On
December 30, 2002, the U.S. Environmental Protection Agency (EPA) released for
public comment the approach it intends to use for selecting the first group of
chemicals to be screened in the Endocrine Disruptor Screening Program (EDSP). Comments on the notice are now due April 1, 2003, extended
from March 1, 2003. This memorandum briefly summarizes EPA's proposed approach.
Background
The notice sets forth the
approach EPA proposes to use for selecting an initial group of chemicals to be
screened in EPA's EDSP. EPA is following a tiered approach in implementing its
statutory mandate under Section 408(p) of the Federal Food, Drug, and Cosmetic
Act (FFDCA), as amended by the Food Quality Protection Act. Section 408(p)
directs EPA to develop a screening program to determine whether certain
substances may have hormonal effects in humans. EPA has expressed
particular concern that certain pesticides, which are defined under the Federal
Insecticide, Fungicide, and Rodenticide Act (FIFRA) to include inerts, as well
as other substances, may modify the normal functioning of human and wildlife
endocrine systems and thus may cause developmental, behavioral, and reproductive
problems.
EPA chartered a scientific
advisory committee to provide advice and recommendations for developing a
strategy to determine whether substances have an effect similar to the one
produced by naturally occurring hormones. The committee, known as the
Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC),
recommended, among other things, that EPA address effects on both humans and
wildlife, examine effects on biological processes involving the estrogen,
androgen, and thyroid (EAT) hormones, and include pesticide chemicals,
commercial chemicals, and environmental contaminants within the scope of the
program. Commercial chemicals and environmental contaminants are included
because EPA believes such substances, like PCBs and other non-pesticidal
chemicals, have been implicated as endocrine disruptors. Following the
recommendations of the EDSTAC, EPA announced the establishment of the EDSP in
1998.EPA first
set forth the basic components of the EDSP on August 11, 1998. EPA offered
additional details on the program on December 28, 1998. In short, EPA will
use a tiered, multi-step approach for determining whether a substance may have
effects similar to those produced by naturally occurring hormones. The
core elements of the approach consist of sorting, priority setting, Tier 1
screening, and Tier 2 testing. Tier 1 screening is envisioned as a battery
of screening assays that would identify substances that have the potential to
interact with EAT hormone systems. EPA has indicated that it intends to
accept a Science Advisory Board (SAB)/Scientific Advisory Panel (SAP)
recommendation to select and screen 50 to 100 chemicals to help EPA refine the
screen, and then convene an external peer review panel to review the results and
assess the integrity of the screen. Tier 2 testing is intended to
determine whether the substance could cause endocrine effects mediated by
EAT-related processes, and to establish a dose-response relationship between an
endocrine-active substance and an observed effect.
The
Approach EPA Proposes
EPA's
approach for selecting the first group of chemicals to be screened focuses on
pesticide active ingredients, high production volume (HPV) chemicals, and some
pesticidal inert chemicals (those with relatively large commercial production
volume). EPA would exclude from this first group any chemical for which
available effects data "clearly show" an endocrine-mediated effect.
These chemicals would be considered for Tier 2 testing. EPA would also
exclude substances EPA anticipates would have a low potential to cause endocrine
disruption, such as FIFRA List 4 inerts, most polymers with number average
molecular weight greater than 1,000 daltons, strong mineral acids, strong
mineral bases, and chemicals no longer produced or used in the United States.
Importantly, EPA is also proposing to defer consideration of testing mixtures
until additional experience is gained on the program.The notice
explains EPA's approach for selecting pesticide active ingredients and for
selecting HPV/Inert chemicals, as the approaches are different. For
selecting pesticides, in general terms, EPA will focus on data that demonstrate
human exposure by four pathways: food consumption, drinking water consumption,
residential use, and through occupational contact with pesticide-treated
surfaces. EPA will give higher priority to pesticides likely to pose
exposure opportunities by all four pathways, followed by those having exposure
through three pathways, and so forth.EPA is
proposing a similar approach to identify HPV/Inert chemicals, which is, however,
different in key respects. Because of the nature of the FIFRA registration
program, EPA has more data on the usage of active ingredients than it does on
HPV/Inert chemicals. EPA intends to focus on several indicators of the
potential for human exposure, including production volume, specific pathways of
exposure, and the presence of an HPV/Inert chemical in human tissue. EPA's step
wise approach is as follows:
EPA
will first review existing databases to identify chemicals that are both
pesticide inerts and HPV chemicals.
EPA
will review existing data to identify HPV/Inert chemicals that have been
found to be present in: human tissue, ecological tissues that have human
food uses, or drinking water or indoor air. In this regard, the
following databases will be reviewed: Third National Health and
Nutrition Examination Survey (NHANES III); the National Report on Human
Exposure to Environmental Chemicals prepared by the Centers for Disease
Control and Prevention (CDC); the National Human Adipose Survey (NHATS); the
Total Exposure Assessment Methodology Study (TEAM Study); the National
Sediment Inventory Fish Tissue Data (NSI Fish Tissue Data); the National
Fish Tissue Study; the National Drinking Water Chemical Occurrence Data Base
(NCOD Date Base); the National Human Exposure Assessment Survey (NHEXAS);
the Total Exposure Assessment Methodology Water Data (TEAM Water Data); the
National Stream Quality Accounting Network (NASQAN); the National Water
Quality Assessment Program (NAWQA); and EPA Office of Research and
Development (ORD) authored journals, the references for which are noted in
the Federal Register notice.
In
terms of identifying priorities, EPA proposes to produce four lists of
chemicals, one for each type of monitoring data. EPA proposes to give
higher priority to chemicals that appear on multiple lists, similar to the
scheme described above for active ingredient pesticides. To establish priorities
within the chemicals appearing on multiple lists, EPA proposes to give greater
priority to chemicals that appear in human biological monitoring data, followed
by drinking water/indoor air, followed by ecological biological monitoring data
relevant to humans. As a final step, EPA proposes to review available effects
information to identify any chemical for which the information
"clearly" indicates an "endocrine-mediated
effect/perturbation." During this last step, EPA would also dismiss
chemicals that EPA would expect to have a low potential to cause endocrine
disruption (e.g., FIFRA List 4 inerts, polymers
with greater than 1,000 daltons molecular weight, etc.).EPA has
requested comment on its proposed approach, as described above, and on specific
issues.
