NTP Proposes Changes to Process for Next Report on Carcinogens

The National Toxicology Program is accepting comments on a revised process for reviewing substances that may be added to its widely cited "Report on Carcinogens." NTP is accepting comments up to Nov. 30th.

The Report is required by Congress to be published every two years, and is designed to provide
information on substances that may pose a hazard to human health by virtue of their  carcinogenicity.  Substances are listed in the report as either known or reasonably anticipated human carcinogens. The 12th Report was published in June, 2011. But now, the NTP is proposing changes to the review process for listing substances in the 13th Report.

The NTP will hold a listening session on November 29, 2011, from 1–5 p.m. (EST), as well, to receive oral comments on the proposed review process.

Under the proposed process, NTP says it would make its substance review process more flexible, and more descriptive of the  reasoning it used to develop a proposed classification of an agent, and  thus would summarize the relevant science and also the agency's reasoning about how the agent should be classified.

Toxic tort practitioners among our readers may want to take a look (and have their experts do so).
 

Latest BPA Update

Here is the latest on BPA:

1. NTP Issues Final Report

The National Toxicology Program issued its final report on bisphenol A (BPA) earlier this month. NTP continued its position from a much publicized draft report (see the post here) that it has some concern that the chemical – used in plastic bottles and other packaging -- could affect the development of the prostate gland and brain and potentially affect the behavior of fetuses, infants, and children. See The Monograph on the Potential Human Reproductive and Developmental Effects of Bisphenol A.

The report provides the NTP’s current opinion on BPA’s potential to cause harm to human reproduction or development. The report is part of a review of the scientific literature on BPA and takes into consideration public and peer review comments received on the earlier draft report. According to NTP, about 2.3 billion pounds were produced in the United States in 2004, with more than 90 percent of the population being exposed to the substance.

The conclusions are based primarily on animal studies. The literature on experimental animal studies is filled with many conflicting findings, NTP says. And NTP admits that there remains considerable uncertainty whether the changes seen in the animal studies are directly applicable to humans, and whether they would result in clear adverse health effects. NTP also states that more research is clearly needed to understand exactly how these findings relate to human health and development. There are a number of remaining uncertainties in the scientific information on BPA, according to the report.

The NTP is an interagency federal research program at the National Institute of Environmental Health Sciences, part of the National Institutes of Health. The report uses a five-level scale ranging from negligible risk to serious concern.

The report expresses “minimal concern” that BPA exposure will affect development of the mammary gland or accelerate puberty in females. (Previously, NTP said it had some concerns about those effects, but a panel of experts concluded that the program overstated its concerns about mammary gland effects and early puberty.) The NTP expressed “negligible concern” that exposure of pregnant woman to BPA will result in fetal or neonatal mortality, birth defects or reduced birth weight and growth in their offspring. And the report also expressed “negligible concern” that exposure to BPA causes reproductive effects in non-occupationally exposed adults and “minimal concern” for workers exposed to higher levels in occupational settings.


The FDA responded to the final report, noting that it would consider this final report at FDA's Science Board meeting concerning the FDA’s draft assessment of bisphenol A.  Which brings us to development No.2.

2. FDA Meeting
FDA held a public meeting last week, with a range of scientists, industry representatives, and consumer advocates debating aspect of bisphenol A usage.

The focus of the meeting was the FDA’s draft risk assessment that found continued use of bisphenol A in food-contact materials would be safe. Among the highlights:

An EPA toxicologist who served on NTP's expert panel said the NTP's statements that it has "some concern" meant more research was needed. It did not imply that the NTP expert panel had concluded that harm was being caused by the chemical.

A toxicologist working at the National Institute of Environmental Health Sciences said that NTP reported it had "some concern" about neurological, behavioral, and prostate effects because the animal studies that found those effects involved exposures at levels similar to those expected for infants.

The head of the pediatrics department of the Medical College of Wisconsin suggested that FDA conduct or fund more exposure research to get a better understanding of infants' exposure. FDA’s estimates and NTP’s estimates of typical exposure were slightly different.

A representative of the polycarbonate business unit of the American Plastics Council noted that there have been at least two studies of bisphenol A levels in infant formula since FDA completed its study, including one by the Environmental Working Group. All have found levels comparable to what FDA used.

Other speakers noted that BPA is a relatively well studied chemical, and compounds that could be used as substitutes are unlikely to have as much information available about their safety. Clearly, some uses of bisphenol A, such as in children's bicycle helmets, provide many safety benefits. BPA has also been found to be safe with an unmatched performance in lining cans. The Environmental Working Group, said there are substitutes, in their view, already on the market for uses such as in baby bottles.

A toxicologist from the University of Missouri-Columbia worried that FDA's recommended tests might mean it would take many more years before the agency might take any necessary regulatory action to reduce exposure.

John van Miller of the American Chemistry Council, cited the multi-dose, multigenerational, significant studies conducted in accordance with internationally agreed-upon protocols that have found bisphenol A to be safe. The "Reproductive Health Technologies Project" disagreed and underscored the need for studies in their view.

The Bisphenol A Subcommittee is to brief FDA's Science Board later this Fall on the subcommittee's recommendations. The Science Board will then develop its own recommendations for BPA.


3. JAMA Study
The Journal of the American Medical Association published a study last week which has been reported in the popular press as showing that subjects with higher levels of bisphenol A in their urine were more likely to report that they had heart disease or diabetes. See Association of Urinary Bisphenol A Concentration with Medical Disorders and Laboratory Abnormalities in Adults.

Higher levels of human urinary BPA were reportedly associated with cardiovascular disease, type 2 diabetes, and liver-enzyme abnormalities, according to the study, which was discussed at the FDA public meeting. The study used data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004. The survey involved the measured urinary bisphenol A concentrations of 1,455 adults, ages 18 through 74 years. 
 

The investigators noted that orally administered BPA is rapidly and completely excreted by humans.  On of the limitations of the analysis is its cross-sectional nature: it does not offer longitudinal data demonstrating that BPA concentrations predict later onsets of biochemical change or disease. The authors cautioned that their method may have resulted in false-positive associations. The authors have recommended an independent replication of the study, and follow-up studies to explore their findings and to provide evidence on whether the associations are causal. Not well reported in the media is the fact that the research team used four methods to measure whether bisphenol A was associated with diabetes, but found that association in only one of the four methods. The study thus is primarily useful for generating hypotheses that can be tested, not for drawing any conclusions on human health effects.

 

Latest BPA Update: Peer Review Panel Weighs In On NTP Draft Report

Latest BPA update. Readers of MassTortDefense know that a recent draft report by the Center for the Evaluation of Risks to Human Reproduction (CERHR) of the National Toxicology Program (NTP) examined bisphenol-A (BPA). The CERHR/NTP draft report, issued April 15th for public comment, expressed "some concern" based on animal studies that the chemical might affect the neurological systems and behavior of fetuses, infants, and children. See our post here.


Officials from the U.S. Food and Drug Administration and the U.S. Consumer Product Safety Commission both told the U.S. Senate Committee on Commerce, Science and Transportation subcommittee on consumer affairs recently that bisphenol-A did not appear to pose sufficient risks that the product should be banned. Although review is ongoing, at this time those agencies have no reason to recommend that consumers stop using products containing BPA. The FDA's associate commissioner for science said that a large body of evidence indicates that currently marketed products containing BPA, such as baby bottles and food containers, are safe and that exposure levels to BPA from these products are well below those that may cause health effects. See our post here on this.


The NTP collected public comments on the draft and scheduled a June 11 peer review meeting for the draft. In comments on the NTP draft report, the American Chemistry Council asserted that the program relied on numerous studies of dubious and limited quality. Certain environmental groups sought stronger statements of concern.

The expert review panel has now concluded that the National Toxicology Program overstated some of the concerns about bisphenol A's potential developmental effects. At a meeting in Research Triangle Park, the panel, called the Board of Scientific Counselors, voted to revise the levels of concern stated in the NTP draft report on bisphenol A. In particular the “some concern" is to change to "minimal concern" regarding the neurological system and behavior of fetuses, infants, and children as might be affected by exposure to low levels of bisphenol A. (The toxicology program regularly uses "statements of concern" about different types of exposures and different groups that may be exposed to a chemical. The five levels of concern used by NTP are from highest to lowest: serious concern, concern, some concern, minimal concern, and negligible concern. )

Following its review of the draft report, the BSC panel decided that NTP had overstated bisphenol A's potential effects on mammary glands and the onset of puberty in young females. The panelists generally felt that there were insufficient scientific data to support any stronger level of concern than minimal.

The review panel said there was sufficient evidence in the studies considered by NTP to support its other statements of concern –minimal and negligible.

• The BSC accepted (7 yes, 4 no, 1 abstention) that the scientific evidence cited in the draft NTP Brief on Bisphenol A supports the conclusion of minimal concern for bisphenol A exposure in fetuses, infants, and children at current human exposures based on effects in the mammary gland. • The BSC accepted (7 yes, 4 no, 1 abstention) that the scientific evidence cited in the draft NTP Brief on Bisphenol A supports the conclusion of minimal concern for bisphenol A exposure in fetuses, infants, and children at current human exposures based on an earlier age for puberty in females.
• The BSC accepted (11 yes, 1 no) that the scientific evidence cited in the draft NTP Brief on Bisphenol A supports the NTP conclusion of negligible concern that exposure of pregnant women to bisphenol A will result in fetal or neonatal mortality, birth defects or reduced birth weight and growth in their offspring.
• The BSC accepted unanimously (12 yes, 0 no) that the scientific evidence cited in the draft NTP Brief on Bisphenol A supports the NTP conclusion of negligible concern that exposure to bisphenol A causes reproductive effects in non-occupationally exposed adults.
• The BSC accepted (11 yes, 0 no, 1 abstention) that the scientific evidence cited in the draft NTP Brief on Bisphenol A supports the NTP conclusion of minimal concern for workers exposed to higher levels of bisphenol A in occupational settings.

The panel also accepted the mid-level “some” concern expressed in two areas.

• The BSC accepted unanimously (12 yes, 0 no) that the scientific evidence cited in the draft NTP Brief on Bisphenol A supports the NTP conclusion of some concern for neural and behavioral effects of bisphenol A in fetuses, infants, and children at current human exposures.
• The BSC accepted (10 yes, 2 no) that the scientific evidence cited in the draft NTP Brief on Bisphenol A supports the NTP conclusion of some concern for bisphenol A exposure in fetuses, infants, and children at current human exposures based on effects in the prostate gland.


The panel called for additional research to better understand bisphenol A's potential effects.

Public comments on the draft , transcripts, list of attendees, etc. found here.