Pharma: September 2008 Archives

 

September 4, 2008

In another entry in the bisphenol-A sweepstakes, Leranth et al. report cognitive impacts in a primate model (abstract only, full text behind paywall) [aside: it's super-annoying how much biomed research gets walled off like this. In CS we've reached this sort of uneasy compromise where people mostly post their papers on their own web sites, but you still have to pay to get the official versions. I suspect there's an interesting story to be told about this cultural divergence...]
Exposure measurements from several countries indicate that humans are routinely exposed to low levels of bisphenol A (BPA), a synthetic xenoestrogen widely used in the production of polycarbonate plastics. There is considerable debate about whether this exposure represents an environmental risk, based on reports that BPA interferes with the development of many organs and that it may alter cognitive functions and mood. Consistent with these reports, we have previously demonstrated that BPA antagonizes spine synapse formation induced by estrogens and testosterone in limbic brain areas of gonadectomized female and male rats. An important limitation of these studies, however, is that they were based on rodent animal models, which may not be representative of the effects of human BPA exposure. To address this issue, we examined the influence of continuous BPA administration, at a daily dose equal to the current U.S. Environmental Protection Agency's reference safe daily limit, on estradiol-induced spine synapse formation in the hippocampus and prefrontal cortex of a nonhuman primate model. Our data indicate that even at this relatively low exposure level, BPA completely abolishes the synaptogenic response to estradiol. Because remodeling of spine synapses may play a critical role in cognition and mood, the ability of BPA to interfere with spine synapse formation has profound implications. This study is the first to demonstrate an adverse effect of BPA on the brain in a nonhuman primate model and further amplifies concerns about the widespread use of BPA in medical equipment, and in food preparation and storage.

As background, this Sigg-sponsored study, which uses pretty extreme conditions (90°ree;C water, 3+ days dwell times) to maximize leaching produces levels of around 70 ppb (110ng/cm^2 of bottle surface) in polycarbonate bottles. The EPA reference ("safe") dose for BPA is 50 ug/kg/day. A 1 liter Nalgene bottle is about 18cm high, which implies a radius (this is a bit tricky to measure with my lousy ruler) of 4.2cm, and an internal surface area of about 600 cm^2 (counting the top and the bottom). At a leaching level of 110ng/cm^2, this comes out to about 66 ug of BPA in a one liter Nalgene bottle. I weigh 75 kg, so even if I drank 10 l of water a day out of a Nalgene bottle, I'd be consuming about a factor of 7 less than the safe dosage. It's also worth noting that the amount of leaching at day 1 was less than a tenth of that at days 2 and 3, so you'd only get this level of exposure if you had a lot of bottles and left your water sitting around in them. Note that I'm not saying that polycarbonate bottles are safe, just trying to get some perspective on what we know about the risk. Obviously, the situation is different for baby bottles and the like because the subject's mass is so much smaller.

Interestingly, the Sigg study shows significant amounts of leaching (19.0 ppb) from "generic aluminum" bottles. This isn't explained, but I suspect that what's going on is that those bottles are lined with a polycarbonate-based plastic (I understand that some aluminum cans are lined that way as well). The Sigg bottles use an (undisclosed) but apparently non-BPA-based lining and so don't leach BPA, which presumably is why they were eager to have such a study.