potent at BLLs below 5 μg/dL. In other words, a disproportionately large amount of the brain damage occurs at the lowest doses. Recent studies have shown subtle intellectual impairments in kids with BLLs as low as 2 μg/dL (which is roughly the mean BLL of American preschoolers today). All great reasons for parents to worry about even tiny exposures to lead, no?

Yes. Absolutely. Parents never want to handicap their children, even if only by an IQ point or two. But here’s what’s crazy: nearly every American in their fifties, forties, or late-thirties today would have clocked in well over the current CDC’s cutoff when they were little. The average BLL of American preschoolers in the late ‘70s was 15 μg/dL – and 88% had BLLs greater than 10 μg/dL.

These stats made me wonder if whole generations of Americans are cognitively and behaviorally impaired from lead poisoning as children. Have we been blaming our intellectually underwhelming workforce on a mismanaged education system, cultural complacency, or the rise of television and video games when we should have been blaming a toxic metal element?

I was sure I wasn’t the first person to wonder about the upshot of poisoning generations of Americans. And lo and behold, a quick Google search led me to this brilliant article on Mother Jones from January. The piece chronicles a rise in urban crime that began in the ‘60s and fell off precipitously in the early-to-mid ‘90s nationwide. The author, Kevin Drum, walks readers through very real evidence that lead fumes from leaded gasoline were a major cause of the rise in crime (and that increased regulation restricting lead in gasoline could be credited for the sudden drop off.)

The idea certainly sounds far-fetched: generations of city-dwellers were more prone to violence as adults because they breathed high levels of lead fumes when they were kids. It doesn’t seem possible. But when you put the pieces together it’s hard to imagine any other outcome. We know that children of the ‘50s, ‘60s, and ‘70s had BLLs high enough to cause irreversible IQ deficits and behavioral problems (of which aggression and impulse control are particularly common). Why is it so hard to imagine that more of these children behaved violently when they became adults?

In the end, this terrible human experiment in mass poisoning has left me pondering two particular questions. First, what does it mean for generations of children to be, in a sense, retroactively damaged by lead? At the time, our levels were considered harmless, but now we know better. Does knowing now, at this point, explain anything about recent history and current events? Does it explain the remarkable intransigence of certain politicians or the bellicosity of certain talk show hosts, athletes, or drivers with a road rage problem? Aside from the crime wave, what other sweeping societal trends might be credited to the poisoning of children past? How might history have played out differently if we had all been in our right minds?

Finally, I’ve been thinking a lot about the leads and asbestoses and thalidomides of today. Pesticides? Bisphenol A? Flame retardants? What is my daughter licking off of those toys of hers and how is it going to harm her twenty years down the line? This is not just a question for parents. Think crime waves. Think lost productivity and innovation. Today’s children grow up to be tomorrow’s adults. Someday when we are old and convalescing they’ll take the reigns of our society and drive it heaven-knows-where. That makes child health and safety an issue for us all. We may never even know how much we stand to lose.

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Photo credit: Zara Evens

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