FDA, endocrinologists at odds over agency’s latest BPA safety claims

Thomas Zoeller
R. Thomas Zoeller
Maricel Maffini
Maricel Maffini

 

The HHS National Toxicology Program issued a draft report in February suggesting that rodents exposed to the endocrine-disrupting chemical bisphenol A experienced only “minimal effects,” leading the FDA to reaffirm its stance that the chemical is “safe for consumers” at current levels in food packaging.

But the FDA’s safety claim, issued in a press release Feb. 23, has alarmed hormone science experts and some toxicologists, who claim the interim data — based on an incomplete report that has not undergone peer review — are premature. In a statement rebutting the FDA’s claim, the Endocrine Society noted that the study did not examine areas of key concern, such as the effect of bisphenol A (BPA) on brain development. The interim report, conducted at the FDA’s National Center for Toxicological Research (NCTR), instead focused on how BPA exposure affected growth, weight and tumor development in animal models, and experts caution that those data, too, are concerning.

“Bisphenol A has a molecular structure that can interact with several different receptors at the same time,” R. Thomas Zoeller, PhD, a member of the Endocrine Society’s EDC Advisory Group committee and professor of biology at the University of Massachusetts, told Endocrine Today. “This is something that is unheard in the natural hormone system. BPA can interact with the estrogen receptor, but also the androgen receptor and the thyroid hormone receptor. It produces this combination effect, and it’s very difficult to track it down [in research] because of that. We don’t have any pharmaceuticals that do such a thing, and, in fact, you wouldn’t want to have any pharmaceuticals that do such a thing.”

Adding more complexity to the BPA debate is the way the chemical can cause hormone receptors to behave within the context of “normal receptor actions,” Zoeller said.

“What that means is BPA can interact with the estrogen receptor and cause it to do what it normally does, but maybe it’s not the right time or place,” Zoeller said. “This is also very difficult to track down. All these industrial chemicals that react with receptors have that feature. None of them produce a perfect hormonal profile. They cause dysregulation.”

Plastic Bottles BPA
The FDA recently issued a statement reaffirming its stance that BPA is “safe for consumers” at current levels in food packaging.
Shutterstock.com

Questioning safety

The interim NCTR report is part of a larger, collaborative effort by the FDA and the National Institute of Environmental Health Sciences called CLARITY-BPA, a consortium established after a 2008 National Toxicology Program report raised concerns about developmental effects in rodents exposed to low doses of BPA. In the NCTR core study, researchers evaluated chronic and early life exposure to five doses of BPA in two groups of rodents, ranging from low (typical human exposure) to high. Overall, the study suggested there were “minimal effects” for rodents exposed to BPA, according to the FDA; however, the report identified an increase in mammary gland tumors at one of the five doses, in one of the rodent groups.

“The significance of these findings will be assessed through the peer-review process,” Stephen Ostroff, MD, deputy commissioner for foods and veterinary medicine at the FDA, said in a press release.

The second component of CLARITY-BPA includes academic studies of BPA’s effects on additional relevant endpoints, conducted by grantees at academic institutions and using offspring of rodents derived from the core NCTR study. An integrated report incorporating the core study with data from grantees will be published later, according to the FDA.

Zoeller said the endpoints studied in the NCTR report do not provide assurance that BPA is safe. The Endocrine Society is also calling on policymakers and regulators to “reserve judgement” until the full CLARITY report is released.
From the point of view of endocrinology, I’m not sure what rat uterine weight means for the human population, but the FDA seems to be OK with that,” Zoeller said. “The FDA is looking at traditional endpoints that are 50 to 70 years old. We know more now about how hormones work and what they do, and there are better endpoints to use. But, those endpoints can be sophisticated, and it doesn’t lend itself readily to a rapid, cheap analysis.”

A common exposure

In 2012, the FDA granted two petitions requesting that the agency amend its food additive regulations to no longer provide for the use of certain BPA-based materials in baby bottles, sippy cups and infant formula packaging because these uses have been abandoned. But the chemical, experts caution, remains almost impossible to avoid. The FDA allows BPA use in polycarbonate plastics and epoxy resins in certain food and beverage can linings (noting it is safe for such authorized uses), and the chemical is also found in other common products, such as thermal cash register receipts.

In a citizen science-based study published in BMJ Open Diabetes Research & Care in February, Lorna Harries, PhD, associate professor in molecular genetics at the College of Life and Environmental Sciences at the University of Exeter, United Kingdom, and colleagues analyzed data from 94 adolescents who partnered with researchers to create real-world diets attempting to avoid BPA exposure for 7 days. The students designed all materials, including study protocols, food diaries, lifestyle questionnaires and patient-information sheets, and were asked to record daily diet details, including food and drink, and any associated packaging for 7 days. Students were asked not to alter diets before the intervention began.

Within the cohort, 86% of participants had at least trace amounts of urinary BPA at baseline. After 7 days, the teens experienced no change in urinary BPA levels and reported difficulty in avoiding the endocrine-disrupting chemical.

“Based on our evidence, it is extremely difficult to reduce one’s own exposure to BPA by actively trying to avoid known sources,” Harries told Endocrine Today. “Our study indicates that the control over exposure to BPA currently does not lie with the consumer. At present, the ubiquitous nature of BPA in our environment and inadequacies in current labeling practices mean that it is very difficult to identify BPA-free foods.”

Maricel Maffini, PhD, an independent consultant with the nonprofit Environmental Defense Fund, said it is difficult to pinpoint specific foods or plastic products that could potentially contain problematic levels of BPA.

“Even if a product’s final package is not polycarbonate or a metal can that is coated with a BPA-base epoxy resin, there is no guarantee that BPA is not in the food because of the supply chain,” Maffini told Endocrine Today. “We don’t know how the individual ingredients were prepared, or if polycarbonate was used at any point in the manufacturing process, or if there were other kinds of metal cans coated with BPA used that are not in the final packaging we see in the supermarket. It is an ongoing issue, and I don’t think labeling is going to be the solution.”

Making changes

Consumers looking to avoid BPA exposure will find it difficult, Maffini said: Even plastic products with a “BPA-free” label could contain another endocrine-disrupting chemical as a replacement, such as bisphenol S or bisphenol F.

“The ideal situation for those concerned about being exposed to BPA is to increase the consumption of frozen, rather than canned, vegetables,” Maffini said. “Buy tomato sauce in a glass jar rather than plastic or canned.”

Additionally, people more sensitive to estrogen exposure, such men and women trying to conceive or women with certain types of breast cancer, may want to take care to avoid polycarbonate plastic as much as possible, Maffini said. That can be difficult, she added, depending on a person’s access to alternative products.

“It is not our responsibility to choose between safe and less safe,” Maffini said. “Everything must be safe when it comes to food additives. People can call the companies and ask, and if they are changing brands because one is advertising BPA-free food, they should ask, ‘What did you use to replace it?’ That’s the other problem. We have very little information on what is being used to replace BPA.”

Zoeller said evidence suggests that changes in behavior will most likely not change a person’s BPA-exposure level, but consumers should avoid plastics as much as possible and should not put plastic items in the microwave or dishwasher.

“You do what you can to mitigate the risk, even if the risk is small, knowing also that there are those entities working hard to maintain the status quo,” Zoeller said.

“It’s clear that plastics can be produced without estrogenic activities,” Zoeller said. “That’s been demonstrated. The only thing keeping us from doing it is political will. It is feasible to eradicate estrogenic chemicals from our food and products, but the social perception or awareness of the risk is an issue that we must deal with, and we have to deal with the relationship between industry and government.” – by Regina Schaffer

References:

HHS. CLARITY-BPA program. Available at: https://ntp.niehs.nih.gov/results/areas/bpa/clarity_bpa/clarity-bpa-program.html.

FDA. Statement from Stephen Ostroff M.D., Deputy Commissioner for Foods and Veterinary Medicine, on National Toxicology Program draft report on Bisphenol A. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm598100.htm.

For more information:

Maricel Maffini, PhD, can be reached at drmvma@gmail.com.

R. Thomas Zoeller, PhD, can be reached at tzoeller@bio.umass.edu.

Disclosures: Maffini and Zoeller report no relevant financial disclosures.

 

 

Thomas Zoeller
R. Thomas Zoeller
Maricel Maffini
Maricel Maffini

 

The HHS National Toxicology Program issued a draft report in February suggesting that rodents exposed to the endocrine-disrupting chemical bisphenol A experienced only “minimal effects,” leading the FDA to reaffirm its stance that the chemical is “safe for consumers” at current levels in food packaging.

But the FDA’s safety claim, issued in a press release Feb. 23, has alarmed hormone science experts and some toxicologists, who claim the interim data — based on an incomplete report that has not undergone peer review — are premature. In a statement rebutting the FDA’s claim, the Endocrine Society noted that the study did not examine areas of key concern, such as the effect of bisphenol A (BPA) on brain development. The interim report, conducted at the FDA’s National Center for Toxicological Research (NCTR), instead focused on how BPA exposure affected growth, weight and tumor development in animal models, and experts caution that those data, too, are concerning.

“Bisphenol A has a molecular structure that can interact with several different receptors at the same time,” R. Thomas Zoeller, PhD, a member of the Endocrine Society’s EDC Advisory Group committee and professor of biology at the University of Massachusetts, told Endocrine Today. “This is something that is unheard in the natural hormone system. BPA can interact with the estrogen receptor, but also the androgen receptor and the thyroid hormone receptor. It produces this combination effect, and it’s very difficult to track it down [in research] because of that. We don’t have any pharmaceuticals that do such a thing, and, in fact, you wouldn’t want to have any pharmaceuticals that do such a thing.”

Adding more complexity to the BPA debate is the way the chemical can cause hormone receptors to behave within the context of “normal receptor actions,” Zoeller said.

“What that means is BPA can interact with the estrogen receptor and cause it to do what it normally does, but maybe it’s not the right time or place,” Zoeller said. “This is also very difficult to track down. All these industrial chemicals that react with receptors have that feature. None of them produce a perfect hormonal profile. They cause dysregulation.”

Plastic Bottles BPA
The FDA recently issued a statement reaffirming its stance that BPA is “safe for consumers” at current levels in food packaging.
Shutterstock.com

Questioning safety

The interim NCTR report is part of a larger, collaborative effort by the FDA and the National Institute of Environmental Health Sciences called CLARITY-BPA, a consortium established after a 2008 National Toxicology Program report raised concerns about developmental effects in rodents exposed to low doses of BPA. In the NCTR core study, researchers evaluated chronic and early life exposure to five doses of BPA in two groups of rodents, ranging from low (typical human exposure) to high. Overall, the study suggested there were “minimal effects” for rodents exposed to BPA, according to the FDA; however, the report identified an increase in mammary gland tumors at one of the five doses, in one of the rodent groups.

PAGE BREAK

“The significance of these findings will be assessed through the peer-review process,” Stephen Ostroff, MD, deputy commissioner for foods and veterinary medicine at the FDA, said in a press release.

The second component of CLARITY-BPA includes academic studies of BPA’s effects on additional relevant endpoints, conducted by grantees at academic institutions and using offspring of rodents derived from the core NCTR study. An integrated report incorporating the core study with data from grantees will be published later, according to the FDA.

Zoeller said the endpoints studied in the NCTR report do not provide assurance that BPA is safe. The Endocrine Society is also calling on policymakers and regulators to “reserve judgement” until the full CLARITY report is released.
From the point of view of endocrinology, I’m not sure what rat uterine weight means for the human population, but the FDA seems to be OK with that,” Zoeller said. “The FDA is looking at traditional endpoints that are 50 to 70 years old. We know more now about how hormones work and what they do, and there are better endpoints to use. But, those endpoints can be sophisticated, and it doesn’t lend itself readily to a rapid, cheap analysis.”

A common exposure

In 2012, the FDA granted two petitions requesting that the agency amend its food additive regulations to no longer provide for the use of certain BPA-based materials in baby bottles, sippy cups and infant formula packaging because these uses have been abandoned. But the chemical, experts caution, remains almost impossible to avoid. The FDA allows BPA use in polycarbonate plastics and epoxy resins in certain food and beverage can linings (noting it is safe for such authorized uses), and the chemical is also found in other common products, such as thermal cash register receipts.

In a citizen science-based study published in BMJ Open Diabetes Research & Care in February, Lorna Harries, PhD, associate professor in molecular genetics at the College of Life and Environmental Sciences at the University of Exeter, United Kingdom, and colleagues analyzed data from 94 adolescents who partnered with researchers to create real-world diets attempting to avoid BPA exposure for 7 days. The students designed all materials, including study protocols, food diaries, lifestyle questionnaires and patient-information sheets, and were asked to record daily diet details, including food and drink, and any associated packaging for 7 days. Students were asked not to alter diets before the intervention began.

PAGE BREAK

Within the cohort, 86% of participants had at least trace amounts of urinary BPA at baseline. After 7 days, the teens experienced no change in urinary BPA levels and reported difficulty in avoiding the endocrine-disrupting chemical.

“Based on our evidence, it is extremely difficult to reduce one’s own exposure to BPA by actively trying to avoid known sources,” Harries told Endocrine Today. “Our study indicates that the control over exposure to BPA currently does not lie with the consumer. At present, the ubiquitous nature of BPA in our environment and inadequacies in current labeling practices mean that it is very difficult to identify BPA-free foods.”

Maricel Maffini, PhD, an independent consultant with the nonprofit Environmental Defense Fund, said it is difficult to pinpoint specific foods or plastic products that could potentially contain problematic levels of BPA.

“Even if a product’s final package is not polycarbonate or a metal can that is coated with a BPA-base epoxy resin, there is no guarantee that BPA is not in the food because of the supply chain,” Maffini told Endocrine Today. “We don’t know how the individual ingredients were prepared, or if polycarbonate was used at any point in the manufacturing process, or if there were other kinds of metal cans coated with BPA used that are not in the final packaging we see in the supermarket. It is an ongoing issue, and I don’t think labeling is going to be the solution.”

Making changes

Consumers looking to avoid BPA exposure will find it difficult, Maffini said: Even plastic products with a “BPA-free” label could contain another endocrine-disrupting chemical as a replacement, such as bisphenol S or bisphenol F.

“The ideal situation for those concerned about being exposed to BPA is to increase the consumption of frozen, rather than canned, vegetables,” Maffini said. “Buy tomato sauce in a glass jar rather than plastic or canned.”

Additionally, people more sensitive to estrogen exposure, such men and women trying to conceive or women with certain types of breast cancer, may want to take care to avoid polycarbonate plastic as much as possible, Maffini said. That can be difficult, she added, depending on a person’s access to alternative products.

“It is not our responsibility to choose between safe and less safe,” Maffini said. “Everything must be safe when it comes to food additives. People can call the companies and ask, and if they are changing brands because one is advertising BPA-free food, they should ask, ‘What did you use to replace it?’ That’s the other problem. We have very little information on what is being used to replace BPA.”

PAGE BREAK

Zoeller said evidence suggests that changes in behavior will most likely not change a person’s BPA-exposure level, but consumers should avoid plastics as much as possible and should not put plastic items in the microwave or dishwasher.

“You do what you can to mitigate the risk, even if the risk is small, knowing also that there are those entities working hard to maintain the status quo,” Zoeller said.

“It’s clear that plastics can be produced without estrogenic activities,” Zoeller said. “That’s been demonstrated. The only thing keeping us from doing it is political will. It is feasible to eradicate estrogenic chemicals from our food and products, but the social perception or awareness of the risk is an issue that we must deal with, and we have to deal with the relationship between industry and government.” – by Regina Schaffer

References:

HHS. CLARITY-BPA program. Available at: https://ntp.niehs.nih.gov/results/areas/bpa/clarity_bpa/clarity-bpa-program.html.

FDA. Statement from Stephen Ostroff M.D., Deputy Commissioner for Foods and Veterinary Medicine, on National Toxicology Program draft report on Bisphenol A. Available at: www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm598100.htm.

For more information:

Maricel Maffini, PhD, can be reached at drmvma@gmail.com.

R. Thomas Zoeller, PhD, can be reached at tzoeller@bio.umass.edu.

Disclosures: Maffini and Zoeller report no relevant financial disclosures.