All posts by CPTFeditor

Airport Security and Radiation

Brain Cancer, Breast Cancer, Diet, Habits, & Other Behaviors, Environmental Exposures, Skin Cancer
Laura Covarrubias, Cancer Prevention and Treatment Fund

Following the September 11th attacks in 2001, the Transportation Security Administration (TSA) was created and given responsibility for protecting the public from security threats in transportation systems, such as airports. Although metal detectors were once the main security devices used at American airports, the TSA introduced new technologies after terror attempts were made using hidden explosives (in shoes and underwear, for example). These backscatter and millimeter scanners have begun replacing metal detectors and are designed to scan a person to determine what weapons or explosives they may have beneath their clothing. Currently, there are about 250 backscatter and 264 millimeter wave scanners in the United States. The TSA hopes to have 1,800 scanners of either type installed by the end of 2014 – which would mean that nearly every airport in the country will have one.

Backscatter scanners look like two large blue boxes. People raise their arms and stand sideways between these two boxes when they are scanned.

In contrast, millimeter wave scanners look like circular glass phone booths, and the person being scanned stands with their arms raised while part of the scanner rotates around them:

If you are not sure which scanner is in use at your airport, ask a TSA official at the security checkpoint.

Privacy

When a millimeter scan is used, the machine determines if the person has any potentially harmful items on his or her body. If so, only the outline of a standard human body is shown with potentially dangerous objects highlighted in yellow. If no dangerous objects are detected, the security officer will only see an empty green screen. The security official does not see an image of the actual individual when the millimeter scan is used.

In contrast, when a backscatter scan is used, a blurred, colorless image of the individual (without clothing) is produced. A security officer views the image and determines if further screening is necessary. In an effort to increase passenger privacy, the TSA updated the software on backscatter machines to make it harder to see details in the images. Still, some people argue that both types of machines violate their privacy.

Radiation

While metal detectors and millimeter scans both use non-ionizing radiation, which until recently was assumed to be safe (see our article Can Cell Phones Harm our Health?), backscatter scans use ionizing radiation, which is used in x-rays and known to potentially increase the risk of cancer. Backscatter scans work a little differently from x-rays. X-rays work by sending high-energy radiation to the body and recording the radiation that passes through the body. Dense parts of the body (like bones) block some of the radiation, resulting in lighter areas on the recorded image.  Backscatter scanners also send radiation toward the body, but at much lower energy than an x-ray. Because it is not as strong as the radiation used in x-rays, the radiation does not pass through the body. Instead, the outer layers of the body “scatter” the radiation, which bounces off the body and back toward the machine. Most of the radiation that is absorbed by the body is deposited in the outer layers (like the skin and ribs), although a 2012 study showed that radiation from these scans may penetrate to other organs.[1] Because the radiation is concentrated in the skin, there are concerns that this could cause skin cancer.

All data on backscatter scans are provided by TSA, a government agency that does not allow independent researchers to examine the machines they use.[2] Researchers must therefore make educated guesses using data provided by the TSA, or they must make models of the scanners based on information that the agency releases.

Scientists differ in their opinions regarding whether small doses of radiation increases the risk of cancer.[3] Some scientists think that very small doses-like those received during backscatter scans-pose zero risk to the individual. Other scientists think that there isn’t enough research on the effects of such low doses of radiation to be able to say how it will affect a person’s cancer risk. However, radiation risk accumulates during a person’s lifetime. This means that even though a single exposure may be very small, it is “added” to every other exposure the person has ever encountered.

The TSA states that backscatter scans use such low doses of radiation that estimating the potential effects of the scan is extremely difficult. [4] 2011 report using information from the TSA found that these backscatter scans expose people to the same amount of radiation that they receive from 3 to 9 minutes of normal daily life or from 1 to 3 minutes of flight. To put this into perspective, we would expect only 6 of the 100 million airline passengers each year to develop a cancer in their entire lives due to the backscatter scans.

Dr. David Brenner, a researcher at Columbia University, produced a different estimate based on the risk that the scanners are to the entire population, not just to an individual. Dr. Brenner multiplied the risk associated with one scan by the number of scans conducted each year to estimate the number of people who may develop cancer in one year because of the scanners. Because up to one billion scans may be performed each year, Brenner estimated that each year 100 people would develop cancer because of their exposure.

In April 2010, a group of scientists from the University of California, San Francisco wrote a letter of concern to Dr. John Holdren, the Assistant to President Obama for Science and Technology, about the backscatter scans. These researchers pointed out that because backscatter scans only penetrate outer layers of the body, it is possible that these layers receive a higher concentration of radiation than previously believed. Because of this, conventional estimates would be inaccurate.[5] This higher concentration of radiation could pose particular risk to certain groups such as:

  • The elderly (due to their susceptibility to skin cancer)
  • Women who have the BRCA gene mutation
  • People with weakened immune systems (such as those with HIV or cancer)
  • Children and adolescents (who have smaller bodies but receive the same amount of radiation as adults with larger bodies)5

The scientists also expressed concern that sperm may mutate because the testicles are close to the surface of the skin and are exposed to radiation during these backscatter scans. In addition, they noted that the effects of radiation on the cornea (the outer surface of the eye) and the thymus (a part of the immune system located in the chest) have not been studied. While this letter only outlined concerns of the scientists and did not present new data, it called for further testing of backscatter scans. The scientists called for more rigorous and independent studies to ensure that the scans are safe for the entire population, as well as for all parts of the body. When Dr. Holdren received the letter, he sent it along to the Food and Drug Administration (FDA). The Food and Drug Administration does not have authority to regulate backscatter scanners because the devices are classified as electronic devices, not medical devices. However, the FDA has experience in regulating radiation-emitting devices used in medicine, such as mammography devices. In a joint reply with the TSA, the FDA stated that the radiation exposures from the backscatter scans were within established legal limits, even for frequent fliers.[6] In reply to the scientists’ concerns that the radiation dose to the skin would be higher, the FDA wrote that their calculations showed that a person would have to pass through the scanner 1000 times in a year in order to begin to absorb the annual limit of what is considered safe.[7]

Not everyone agrees with the FDA, and some people have pointed out that TSA agents operating the scanners may improperly manage the devices or that mechanical errors may occur, either of which could cause the machines to emit more radiation than they are supposed to. From May 2010 to May 2011, there were 3,778 calls for mechanical problems on backscatter machines, but only 2% of those machines were evaluated for radiation safety. Anyone who is concerned about the radiation from the scanners has the legal right to refuse to undergo a scan, as long as they agree to a full-body pat-down by a security officer.

For more information on other types of radiation, see our article Everything You Wanted to Know About Radiation and Cancer, But Were Afraid to Ask.

References:

  1. Schmidt T, Hoppe M. Estimation of organ and effective dose due to Compton backscatter security scans. Medical Physics. 2012;39(3396).
  2. Mehta P, Smith-Bindman R. Airport full-body screening: what is the risk? Archives of internal medicine. 2011;171(12):1112-5. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21444831. Accessed March 17, 2012.
  3. Brenner DJ. Are x-ray backscatter scanners safe for airport passenger screening? For most individuals, probably yes, but a billion scans per year raises long-term public health concerns. Radiology. 2011;259(1):6-10. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21436091
  4. Cerra F. Assessment of the Rapiscan Secure 1000 Body Scanner for Conformance with Radiological Safety Standards. 2006. Available at: http://scholar.google.com/scholar?hl=en&btnG=Search&q=intitle:Assessment+of+the+Rapiscan+Secure+1000+Body+Scanner+for+Conformance+with+Radiological+Safety+Standards#0. Accessed June 18, 2012.
  5. Sedat J, Agard D, Shuman M, Stroud R. Letter to Dr. John P. Holdren. 2010.
  6. Rabin R.C.. X-Ray Scans at Airports Leave Lingering Worries. The New York Times. August 6, 2012. Available at http://well.blogs.nytimes.com/2012/08/06/x-ray-scans-at-airports-leave-lingering-worries/. Accessed August 7, 2012.
  7. McCrohan J, Shelton Waters K. Letter to Dr. John P. Holdren. 2010.

 

Letter to Senator Patrick Leahy, in support of the Camp Lejeune Historic Drinking Water Consolidated Document, August 31, 2012

Legislation
August 31, 2012

The Honorable Patrick J. Leahy

Chairman, Senate Judiciary Committee
437 Russell Senate Bldg.
United States Senate
Washington, DC  20510

Dear Senator Leahy:

The Cancer Prevention and Treatment Fund thanks you for your leadership regarding the Camp Lejeune Historic Drinking Water Consolidated Document Repository. The contamination of drinking water at Camp Lejeune Marine Corps Base, an unprecedented environmental disaster affecting the courageous men and women of our military, is of great concern to our organization.

We are especially concerned about the alarming number of breast cancer cases that have been documented in men who lived or worked at Camp Lejeune from the mid 1950’s until 1987. As you know, breast cancer is a rare occurrence among men, and is especially dangerous because men often do not recognize the symptoms or seek treatment in a timely manner. In addition, men with breast cancer often experience unique and significant physical, social and psychological issues. One study of over 160 men with breast cancer reported that almost 25% of the men were experiencing “traumatic stress,” with some having clinical levels of depression and anxiety as a result of their diagnosis and related treatment. Because breast cancer support groups and other resources typically target women, men may feel isolated and become reluctant to seek help.

The Cancer Prevention and Treatment Fund is dedicated to helping children and adults reduce their risks of getting all types of cancer, and assists them in choosing the safest and most effective treatments. We use research-based information to encourage more effective programs, policies and medical treatments. We hope that the release of these documents will encourage better research investigating the link between exposure to trichloroethylene (TCE) and other known contaminants in the Camp Lejeune drinking water, and an increased risk for male breast cancer as well as other diseases.  It is likely that the exposures could cause other types of cancer as well, but those other cancers may not be as noticeable as male breast cancer, which is usually rare.

Again, thank you for your tireless efforts to shed light on this tragic problem, and to support increased­­­­­ access to vital information, health care and services for these veterans and their families.  Please let us know if we can be helpful to you or your staff on this or other important health/environmental justice issues.

Sincerely,

 

Diana Zuckerman, PhD
President
Cancer Prevention and Treatment Fund

Pomegranate Juice and Prostate Health

Diet, Habits, & Other Behaviors, Prostate Cancer, Prostate Cancer
Laura Covarrubias, Cancer Prevention and Treatment Fund

Pomegranate juice contains plenty of antioxidants, but does it improve health, as the ads imply? Pom Wonderful, a large company that makes pomegranate juice and other products from pomegranates, would like you to believe that the juice can prevent or treat a number of health problems, including prostate cancer and erectile dysfunction. However, a close look at the science behind these claims shows that drinking pomegranate juice to treat or prevent prostate cancer and erectile dysfunction might not be worth the cost or the calories.

Prostate cancer is the most common cancer among men, other than skin cancer. (For more on skin cancer, read Tanning Beds: Safe Alternative to Sun? and Running and Skin Cancer Prevention.) Since almost everyone knows someone with prostate cancer, and since treatments can cause erectile dysfunction and incontinence, there is a tremendous desire to find a way to prevent the disease.

Even among men who have not had prostate cancer, erectile dysfunction-the inability to have or maintain an erection (called “ED” in advertisements)-is common. Many men suffering from erectile dysfunction want treatments that are less expensive and more natural than Viagra and other prescription medications.

Drinking pomegranate juice has been touted as an easy solution to decreasing the risk of prostate cancer and improving erectile dysfunction, but does it work? Nearly all of the studies are sponsored by Pom Wonderful, which is selling the products that the studies are evaluating. The company reports having spent at least $35 million on the research; unfortunately, studies sponsored by a product’s manufacturer tend to be biased in favor of the products.[1]

A May 2012 ruling by the Federal Trade Commission (FTC) concluded that Pom Wonderful’s promotional materials about the health benefits of their products are misleading and that their claims that pomegranate juice can treat, prevent, or reduce the risk of certain health conditions (including prostate cancer, erectile dysfunction, and heart disease) were deceptive.[2] Because of federal laws against making misleading disease prevention and treatment claims, the court issued a cease-and-desist order to Pom Wonderful. While the ruling prohibits Pom Wonderful from promoting its juice as a treatment for prostate cancer or erectile dysfunction, it doesn’t prevent the company from making broad claims about pomegranate juice such as that it “promotes prostate health.”

What the Science Says about Prostate Cancer and Pomegranate Juice

Only one study has been published in a peer-reviewed medical journal that looks at the effect of drinking pomegranate juice on prostate cancer. This 2006 study, funded by Pom Wonderful, is often used by the company to back its claims that their juice can help fight prostate cancer.[3] Only 46 men treated with either surgery or radiation for prostate cancer participated. All the men had rising prostate-specific antigen (PSA) levels, which is interpreted as a sign that their prostate cancer had come back, and all were given 8 ounces of Pom Wonderful to drink daily for a period of two years. The study found that the men’s rising PSA levels slowed, which can mean that their cancers were no longer growing as fast. To read more about PSA tests, click here.

In most scientific research, some patients receive a new treatment and the others receive either a placebo (sugar pill) or an older treatment. The Pom study was poorly designed because all the men drank the juice, making it impossible to evaluate the impact of the juice. Since PSA levels vary over time, we can’t know if PSA levels dropped because of the juice or would have dropped even without the juice.  In addition, the study only evaluated 46 men, all of whom had been treated for prostate cancer.  This small number of prostate cancer patients is not large enough to draw conclusions about all men, or even all men who have been treated for prostate cancer.

This 2006 study also looked at samples of cancer cells that were taken from other men with prostate cancer-not the same men who drank the pomegranate juice. These cancer cells were then treated with serum – a component of blood – from the men who drank pomegranate juice to see if the cancer cells stopped growing. The study found that cancer cells died when treated with the serum.  That sounds impressive, but there are many reasons why the serum could have caused the cancer cells to die. The researchers called for a future study with a control group (where cancer cells are treated with nothing), but six years later no study like that has been published.

Studies of pomegranate juice on mice and on human cells were more promising, but also not conclusive. One study funded by the U.S. Public Health Service, a government agency, looked at the effect of pomegranate extract – a very concentrated form of pomegranate juice – on prostate cancer cells that were taken from patients but grown outside of the body.[4] They found that the growth of cancer cells treated with the pomegranate extract was slower in comparison to the cancer cells not treated with the extract. In this same study, scientists also looked at the effects of pomegranate extract on the tumor size of mice with prostate cancer. They saw that the growth rate of the tumors in mice treated with the extract was slower in comparison to the growth rate of tumors in the mice that were not treated.

Another laboratory study found that more prostate cancer cells died in the samples treated with pomegranate juice concentrate provided by Pom Wonderful than in samples treated with different types of pomegranate extract.[5] The researchers believe that the many different chemical compounds in pomegranate juice work together to kill cancer cells, and that the pomegranate extract did not have all of these compounds and so did not have as strong of an effect. However, this study does not tell us if drinking pomegranate juice-rather than applying it to cancer cells-can prevent or treat cancer.  Even if there were research indicating a benefit from drinking the juice, how much juice would men have to drink?

Pom has also funded studies on clogged arteries and diabetes, which required people to drink 8 ounces of pomegranate juice every day (these studies were also inconclusive about the effects of pomegranate juice).[6,7] Even if 8 ounces a day was effective at lowering prostate cancer risk or improving health, this is a solution that not everyone could afford.  The cost of the juice, which would not be covered by health insurance, would be about $780 a month.[8] Drinking 8 ounces of Pom Wonderful adds an additional 160 calories per day, which equals 1,120 calories a week and 4,800 calories a month.  Unless the juice replaces an equally caloric drink, this could increase a person’s weight, which in turn increases the risk of prostate cancer and several other types of cancer (Weight and Cancer: The Latest Research).

What other alternatives are there?  Diets high in fiber and low in meat products and saturated fats have been linked to a lower risk of prostate cancer in men, and these diets also have other positive health effects such as reducing the risk of developing diabetes, heart disease, and stroke.[9,10,11] To learn more about the connections between diet and prostate cancer, read here.

What the Science Says about Erectile Dysfunction and Pomegranate Juice

There is even less evidence behind Pom Wonderful’s claims that drinking pomegranate juice decreases erectile dysfunction than there is about prostate cancer or other illnesses. Two studies used by Pom Wonderful to back these claims were conducted on rabbits – not humans.[12,13]These studies found that antioxidants (not pomegranate juice specifically) may be useful against erectile dysfunction, although no definite conclusions were made even for rabbits, and certainly not for humans.

The only study of humans used by Pom Wonderful divided the 53 participants with erectile dysfunction into two groups.[14] One group was assigned to drink pomegranate juice every day for the first 28 days, while the other group drank a placebo drink. After 28 days, the men answered questions about their erectile function. For the next two weeks, both groups stopped drinking their assigned drink (juice or placebo) – this time is known as a “washout” period. Research studies use washout periods to make sure that any effects of the treatment do not continue to be measured when the person begins drinking the new drink. After the washout period, the groups switched drinks so that the group that drank pomegranate juice drank the placebo for 28 days (and vice versa). Again, the men answered the same questions about their erectile function. Overall, the researchers did not find any statistically significant difference between the two groups.  Although there was a slight decrease in erectile dysfunction among the men drinking the pomegranate juice, the difference was small and could have occurred by chance. The researchers called for a larger and longer study to determine if pomegranate juice really does improve erectile dysfunction. We agree.

More Research Needed

Better research on men is needed to determine if regularly drinking pomegranate juice or taking pomegranate extract pills prevents or helps treat prostate cancer, erectile dysfunction, or other conditions. In the meantime, there is no harm in drinking pomegranate juice as long as it does not contribute to overweight or obesity.  Men who choose to drink pomegranate juice should consider the extra calories and cost.

Bottom Line:

  • There is no strong evidence to support the claim that pomegranate juice protects against prostate cancer or helps with erectile dysfunction.
  • Age increases the likelihood of prostate cancer and erectile dysfunction, and weight gain can also increase the chances of getting prostate cancer or having it return after treatment.[15]
  • If you or a loved one is undergoing treatment for prostate cancer, pomegranate juice is not an effective alternative.

References:

  1. Lexchin J, Bero L, Djulbegovic B. Pharmaceutical industry sponsorship and research outcome and quality: systematic review. Bmj. 2003;326(May). Available at: http://www.bmj.com/content/326/7400/1167.short. Accessed June 6, 2012.
  2. United States of America Federal Trade Commission. Initial Decision. 2012. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1245105.
  3. Pantuck AJ, Leppert JT, Zomorodian N, et al. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2006;12(13):4018-26. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16818701. Accessed March 28, 2012.
  4. Malik A, Afaq F, Sarfaraz S, et al. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proceedings of the National Academy of Sciences of the United States of America. 2005;102(41):14813-8. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1253570&tool=pmcentrez&rendertype=abstract.
  5. Seeram NP, Adams LS, Henning SM, et al. In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. The Journal of nutritional biochemistry. 2005;16(6):360-7. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15936648. Accessed May 24, 2012.
  6. Aviram M, Rosenblat M, Gaitini D, et al. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clinical nutrition (Edinburgh, Scotland). 2004;23(3):423-33. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15158307. Accessed May 2, 2012.
  7. Rosenblat M, Hayek T, Aviram M. Anti-oxidative effects of pomegranate juice (PJ) consumption by diabetic patients on serum and on macrophages. Atherosclerosis. 2006;187(2):363-71. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16226266. Accessed May 13, 2012.
  8. United States of America Federal Trade Commission. Initial Decision. 2012. Available at: http://www.ncbi.nlm.nih.gov/pubmed/1245105.
  9. Cohen JH, Kristal a R, Stanford JL. Fruit and vegetable intakes and prostate cancer risk. Journal of the National Cancer Institute. 2000;92(1):61-8. Available at: http://www.ncbi.nlm.nih.gov/pubmed/10620635.
  10. Ma RW-L, Chapman K. A systematic review of the effect of diet in prostate cancer prevention and treatment. Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2009;22(3):187-99; quiz 200-2. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19344379. Accessed June 10, 2012.
  11. Anderson JW, Baird P, Davis RH, et al. Health benefits of dietary fiber. Nutrition reviews. 2009;67(4):188-205. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19335713. Accessed March 3, 2012.
  12. Azadzoi KM, Schulman RN, Aviram M, Siroky MB. Oxidative stress in arteriogenic erectile dysfunction: prophylactic role of antioxidants. The Journal of urology. 2005;174(1):386-93. Available at: http://www.ncbi.nlm.nih.gov/pubmed/15947695. Accessed July 16, 2012.
  13. Zhang Q, Radisavljevic ZM, Siroky MB, Azadzoi KM. Dietary antioxidants improve arteriogenic erectile dysfunction. International journal of andrology. 2011;34(3):225-35. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20584092. Accessed July 16, 2012.
  14. Forest CP, Padma-Nathan H, Liker HR. Efficacy and safety of pomegranate juice on improvement of erectile dysfunction in male patients with mild to moderate erectile dysfunction: a randomized, placebo-controlled, double-blind, crossover study. International journal of impotence research. 2007;19(6):564-7. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17568759. Accessed July 16, 2012.
  15. Kaluza J, Wolk A, Larsson SC. Red Meat Consumption and Risk of Stroke: A Meta-Analysis of Prospective Studies. Stroke; a journal of cerebral circulation. 2012. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22851546. Accessed August 9, 2012.

BPA-Free Baby Bottles Now Law, But We’re Not in the Clear

News Stories & Editorials
By Kristin Wartman for Huffington Post
August 14, 2012

Recently, the U.S. Food and Drug Administration (FDA) announced a ban on the use of bisphenol A, or BPA, in baby bottles and children’s cups. BPA is an estrogen-mimicking chemical that has been used in hard plastics, the linings of cans, food packaging, dental fillings and even receipts for years. This move essentially made official a practice that many manufacturers of baby bottles and cups already follow in response to growing pressure from consumers.

Questions of safety remain when it comes to the use of any plastic products that come in contact with our foods. The FDA ban is raising concern and creating headlines about what manufacturers will substitute in place of the BPA. A 2011 study published in Environmental Health Perspectives found that all plastics contain estrogenic activity (EA) and in some cases, those labeled “BPA free” leached more chemicals with EA than did BPA-containing products. The study’s authors write, “Almost all commercially available plastic products we sampled — independent of the type of resin, product, or retail source — leached chemicals having reliably detectable EA, including those advertised as BPA free.”

EA interferes with our endocrine system, a complex signaling network that is made up of glands (the thyroid) as well as glandular tissue and cells within organs (testes, ovaries, pancreas, etc). Our endocrine systems use hormones that send signals to our various organs and tissues that work over minutes, hours, weeks and years. The processes these hormones regulate include metabolism, growth and development, and sexual reproduction. As hormones travel in the blood to reach each body part, the specific molecular shape of each hormone fits like a key-in-a-lock into receptors on target tissues. Endocrine disrupting chemicals may interfere with, block or mimic the action of our hormones. As a result, EA and endocrine disruptors have been linked in hundreds of studies to brain development problems, breast and prostate cancer, birth defects, learning and behavioral problems in children, early onset of puberty, and obesity.

Manufacturers are now flaunting their “BPA-free” versions of products as though they are safe and free of toxins — but it turns out BPA is possibly just the tip of the iceberg. Bisphenol S, or BPS, is another chemical that manufacturers are using to replace BPA and it may be just as harmful. In a study this year in Environmental Science and Technology, researchers wrote,

“As the evidence of the toxic effects of bisphenol A (BPA) grows, its application in commercial products is gradually being replaced with other related compounds, such as bisphenol S (BPS). Nevertheless, very little is known about the occurrence of BPS in the environment.”

In this study, the authors found BPS present in 16 types of paper products, including thermal receipts, paper currencies, flyers, magazines, newspapers, food contact papers, airplane luggage tags, printing paper, paper towels and toilet paper. The thermal receipt paper samples contained concentrations of BPS that were similar to the concentrations of BPA reported earlier and raised alarm for some scientists. BPS was also detected in 87 percent of currency bill samples. The authors write that several other related compounds are also used to replace BPA: bisphenol B, bisphenol F and bisphenol AF. BPA and BPS are found in high concentrations in canned foods, BPF has been found in surface water, sewage sludge, and sediments, and BPB was found in human serum in Italy. “Limited studies have shown that BPS, BPB and BPF possess acute toxicity, genotoxicity, and estrogenic activity, similar to BPA,” the authors write, adding, “The environmental biodegradation rates of BPS and BPB were similar to or less than those of BPA. Although considerable controversy still surrounds the safety of BPA, the potential for human exposure to alternatives to BPA cannot be ignored.” The researchers also note that people may be absorbing BPS in much larger doses — 19 times more than the BPA they absorbed when it was more widely used.

Bruce Blumberg, professor of developmental and cell biology and pharmaceutical sciences at the University of California, Irvine, wrote in an email,

“There are emerging data to show that BPS is an estrogen but relatively less on the other chemicals. Therefore, it is hard to say with certainty at the moment whether the BPA replacements lack estrogenic activity. BPA free means simply that — that the product is stated to be BPA free.”

I asked Diana Zuckerman, president of the National Research Center for Women and Families if she was concerned about the substitutes being used in place of BPA:

“We are very concerned that BPA could be replaced with products that are just as risky, or even more risky. The federal government is not doing what is needed to protect the American public, either in their regulation of BPA or any of these potential substitutes.”

But the FDA continues to insist that BPA is still safe. In a recent New York Times article, Michael Taylor, deputy commissioner for foods, said that the agency “has been looking hard at BPA for a long time, and based on all the evidence, we continue to support its safe use.”

Zuckerman added that part of the problem lies in the heavy influence that industry has on members of Congress and the FDA.

“Whenever the FDA does something to improve patient safeguards, Members of Congress get lobbied by the industry involved and some of those Members pressure [the] FDA to back off,” she wrote in an email. “This has happened for years but the last few years have been even worse than usual.”

At Mother Jones, Tom Philpott points out that the heavily monied interests behind BPA are none other than the chemical giants Dow and Bayer, which produce the bulk of BPA. Frederick S. vom Saal, curators’ professor at the University of Missouri-Columbia and BPA researcher, told me that BPA represents a $10 billion a year industry. It’s important to note that the recent FDA ban comes at the behest of the American Chemistry Council, an industry trade group that denies any negative health effects from BPA. Why would they have done this?

“[The American Chemistry Council’s] petition to the FDA puts it plainly: ‘All Major Product Manufacturers Have Abandoned the Use of Polycarbonate’ (BPA). In other words: Go ahead and ban it — it’s already been phased out and a ban gives the appearance of strict oversight,” Philpott writes.

By creating the ban, the FDA at least acknowledges that babies and children should lessen their exposure to BPA. But what about the rest of the population?

“BPA remains in millions of food and beverage containers that affect the BPA levels of pregnant women, children of all ages, and all adults,” Zuckerman wrote to me in an email. “The impact on the developing fetus and young children, and on breast cancer patients undergoing chemotherapy, are of particular concern to our Center. One study indicates that BPA may interfere with the effectiveness of chemo for breast cancer patients.”

The FDA should concede that if BPA is a risk for babies and children, it is most likely a risk to all of us. And what about the various substitutes that will be used for BPA and the numerous other toxins lurking in the plastics and other containers that package our foods and drinks? “FDA’s decision is a step in the right direction, but it is a baby step,” Zuckerman said. “They have done the minimum.”

Blumberg added that the answers to all of these questions are complex. “We do not know nearly as much as we need to know,” he said. “I think that it is prudent to reduce our consumption of packaged foods of all sorts for a variety of reasons, including reducing exposure to contaminants from the containers.”

A version of this post appeared on Civil Eats

Haz-Map: Is Your workplace putting your health at risk? How you can find out

Environmental Exposures, Prevention
By Danielle Pavliv
2012

Have you ever wondered if where you work could be harming your health? Now you can find out. The National Library of Medicine’s Environmental Health and Toxicology division has an online database that lets you see what hazards, if any, you are being exposed to. It’s called “Haz-Map,” and it links jobs with illnesses and injuries that have been reported. Haz-Map is the product of occupational health science, which studies workplace safety and is “devoted to the anticipation, recognition, evaluation, and control” of workplace conditions which may cause illness or injury.[end Industrial Hygiene. Occupational Safety & Health Administration. United States Department of Labor. Available at: http://www.osha.gov/dte/library/industrial_hygiene/industrial_hygiene.html.]

Haz-Map began in 1991 with about 700 chemicals. Over time, chemical and biological agents known to cause health problems were added. Currently, it covers about 6000 chemical and biological agents and 235 occupational diseases.[end Fact Sheet: Haz-Map. U.S. National Library of Medicine. National Institutes of Health. May 2011. Available at: http://www.nlm.nih.gov/pubs/factsheets/hazmap.html.] Information on the website is regularly updated as new research is conducted. The new Haz-Map design allows you to search by job, disease, chemical or biological agent, or even by symptom or medical problem: click here to see it.

Interested in learning about the risks associated with your job? Simply click on “High Risk Jobs” or “Industries,” and search alphabetically or by the type of job. Are you a bartender? It turns out that working with the limes and celery often used for cocktails can cause rashes, and working continuously with wet hands may result in inflammation near your fingernails. Haz-Map shows that exposure to secondhand smoke increases the risk of lung cancer (smoking is banned in bars and restaurants in many states, but not all). Hairdresser? Working with dyes and bleach can cause asthma-and so can wearing latex gloves! Law enforcement officer? Policeman and detectives can both at risk of heat-related illnesses, and the firing ammunition can increase the risk of lead poisoning. Physicians and other types of health care providers are exposed to many different risky pathogens by handling needles and caring for sick patients, but can lower those risks by taking proper precautions.

You can also search Haz-Map by disease to see what jobs are associated with certain illnesses. Leukemia, for example, is more prevalent among workers exposed to radiation (such as health professionals working with X-rays and people who work at nuclear power plants) and workers who are regularly exposed to benzene, such as painters, printing press operators, and gas station attendants (since benzene is used in inks, rubber, paint removers, and gasoline). Mesothelioma, a rare cancer with a poor prognosis, is usually caused by exposure to asbestos, which is less likely today but is still in old insulation, textiles, cement and roof shingles.

Facts and Figures

How many people are harmed by their job? The most recent data from the Bureau of Labor Statistics (from 2010) show that fatal and nonfatal workplace injuries and illnesses have decreased since the 1990s.[end Injuries, Illnesses, and Fatalities. Bureau of Labor Statistics. United States Department of Labor. 2012. Available at: http://www.bls.gov/iif/home.htm.] The reason might be because there have been many safety measures implemented to limit exposure to chemical, biological and physical dangers and minimize health risks in case of an emergency. However, a trend away from industrial jobs and more toward service and other “desk” jobs that don’t pose the same kinds of dangers may be another factor.

Fatal occupational injuries in 2010: 4,690 total

  • Sex: 4,322 men and 368 women died on the job
  • Age: more deaths occurred in the 45-54 age range (1,189) than any other
  • Race: 3363 fatalities among white men and women occurred, while 412 black people and 707 Hispanics died.
  • Occupation: Most of the deaths (1,160) occurred in transportation-related occupations, 780 to construction workers, 545 in management, 363 to workers performing installation, maintenance and repair
  • Event: 1,857 deaths were attributed to transportation accidents. Many of these were among individuals working in the transportation industry, such as truck drivers, but some worked in other occupations that involve transporting, such as drilling workers driving diesel trucks to drilling sites. Assaults and violent acts resulted in 832 workplace fatalities. Contact with objects and equipment caused 738 deaths, and 646 people fell to their death. A smaller number (414) died from exposures to harmful substances.

We have a long way to go but times have changed

In 1995, 6,275 fatal occupational injuries occurred-almost 2,000 more than in 2010. Of these, 605 were due to exposure to harmful substances, as compared to 414 in 2011. The rate of fatal work injuries per 100,000 workers decreased from 5 in 1995 to 3.6 in 2010. Instances of nonfatal injuries and illnesses also decreased significantly, from 8.1% of workers in 1995 to 3.8% in 2010.

Organizations that study and regulate workplace health and safety

All of the organizations below are devoted to the study and regulation of workplace hazards:

  • The American Conference of Governmental Industrial Hygienists, or ACGIH, is an independent organization that formed in 1938.[end About: History. American Conference of Governmental Industrial Hygienists. May 2012. Available at: http://www.acgih.org/about/history.htm.] Originally, the organization offered membership to industrial hygiene (also known as occupational health) professionals in the U.S. and all governmental industrial hygiene professionals in other countries. Today, all occupational and environmental health professionals in the U.S. and other countries around the world can obtain a membership. Nine ACGIH committees focus on different aspects of the field such as agricultural safety and health, small businesses, and limits for chemical substances.
  • Several decades later, under the Nixon Administration, the OSH (Occupational Safety and Health) Act was passed in 1970.[end Occupational Safety and Health Act of 1970. Occupational Safety and Health Administration. December 1970. Available at: http://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=OSHACT&p_id=2743.] With this act, Congress established OSHA, the Occupational Safety and Health Administration. OSHA creates and enforces standards to ensure safe working conditions for Americans.
  • The OSH Act also created the National Institute of Occupational Safety and Health, or NIOSH, which focuses on performing research and making recommendations to reduce the likelihood of workplace injury and illness.

How much exposure is too much?

Both OSHA and ACGIH have set standards or regulations for exposure to workplace health hazards. ACGIH created the term “threshold limit value” or TLV.[end Policy Statement on the Uses of TLVs and BEIs. American Conference of Governmental Industrial Hygienists. February 2008. Available at: http://www.acgih.org/TLV/PolicyStmt.htm.] This is the amount of a chemical substance a worker can be exposed to daily for his or her entire career without experiencing health problems related to the chemical. The TLV is just a guideline or recommendation, so it cannot be legally enforced.

The permissible exposure limit (PEL), on the other hand, is a legal limit set by OSHA. Unlike a TLV, PELs are not based on daily exposure over an entire working lifetime. Rather, they are typically given as a time-weighted average (TWA), which is measured over the course of an 8-hour workday.[end Permissible Exposure Limits (PELs). Occupational Safety and Health Administration. United States Department of Labor. October 2006. Available at: http://www.osha.gov/SLTC/pel/.] Sometimes, a PEL is measured as a ceiling limit, which is the amount of chemical that should never be exceeded at any time. A short-term exposure limit (STEL) is the amount of chemical in the air averaged over 15 minutes. Why are there so many different standards? In most jobs, chemical concentration fluctuates significantly throughout the day, so it is best to assess chemical presence and hazards in several different ways.

Safety measures

There are many safety efforts that have been designed and implemented to protect workers from various dangers. For instance, construction workers often use hard hats, shoes that will guard their feet from heavy objects, and earplugs if they will be around loud noises. Doctors and other health care professionals wear antibacterial gloves, and they must wear masks to protect themselves around contagious patients, and to protect immune-compromised patients from the germs doctors may be carrying. For workers who come into contact with dangerous chemicals, rubber gloves and air respirators are used to reduce risk. It is better to focus on minimizing exposure to harmful substances or other dangerous situations than to use protective equipment, but these safety measures can save lives when there is no viable alternative.

The Haz-Map can be a useful tool if you are curious about potential hazards at your workplace or a loved one’s, or if you just want to know more about different chemical and biological agents and how people can be exposed to them. Explore the Haz-Map using the search function, or just browse by job, disease, or hazardous agent.

Statement of Dr. Diana Zuckerman, President, Cancer Prevention and Treatment Fund: Supreme Court Ruling on the Affordable Care Act

Press Releases
Diana Zuckerman, PhD, Cancer Prevention and Treatment Fund June 28, 2012

Whether you call it Obamacare or RomneyCare, or as I prefer, USACare, the health care law that survived the Supreme Court will save lives and improve the quality of life for millions of Americans.  It already has improved the lives of many adults and children, by adding children up to age 26 to their parent’s health insurance policies and preventing insurance companies from refusing coverage for kids with “pre-existing” conditions.

The law will continue to be a political football, but let’s forget the politics and call it what it is: a gift to millions of Americans who need and deserve essential health benefits but couldn’t afford them until now.

Some politicians say the bill is a job killer.  That’s ridiculous.  This law is increasing the availability and affordability of health care, and that means more jobs for doctors and nurses and technicians and food service workers and janitors in hospitals and clinics, and more jobs in companies that make medical products such as prescription drugs and medical devices.

Testimony of Brandel France de Bravo, MPH, at the Medical Devices Advisory Committee to the FDA on MarginProbe

Testimony & Briefings
Brandel France de Bravo, Cancer Prevention and Treatment Fund, June 21, 2012

I am pleased to have the opportunity to testify on behalf of the Cancer Prevention and Treatment Fund.  We are dedicated to improving the health and safety of adults and children, and we do that by scrutinizing medical and scientific research to determine what is known and not known about specific treatments and prevention strategies.

According to a recent study in JAMA, 1 in 4 women who undergo a lumpectomy will have to have a second surgery because the pathology report found that the margins were not clear. For Ductal Carcinoma In Situ (DCIS), re-surgery rates are even higher, ranging from 21% to 50% -something we heard first hand last year when we conducted in-depth interviews with women treated for DCIS.  Most patients were thoroughly unprepared for the possibility of a second surgery and all that it entailed; and several got fed up with the surgeon not being able to “get all the cancer out,” and opted for a mastectomy that was absolutely not medically necessary. In addition to the high re-lumpectomy rates, prophylactic mastectomies among DCIS patients are on the rise. Not surprisingly, we would welcome a device that reduces the likelihood of re-lumpectomy and makes breast conserving surgery a one-time solution, as mastectomy already is. Our organization has worked on DCIS for a decade so we were very heartened to learn that in a post market study carried out in Germany MarginProbe cut the re-operation rate for women with DCIS by half.  Unfortunately, the re-operation rates in the Pivotal Study were not nearly so impressive: 20.8% in the device arm vs. 25.8% in the control arm.

In addition, we share some of the FDA’s concerns about the device, namely:

  • Did the device perform better in Israel due to more extensive training prior to use, or because the design dataset was generated by an Israeli population that is not reflective of the U.S. one? Either way, what are the implications for women in the U.S.?
  • Did the device perform better in the Pivotal Study because of design bias giving surgeons an additional opportunity to shave compared to the standard-of-care control arm?
  • Also, why was the mastectomy conversion rate higher in the device arm? Was the slightly higher tissue volume causing women faced with re-operation to opt for mastectomy because they were dissatisfied with their appearance following the primary lumpectomy? Any future study would need to include qualitative data from patients after their primary lumpectomy and any subsequent lumpectomies regarding satisfaction with their appearance.

The FDA asks whether the device’s sensitivity is worth its poor specificity. We are somewhat less concerned than the FDA about the false positives and excessive tissue removal because that occurs with or without this device and patients can be informed about this choice.  Patients should be asked: Is it more important to you to avoid repeat surgeries or to preserve as much breast tissue as possible?

Given that routine or complete shaving of the lumpectomy cavity is just as effective at converting to negative final margins, with only slightly more tissue removed, is the device worthwhile? The FDA worries that the extra 5 minutes of intraoperative time in the device arm muddied the results, favoring the device. We believe that this is a positive aspect of the device: it forced surgeons to spend more time assessing the margins.

While many of the FDA’s concerns could be effectively addressed in a post-market study, we know from long experience that post-market studies are rarely implemented with the rigor of pre-market studies, in part because the incentives to retain patients simply are not there: why eat your veggies after you’ve already been given dessert?  Has the FDA ever withdrawn approval of a device because post-market studies weren’t carried out or because of poor results?  I don’t think so, but certainly that is rare if it happens. Given Dune’s track record of responding “too little and too late” to FDA requests, there is no reason to believe that the company will follow FDA requirements better post-market than it did pre-market.

In summary, the benefits of this device are important, and the manufacturers have provided adequate proof of safety, but that is not the only issue here. While the POTENTIAL benefits of the device clearly outweigh the risks-the main risk being the possible removal of noncancerous tissue-the device’s actual benefits have not yet been fully established for the intended use in the U.S.  At the very least, the large number of confusing outcome measures should be reduced and clarified prior to the FDA’s decision, so that patients and physicians can make an informed choice.

Testimony of Sonia Nagda, MD, MPH, at the FDA’s Oncologic Drugs Advisory Committee Meeting on Semuloparin

Testimony & Briefings
June 20, 2012
Statement to an FDA Advisory Committee Concerning the Approval of Semuloparin for the Prophylaxis of DVT in Chemotherapy Patients

Good morning. Thank you for the opportunity to testify on behalf of the Cancer Prevention and Treatment Fund. My name is Sonia Nagda. I am a physician, and I received my training in public health at Harvard University. Our organization is dedicated to improving the health of adults and children, and we do that by scrutinizing scientific research. We do not accept contributions from companies that make medical products, so I have no conflicts of interest.

The data that evaluate the use of semuloparin for thromboprophylaxis in chemotherapy patients is based on 1 study of 1,600 patients on the study drug. However, 36% of these patients did not complete three months on the therapy. Of these, 255 patients discontinued treatment due to adverse side effects.

Semuloparin reduced the absolute risk of DVT and fatal and nonfatal pulmonary embolism by 2.2% compared to placebo, but there are serious side effects.  There were 19 instances of major bleeding in the semuloparin group, and of these 5 were in a critical location, including pericardial, intracranial, splenic, and intraocular events, compared with no critical bleeds in the placebo group. The drug was tested in patients with colon or rectal, stomach, bladder, ovarian, lung, and pancreatic cancer, but was only found to reduce the risk of thromboembolism in patients with lung and pancreatic cancer. Because there were so few patients with each type of cancer, it would be necessary to include more patients to shed light on the impact that semuloparin has on the development of blood clots.

Many of you have already commented on the questionable heterogeneity of the patient population in the study, and it appears that the sponsor has flung a number of arrows with the hope that one of these would hit the target.

Patients in the study were most commonly on fluoururacil, cisplatin, or carboplatin, and some were on a chemotherapy regimen of more than one agent. The sponsor just provided the analysis based on this factor, and found a statistically significant reduction in the risk of thromboembolism in only 1 chemotherapy subgroup.  Further evaluation is necessary to determine which patients, if any, would derive the most benefit from semuloparin.

The secondary outcome of this study was 1-year survival, and there was no difference between the 2 groups, with 40% mortality in semuloparin patients and 41.5% mortality in placebo. This high mortality rate demonstrates the severity of illness facing these patients, and the importance of determining which patients are most likely to benefit without being subjected to additional harm.

With minimal gains in efficacy over the currently accepted treatment regimen, and with risks that should not be overlooked, particularly noting that the number needed to treat is greater than the number needed to harm, we recommend that semuloparin be studied more extensively prior to approval.  Making it available prior to determining whether there are some types of patients who are more likely to benefit could be harmful to many patients, and helpful to few.

Comments of Patient and Consumer Coalition on Draft Guidance for Industry "Limiting the Use of Certain Phthalates as Excipients in CDER-Regulated Products"

Testimony & Briefings
May 31, 2012

Division of Dockets Management
Food and Drug Administration
5630 Fishers Lane, Room 1061 (HFA-305)
Rockville, Maryland 20852
Via: http://www.regulations.gov
Fax: (301) 827-6870

May 31, 2012

Comments of Patient and Consumer Coalition on Draft Guidance For Industry
“Limiting the Use of Certain Phthalates as Excipients in CDER-Regulated Products”
[Docket No. FDA-2012-D-0108]

The members listed below of the Patient, Consumer, and Public Health Coalition appreciates the opportunity to comment on the draft guidance, “Limiting the Use of Certain Phthalates as Excipients in CDER-Regulated Products,” which recommends that industry avoid the use of dibutyl phthalate (DBP) and  di(2-ethylhexyl) phthalate (DEHP) as excipients in drug and biologic products.

Although limiting the use of these phthalates is a step in the right direction, the draft guidance should ban the use of DBP and DEHP as excipients because these phthalates have been “shown to be developmental and reproductive toxicants in laboratory animals” and “epidemiological studies suggest certain phthalates may affect reproductive and developmental outcomes” in humans.

We are deeply disappointed that the draft guidance would still allow the packaging materials for drugs and biologic products to contain DBP or DEHP, especially since the draft guidance notes that these phthalates can leach from the packaging materials into the drugs, and that “the ubiquitous presence of phthalates in the environment and the potential consequences of human exposure to phthalates have raised concerns, particularly in vulnerable populations such as pregnant women and infants.”  Also, setting safety standards for phthalates individually or for individual products without considering their interactions and cumulative effects could underestimate the real-world risks of phthalates in the health of children and adults.

Serious Adverse Effects

Phthalates are called “endocrine disruptors” because they limit or block the body’s natural levels of estrogen, testosterone, and other hormones.

Researchers have shown that, unlike other chemicals, phthalates appear to have more serious effects at lower levels than at higher levels. It is often assumed that the higher the dose or exposure, the greater the harm, but endocrine disruptors play by different rules.  That is why the director of the National Institute of Environmental Health Sciences, Dr. Linda Birnbaum, says that chemical manufacturers are asking “old questions” when they test for safety even though “science has moved on.”

In animals, DBP and DEHP have been associated with “the disruption of the development of the male reproductive system.”1 Research indicates that boys exposed to phthalates may be more likely to develop smaller genitals and incomplete descent of the testicles. Boys who are born with undescended testicles are 2-8 times more likely to develop testicular cancer later on than men born with both testicles descended,  Additionally, studies by Harvard researchers have shown phthalates may alter human sperm DNA and semen quality., , , Phthalates are believed to also affect girls’ hormones, but the impact on breast cancer and other health outcomes are not yet known.

A number of research studies reveal poor health and behavioral outcomes for children exposed to phthalates.  For example, there is an association between children’s exposure to phthalates and the risk of asthma, allergies and bronchial obstruction.,,

Mount Sinai School of Medicine researchers in 2011 studied the impact of prenatal exposure to “low molecular weight” phthalates-the kind often found in personal care products and the coatings of some medications-on the social behavior of children ages 7 to 9.  Children who were exposed to higher levels of these phthalates had worse scores for social learning, communication, and awareness.  These children were less able to interpret social cues, use language to communicate, and engage in social interactions.

Columbia University researchers in 2011 discovered that 3-year olds with high prenatal exposure to phthalates were more likely to have motor delays. They also reported that phthalates were linked to certain behavior problems in three-year olds, such as social withdrawal.

Closer Regulation of Phthalates

As noted in the draft guidance, Congress prohibits the use of DBP and DEHP in children’s toys; the European Commission prohibits their use as ingredients in cosmetics; the Environmental Protection Agency added them to the list of chemicals of concern; and the Center for Devices and Radiological Health recommends minimizing exposure to PVC devices containing DEHP.  It is past time for FDA to issue guidance on the use of phthalates as excipients.

Conclusions

The draft guidance recommends that industry should avoid the use of DBP and DEHP as excipients in drug and biologic products.  This recommendation is not strong enough.  The FDA should ban the use of DBP and DEHP in excipients especially since “safer alternatives are available.”1 FDA should also ban the use of these phthalates in packaging materials since DBP and DEHP can leach from the packages into the drug and biologic products.  Banning DBP and DEHP will help to reduce the “widespread exposure of the general population to phthalates,” and reduce the real-world, cumulative negative effects of phthalates in the health of children and adults.1

American Medical Women’s Association
Annie Appleseed Project
Breast Cancer Action
Cancer Prevention and Treatment Fund
Connecticut Center for Patient Safety
National Women’s Health Network
Our Bodies Ourselves
Public Citizen
Reproductive Health Technologies Project
U.S. PIRG
WoodyMatters

For more information, contact Paul Brown at (202)223-4000 or pb@center4research.org

1 Food and Drug Administration Center for Drug Evaluation and Research (March 2012).  Guidance for Industry Limiting the Use of Certain Phthalates as Excipients in CDER-Regulated Products.

2 Vandenberg et al. (2012). Hormones and Endocrine Disrupting Chemicals: Low-dose Effects and Nonmonotonic Dose Responses. Endocrine Reviews. First published ahead of print March 14, 2012 as doi:10.1210/er.2011-1050

3 Cone, Marla and Environmental Health News. Low Doses of Hormone-Like Chemicals May Have Big Effects. Scientific American. March 15, 2012. http://www.scientificamerican.com/article.cfm?id=low-doses-hormone-like-chemicals-may-have-big-effects

4 Main KM, Skakkebaek NE, Virtanen HE, Toppari J (2010). Genital anomalies in boys and the environment. Best Pract Res Clin Endocrinol Metab.Apr;24(2):279-89.

5 Toppari J, Kaleva M. Maldescendus testis. Horm Res 1999;51:261-9

6 Duty, S. M., M. J. Silva, et al., (2003). Phthalate exposure and human semen parameters. Epidemiology 14(3): 269-77.

7 Duty, S. M., N. P. Singh, et al., (2003). The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay. Environ Health Perspect 111(9): 1164-9.

8 Duty, S. M., A. M. Calafat, et al., (2004). The relationship between environmental exposure to phthalates and computer-aided sperm analysis motion parameters. J Androl 25(2): 293-302.

9 Duty, S. M., A. M. Calafat, et al., (2005). Phthalate exposure and reproductive hormones in adult men. Hum Reprod 20(3): 604-10.

10 Jaakkola JJ, Knight TL (2008 July). The Role of exposure to phthalates from polyvinyl chloride products in the development of asthma and allergies: a systematic review and meta-analysis. Environ Health Perspect, 116(7): 845-53.

11 Kanazawa A, Kishi R (2009 May). Potential risk of indoor semivolatile organic compounds indoors to human health. Nippon Eiseigaku Zasshi, 64(3): 672-82.

12 Hsu NY, Lee CC, Wang JY, et al. (2011). Predicted risk of childhood allergy, asthma, and reported symptoms using measured phthalate exposure in dust and urine. Indoor Air. Oct 13. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/21995786

13 Miodovnik A, Engel SM, Zhu C, et al. (2011). Endocrine disruptors and childhood social impairment.  Neurotoxicology Mar;32(2):261-7.

14 Whyatt RM, Liu X, Rauh, VA, Calafat AM, Just AC, Hoepner L, Diaz D, et al. (2012). Maternal prenatal urinary phthalate metabolite concentrations and child mental, psychomotor and behavioral development at age three years.  Environmental Health Perspectives 120(2):290-5