An interesting piece of news in the current issue of Environmental Health Perspectivesis research indicating that bisphenol A (BPA) causes insulin resistance in mice similar to that seen just before the onset of type 2 diabetes. The BPA dose that was high enough to cause insulin resistance in mice was in the same range as the 50 ug/kg-day Reference Dose developed by EPA.
This is pretty interesting stuff, as well as potentially highly significant in a public health context, when you consider the prevalence of diabetes and the widespread potential for exposure to BPA.
One of the things I would like to get from the paper (it’s late in the evening – I’ll read it later this week) is how dose-dependent the effect might be. The finding that effects are observed in animals in the range of the RfD makes me wonder what might be happening to plastics workers who probably receive higher exposures to BPA than the general public. Is it possible for workplace exposures to BPA to be associated with an incidence of diabetes that could be observed epidemiologically?
Remember Paul Ehrlich’s bet with Julian Simon regarding the sustainability of metals reserves? Julian L. Simon and Paul Ehrlich entered in a famous wager in 1980, betting on a mutually agreed upon measure of resource scarcity over the remainder of the 1980s. Prices went down and Ehrlich lost the bet. However, it appears that his arithmetic was just of by a couple of decades. A materials flow analysis conducted recently by Thomas Graedel and colleagues at Yale concludes:
Providing today's developed-country level of services for copper worldwide (as well as for zinc and, perhaps, platinum) would appear to require conversion of essentially all of the ore in the lithosphere to stock-in-use plus near-complete recycling of the metals from that point forward.
Another interesting factoid, found here, is that 26 percent of extractable copper in the Earth's crust is now lost in “non-recycled wastes”, or stated less-technically, it’s in landfills. I don’t think that should mean it’s lost, just that resource reclamation through landfill mining may be the growth industry of the next decade.
More on this later. I don’t have a subscription to PNAS, and need to cough up $10 for the paper.
I guess the “global climate change is really happening” message has become part of the conventional wisdom, since it was published in the not-so-liberal Washington Post. Also, the “why-are-they-afraid-of-a-little-transparency” Bush Administration appears to be sitting on James Hansen, director of the Goddard Center for Space Studies, preventing him from speaking about global climate change. I guess the truth hurts.
If you haven’t started doing it already, you might want to be reading less about greenhouse gas emissions and mitigation strategies, and reading more about impacts and how to live with them. I started a resource guide here, which I’ll add to from time to time.
The high temperature was 51 degrees F today, here in southwestern Ohio.
This week, the California Air Resources Board (ARB) identified environmental tobacco smoke (ETS) as a Toxic Air Contaminant. An analysis conducted by the Office of Environmental and Health Hazards Assessment (which gives you the inelegant-sounding acronym OEHHA) identifying relationships between ETS exposure and a range of adverse effects provided the basis for ARB’s determination.
OEHHA’s report concluded there were associations between ETS exposure and premature births, low birth-weight babies, and Sudden Infant Death Syndrome. Other effects of ETS on children include the induction and exacerbation of asthma, and infections of the middle-ear and respiratory system. OEHHA also reported that ETS exposure was associated with increased incidences of breast cancer in non-smoking, pre-menopausal women, incidences of lung and nasal sinus cancers in adults, heart disease, eye and nasal irritation, and asthma.
In 2001, ARB and OEHHA initiated a process to update the information on ETS and to identify ETS as a toxic air contaminant (TAC) as mandated by the air toxics regulatory program referred to as Assembly Bill 1807. Under AB1807, ARB is required to identify substances in air that may pose a threat to public health as toxic air contaminants. This involves a two-step process, risk identification and risk management. What was published this week was the risk identification step for ETS.
Regulatory action that might be needed to control the identified risks is addressed in the second step (risk management). The risk management step includes a review of controls already in place, the available technologies and associated costs for reducing emissions, and the associated risk reduction. Extensive public involvement is included in the development of the control measures. ARB takes into consideration cost-effectiveness, and the balance between public health protection and economic growth, in developing the control plan. With ARB's determination, ETS essentially has been elevated to the same status as benzene emissions from oil refineries, hexavalent chromium emissions from aerospace manufacturing and diesel particulates from engines everywhere. This is a significant fusion of public health and environmental protection initiatives. It is difficult to imagine USEPA’s urban air toxics program addressing ETS.
The ETS report, findings from ARB’s Scientific Review Panel, proposed rulemaking and 571 pages of public comments, can be found here.
Controlling ETS has to be a good thing – even the ACSH is somewhat behind it.
This news emerges at the same time as the controversy among tobacco control activists about firing employees who smoke, or as the World Health Organization is doing, not hiring smokers. It’s a disquieting trend; but, at the same time, do smokers have the right to add to the healthcare burden of this country?
The ARB is an arm of the California Environmental Protection Agency (Cal-EPA). I know from personal experience (I used to work for an agency that is now part of Cal-EPA) that Cal-EPA has not always been popular with it’s federal counterpart, the USEPA. However, what is valuable about state regulatory programs in populous states such as California, New York and New Jersey, is that they can lead the way for other states and eventually the federal government. It’s hard to imagine federal agencies under the thumb of the Bush Administration taking such a bold step.
In the Independent this week is a story that researchers at UC Riverside are reporting that male hornyhead turbot and English sole, feeding near sewage outfalls, are being feminized, with the likely culprit being chemicals used in sunscreens. One chemical identified in these studies is oxybenzone, which protects the skin from the effects of ultraviolet radiation.
Other studies by Swiss researchers indicate that potentially endocrine-disrupting substances used in sunscreen and lip balm, octocrylene and 4-methylbenzylidene camphor, also bioaccumulate in fish.
Cosmetic industry representatives argue the benefits of sunscreens in preventing melanoma. A competing point brought out in the article, and something I hadn’t considered before, is the effect of sunscreens in reducing Vitamin D production. I don’t know how real that one is, and further exploration of it will have to occur some other time (I’m traveling the rest of the week).
What comes to mind is that these chemicals are either being discharged to water in large quantities, or they are potent endocrine disruptors. If it’s the latter, you have to wonder about the human health hazards for users of the products as well as for workers producing them. I’ll try and return to this subject at a later time. If you want to read ahead, you can start here.
I was asked recently about the potential for mercury exposure to an infant during breast feeding. Not much is known about it, but a Swedish study was published late last year in Environmental Health Perspectives. This study of 20 mothers and their infants showed that a small amount of methylmercury was transferred to an infant from breast milk. Infant exposures declined throughout the first 13 weeks of life, which was not entirely expected because infants do not readily detoxify methylmercury through demethylation. The decline is thought to be due to rapid infant growth. Median blood-methylmercury levels in the infant declined from 1.1 ug/L four days after birth to 0.38 ug/L after 13 weeks. The highest blood-methylmercury in an infant four days after birth was 4.4 ug/L and 1.1 ug/L at 13 weeks. These levels fall below the 5.8 ug/L level used to develop the Reference Dose for methylmercury. The most interesting observation by the investigators was that the women apparently complied well with mercury advisories in fish, and limited their consumption of freshwater fish that might contain high mercury concentrations (marine fish consumption was not recorded, a bit of an oversight for our uses, given the popularity of tuna as a source for fish in the diet). Maternal blood-methylmercury levels generally were less than 2 ug/L (in the NHANES survey, the 75th percentile blood-methylmercury level for all women ages 16 to 49 was 1.7 ug/L). The NHANES survey reported that half of the women who reported eating fish at least twice a week had a blood-methylmercury of 3 ug/L or greater.
The lack of data on seafood consumption limits the use of this study, but overall it appears that if you are concerned about limiting methylmercury exposure to your infant, you’ll continue to adhere to fish consumption advisories while breast feeding. Don’t forget to take your fish oil capsules.
I saw this cheery bit of commentary from James Lovelock in the Independent last week. His view of humankind’s future is seen through the lens of the Gaia Hypothesis, in which the, oceans, atmosphere, lithosphere and biosphere are viewed as integrated components of a single, self-regulating organism – Earth as Gaia, the earth mother in Greek and Roman mythology. His book Gaia: A New Look at Life on Earth had an important role in forming my perspectives on the environment. Some might view the Gaia Hypothesis as simply anthropomorphic thinking, but it is still a powerful meme for the interdependency of natural systems. It explains the tone of his article when he says:
This article is the most difficult I have written and for the same reasons. My Gaia theory sees the Earth behaving as if it were alive, and clearly anything alive can enjoy good health, or suffer disease. Gaia has made me a planetary physician and I take my profession seriously, and now I, too, have to bring bad news.
The bad news being that through greenhouse gas emissions, modification of the landscape (particularly clearing the rain forests), loss of species diversity and probably several other things, we’ve probably created a new equilibrium condition for Earth, one that’s not going to be particularly hospitable to humans in the long run:
Our planet has kept itself healthy and fit for life, just like an animal does, for most of the more than three billion years of its existence. It was ill luck that we started polluting at a time when the sun is too hot for comfort. We have given Gaia a fever and soon her condition will worsen to a state like a coma. She has been there before and recovered, but it took more than 100,000 years. We are responsible and will suffer the consequences: as the century progresses, the temperature will rise 8 degrees centigrade in temperate regions and 5 degrees in the tropics.
Much of the tropical land mass will become scrub and desert, and will no longer serve for regulation; this adds to the 40 per cent of the Earth's surface we have depleted to feed ourselves.
Curiously, aerosol pollution of the northern hemisphere reduces global warming by reflecting sunlight back to space. This "global dimming" is transient and could disappear in a few days like the smoke that it is, leaving us fully exposed to the heat of the global greenhouse. We are in a fool's climate, accidentally kept cool by smoke, and before this century is over billions of us will die and the few breeding pairs of people that survive will be in the Arctic where the climate remains tolerable.
By failing to see that the Earth regulates its climate and composition, we have blundered into trying to do it ourselves, acting as if we were in charge. By doing this, we condemn ourselves to the worst form of slavery. If we chose to be the stewards of the Earth, then we are responsible for keeping the atmosphere, the ocean and the land surface right for life. A task we would soon find impossible - and something before we treated Gaia so badly, she had freely done for us.
Airborne particulate matter as a protective mechanism for global warming means real problems for respiratory health in the short term. What a trade-off.
A different perspective is presented in this article from the Christian Science Monitor. It’s a more hopeful message from the Millenium Ecosystem Assessment, asserting that we have the tools to put things back onto a more sustainable course.
. . . the report makes clear that people must view Earth's ecosystems as one interlinked system, rather than as fragments. People must begin to actively manage those ecosystems in ways that ensure that they will receive the benefits those ecosystems provide - from blunting the surge from ocean storms and filtering water to feeding a hungry world. Indeed, with efforts now under way to develop worldwide observing systems to monitor the oceans, atmosphere, and land use, technology is moving into place to support such broad management efforts.
That’s also assuming that we act promptly. Note the difference from Lovelock’s perspective, which is that the task of being stewards of the Earth is a task that is beyond our abilities. Of course, in the short-term, we may not have left ourselves with too many alternatives.
Then I’ll read something like this article about exurban sprawl (people commuting to Washington D.C. from the West Virginia border – it’s worse in California; people commute from my hometown of Salinas to Santa Clara) which shows that we’re still off in the wrong direction. James Howard Kunstler reminds us regularly that we’re behaving idiotically but it doesn’t seem to be sinking in yet.
Oil prices are going up again. Maybe that will help with the reeducation.
So now being fat is good for the economy, according to the WaPo. Next, we’ll be told that it’s a patriotic virtue. This somewhat twisted perspective shouldn’t be too surprising when you understand that the Gross Domestic Product, the measure of economic success, is a Mad Hatter’s accounting system where Oreo sales and quadruple bypass surgeries are all added together into a giant blob of economic prosperity.
In the last post on this topic, I introduced how do we figure out whether or not a chemical is a carcinogen, noting that the primary sources of information used in carcinogen identification are epidemiological evidence and results from bioassays with laboratory animals. Epidemiology is an observational science. Epidemiology is a very challenging endeavor because it takes natural settings, which are inherently messy things as it finds them. Because of this, the ability for epidemiology to make inferences about the relationship between patterns of disease and exposure to specific substances can be confounded by different factors. In addition, attributing causation using epidemiology involves filtering study results through a set of guidelines or “viewpoints” (referred to by many as Austin Bradford Hill’s nine criteria, though he reportedly never viewed them as so clear-cut. This reflects a fundamental limitation of empirical science that cause and effect relationships cannot be observed directly or proven true by logic, and therefore must be inferred by inductive reasoning.
Studies with laboratory animals are experiments, which allow more control over the confounding factors, so that an investigator can study in isolation the relationship, “ingestion of substance A in a particular rat species results in the occurrence of adverse effect B”. The drawback with animal studies is that difficulties can arise in extrapolating the results to human exposure situations. In addition, cancer bioassays have their own set of possible confounders. The complexities involved with using animal studies can be seen by reviewing the guidelines EPA uses to evaluate animal studies and apply the results for assessing human health risks. Are you done looking at them? I’m sure that’s cleared things up a bit.
Let’s get down to a few cases. Liver cancer in mice is considered by EPA to be some of the strongest evidence that TCE is carcinogenic in humans. Even the solvents industry acknowledges that TCE is an animal carcinogen; but they will argue that the tumors don’t have relevance to human heath (TCE is thought to cause cancer in other organs – we’ll try and get to those later).
According to EPA’s reassessment, TCE causes liver cancer in mice. It has been suggested that TCE induces liver tumors through its metabolites, such as trichloroacetic acid (TCA), dichloroacetic acid (DCA) and chloral hydrate (CH); all three have been shown in separate studies to cause liver cancer in mice. EPA offers that “[t]he prevailing view of TCE-induced mouse liver carcinogenesis has been that these tumors arise in parallel with peroxisome proliferation** in the liver by TCE metabolites.” At one time, it was thought that the mechanism for liver tumors caused by peroxisome proliferators was due to oxidative damage caused by increases in free radical-generating enzymes and peroxisomal beta-oxidation that initiated carcinogenesis. Under this hypothesis, it was generally believed that because peroxisome proliferation has not been observed in humans, agents that produced this result in rodents would not present a carcinogenic hazard to humans. EPA has noted that a number of public comments on the draft TCE assessment expressed support for this point of view. Take a guess on who some of these commentors might be. At the same time, EPA’s Science Advisory Board suggested giving less weight to peroxisome proliferation as a liver cancer mechanism compared with other hypotheses.
However, in one of a series of white papers provided by EPA to the National Academy of Sciences panel looking into to TCE, more recent data is presented suggesting that chemicals causing peroxisome proliferation cannot be so easily ruled out as human carcinogens. The categorical statement that peroxisome proliferation doesn’t occur in humans, and the corollary that chemicals which are carcinogenic in animals through peroxisome proliferation aren’t going to be human carcinogens, may be a bit premature. Supposedly, peroxisome proliferation doesn’t occur in humans, because the human liver has very low levels of a macromolecule known as peroxisome proliferator-activated receptor-alpha (or PPAR), compared with the animal species that are sensitive to carcinogens acting through peroxisome proliferation. These carcinogens activate PPAR, which causes various metabolic effects, some of which resulting in tumor promotion.
There appears to be sufficient PPAR activity in humans to develop pharmaceuticals (hypolipidemic fibrates used to control triglyceride levels and thiazolidinediones used to reduce insulin resistance and blood glucose levels) that bind to PPAR and produce biological effects. One review from 2001 says:
Hypolipidemic fibrates have been shown to induce hypolipidemia in humans and to modulate gene expression (e.g., genes regulating lipid homeostasis) in human hepatocytes by PPAR activation. Thus, humans are responsive to agents that induce peroxisome proliferation in rats and mice.
A search of PubMed shows that hundreds of papers on PPAR activation have been published in the just the past few years alone. Of course, there’s a wide range of opinions and a lot of argument about how important PPAR activation is to human cancers (EPA’s white paper on the PPAR mechanism of action gives a voice to that range). However, I had previously accepted somewhat uncritically the argument that animal carcinogens acting as peroxisome proliferators weren’t human cancer risks. It’s been interesting to learn that humans are sensitive enough to PPAR activation to design drugs around it, and a message to be cautious about dismissing these kinds of chemicals as potential human carcinogens.
Critics of EPA’s reassessment state that TCE metabolites such as trichloroacetic (TCA) and dichloroacetic acid (DCA) are responsible for liver carcinogenicity in mice (in particular, some would argue that DCA should be viewed as the ultimate carcinogen – the chemical metabolized from TCE that actually causes liver cancer in mice). The argument goes that mice but not humans or rats produce appreciable levels of DCA as a metabolite of TCE; and TCE does not cause liver tumors in rats, so. . . TCE shouldn’t be considered a liver carcinogen in humans. Again, things probably aren’t so clear-cut and simple. Interactions between TCE metabolites and peroxisome proliferation by metabolites, including TCA which is formed in humans, are being offered as rationales for why liver tumors observed in animals exposed to TCE should be a concern for human health. EPA also has written a white paper on the topic of interactions between metabolites. The state of the science paper on mechanisms of TCE toxicity can be found here.
Another argument offered by critics of EPA’s TCE reassessment for why liver tumors in mice are not relevant to human health risks is that the test species used has a high spontaneous liver tumor rate. However, as discussed in EPA’s cancer risk assessment guidelines, animal bioassays are conducted using concurrent controls (a control population during the study) and historical controls (recorded trends in cancer incidence in lab animals across multiple studies) to address this background issue. Also, tumor incidence in a species with a high background incidence shouldn’t be a reason to dismiss the results outright; it provides an avenue for trying to further understand the mode of action in animals and how that might apply to humans. A high background tumor rate might affect how study results are used to quantify the potential cancer risk in humans; but that’s a different matter than using animal bioassays to identify chemicals as human carcinogens.
You can get a sense of the range of opinions on TCE from reading the comments on EPA’s reassessment (these can be found on http://www.regulations.gov/fdmspublic-rel11/component/main, using the advanced search feature and searching for the docket using the key word “trichloroethylene”) and EPA’s white papers.
There are more examples to explore – kidney cancer and non-Hodgkin’s lymphoma, and I’ll be visiting these, as we get closer to the National Academy Sciences committee on TCE’s report (due out sometime the middle of this year).
**A peroxisome is an organelle present in nearly all cells that plays an important role in the metabolism of long chain fatty acids and amino acids, and in synthesis of bile acids and cholesterol that are further used in digestion and hormone synthesis.
This is a bit off-topic for the environmental health blog, but I really should get something posted while I struggle to complete the next installment of “Cancer, Animals and Man” (I picked a really hard chemical to review, and there’s lots of other things going on at the same time right now . . . ). According to the WaPo yesterday, health care now consumes about 16 percent of the nation’s economic output. And, this is buried in a report noting that the growth in health care spending is decreasing over time, something I suppose should be treated as good news. The actual paper is behind a subscription firewall at Health Affairs. The abstract notes the 16 percent figure is nearly the same as in 2003, which makes me wonder what the WaPo means by “record” spending. Doesn’t matter – at least they published it.
Other trends noted here are the concerns that health care costs were increasing faster than wages or inflation, that they threaten to financially swamp many employers, and that there are still substantial ethnic and racial disparities in the level of care.
What leads me to title this a disgrace is this report in today’s NYTimes, which notes that several diabetes centers opened by hospitals in New York City and oriented towards prevention have now closed because they were money-losers:
At four hospitals across the city, they set up centers that featured a new model of treatment. They would be boot camps for diabetics, who struggle daily to reduce the sugar levels in their blood. The centers would teach them to check those levels, count calories and exercise with discipline, while undergoing prolonged monitoring by teams of specialists.
Sounds good, so far, but:
But seven years later, even as the number of New Yorkers with Type 2 diabetes has nearly doubled, three of the four centers, including Beth Israel's, have closed.
They did not shut down because they had failed their patients. They closed because they had failed to make money. They were victims of the byzantine world of American health care, in which the real profit is made not by controlling chronic diseases like diabetes but by treating their many complications.
Insurers, for example, will often refuse to pay $150 for a diabetic to see a podiatrist, who can help prevent foot ailments associated with the disease. Nearly all of them, though, cover amputations, which typically cost more than $30,000.
Patients have trouble securing a reimbursement for a $75 visit to the nutritionist who counsels them on controlling their diabetes. Insurers do not balk, however, at paying $315 for a single session of dialysis, which treats one of the disease's serious complications.
Not surprising, as the epidemic of Type 2 diabetes has grown, more than 100 dialysis centers have opened in the city.
An operator of one of the failed centers is quoted, "[i]t's almost as though the system encourages people to get sick and then people get paid to treat them".
But, life expectancy is rising in this country, which is good news, right? However, the real question should be, “are the added years quality ones”? And, does it have to cost so much?
The Times article goes on to note:
. . . the lone hope on the horizon is a restructured reimbursement system that puts the business of chronic care on a more competitive footing with acute care. Experts say this restructuring could start if government insurance programs like Medicaid began paying more for preventive efforts like education, a move that the private sector would be likely to follow.
You can’t blame the hospitals and insurers entirely (considerably, but not entirely). The Times article closes with a pathetic story of a diabetic, a client of the now-closed center, slipping back into her old high-risk habits and opining, “I needed reminding”. You mean needed reminding not to suffer needlessly and die early? This should be a wakeup call for all of us to reclaim our human dignity and stop acting like we’re simply a market segment for the healthcare industry.
Making chronic care cost-competitive. What a concept. From a good governance perspective, it makes sense. However, perhaps viewing peoples’ ill-health as assets to be strip-mined makes more sense from a business perspective.
