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[Federal Register: July 23, 2008 (Volume 73, Number 142)]
[Rules and Regulations]
[Page 42683-42713]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr23jy08-6]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2002-0302; FRL-8372-5]
Dichlorvos (DDVP); Order Denying NRDC's Objections and Requests
for Hearing
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final Order.
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SUMMARY: In this order, EPA denies objections to, and requests for
hearing on, a prior order denying a petition requesting that EPA revoke
all pesticide tolerances for dichlorvos under section 408(d) of the
Federal Food, Drug, and Cosmetic Act. The objections and hearing
requests were filed on February 1, 2008, by the Natural Resources
Defense Council (``NRDC''). The Original petition was also filed by
NRDC.
DATES: This order is effective July 23, 2008.
ADDRESSES: EPA has established a docket for this action under docket
identification (ID) number EPA-HQ-OPP-2002-0302. To access the
electronic docket, go to http://www.regulations.gov, and search for the
docket number. Follow the instructions on the regulations.gov website
to view the docket index or access available documents. All documents
in the docket are listed in the docket index available in
regulations.gov. Although listed in the index, some information is not
publicly available, e.g., Confidential Business Information (CBI) or
other information whose disclosure is restricted by statute. Certain
other material, such as copyrighted material, is not placed on the
Internet and will be publicly available only in hard copy form.
Publicly available docket materials are available in the electronic
docket at http://www.regulations.gov, or, if only available in hard
copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac
Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket
Facility is open from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The Docket Facility telephone number is (703)
305-5805.
FOR FURTHER INFORMATION CONTACT: Susan Bartow, Special Review and
Reregistration Division (7508P), Office of Pesticide Programs,
Environmental Protection Agency, 1200 Pennsylvania Ave., NW.,
Washington, DC 20460-0001; telephone number: 703-603-0065; e-mail
address: bartow.susan@epa.gov.
SUPPLEMENTARY INFORMATION:
I. General Information
A. Does this Action Apply to Me?
In this document EPA denies objections and hearing requests by the
Natural Resources Defense Council (``NRDC'') concerning EPA's denial of
NRDC's petition to revoke pesticide tolerances. This action may also be
of interest to agricultural producers, food manufacturers, or pesticide
manufacturers. Potentially affected entities may include, but are not
limited to those engaged in the following activities:
Crop production (North American Industrial Classification
System (``NAICS'') code 111), e.g., agricultural workers; greenhouse,
nursery, and floriculture workers; farmers.
Animal production (NAICS code 112), e.g., cattle ranchers
and farmers, dairy cattle farmers, livestock farmers.
Food manufacturing (NAICS code 311), e.g., agricultural
workers; farmers; greenhouse, nursery, and floriculture workers;
ranchers; pesticide applicators.
Pesticide manufacturing (NAICS code 32532), e.g.,
agricultural workers; commercial applicators; farmers; greenhouse,
nursery, and floriculture workers; residential users.
This listing is not intended to be exhaustive, but rather to
provide a guide for readers regarding entities likely to be affected by
this action. Other types of entities not listed in this unit could also
be affected. The NAICS codes have been provided to assist you and
others in determining whether this action might apply to certain
entities. If you have any questions regarding the applicability of this
action to a particular entity, consult the person listed under FOR
FURTHER INFORMATION CONTACT.
B. How Can I Access Electronic Copies of this Document?
In addition to accessing an electronic copy of this Federal
Register document through the electronic docket at http://
www.regulations.gov, you may access this Federal Register document
electronically through the EPA Internet under the ``Federal Register''
listings at http://www.epa.gov/fedrgstr. You may also access a
frequently updated electronic version of EPA's tolerance regulations at
40 CFR part 180 through the Government Printing Office's pilot e-CFR
site at http://www.gpoaccess.gov/ecfr.
C. Acronyms
The following is a list of acronyms used in this order:
CSFII - Continuing Survey of Food Intakes by Individuals
CNS - Central Nervous System
DDVP - dichlorvos
EDSTAC - Endocrine Disruptor Screening and Testing Advisory
Committee
EPA - Environmental Protection Agency
FACA - Federal Advisory Committee Act
FDA - Food and Drug Administration
FIFRA - Federal Insecticide, Fungicide, and Rodenticide Act
FFDCA - Federal Food, Drug, and Cosmetic Act
FQPA - Food Quality Protection Act of 1996
HSRB - Human Studies Review Board
IRED - Interim Reregistration Eligibility Decision
LOAEL - Lowest Observed Adverse Effect Level
MOE - Margin of Exposure
MRID - Master Record Identification
NOAEL - No Observed Adverse Effect Level
NRDC - Natural Resources Defense Council
OECD - Organisation for Economic Co-operation and Development
PAD - Population Adjusted Dose
ppm - parts per million
RBC - red blood cell
RED - Reregistration Eligibility Decision
RfD - Reference Dose
SDWA - Safe Drinking Water Act
SOP - Standard Operating Procedure
USDA - United Stated Department of Agriculture
II. Introduction
A. What Action Is the Agency Taking?
In this order, EPA denies objections, and requests for a hearing on
those objections, to an earlier EPA order, (72 FR 68662 (December 5,
2007)), denying a petition to revoke all tolerances established for the
pesticide dichlorvos (``DDVP'') under the Federal Food, Drug, and
Cosmetic Act (``FFDCA''), 21 U.S.C. 346a. (Refs. 1 and 2). Both the
objections and hearing requests, as well as the petition, were filed
with EPA by NRDC.
NRDC's petition, filed on June 2, 2006, pursuant to FFDCA section
408(d)(1), asserted numerous grounds as to why the DDVP tolerances
allegedly fail to meet the FFDCA's safety standard. This petition was
filed as EPA was completing its reassessment of the safety of the DDVP
tolerances pursuant to FFDCA section 408(q). (Ref. 3). In response to
the petition, EPA undertook an extensive review of its DDVP safety
evaluation in the tolerance reassessment decision. Based on certain
concerns raised by NRDC, EPA determined it was necessary to incorporate
updated data on numerous points and to adopt revised and more
conservative assumptions, in its DDVP risk assessments. This led to
complete revisions of both EPA's assessments of
[[Page 42684]]
dietary and residential risks from exposure to DDVP. (72 FR at 68678,
68687-68691). Nonetheless, EPA concluded that its revised risk
assessments demonstrated that DDVP met the FFDCA safety standard and,
therefore, denied the petition. (Id. at 68695). EPA's denial was issued
in the form of an order under FFDCA section 408(d)(4)(iii). (21 U.S.C.
346a(d)(4)(iii)).
NRDC then filed objections with EPA to the petition denial order
and requested a hearing on its objections. These objections and hearing
requests were filed pursuant to the procedures in the FFDCA section
408(g)(2). (21 U.S.C. 346a(g)(2)). The objections narrowed NRDC's
claims to two main topics - that, in assessing the risk to DDVP, EPA
unlawfully reduced the statutory safety factor for the protection of
infants and children and EPA unlawfully relied on a human toxicity
study. As to these claims, NRDC largely repeats the arguments as
presented in its petition without addressing EPA's substantial
revisions to the DDVP risk assessment and proffers little to no
evidence in support of its requests for a hearing. After carefully
reviewing the objections and hearing requests, EPA has determined that
NRDC's hearing requests do not satisfy the regulatory requirements for
such requests and that its substantive objections are without merit.
Therefore, EPA, in this final order, denies NRDC's objections and its
requests for a hearing on those objections.
B. What Is the Agency's Authority for Taking This Action?
NRDC petitioned to revoke the DDVP tolerances pursuant to the
petition procedures in FFDCA section 408(d)(1). (21 U.S.C. 346a(d)(1)).
Under section 408(d), EPA may respond to such a petition by either
issuing a final or proposed rule modifying or revoking the tolerances
or issuing an order denying the petition. (21 U.S.C. 346a(d)(4)). Here,
EPA responded by issuing an order under section 408(d)(4)(iii) denying
the petition. (72 FR 68622 (December 5, 2007)).
Orders issued under section 408(d)(4)(iii) are subject to a
statutorily-created administrative review process. (21 U.S.C.
346a(g)(2)). Any person may file objections to a section 408(d)(4)(iii)
order with EPA and request a hearing on those objections. (Id.). EPA is
required by section 408(g)(2)(C) to issue a final order resolving the
objections to the section 408(d)(4)(iii) order. (21 U.S.C.
346a(g)(2)(C)).
III. Statutory and Regulatory Background
In this Unit, EPA provides background on the relevant statutes and
regulations governing NRDC's objections and requests for hearing as
well as on pertinent Agency policies and practices. As noted, NRDC's
objections and requests for hearing raise two main claims: (1) that EPA
has unlawfully failed to retain the full tenfold safety factor for the
protection of infants and children; and (2) that it was unlawful for
EPA to rely on a toxicity study for DDVP that was conducted with
humans. The children's safety factor claim is based on assertions
regarding DDVP's potential endocrine effects and the adequacy of EPA's
data and risk assessments pertaining to exposure to DDVP in food as a
result of the use of DDVP (and similar pesticides) in agriculture or
food storage and through use of DDVP in residential settings. The human
studies claim involves a challenge to the EPA regulation governing
reliance on human studies as well as to EPA's application of that rule
to a particular human study. The human study in question measured
cholinesterase inhibition in humans resulting from administration of
DDVP. Background information on each of these topics is included in
this Unit.
Unit III.A. summarizes the requirements and procedures in section
408 of the FFDCA and applicable regulations pertaining to pesticide
tolerances, including the procedures for petitioning for revocation of
tolerances and challenging the denial of such petitions and the
substantive standards for evaluating the safety of pesticide
tolerances. This unit also discusses the closely-related statute under
which EPA regulates the sale, distribution, and use of pesticides, the
Federal Insecticide, Fungicide, and Rodenticide Act (``FIFRA''), (7
U.S.C. 136 et seq.).
Unit III.B. provides an overview of EPA's risk assessment process.
It contains an explanation of how EPA identifies the hazards posed by
pesticides, how EPA determines the level of exposure to pesticides that
pose a concern (``level of concern''), how EPA measures human exposure
to pesticides, and how hazard, level of concern conclusions, and human
exposure estimates are combined to evaluate risk. Further, this unit
presents background information on two Agency policies with particular
relevance to this action, EPA's policy with regard to the statutory
safety factor for the protection of infants and children and its policy
with regard to cholinesterase inhibition.
Unit III.C. summarizes EPA's program for implementing the statutory
requirement to screen pesticides for potential endocrine effects. Unit
III.D. describes the EPA regulation on use of human studies.
A. FFDCA/FIFRA and Applicable Regulations
1. In general. EPA establishes maximum residue limits, or
``tolerances,'' for pesticide residues in food under section 408 of the
FFDCA. (21 U.S.C. 346a). Without such a tolerance or an exemption from
the requirement of a tolerance, a food containing a pesticide residue
is ``adulterated'' under section 402 of the FFDCA and may not be
legally moved in interstate commerce. (21 U.S.C. 331, 342). Monitoring
and enforcement of pesticide tolerances are carried out by the U.S.
Food and Drug Administration (``FDA'') and the U.S. Department of
Agriculture (``USDA''). Section 408 was substantially rewritten by the
Food Quality Protection Act of 1996 (``FQPA''), which added the
provisions discussed below establishing a detailed safety standard for
pesticides, additional protections for infants and children, and the
estrogenic substances screening program. (Public Law 104-170, 110 Stat.
1489 (1996)).
EPA also regulates pesticides under the Federal Insecticide,
Fungicide, and Rodenticide Act (``FIFRA''), (7 U.S.C. 136 et seq).
While the FFDCA authorizes the establishment of legal limits for
pesticide residues in food, FIFRA requires the approval of pesticides
prior to their sale and distribution, (7 U.S.C. 136a(a)), and
establishes a registration regime for regulating the use of pesticides.
FIFRA regulates pesticide use in conjunction with its registration
scheme by requiring EPA review and approval of pesticide labels and
specifying that use of a pesticide inconsistent with its label is a
violation of federal law. (7 U.S.C. 136j(a)(2)(G)). In the FQPA,
Congress integrated action under the two statutes by requiring that the
safety standard under the FFDCA be used as a criterion in FIFRA
registration actions as to pesticide uses which result in dietary risk
from residues in or on food, (7 U.S.C. 136(bb)), and directing that EPA
coordinate, to the extent practicable, revocations of tolerances with
pesticide cancellations under FIFRA. (21 U.S.C. 346a(l)(1)).
2. Safety standard for pesticide tolerances. A pesticide tolerance
may only be promulgated by EPA if the tolerance is ``safe.'' (21 U.S.C.
346a(b)(2)(A)(i)). ``Safe'' is defined by the statute to mean that
``there is a reasonable certainty that no harm will
[[Page 42685]]
result from aggregate exposure to the pesticide chemical residue,
including all anticipated dietary exposures and all other exposures for
which there is reliable information.'' (21 U.S.C. 346a(b)(2)(A)(ii)).
Section 408(b)(2)(D) directs EPA, in making a safety determination, to:
consider, among other relevant factors- ...
(v) available information concerning the cumulative effects of
such residues and other substances that have a common mechanism of
toxicity;
(vi) available information concerning the aggregate exposure
levels of consumers (and major identifiable subgroups of consumers)
to the pesticide chemical residue and to other related substances,
including dietary exposure under the tolerance and all other
tolerances in effect for the pesticide chemical residue, and
exposure from other non-occupational sources;
(viii) such information as the Administrator may require on
whether the pesticide chemical may have an effect in humans that is
similar to an effect produced by a naturally occurring estrogen or
other endocrine effects. ...
(21 U.S.C. 346a(b)(2)(D)(v), (vi) and (viii)).
EPA must also consider, in evaluating the safety of tolerances,
``safety factors which . . . are generally recognized as appropriate
for the use of animal experimentation data.'' (21 U.S.C.
346a(b)(2)(D)(ix).
Risks to infants and children are given special consideration.
Specifically, section 408(b)(2)(C) states that EPA:
shall assess the risk of the pesticide chemical based on-- ...
(II) available information concerning the special susceptibility
of infants and children to the pesticide chemical residues,
including neurological differences between infants and children and
adults, and effects of in utero exposure to pesticide chemicals; and
(III) available information concerning the cumulative effects on
infants and children of such residues and other substances that have
a common mechanism of toxicity. ...
(21 U.S.C. 346a(b)(2)(C)(i)(II) and (III)).
This provision also creates a presumptive additional safety factor
for the protection of infants and children. Specifically, it directs
that ``[i]n the case of threshold effects, ... an additional tenfold
margin of safety for the pesticide chemical residue and other sources
of exposure shall be applied for infants and children to take into
account potential pre- and post-natal toxicity and completeness of the
data with respect to exposure and toxicity to infants and children.''
(21 U.S.C. 346a(b)(2)(C)). EPA is permitted to ``use a different margin
of safety for the pesticide chemical residue only if, on the basis of
reliable data, such margin will be safe for infants and children.''
(Id.). The additional safety margin for infants and children is
referred to throughout this order as the ``children's safety factor.''
3. Procedures for establishing, amending, or revoking tolerances.
Tolerances are established, amended, or revoked by rulemaking under the
unique procedural framework set forth in the FFDCA. Generally, a
tolerance rulemaking is initiated by the party seeking to establish,
amend, or revoke a tolerance by means of filing a petition with EPA.
(See 21 U.S.C. 346a(d)(1)). EPA publishes in the Federal Register a
notice of the petition filing and requests public comment. (21 U.S.C.
346a(d)(3)). After reviewing the petition, and any comments received on
it, EPA may issue a final rule establishing, amending, or revoking the
tolerance, issue a proposed rule to do the same, or deny the petition.
(21 U.S.C. 346a(d)(4)).
Once EPA takes final action on the petition by either establishing,
amending, or revoking the tolerance or denying the petition, any person
may file objections with EPA and seek an evidentiary hearing on those
objections. (21 U.S.C. 346a(g)(2)). Objections and hearing requests
must be filed within 60 days. (Id.). The statute provides that EPA
shall ``hold a public evidentiary hearing if and to the extent the
Administrator determines that such a public hearing is necessary to
receive factual evidence relevant to material issues of fact raised by
the objections.'' (21 U.S.C. 346a(g)(2)(B). EPA regulations make clear
that hearings will only be granted where it is shown that there is ``a
genuine and substantial issue of fact,'' the requestor has identified
evidence ``which, if established, resolve one or more of such issues in
favor of the requestor,'' and the issue is ``determinative'' with
regard to the relief requested. (40 CFR 178.32(b)). EPA's final order
on the objections is subject to judicial review. (21 U.S.C.
346a(h)(1)).
4. Tolerance reassessment and FIFRA reregistration. The FQPA
required that EPA reassess the safety of all pesticide tolerances
existing at the time of its enactment. (21 U.S.C. 346a(q)). EPA was
given 10 years to reassess the approximately 10,000 tolerances in
existence in 1996. In this reassessment, EPA was required to review
existing pesticide tolerances under the new ``reasonable certainty that
no harm will result'' standard set forth in section 408(b)(2)(A)(i).
(21 U.S.C. 346a(b)(2)(A)(i)). This reassessment was substantially
completed by the August 3, 2006 deadline. Tolerance reassessment was
generally handled in conjunction with a similar program involving
reregistration of pesticides under FIFRA. (7 U.S.C. 136a-1).
Reassessment and reregistration decisions were generally combined in a
document labeled a Reregistration Eligibility Decision (``RED'').
5. Estrogenic substances screening program. The FQPA also imposed
requirements regarding creation of an estrogenic substances screening
program. Section 408(p) gives EPA 2 years from enactment of the FQPA to
``develop a screening program ... to determine whether [pesticide
chemicals and certain other substances] may have an effect in humans
that is similar to an effect produced by a naturally occurring
estrogen, or such other endocrine effect as the Administrator may
designate.'' (21 U.S.C. 346a(p)(1)). This screening program must use
``appropriate validated test systems and scientifically relevant
information.'' (Id.). Once the program is developed, EPA is required to
take public comment and seek independent scientific review of it.
Following the period for public comment and scientific review, and not
later than 3 years following enactment of the FQPA, EPA is directed to
``implement the program.'' (21 U.S.C. 346a(p)(2)).
The scope of the estrogenic screening program was expanded by an
amendment to the Safe Drinking Water Act (``SDWA'') passed
contemporaneously with the FQPA. That amendment gave EPA the authority
to provide for the testing, under the FQPA estrogenic screening
program, ``of any other substance that may be found in sources of
drinking water if the Administrator determines that a substantial
population may be exposed to such substance.'' (42 U.S.C. 300j-17).
B. EPA Risk Assessment for Tolerances--Policy and Practice
1. The safety determination - risk assessment. To assess risk of a
pesticide tolerance, EPA combines information on pesticide toxicity
with information regarding the route, magnitude, and duration of
exposure to the pesticide. The risk assessment process involves four
distinct steps: (1) Identification of the toxicological hazards posed
by a pesticide; (2) determination of the ``level of concern'' with
respect to human exposure to the pesticide; (3) estimation of human
exposure to the pesticide; and (4) characterization of risk posed to
humans by the pesticide based on comparison of human exposure to the
level of concern.
a. Hazard identification. In evaluating toxicity or hazard, EPA
reviews toxicity studies, primarily in laboratory animals,
[[Page 42686]]
to identify any adverse effects on the test subjects. Animal studies
typically involve investigating a broad range of endpoints including
gross and microscopic effects on organs and tissues, functional effects
on bodily organs and systems, effects on blood parameters (such as red
blood cell count, hemoglobin concentration, hematocrit, and a measure
of clotting potential), effects on the concentrations of normal blood
chemicals (including glucose, total cholesterol, urea nitrogen,
creatinine, total protein, total bilirubin, albumin, hormones, and
enzymes such as alkaline phosphatase, alanine aminotransfersase and
cholinesterases), and behavioral or other gross effects identified
through clinical observation and measurement. EPA examines whether
adverse effects are caused by either short-term (e.g., ``acute'') or
longer-term (e.g., ``chronic'') pesticide exposure and the effects of
pre-natal and post-natal exposure in animals.
EPA also considers whether the adverse effect has a threshold - a
level below which exposure has no appreciable chance of causing the
adverse effect. For non-threshold effects, EPA assumes that any
exposure to the substance increases the risk that the adverse effect
may occur. At present, EPA only considers one adverse effect, the
chronic effect of cancer, to potentially be a non-threshold effect.
(Ref. 4 at 8-9). Not all carcinogens, however, pose a risk at any
exposure level (i.e., ``a non-threshold effect or risk''). Advances in
the understanding of the mode of action of carcinogenesis have
increasingly led EPA to conclude that some pesticides that cause
carcinogenic effects in animal studies only cause such effects above a
certain threshold of exposure. EPA has traditionally considered non-
cancer adverse effects on the endocrine system to be threshold effects;
that determination is being reexamined in conjunction with the
endocrine disruptor screening program.
b. Level of concern/dose-response analysis. Once a pesticide's
potential hazards are identified, EPA determines a toxicological level
of concern for evaluating the risk posed by human exposure to the
pesticide. In this step of the risk assessment process, EPA essentially
evaluates the levels of exposure to the pesticide at which effects
might occur. An important aspect of this determination is assessing the
relationship between exposure (dose) and response (often referred to as
the dose-response analysis). EPA follows differing approaches to
identifying a level of concern for threshold and non-threshold hazards.
i. Threshold effects. In examining the dose-response relationship
for a pesticide's threshold effects, EPA evaluates an array of toxicity
studies on the pesticide. In each of these studies, EPA attempts to
identify the lowest observed adverse effect level (``LOAEL'') and the
next lower dose at which there are no observed adverse affect levels
(``NOAEL''). Generally, EPA will use the lowest NOAEL from the
available studies as a starting point (called ``the Point of
Departure'') in estimating the level of concern for humans. (Ref. 4 at
9 (The Point of Departure ``is simply the toxic dose that serves as the
`starting point' in extrapolating a risk to the human population.'')).
At times, however, EPA will use a LOAEL from a study as the Point of
Departure when no NOAEL is identified in that study and the LOAEL is
close to, or lower than, other relevant NOAELs. The Point of Departure
is in turn used in choosing a level of concern. EPA will make separate
determinations as to the Points of Departure, and correspondingly
levels of concern, for both short and long exposure periods as well as
for the different routes of exposure (oral, dermal, and inhalation).
In estimating and describing the level of concern, the Point of
Departure is at times used differently depending on whether the risk
assessment addresses dietary or non-dietary exposures. For dietary
risks, EPA uses the Point of Departure to calculate an acceptable level
of exposure or reference dose (``RfD''). The RfD is calculated by
dividing the Point of Departure by all applicable safety or uncertainty
factors. Typically, EPA uses a baseline safety/uncertainty factor equal
to 100. That value includes a factor of ten (``10X'') where EPA is
using data from laboratory animals to reflect potentially greater
sensitivity in humans than animals and a factor of 10X to account for
potential variations in sensitivity among members of the human
population as well as other unknowns. Additional safety factors may be
added to address data deficiencies or concerns raised by the existing
data. Under the FQPA, an additional safety factor of 10X is
presumptively applied to protect infants and children, unless reliable
data support selection of a different factor. This FQPA additional
safety factor largely replaces pre-FQPA EPA practice regarding
additional safety factors. (Ref. 5 at 4-11).
In implementing FFDCA section 408, EPA's Office of Pesticide
Programs, also calculates a variant of the RfD referred to as a
Population Adjusted Dose (``PAD''). A PAD is the RfD divided by any
portion of the FQPA safety factor that does not correspond to one of
the traditional additional safety factors used in general Agency risk
assessments. (Ref. 5 at 13-16). The reason for calculating PADs is so
that other parts of the Agency, which are not governed by FFDCA section
408, can, when evaluating the same or similar substances, easily
identify which aspects of a pesticide risk assessment are a function of
the particular statutory commands in FFDCA section 408. Today, RfDs and
PADs are generally calculated for both acute and chronic dietary risks
although traditionally a RfD or PAD was only calculated for chronic
dietary risks. Throughout this document general references to EPA's
calculated safe dose are denoted as a RfD/PAD.
For non-dietary, and combined dietary and non-dietary, risk
assessments of threshold effects, the toxicological level of concern is
not expressed as a RfD/PAD but rather in terms of an acceptable (or
``target'') margin of exposure (``MOE'') between human exposure and the
Point of Departure. The ``margin'' of interest is the ratio between
human exposure and the Point of Departure which is calculated by
dividing human exposure into the Point of Departure. An acceptable MOE
is generally considered to be a margin at least as high as the product
of all applicable safety factors for a pesticide. For example, if a
pesticide needs a 10X factor to account for inter-species differences,
10X factor for intra-species differences, and 10X factor for the FQPA
children's safety provision, the safe or target MOE would be a MOE of
at least 1,000. What that means is that for the pesticide to meet the
safety standard, human exposure to the pesticide would have to be at
least 1,000 times smaller than the Point of Departure. Like RfD/PADs,
specific target MOEs are selected for exposures of different durations.
For non-dietary exposures, EPA typically examines short-term,
intermediate-term, and long-term exposures. Additionally, target MOEs
may be selected based on both the duration of exposure and the various
routes of non-dietary exposure - dermal, inhalation, and oral.
ii. Non-threshold effects. For risk assessments for non-threshold
effects, EPA does not use the RfD/PAD or MOE approach to choose a level
of concern if quantification of the risk is deemed appropriate. Rather,
EPA calculates the slope of the dose-response curve for the non-
threshold effects from relevant studies using a linear, low-dose
extrapolation model that assumes that any amount of exposure will lead
to some degree of risk. This dose-response
[[Page 42687]]
analysis will be used in the risk characterization stage to estimate
the risk to humans of the non-threshold effect. Linear, low-dose
extrapolation is typically used as the default approach for estimating
the risk to carcinogens, unless there are mode of action data
indicating a threshold response (or nonlinearity).
c. Estimating human exposure. Risk is a function of both hazard and
exposure. Thus, equally important to the risk assessment process as
determining the hazards posed by a pesticide and the toxicological
level of concern for those hazards is estimating human exposure. Under
FFDCA section 408, EPA is concerned not only with exposure to pesticide
residues in food but also exposure resulting from pesticide
contamination of drinking water supplies and from use of pesticides in
the home or other non-occupational settings. (See 21 U.S.C.
346a(b)(2)(D)(vi)).
i. Exposure from food. There are two critical variables in
estimating exposure in food: (1) The types and amount of food that is
consumed; and (2) the residue level in that food. Consumption is
estimated by EPA based on scientific surveys of individuals' food
consumption in the United States conducted by the USDA. (Ref. 4 at 12).
Information on residue values comes from a range of sources including
crop field trials, data on pesticide reduction (or concentration) due
to processing, cooking, and other practices, information on the extent
of usage of the pesticide, and monitoring of the food supply. (Id. at
17).
In assessing exposure from pesticide residues in food, EPA, for
efficiency's sake, follows a tiered approach in which it, in the first
instance, assesses exposure using the worst case assumptions that 100
percent of the crop in question is treated with the pesticide and 100
percent of the food from that crop contains pesticide residues at the
tolerance level. (Id. at 11). When such an assessment shows no risks of
concern, a more complex risk assessment is unnecessary. By avoiding a
more complex risk assessment, EPA's resources are conserved and
regulated parties are spared the cost of any additional studies that
may be needed. If, however, a first tier assessment suggests there
could be a risk of concern, EPA then attempts to refine its exposure
assumptions to yield a more realistic picture of residue values through
use of data on the percent of the crop actually treated with the
pesticide and data on the level of residues that may be present on the
treated crop. These latter data are used to estimate what has been
traditionally referred to by EPA as ``anticipated residues.''
Use of percent crop treated data and anticipated residue
information is appropriate because EPA's worst-case assumptions of 100
percent treatment and residues at tolerance value significantly
overstate residue values. There are several reasons this is true.
First, all growers of a particular crop would rarely choose to apply
the same pesticide to that crop; generally, the proportion of the crop
treated with a particular pesticide is significantly below 100 percent.
(70 FR 46706, 46731 (August 10, 2005)). Second, the tolerance value
represents a high end or worst case value. Tolerance values are chosen
only after EPA has evaluated data from experimental crop field trials
in which the pesticide has been used in a manner, consistent with the
draft FIFRA label, that is likely to produce the highest residue in the
crop in question (e.g., maximum application rate, maximum number of
applications, minimum pre-harvest interval between last pesticide
application and harvest). (Refs. 4 and 6). These crop field trials are
generally conducted in several fields at several geographical
locations. (Id. at 5, 7 and Tables 1 and 5). Several samples are then
gathered from each field and analyzed. (Id. at 53). Generally, the
results from such field trials show that the residue levels for a given
pesticide use will vary from as low as non-detectable to measurable
values in the parts per million (``ppm'') range with the majority of
the values falling at the lower part of the range. (70 FR at 46731).
EPA uses a statistical procedure to analyze the field trial results and
identify the upper bound of expected residue values. This upper bound
value is used as the tolerance value. (Ref. 7). There may be some
commodities from a treated crop that approach the tolerance value where
the maximum label rates are followed, but most generally fall
significantly below the tolerance value. If less than the maximum legal
rate is applied, residues will be even lower. Third, residue values in
the field do not take into account the lowering of residue values that
frequently occurs as a result of degradation over time and through food
processing and cooking.
EPA uses several techniques to refine residue value estimates.
(Ref. 4 at 17-28). First, where appropriate, EPA will take into account
all the residue values reported in the crop field trials, either
through use of an average or individually. Second, EPA will consider
data showing what portion of the crop is not treated with the
pesticide. Third, data can be produced showing pesticide degradation
and decline over time, and the effect of commercial and consumer food
handling and processing practices. Finally, EPA can consult monitoring
data gathered by the FDA, the USDA, or pesticide registrants, on
pesticide levels in food at points in the food distribution chain
distant from the farm, including retail food establishments.
Another critical component of the exposure assessment is how data
on consumption patterns are combined with data on pesticide residue
levels in food. Traditionally, EPA has calculated exposure by simply
multiplying average consumption by average residue values for
estimating chronic risks and high-end consumption by maximum residue
values for estimating acute risks. Using average residues is a
realistic approach for chronic risk assessment due to the fact that
variations in residue levels and consumption amounts average out over
time. Using average values is inappropriate for acute risk assessments,
however, because in assessing acute exposure situations it matters how
much of each treated food a given consumer eats and what the residue
levels are in the particular foods consumed. Yet, using maximum residue
values for acute risk assessment tends to greatly overstate exposure
because it is unlikely that a person would consume at a single meal
multiple food components bearing high-end residues. To take into
account the variations in short-term consumption patterns and food
residue values for acute risk assessments, EPA has more recently begun
using probabilistic modeling techniques for estimating exposure when
more simplistic models appear to show risks of concerns.
All of these refinements to the exposure assessment process, from
use of food monitoring data through probabilistic modeling, can have
dramatic effects on the level of exposure predicted, reducing worst
case estimates by 1 or 2 orders of magnitude or more. (Ref. 8 at 16-17;
70 FR 46706, 46732 (August 10, 2005).
ii. Exposure from water. EPA may use either or both field
monitoring data and mathematical water exposure models to generate
pesticide exposure estimates in drinking water. Monitoring and modeling
are both important tools for estimating pesticide concentrations in
water and can provide different types of information. Monitoring data
can provide estimates of pesticide concentrations in water that are
representative of specific agricultural or residential pesticide
practices and under environmental conditions associated with a sampling
design. Although monitoring data can provide a
[[Page 42688]]
direct measure of the concentration of a pesticide in water, it does
not always provide a reliable estimate of exposure because sampling may
not occur in areas with the highest pesticide use, and/or the sampling
may not occur when the pesticides are being used.
In estimating pesticide exposure levels in drinking water, EPA most
frequently uses mathematical water exposure models. EPA's models are
based on extensive monitoring data and detailed information on soil
properties, crop characteristics, and weather patterns. (69 FR 30042,
30058-30065 (May 26, 2004)). These models calculate estimated
environmental concentrations of pesticides using laboratory data that
describe how fast the pesticide breaks down to other chemicals and how
it moves in the environment. These concentrations can be estimated
continuously over long periods of time, and for places that are of most
interest for any particular pesticide. Modeling is a useful tool for
characterizing vulnerable sites, and can be used to estimate peak
concentrations from infrequent, large storms.
iii. Residential exposures. Generally, in assessing residential
exposure to pesticides EPA relies on its Residential Standard Operating
Procedures (``SOPs''). (Ref. 9). The SOPs establish models for
estimating application and post-application exposures in a residential
setting where pesticide-specific monitoring data are not available.
SOPs have been developed for many common exposure scenarios including
pesticide treatment of lawns, garden plants, trees, swimming pools,
pets, and indoor surfaces including crack and crevice treatments. The
SOPs are based on existing monitoring and survey data including
information on activity patterns, particularly for children. Where
available, EPA relies on pesticide-specific data in estimating
residential exposures.
d. Risk characterization. The final step in the risk assessment is
risk characterization. In this step, EPA combines information from the
first three steps (hazard identification, level of concern/dose-
response analysis, and human exposure assessment) to quantitatively
estimate the risks posed by a pesticide. Separate characterizations of
risk are conducted for different durations of exposure. Additionally,
separate and, where appropriate, aggregate characterizations or risk
are conducted for the different routes of exposure (dietary and non-
dietary).
For threshold risks, EPA estimates risk in one of two ways. Where
EPA has calculated a RfD/PAD, risk is estimated by expressing human
exposure as a percentage of the RfD/PAD. Exposures lower than 100
percent of the RfD/PAD are generally not of concern. Alternatively, EPA
may express risk by comparing the MOE between estimated human exposure
and the Point of Departure with the acceptable or target MOE. As
described above, the acceptable or target MOE is the product of all
applicable safety factors. To calculate the actual MOE for a pesticide,
estimated human exposure to the pesticide is divided into the Point of
Departure. In contrast to the RfD/PAD approach, the higher the MOE, the
safer the pesticide. Accordingly, if the target MOE for a pesticide is
100, MOEs equal to or exceeding 100 would generally not be of concern.
As a conceptual matter, the RfD/PAD and MOE approaches are
fundamentally equivalent. For a given risk and given exposure of a
pesticide, if exposure to a pesticide were found to be acceptable under
an RfD/PAD analysis it would also pass under the MOE approach, and
vice-versa. However, for any specific pesticide, risk assessments for
different exposure durations or routes may yield different results.
This is a function not of the choice of the RfD/PAD or MOE approach but
of the fact that the levels of concern and the levels of exposure may
differ depending on the duration and route of exposure.
For non-threshold risks (generally, cancer risks), EPA uses the
slope of the dose-response curve for a pesticide in conjunction with an
estimation of human exposure to that pesticide to estimate the
probability of occurrence of additional adverse effects. For non-
threshold cancer risks, EPA generally considers cancer risk to be
negligible if the probability of increased cancer cases falls within
the range of 1 in 1 million. Risks exceeding values within that range
would raise a risk concern.
2. EPA policy on the children's safety factor. As the above brief
summary of EPA's risk assessment practice indicates, the use of safety
factors plays a critical role in the process. This is true for
traditional 10X safety factors to account for potential differences
between animals and humans when relying on studies in animals (inter-
species safety factor) and potential differences among humans (intra-
species safety factor) as well as the FQPA's additional 10X children's
safety factor.
In applying the children's safety factor provision, EPA has
interpreted it as imposing a presumption in favor of applying an
additional 10X safety factor. (Ref. 5 at 4, 11). Thus, EPA generally
refers to the additional 10X factor as a presumptive or default 10X
factor. EPA has also made clear, however, that this presumption or
default in favor of the additional 10X is only a presumption. The
presumption can be overcome if reliable data demonstrate that a
different factor is safe for children. (Id.). In determining whether a
different factor is safe for children, EPA focuses on the three factors
listed in section 408(b)(2)(C) - the completeness of the toxicity
database, the completeness of the exposure database, and potential pre-
and post-natal toxicity. In examining these factors, EPA strives to
make sure that its choice of a safety factor, based on a weight-of-the-
evidence evaluation, does not understate the risk to children. (Id. at
24-25, 35).
3. EPA policy on cholinesterase inhibition as a regulatory
endpoint. Cholinesterase inhibition is a disruption of the normal
process in the body by which the nervous system chemically communicates
with muscles and glands. Communication between nerve cells and a target
cell (i.e., another nerve cell, a muscle fiber, or a gland) is
facilitated by the chemical, acetylcholine. When a nerve cell is
stimulated it releases acetylcholine into the synapse (or space)
between the nerve cell and the target cell. The released acetylcholine
binds to receptors in the target cell, stimulating the target cell in
turn. As EPA has explained, ``the end result of the stimulation of
cholinergic pathway(s) includes, for example, the contraction of smooth
(e.g., in the gastrointestinal tract) or skeletal muscle, changes in
heart rate or glandular secretion (e.g., sweat glands) or communication
between nerve cells in the brain or in the autonomic ganglia of the
peripheral nervous system.'' (Ref. 10 at 10).
Acetylcholinesterase is an enzyme that breaks down acetylcholine
and terminates its stimulating action in the synapse between nerve
cells and target cells. When acetylcholinesterase is inhibited,
acetylcholine builds up prolonging the stimulation of the target cell.
This excessive stimulation potentially results in a broad range of
adverse effects on many bodily functions including muscle cramping or
paralysis, excessive glandular secretions, or effects on learning,
memory, or other behavioral parameters. Depending on the degree of
inhibition these effects can be serious, even fatal.
EPA's cholinesterase inhibition policy statement explains EPA's
approach to evaluating the risks posed by cholinesterase-inhibiting
pesticides such as DDVP. (Ref. 10). The policy focuses on three types
of effects associated with cholinesterase-
[[Page 42689]]
inhibiting pesticides that may be assessed in animal and human
toxicological studies: (1) Physiological and behavioral/functional
effects; (2) cholinesterase inhibition in the central and peripheral
nervous system; and (3) cholinesterase inhibition in red blood cells
and blood plasma. The policy discusses how such data should be
integrated in deriving an acceptable dose (RfD/PAD) for a
cholinesterase-inhibiting pesticide.
Clinical signs or symptoms of cholinesterase inhibition in humans,
the policy concludes, provide the most direct evidence of the adverse
consequences of exposure to cholinesterase-inhibiting pesticides.
Nonetheless, as the policy notes, due to strict ethical limitations,
studies in humans are ``quite limited.'' (Id. at 19). Although animal
studies can also provide direct evidence of cholinesterase inhibition
effects, animal studies cannot easily measure cognitive effects of
cholinesterase inhibition such as effects on perception, learning, and
memory. For these reasons, the policy recommends that ``functional data
obtained from human and animal studies should not be relied on solely,
to the exclusion of other kinds of pertinent information, when weighing
the evidence for selection of the critical effect(s) that will be used
as the basis of the RfD or RfC.'' (Id. at 20).
After clinical signs or symptoms, cholinesterase inhibition in the
nervous system provides the next most important endpoint for evaluating
cholinesterase-inhibiting pesticides. Although cholinesterase
inhibition in the nervous system is not itself regarded as a direct
adverse effect, it is ``generally accepted as a key component of the
mechanism of toxicity leading to adverse cholinergic effects.'' (Id. at
25). As such, the policy states that it should be treated as ``direct
evidence of potential adverse effects'' and ``data showing this
response provide valuable information in assessing potential hazards
posed by anticholinesterase pesticides.'' (Id.). Unfortunately, useful
data measuring cholinesterase inhibition in the central and peripheral
nervous systems has only been relatively rarely captured by standard
toxicology testing, particularly as to peripheral nervous system
effects. For central nervous system effects, however, more recent
neurotoxicity studies ``have sought to characterize the time course of
inhibition in ... [the] brain, including brain regions, after acute and
90-day exposures.'' (Id. at 27).
Cholinesterase inhibition in the blood is one step further removed
from the direct harmful consequences of cholinesterase-inhibiting
pesticides. According to the policy, inhibition of blood
cholinesterases ``is not an adverse effect, but may indicate a
potential for adverse effects on the nervous system.'' (Id. at 28). The
policy states that ``[a]s a matter of science policy, blood
cholinesterase data are considered appropriate surrogate measures of
potential effects on peripheral nervous system acetylcholinesterase
activity in animals, for central nervous system (``CNS'')
acetylcholinesterase activity in animals when CNS data are lacking and
for both peripheral and central nervous system acetylcholinesterase in
humans.'' (Id. at 29). The policy notes that ``there is often a direct
relationship between a greater magnitude of exposure [to a
cholinesterase-inhibiting pesticide] and an increase in incidence and
severity of clinical signs and symptoms as well as blood cholinesterase
inhibition.'' (Id. at 30). Thus, the policy regards blood
cholinesterase data as ``appropriate endpoints for derivation of
reference doses or concentrations when considered in a weight-of-the-
evidence analysis of the entire database ....'' (Id. at 29). Between
cholinesterase inhibition measured in red blood cell (``RBC'') or blood
plasma, the policy states a preference for reliance on RBC
acetylcholinesterase measurements because plasma is composed of a
mixture of acetylcholinesterase and butyrylcholinesterase, and
inhibition of the latter is less clearly tied to inhibition of
acetylcholinesterase in the nervous system. (Id. at 29, 32).
If a measure of cholinesterase inhibition (e.g., RBC
cholinesterase) is being considered as a potential adverse effect or
surrogate for an adverse effect, the policy advises that the level of
inhibition must be critically evaluated ``in the context of both
statistical and biological significance.'' (Id. at 37) (emphasis in
Original). The policy notes that ``[n]o fixed percentage of change
(e.g., 20% for cholinesterase enzyme inhibition) is predetermined to
separate adverse from non-adverse effects.'' (Id.). Rather, the policy
explains that ``OPP's experience with the review of toxicity studies
with cholinesterase-inhibiting substances shows that differences
between pre- and post-exposure of 20% or more in enzyme levels is
nearly always statistically significant and would generally be viewed
as biologically significant.'' (Id. at 37-38). The policy recommends
that ``[t]he biological significance of statistically-significant
changes of less than 20% would have to be judged on a case-by-case
basis, noting, in particular the pattern of changes in the enzyme
levels and the presence or absence of accompanying clinical signs and/
or symptoms.'' (Id. at 38). The policy notes that similar or higher
levels of cholinesterase inhibition are used ``in monitoring workers
for occupational exposures (even in the absence of signs, symptoms, or
other behavioral effects).'' (Id. at 31). For example, the policy
points out that the California Department of Health Services requires
that workers exposed to toxic chemicals such as organophosphate
pesticides be removed from the workplace if ``red blood cell
cholinesterase levels show 30% or greater inhibition,'' and that the
World Health Organization ``has guidelines with the same RBC action
levels (i.e., 30% or greater inhibition).'' (Id.).
C. Endocrine Disruptor Screening Program
The 1996 FQPA and SWDA amendments directed EPA to develop and
implement an endocrine screening program. To aid in the design of this
program called for in the FQPA and SDWA amendments, EPA created the
Endocrine Disruptor Screening and Testing Advisory Committee
(``EDSTAC''), which was comprised of members representing the
commercial chemical and pesticides industries, federal and state
agencies, worker protection and labor organizations, environmental and
public health groups, and research scientists. (63 FR 71542, 71544,
Dec. 28, 1998). The EDSTAC presented a comprehensive report in August
1998 addressing both the scope and elements of the endocrine screening
program. (Ref. 11). The EDSTAC's recommendations were largely adopted
by EPA.
As recommended by EDSTAC, EPA expanded the scope of the program
from focusing only on estrogenic effects to include other effects on
the endocrine system (i.e., androgenic and thyroid effects). (63 FR at
71545). Further, EPA, again on the EDSTAC's recommendation, chose to
include both human and ecological effects in the program. (Id.).
Finally, based on EDSTAC's recommendation, EPA established the universe
of chemicals to be screened to include not just pesticides but also a
wide range of other chemical substances. (Id.). As to the program
elements, EPA adopted EDSTAC's recommended two-tier approach with the
first tier involving screening ``to identify substances that have the
potential to interact with the endocrine system'' and the second tier
involving testing ``to determine whether the substance causes adverse
effects,
[[Page 42690]]
identify the adverse effects caused by the substance, and establish a
quantitative relationship between the dose and the adverse effect.''
(Id.). Tier 1 screening is limited to evaluating whether a substance is
``capable of interacting with'' the endocrine system, and is ``not
sufficient to determine whether a chemical substance may have an effect
in humans that is similar to an effect produced by naturally occurring
hormones.'' (Id. at 71550). Based on the results of Tier 1 screening,
EPA will decide whether Tier 2 testing is needed. Importantly, ``[t]he
outcome of Tier 2 is designed to be conclusive in relation to the
outcome of Tier 1 and any other prior information. Thus, a negative
outcome in Tier 2 will supersede a positive outcome in Tier 1.'' (Id.
at 71554-71555).
The EDSTAC provided detailed recommendations for Tier 1 screening
and Tier 2 testing. The panel of the EDSTAC that devised these
recommendations was comprised of distinguished scientists from
academia, government, industry, and the environmental community. (Ref.
11 at Appendix B). As suggested by the EDSTAC, EPA has proposed a
battery of short-term in vitro and in vivo assays for the Tier 1
screening exercise. (63 FR at 71550-71551). Validation of all but one
of these assays is complete. As to Tier 2 testing, EPA, on the
recommendation of the EDSTAC, has proposed using five longer-term
reproduction studies that, with one exception, ``are routinely
performed for pesticides with widespread outdoor exposures that are
expected to affect reproduction.'' (Id. at 71555). EPA is examining,
pursuant to the suggestion of the EDSTAC, modifications to these
studies to enhance their ability to detect endocrine effects.
EPA has published a draft list of the first group of chemicals that
will be tested under the Agency's endocrine disruptor screening
program. (72 FR 33486 (June 18, 2007)). The draft list was produced
based solely on the exposure potential of the chemicals and EPA has
emphasized that ``[n]othing in the approach for generating the initial
list provides a basis to infer that by simply being on this list these
chemicals are suspected to interfere with the endocrine systems of
humans or other species, and it would be inappropriate to do so.''
(Id.)
D. EPA's Human Research Rule
EPA decisions regarding the ethics of human studies are governed by
the Protection for Subjects in Human Research final rule (``Human
Research rule''), which significantly strengthened and expanded
protections for subjects of human research. (71 FR 6138 (February 6,
2006)). The framework of the Human Research rule rests on the basic
principle that EPA will not, in its actions, rely on data derived from
unethical research. The rule divides studies involving intentional
dosing of human subjects into two groups: ``new'' studies - those
initiated after April 7, 2006 (the effective date of the rule) - and
``old'' studies - those initiated before April 7, 2006. The Human
Research Rule forbids EPA from relying on data from any ``new'' study,
unless EPA has adequate information to determine that the research was
conducted in substantial compliance with the ethical requirements
contained therein. (40 CFR. 26.1705). These ethical rules are derived
primarily from the ``Common Rule,'' (40 CFR part 26), a rule setting
ethical parameters for studies conducted or supported by the federal
government. In addition to requiring informed consent and protection of
the safety of the subjects, among other things, the rule specifies that
``[r]isks to subjects [must be] reasonable in relation to . . . the
importance of the knowledge that may reasonably be expected to result
[from the study].'' (40 CFR 26.1111(a)(2)). In other words, a study
would be judged unethical if it did not have scientific value
outweighing any risks to the test subjects.
As to ``old'' studies, the Human Research Rule forbids EPA from
relying on such data if there is clear and convincing evidence that the
conduct of the research was fundamentally unethical or significantly
deficient with respect to the ethical standards prevailing at the time
the research was conducted. (40 CFR 26.1704). EPA has indicated that in
evaluating ``the ethical standards prevailing at the time the research
was conducted'' it will consider the Nuremburg Code, various editions
of the Declaration of Helsinki, the Belmont Report, and the Common
Rule, as among the standards that may be applicable to any particular
study. (71 FR at 6161). Further, reflecting the concern that
scientifically invalid data are ``always unethical,'' (71 FR at 6160),
the rule limits the human research that can be relied upon by EPA to
``scientifically valid and relevant data.'' (40 CFR 26.1701).
Whether the data are ``new'' or ``old,'' the Human Research rule
forbids EPA from relying on data from any study involving intentional
exposure of pregnant women, fetuses, or children subject to a very
limited exception. (40 CFR 26.1703, 1706).
To aid EPA in making scientific and ethical determinations under
the Human Research rule, the rule established an independent Human
Studies Review Board (``HSRB'') to review both proposals for new
research (``new'' studies) and reports of completed human research
(``old'' studies) on which EPA proposes to rely. (40 CFR 26.1603). The
rule directs that HSRB shall be comprised of non-EPA employees ``who
have expertise in fields appropriate for the scientific and ethical
review of human research, including research ethics, biostatistics, and
human toxicology.'' (40 CFR 26.1603(a)). If EPA decides to rely on the
results from ``old'' research conducted to identify or measure a toxic
effect, EPA must submit the results of its assessment to the HSRB for
evaluation of the ethical and scientific merit of the research. (40 CFR
26.1602(b)(2)).
EPA has established the HSRB as a federal advisory committee under
the Federal Advisory Committee Act (``FACA'') to take advantage of
``the benefits of the transparency and opportunities for public
participation'' that accompany a FACA committee. (71 FR at 6156). The
HSRB, as appointed by EPA, contains approximately 16 distinguished
experts in the fields of bioethics, biostatistics, human health risk
assessment and human toxicology, primarily from academia. (Ref. 12).
NRDC and other parties have challenged the legality of the Human
Research rule. (NRDC v. U.S. EPA, No. 06-0820-ag (2d Cir.)). A decision
on this challenge is presently pending before the United States Court
of Appeals for the Second Circuit.
IV. Regulatory History of DDVP
A. In General
1. DDVP use. Dichlorvos (2, 2-dichlorovinyl dimethyl phosphate),
also known as DDVP, is an insecticide used in controlling flies,
mosquitoes, gnats, cockroaches, fleas, and other insect pests. (Ref.
3). DDVP is registered for use on agricultural sites; commercial,
institutional, and industrial sites; and for domestic use in and around
homes. Agricultural and other commercial uses include in greenhouses;
mushroom houses; storage areas for bulk, packaged and bagged raw and
processed agricultural commodities; food manufacturing/processing
plants; animal premises; and non-food areas of food-handling
establishments. It is also registered for treatment of cattle, poultry
and swine. DDVP is not registered for direct use on any field grown
commodities. Currently, there are 27 tolerances listed in 40 CFR
180.235 for DDVP on agricultural (food and feed) crops and animal
commodities. DDVP is
[[Page 42691]]
applied with aerosols, fogging equipment, and spray equipment, and
through use of impregnated materials such as resin strips which result
in slow release of the pesticide. The current registrant for the
technical active ingredient, DDVP, is Amvac Chemical Corporation
(``Amvac'').
2. DDVP risks. The following information on the assessment of the
risks posed by DDVP is drawn from EPA's decision on the reassessment of
DDVP tolerances and its response to NRDC's petition.
DDVP is a chlorinated organophosphate pesticide which inhibits
plasma, RBC, and brain cholinesterase in a variety of species. (Ref. 3
at 122-123). Subchronic and chronic oral DDVP exposures to rats and
dogs as well as chronic inhalation DDVP exposure to rats resulted in
significant decreases in plasma, RBC and/or brain cholinesterase
activity. However, DDVP does not cause delayed neurotoxicity in the
hen. Repeated, oral subchronic DDVP exposures in male humans were
associated with statistically and biologically significant decreases in
RBC cholinesterase inhibition. There was no evidence of increased
susceptibility to young animals following in utero DDVP exposure to rat
and rabbit fetuses as well as pre/post natal DDVP exposure to rats in
developmental, reproduction, and comparative cholinesterase studies.
Evidence of sensitivity in the young was seen in one parameter,
auditory startle amplitude, in a developmental neurotoxicity study;
however, the effects in the rat pups here was at levels well above
levels which result in RBC cholinesterase inhibition. Cancer studies
with DDVP provide suggestive evidence of DDVP's potential human
carcinogenicity; however, following the advice of numerous independent
scientific panels, EPA has determined that DDVP poses a negligible
cancer risk to humans due to the lack of relevance to humans of the
tumors identified in the DDVP cancer studies. (72 FR at 68671-68673).
Inhibition of cholinesterase activity was the toxicity endpoint
selected to assess hazards for all acute and chronic dietary exposures,
as well as short-, intermediate-, and long-term (chronic) dermal,
inhalation, and incidental oral residential exposures. Doses selected
for the Point of Departure in determining the level of concern - i.e.,
RfD/PADs and acceptable MOEs - were based on both human and animal
studies. (Ref. 3 at 130-135). Animal studies were used in choosing
levels of concern for evaluating risk from acute and chronic dietary
exposure; acute dermal exposure; and acute and chronic inhalation
exposure. A human study was used evaluating risk from short-term
incidental oral exposure; short-, intermediate-, and long-term dermal
exposure; and short- and intermediate-term inhalation exposure.
Safety factor determinations used in selecting the level of concern
differed based on whether EPA relied on one of several different animal
studies or a human study. For levels of concerns derived from a Point
of Departure from an animal study, EPA generally applied a 100X safety
factor (10X for inter-species variability and 10X for intra-human
variability). EPA removed the 10X children's safety factor for risk
assessments based on an animal study. For levels of concerns derived
from a Point of Departure from the human study, EPA applied a 10X
safety factor for intra-human variability and a 3X children's safety
factor. (Id.).
EPA based its decision to remove the children's safety factor when
relying on animal data on its conclusions that (1) the toxicity
database was complete; (2) most of the data indicated no sensitivity in
the young and the only evidence of sensitivity occurred at levels well
above the Points of Departure used for establishing the levels of
concern; and (3) its estimate of human exposure to DDVP was not
understated. EPA retained a portion of the children's safety factor
when relying on the human study because that study did not determine a
NOAEL. EPA concluded, however, that reliable data supported reduction
of the 10X factor because the effect seen at the LOAEL in that study
was so marginal that a lower dose would have been unlikely to detect
any adverse effect. (72 FR 68694-68695).
EPA has estimated exposure to DDVP taking into account the
potential for DDVP residues in food, drinking water, and in the home as
the result of the use of DDVP pest strips. DDVP exposure may result not
only from use of DDVP but use of two closely-related pesticides, naled
and trichlorfon, which metabolize or degrade to DDVP in food, water, or
the environment. In assessing the risks of DDVP, EPA has taken into
account exposure to DDVP resulting from use of all three of these
pesticides. (Ref. 3 at 147-149). Additionally, DDVP, naled, and
trichlorfon are within a family of pesticides known as the
organophosphates. EPA has classified the organophosphate pesticides and
their common cholinesterase-inhibiting degradates as having a common
mechanism of toxicity. Thus, in addition to assessing the risks posed
by exposure to organophosphate pesticides individually, EPA has
assessed the potential cumulative effects from concurrent exposure to
organophosphate pesticides. (Ref. 13).
As discussed in Unit IV.B.1. below, taking all of the above
information into account, EPA concluded that the tolerances for DDVP
were safe.
B. FFDCA Tolerance Reassessment and FIFRA Pesticide Reregistration
1. In general. As required by the FQPA of 1996, EPA reassessed the
safety of the DDVP tolerances under the new safety standard established
in the FQPA. EPA released for comment a preliminary risk assessment for
DDVP in October, 2000. (65 FR 60430 (October 11, 2000)). Subsequently,
after consideration of public comment, EPA, on June 30, 2006, issued an
Interim Reregistration Eligibility Document (``IRED'') for DDVP. In
that document, EPA determined that aggregate exposure to DDVP as a
result of use of DDVP, naled, and trichlorfon, complied with the FQPA
safety standard. (Ref. 3 ). Separately, on July 31, 2006, EPA
determined that cumulative ffects from exposure to all organophosphate
residues were safe. (Ref. 14). In combination, these findings satisfied
EPA's obligation to review the DDVP tolerances under the new safety
standard.
As a result of the FIFRA reregistration and FFDCA tolerance
reassessment process there were numerous changes made to DDVP's
registration that affect non-occupational exposure to DDVP.
Specifically, on May 9, 2006, EPA received from Amvac, the only
registrant of DDVP as a product for manufacturing end-use DDVP
products, an irrevocable request to cancel certain uses and include
additional pest strip label restrictions on the DDVP active ingredient
product labels. Pursuant to section 6(f) of FIFRA, on June 30, 2006,
the Agency published a notice in the Federal Register that it had
received the request and sought comment on EPA's intention to grant the
request and cancel the specified uses. (71 FR 37570 (June 30, 2006)).
On October 20, 2006, EPA issued the final cancellation order. (71 FR
61968 (October 20, 2006)).
The added restrictions on the use of the pest strip products were
approved on October 11, 2006, and provided, among other things, that
large pest strips could no longer be used in homes except for garages,
attics, crawl spaces, and sheds that are occupied for less than 4 hours
per day. The only pest strips permitted for use in occupied areas
inside the home were significantly smaller strips for use in closets,
wardrobes, or cupboards. Additionally, in early March, 2007, Amvac
requested the voluntary cancellation of all its pet
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collar and bait registrations and deletion of those uses from its
technical label. Pursuant to section 6(f) of FIFRA, Amvac's requests to
cancel the pet collar and bait registrations as well as deleting such
uses from the technical label were published in the Federal Register on
March 23, 2007. (72 FR 13786 (March 23, 2007)). On June 27, 2007, EPA
issued the final cancellation notice for the pet collar and bait
registrations. (72 FR 35235 (June 27, 2007)).
Cancellation of uses and label restrictions imposed on Amvac's
registration apply to all formulated DDVP end-use products because it
is unlawful to use a pesticide in a manner inconsistent with its label.
(7 U.S.C. 136(ee)). This bar on use inconsistent with the label applies
to the formulation of end-use pesticide products from manufacturing use
products. Accordingly, because Amvac holds the only registration for a
DDVP manufacturing use product, the removal of uses and the addition of
restrictions with respect to Amvac's manufacturing use product label
has the effect of imposing those use cancellations and label
restrictions on all DDVP end-use products.
2. Review of human study. Completion of the DDVP IRED was delayed,
in part, by questions regarding whether it was appropriate for EPA to
rely on several human toxicity studies conducted with DDVP which were
submitted by Amvac. The study receiving principal attention was a study
involving repeated dosing over several days conducted in 1997 by A.J.
Gledhill. (Refs. 3 at 133; and 15). That study is identified by the
Master Record Identification (``MRID'') number of 44248801. Amvac also
cited approximately a dozen other human studies, several of which were
also conducted by Gledhill. (Ref. 16).
Following promulgation of the Human Research rule, EPA evaluated
whether the human data submitted by Amvac complied with the rule, and,
pursuant to the rule's requirements, presented these data and its
recommendations to the Human Studies Review Board (``HSRB'') for
review. On March 9, 2006, the HSRB published a notice in the Federal
Register announcing that a public meeting would be held to consider the
DDVP studies as well as human studies for several other pesticides. (71
FR 12194 (March 9, 2006)). The meeting was scheduled for April 4-6,
2006. The notice alerted the public of the opportunity to file both
written comments with the HSRB and to make oral comments at the April
meeting. The members of the HSRB at the time of this meeting are listed
in Appendix 1.
NRDC filed written comments with the HSRB concerning DDVP, (Ref.
17), and also presented oral testimony at the public meeting. (Ref.
18). NRDC's comments and oral remarks specifically focused on whether
the Gledhill study had sufficient statistical power ``to detect an
effect when it may occur'' and the fact that the Gledhill study only
used healthy, male test subjects. (Ref. 7 at 13). Other subjects
discussed at the meeting included the relative strengths and weaknesses
of the Gledhill study such as its repeat dosing regime, the failure to
test blood plasma cholinesterase, the failure to monitor subjects after
testing, and the study's consent form. (Id.; Ref. 18 at 18, 20-23). On
May 23, 2006, the HSRB published a notice in the Federal Register
alerting the public that it had released a draft report (dated May 16,
2006) and would be holding a public teleconference meeting on June 6,
2006 to discuss its draft report. (71 FR 29624 (May 23, 2006)). The
notice included instructions on how members of the public could
participate in the teleconference and explained the procedure for
providing oral and written comments. (Ref. 19). NRDC did not file
comments on the draft report. (Ref. 20).
On June 26, 2006, the HSRB issued its finding that reliance on the
Gledhill human study was appropriate given that the study had
scientific value and there was no clear and convincing evidence that
the study was fundamentally unethical. (Ref. 21). The HSRB concluded
that the other DDVP human studies should not be used in the DDVP risk
assessment. These findings were unchanged from its May 16, 2006 draft
report.
EPA agreed with the findings of the HSRB and relied upon the HSRB's
reasoning in using the Gledhill study in its DDVP risk assessment. (72
FR at 68675).
V. NRDC Petition Regarding DDVP
On June 2, 2006, the NRDC filed a petition with EPA which, among
other things, requested that EPA: (1) Conclude the DDVP Special Review
by August 3, 2006, with a finding that DDVP causes unreasonable adverse
effects on the environment; (2) conclude the DDVP FIFRA reregistration
process by August 3, 2006, with a finding that DDVP is not eligible for
reregistration; (3) submit draft notices of intent to cancel all DDVP
registrations to the FIFRA Scientific Advisory Panel and USDA by August
3, 2006, and issue those notices 60 days thereafter; (4) conclude the
DDVP tolerance reassessment process by August 3, 2006, with a finding
that the DDVP tolerances do not meet the FFDCA safety standard; and (5)
issue a final rule by August 3, 2006, revoking all DDVP tolerances.
(Ref. 2). Shortly after the petition was filed, on June 30, 2006, EPA
released the IRED for DDVP which addressed DDVP's eligibility for
reregistration under FIFRA and assessed, in part, whether DDVP's
tolerances met the new safety standard enacted by the FQPA. NRDC
submitted comments on the IRED and some of these comments bore on
issues in its petition. (Ref. 3).
NRDC's petition contained dozens of claims as to why DDVP's
registration under FIFRA should be canceled and its FFDCA tolerances
revoked. These issues are not presented in detail here because many
raised solely FIFRA concerns and NRDC has not pursued most of its
tolerance-related claims in its objections and hearing requests.
EPA published notice of the petition for comment on October 11,
2006. (71 FR 59784 (October 11, 2006)). EPA received roughly 1,500
brief comments in support of the petition. These comments added no new
information pertaining to whether the tolerances were in compliance
with the FFDCA. Detailed comments in opposition to the petition were
submitted by Amvac. (Ref. 22).
EPA responded to the petition in three separate documents: (1) It
issued an order closing out the DDVP Special Review; (72 FR 72709
(December 21, 2007)); (2) it issued an order denying the request to
cancel DDVP's FIFRA registration (72 FR 68581(December 5, 2007)); and
(3) it issued an order pursuant to FFDCA section 408(d)(4)(iii) denying
the request to revoke DDVP's FFDCA tolerances (78 FR 68662 (December 5,
2007). Today's final order only concerns the objections filed to the
section 408(d)(4)(iii) order denying the request to revoke tolerances.
VI. EPA Response to the Petition to Revoke DDVP Tolerances
EPA issued a section 408(d)(4)(iii) order responding to the
petition's request to revoke DDVP tolerances on December 5, 2007
(hereinafter referred to as EPA's ``petition response'' or ``petition
denial order''). (72 FR 68662 (December 5, 2005). That order denied the
petition finding that none of the grounds asserted by NRDC demonstrated
that the DDVP tolerances should be revoked. Nonetheless, EPA did
conclude that NRDC raised several pertinent concerns with EPA's
assessment of the risks posed by DDVP.
To respond to NRDC's concerns, EPA completely revamped both its
dietary
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and residential risk assessments. In its new risk assessments, EPA
included updated information on residue levels of DDVP in food, the
amount of usage of DDVP and related pesticides in agriculture, and food
consumption patterns of infants and children. EPA also adopted modified
and more conservative assumptions regarding exposure patterns to DDVP
in residential settings and exposure to DDVP from naled's use to
control mosquitoes. Because, however, EPA concluded that the revised
risk assessments still showed that the DDVP tolerances are safe, EPA
denied NRDC's petition.
EPA's specific responses to the claims in the petition that are
relevant to NRDC's objections are summarized in the portion of this
order responding to the objections and hearing requests.
VII. NRDC's Objections and Requests for Hearing
On February 1, 2008, NRDC filed, pursuant to FFDCA section
408(g)(2), objections to EPA's denial of its tolerance revocation
petition and requested a hearing on those objections. As indicated
above, NRDC's objections and requests for hearing raise two main
claims: (1) that EPA has unlawfully failed to retain the full 10X
safety factor for the protection of infants and children; and (2) that
it was unlawful for EPA to rely on a toxicity study for DDVP that was
conducted with humans.
NRDC cites three grounds for its assertion that EPA unlawfully
lowered the 10X children's safety factor: (1) that EPA lacked adequate
data on DDVP's potential effects on the endocrine system; (2) that EPA
lacked adequate data on several matters related to assessing dietary
exposure to DDVP residues in food; and (3) that EPA has inadequate data
on exposure to DDVP from its use in residential pest strips. As to the
DDVP human study, NRDC claimed that EPA's regulation concerning use of
human studies is unlawful and that the study is scientifically flawed
and ethically compromised. In analyzing NRDC's claims, EPA has broken
NRDC's two main claims down into 19 separate sub-issues. Each sub-issue
is described in detail and responded to separately in Unit VIII.
In support of its request for hearing, NRDC proffered the following
documents as evidence that a hearing would be appropriate:
(1) the Interim Reregistration Eligibility Determination for
DDVP; (2) the entire record for the IRED and the documents
referenced and cited therein; (3) NRDC's comments on the IRED; (4)
EPA's petition denial and the references cited in that denial; (5)
NRDC's petition and all references cited in the petition; and (6)
the arguments, citations, and attachments contained in these
objections.
(Ref. 1 at 3) (citations and references to attachments omitted).
VIII. Response to Objections and Requests for Hearing
A. Overview
EPA denies each of NRDC's objections as well as its hearing
requests. NRDC's hearing requests fail to meet the statutory and
regulatory requirements for holding a hearing. NRDC has failed to
proffer evidence on its hearing requests which would, if established,
resolve one or more issues in its favor. Rather, NRDC relies on mere
allegations and general denials and contentions. Further, many of
NRDC's claims do not present genuine and substantial issues of fact
and/or are immaterial to the relief requested. On the merits, NRDC's
objections are denied for substantially the same reasons given in EPA's
petition denial order. NRDC's objections largely restate the claims in
its petition. Significantly, NRDC does not acknowledge or respond to
the substantial revisions to the DDVP dietary and residential risk
assessments made in response to the NRDC petition. Similarly, NRDC does
not acknowledge or respond to EPA's detailed summary of why it adopted
the conclusion by the independent HSRB that the Gledhill human study
complied with EPA's Human Research rule.
The remainder of this Unit is organized in the following manner.
Unit VIII.B. describes in greater detail the requirements pertaining to
when it is appropriate to grant a hearing request. Unit VIII.C.
examines the evidence proffered by NRDC in support of its hearing
requests. Units VIII.D. and E. provide EPA's response to the NRDC's
objections and hearing requests. Unit VIII.D. addresses NRDC's claims
regarding the children's safety factor and subunit E addresses NRDC's
arguments concerning reliance on the Gledhill human study. EPA's
conclusions on the hearing requests and objections are summarized in
Units VIII.F. and G., respectively.
EPA has adopted a 4-part format in Units VIII.D. and E. for
explaining its ruling on each of the 19 sub-issues EPA identified in
the objections. First, NRDC's claim and any arguments or evidence
tendered to support that claim are described. Second, background
information on the claim is provided including whether and how the
claim was presented in NRDC's petition and, if it was presented, EPA's
reasons for denying the claim in its earlier petition denial order.
Third, EPA explains its reasons for denying a hearing on that claim.
Finally, EPA explains its reasons for denying the claim on the merits.
B. The Standard for Granting an Evidentiary Hearing
EPA has established regulations governing objections to tolerance
rulemakings and tolerance petition denials and requests for hearings on
those objections. (40 CFR Part 178; 55 FR 50291 (December 5, 1990)).
Those regulations prescribe both the form and content of hearing
requests and the standard under which EPA is to evaluate requests for
an evidentiary hearing.
As to the form and content of a hearing request, the regulations
specify that a hearing request must include: (1) a statement of the
factual issues on which a hearing is requested and the requestor's
contentions on those issues; (2) a copy of any report, article, or
other written document ``upon which the objector relies to justify an
evidentiary hearing;'' and (3) a summary of any other evidence relied
upon to justify a hearing. (40 CFR 178.27).
The standard for granting a hearing request is set forth in section
178.32. That section provides that a hearing will be granted if EPA
determines that the ``material submitted'' shows all of the following:
(1) There is a genuine and substantial issue of fact for resolution
at a hearing. An evidentiary hearing will not be granted on issues
of policy or law.
(2) There is a reasonable possibility that available evidence
identified by the requestor would, if established, resolve one or
more of such issues in favor of the requestor, taking into account
uncontested claims or facts to the contrary. An evidentiary hearing
will not be granted on the basis of mere allegations, denials, or
general descriptions of positions and contentions, nor if the
Administrator concludes that the data and information submitted,
even if accurate, would be insufficient to justify the factual
determination urged.
(3) Resolution of the factual issue(s) in the manner sought by the
person requesting the hearing would be adequate to justify the
action requested. An evidentiary hearing will not be granted on
factual issues that are not determinative with respect to the action
requested. For example, a hearing will not be granted if the
Administrator concludes that the action would be the same even if
the factual issue were resolved in the manner sought.
(40 CFR 178.32(b)).
This provision essentially imposes four requirements upon a hearing
requestor. First, the requestor must show it is raising a question of
fact, not
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one of law or policy. Hearings are for resolving factual issues not for
debating law or policy questions. Second, the requestor must
demonstrate that there is a genuine dispute as to the issue of fact. If
the facts are undisputed or the record is clear that no genuine dispute
exists, there is no need for a hearing. Third, the requestor must show
that the disputed factual question is material - i.e., that it is
outcome determinative with regard to the relief requested in the
objections. Finally, the requestor must make a sufficient evidentiary
proffer to demonstrate that there is a reasonable possibility that the
issue could be resolved in favor of the requestor. Hearings are for the
purpose of providing objectors with an opportunity to present evidence
supporting their objections; as the regulation states, hearings will
not be granted on the basis of ``mere allegations, denials, or general
descriptions of positions or contentions.'' (40 CFR 178.32(b)(2)).
EPA's hearing request requirements are based heavily on FDA
regulations establishing similar requirements for hearing requests
filed under other provisions of the FFDCA. (53 FR 41126, 41129 (October
19, 1988)). FDA pioneered the use of summary judgment-type procedures
to limit hearings to disputed material factual issues and thereby
conserve agency resources. FDA's use of such procedures was upheld by
the Supreme Court in 1972, (Weinberger v. Hynson, Westcott & Dunning,
Inc., 412 U.S. 609 (1973)), and, in 1975, FDA promulgated generic
regulations establishing the standard for evaluating hearing requests.
(40 FR 22950 (May 27, 1975)). It is these regulations upon which EPA
relied in promulgating its hearing regulations in 1990.
Unlike EPA, FDA has had numerous occasions to apply its regulations
on hearing requests. FDA's summary of the thrust of its regulations,
which has been repeatedly published in the Federal Register in orders
ruling on hearing requests over the last 24 years, is instructive on
the proper interpretation of the regulatory requirements. That summary
states:
A party seeking a hearing is required to meet a `threshold
burden of tendering evidence suggesting the need for a hearing.' []
An allegation that a hearing is necessary to `sharpen the issues' or
`fully develop the facts' does not meet this test. If a hearing
request fails to identify any evidence that would be the subject of
a hearing, there is no point in holding one.
A hearing request must not only contain evidence, but that
evidence should raise a material issue of fact concerning which a
meaningful hearing might be held. [] FDA need not grant a hearing in
each case where an objection submits additional information or
posits a novel interpretation of existing information. [] Stated
another way, a hearing is justified only if the objections are made
in good faith and if they ``draw in question in a material way the
underpinnings of the regulation at issue.'' Finally, courts have
uniformly recognized that a hearing need not be held to resolve
questions of law or policy.
(49 FR 6672, 6673 (February 22, 1984); 72 FR 39557, 39558 (July 19,
2007) (citations omitted)). EPA has been guided by FDA's application of
its regulations in this proceeding.
Congress confirmed EPA's authority to use summary judgment-type
procedures with hearing requests when it amended FFDCA section 408 in
1996. Although the statute had been silent on this issue previously,
the FQPA added language specifying that when a hearing is requested,
EPA ``shall . . . hold a public evidentiary hearing if and to the
extent the Administrator determines that such a public hearing is
necessary to receive factual evidence relevant to material issues of
fact raised by the objections.'' (21 U.S.C. 346a(g)(2)(B)). This
language grants EPA broad discretion to determine whether a hearing is
``necessary to receive factual evidence'' to objections.
C. Evidentiary Proffer by NRDC
As noted above, the purpose for holding hearings is ``to receive
factual evidence.'' (U.S.C. 346a(g)(2)(B); 53 FR 41126, 41129
(``Hearings are for the purpose of gathering evidence on disputed
factual issues . . . .'')). A requestor must identify evidence relied
upon to justify a hearing and either submit copies of that evidence or
summarize it. (40 CFR 178.27). After reviewing the proffer, EPA must
find that there is a reasonable possibility that the proffered
evidence, if established, would resolve one or more genuinely-disputed,
material factual issues in a requestor's favor. (40 CFR 178.32(b)).
Because a substantial portion of NRDC's evidentiary proffer is
deficient on its face, EPA finds it most efficient to preliminarily
review the proffer before turning to the individual issues raised by
NRDC.
As previously mentioned, NRDC proffered the following items as
evidence supporting its requests for hearing:
(1) the Interim Reregistration Eligibility Determination for
DDVP; (2) the entire record for the IRED and the documents
referenced and cited therein; (3) NRDC's comments on the IRED; (4)
EPA's petition denial and the references cited in that denial; (5)
NRDC's petition and all references cited in the petition; and (6)
the arguments, citations, and attachments contained in these
objections.
(Ref. 1 at 3). These items can be divided into two groups: (1) items
produced or assembled by EPA (the IRED; the IRED record; and EPA's
petition denial); and (2) items produced by NRDC (NRDC's comments on
the IRED; NRDC's petition; and NRDC's objections).
The items in the first group - the EPA documents - clearly do not
constitute a proper proffer. Essentially, this is a non-specific
identification of every document and piece of data EPA has considered
and relied upon in the multi-year process of conducting the FIFRA
reregistration and FFDCA tolerance reassessment for DDVP and in
responding to NRDC's DDVP petition. This could easily encompass
hundreds, if not thousands of documents, and tens of thousands of pages
of analysis and data. EPA's petition response alone cited 82 documents
and those documents generally were EPA analytical papers and not the
underlying data. EPA concludes that NRDC's citation to the thousands of
pages in the IRED, the IRED record, and the petition denial is so vague
a proffer as to not constitute a proffer at all. It would be as if a
lawyer, in responding to a court's request for case law authority for a
principle he or she was defending, cited the court to West's Federal
Reporter, 3rd Series. While somewhere in those hundreds of volumes a
case may exist that supports the asserted principle, the lawyer cannot
be said to have identified it by a vague wave at a substantial portion
of the law library. Further, given that the purpose of a hearing is to
gather or receive evidence, proffering evidence already considered and
relied upon by EPA would not seem to be grounds for holding a hearing.
Finally, as a matter of law, EPA does not understand how it can be
argued that a proffer consisting of a general reference to a record of
decision which EPA has found supported one result could constitute
evidence that if established, would justify the opposite conclusion. At
bottom, the proffer of the items in the first group fails to
``identify'' evidence which would, if established, resolve an issue in
NRDC's favor.
NRDC's second group of documents consists of NRDC's comments on the
IRED; NRDC's petition; and NRDC's objections. In analyzing this
proffer, EPA has focused on NRDC's objections because the objections
appear to contain, almost word-for-word, the arguments and claims put
forward in its petition and IRED comments with regard to the children's
safety factor and reliance on human studies. The objections reference
16 documents. For the reasons explained below, 10 of these documents
can be rejected on their face
[[Page 42695]]
as not justifying a hearing. Four of the documents, however,
potentially include factual evidence supporting a hearing and are
analyzed more thoroughly in connection with the specific issue in the
hearing request to which they are tied. The other two documents that
are referenced are NRDC's DDVP petition and NRDC's comments on the DDVP
IRED. As described above, these documents do not add anything beyond
what is in the objections.
1. Documents that clearly do not proffer evidence of a genuinely-
disputed, material issue of fact. (10 items)
Five Newspaper Stories. NRDC cites to an Associated Press
story from 2002 and four Los Angeles Times stories from 2007. These
news stories contain basic background information about DDVP; general
contentions from Amvac, NRDC, and EPA regarding the safety of DDVP; and
no more than a cursory, passing reference to any of the issues raised
in the petition. There can be no serious contention that these articles
present evidence justifying a hearing.
NRDC comments to HSRB. NRDC references the comments it
submitted to the HSRB with regard to the HSRB's review of the human
studies conducted with DDVP. The comments - three pages of bulleted
talking points and one graph - are a summary of the slightly more
detailed arguments contained in NRDC's objections. This document adds
no justification for a hearing not otherwise included in NRDC's
objections.
2. Legal Briefs in NRDC v. EPA, No. 06-0820-ag (2d Cir.). NRDC
cites to its opening and reply briefs in NRDC v. EPA, the case
adjudicating NRDC's challenge to EPA's Human Research rule. These
briefs contain legal arguments regarding the lawfulness of the Human
Research rule. They contain no factual evidence justifying NRDC's DDVP
hearing requests.
Three Law Review Articles. NRDC references: (1) a short
article by a NRDC attorney summarizing his legal objections to EPA's
Human Research rule; (2) an article concerning EPA's implementation of
the FQPA; and (3) an article focusing on how tort law might be used to
supplement the FQPA to protect children. None of these articles mention
DDVP and no serious contention can be made that they provide factual
evidence justifying a hearing.
3. Documents which may present evidence of a genuinely-disputed,
material issue of fact. (4 items)
Lockwood Articles. NRDC cites two articles by Dr. Alan
Lockwood which discuss science and ethical issues with regard to
several human intentional dosing studies involving pesticides. Several
of the human studies addressed were DDVP studies, one of which is the
Gledhill human study that is the focus of this proceeding. Whether the
information presented in these articles supports NRDC's hearing
requests is examined in Unit VIII.E.3.a.
Sass Letters. NRDC cites two letters published in the
journal Environmental Health Perspectives co-authored by Dr. Jennifer
Sass of NRDC. These letters discuss science and ethical issues with
regard to two human studies, including the DDVP human study in question
in this proceeding. Whether the information presented in these letters
supports NRDC's hearing requests is examined in Unit VIII.E.3.a.
D. Response to Specific Issues Raised in Objections and Hearing
Requests - Children's Safety Factor
1. Failure to support children's safety factor decision with DDVP-
specific data-- a. Objection/hearing request sub-issue. NRDC asserts
that EPA, in choosing a 3X children's safety factor for DDVP, did not
rely on reliable data showing that such a factor was safe for infants
and children because EPA's choice of 3X ``is not based on any data
specific to DDVP.'' (Ref. 1 at 5). NRDC's argument is that EPA erred by
not deriving a precise safety factor for DDVP but instead used a value
that EPA considered to be half of the 10X safety factor. NRDC claims
that ``EPA could not have determined that `such margin' [i.e., 3X] will
be safe, when the replacement safety factor is simply a generic stand-
in for EPA's conclusion that `something less than 10X' is enough.''
(Id.). According to NRDC, EPA should have explained ``what reliable
data supports a 3X safety factor in particular, as opposed to 4X or
some other number, for DDVP specifically.'' (Id.).
b. Background. Similar assertions were made in NRDC's petition and
its IRED comments. For example, the petition claimed that ``[t]he
Agency did not explain why it chose 3X as opposed to 4X or any other
factor,'' (Ref. 2 at 14), and the IRED comments asserted that there was
a ``complete lack of explanation'' for EPA's safety factor decisions.
(Ref. 23 at 5). Both documents also alleged there were inadequacies in
the toxicity and exposure databases. (Refs. 2 at 15, and 38-41; and 23
at 8-9).
In response to these claims by NRDC, EPA, in the petition response,
comprehensively restated its reasoning for its decisions on the
children's safety factor for DDVP in the IRED. (72 FR at 68694-68695).
EPA noted that it had a complete toxicity database for DDVP and it
carefully reviewed the evidence regarding the sensitivity of the young
to DDVP and explained why an additional safety factor was not needed to
protect infants and children. Further, EPA detailed why it had
concluded that its exposure assessments would not understate human
exposure to DDVP.
For some DDVP risk assessments EPA chose to remove the children's
safety factor entirely, and for others EPA reduced the safety factor to
3X. EPA explained that it retained a 3X children's safety for certain
assessments because the toxicity study which was relied upon in
conducting those risk assessments had not identified a ``no adverse
effect level'' (``NOAEL'') in its subjects but rather only a ``lowest
adverse effect level'' (``LOAEL''). Despite the failure to identify a
NOAEL in the study, EPA concluded that ``a 3X factor'' would be more
than adequate to identify a NOAEL based upon the slight adverse effect
(marginal RBC cholinesterase inhibition in a human study) observed at
the LOAEL.'' (72 FR at 68695). EPA noted that an independent science
review board had confirmed that lower doses were unlikely to produce a
measurable effect. Finally, EPA explained why it chose 3X instead of 4X
or some other value. (Id.). The petition response noted that ``where
the data does not warrant a full 10X, EPA generally does not attempt to
mathematically derive a precise replacement safety factor because
regulatory agencies' traditional use of 10X safety factors (upon which
the FQPA safety factor was modeled) was based on rough estimates rather
than detailed calculations. Instead, where a 10X factor would clearly
overstate the uncertainty, EPA simply applies a factor valued at half
of 10X.'' (Id.). EPA explained that it considers 3X to be half of 10X
assuming a lognormal distribution of effects. (Id.).
c. Denial of hearing request. In analyzing whether a hearing would
be appropriate on this sub-issue, it is helpful to break the sub-issue
down into three separate, but related, questions: (1) Whether EPA, in
selecting a children's safety factor lower than 10X, is required to
justify with precision why it chose one factor over another; (2)
whether EPA offered a justification for the children's safety factor it
chose; and (3) whether EPA relied upon DDVP specific information in
choosing a safety factor or instead relied upon ``generic assertions.''
When broken down in this way, it is clear that none of these questions
meets the standard for a hearing.
[[Page 42696]]
The first question is a pure question of law - does FFDCA section
408(c) require EPA to offer a reasoned explanation for its choice of a
children's safety factor, including an explanation as to why a
different factor is not needed. A question of fact, not of law, is
required to justify a hearing. (40 CFR 178.32(b)(1)).The second and
third questions fail to present a matter of genuinely-disputed facts
because it is plain on the record that EPA did offer a reasoned
justification for its decision and, in that justification, relied upon
DDVP-specific facts. EPA's petition response to NRDC's 10X arguments
laid out in careful detail information regarding the extent of the
toxicity and exposure database on DDVP and the data bearing on DDVP's
effects on young animals. (72 FR at 68694-68695 (discussing the
completeness of the DDVP toxicity database, DDVP studies bearing on
pre- and post-natal toxicity, and the basis for DDVP exposure
estimates)). Further, NRDC proffers no evidence - because there is none
to proffer - suggesting that EPA did not consider DDVP-specific
information in making its children's safety factor decision. Therefore,
this question does not meet the standard for a hearing both because
there are no genuinely-disputed facts and NRDC has proffered no
evidence which, if established, could resolve this issue in its favor.
57 FR 6667, 6672 (February 27, 1992) (``A hearing must be based on
reliable evidence, not on mere allegations or on information that is
inaccurate and contradicted by the record.'')
d. Denial of objection. EPA agrees with NRDC that general
principles of administrative law require it to provide a reasoned
explanation for its decision on selection of a children's safety
factor. (Baltimore Gas & Electric Co. v. NRDC, 462 U.S. 87, 103
(1983)). EPA disagrees with NRDC, however, to the extent it is
suggesting that as part of this reasoned explanation for its selection
of a children's safety factor, EPA must show why it did not choose some
other mathematical value. Rather, the statute imposes upon EPA, if it
decides to vary from the presumptive 10X children's safety factor, the
burden to show that any ``different'' safety factor is safe. Once EPA
has made that showing, its obligation to offer a reasoned explanation
is complete. Because EPA offered a reasoned explanation as to why the
children's safety factors it chose protect the safety of infants and
children, (72 FR 68694-68695), EPA denies NRDC's objection on this
point.
As to the substance of EPA's explanation of why it chose a 3X
safety factor for certain DDVP risk assessments, NRDC claims that EPA
erred because its choice of 3X is based on ``a generic assertion not []
on any data specific to DDVP.'' (Ref. 1 at 5). NRDC is wrong. The
generic assertion NRDC mentions is EPA's explanation of why 3X is half
of 10X. EPA's choice of 3X, however, is not based on its conclusion
that 3X is half of 10X but on the data in the DDVP human study at
issue. As noted above, the petition response explained in detail that a
full 10X safety factor was not needed to address the uncertainty raised
by the failure of the DDVP human study to identify a NOAEL. The effects
seen in that study at the LOAEL were only marginally adverse at best,
and therefore, EPA concluded that applying the full 10X safety factor
(i.e., dividing the LOAEL by another factor of 10X in addition to the
10X factor for intra-human variability) was more than was needed to
address the lack of a NOAEL. The HSRB confirmed as much when it wrote:
``because the decreased activity in RBC cholinesterase activity
observed in this study was at or near the limit of what could be
distinguished from baseline values, it was unlikely that a lower dose
would produce a measurable effect in RBC cholinesterase activity.''
(Ref. 21 at 41).
EPA chose a safety factor of 3X for DDVP based on its conclusion
that not only was 10X overprotective but that 3X would be protective
given the results seen in the relevant DDVP study. (72 FR at 68695). As
EPA concluded in the petition denial order: ``a 3X safety factor would
be more than adequate to identify a NOAEL based upon the slight adverse
effect (marginal RBC cholinesterase inhibition in a human study)
observed at the LOAEL.'' (Id.). Generally, EPA uses a 3X safety factor
as the default value when reducing a 10X safety factor. (Refs. 5 at 9-
10, 26; and 24 at 4-40 - 4-41; ). A safety factor of 3X is deemed to be
approximately half the value of a safety factor of an order of
magnitude (10X). As EPA explained in the petition denial order:
In choosing a safety factor in circumstances where the data does
not warrant a full 10X, EPA generally does not attempt to
mathematically derive a precise replacement safety factor because
regulatory agencies' traditional use of 10X safety factors (upon
which the FQPA safety factor was modeled) was based on rough
estimates rather than detailed calculations. Instead, where a 10X
factor would clearly overstate the uncertainty, EPA simply applies a
factor valued at half of 10X. In determining half of a 10X factor,
EPA assumes that the distribution of effects within the range of a
safety factor is distributed lognormally (which is generally the
case for biological effects), and reduction of a lognormal
distribution by half is equal to half a log (10-5) or
approximately 3X. A lognormal distribution is a distribution which
if plotted based on the logarithm of each of its values would yield
a bell-shaped (normal) distribution but if plotted according to
actual values would be skewed having a clumping of values along the
vertical axis of the plot.
(72 FR at 68695) (citations omitted).
NRDC does not challenge EPA's reasoning regarding whether the
choice of 3X is justified based on the results of a DDVP-specific study
and thus, the merits of EPA's DDVP-specific reasoning is not here at
issue. Rather, NRDC denies that EPA engaged in DDVP-specific reasoning
in choosing 3X. Because NRDC's argument is contradicted on the face of
the petition response, it is denied.
2. Endocrine effects. As described below, NRDC claims that EPA
cannot remove the children's safety factor because it has not completed
the endocrine screening program for DDVP under section 408(p) and
because EPA has inadequate endocrine data for DDVP. Although NRDC did
argue in its petition that EPA cannot make a safety finding without
completing the endocrine screening program, it did not assert claims
regarding endocrine data and the children's safety factor. EPA has
previously ruled that a petitioner may not raise new issues in filing
objections to EPA's denial of its Original petition. (72 FR 39318,
39324 (July 18, 2007) (``The FFDCA's tolerance revocation procedures
are not some sort of `game,' whereby a party may petition to revoke a
tolerance on one ground, and then, after the petition is denied, file
objections to the denial based on an entirely new ground not relied
upon by EPA in denying the petition.'')). Accordingly, NRDC's
objections and hearing requests as to the children's safety factor and
endocrine data are denied.
Even if these claims were properly presented in these objections,
for the reasons set forth below they neither entitle NRDC to a hearing
nor justify the relief sought.
a. Endocrine disruptor screening program--i. Objection/hearing
request sub-issue. NRDC argues that EPA must retain the 10X children's
safety factor because EPA has not fulfilled its obligations under FFDCA
section 408(p) to screen pesticides, including DDVP, for endocrine
disruption potential. (Ref. 1 at 5). Essentially, NRDC argues that EPA
must retain the children's safety factor for any pesticide until
testing under the endocrine screening program is completed for that
pesticide.
ii. Background. In its petition, NRDC claimed that failure to
conduct the
[[Page 42697]]
endocrine screening program for DDVP under section 408(p) made it
impossible for EPA to conclude that the DDVP tolerances are safe. (Ref.
2 at 49). EPA responded to this argument by citing its denial of a
petition to revoke various pesticide tolerances in which the claim was
made that EPA could not remove the children's safety factor if
endocrine screening under section 408(p) had not been conducted. (72 FR
at 68676). There, EPA concluded that the statute did not impose a
mandatory bar upon removal of the children's safety factor until
completion of the endocrine screening program. (71 FR 43906, 43920
(August 2, 2006)). EPA also found in responding to the prior petition
that it had sufficient data on endocrine screening for the pesticide in
question to make a safety finding. (71 FR at 43920-43921). After
analyzing the endocrine data for DDVP, EPA concluded that it had
sufficient data to make a safety finding as to DDVP. (72 FR at 68676 -
68677).
iii. Denial of hearing request. The question of whether completion
of the endocrine screening program under FFDCA section 408(p) is a
mandatory prerequisite to removal of the children's safety factor is a
legal issue. A question of fact, not of law, is required to justify a
hearing. (40 CFR 178.32(b)(1)).
iv. Denial of objection. In response to a prior pesticide tolerance
revocation petition, and objections filed as to EPA's denial of that
petition, EPA has already rejected the legal claim presented in this
objection. (71 FR at 43920; 72 FR 39318, 39327-39328 (July 18, 2007).
After analyzing the statutory language, structure, and legislative
history, EPA concluded that section 408(p) does not override the
``clear and unmistakable language[] [in section 408(b)(2)(C)]
grant[ing] EPA discretion to make a fact-based determination of whether
a safety factor different than the 10X default value is safe for
children.'' (71 FR at 43920). EPA summarized its reasoning as follows:
under section 408(b)(2)(C) EPA clearly has the discretion to
determine, in any given case, whether it has reliable data to choose
a factor different than the 10X default value. Not only is there no
statutory language supporting the [petitioners'] argument in favor
of automatic retention of the 10X until completion of the endocrine
screening program but the legislative history is in no way
supportive of construing the enactment of the program as intended to
have such a dramatic impact. Further, since the enactment of the
FQPA, EPA's contemporaneous and consistent approach to the endocrine
screening program has been to treat that information-gathering
exercise as not imposing some type of statutorily-prescribed,
automatic injunction barring removal of the children's safety factor
until completion of information-gathering under the program.
(Id.). EPA also catalogued the extensive data requirements already in
place for pesticides that produced information on a pesticide's
potential endocrine effects. (71 FR at 43920-43921). EPA concluded that
``in many instances the totality of the information gleaned from
current data required for pesticides used on food will make it possible
to develop a meaningful weight-of-the-evidence determination on the
potential of the pesticide to adversely affect the endocrine system.''
(Id.).
NRDC has done nothing more than state in a conclusory fashion that
completion of endocrine screening under section 408(p) is necessary to
a decision to remove the children's safety factor. Accordingly, EPA
denies this objection for the reasons stated in its previous two orders
addressing this claim. (71 FR at 43920 - 43921; 72 FR at 39327-39328).
b. DDVP endocrine data--i. Objection/hearing request sub-issue. In
its objections, NRDC argues that EPA has inadequate data on endocrine
effects to remove the children's safety factor. As support for this
argument NRDC asserts: (1) that the studies relied upon by EPA ``were
not designed to detect endocrine disruption . . . ;'' and (2) that the
two-generation rat reproduction study does not meet EPA's 1998
guideline for such studies and, given that the reproduction study did
show endocrine effects, a ``[p]roper histopathology in the two
generation rat reproduction study could have revealed adverse effects
at lower levels than'' the levels at which cholinesterase inhibition
was seen in DDVP studies. (Ref. 1 at 6).
ii. Background. As noted above, NRDC's petition argued that EPA
could not make a safety finding for DDVP in the absence of data
collected under the section 408(p) screening program. EPA responded to
this claim by examining the data on DDVP bearing on its potential
endocrine effects. EPA concluded that it could make a safety finding
for DDVP in absence of further endocrine data given that: ``(1) data
bearing on potential endocrine effects from a two-generation
reproduction study as well as other chronic data in which effects on
reproductive organs were examined; (2) EPA well understands DDVP's most
sensitive mechanism of toxicity (cholinesterase inhibition); and (3)
the potential endocrine-related effects seen for DDVP appeared in the
presence of significant cholinesterase inhibition and at levels nearly
two orders of magnitude above the most sensitive cholinesterase
effects. . . .'' (72 FR at 68677).
iii. Denial of hearing request. A hearing on this sub-issue is not
appropriate because NRDC's request is based on mere allegations,
general contentions, and speculation. NRDC claims that the studies EPA
relied upon were not ``designed'' to investigate endocrine effects;
however, NRDC proffers no evidence to support such an allegation.
Further, such a claim has little, if any, materiality, given that the
important question is not whether the studies were ``designed'' to
measure endocrine effects but whether they actually measure such
effects. Notably, NRDC does not, and cannot upon this record, make the
latter contention. (See 72 FR at 68676 (discussing the numerous
endocrine-related endpoints assessed in the DDVP database)). Further,
NRDC's claim that if the DDVP two-generation rat reproduction study had
been conducted pursuant to the 1998 guidelines it might have shown
endocrine effects at lower doses than the doses at which DDVP's
cholinesterase effects were seen is nothing more than speculation. In
applying its hearing regulations, FDA has routinely denied hearings on
speculation about what redoing a study might show. For example, in a
proceeding establishing a food additive regulation for acesulfame
potassium, FDA denied a hearing to an objector who challenged FDA's
rejection of a study for only containing partial histopathological
data. (57 FR 6667 (February 27, 1992)). The objector had argued that
full histopathological data might have altered FDA's conclusion. FDA
found such an argument unconvincing: ``Because complete
histopathological examination of tissues from all animals in the first
rat study was not done and cannot be done now, any prediction of the
results of such an examination is simply speculation. Speculation
regarding data that do not exist cannot serve as the basis for a
hearing.'' (Id. at 6671). For all of the above reasons, the hearing
request on this sub-issue is denied.
iv. Denial of objection. EPA denies NRDC's objection that EPA does
not have adequate endocrine data on DDVP to remove the children's
safety factor. First, NRDC is wrong to imply that existing, required
toxicity studies do not provide valuable information on potential
endocrine effects. EPA discussed this issue in detail in an earlier
order involving similar claims concerning a different pesticide. There,
EPA pointed out that:
The primary proposed Tier 2 study [for the Endocrine Disruptor
Screening Program]
[[Page 42698]]
relevant to endocrine effects on humans is the 2-generation
reproductive toxicity study in rats. This is one of the core studies
required for all food-use pesticides since 1984. In this
reproduction study, potential hormonal effects can be detected
through behavioral changes, ability to become pregnant, duration of
gestation, signs of difficult or prolonged parturition, apparent sex
ratio (as ascertained by anogenital distances) of the offspring,
feminization or masculinization of offspring, number of pups,
stillbirths, gross pathology and histopathology of the vagina,
uterus, ovaries, testis, epididymis, seminal vesicles, prostate, and
any other identified target organs. In fact, EPA, in 1998, in
discussing this study's use in Tier 2, identified 39 endpoints
examined in this study relevant to estrogenic, androgenic, or
thyroid effects. At that time, EPA noted that it was evaluating
whether to add another 10 endocrine-related endpoints to the study
protocol to enhance the utility of the study to detect endocrine
effects. Despite the ongoing evaluation of additional endpoints, EPA
has concluded that the existing 2-generation mammalian assay is
valid for the identification and characterization of reproductive
and developmental effects, including those due to endocrine
disruption, based on the long history of its use, the endorsement of
the 1998 test guideline by the FIFRA Scientific Advisory Panel, and
acceptance by member countries of the Organizations for Economic
Cooperation and Development (OECD).
(71 FR 43906, 43921 (August 2, 2006) (citations omitted)). That order
also catalogued the numerous endocrine-related endpoints in other
chronic toxicities routinely-required for pesticides used on
agricultural commodities. (Id.).
Specifically as to DDVP, in its response to NRDC's petition, EPA
detailed four long-term DDVP toxicity studies, submitted under EPA data
requirements that provided data on numerous effects that are relevant
to potential endocrine disruption. EPA wrote:
EPA has adequate data on DDVP's potential endocrine effects to
evaluate DDVP's safety. In the 1989 NTP cancer studies with rats and
mice, male and female reproductive organs (prostate, testes,
epididymis, ovaries, uterus) were examined and no changes
attributable to DDVP were found. The 52-week dog study with DDVP
also was without effect in the reproductive organs (testes,
prostate, epididymides, cervix, ovaries, uterus, vagina). EPA also
has a 1992 two-generation rat reproduction study with DDVP (via
drinking water) that is similar to the most recent guidelines (1998)
for conduct of such a study with respect to endocrine-related
endpoints. Although that study did not include certain evaluations
that the 1998 guidelines recommended related to endocrine-related
effects (age of vaginal opening and preputial separation), it did
incorporate other aspects of the 1998 guidelines such as an
examination of esterous cycling in females and sperm number,
motility, and morphology in males. The study did identify an adverse
effect on esterous cycling in females but only at the high dose (8.3
mg/kg/day). All doses in the study showed significant cholinesterase
inhibition. Further, the NOAEL and LOAEL from the esterous cycling
endpoint in the reproduction study are nearly two orders of
magnitude higher than the NOAEL and LOAEL used as a Point of
Departure in setting the chronic RfD/PAD for DDVP.
(72 FR at 68676 (citations omitted). Further, the petition response
additionally discussed a DDVP study from the scientific literature
examining endocrine-related effects. (Id.).
NRDC's speculation - that further testing of DDVP might reveal
endocrine effects at levels below those at which cholinesterase
inhibition has been measured - does not convince EPA that there is not
a reliable basis for removing the children's safety factor as regards
endocrine effects. As EPA indicated in its denial of the NRDC petition,
it has several studies addressing numerous endpoints bearing on DDVP's
potential endocrine effects, DDVP's cholinesterase inhibition effects
are well-defined by existing data, and the only endocrine effect seen
in the DDVP data occurred in the presence of significant cholinesterase
inhibition and at a level two orders of magnitude (i.e., 100X) greater
than the level at which the most sensitive cholinesterase effects were
seen. As a pesticide, DDVP is subject to testing under the endocrine
disruptor screening program; however, EPA expects that that data will
confirm its conclusion regarding DDVP's potential endocrine effects.
NRDC's objection on this point is denied.
3. Dietary exposure--a. Objection/hearing request sub-issue. NRDC
claims that there are numerous uncertainties in EPA's estimate of
dietary exposure to DDVP from food and that these uncertainties
preclude EPA from departing from the 10X children's safety factor.
(Ref. 1 at 6). Specifically, NRDC cites to a list of uncertainties
noted by EPA in a preliminary risk assessment for DDVP released in
2000. Those uncertainties involve the number of infants surveyed for
the food consumption database; foods consumed from farm stands; use of
data on residue decline from cooking studies; reliance on the residue
sampling from the FDA Total Diet Study; and lack of monitoring data,
and extensive use of data translation, for fumigated commodities. With
the exception of the infant consumption issue, NRDC makes no claim
other than to allege that ``[e]ach of these shortcomings poses a
serious risk of understating the risks posed by DDVP contamination of
food.'' (Id.). As to the infant consumption data, NRDC offers various
challenges to the size and representativeness of the group of infants
sampled in conjunction to the 2000 preliminary risk assessment. NRDC
acknowledges that EPA, in its response to the NRDC petition, states
that it used updated infant consumption data but NRDC objects that
``EPA does not assert that these data represent a statistically
adequate or representative sample.'' (Id.). Finally, NRDC implies that
EPA thinks the data are not reliable by citing an EPA statement
regarding the reliability of monitoring data.
b. Background. NRDC made almost identical claims in its petition to
revoke DDVP tolerances. EPA responded with a detailed examination of
each of the factors cited by NRDC as well as several additional
factors. (72 FR at 68684-68686). Where EPA identified weaknesses in the
exposure database it either incorporated new, updated data in its risk
assessment (for example, replacing data from the FDA Total Diet Study
with data from USDA's Pesticide Data Program) or explained how that
weakness had been addressed by conservative assumptions. (72 FR at
68684). This led to an entirely revised dietary exposure and risk
assessment for DDVP. As to this revised assessment, EPA concluded that
``its assessment of exposure to DDVP from food will not under-estimate
but rather over-estimate, and in all likelihood substantially over-
estimate, DDVP exposure.'' (72 FR at 68686). EPA also noted that the
largest ``driver'' or contributor to dietary exposure of DDVP was DDVP
in drinking water and not DDVP in food. (Id.). Specifically, as to food
consumption data for infants, EPA stated that it had incorporated the
most recent consumption data for infants that is used in all EPA
pesticide risk assessments currently in its revised risk assessment for
DDVP. This most recent data was collected at the direction of Congress
in the FQPA. (Public Law 104-170, sec. 301; 110 Stat. 1489, 1511).
c. Denial of hearing request. NRDC's objection and request for a
hearing on this sub-issue suffers from several infirmities. First, NRDC
has objected to an outdated document, EPA's preliminary risk assessment
for DDVP. With the exception of the issue concerning food consumption
data for infants, NRDC has made no effort to object to EPA's current
assessment of the reliability of various factors cited by NRDC in EPA's
petition response issued under FFDCA section 408(d)(4)(iii). When an
objector does not challenge EPA conclusions in the section
408(d)(4)(iii) order but rather challenges some prior conclusion that
was
[[Page 42699]]
superseded by the section 408(d)(4)(iii) order, the objector has not
raised a live controversy as to an issue material to the section
408(d)(4)(iii) order. (See 53 FR 53176, 53191 (December 30, 1988)
(where FDA responds to a comment in the final rule, repetition of the
comment in objections does not present a live controversy unless the
objector proffers some evidence calling FDA's conclusion into
question)). In fact, in these circumstances, it is questionable whether
EPA has jurisdiction to consider the objection and hearing request
because objections may only be filed as to a section 408(d)(4)(iii)
order or other statutorily-specified action. (21 U.S.C. 346a(g)(2)(A)).
Second, NRDC has made no proffer of evidence supporting its claim
that each of the factors cited from EPA's preliminary risk assessment
``poses a serious risk of understating the risks posed by DDVP
contamination of food.'' (Ref. 1 at 6). NRDC's entire argument
concerning the effect these factors (other than the infant food
consumption data issue) would have on the DDVP exposure assessment is a
single conclusory sentence. A hearing will not be granted on ``mere
allegations'' or ``general contentions.'' (40 CFR 178.32(b)(2)).
Although NRDC discusses the infant food consumption data issue at
greater length, this discussion provides no support for granting a
hearing. NRDC's discussion is limited to: (1) a presentation of a short
analysis of the adequacy of the superseded consumption data as opposed
to the data up |
