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Vol. 13 Issue 2, Spring 2008
By Suzanne Snedeker, Ph.D., Associate Director for Translational Research, BCERF
The purpose of the National Toxicology Program’s Center for the Evaluation of Risks to Human Reproduction (NTP-CERHR) is to provide unbiased evaluations, based on the current strength of scientific evidence, on whether exposure to certain chemicals in the environment could cause harmful effects on human reproduction or development. On April 14, 2008 they released a draft report on the potential for the chemical bisphenol A (BPA) to affect human reproduction and development, including possible developmental effects on the mammary gland. The NTP report calls for more studies to determine BPA’s potential to affect the development of the mammary gland in laboratory animal models, since this is needed to assess possible human implications for low-level exposures and effects on breast cancer risk.
What is the purpose of the report? This draft report, called a Brief, is considered to be a preliminary report. It provides both the public and government-based health, regulatory and research agencies with the NTP’s conclusions on the potential for BPA to adversely affect human reproduction and the development of children. The NTP’s conclusions in the Brief will be peer reviewed by a panel of experts on June 11, 2008. The draft report is not a comprehensive evaluation of all toxicological aspects of BPA; it only covers areas in the realm of reproduction and development. Why, then, did this report also review data on certain aspects of BPA’s ability to affect breast cancer risk? This is because animal modeling studies that have looked at the question of whether early fetal exposure to BPA, when the mammary gland is in its early development phase, results in the formation of any pre-cancerous mammary lesions later in life. Such an effect would be considered to be a developmental effect, since chemical exposure occurred during a critical window of mammary gland development.
What is BPA? BPA is a high-volume industrial chemical primarily used in making certain plastics and resins. Over 6 billion pounds of BPA are produced globally each year, and according to the report, this includes 2.3 million pounds produced per year in the US. The major use of this chemical is to produce a hard, transparent plastic called polycarbonate, used in the manufacturing of sports water and baby bottles, goggles, sports equipment, CDs and DVDs. BPA is also used in epoxy resins used to coat the inside of metal food cans.
Is there evidence for exposure in people? Yes, the report cites biomonitoring studies by the Centers for Disease Control and Prevention (CDC) that report low-level, widespread exposure of BPA in the general US population. In a study of urinary levels of BPA and its metabolites, BPA was detected in 93% of the 2,517 urine samples analyzed by the CDC. The major source of BPA is from food and beverages. BPA can migrate from the lining of epoxy coated food cans into food, and from polycarbonate plastics (sports bottles and baby bottles) into beverages. High heat (e.g. high canning temperature in canned foods, and hot beverages in sports or baby bottles) is the major condition that causes BPA to migrate from containers into the food and beverages. BPA has also been detected in breast milk. The report states that the highest levels of exposure in the general population occur in infants and children, because they eat and drink more per pound of body weight than adults, they mouth plastic items, and have more hand-to-mouth behaviors that enhance the level of exposure compared to adults.
Infant exposure is of concern because it is thought that the body handles BPA differently in infants and children, compared to adults. BPA that is in a “free” form seems to act like a number of hormones, including as a weak estrogen mimic. Eventually, BPA is converted from the free form to a “conjugated” form by the liver, and in humans this conjugated form is excreted in the urine. This conjugated form does not appear to be estrogenic. In laboratory animal studies, young animals are less efficient at converting the free form to the conjugated form compared to adults. Hence, the concern is that there is a greater potential for children not only to be exposed to more BPA than adults, but they also may be exposed to the hormonally active free form of BPA more than adults.
Is there evidence early exposure to BPA can affect breast cancer risk? There is some, limited concern. There have been no studies on early exposures to BPA in humans and subsequent effects on breast cancer risk later in life. There are, however, studies conducted in laboratory animals that show early life exposures to BPA can cause pre-cancerous mammary gland (breast) lesions to form later in life. Researchers at Tufts University used small pumps under the skin to deliver low doses of BPA to fetal rat pups during pregnancy. As the pups grew older and approached adulthood, there was a higher frequency of pre-cancerous lesions, including hyperplasias, in the animals that had early-life exposures to BPA compared to those that only received the solvent used to deliver the BPA. It is thought that early exposure to BPA may be causing developmental changes in the mammary gland that may be linked to the pre-cancerous changes observed later in life. If the BPA-treated animals were challenged when they were adults with another chemical that was a known carcinogen, there was some evidence of a higher level of mammary tumors, but this effect was not statistically significant.
The NTP report states that there are similarities between the development of rat and human breast tumors. For instance, in both species hyperplasias and other precancerous lesions are considered to be an intermediary step in tumor formation. Hence, the preneoplastic lesions observed in rodent models are relevant to human risk. However, they cautioned that more studies are needed on BPA. As with any scientific finding, the observation that gestational exposure to BPA in fetal rats caused changes that resulted in precancerous lesions later in life needs to be confirmed by other investigators. Studies also need to include a sufficient number of animals so they can be followed for longer periods of time to see to what extent BPA-induced hyperplasias have the capacity to progress to invasive mammary tumors as the animals age. The NTP states that additional studies are needed “to more completely understand the possible long-term consequences of disrupting mammary gland development in animals by BPA exposure and its significance for human health” (CEHR, 2008, BPA Brief, pg. 22).
Conclusions of the NTP Report as they pertain to breast risk factors. The NTP states, “The evidence is not sufficient to conclude that bisphenol A is a rodent mammary gland carcinogen or that bisphenol A presents a breast cancer hazard to humans” (CEHR, 2008, pp 20). But, the NTP also states that it cannot be dismissed that BPA may have developmental effects in humans. Therefore they express “some concern for bisphenol A exposure” in fetuses, infants and children, based on effects on the mammary gland, as well as effects on other tissues.
Reference
NTP-CERHR (2008) Draft NTP Brief on Bisphenol A, National Toxicology Program, Center for the Evaluation of Reproduction and Health, National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Dept. of Health and Human Services, Report Date: April 18, 2008 cerhr.niehs.nih.gov/chemicals/bisphenol/BPADraftBriefVF_04_14_08.pdf.
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