NotAIDS! Investigation
June 30, 2007

It is likely that very few people have heard of the chemical, bisphenol A (BPA).

While billions of dollars and the world's attention is focused on chasing the shadows of a nonspecific collection of antigens, with different combinations thereof called HIV, depending on where you are, the plastics that we use each day are wreaking havoc on our bodies and immune systems.

Fortunately, a flurry of recent research and the actions of certain progressive local governments are beginning to draw attention to the dangers of bisphenol A, a key component of plastics used in infant feeding bottles, refillable plastic water bottles, beverage cans, and countless other containers used for food and beverages destined for human consumption everywhere.

The extent of damage caused by only nominal exposure to this ubiquitous chemical is dramatic, and ranges from prostate cancer, to growth of breasts in men, diabetes, immune system damage, and numerous others. In fact, studies on laboratory mice demonstrated that at nominal levels, BPA can cause damage both to the unborn fetus and to adults. The list is shocking:

• Enlarged prostates
• Genital deformities
• Disrupted puberty
• Increased cancer rates in certain organs and cell lines
• Pancreatic changes that promote insulin resistance
• Pubescent mammary gland developmental changes
• Altered to thyroid regulation
• Structural damage to the brain
• Hyperactivity
• Abnormal sexual behavior
• Increased fat formation
• Down's syndrome
• Disrupted reproductive cycles

An April, 2007 paper, "Bisphenol A induces permanent squamous change in mouse prostatic epithelium." by Yuji Ogura, and Kenichiro Ishii et. al. report:

Results indicate that in mouse, BPA can directly elicit CK10 expression in prostatic epithelium, and that this change can be elicited by doses as low as 20 mug/kg/day. We speculate that low-dose BPA during fetal life may also induce permanent squamous change in human prostate.

Bisphenol A's connection to diabetes is explored in depth on the website, Our Stolen Future,devoted to the health of future generations.

In their report, "The Estrogenic Effect of Bisphenol-A Disrupts the Pancreatic ß-Cell Function in vivo and Induces Insulin Resistance," published in Environmental Health Perspectives," the website's authors describe an important study by Alonso-Magdalena, P, S Morimoto, C Ripoll, E Fuentes and A Nadal completed in 2006, where they

"...demonstrate that low-level, chronic exposure to bisphenol A (BPA) induces insulin resistance in adult mice. Their work provides the first experimental link between endocrine disruption and diabetes.

The doses they used in these experiments were within the range of current human exposure, 5000 times below the dose identifed by the US EPA as the lowest level causing effects."

In another report by Toyoko Hiroi and Kazushi Okada et. al. of the Department of Chemical Biology, Osaka City University Medical School, in Japan, they summarize the damaging effects of this commonly found chemical ingredient in plastics that millions use.

BPA and its derivatives are common pollutants of rivers, lakes, and seawater, resulting in chronic exposure of humans and wildlife to BPA.

In fact, BPA has been detected in the sera and placentas of pregnant women as well as in amniotic fluid. High concentrations of BPA (30 µg/ml; 131 µM) also have been detected in saliva after dental treatment (7). BPA is considered to be one of the most widespread endocrine-disrupting chemicals (EDCs), and recently, its adverse effects on human health and wildlife are being increasingly recognized.

Mounting evidence from numerous studies of BPA reveals that BPA has diverse influences on various physiological functions related to steroid hormones, thyroid hormones, the nervous system, the immune system, and other cell signaling pathways. For example, BPA possesses estrogenic and antiandrogenic activities in vitro, and influences reproductive functions, sexual differentiation, and behavioral patterns in vivo. BPA is also demonstrated to ... cause up-regulation of immune responses, especially T helper 1 responses in adulthood.

Research comparing purported HIV antigen reactivity and protein expression as well as pathogenic reactions common to HIV and bisphenol A reveals important linkages.

The antigen expressed at 53 kilodaltons, known as the protein p53 is attributed to HIV-2. Interestingly, this is protein is common to bisphenol A in mammalian antigenic response.

"The purified fraction eluted from BPA-Sepharose affinity resin showed a single protein band on SDS-PAGE analysis (Fig. 3A, lane 5). The molecular mass of this protein was calculated to be 53 kDa on an SDS-PAGE gel."

Products to Avoid

The website Sixwise advises:

If you want to avoid products with BPA, keep in mind the following:

• Plastic that contains BPA carries the #7 recycling symbol.
• Most clear plastic baby bottles and child cups are made of BPA-containing plastic.
• Dental sealant may leach BPA; this is being debated. You may want to avoid dental sealants on your children's baby teeth.

You can minimize your BPA exposure by:

• Replacing plastic food and drink containers and utensils with glass, ceramic or metal varieties.
• Purchasing glass baby bottles.
• Using baby bottles and sippy cups made of polyethylene plastic (#1, #2, #4 recycling symbols) or polypropylene (#5) (these are usually colored, not clear, and should still not be heated).
• Not using canned foods or foods wrapped in plastic.
• Not letting children put plastic toys in their mouths.
• Being careful with BPA-containing plastics, if you choose to use them. This means not exposing them to heat (microwave, dishwasher) or harsh detergents (bleach, etc.) and not letting food or beverages sit in the containers for too long.

Scientist's endorsement of bisphenol A under review
MARTIN MITTELSTAEDT
Globe and Mail

The head of the Health Canada scientific team studying the safety of bisphenol A has been abruptly reassigned, while the department investigates claims he is too biased in favour of the chemical to objectively analyze it. Speaking at a medical conference in the U.S. in March, Mark Richardson, manager of Health Canada's contaminated-sites division, endorsed the use of bisphenol A after he had been selected to undertake a review of the health impacts of the chemical.

Bisphenol A On Trial
BETTE HILEMAN
Chemical and Engineering News
Only an unbiased panel with appropriate expertise can resolve apparently conflicting results of health studies
In industrialized countries, nearly everyone is exposed to bisphenol A (BPA), a weak synthetic estrogen.

Most of the 2 billion to 3 billion pounds produced in the U.S. each year is used to make polycarbonate food containers, baby bottles, refillable water containers, compact discs, and resins that line metal food and beverage cans.

The Centers for Disease Control & Prevention has found measurable levels—0.4 to 8.0 parts per billion—of BPA in 95% of U.S. urine samples.

Although BPA is only one of thousands of synthetic chemicals the U.S. population encounters, it may be the most important for the developing fetus and perhaps young children.

Every time children consume food or drink from a can, they are exposed to a small amount of BPA. Every time babies drink from clear polycarbonate plastic bottles, they ingest the chemical.

Because of this widespread exposure, researchers have conducted many studies of the health effects of low doses of BPA. Among government-funded experiments on lab animals and tissues, 153 found adverse effects and 14 did not.

Contrarily, all 13 studies of BPA funded by chemical corporations reported no harm.

The studies indicating harm report a variety of deleterious effects in rodent offspring exposed in the womb: abnormal weight gain, insulin resistance, prostate cancer, and excessive mammary gland development.

What can explain the vast discrepancies in the findings of government-funded and industry experiments? In a commentary in Environmental Health Perspectives, University of Missouri biologist Frederick S. vom Saal points to several reasons low-dose studies failed to find adverse effects.

One is the strain of rodent used. For example, two large industry-funded studies used the Sprague-Dawley rat, a strain known to be insensitive even to strong, well-characterized estrogens, such as diethylstilbestrol. So it is not surprising that these rats show no response to the weaker estrogen BPA. Many other rodent strains are far more sensitive, vom Saal wrote.

Another reason is that different batches of the feed used in several industry studies had highly variable estrogenic activities. Phytoestrogens, such as genistein in soy, as well as other estrogenic components, can be present in variable amounts in different batches, vom Saal reports. In some studies, estrogenic substances in the feed may have masked the effects of BPA, he says.

In light of the potential health effects of BPA exposure and the inconsistent study outcomes, it is especially important that an unbiased panel with no conflicts of interest and with a detailed knowledge of the field evaluate the literature on BPA, consider the weight of evidence in regard to adverse effects, and choose valid studies to include in its report.

Bias is the reason for the recent outcry from environmental groups and lawmakers when they became aware that outside contractor Sciences International (SI) was deeply involved in the National Toxicology Program's assessment of BPA (C&EN, March 12, page 13). SI helped select the scientific panel, reviewed the literature, and wrote the original draft report—essentially a literature review—on BPA for NTP's Center for the Evaluation of Risks to Human Reproduction. SI has worked for two BPA manufacturers, Dow Chemical and BASF. NTP is housed at the National Institute of Environmental Health Sciences (NIEHS).

It would seem that a scientific literature review would be an objective, cut-and-dried exercise where conflicts of interest could have little influence. But reality is almost the opposite.

For example, researchers in the field know that the biologically active fraction of total circulating BPA is the part that is not bound to plasma proteins, because protein-bound BPA cannot diffuse through cell membranes. So it is the levels of unbound BPA that must be compared when evaluating study results.

But some sections of the original draft report on BPA compared results of studies that were measuring total BPA to others that were measuring only the unbound fraction.

Another source of bias is omission of critical information from a review.

Because BPA causes adverse effects in rodents that are almost identical to some of the health problems that have recently increased in human populations, many researchers believe BPA may be partially responsible.

The incidence of human prostate cancer rose 85% from 1975 to 2002, and insulin resistance, which leads to type 2 diabetes, became a much more prevalent health problem. The incidence of childhood obesity has more than quadrupled over the past 40 years.

When newborn rats are exposed to low doses of BPA, they develop early-stage prostate cancer as adults. Low doses of BPA also cause insulin resistance in lab animals.

Several of the most alarming studies released recently link obesity with BPA. After vom Saal and other researchers exposed pregnant rodents to low levels of BPA, their pups gained weight rapidly and stayed overweight for the rest of their lives, while the control animals grew normally.

A similar phenomenon has been observed recently in humans, says Jerry Heindel of the NIEHS. Some full-term infants gain weight abnormally fast and stay obese throughout childhood.

He believes that in utero exposure to BPA, or to a mixture of environmental chemicals, may be playing some role in childhood obesity. High-calorie diets and lack of exercise are certainly important but may not be the only factors leading to excessive weight gain in children.

It seems urgent to investigate whether exposure to certain chemicals in the womb is one possible cause of prostate cancer, insulin resistance, and childhood obesity.

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