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FEATURE ARTICLE

Assessing Risks from Bisphenol-A

Evaluating human health risks from endocrine disruptors such as BPA is difficult, but animal studies suggest trouble is afoot

Heather Patisaul

Figure 1. A factory worker lifts a water containerClick to Enlarge ImageThe industrialized world produces an immense amount of plastic, more than 45 billion kilograms annually in the United States alone. But what is it made of, and is it all safe? Some reusable water bottles sold in Wal-Mart and other retail stores in the United States now display stickers proudly marketing themselves as “BPA-free.” The labeling results from consumer concern over scientific evidence that bisphenol A (BPA), a common ingredient in many hard plastics, may be harmful to the human reproductive system because it interferes with hormones. The plastics industry and the U.S. Food and Drug Administration (FDA) say BPA is not dangerous at the levels people are currently exposed to. In contrast, in September of 2008, the U.S. National Toxicology Program (NTP) concluded that there is “some concern” for adverse effects on the “brain, behavior and prostate gland in fetuses, infants, and children.” This concern prompted members of Congress to pressure the FDA to take another look, a process that is now underway.

Inconsistent messages about BPA safety have generated considerable public rancor, highlighting how human risk assessment of BPA (and compounds like it) is both uncoordinated and controversial. Consensus regarding BPA’s safety has evaded U.S. health agencies for multiple reasons. Most pressing is the lack of clear guidelines for how much or what type of scientific evidence is needed to judge risks from hormone-disrupting compounds such as BPA. It would be unethical to directly assess those risks in people through controlled, double-blinded exposure experiments. At the same time, there are uncertainties about when exposure data from animal studies are relevant to human health. In a global environment where BPA production and exposure have grown rapidly, there is a pressing need to overcome these challenges. That is especially true because BPA is only one of thousands of chemicals thought to possibly have unintended effects on reproductive health.

In the U.S., BPA ranks in the top 2 percent of high-production-volume chemicals. BPA is a monomer that makes polycarbonate plastics harder and more resilient. Polycarbonate plastics are typically clear and often designated by a “7” within their triangular recycle symbols. BPA is also found in the epoxy resins that line the inside of metallic cans (such as soup and soda cans) and water storage tanks. BPA is also in thousands of other products, including compact discs, eyeglasses, thermal paper, polycarbonate water pipes, medical devices and dental sealants. Consumption is thought to be the most common route of human exposure because BPA readily leaches from food containers into their contents, especially when its heated, including in a microwave. Centers for Disease Control and Prevention (CDC) scientists have estimated that more than 92 percent of Americans have BPA in their bodies, and the highest levels are typically found in children.

BPA is an endocrine disruptor, which the Environmental Protection Agency (EPA) defines as “an exogenous chemical substance or mixture that alters the structure or function(s) of the endocrine system and causes adverse effects” in individuals, their offspring or populations. Hormones have many modes of action, including the ability to initiate or suppress gene transcription. Endocrine disruptors interfere with those genetic-level processes. The timing of exposure is critical because vulnerability changes over a lifespan. In an adult, where sex-specific physiology and behaviors have matured and function properly, interference with hormone action is likely reversible once exposure ends. This is not thought to be the case in the developing fetus or young child. Therefore, fetuses and infants are the groups most at risk for adverse effects from an endocrine disruptor such as BPA.

Over the course of development, hormones actually help shape the vertebrate brain and reproductive organs that allow sex-specific physiology and behaviors to emerge. Much of this happens in discrete developmental windows that span gestation through the postnatal period and, to some degree, into adolescence. Disruption of this developmental progression can permanently alter the organization of sexually dimorphic neuroendocrine circuits in the brain, the cellular composition of reproductive organs, the timing of puberty, the development of sex-typical behaviors and, ultimately, the capacity to reproduce. BPA exposure, even at levels humans are likely exposed to, appears to produce every one of these effects in laboratory rats and mice. But does it produce similar reproductive disorders in humans?

The reproductive effects found in laboratory rodents mirror some disturbing human health trends in industrialized nations. For example, an analysis of more than 100 research studies concluded that sperm counts in the United States and Europe appear to have declined by roughly half over the past 50 years. Researchers in Denmark now estimate that more than 10 percent of men in that country have sperm counts in the infertile range and up to 30 percent in the subfertile range. Rates of testicular cancer appear to be increasing. There are indications that female fecundity is declining, even among young women, although the rate and degree have been difficult to quantify. Median ages at menarche, first breast development and sexual precocity are dropping, especially among minority populations in the U.S. Similar trends have been noted in Europe and among children adopted from developing countries by parents in industrialized settings. The cause is likely complex and multifaceted, but the rapidity of the changes suggests an environmental component. Whether BPA might be involved hinges on whether effects observed in rodents reasonably predict what could be happening in humans.




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