National Institutes of Health (NIH).
Request for information.
The NIEHS Division of Extramural Research and Training (DERT) and the NTP are seeking input on a number of key research areas that have been identified in recent evaluations of bisphenol A (BPA). Information provided will be used to help focus future research and testing activities on BPA. This Request for Information (RFI) is for planning purposes only and should not be construed as a funding opportunity or grant program. The NIEHS and NTP welcome input from the lay public, environmental health researchers, healthcare professionals, educators, policy makers, industry, and others with an interest in BPA.
Please respond online at the Bisphenol A Request for Information Web page by December 1, 2008, at http://ntp.niehs.nih.gov/go/rfibpa.Start Further Info
FOR FURTHER INFORMATION CONTACT:
Other correspondence regarding this RFI should be directed to either (1) Dr. Jerry Heindel, DERT Program Administrator, NIEHS, P.O. Box 12233, MD EC-23, Research Triangle Park, NC 27709, (phone) 919-541-0781, (e-mail) email@example.com or (2) Dr. Paul Foster, NTP Acting Toxicology Branch Chief, NIEHS, P.O. Box 12233, MD EC-34, Research Triangle Park, NC 27709, (phone) 919-541-2513, (e-mail) firstname.lastname@example.org.End Further Info End Preamble Start Supplemental Information
The NTP is an interagency program whose mission is to evaluate agents of public health concern by developing and applying tools of modern toxicology and molecular biology. The NTP was established as a cooperative effort to (1) Coordinate toxicology testing programs within the federal government, (2) strengthen the science base in toxicology, (3) develop improved testing methods, and (4) provide information about potentially toxic chemicals to health, regulatory, and research agencies, scientific and medical communities, and the public. To meet these goals, NTP designs and conducts large-scale laboratory animal research and testing programs and analyzes and reports its findings to assess potential hazards to human health from exposure to environmental agents. The NTP also carries out formal review and literature analysis activities.
The NIEHS mission is to understand the complex relationship between environmental risk factors and human biology within affected individuals and populations and to use this knowledge to prevent illness, reduce disease, and promote health. To accomplish this, the NIEHS supports research and professional development in environmental health sciences, environmental clinical research, and environmental public health. These extramural research and development activities are managed through NIEHS/DERT.
Recently, both the NTP and NIEHS/DERT conducted assessments related to understanding the potential human health and environmental risks posed by BPA. The NTP evaluation was conducted through its Center for the Evaluation of Risks to Human Reproduction (CERHR) and focused on whether current exposures may pose health risks to human reproduction and development. The final results of this evaluation were released on September 3, 2008, as the NTP-CERHR Monograph on Bisphenol A. The monograph and details of this evaluation are available at http://cerhr.niehs.nih.gov/chemicals/bisphenol/bisphenol.html. The NIEHS workshop, “Bisphenol A: An Examination of the Relevance of Ecological, In Vitro and Laboratory Animal Studies for Assessing Risks to Human Health” (for consensus statement see vom Saal et al., Reproductive Toxicol. 2007. 24:131-138) was co-sponsored with a number of other organizations and was broader in scope compared to the NTP-CERHR evaluation as it included consideration of ecological effects and human health effects not directly related to development or reproduction.
The NTP and NIEHS review activities resulted in a number of research recommendations to better characterize the sources and levels of human exposures to BPA and to help determine what, if any, adverse health effects might result from such exposures. Similarly, a number of research needs have been identified by the Food and Drug Administration in its draft assessment of BPA in food contact applications (http://www.fda.gov/ohrms/dockets/ac/oc08.html#Scienceboard see “Science Board to the Food and Drug Start Printed Page 62506Administration” meeting information for September 16, 2008).
Currently the NTP is pursuing studies of absorption, distribution, metabolism, and excretion (ADME) in experimental animals (rodents and non human primates) as well as the kinetics associated with these processes, following exposures to BPA from the perinatal period through adulthood, over a wide range of doses, by multiple routes of administration. These studies have been identified as high priority needs in all recent reviews and reflect the general lack of information on concentrations of BPA in blood and target tissues in animal studies reporting effects of “low” doses of BPA on various aspects of development.
In addition to ADME studies, other areas of research have been suggested to better characterize possible hazards associated with BPA exposures in humans. They include studies to (1) Examine pathways of human exposures, (2) identify cellular targets for BPA at low and high doses for consistency with an estrogenic mechanism of action, (3) identify interactions with other estrogenic substances including naturally occurring hormones, and (4) investigate further the “low” dose effects reported in experimental animals.
The findings from the ADME studies and the information collected as a result of this RFI will be analyzed and considered for use in the further development of NTP and NIEHS/DERT research and testing programs on BPA.
The NTP and NIEHS/DERT request information on the following:
- Ongoing or planned research activities that you are aware of related to this RFI.
- Specific data needs for any or all of the priority areas identified below.
- Suggestions for beneficial research collaborations.
To aid in the development of a listing of prioritized data needs, a summary listing of the research needs identified in the NTP CERHR evaluation, the NIEHS co-sponsored workshop, or the draft FDA assessment are included below. This list may be used as a starting point for developing a prioritized listing of research needs related to the health effects of BPA.
1. Studies of the concentrations of BPA and metabolites in human blood, urine, breast milk, amniotic fluid, placenta and other tissues, particularly in infants and young children, where appropriate.
2. More complete assessment of sources of human exposure to BPA.
3. In vitro studies examining interactions of BPA with multiple cellular targets (toxicity pathways) across a range of concentrations, and comparing these results with similar studies of other known estrogenic agents and combinations of estrogenic agents with BPA.
4. Studies of gestational and lactational exposure of experimental animals to “low” doses of BPA regarding effects on development and onset of adult disease including:
a. The sensitivity of the developing brain to BPA induced structural, functional, and biochemical alterations.
b. The relevance to primates of diminished estrogen-dependent brain and behavioral sexual dimorphisms in rodents exposed to BPA during development.
c. Confirmation of rodent studies reporting behavioral effects following BPA exposure during development related to the dopaminergic systems such as novelty-seeking, socio-sexual behaviors, and response to addictive drugs.
d. The susceptibility of the mammary gland and prostate gland to alterations in development from exposures to BPA.
e. The predilection of BPA-induced changes in mammary gland and prostate gland development to neoplasia later in life.
5. The robustness and biologic basis for altered puberty following BPA exposure in multiple species.
6. The potential for effects on the immune system.
7. The potential for metabolic disruptions leading to obesity, diabetes, or other metabolic diseases.
8. The potential for disruptions to the male reproductive tract including effects on sperm quantity and quality.
9. The potential for aneuploidy or chromosomal disruption to female germ cells and for proliferative and/or cystic changes to the ovary and uterus later in life.
10. Other areas not previously identified.
All responses to information requested within this RFI are optional. The information collected will be analyzed and considered for use in the further development of NTP and NIEHS/DERT research and testing programs on BPA. The summarized data (without identifiers) may appear in future reports. Although the NIH will provide safeguards to prevent the release of identifying information there is no guarantee of confidentiality. This RFI is for planning purposes and shall not be construed as a solicitation for applications nor as an obligation on the part of the Government. The Government will not pay for the preparation of any information submitted or for the Government's use of that information. Respondents will not be notified of the Government's assessment of the information received. No basis for claims against the Government shall arise as a result of responses to this RFI, or in the Government's use of such information as part of its evaluation process.Start Signature
Dated: October 7, 2008.
Samuel H. Wilson,
Acting Director, National Institute of Environmental Health Sciences and National Toxicology Program.
[FR Doc. E8-25053 Filed 10-20-08; 8:45 am]
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