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New independent study by EPA refutes BPA risk

Trevor Butterworth, October 30, 2009
Updated, Nov 16, 2009 with additional extracts from the study paper

A major independently-funded study by the EPA fails to find evidence of low dose effects from Bisphenol A.

The case against Bisphenol A (BPA), a chemical used to prevent food contamination in canned goods, has just gotten a whole lot weaker. Environmental activists and a small number of scientists have long protested that small amounts of BPA ingested through food and drink are the biological equivalent of global warming or akin to giving a baby a contraceptive pill. Activists have charged that risk assessments by the Food and Drug Administration and other agencies have relied exclusively on flawed industry-funded studies to cover up the risk to the public, while “independent” studies have demonstrated these risks.

But regulatory agencies around the world have rejected many of these independent studies, noting that they are either methodologically flawed or irrelevant for the purposes of assessing risks in humans. Multigenerational studies with large samples, high statistical rigor, and strong experimental design have failed to confirm any risk, and these studies have been either independent, or funded by industry but designed and supervised by independent scientists (such as those employed by the European Union).

Now, a second independent study by the Environmental Protection Agency, published in the leading toxicological journal, Toxicological Sciences, has failed to find evidence of the low-dose hypothesis claimed by environmental activists and widely reported in the media.

In the study, “In Utero and Lactational Exposure to Bisphenol A, in contrast to Ethinyl Estradiol, Does not Alter Sexually Dimorphic Behavior, Puberty, Fertility and Anatomy of Female LE Rats” (Ryan et al) researchers fed one group of pregnant rats a range of doses of BPA and another group a range of doses of the synthetic estrogen used in birth control pills ethinyl estradiol

The choice of the Long Evans Hooded rat was significant, since activists have claimed the findings of a previous multigenerational study using the Sprague Dawley rat (Tyl et at, 2003) were invalid due to the breed being insensitive to estrogens. As Newsweek put it in claiming that the activists were correct,

“…[R]esearch in 2002 used a strain of rat that is extremely insensitive to estrogen; it doesn't even show hormonal effects if it's given 100 times the dose of estrogen in human birth-control pills. Since BPA acts like an estrogen, finding no effect in this insensitive rat is about as illuminating as not finding an effect of rain on a waterproof watch. That doesn't tell you that water can't harm machinery.”

The Center for Evaluation of Risks to Human Reproduction disagreed, noting that

“In no case has it been demonstrated that the SD strain is completely insensitive to any known estrogen. It is evident that different traits map to different chromosomes and the degree of estrogen sensitivity varies from tissue to tissue, likely depending on the tissue-specific gene regulated by ER on the chromosome. Therefore, one cannot conclude that the SD is insensitive to estrogens and the results of BPA studies with BPA should be ignored.”

The new paper bypasses this firefight. The LE Rats demonstrated significant sensitivity to estradiol and the researchers report reduced body weights, genital malformations and defeminization in pups whose mothers were gavaged (fed by tube) with the hormone.

The pregnant rats gavaged with BPA showed no effects.

Just as significant, the researchers looked at behaviors controlled by estrogens – a topic of “some concern” for the National Toxicology Program based on several papers with limited data. They write:

“… the potential effects of exposure to BPA on the development of sexually dimorphic behavior have been noted as an area of special concern by the National Toxicology Program (NTP). The NTP expressed ‘some concern’ for adverse effects of BPA on the brain and behavior based upon ‘limited evidence of adverse effects’ of low doses in rodent studies. When the Center for the Evaluation of Risk to Human Reproduction (CERHR) Expert Panel on BPA (Chapin et al. 2008) and NTP (2008) evaluated the studies on the neural and behavioral effects of BPA, the majority of the more than 40 studies were found to be ‘inadequate’ for further evaluation and, for this reason, the NTP monograph cites only seven rodent (four with mice, three with rats) behavioral studies in its determination of ‘some concern’ for low dose neural and behavioral effects of BPA. Relevant to the current study which examined the effects of exposure to BPA on the behavior of the female rat, it is noteworthy that only one of these three studies exposed rats during perinatal life (Negishi et al, 2004) and only male offspring were examined."

In 2008, the European Food Safety Authority (EFSA) concluded that “due to the low confidence in the reliability” of these studies and “the lack of consistency in the results of behavioural testing” that it was impossible to draw conclusions on developmental neurotoxicity. Norway and Denmark also did separate studies and reached similar conclusions. The EPA study now provides more positive evidence that there is not a risk. As Ryan et al note:

“… we chose to study saccharin preference and lordosis behavior in female rats because the defeminizing role of neonatal hormones has been well established for these behaviors and exposure to exogenous steroids produces robust changes in the behavior of treated female rats. Female rats neonatally defeminized by steroidal hormones display reduced saccharin preference… and lower levels of female sex behavior…

The lack of effect of BPA on this [lordosis] behavior clearly indicates the estrogen pathway in the brain controlling this behavior was not defeminized by BPA… BPA did not significantly affect [saccharin preference] at any dosage level."

This new study builds on research by the EPA’s Kembra Howdeshell, which found that lactational and gestational exposure to both estradiol and BPA over a broad range of orally-administered low dose endpoints in rats only produces effects for estradiol.

Undoubtedly, the activists and journalists who have subscribed to the view that BPA is deadly and that anyone who says it isn’t is shilling for industry will protest that estradiol shouldn’t be used as a control. As Newsweek once again argued in claiming that the activists on BPA had the better science,

“…Estradiol had never been used to provide such a baseline, so concluding that BPA is less potent than estradiol--as industry does--is like saying one temperature is higher than another when you don't even know if the thermometer works.”

In fact, estradiol has been used as a baseline in studying chemicals with estrogen-like activities since 1998 (Biegel et al.). It was used in Howdeshell (2007) and multiple studies by Tyl et al on BPA. If Newsweek’s claim was correct, it’s hard to see how any of these studies would pass peer-review, let alone form the basis for risk assessment all over the world.

The new study adds a growing body of evidence that BPA does not pose a risk at levels humans are exposed to. Since the European Union’s risk assessment in 2006, there has been a review by Japan’s National Institute of Advanced Industrial Science and Technology (2007), an examination of claims of neurotoxicity by the Norwegian Scientific Committee for Food Safety, (2008), an update to the European Union’s risk assessment  (2008), an evaluation by the French Food Safety Agency (2008), a risk assessment by NSF International, a World Health Organization collaborative center (2008), a review of new data by the German Federal Institute for Risk Assessment (2008), a joint regulatory review for manufacturers by the FDA and Health Canada, a survey by Health Canada (2009), a risk assessment by Food Standards Australia/New Zealand (2009), two more surveys by Health Canada, one on canned powdered infant formula, the second on bottled water products (2009), a hazard assessment by California’s Environmental Protection Agency (2009), and a modeling study of BPA in humans by the German Federal Institute for Risk Assessment (2009).



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