Even more on grapefruit juice

Ok, this is it. One last word on grapefruit juice. As both JLowe at Impact Analysis and my sister who actually reads the Wall Street Journal just informed me, grapefruit juice is now being pharmacueticalized if there is such a word. That is, someone's finally decided to capitalize the inhibitory potential of grapefruit juice extracts.

You can read a more detailed analysis at Terra Sigillata who suggests that trying to boost drug activity (and minimize dose) may be asking for trouble. But then, as the WSJ article suggests there are some cases where boosting the efficacy of a poorly absorbed drug might be advantageous.

My take - after all this discussion of drug interactions - is why add yet another drug (unless absolutely necessary) when it's clear as Terra suggests that we're not only looking at combining drugs but also interindividual differences in how each body handles drugs - which depends on many factors including genetics, nutrition, gender, age, etc.

More on grapefruit juice and drugs

A few weeks back, I wrote about drug interactions. On the recommendation of my editor (it was originally for the local paper,) I'd removed the details of how certain drugs are metabolized - the part I found most interesting, and the part he thought would most likely lead to bored and frustrated readers.

At the time I'd agreed with him and cut. But then, over the Thanksgiving Holiday, when I'd jokingly commented on the cranberry juice cocktail my friend was about to finish off, she said,

"...but I only take the Lipitor at night. Drinking a glass of cranberry juice during the day shouldn't matter."

Maybe, maybe not. I don't know much about the combination of Lipitor (atorvastatin calcium) and cranberry juice but the comment reminded me of why I'd written about the details of drug metabolism in the first place.

While the science of drug metabolism is complicated enough, when one adds the potential for drug-drug or drug-food interactions the level of complexity can skyrocket.

First, a quick introduction to drug metabolism. Lipitor is a drug metabolized primarily by enzymes belonging the CYP detoxification or drug metabolizing system. Years ago the CYP system was one of the few recognized detoxification systems in the body. That is, a collection of enzymes working together to metabolize toxic chemicals and send them on their way before they can cause any damage. Back then we knew of only a couple of enzymes, now there are dozens and dozens grouped into "families" of CYP enzymes. In the case of Lipitor, CYP3A4 is key for proper metabolism and eventual excretion of the drug.

For chemicals that require metabolism by CYP enzymes prior to excretion, the CYPs play an important role in determining the half-life of a drug or chemical.

Half-life refers to the length of time required for a drug or chemical to be reduced to one-half the initial concentration. Knowing the half-life is necessary to determing dosage ensuring that 1) there is sufficient levels of drug in the system and 2) concentrations don't get too high that they become toxic.

Anything that screws with the half-life of a chemical is potentially very dangerous. For chemicals that must be metabolized in order to be excreted, an increase in CYP metabolism would reduce half-life, resulting in drug concentrations that may no longer effective. Conversely, a reduction of CYP metabolism, or inhibition of metabolism can increase half-life, causing drugs to accumulate to toxic, possibly even lethal concentrations.

And even asking "what's the half-life" of a drug under normal conditions isn't so simple. Take the example of Lipitor. While the parent compound Lipitor (the actual drug that you ingest) may have a half-life of only fourteen hours, the metabolites of the drug - which in this case are most active - have a much longer half-life of twenty to thirty hours. That means that it can take up to thirty hours for half the initial concentration of active metabolites to exit your body.

Now lets consider the interaction between grapefruit juice (really certain chemicals in grapefruit juice) which act as inhibitors of CYP3A4. In this case, those CYP enzymes responsible for metabolic breakdown of Lipitor would be inhibited, essentially extending the half-life of the drug possibly leading to potentially toxic concentration of the drug.

And, what makes this all really complicated is that depending on how an inhibitor like grapefruit juice does it's dirty-work, the inhibitory effects may either very short-term or can last for days. In the case of grapefruit, according to one article in Pharmacy Times drinking grapefruit juice not only has immediate (within 30 minutes) impacts on metabolism, but, depending on how long and how much one has been drinking, inhibitory effects can last up to three days. This is because the chemicals responsible for inhibition by grapefruit juice, essentially combine irreversibly to CYP3A4, taking them out of action for good, necessitating synthesis of new enzyme.

Phew - maybe my editor was right! Well, you get the point I hope.

When taking new drugs or adding new food and beverages to your diet, it's well worth the little extra effort to inform your doctor or your pharmacist of the changes.

Environmental Impact of Clothing Revealed

It's not easy finding information on the waste products, the energy used, or the carbon dioxide produced by your favorite shoe manufacturer or clothing company, but that's exactly what Patagonia (you know, the expensive but generally well-made and stylish outdoor adventure clothing company) does on their site, called the "Footprint Chronicles^TM ."

Of course not many of us really want to know. But this winter I'll be working with students at a local high school building a website that focuses on the environmental impacts of their favorite outfits. When I came across the Patagonia site, I knew I had my model.

They highlight a few key products (an organic cotton t-shirt, a waterproof shell, a wool sweater and a leather shoe,) covering the major categories of textiles, and provide details on the carbon dioxide production, energy use, and waste production.

For example according to the site, fiber for the cotton T originated in Izmir Turkey, traveled to Bangkok for spinning and sewing and then on to Reno, Nevada for distribution, traveling 14,100 miles, and generating 27 pounds of CO2 (remember this is a gas!), ten ounces of waste, and using enough electricity to power an 18w compact fluorescent bulb for 72 days.

After trying in vain to gather information on the ubiquitous Crocs ( a couple of emails to Tia Mattson their public relations manager asking questions about recycling and the chemistry of crosslite (PCCR) the primary material - only left me waiting by the phone for her call which never came), the apparent openness of Patagonia was a welcome find.

Of course, ever the skeptic I tried to find the holes. What about tanning? What about other toxics surely used in dying processes? Well, I couldn't find much on dying, but on their discussion page, readers did raise questions about tanning, and, the "localcrew" responded to reader's comments with seemingly honest and useful information. Patagonia also notes that although they still use PFOA in their "Eco-Rain Shell" they are seeking alternatives to the persistent environmental contaminant. Finally, a closer look at endpoints like "waste generated" reveals that this includes only solid waste, and not liquid or hazardous waste.

At the very least, it'll be a great place for students to begin, for in addition to maps and videos of manufacturing locations, they also provide detailed references which include several websites on Life-cycle analysis for various materials, energy use, and CO2 emissions.

Check it out, and thank you Patagonia for doing (at least part of) my howework!

Bindeez and Aqua Dots

As many are aware by now, there's been a lot of interest in Bindeez beads, the toy beads that can turn toxic if or when ingested. I first read about this in the New York Times, which reported how doctors treating a comatose child in Australia, first discovered that a solvent used in production of the beads, once ingested, can be metabolized into the infamous date-rape drug, GHB.

According to news reports, ingestion of these beads have led to additional hospitalizations, both in Austrailia and here in the U.S. where the beads were sold as Aqua-beads.

Both countries have issued recalls or bans for the products.

That industrial solvent, 1,4-butanediol according to an article by Rueters was apparently used by some manufacturers in China, in place of the less potentially toxic solvent 1,5-pentanediol. The intense news coverage has led Science blogs to name 1,4-butanediol "Molecule of the Day."

Scienceblogs provides brief description of how our alcohol-metabolizing enzymes convert the industrial solvent 1,4-butanediol into GHB. There's also an interesting educational site about the conversion of 1,4-butanediol at Neuroscience for Kids.

Drug Interactions: more common than you might think

Many years ago, my father suffered a TIA or transient ischemic attack – a sort of mini-stroke. This episode occurred in association with a very common type of cardiac irregularity called atrial fibrillation. And what should have been a relatively short hospital stay turned into an all too real example of the adverse effects resulting from multi-drug interactions.

Following the TIA, thanks to a quick response by the local ambulance company, by the time my father reached the hospital he was relatively symptom free. A fact apparent to all but the admitting doctor who, upon checking for impaired mental capacity, asked him to recite the months backwards, beginning with the current month.

He said, “Enuj.”

It was the month of June, and that was my dad.

But as doctors struggled to find a safe and effective dosage of Coumadin (known generically as warfarin), a common blood thinner used to prevent future and more severe blood clots that can cause TIAs and worse, my dad’s blood levels of Coumadin bounced around, predictably unpredictable, thanks in part to his well developed drug metabolism system. You see, in his early twenties, following a bout of spinal meningitis, my father was diagnosed with epilepsy. For the rest of his life, he relied upon a combination of Meberal and Tegretol, two powerful medications to keep the seizures at bay.

Meberal is a derivative of phenobarbital, a drug that I’d been using in the toxicology laboratory at that time to increase the amounts of specific drug metabolizing enzymes. Tegretol will do the same. These enzymes belong to a system of detoxification enzymes that essentially alter toxic chemicals into more excretable compounds sending them on their way out of the body before they can cause any damage. Most likely, it was those same enzymes, induced by years of Meberal and Tegretol, which wreaked havoc with my father’s early Coumadin levels, measured then as “pro-time”, or anticoagulant activity.

To be fair, Coumadin is one of the most difficult drugs to manage, in part, because it is so susceptible to interactions with other drugs and nutrients (more on that later). Says Ed Tessier Pharm.D, and clinical pharmacist at Baystate Franklin Medical Center in Greenfield, MA, “It’s a life saving drug, but it’s known nationally as one of the most difficult to manage, not only because of drug interactions but genetics as well.” As with most biological systems, there is a strong genetic component of the detoxification system. Some of us are rapid metabolizers, some of us are not.

But here’s the thing. Although many of us don’t think we’re prime candidates for Who Wants to Host a Complex Drug Interaction, many of us do occasionally ingest potentially toxic combinations of drugs and chemicals in our food and drink without a second thought. Sometimes one of these combinations render drugs ineffective, sometimes it turns them toxic.

Take caffeine and Tylenol (or acetaminophen) for example. Acetaminophen is one of those drugs metabolized by the liver enzymes mentioned above and according to an article published online by eMedicine by Dr. Susan Farrell, assistant professor in the Department of Emergency Medicine at Harvard Medical School, “Acetaminophen is the most widely used pharmaceutical analgesic and antipyretic agent in the United States and the world….. As such, acetaminophen is one of the most common pharmaceuticals associated with both intentional and accidental poisoning.”

Most of the time, most of the acetaminophen we ingest is metabolized by specific detoxification enzymes to nontoxic by-products or metabolites, which we excrete without a problem. But sometimes, depending on the amount ingested, or, since we are talking about drug interactions, whatever else we may have ingested prior to, or along with the acetaminophen, some of it takes the toxic route, resulting in highly toxic metabolites. If you’re a cat owner, this may sound familiar. Acetaminophen and cats are a potentially lethal combination because in cats, unlike in humans, most acetaminophen is routinely metabolized via this toxic route.

Since most of this drug metabolizing drama takes place in the liver, it is the liver that is most susceptible to toxic metabolites. Notes Farrell, “In the United States, acetaminophen toxicity has replaced viral hepatitis as the most common cause of acute hepatic failure, and it is the second most common cause of liver failure requiring transplantation in the United States.”

Now say we drink a few too many Starbucks Grandes in addition to ingesting a hefty dose of Tylenol. According to Dr. Sidney Nelson, Professor of Medicinal Chemistry at the University of Washington, and lead author of a recent article in Chemical Research and Toxicology on the interaction between APAP and caffeine, “…very high concentrations of caffeine (the amounts individuals might achieve by drinking approximately 20 cups of coffee) can triple the amount of a liver toxic metabolite of acetaminophen.”

Twenty cups? That seems like an awful lot, although these days between high-test coffee and higher-test energy drinks, it would be wise for those heavy drinkers to take note. Not only that, but if one were to add a night of excessive drinking (this time I mean alcohol), followed by a morning requiring Tylenol and caffeine, it may not take twenty cups before your liver begins to suffer the consequences.

Says Dr. Nelson “…There is a period of 12-36 hours [after acute alcohol consumption] during which more acetaminophen toxic metabolite will be formed because of increased amounts of the metabolizing enzyme.”

You see alcohol, like my dad’s anti-seizure drugs also increases specific enzymes involved in certain detoxification (sometimes toxification) systems. And unfortunately, it’s not just “recreational drugs” like caffeine and alcohol that can interact with other drugs in potentially devastating ways. For a few years following my father’s TIA, after doctors figured out the correct Coumadin dosage, his blood levels of the drug remained relatively stable. He was an extremely attentive patient, interested in tracking levels of the drug as the doctors made them available, well aware of potential interactions of drugs and diet.

Then one day his Coumadin level shot up. This time, his medications weren’t to blame, nor was his overactive liver. Something was inhibiting the metabolism. The culprit, doctors eventually discovered, was his latest favorite beverage, grapefruit juice. Once again, my father’s real-life experience reflected what I had learned in toxicology. To inhibit detoxification enzymes in some of our experiments, we had used quercitin, one of the active substances in grapefruit.

According to Ed Tessier, for most Coumadin patients grapefruit juice may not be as important as other food and drug interactions, however, “grapefruit does affect metabolism of a great number of other drugs, including most of the “statin” drugs to lower cholesterol (such as atorvastatin – Lipitor®) and can lead to rhabdomyolysis - a life threatening condition which results in muscle tissue injury and possible kidney failure.”

As we add new foods to our diet, and new pharmaceuticals and herbal remedies to our medicine cabinets the potential for interaction is never-ending. One more product I am compelled to mention is St. John’s Wort, the herbal remedy commonly used to treat depression, also induces detoxification enzymes.

According to Nelson, “Chronic ingestion of St. John’s Wort….may increase the formation of the toxic metabolite of acetaminophen. If acetaminophen is taken in therapeutic doses, it is very unlikely that there would be any problem. However, if the individual taking these drugs takes larger doses of acetaminophen and drinks large amounts of caffeinated beverages (say 8 cups or more of strong coffee) or takes large amounts of caffeine-containing drugs, they would form significantly more of the toxic metabolite that could put them at risk of liver damage.”

And, among the many medications that may fall prey to enzymes induced by St. John’s Wort are most antidepressants, as well as many migraine medications, HIV medications, and birth control pills. Only in the case of some of these drugs -- including birth control pills -- the result of increased metabolism isn’t increased toxicity, but reduced efficacy.

Should this brief lesson in drug interaction scare you off your meds, fear not. These days, doctors like Kathleen McGraw MD, Medical Director of Hospital Medicine at Baystate Franklin Medical Center are blessed with instant access to reams of information on drug interactions through the web some of which can be downloaded onto hand held computing devices.

Within minutes of my mentioning St. John’s Wort, McGraw was on her PDA running the Epocrates program, scrolling through lists of drugs known to be adversely impacted by St. John’s Wort. Just as quickly she rattled off drugs affected by grapefruit juice.

To avoid problems caused by the potent chemicals in grapefruit juice, says McGraw, “I tell patients they need to give it up totally (same with cranberry juice) unless it is something they can't live without in which case they have to commit to having the same amount every single day. Given that choice, everyone says they'll quit.”

Adds McGraw, “I encourage every patient on Coumadin to remind any physician giving them a prescription for a new medication (especially antibiotics) about the Coumadin and ask if it will be affected.”

Thankfully, since the days of my dad’s TIA, the science and the awareness of drug-drug and drug-food interactions have come a long way. But it’s a two-way proposition. For pharmacists and doctors to do their part, we have to do ours, whether it’s disclosing that we’re on Coumadin, Viagra, birth control pills, herbal medications, Starbucks Grandes or the newest favorite, pomegranate juice.

UPDATE March 2010: it is well known that individual metabolic differences can dramatically impact drug metabolism. Particularly important for drugs like warfarin (coumadin.) A recent study shows that by tailoring doses based on genetic testing may help reduce hospitalizations due to drug imbalance. Read more here: http://www.businessweek.com/lifestyle/content/healthday/637031.html

Reprinted from the Montague Reporter, please feel free to quote using proper attribution.

Back to the Tap

The following article about Nestle's interest in our local water isn't my usual entry, but after noticing that the moderate sized tanker truck I was following down Route 2 in Massachusetts, was carrying none other than "Water," my stomach turned as a I imagined a future of similar "Water" trucks, removing water from one town, selling it to another, all for corporate profit.

So, I am posting this, with hopes that it will encourage citizens around the country to keep close tabs on their own water - before it's sold off - and to consider getting their drinking water (whenever possible) the "old fashioned way" - from the tap.

(Reprinted from The Montague Reporter)

This week, Nestle Water North America announced it was suspending its plan to explore the aquifir below the Montague Plains as the source for a potential water bottling plant in our community. So it seems Montague residents won’t be paying $2 a bottle to purchase our own pure Montague Plains water, at least not from Nestle, and at least not in the near future.

But that’s no reason to let down our guard. That was the message from Tuesday evening’s meeting held by the Montague Alliance to Protect our Water. Following a detailed “tour” of water flow in the plains, and the aquifer below, hydrogeologist Nancy Caffall (formerly with the state Department of Environmental Protection,) noted that “this kind of formation is particularly attractive for bottling companies.”

That’s one reason to keep on guard. Although Nestle’s may have found drilling on State land too “complicated,” because of the nature of the aquifer, and the profitability of a good water source, there’s always the potential for Nestle or another corporate bottler to pursue access through private land abutting the state owned plains.

“A municipal official from the town of Montague should ask if Nestle is talking to other property owners in the area,” suggested Russ Cohen, of the Department.of Fish and Game Riverways Program, prompting discussion of how best to inform nearby property owners of the larger impact, and potential risks of opening the door to a Nestle representative.

What would it take to discourage or deny drilling permits in the state of Massachusetts? In addition various MA DEP regulations, says Nancy Caffall, there is also the Massachusetts Water Management Act which requires that water withdrawals not stress the host river basin. That is, all withdrawals to a particular basin are considered rather than a more piecemeal approach, or one that considers only the impact on nearby surface waters.

Ironically, what makes spring water Spring Water is that it must be withdrawn from a location that is hydrogeologically connected to a surface stream. In other words, sites that are often more ecologically sensitive – with nearby habitat, freshwater fish streams etc.

And, says Kirt Mayland, Director of the New England Office of the Eastern Water Project of Trout Unlimited, the water industry wants to keep it this way – rather than going to sites where there’d be less impact. For example in Wisconsin, bottlers have drilled wells near some of the best trout streams in the region.

The case of Montague verses Nestles didn’t get as far as evaluation of impacts on nearby streams, or host river basins, in part thanks to the now famous Article 97. In addition to guaranteeing the people’s right to public resources, Article 97 also grants that removal of natural resources from public lands must be in the best interest for wildlife and wildlife habitat. So, unless like us, critters living on the plains have turned to bottled water, it’s hard to envision how corporate withdrawal would be of benefit to them, or to the public.

But as one meeting participant pointed out, “While Article 97 seemed like a real silver bullet, and although it has the most wonderful language for resource protection, there are a lot of terrible plans that happen – in this case the state may have been sensitive to all the opposition because it’s on state land.” Since most legislation regulating and protecting water was passed in the old days, when we drank water from the kitchen sink, or the bubbler down the hall, and before the rise of the multi-billion dollar bottled water industry, there are plenty of loopholes that corporations with deep pockets can ferret out. In short, there’s plenty of work to be done identifying and filling in the loopholes of state water legislation.

Not only is the extraction of a common trust resource, one that should be as free and accessible as the air we breath an issue, but between the trucking and the bottling there are plenty of other environmental impacts of the bottled water industry.

“There’s a whole lot of trucking,” impressed Mayland who noted that because the industry is so reliant on trucking, and because fuel prices are soaring, and because we here in the Northeast are major consumers of bottled water, the Route 91 corridor is of particular interest to bottled water developers, as are other locations in the Northeast that combine access to good water with access to good roads.

There is no doubt we have, in part, brought this upon ourselves by becoming a culture reliant upon bottled water. According to the group Corporate Accountability International “One of the most visible examples of corporate control of water is bottled water. It is the fastest growing sector of the US beverage market and just three corporations – Coke, Pepsi and Nestlé – make up over half of the US bottled water market. These corporations are privatizing our water, bottling it and selling it back to us at prices hundreds, even thousands of times what tap water costs. They have turned a shared common resource into a $100 billion global market – and one of the world’s fastest growing branded beverages.”

But if corporate greed isn’t enough to make you think twice about purchasing that next bottle of Aquafina, Poland Springs, or Evian, then think locally. We all know what happens to bottles that aren’t recycled, they’re tossed into garbage, flattened along the road side, or floating down the river. Then there is the toxic side of plastic bottles, and the potential for bottles, depending on the plastic to leach small amounts of toxicants into drinking water.

It’s time to turn back to the tap, relinquishing the bottle, and protect our municipal waters.

Polycarbonate plastics: if only toxicology could be that clear

An ongoing debate about the health impacts of bisphenol A (BPA), the ubiquitous chemical used in production of polycarbonate - that hard clear plastic we use for eating, drinking, and storing food – continues, according to a recent article by Janet Raloff published in the September 29 issue of Science News. Her analysis provides good insight into why we often hear conflicting reports when it comes to environmental and health impacts of chemicals.

Raloff reports on the conflicting results of two different panels recruited by the National Toxicology Program (NTP) and charged with reviewing and evaluating the potential developmental and reproductive impacts of BPA. While one panel “labeled ‘as confident’ its assessment that BPA at low doses has had negative effects on experimental animals,” and that such findings were suggestive of impacts in humans, the other panel “concluded that current BPA exposures appear to pose little risk to humans.”

According to Raloff, one of the differences cited in this analysis, leading to conclusions ranging from don’t use the stuff if you don’t have to, to it’s a non-issue, were concerns about the basic experimental design used by scientists evaluating BPA. When laboratory animals are exposed to experimental chemicals there is often a trade-off between ensuring exposure to the chemical, verses exposing the animal in a realistic manner. Way back when, when I was interested in the effects of PCBs in fish populations, I’d load up syringe and inject. Now unless fish were mainlining PCBs (and concentrations in some wild fish were certainly suggestive of that!) clearly this wasn’t realistic. But, what it did provide us with was an exposure where we were sure that PCBs got to where we wanted them to go. Confident of our exposures (we’d also do some chemical analysis – which was the most costly part of the study back then, and so something toxicologists would like to avoid if at all possible), we could more efficiently get down to our intended business, evaluating the effects. Our option would have been to develop food with amounts of PCBs that fish would eat in amounts that we could somehow measure (you ever watch fish eat? Biting off pieces of food, letting the rest drift to the bottom, possibly snatched up by less aggressive fishes), that wouldn’t leave us with gallons of toxic water to cleanse in the end. The fact is there are often good reasons to use the needle, although as pointed out by the panels, there are limitations to these kinds of unrealistic exposures, one of them is interpreting experimental results to a broader range of more realistic exposure scenarios.

Raloff outlines other differences in the panels, for example, she writes that the panel which concluded impacts are likely, had either worked with the chemical or similar chemicals, while the panel that came to nearly an opposite conclusion “were selected precisely because they had no direct BPA experience and, therefore, no obvious vested interest in judging the quality of the data on the chemical.” Fair enough, I suppose. You’d hope scientists can see past their own interests, although I’ve always thought it’d be interesting to see a study correlating the evaluation of experimental data with sustained funding for a particular subject over a period of time.

For more details on the subject, the article is available on the Science News site, and, according to Raloff, “ultimately, NTP will issue a single report that integrates conclusions from both panels, along with any new information on BPA that comes to light during the next few months.” Now that ought to be an interesting read.

Bodily defense: detoxification update

Years ago as a budding toxicologist I studied a fascinating system called cytochrome P450, so called because under certain conditions one could measure a peak at the light wavelengths of 450nm. What was so fascinating was that it was, at the time, one of the few recognized detoxification systems. That is, this system, which consists of various proteins, could metabolize certain toxic chemicals and send them on their way out of the body. Now almost two decades later a recent paper, published in Developmental Biology by Goldstone and others, presents the “chemical defensome,” described as an “integrated network of genes and pathways that allow an organism to mount an orchestrated defense against toxic chemicals.” Though it sounds like something that belongs on a football field, it’s a little more highly evolved than that.

Back in the simple days, before scientists had the capability to identify each and every gene in our bodies, toxicology students studied the fate of fairly simple chemicals like polyaromatic hydrocarbons – those ubiquitous chemicals found in combustion products from the tip of a cigarette to the tip of your tailpipe – chemicals that basically sealed their doom by activating the system responsible for their own destruction. You see this particular detoxification system required activation or binding to a receptor, sort of the old lock and key - now an obsolete analogy but still good enough to get the basic idea across. A chemical binds to a receptor, and opens the door for specific proteins to be produced, in this case specific cytochrome P450 enzymes, which then go to work metabolizing the chemical sending it on its way to eventual detoxification.

Learning the story of P450 and polyaromatic chemicals was a must for nascent toxicologists. That was back in the old days, before the cigarette industry acknowledged the connection between inhaling a lungful of chemicals and cancer, but even back then we all knew that once some of those chemicals entered the lungs, little PAH keys entered PAH locks, or what we called aryl hydrocarbon receptors, activating genes necessary for P450 induction all around the body, in lung cells, liver cells, and kidney cells. We also knew that this process presented the proverbial “double-edged sword.” That is, detoxification of some chemicals, particularly PAHs, required several steps – some of them resulting in activation of a chemical to a more toxic or reactive state – before eventual detoxification and finally excretion. And, in the case of PAH, activation meant that the reactive PAH could bind to genetic material in way that could promote formation of cancerous tumors. We also knew there was a genetic component - even if we didn't know much about the genetics of the system. We knew then that the detoxification pathway proceeded differently and to different extents in some folks compared with others.

But at that time we were aware of just a few kinds of P450 enzymes, and, we had no idea of the breadth of the detoxification system, or the basic genetics of a system we now know we share with creatures ranging from tunicates, our slimy cousins that still cling to rocks by the seashore, to the pesky fruit flies that zip around the bruised fruit in my kitchen.

It made sense though, that given the harsh earthly conditions in which they evolved, our ancestors would need to protect themselves from constant chemical assault. But even so, back then, toxicologists wondered if receptors like the aryl hydrocarbon or PAH receptor evolved as a defense mechanism, or if its role in detoxification of foreign chemicals was a surreptitious side effect. Maybe, the system had evolved to deal with what are called endogenous chemicals, a way to get rid of the body’s own powerful chemicals once they no longer serve their purpose, like steroids for example (which, at least in my teen seems toxic enough, though to be fair, without them we’d probably still be clinging to rocks in some tide pool alongside our tunicate cousins.)

Now, a decade and a half later, scientists have unveiled a diverse and sprawling system of detoxification, or defense mechanisms from a plethora of P450 enzymes to antioxidants responsible for quenching the highly reactive oxygen produced by many metabolic processes protecting us from a range of potentially deadly chemicals, including microbial and plant toxins, PAHs and heavy metals.

In a paper that goes into genetic detail way beyond what my tunicate brain can comprehend, J.V. Goldstone and others introduce these systems collectively as a “defensome,” a fascinating concept of protective mechanisms that we humans take for granted, as we challenge our bodies with ever more complex combinations of naturally occurring and manmade chemicals. Let's just hope that unlike the typical Superbowl blowouts, we won't suffer a similar defensome overload, leaving us at the mercy of our natural and unnatural environment.

All the genetic details (and a hint to the youthful secrets of elderly sea urchins) can be found in Goldstone, J.V. et al. “The chemical defensome: Environmental sensing and response genes in the Strongylocentrotus purpuratus genome,” Developmental Biology 300:366-384.

The fire-retardants, they are a’changing

Say goodbye to PBDEs (well... at least in some states, in some products in the near future.)

There’s one of those rare heartening reports just published in the this week's online News section of Environmental Science and Technology, Formulating Environmental Friendly Flame Retardants. It’s good to hear every once in a while that industrial processes can change, even if not completely voluntary, particularly when it comes to chemicals that we know are a problem.

Take for example, the polybrominated Diphenyl Ethers (PBDEs) that are commonly used as flame retardants when added to plastics including computer plastics, furniture plastics (polyurethane is highly flammable), plastic plastics, and other plastics. PBDE’s are just about every where now, from my neighbor’s breast milk here in Western Mass to big momma polar bear’s milk in Alaska, to overly thin, hyperactive, perpetually hungry hyperthyroid house cats.

According to ES&T, in response to legislative pressures (certain PBDEs have already been discontinued, others are now banned in a few states), and pressure from consumers and plastics' producers, “The industry is responding with new approaches for making flame retardants, and some design teams are actively adopting the tenets of green chemistry. In the long run, the work now under way could result in the development of materials that are inherently resistant to fire.”

As industry moves away from halogenated flame retardants ( chemicals like bromine, fluorine and chlorine) a positive move, and turns instead to phosphorus-based flame retardants, metal hydroxide flame retardants, and nanoclay flame retardants, let’s just hope there’s enough foresight, oversight and whatever else, such that the use and development of these new products won’t bypass careful environmental and health evaluation. Otherwise we might end up in another twenty or thirty years wondering why Isidora the house cat, after spending her life lounging around on the carpet, the new couch, or the new bed (the slim high def television will no longer be an option) isn't acting quite right.

UPDATE: A letter in the October 12 2007 issue of Science by biophysical chemist Arlene Blum addresses "The Fire Retardant Dilemma." While pointing out that replacements for pentabrominated fire-retardants may be no safer than the chemicals they replace, Blum calls for the United States to follow the example set by the Europeans. Writes Blum, "New European regualtions for the Registration, Evaluation, and Authorization of Chemicals (REACH) require industry to provide data to establish the safety of new and existing chemicals. The United States should follow suit." Adding that "Fire-retardant chemicals in our homes should not pose a greater hazard to our health and environment than the risk of the fires they are supposed to prevent."

Well said.

On the Life Cycle and Environmental Impact of Last Year's Fashion Must Haves

We recycle bottles, computers and paper. But what about clothing? Many of us think we’re doing some good by sorting through t-shirts and shorts our kids wore last summer, or through our own closets adhering to the fashion mantra, “if you haven’t worn it for two seasons, toss it.” We pack away anything that’s not too dirty or torn and cart it off to Goodwill or the Salvation Army. But really, for those who are environmentally inclined, we’d do best by remembering the first R, of the Reduce, Recycle, Reuse slogan, and consider the impact of our clothing on earth’s environments and inhabitants.

In the September issue of Environmental Health Perspectives, there’s a fascinating article, “Waste Couture: Environmental Impact of the Clothing Industry”, by Luz Claudio, revealing the full life-cycle of clothes. Might just make you want to keep your shirt on for a little bit longer.

Luz highlights the trend for cheap "disposable" clothing - or "fast fashion," and the impacts not only of clothing production, but its afterlife as well.

Aside from the pesticides used for cotton - and the U.S. is the largest exporter of cotton, which accounts for a large chunk pesticides used in the U.S. - there's the petroleum based synthetic fibers, the toxic chemicals used for treating and dyeing textiles and the energy required to keep our cottons and other materials crisp and clean.

There's hope though, as Claudio notes, the fashion industry is just beginning to embrace "sustainably grown cotton, hemp, bamboo and other fiber crops that require less pesticides, irrigation, and other imputs." Additionally, some companies are looking to reduce their footprint futher, by recycling materials Patagonia, for example not only uses recycled PET bottles, but recycles certain garments (including Capilene undergarments and their cotton T's.) And, still others are experimenting with biodegradable materials.

"Well Dressed," a report on the clothing industry (detailing production, human and environmental cost) by researchers at Cambridge University suggests that reductions in the environmental impact of clothing will require major changes in both industrial and consumer behavior. A few examples of industrial changes include increased recycling of certain materials, changes in production (such as a switch from conventional to organic cotton, ) and innovations that result in an extended consumer lifetime for products, and less energy intensive upkeep. Reducing the need for frequent washings, for example, or reducing water temperatures required for cleansing and drying.

Likewise, according to the report, we all can contribute by choosing more durable clothing, buying garments produced in both a socially and environmentally equitable manner, washing less often - using cooler water and line-drying, and, when we're finished with our duds, sending them off to a second hand store, or a reliable clothing recycler.

Electronics Recycling Can be a Dirty Business, or Not....

Electronic Recycling Parts I and II: Reprinted from the Montague Reporter

Part I

When I mentioned I was doing some research into e-waste, or electronic waste, meaning anything from iPods to computers, my neighbor Patrick groused, “I’ve got a ware-house half-full of computers. I don’t know what to do with them.” Patrick owns several Turn it Up! record and CD stores, providing plenty of opportunity for e-waste. Later that day I mentioned the e-waste issue to William, a self-employed computer repair and software expert. He pointed to a tall shelf stuffed with old computer parts.

Patrick and William aren’t alone. We’ve all got some, haunting us with their lack of utility, taking up space. I’ve got an old monitor in my shed, a laptop no one wants (not even the kids) under the couch, and then there’s the box labeled, “Misc. electronics stuff.”

In a recent report on e-waste, the U.S. Environmental Protection Agency estimates that of the almost two billion electronics sold (this includes things like laptops, desktops, cell phones, keyboards) over the past twenty-four years, roughly 180 million units are in storage somewhere, lurking in basements, attics and sheds around the nation.

William told me a while back he’d carted a bunch of his old computer parts down to his local elementary school, “They were recycling a bunch of their own stuff – I asked their permission, of course – but I have no idea what happened after that.”

What happens after that it the big question. A question all of use who use computers, digital cameras, cell phones and iPods ought to be asking. As many of us already know – for the most part – you can’t give the stuff away, particularly things like computers, even if they’re still in fine working condition. Many years ago, when computers were room-sized modern miracles, my father helped pioneer the Used Computer business, buying and selling the behemoths across the country and around the world. But, over the period of a couple of decades as computer chips shrank, and the million dollar equipment that used to require its own air-conditioned room evolved into desk-top computers that cost a few hundred dollars, he also observed the demise of the used computer business. A decade ago, when visiting Israel, he was shown an empty classroom. “Our computer room,” they hinted. He offered to fill it with completely functional used desktops for free – they declined. They wanted new.

These days new doesn’t last long. In fact my four-year old IBM is at the shop around the corner– and I can only hope if my hard drive has taken its last spin, that Veronica and Cathy who are tending to it, can save the e-mails that were never backed up, the early drafts, the photos and all those iTunes my son downloaded.

“I know how many we see die, and the landfill thing just kills me,” said Veronica, when I mentioned e-waste. As I imagine is the case with most computer ER’s like Veronica’s, the workshop was filled with computer cases, monitors and cables. I asked Veronica about rebuilding, or updating old computers. “We can take an old case,” she said, “but the new motherboards just don’t fit in them.” We were standing over a large box filled with circuit boards bound for the recyclers, each board a different concoction of colorful wires, copper, precious metals (gold, silver, and platinum) and plastic. These boards are the heart and soul of our computers and sought out by recyclers around the world interested in recovering metals, and this is where my own journey into the toxicology and politics of e-waste really begins.

Recently two disturbing articles on e-waste published in the journal Environmental Science and Technology caught my eye. The title of the first article, by Huiru Li and others, is Severe PCDD/F and PBDD/F Pollution in Air around an Electronic Waste Dismantling Area in China and the other by Xinhui Bi and others is Exposure of Electronics Dismantling Workers to Polybrominated Diphenyl Ethers, Polychlorinated Biphenyls and Organochlorine Pesticides in South China. The titles say it all. Together these articles describe the exceedingly high concentrations of toxic chemicals released from e-waste plastics that contaminate not only the workers who dismantle and “recycle” e-waste.

But what has this got to do with me and my useless electronics?

According to the authors, upwards of one million tons of electronic waste is shipped to China from the United States, Europe and other countries, and as they note, “Unfortunately, appropriate methods and advanced techniques to deal with such a great quantity of EW [e-waste] in China are lacking. Cheap and primordial methods, like manual disassembly, roasting, and combustion, are often used to dismantle the EW to recover valuable metals, plastics, and electronic devices.”

Roasting. We’re talking toxic metals and plastics like polyvinyl chloride and polyethylene which often contain chlorides and flame retardants including polybrominated diphenyl ethers or PBDEs. Although the impacts of PBDE exposure on humans is unclear, in animal studies they impair thyroid function (in fact, a recent study associates PBDEs with hyperthyroidism in house cats), additionally these chemicals are widespread in the environment, and like their polychlorinated cousins (for example PCBs and dioxins) are persistent in the environment, accumulating in both humans and in wildlife. But that’s not all folks, when heated the plastics and the chemicals with which they’re impregnated melt and recombine to form even more toxic products including polychlorinated and polybrominated dioxins, which then contaminate not only the worker’s air, but the air of local villages, delivering these hazardous chemicals to both the oldest and youngest residents. In fact, based on concentrations in local air, the authors estimate that residents may be exposed to upwards of fifty times the total daily intake of toxic equivalents established by the World Health Organization (because chemicals like dioxins really represent a large family of similarly shaped chemicals with a broad range of toxicity – toxic equivalents are used to establish a single number that can be used to refer to toxic doses of dioxin and like-chemical mixtures), and, they add, workers are likely exposed to much higher amounts.

My thoughts turned to the monitor in the shed, and the laptop under the couch. In our Massachusetts town, for five dollars a piece I cart the monitor and laptop over to the local transfer station. But surely they don’t end up in one of those communities I’d read about? Or do they?

Part II

“Great question,” says Jan Ameen, the executive director of my county’s solid waste management district. “The company most towns use had been processing everything in the U.S.China. I heard they don’t do that anymore. We are looking into different companies that appear to have a better market.” They got bought out a couple of years ago and I just thought to ask about their markets. A bunch of end product goes overseas. …the company Montague uses was sending things on a box car to

My heart sank. Our little town of Montague tends towards the progressive. We’ve got great recycling, Prius’s zip through town, and biodiesels abound. Solar panels glint from rooftops and good luck to the Nestle Corporation, currently considering sucking spring water from the Montague Plains. After a few more e-mail exchanges with Jan, I began to wonder if it was even possible to ensure that our e-waste did not sicken workers nor contaminate their local environment.

I was on a mission. Jan gave me the names of a few local companies that collect e-waste and after Googling e-waste and recycling, I sent a raft of emails to various companies around the country. “I am interested in learning about e-waste recycling and dismantling,” I wrote, and attached a list of questions I’d hope would get some answers. Perhaps I shouldn’t have included that I was a toxicologist and a writer. I received just one response.

“Almost any electronic waste can be recycled,” wrote Andrew McManus, Environmental Engineer at Metech International, a large precious metal and electronic waste recycler with facilities in Worcester, MA and Gilroy, CA, which serves commercial businesses and equipment manufacturers. In response to the questions I’d sent, he provided a detailed narrative of what happens to the plastics, metals, and batteries once they leave our homes and enter their facility.

“Current historic high prices for base and precious metals, rapid changeover of technology, data security systems, and high labor costs,” explained McManus, “favor shredding domestically.

Current standard shredding process is as follows: Desktop computers usually have one small "button-cell" lithium metal battery inside which functions as the computer memory clock. Typically the case is opened, the main circuit board is pulled out, and the battery is removed. The entire CPU frame is placed on a conveyor and shredded. A magnetic belt removes the steel after shredding, sometimes followed by an Eddy Current separator to remove non-ferrous metals like aluminum and copper materials. The remaining mixed material contains circuit boards, some mixed metals, and plastic.”

This was all very interesting, and positive, until I got to the following:

“This is sent overseas to a smelter for recovery of the copper, precious metals, and other base metals while the remaining plastic/circuit board is consumed as fuel in the process. There are no facilities in the U.S. that can take circuit boards and effectively recover metals.”

“Overseas,” I responded, “as in Asia? Why are there no facilities in the U.S.?” I thought about the box of circuit boards at Veronica’s, and imagined them waiting to be roasted in Guiyu, China. Knowing that the conditions in China and elsewhere was likely a sensitive topic, thanks in part to the Basal Action Network, a nonprofit toxic-trade watchdog group, responsible for the documentary, “Exporting Harm: The High-Tech Trashing of Asia,” and more recently “The Digital Dump: Exporting Re-use and Abuse to Africa,” I wondered if McManus would answer.

The response was swift, maybe for those reasons above, he was quick to point out they do not ship circuit boards to Asia.

“We send our circuit boards to Germany, Sweden, or Belgium. There are also large smelters in Canada and Japan.”

In response to my question about why no U.S. facilities, McManus wrote, “In my opinion there are none in the U.S. because our government in unwilling to establish conditions favorable to operate. Regulations are no stricter than other places in the world. Our environmental agencies do not co-operate with business, and our legal system makes lawsuits by almost any party a constant risk. The complexity of materials would require an enormous capital investment. The German smelter, Norddeutsche Affinerie, recently announced they plan to build a secondary copper smelter to recover electronic waste in Louisiana.”

His comments about difficulties with recycling in our own country where we’ve got electronic gadgets galore, made me wonder about who ought to be responsible for recycling, aside from the consumer, many of whom would like to do the right thing but who just don’t have the time to investigate what happens to their cast-offs once they’ve deposited them at the town transfer station.

Turns out this is a question that states across the country have been asking in recent years, with California, of course, leading the way. Back in 2003 California enacted “The Electronic Waste Recycling Act of 2003” requiring retailers to collect e-waste recycling fees from consumers, which then cover the cost of collection and recycling of unwanted electronics. This is just one approach. Another is to hold the producer responsible. According to Dennis Brown Vice President of State Government Relations for the Equipment Leasing and Finance Association, eight states so far have passed electronic recycling legislation with seven of the eight enacting producer responsibility legislation and it looks like Massachusetts may follow suit.

“Massachusetts is all the more unlikely to do what California did if it results in a ten dollar tax – New Hampshire would throw a party for the legislature if they did,” says Brown, adding that, “producer responsibility to develop programs for recycling also spurs development of more green products.”

And some producers are already reclaiming their own materials. Most recently, Sony announced a take-back program for any Sony product, joining computer companies Dell, Hewlett-Packard and Apple, all of which now have some version of recycling (Dell for example will take back any brand of computer upon purchase of a new Dell.)

This all seems like great news, but none of it answers the “Then What,” question. Most companies refer to their “environmentally responsible practices,” but it would take some digging to learn specifics. What would Massachusetts do if they enacted legislation requiring some sort of recycling?

According to Greg Cooper of the Massachusetts Department of Environmental Protection, “The legislation would hopefully build on the existing collection and processing infrastructure that Massachusetts has built since its, first in the nation, ban on the disposal of televisions and computer monitors and ensure that e-waste is managed in an environmentally sound manner."

Thankfully, I don’t need to think about recycling the old IBM just yet – Veronica and Cathy fixed it up just fine - but hopefully when the day comes for the blue screen of death to rear it’s ugly head – I’ll be able to send her off for disassembly and recycling without contaminating workers and their families half-way around the world.

For more information check out EPA's site on e-waste and the Basal Action Network's site. If you want a whole book about it, read High Tech Trash, by Elizabeth Grossman, published by Island Press.

For detailed information on Cell Phone recycling see: Cell Phone Recycling

Please feel free to distribute or reprint with proper attribution: E. Monosson, theneighborhoodtoxicologist.blogspot.com

Poisoning by Water

As any toxicologist will tell you, and as most of us know, too much of a good thing - or in toxicology, too much of just about anything can be bad. Whenever I introduce students to toxicology, I usually begin with very accessible examples, like anti-inflammatory medication. I also like to use personal examples whenever possible, like the time our dog Bruno, after placing himself in front of a van and winding up with a broken leg and a severely dislocated hip – decided to consume a whole bottle of doggie anti-inflammatory medication, blue plastic and all. To his defense the things were disguised as meaty treats, and after getting his stomach pumped, and kidney and liver function tested, all was well.

Another example is that of water, although, having too much water always seemed a bit far-fetched. That is, until this past weekend when my husband Ben, almost passed on to hilly bicycle heaven – after a bout of water poisoning – or hyponatremia. I might sound glib about this now, but perhaps that’s to assuage my own anxiety over potentially loosing someone I love to something so preventable.

In his case, he didn't just drink too much water, he lost too much sodium. He might be described as a passionate biker. When he rides the seven miles to work, he takes the long way home, logging twenty to forty miles a day. When he rides on weekends he takes the long way to anywhere, riding from thirty to sixty miles. When he rides for fundraisers, he chooses the 100 mile ride – or in this case the 120 mile, 10,000 feet of climbing, dirt road ride. In other words, riders like Ben are not like you and me (well at least not like me – these days, fifty is my limit.)

Now Ben is an experienced rider, who knows to watch his water and electrolyte intake. Electrolytes are ions that exist in solution and include sodium, potassium, calcium, and chloride. In our blood these ions and others are essential for normal cell function. You might be familiar with the multitude of electrolyte replacement drinks available in a range of wholly unappetizing colors (Neon Green, Antifreeze blue etc.) marketed to both the general public and to athletes. The idea is when you exercise you sweat out not just water but electrolytes, and so you need to replace accordingly (they also contain carbos for energy I suppose.)

What Ben didn’t know on that fateful day was how carefully to watch that balance, and that riding over 100 miles, on a steamy August day (one of the most unbearable of the summer), though the hilltowns of western Massachusetts, would not only wring the salt right out of him, but also cause him to over drink. Though he quaffed electrolyte drinks, and consumed little powdery packets of the stuff, none of it had sufficient amounts of sodium to maintain the balance.

The result? An ambulance trip to the ER, an overnight stay in the hospital, one very concerned wife. When the nurses asked simple questions like, “Where are you?” “What month is it?” “When is your birthday?” he was unable to respond (though he didn’t miss a beat when she inquired about our current president, Dubya, an unfortunately tough thing to forget.)

Turns out, his sodium concentration had fallen to below 121 milliequivalents per liter (mEq/L) of blood. The normal range is 136 to 145 mEq/L, and anything below that is considered hyponatremia. Ben had a severe case of hynonatremia. Proper sodium (and other electrolytes) concentration in the blood is essential for life, and keeps our cells in balance with the fluids that surround them. When the sodium concentration in our blood becomes too dilute, the cells take up water, causing them to swell. Hence, Ben’s swollen brain forgot most things. In the worst cases seizure and death can result.

Thankfully, Ben was plugged into a saline I.V. drip moments after the ambulance arrived. Several I.V. bags later, he could finally recall our kids ages, state that he was indeed in the hospital and recall our anniversary date (well, he missed by eleven days but at this point who’s counting?)

So, there you have it – an unfortunately personal but thankfully nonfatal example of poisoning by water. Hopefully his tale and the articles below will help others avoid his fate.

For more about hyponatremia, warning signs, and how to prevent, check out the following sites:

Salt and the Athlete

Fluid Balance and Electrolyte Balance and Endurance Exercise: What can we learn from recent research?

Hyponatremia, Mayo Clinic

New Statement on Exercise-Associated Hyponatremia Issued

From Our Town Dump to.....The fate of high tech waste, the journey begins

Crossposted from Earth Forum:

Sidney's post on Waste Management, prompted me to add this post. When I read his title, my own thoughts jumped to management of e-waste (and wondered if this would be covered at that meeting.)

From my impression, this one of those waste issues where growing awareness is making a difference. In my own town, for example, you can rid yourself of computers, televisions and any electronic waste for something like five dollars. But the question is - then what? Turns out it "used" to go into a box car and then apparently on to China. I emphasize "used to" because that's only what I am told. The change, presumably, occurred because of environmental and health concerns. But at the moment no one can tell me if they've really changed their practices (it's something I'm looking into for a future article on the stuff.)

Two articles recently published in Environmental Science and Technology reveal the high risk to residents and workers caused by the dismantling of e-waste in regions where environmental laws are lax or nonexistent. The first article, by Huiru Li and others, is entitled " Severe PCDD/F and PBDD/F Pollution in Air around an Electronic Waste Dismantling Area in China " and the other by Xinhui Bi and others "Exposure of Electronics Dismantling Workers to Polybrominated Diphenyl Ethers, Polychlorinated Biphenyls and Organochlorine Pesticides in South China," describe the exceedingly high concentrations of these toxic chemicals to which not only workers but local residents are exposed during the dismantling processes.

For those interested in further reading on the subject, check out "High Tech Trash," written by Elizabeth Grossman, published by Island Press. An informative and sobering book, through which I'm slowing making my way.

Doh! There's more to bioaccumulation than we thought!

Here’s one for the “why didn’t we figure this out sooner” file, or maybe the “gee – those of us air-breathers really are different from our gilled cousins!” You see, for years one of the primary methods of determining the ability of a chemical to accumulate in living creatures was to study the accumulation (or bioaccumulation) of the chemical in fish. The model is based on the idea that fat-loving chemicals, which includes most bioaccumulative chemicals, are essentially absorbed from the surrounding water by fish, or, more or less technically, by “swimming bags of lipid.” Those that are not rapidly metabolized are retained in the fat, allowing not only for accumulation in our little fish, but also for the proverbial big fish that eats the little fish all the way up the food chain to polar bears, bald eagles and homo sapiens. Some infamous lipid-loving chemicals that we all know and fear include certain PCBs, dioxins, and DDTs.

Most governments, including the U.S., have thankfully learned (after…umm decades) to consider carefully a chemical’s potential for persistence, or ability to hang around the environment, and bioaccumulation when evaluating and regulate commercial chemicals.

Great! No more bioaccumlative chemicals climbing up the food chain. Problem solved. Or is it? A recent report by Barry Kelly, Frank Gobas and others, published in Science (Volume 317, pages 236-239) suggests that our current method for evaluating bioaccumulation may miss – and in a big way. According the study, some chemicals that don’t accumulate in fish, or chemicals that might pass the “swimming lipid bag” test with flying colors, can accumulate land mammals and marine mammals.

What’s the difference? After all fat is fat – be it a swimming or walking bag of lipid (which I must admit sometimes I’ve felt myself as I struggle to squeeze into my favorite jeans at the end of the summer.) Turns out, as with anything, there’s more to bioaccumulation than hanging out in fat. Living organisms are dynamic creatures, and most things that enter the body have the potential to be metabolized and/or excreted. Even chemicals that hide out in fat can be eliminated given enough time. But what’s different between fish and polar bears or fish and humans (among other things) is that according to Kelly and others, “…air-breathing organisms in this analysis exhibit higher [biomagnification factors] than those in water-respiring organisms because of their greater ability to absorb and digest their diet, which is related to differences in digestive tract physiology and body temperature.” Additionally, note the author, air-breathers may be less efficient when it comes to eliminating certain chemicals from their bodies than water-respirers.

Go figure. This is where, as a toxicologist who bought into the “bag of lipid” model years ago without question, now wonders – what was I thinking? Chemicals that might pass (and have passed) the fish bioaccumulation test, wouldn't pass a mammalian test, according to the authors who note that these chemicals, “representing a third of organic chemicals in commercial use, constitute an unidentified class of potentially bioaccumulative substances that require regulatory assessment to prevent possible ecosystem and human-health consequences.”

Time once again, to reconsider how we evaluate and regulate, and release chemicals into our environment.

Our bodies, the ultimate transformers: PFOA and other perfluorinated chemicals in our bodies

Our bodies are constantly working, transforming chemicals from one form to another like that bagel and cream cheese I had for breakfast into something hopefully more useful or, the chemicals from that greaseproof food-packaging paper into something more toxic. Whoa. What?

A few posts back I wrote about perfluorinated chemicals – known as PFOA and PFOS - used for waterproofing and nonstick pans. Then I added a post about PFOA and popcorn bags. Now it’s even more insidious and complicated than being exposed to just PFOA. Considering recently reported concentrations of these chemicals in human blood, Jessica D’Eon and Scott Mabury, in a study just published in Environmental Science and Technology suggest that concentrations in humans are likely the result of “exposure to current-use fluorinated materials and not the historical load present in the environment,” (Certain perfluorinated chemicals have been phased out of use by major producers once recognized as human and environmental contaminants.)

These current-use chemicals, particularly those used to manufacture waterproof or greaseproof paper (think microwave popcorn,) known as polyfluoroalkyl phosphate surfactants or PAPs, can be transformed once transferred from say, that greasy microwave popcorn bag to our fingers or popcorn and then to our guts, not only into PFOA (which a recent draft assessment by EPA suggests is a carcinogen) but also chemical compounds which might be more immediately toxic.

Referring to the byproducts of metabolism D’Eon and Mabury write,“Due to their inherent reactivity, exposure to these transient metabolites is likely of greater toxicological concern than exposure to PFCAs [which includes PFOA] alone.”

Huh. Ain’t that funky now.

Of course further work is necessary before the potential impacts of these kinds of exposures can be fully understood, including a better understanding of how (and how much of) these chemicals migrate into food, what kinds of food are most important for this kind of exposure, and how much of these foods we consume. Microwave popcorn anyone?

You can find the full article, in issue 41, of Environmental Science & Technology, pages 47-99-4805.

New Report on EPA and Nanotech - just what I've been waiting for!

For those of us concerned with health and environmental impacts of new and old chemicals, the production and use of nanomaterials presents a fascinating opportunity to consider and then reconsider the mechanisms by which chemicals are tested and controlled in the United States. While I've been trying to keep up with the toxicology of nanomaterials, I've wondered about the adequacy of our current regulatory framework to evaluate and manage these materials. Fortunately for me and anyone else wondering the same thing, a recent report by Dr. Terry Davies entitled EPA and Nanotechnology: Oversight for the 21^st Century opens the door for us, by reviewing the principle laws and regulations developed to manage and control chemicals and considers the effectiveness of their application down in Whoville, where all things are nano.

As Davies notes, “In a few decades, almost every aspect of our existence….is likely to be changed for the better by nano. However, if the potential for good is to be realized, society must also faces nano’s potential for harm.”

One of the primary issues for toxicologists investigating nanomaterials, is my favorite, “It’s hard to find what you don’t know you’re looking for,” or it’s pretty difficult anyway…unless one is trained to expect the unexpected. And it seems that nanomaterials have the potential to behave quite differently not only from their non-nano counterparts, but also from different formulations of the same material. In some cases, as Davies notes, contrary to current underlying toxicological concept that smaller doses tend to be less toxic (in general – there’s a whole ‘nother discussion to be had about hormesis – the differential behavior of some chemicals at very low concentrations) in some cases nanomaterials may behave differently and potentially more toxic when present in lower concentrations than their non-nano counterparts. Just that issue alone has the potential to turn our current toxicity testing, assessment and regulatory practices upside down when it comes to nanomaterials!

But really the focus of Davies report is the “so what” question. Given where we are now – in terms of understanding the potential health and environmental impacts of these materials – what can be done in terms of regulation and management? As Davies points out, while some of EPA’s programs, as they are now, may provide adequate oversight of nanomaterials (he cites FIFRA – which has jurisdiction over all pesticides – as a program that has “strong legal adequacy” when it comes to nanomaterials) TSCA, the Toxic Substances Control Act, which has the greatest potential to cover the most nanomaterials, is “particularly deficient” for a number of chemical oversight functions. According to Davies “the Act desperately needs to be amended, both to deal with nano and to adequately address all types of chemicals.”

This is an informative and readable report, and if you’re at all interested in nanomaterials, you might want to take a look.

The full report is available free and online through the Project on Emerging Nanotechnologies, an initiative of the Woodrow Wilson International Center for Scholars and the Pew Charitable Trusts, www.nanotechproject.org.

What's Emerging in your Water?

There is a nice review of Emerging Contaminants, recently published in the journal Analytical Chemistry, by Susan Richardson. In it is a review of the "oldies" like PFOA, PFOS, and polybrominated flame retardants and newbies like nanomaterials and ethylene dibromide or EDB, a gasoline additive from back in the day when gasoline was leaded.

In the excerpt below she discusses the term “Emerging,” a term over which I sometimes stumble. Which chemicals fit into the category of emerging contaminants? Why are some chemicals which have been around for decades suddenly appear as “emerging” and, why are others, which have yet to be detected in major quantities (like the category of nanomaterials – which describes a type of chemical rather than any one specific chemical) on the list?

“Emerging environmental contaminants were the focus of a recent issue of Environmental Science & Technology (December 1, 2006), where current research on emerging chemical and microbial contaminants was highlighted. This is a must-read issue, and several of those papers will be discussed in this review. The guest editors of this issue also published an excellent perspective on "What is emerging?" as a lead-off editorial to this issue, which points out that the longevity of a contaminant's "emerging" status is typically determined by whether the contaminant is persistent or has potentially harmful human or ecological effects (2). It is often the case that emerging contaminants have actually been present in the environment for some time (in some cases, decades), but they are discovered through a wider search of potential contaminants (as in the case of ethylene dibromide, in this current review) or through the use of new technologies (such as LC/MS) that have enabled their discovery and measurement in the environment for the first time (as in the case of many pharmaceuticals).”

Although a bit technical in spots (this is Analytical Chemistry afterall,) the current literature for each emerging contaminant is reviewed in a readable manner, and there is an impressive list of over 200 citations for those looking to learn more.

What do nonstick pans, carpets, polar bears and newborn cord blood have in common? Perfluorinated chemicals in the news again

Once again, the “miracle” chemicals that coat most of our fry pans, raincoats and the ever-white (well maybe after 10 years of leg-sweat and black dogs - off-white) stain repellant couch in the living room are in the news. I’m referring to that most complex family of perfluorinated chemicals which includes perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) (and I promise not to mention the whole chemical name again in this entry!)

I wrote about PFOA and PFOS earlier, some of the legal loopholes that led to this current situation, and the ongoing phase-out of certain types of these chemicals, and now there is an excellent article summarizing the current research on the toxic effects of these chemicals written by Kellyn Betts and published in the Environews section of Environmental Health Perspectives.

After decades of use, these wondrous and now infamous chemicals are a part of us all. Scientists have measured the chemicals in the bodies and tissues of humans and wildlife around the globe. In fact, a recent study published in Environmental Science and Technology reported the presence of these chemicals in “99-100% of umbilical cord sera” of newborn babies tested in Baltimore, MD.

What I find most frustrating is that though these chemicals have been used (and released) by the ton for decades, once again toxicologists are playing catch-up. The great majority of toxicity studies about how a chemical behaves in a body, and its toxicity depends upon experimental exposures to laboratory animals. The difficulty lies in translating these effects to the “target” species; it may be humans or it maybe certain wildlife species that are at greatest risk of exposure (for example – Atlantic dolphins.) One key, among many, to extrapolating from laboratory animals to target species is understanding the similarities, and differences of how a chemical moves through the body. Where it goes, how long it remains and what happens to it (is it broken down, metabolized, excreted?) But according to EPA scientists interviewed by Betts, for chemicals like PFOA and PFOS there are very large differences in how long the chemical remains in the body, not only between species but between sexes, that they don’t understand just yet. For example while PFOA might be eliminated in a few hours from a female laboratory rat, it might be days for a male rat, and years for a human.

Among the findings reported in this recent Environmental Health Perspectives article are a summary of studies indicating that both PFOA and PFOS suppress immune function, in some cases at concentrations that occur in wildlife (some of the highest concentrations reported in wildlife have been found in Atlantic dolphins, according to the article,) in addition, researchers report impacts on growth and development of offspring born to exposed mothers, and neonatal morality. For more, read the article published in Environmental Health Perspectives Volume 115, Number 5, May 2007

Update Nov 1, 2007: Another study just published in Environmental Health Perspectives evaluates the relationship between PFOA and PFOS concentrations in cord blood with birth size and weight. Although the authors report a small negative relationship between PFOA, PFOS and birth weight and head circumference, the authors suggest "...cautious interpretation of this study until the findings can be replicated in other populations."