[Federal Register Volume 73, Number 204 (Tuesday, October 21, 2008)]
[Notices]
[Pages 62505-62506]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-25053]


-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES


National Institute of Environmental Health Sciences (NIEHS); 
National Toxicology Program (NTP); Request for Information (NOT-ES-09-
001): Ongoing Research and Research Needs for Biological Effects of 
Exposure to Bisphenol A (BPA)

AGENCY: National Institutes of Health (NIH).

ACTION: Request for information.

-----------------------------------------------------------------------

SUMMARY: 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.

DATES: Please respond online at the Bisphenol A Request for Information 
Web page by December 1, 2008, at http://ntp.niehs.nih.gov/go/rfibpa.

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 protected] 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) [email protected].

SUPPLEMENTARY INFORMATION: 

Background

    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

[[Page 62506]]

Administration'' 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.

Information Requested

    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.

    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]
BILLING CODE 4140-01-P