Dichlorvos (DDVP); Order Denying NRDC's Petition to Revoke All Tolerances

[Federal Register: December 5, 2007 (Volume 72, Number 233)]
[Rules and Regulations]
[Page 68661-68698]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr05de07-21]
[[Page 68662]]

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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2002-0302; FRL-8341-9]

AGENCY: Environmental Protection Agency (EPA).
ACTION: Order.

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SUMMARY: In this Order, EPA denies a petition requesting that EPA
revoke all pesticide tolerances for dichlorvos (DDVP) under section
408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA). The
petition was filed on June 2, 2006, by the Natural Resources Defense
Council (NRDC).

DATES: This order is effective December 5, 2007. Objections and
requests for hearings must be received on or before February 4, 2008,
and must be filed in accordance with the instructions provided in 40
CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).

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, select ``Advanced
Search,'' then ``Docket Search.'' Insert the docket ID number where
indicated and select the ``Submit'' button. 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 a petition by the Natural Resources
Defense Council (``NRDC'') 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. Can I File an Objection or Hearing Request?

Under section 408(g) of FFDCA, any person may file an objection to
any aspect of this order and may also request a hearing on those
objections. You must file your objection or request a hearing on this
order in accordance with the instructions provided in 40 CFR part 178.
To ensure proper receipt by EPA, you must identify docket ID number
EPA-HQ-OPP-2002-0302 in the subject line on the first page of your
submission. All requests must be in writing, and must be mailed or
delivered to the Hearing Clerk as required by 40 CFR part 178 on or
before February 4, 2008.
In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of
the filing that does not contain any CBI for inclusion in the public
docket that is described in ADDRESSES. Information not marked
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA
without prior notice. Submit this copy, identified by docket ID number
EPA-HQ-OPP-2002-0302, by one of the following methods:
• Federal eRulemaking Portal: http://www.regulations.gov.
Follow the on-line instructions for submitting comments.
• Mail: Office of Pesticide Programs (OPP) Regulatory Public
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460-0001.
• Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only
accepted during the Docket's normal hours of operation (8:30 a.m. to 4
p.m., Monday through Friday, excluding legal holidays). Special
arrangements should be made for deliveries of boxed information. The
Docket Facility telephone number is (703) 305-5805.

II. Introduction

A. What Action Is the Agency Taking?

On June 2, 2006, the Natural Resources Defense Council (NRDC) filed
a petition with EPA which, among other things, requested that EPA
revoke all tolerances for the pesticide dichlorvos (DDVP) established
under section 408 of the Federal Food, Drug, and Cosmetic Act
(``FFDCA''), 21 U.S.C. 346a. (Ref. 1). NRDC's petition asserts that the
DDVP tolerances are unsafe and should be revoked for numerous reasons,
including: EPA has improperly assessed the toxicity of DDVP; EPA has
erred in

[[Page 68663]]

estimating dietary and residential exposure to DDVP; and EPA has
unlawfully removed the additional safety factor for the protection of
infants and children. This order finds NRDC's claims regarding the DDVP
tolerances to be without merit and, accordingly, denies that aspect of
NRDC petition. The other aspects of NRDC's petition are addressed in
another EPA action.

B. What Is the Agency's Authority for Taking This Action?

Under section 408(d)(4) of the FFDCA, EPA is authorized to respond
to a section 408(d) petition to revoke tolerances either by issuing a
final rule revoking the tolerances, issuing a proposed rule, or issuing
an order denying the petition. (21 U.S.C. 346a(d)(4)).

III. Statutory and Regulatory Background

A. Statutory Background

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 and the U. S. Department of Agriculture.
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.
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 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)).
Section 408(b)(2)(C) requires EPA to give special consideration to
risks posed to infants and children. Specifically, this provision
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 further 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, the
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 affected party has 60 days to file objections with EPA
and seek an evidentiary hearing on those objections. (21 U.S.C.
346a(g)(2)). 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
requires, among other things, that EPA reassess the safety of all
pesticide tolerances existing at the time of its enactment. (21 U.S.C.
346a(q)). In this reassessment, EPA is 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 is generally handled in
conjunction with a similar program involving reregistration of
pesticides under FIFRA. (7 U.S.C. 136a-1). Reassessment and
reregistration decisions are generally combined in a document labeled a
Reregistration Eligibility Decision (``RED'').
5. Estrogenic Substances Screening Program. Section 408(p) of the
FFDCA creates the estrogenic substances screening program. This
provision gives EPA 2 years from enactment of the FQPA to ``develop a
screening program ... to determine whether certain substances may have
an effect in humans that is similar to an effect produced by a
naturally occurring

[[Page 68664]]

estrogen, or such other endocrine effect as the Administrator may
designate.'' This screening program must use ``appropriate validated
test systems and scientifically relevant information.'' (21 U.S.C.
346a(p)(1)). 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 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. Setting and Reassessing Pesticide Tolerances Under the FFDCA

1. In general. The process EPA follows in setting and reassessing
tolerances under the FFDCA includes two steps. First, EPA determines an
appropriate residue level value for the tolerance taking into account
data on levels that can be expected in food. Second, EPA evaluates the
safety of the tolerance relying on toxicity and exposure data and
guided by the statutory definition of ``safety'' and requirements
concerning risk assessment. Only on completion of the second step can a
tolerance be established or reassessed. Both stages of this process are
relevant to EPA's analysis of petitions to revoke tolerances based on
risk concerns because both stages bear on the assessment of risk.
2. Choosing a tolerance value. In the first step of the tolerance
setting or reassessment process (choosing a tolerance value), EPA
evaluates 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. 2 and 3). 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. 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. 4). (As discussed below, the safety of the
tolerance value chosen is separately evaluated.).
There are three main reasons for closely linking tolerance values
to the maximum value that could be present from maximum label usage of
the pesticide. First, EPA believes it is important to coordinate its
actions under the two statutory frameworks governing pesticides. (See
61 FR 2378, 2379 (January 25, 1996)). It would be illogical for EPA to
set a pesticide tolerance under the FFDCA without considering what
action is being taken under FIFRA with regard to registration of that
pesticide use. (Cf. 40 CFR 152.112(g) (requiring all necessary
tolerances to be in place before a FIFRA registration may be granted)).
In coordinating its actions, one basic tenet that EPA follows is that a
grower who applies a pesticide consistent with the FIFRA label
directions should not run the risk that his or her crops will be
adulterated under the FFDCA because the residues from that legal
application exceed the tolerance associated with that use. Crop field
trials require application of the pesticide in the manner most likely
to produce maximum residues to further this goal. Second, choosing
tolerance values based on FIFRA label rates helps to ensure that
tolerance levels are established no higher than necessary. If tolerance
values were selected solely in consideration of health risks, in some
circumstances, tolerance values might be set so as to allow much
greater application rates than necessary for effective use of the
pesticide. This could encourage misuse of the pesticide. Finally,
closely linking tolerance values to FIFRA labels helps EPA to police
compliance with label directions by growers because detection of an
over-tolerance residue is indicative of use of a pesticide at levels,
or in a manner, not permitted on the label.
3. The safety determination - risk assessment. Once a tolerance
value is chosen, EPA then evaluates the safety of the pesticide
tolerance using the process of risk assessment. To assess risk of a
pesticide, EPA combines information on pesticide toxicity with
information regarding the route, magnitude, and duration of exposure to
the pesticide.
In evaluating toxicity or hazard, EPA examines both short-term
(e.g., ``acute'') and longer-term (e.g., ``chronic'') adverse effects
from pesticide exposure. (Ref. 2 at 8-10). EPA also considers whether
the ``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. 2 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 carcinogenesis have
increasingly led EPA to conclude that some pesticides that cause
carcinogenic effects only cause such effects above a certain threshold
of exposure. EPA has traditionally considered adverse effects on the
endocrine system to be a threshold effect; that determination is being
reexamined in conjunction with the endocrine disruptor screening program.
Once the hazard for a durational scenario is identified, EPA must
determine the toxicological level of concern and then compare estimated
human exposure to this level of concern. This comparison is done
through either calculating a safe dose in humans (incorporating all
appropriate safety factors) and expressing exposure as a percentage of
this safe dose (the reference dose (``RfD'') approach) or dividing
estimated human exposure into an appropriate dose from the relevant
studies at which no adverse effects from the pesticide are seen (the
margin of exposure (``MOE'') approach). How EPA determines the level of
concern and assesses risk under these two approaches is explained in
more detail below. EPA's general approach to estimating exposure is
also briefly discussed.
a. Levels of concern and risk assessment--i. Threshold effects. In
assessing the risk from a pesticide's threshold effects, EPA evaluates
an array of toxicological 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 in
estimating the level of concern for humans. In estimating and
describing the level of

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concern, however, the chosen NOAEL is at times manipulated differently
depending on whether the risk assessment addresses dietary or non-
dietary exposures.
For dietary risks, EPA uses the chosen NOAEL to calculate a safe
dose or RfD. The RfD is calculated by dividing the chosen NOAEL by all
applicable safety or uncertainty factors. Typically, a combination of
safety or uncertainty factors providing a hundredfold (100X) margin of
safety is used: 10X to account for uncertainties inherent in the
extrapolation from laboratory animal data to humans and 10X for
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. Further,
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. 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.
To quantitatively describe risk using the RfD/PAD approach,
estimated exposure is expressed as a percentage of the RfD/PAD. Dietary
exposures lower than 100 percent of the RfD are generally not of concern.
For non-dietary, and often for combined dietary and non-dietary,
risk assessments of threshold effects, the toxicological level of
concern is not expressed as a safe dose or RfD/PAD but rather as the
margin of exposure (MOE) that is necessary to be sure that exposure to
a pesticide is safe. A safe 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 interspecies differences, 10X factor for intraspecies differences,
and 10X factor for FQPA, the safe or target MOE would be a MOE of at
least 1,000. To calculate the MOE for a pesticide, human exposure to
the pesticide is divided into the lowest NOAEL from the available
studies. In contrast to the RfD/PAD approach, the higher the MOE, the
safer the pesticide. Accordingly, if the level of concern for a
pesticide is 1,000, MOEs exceeding 1,000 would generally not be of
concern. Like RfD/PADs, specific MOEs are calculated for exposures of
different durations. For non-dietary exposures, EPA typically examines
short-term, intermediate-term, and long-term exposures. Additionally,
non-dietary exposure often involves exposures by various routes
including dermal, inhalation, and oral.
The RfD/PAD and MOE approaches are fundamentally equivalent. For a
given risk and given exposure of a pesticide, if the pesticide were
found to be safe under an RfD/PAD analysis it would also pass under the
MOE approach, and vice-versa.
ii. Non-threshold effects. For risk assessments for non-threshold
effects, EPA does not use the RfD/PAD or MOE approach if quantitation
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 model that assumes that any amount of exposure will
lead to some degree of risk. The slope of the dose-response curve can
then be used to estimate the probability of occurrence of additional
adverse effects as a result of exposure to the pesticide. For non-
threshold cancer risks, EPA generally is concerned if the probability
of increased cancer cases exceeds the range of 1 in 1 million.
b. Estimating human exposure. Equally important to the risk
assessment process as determining the toxicological level of concern 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. (A) In General. 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
U.S. Department of Agriculture. (Ref. 2 at 12). Information on residue
values comes from a range of sources including crop field trials, data
on pesticide reduction 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, conducts its exposure assessment using the extreme 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.
Second, as discussed above, the tolerance value is set above the
highest value observed in crop field trials using maximum use rates.
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. (Id.
at 17-28).

[[Page 68666]]

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
Food and Drug Administration, the U.S. Department of Agriculture, 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. Although 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 maximum residue values for acute risk assessment tends to
greatly overstate exposure in narrow increments of time where it
matters how much of each treated food a given consumer eats and what
the residue levels are in the particular foods consumed. 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.
(B) Computer modeling of dietary exposure. EPA uses a computer
program known as the Dietary Exposure Evaluation Model - Food Commodity
Intake Database (``DEEM-FCID'') to estimate exposure by combining data
on human consumption amounts with residue values in food commodities.
DEEM-FCID also compares exposure estimates to appropriate RfD/PAD
values to estimate risk. DEEM-FCID can estimate exposure for the
general U.S. population as well as 32 subgroups based on age, sex,
ethnicity, and region. DEEM-FCID is closely modeled on its predecessor
program DEEM. DEEM-FCID includes the DEEM software modeling program but
has revised inputs bearing on consumption patterns that were developed
by EPA to insure that all underlying aspects of the model are publicly
available. (Ref. 6).
EPA uses a computer program to make exposure and risk estimates
because EPA has great volumes of data on human consumption amounts and
residue levels. Matching consumption and residue data can be done more
efficiently by computer. Additionally, certain risk assessment
techniques involve thousands of repeated analyses of the consumption
database and this cannot practically be done by hand. However, the
actual structure and logic of DEEM-FCID is relatively simple.
DEEM-FCID contains consumption and demographic information on the
individuals who participated in the USDA's Continuing Surveys of Food
Intake by Individuals (``CSFII'') in 1994-1996 and 1998. The 1998
survey was a special survey required by the FQPA to supplement the
number of children survey participants. DEEM-FCID also contains
translation factors that convert foods as consumed (e.g., pizza) back
into their component raw agricultural commodities. This is necessary
because residue data are generally gathered on raw agricultural
commodities rather than on finished ready-to-eat food. Data on residue
values for a particular pesticide and the RfD/PADs for that pesticide
have to be inputted into the DEEM-FCID program to estimate exposure and
risk.
DEEM-FCID can make three types of risk estimates: a single point
estimate; a simple distribution; or a probabilistic distribution. A
point estimate provides a single exposure and risk value for each
population subgroup. Generally, these exposure and risk values are
derived by combining single values for consumption and residue amount
on consumed commodities. For example, point estimates are commonly
computed for chronic exposure and risk by combining data on average
consumption with data on average residue levels. (Ref. 7-).
In contrast to a point estimate, DEEM-FCID can also do two types of
distributional analyses. A simple distribution combines a single
residue value for each food with the full range of data on individual
consumption amounts to create a distribution of exposure and risk
levels. More specifically, DEEM-FCID creates this distribution by
calculating an exposure value for each reported day of consumption per
person (``person/day'') in CSFII assuming that all foods potentially
bearing the pesticide residue contain such residue at the chosen value.
The exposure amounts for the thousands of person/days in the CSFII are
then collected in a frequency distribution.
Added complexity is introduced if DEEM-FCID computes a distribution
taking into account both the full range of data on consumption levels
and the full range of data on potential residue levels in food.
Combining these two independent variables (consumption and residue
levels) into a distribution of potential exposures and risk requires
use of probabilistic techniques.
The probabilistic technique that DEEM-FCID uses to combine
differing levels of consumption and residues involves the following steps:
1. for each person/day in the CSFII, identification of any food(s)
that could possibly bear the residue of the pesticide in question;
2. calculation of an exposure level for each person/day based on
the foods identified in Step #1 by randomly selecting residue
values for the foods from the residue database;
3. repetition of Step #2 one thousand times for each person/day; and
4. collection of all of the hundreds of thousands of potential
exposures estimated in Steps #2 and #3 in a frequency distribution.
In this manner, a probabilistic assessment presents a range of
exposure/risk estimates.
Point estimates are used for chronic risk assessments. EPA does not
use DEEM-FCID to calculate distributional assessments for chronic risk
because EPA's current view is that its consumption database is not
sufficiently robust to support a distributional analysis for chronic
exposure. Both simple and probabilistically-derived distributions are
used for acute risk assessment. EPA generally estimates exposure and
risk from a simple distribution based on the 95th percentile of such a
distribution. EPA's reason for relying on the 95th percentile with
simple distribution assessments is that for these assessments EPA
typically uses very conservative assumptions regarding residue levels
(100 percent of the crop is treated and all treated food bears residues
at the tolerance level) and thus the 95th percentile is protective of
the general population as well as all major, identifiable population
subgroups. Because probabilistic assessments generally use more
realistic residue levels, EPA's starting point for estimating exposure
and risk for such assessments is the 99.9th percentile.

[[Page 68667]]

This value can change depending on the degree of conservatism in the
residue estimates. (Ref. 8).
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 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.
EPA has developed models for estimating exposure in both surface
water and ground water. EPA uses a two-tiered approach to modeling
pesticide exposure in surface water. In the initial tier, EPA uses the
FQPA Index Reservoir Screening Tool (FIRST) model. FIRST replaces the
GENeric Estimated Environmental Concentrations (GENEEC) model that was
used as the first tier screen by EPA from 1995-1999. If the first tier
model suggests that pesticide levels in water may be unacceptably high,
a more refined model is used as a second tier assessment. The second
tier model is actually a combination of the models, Pesticide Root Zone
Model (PRZM) and the Exposure Analysis Model System (EXAMS). For
estimating pesticide residues in groundwater, EPA uses the Screening
Concentration In Ground Water (SCI-GROW) model. Currently, EPA has no
second tier groundwater model.
EPA's water exposure models have been extensively peer-reviewed
and/or validated, and have proved highly conservative in practice. In
fact, an evaluation conducted in conjunction with NRDC objections to
tolerances for other pesticides found that EPA's surface water models
never under-estimated the highest values measured in monitoring
studies, and that EPA's groundwater model had only rarely under-
estimated such results, and those underestimations were relatively
small. (69 FR at 30061-30064).
Whether EPA estimates pesticide exposure in drinking water through
monitoring data or modeling, EPA uses the higher of the two values from
surface and ground water in quantifying overall exposure to the
pesticide. In most cases, pesticide concentrations in surface water are
significantly higher than in groundwater.
iii. Residential exposures. Generally, in assessing residential
exposure to pesticides EPA relies on its Residential Standard Operating
Procedures (``SOPs''). 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.

C. EPA Policy on Cholinesterase Inhibition as a Regulatory Endpoint

On August 18, 2000, EPA issued a science policy document entitled
``The Use of Data on Cholinesterase Inhibition for Risk Assessments of
Organophosphorous and Carbamate Pesticides.'' (Ref. 9). Although
assessing the risk from organophosphorous and carbamate pesticides was
a primary reason for updating EPA guidance on cholinesterase
inhibition, the policy addressed the topic generally and not just in
the context of these two families of pesticides.
Cholinesterase inhibition is a disruption of the normal enzymatic
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 enzyme, 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 the policy explains, ``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.'' (Id. 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.
The cholinesterase inhibition policy statement explains EPA's
approach to evaluating the hazard posed by cholinesterase-inhibiting
pesticides. The policy focuses on three types of effects associated
with cholinesterase-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 a safe 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. Due
to strict ethical limitations, however, 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

[[Page 68668]]

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).
The policy advises that, in selection of a Point of Departure for
deriving a RfD/PAD, all data on clinical signs and cholinesterase
inhibition should be considered in a weight-of-the-evidence analysis.
This weight-of-the-evidence analysis should focus, according to the
policy, on (1) ``[a] comparison of the pattern of doses required to
produce physiological and behavioral effects and cholinesterase
inhibition'' in the central and peripheral nervous systems and in
blood; (2) ``comparisons of the temporal aspects (e.g., time of onset
and peak effects and duration of effects) of each relevant endpoint;''
and (3) ``the potential for differential sensitivity/susceptibility of
adult versus young animals (i.e., effects following perinatal or
postnatal exposures).'' (Id. at 35). This analysis can lead EPA to
``select as the critical effects any one or more of the behavioral and
physiological changes or enzyme measures listed above.'' (Id.). In
comparing studies across the entire database to select an endpoint for
the Point of Departure, the policy stresses that ``parallel analyses of
the dose-response (i.e., changes in magnitude of enzyme inhibition or
of a different effect with increasing dose) and the temporal pattern of
all relevant effects will be compared across all of the different
compartments affected (e.g., plasma, RBC, peripheral nervous system,
brain), and for the functional changes to the extent the database
permits.'' (Id. at 38). Further, the policy states that ``[t]he
consistency (or, the lack thereof) of LOAELs, NOAELs, or BMDs for each
category of effects (e.g., clinical signs, cholinesterase inhibition in
the various compartments, etc.) for the test species/strains/sex available
and for each duration and route of exposure should be noted.'' (Id.).

D. 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
differences between animals and humans when relying on studies in
animals (inter-species safety factor) and differences among humans
(intra-species safety factor) as well as the additional 10X children's
safety factor added by the FQPA.
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).

E. Endocrine Disruptor Screening Program

To aid in the design of the endocrine screening 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. 10). 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 androgenic and
thyroid effects as well. (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

[[Page 68669]]

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, 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.
(Endocrine Disruptor Screening and Testing Advisory Committee Final
Report, 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 these assays,
however, is not yet 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.
Recently, 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.)

IV. DDVP Tolerances

A. Regulatory Background

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. 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 108.235 for DDVP on agricultural (food and
feed) crops and animal commodities. DDVP is 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.
DDVP is closely related to the pesticides naled and trichlorfon.
Naled and trichlorfon both metabolize or degrade to DDVP in food,
water, or the environment. All three pesticides 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 and thus, in
addition to assessing the risks posed by exposure to these pesticides
individually, EPA has assessed the potential cumulative effects from
concurrent exposure to organophosphate pesticides.

B. FFDCA Tolerance Reassessment and FIFRA Pesticide Reregistration

As required by the Food Quality Protection Act of 1996, EPA
reassessed the safety of the DDVP tolerances under the new safety
standard established in the FQPA. In the Interim Reregistration
Eligibility Document (``IRED'') for DDVP, EPA determined that aggregate
exposure to DDVP as a result of use of DDVP, naled, and trichlorfon,
complied with the FQPA safety standard. (Ref. 11). Separately, EPA
determined that cumulative effects from exposure to all organophosphate
residues were safe. (Ref. 12). 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 the only technical
product registrant, Amvac Corporation (``Amvac''), an irrevocable
request to cancel certain uses and include additional pest strip label
restrictions on the DDVP technical 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. Additionally, in early March, 2007, Amvac requested the voluntary
cancellation of all its pet 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)).

C. Toxicity Overview

Animal and human studies with DDVP demonstrate that the toxic
effect of concern for DDVP is inhibition of cholinesterase activity.
These studies showed decreases in cholinesterase activity in plasma,
red blood cell, and the brain. These effects were consistently found
whether the exposure duration was acute or chronic and across all
tested routes of exposure. Studies involving in utero, as well as pre-
and post-natal, exposure of young animals showed no evidence of
increased sensitivity in the young to these effects. Cholinesterase
inhibition was also the effect used to assess potential cumulative
effects from exposure to organophosphate pesticides. Based on numerous
cancer studies with DDVP, EPA has classified the evidence

[[Page 68670]]

on DDVP's potential carcinogenicity as ``suggestive;'' however, due to
the lack of relevance to humans of the tumors identified, EPA has
determined that DDVP poses a negligible cancer risk to humans.

D. Exposure Overview

Exposure to DDVP can occur through the consumption of food treated
with DDVP, naled, or trichlorfon, consumption of drinking water bearing
DDVP residues, or from exposure in the residential setting from use of
DDVP or trichlorfon. EPA has extensive food monitoring data on DDVP.
These data show that with one exception, strawberries, DDVP is rarely
found at detectable amounts in food. About 5 percent of sampled
strawberries have shown detectable DDVP residues. These monitoring
results are consistent with metabolism data on DDVP which shows that it
is rapidly degraded into non-toxic substances. EPA has limited water
monitoring data showing no detectable residues of DDVP. Due to the fact
that these data do not identify whether they were collected from areas
of DDVP, naled, or trichlorfon usage and the lack of data from shallow
groundwater wells, EPA has relied upon conservative modeling estimates
of drinking water. EPA has estimated residential exposure to DDVP based
primarily on one of several monitoring studies conducted using DDVP
pest strips in houses.

V. The Petition to Revoke Tolerances

On June 2, 2006, the Natural Resources Defense Council (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 SAP 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. 1). Shortly after the petition was filed, on
June 30, 2006, EPA released the Interim Reregistration Eligibility
Decision (``IRED'') for DDVP which addressed DDVP's eligibility for
reregistration under FIFRA and assessed 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. 13).
NRDC asserted numerous grounds as to why the DDVP tolerances do not
meet the FQPA safety standard and should be revoked. EPA has divided
NRDC's grounds for revocation into four categories - toxicology;
dietary exposure; residential exposure; and risk characterization - and
addressed separately each claim under these categories. Each specific
claim of NRDC is summarized in Unit VII immediately prior to EPA's
response to the claim.

VI. Public Comment

In response to the aspects of the petition addressing the DDVP
tolerances, 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, the party holding the registration for DDVP under
FIFRA. (Ref. 14). Amvac's comments on the specific claims by NRDC are
summarized in Unit VII immediately following the summary of NRDC's
claim but prior to EPA's response to the claim.

VII. Ruling on Petition

This order addresses NRDC's petition to revoke DDVP tolerances. As
noted, in responding to NRDC's petition, EPA has broken the issues into
four categories -- toxicology; dietary exposure; residential exposure;
and risk characterization. Below, EPA addresses each of the claims
raised in these categories and explains why they do not support
revocation of the tolerances.
EPA has not addressed claims that concern DDVP uses that have been
canceled since the time of the petition. Specific uses cancelled were
the largest (100 gram) pest strip; lawn, turf, and ornamentals; pet
collars; and in-home crack and crevice. Additionally, the remaining
``large'' pest strips (80 and 65 grams) were limited to unoccupied
portions of the home. The only pest strips permitted in occupied areas
were smaller strips (16, 10.5, 5.25 grams) for use in closets,
wardrobes, and cupboards.

A. Toxicological Issues

1. Cancer--a. NRDC's claims. NRDC claims that ``the rejection by
EPA of the `probable carcinogen' cancer classification of previous
Agency reviews is inadequately supported .. ..'' (Ref. 1 at 17).
According to NRDC, EPA has not explained why its prior analysis was
``flawed,'' and the reasons EPA has given for the change in cancer
classification are ``speculative, at best.'' (Id.). NRDC urges EPA to
drop its new classification of DDVP as having ``suggestive'' evidence of
carcinogenicity and restore the ``original classification.'' (Id. at 18).
Specifically, NRDC argues with EPA's decision to discount, in its
weight-of-the-evidence evaluation for DDVP, mononuclear cell leukemia
(MCL) seen in a rat study and forestomach tumors identified in a mouse
study. NRDC claims that EPA's assertion that a finding of MCL in the
Fischer rat is of limited usefulness due to variability of occurrence
of this cancer in the Fischer rat ``may be an artifact of the design of
such studies and is not an adequate basis for ignoring a positive
result.'' (Id. at 17). NRDC suggests that a larger scale study could
have resolved this issue. As to forestomach tumors, NRDC disputed EPA's
conclusion that these tumors have limited relevance to humans given
that humans do not have forestomachs. NRDC notes that all animals have
some difference in their organs and tissues and thus the lack of a
forestomach in humans does not ``automatically mean that the effect is
irrelevant to humans.'' (Id.). According to NRDC, EPA ``must provide
convincing explanations based on reliable data that their rejection of
forestomach tumors is a reasonable certainty and will adequately
protect the public health.'' (Id.).
NRDC also suggests that a study in Denver, Colorado ``specifically
linked'' DDVP pest strips to leukemia in children under 15 (Leiss,
J.K., Savitz, D.A. ``Home pesticide use and childhood cancer: a case-
control study,'' American Journal of Public Health 1995; 85:249-52) and
a study of adult men with leukemia in Iowa and Minnesota (Brown, L.M.,
Blair, A., Gibson, R., et al. ``Pesticide exposures and other
agricultural risk factors for leukemia among men in Iowa and
Minnesota,'' Cancer Research 1990;50(20):6585-91) found that these men
were twice as likely to have a history of exposure to DDVP.
b. Amvac's comments. Disagreeing with NRDC's claims, Amvac argues
that NRDC has ignored an extensive DDVP cancer database and the
confounding effect that corn oil played in the two positive studies
relied upon by NRDC. (Ref. 14 at 27-28). Amvac asserts that 11 cancer
studies have been performed with DDVP, involving both oral and
inhalation exposure routes, and that the only two positive studies were
gavage studies in which the DDVP was administered by gavage in corn oil.

[[Page 68671]]

Amvac claims that it is well-recognized that corn oil as a confounding
factor in cancer studies and that, in fact, the National Toxicology
Program (``NTP'') has found corn oil to be carcinogenic. Finally, Amvac
cites to a recent review by the European Food Safety Agency, which
Amvac asserts concluded, after reviewing all of the evidence, ``that
the carcinogenic risk from exposure to DDVP is very low.'' (Ref. 15).
c. EPA's response. Initially, EPA responds to NRDC's claims
regarding EPA's cancer classification by noting that NRDC's request to
amend the cancer classification is not a sufficient ground for seeking
revocation of the DDVP tolerances. A cancer classification does not
determine whether a pesticide is safe or not; rather, a cancer
classification is one step in a multi-stage risk assessment process
that ascertains and examines not only the toxicological effects a
pesticide causes, but also the potency of the pesticide and the extent
of human exposure to the pesticide. A pesticide found to be a
``probable'' human carcinogen may nonetheless meet the FFDCA section
408 safety standard if it has a low potency and/or low exposure. NRDC's
petition contains no arguments or evidence that if DDVP is reclassified
as a probable human carcinogen, a cancer risk assessment would show
that DDVP is not safe. Accordingly, EPA denies NRDC's petition to
revoke DDVP tolerances to the extent that the petition cites EPA's
alleged cancer misclassification of DDVP as grounds for such a revocation.
Nonetheless, to clarify the issue, EPA will explain the basis for
its revision of the cancer classification of DDVP. EPA's Cancer
Assessment Review Committee (CARC) in the Health Effects Division of
the Office of Pesticide Programs has held six cancer reviews for DDVP
over the past two decades. These multiple reviews have been necessary
due to the development of new information on DDVP as well as on
carcinogenicity generally. What these reviews show is that EPA has
taken a conservative approach to the cancer classification of DDVP,
only weakening the classification (i.e., adopting a classification of
lower human carcinogenic potential) upon the repeated advice of
independent expert scientific panels.
EPA's reviews bridge two versions of its cancer assessment
guidelines. These guidelines have slightly different descriptive
categories for classifying chemicals as to their carcinogenic
potential. In its 1986 Cancer Assessment Guidelines, EPA created the
following categories regarding cancer potential: ``human carcinogen''
(Group A), ``probable human carcinogen'' (Group B), ``possible human
carcinogen'' (Group C), ``not classifiable as to human
carcinogenicity'' (Group D), and ``evidence of non-carcinogenicity for
humans'' (Group E). (51 FR 33992 (September 24, 1986)). Under the 1986
Guidelines, Group B was further subdivided into Groups B1 and B2 with
the former for chemicals categorized on the basis of data from humans
and the latter based on data in animals. In an update to these
guidelines in 2005, EPA adopted the following classifications:
``carcinogenic to humans,'' ``likely to be carcinogenic to humans,''
``suggestive evidence of carcinogenic potential,'' ``inadequate
information to assess carcinogenic potential,'' and ``not likely to be
carcinogenic to humans.'' (70 FR 17765, April 7, 2005). The revised
guidelines dropped the alphabetic labeling of the classifications.
In its first review of DDVP in June 1987, the CARC's predecessor,
the Carcinogenicity Cancer Peer Review Committee [hereinafter referred
to as the CARC for simplicity], classified DDVP as a probable human
carcinogen (Group B2), under EPA's 1986 cancer classification system.
(Ref. 16). The CARC's classification of DDVP as a probable human
carcinogen was based on its conclusion that the evidence showed DDVP
satisfied two separate criteria for a ``probable human carcinogen:''
(1) carcinogenicity seen in multiple species; and (2) carcinogenicity
seen in an unusual degree in a single experiment. To show cancer in
multiple species, the CARC cited (1) a finding of statistically
significant dose-related trend and statistically significant increase
in forestomach tumors (combined papillomas and carcinomas) in female
mice in a cancer study in the mouse conducted by the National
Toxicology Program (NTP); and (2) a finding of a statistically
significant dose-related trend and statistically significant increase
in mononuclear cell leukemia (MCL) and pancreatic acinar adenomas in
male rats in a cancer study in the rat conducted by the NTP. These two
findings were supported by a significant positive trend for forestomach
tumors in male mice in the NTP mouse study and a finding of
statistically significant increased (but overall numbers within the
range of historical controls) lung adenomas and combined mammary
fibroadenomas and carcinomas in male and female rats, respectively, in
the NTP rat study. To satisfy the criterion of cancer in an unusual
degree in a single study, the CARC noted that forestomach tumors are a
rare tumor in the female mouse. Finally, the CARC relied on positive in
vitro mutagenicity data in support of the ``probable human carcinogen''
classification.
In September, 1987, the CARC's classification was evaluated by the
FIFRA Scientific Advisory Panel (``SAP''), an independent expert panel
created by statute for the purpose of providing EPA advice on
scientific matters concerning pesticides. The SAP disagreed with EPA's
classification and recommended that DDVP be classified as only a
possible human carcinogen (Group C) based on its conclusions that: (1)
DDVP only induced benign tumors; (2) the tumors did not show a dose-
related trend; and (3) DDVP was not mutagenic in in vivo assays. (Ref. 17).
The CARC met for a second time on DDVP in September, 1987, to take
the SAP's view into consideration. The CARC refused to alter its Group
B2 carcinogen classification. It cited essentially the same reasons
from the first review and emphasized the following evidence of
malignancy to explain its difference with the SAP: (1) MCL is
considered a malignant tumor; (2) both the pancreatic adenomas in rats
and forestomach papillomas in mice had the potential to progress to
malignancies; and (3) the presence of ``some'' rare forestomach
carcinomas in female mice. (Id.)
A third meeting of the CARC was held in July, 1988 to review a
report from the NTP Panel of Experts on the classification of DDVP.
(Ref. 18). NTP scientists had reexamined the pancreata of the rats in
the NTP rat study and concluded that the statistically significant
increase in pancreatic lesions was diminished. For this reason, the NTP
recommended that the evidence for carcinogenicity in male rats be
downgraded from ``clear'' evidence to ``some'' evidence. Nonetheless,
the CARC again refused to change DDVP's cancer classification relying
on the MCL finding in rats, findings of multiple benign tumors in rat
and mouse NTP studies, and DDVP's mutagenic properties. The CARC noted
this classification was interim until new cancer and mutagenicity data
could be reviewed.
A fourth meeting of the CARC in September, 1989, again reviewed the
reanalysis of the pancreatic lesions in the rat, and also examined new
cancer studies. (Ref. 19). The CARC noted that, although the NTP
reexamination had found pancreatic tumors in treated rats to be
statistically increased, albeit to a diminished degree than first
thought, a new statistical review by EPA using two common statistical
procedures found no statistical significance at all. Further, the CARC
examined a DDVP inhalation cancer study in rats and two cancer

[[Page 68672]]

studies in which DDVP was administered in drinking water. The
inhalation study was negative for cancer effects. The drinking water
studies had several deficiencies making quantitative analysis
inappropriate but had qualitative evidence that showed some of the
tumors seen in previous studies. Taking this information into account,
as well as new information questioning the relevance of MCL in rats and
forestomach tumors in mice to humans, the CARC downgraded DDVP to a
possible human carcinogen (Group C). Nonetheless, the CARC maintained
that a quantitative cancer assessment was warranted using the geometric
mean of the tumor rates of MCL in rats and forestomach tumors in mice.
The fifth meeting of the CARC, in March 1996, considered new
information from Amvac including an evaluation of the severity of the
MCL seen in the NTP rat study, studies on the mechanism of forestomach
tumors, and in vivo mutagenicity testing. (Ref. 20). The evaluation of
the severity of the rat MCL in the NTP study showed that there was no
statistically significant difference in the severity of the MCL between
control and treated animals. (Ref. 21 at 10). Further, the new in vivo
testing was negative. The CARC, however, rejected Amvac's argument that
the studies it submitted demonstrated the mechanism of tumor formation
for the mouse forestomach tumors. Weighing all of this information, the
CARC retained the possible human carcinogen classification (Group C)
and recommendation for quantitative low dose linear cancer assessment.
Based on its conclusion that the MCL in rats but not the forestomach
papillomas are malignant tumors, however, the CARC concluded that the
linear low dose extrapolation should be based on the MCL in rats alone.
The sixth cancer review, finalized in February, 2000, principally
focused on the significance of the MCL in the rat NTP study taking into
account three new analyses of this cancer. (Ref. 22). The first was a
report submitted by Amvac titled ``An Evaluation of the Potential
Carcinogenicity of Dichlorvos: Final Report of the Expert Panel.''
(Ref. 23). That report was prepared by various experts in the field,
primarily academics, who had been assembled by a consulting firm hired
by Amvac. The report describes the steps taken to avoid conflicts of
interest and to insure that the substance of the report was not
influenced by its sponsor. The report concludes that the ``incidence of
MCL in the NTP DDVP rat study (1989) . . . does not support a
conclusion of carcinogenicity.'' (Id. at 21). The report summarized the
main reasons for this conclusion as follows:
1. The results are species-, strain-, and sex-specific.
2. The endpoint is dramatically affected by administration of corn
oil by gavage.
3. There was no significant effect on the relative severity of the
disease, time-to-tumor latencies or percentage of rats surviving to
study termination.
4. The data do not demonstrate a classic dose-response.
5. The results are not replicated in a very large number of
carcinogenicity studies on DDVP and related substances (e.g.,
Trichlorfon, Metrifonate, Naled).
6. Many other studies are more appropriate to estimate human risks
since the routes of administration employed more closely approximated
potentially hazardous routes in man (e.g., inhalation, dietary or in
drinking water) rather than the gavage method employed in the NTP study.
7. The incidences are similar to normal background rates that are
increasing over time.
(Id.). The report further stated that effects seen in the NTP rat study
showed ``the extremely wide variability that is typically observed with
this tumor.'' (Id.). The finding of a lack of carcinogenicity, the
report asserted, is consistent with ``similar positions taken by other
organizations (e.g., Joint FAO/WHO Panel of Experts on Pesticide
Residues, NTP, and OSTP).'' (Id.). Additionally, the report concluded
that ``metabolic considerations and the genotoxic potential of DDVP''
do not support a finding of carcinogenicity. Finally, the report
concluded that DDVP does cause forestomach tumors in mice but that this
``endpoint has no relevance to man and therefore, should not be
employed for extrapolation to human risk.'' (Id.).
The second new analysis was from the SAP review of the CARC's
fourth review of the carcinogenicity of DDVP. (Ref. 24). The SAP
concluded that ``[t]here is compelling evidence to disregard MCL in the
Fischer rat.'' The SAP gave several reasons for this conclusion based
both on general information on MCL in Fischer rats and specific
information on the NTP rat cancer study with DDVP. In terms of general
evidence, the SAP explained that (1) ``MCL is one of the most common
background tumor types'' in the Fischer rat; (2) that there is a high
variability in MCL in Fischer rats; and (3) MCL is a strain specific
cancer. (Id. at 17). On this last point, the SAP noted that MCL ``has
been referred to as Fischer rat leukemia . . . [and] [o]ther rat
strains and mice do not develop MCL, and there is no human correlate to
this disease.'' (Id.). Turning to the NTP rat study with DDVP, the SAP
noted that (1) although MCL was seen at both the low and high doses in
the study there was no clear dose-response relationship seen in the
study; and (2) chemically-related increases in MCL are marked by
advanced severity of the MCL but that the NTP rat study ``showed no
significant increase in severity of the MCL with increasing dose,
indicating that these lesions are background.'' (Id.).
The SAP also ratified the CARC's earlier position that the
forestomach tumors in the NTP mouse study should not be relied upon to
estimate risk to humans. The SAP explained that these tumors are
``likely due to the chronic irritancy, inflammation, and cytotoxicity
during chronic bolus dosing, resulting in extraordinary high local
concentration of the chemical.'' (Id.). Such conditions would not exist
outside of the laboratory. Further, such tumors have only limited
relevance to humans because ``the forestomach in rodents acts as a
storage site where irritant chemicals in food have prolonged contact
with the sensitive squamous epithelium lining, a situation that does
not pertain to humans.'' (Id.).
The SAP reached an overall conclusion that ``the weight of the
evidence suggests carcinogenicity in animals treated with DDVP with a
non-linear dose-response. However, the compound is considered a weak
carcinogen acting via a secondary or indirect mechanism.'' (Id. at 18.).
The third new analyses was a short memorandum summarizing a
conversation with Dr. Gary Boorman of the NTP. (Ref. 25). Dr. Boorman
opined that the MCL ``tumor type in males[] [Fisher rats] had a high
and variable background.'' (Id.). Further, Dr. Boorman is cited as
stating that although ``this tumor type can not be dismissed as
[ir]relevant to humans, [] it does seem to be found mainly in the
Fisher rat and does not appear to be the same type of leukemia as found
in [human] adults or children.'' (Id.).
Relying heavily on the advice of these expert scientific opinions
(particularly, the views of the SAP), the CARC in its sixth report
softened its view regarding the importance of the MCL seen in the NTP
rat study and reaffirmed its view that the forestomach tumors in the
NTP mouse study were a localized tumor of limited relevance to humans.
Although the CARC maintained that the MCL in the rat study could ``not
be totally disregarded,'' it accepted the advice of the expert panel of
the SAP and as well

[[Page 68673]]

as the report commissioned by Amvac that the evidence on MCL did not
warrant use of this cancer to quantitatively estimate cancer risk to
humans using a low-dose linear extrapolation. The CARC specifically
cited the high background rates and variability of MCL in the Fischer
rat, the lack of a dose-response effect in the NTP rat study, and
negative results in other cancer studies as justifying its decision to
change the cancer classification of DDVP from a ``possible human
carcinogen'' to ``suggestive evidence of carcinogenic potential'' and
to recommend that the data did not support a quantitative cancer risk
assessment.
To recap, EPA's initial DDVP cancer classification of ``probable
human carcinogen'' was based on a MCL and pancreatic adenomas in the
rat, forestomach papillomas in the mouse, and positive in vitro
mutagenicity data. EPA only downgraded this classification following:
(1) a re-analysis of the rat study showed no statistically significant
increase in pancreatic adenomas; (2) presentation of strong evidence
concerning the non-relevance of MCL in rats and forestomach tumors in
mice to humans; (3) submission of a negative DDVP cancer study in rats
by the inhalation route; (4) submission of in vivo data showing a lack
of mutagenicity for DDVP; and (5) repeated recommendations from
independent scientific groups to downgrade the DDVP cancer classification.
A recent review by the European Food Safety Agency (``EFSA'')
supports EPA's DDVP cancer assessment. (Ref. 15). The EFSA found the
only treatment-related tumors from the DDVP studies to be the mouse
forestomach tumors: ``[The Scientific Panel on Plant health, Plant
protection products and their Residues] concludes that with the
exception of tumours of the forestomach in the mouse, there was no
convincing evidence for a compound-related, relevant tumour response.
Tumours observed in other tissues (pancreas, mammary, mononuclear
leukaemia) showed no dose-response, were inconsistent between studies
and sexes, were reduced in control animals relative to historical
control data, or were unique to the experimental conditions of the
assay.'' (Id. at 33). Further, the EFSA found the forestomach tumors to
be ``a site of contact effect, and a consequence of the very high,
sustained concentrations of dichlorvos to the forestomach that would be
achieved by gavage dosing in corn oil.'' (Id.). These tumors, the EFSA
concluded, were subject to a threshold dose unlikely to be exceeded in
humans due to cholinesterase inhibition effects at a much lower
threshold. (Id. at 34).
NRDC is wrong to suggest that variability in MCL occurrence alone
drove EPA's decision to change its views regarding the importance of
the MCL findings. To the contrary, variability along with several other
factors were considered in EPA's weight of the evidence approach. If
anything, EPA took a more conservative approach to this cancer than its
scientific advisory panel. Further, EPA did not discount the
forestomach tumors simply because humans do not have forestomachs.
Rather, both EPA and the SAP explained why the unique aspects of the
rodent forestomach in connection with the artificial condition of corn
oil bolus dosing are likely to produce results of limited relevance to
humans.
Further, NRDC's reliance on epidemiological studies by Liess and
Brown is misplaced. EPA reviewed the Liess study and identified biases
and confounders in the studies that are a more likely explanation for
the findings of increased cancer than exposure to pest strips. (Ref. 11
at 142). As to the Brown study, EPA has rejected it as inadequate
because the subjects were exposed to other pesticides in addition to
DDVP and there was no adjustment made for these other exposures. Other
confounders such as multiple statistical comparisons were identified as
well. (Ref. 26).
2. NOAEL/LOAEL--a. NRDC's claims. NRDC notes that a NOAEL for
cholinesterase inhibition was not established in a mouse oncogenicity
study relied upon by EPA. NRDC claims that failure to identify a NOAEL
not only renders the mouse oncogenicity study invalid but ``undermines
the entire risk assessment and precludes the Agency from finding that
the DDVP tolerances are safe . . . .'' (Ref. 1 at 47). NRDC argues that
if there is no NOAEL identified in a study, the LOAEL from that study
is ``virtually meaningless information.'' (Id.). Finally, NRDC argues
that EPA cannot legally make the reasonable certainty of no harm
finding for DDVP or any other pesticide if EPA is relying on a LOAEL
rather than a NOAEL.
b. EPA's response. EPA has repeatedly rejected NRDC's legal
arguments concerning reliance on LOAELs in making safety findings under
FFDCA section 408. (70 FR 46706, 46729; 69 FR 30042, 30066-30067; Ref.
27 at 165-166). EPA incorporates those prior responses herein. Further,
EPA disagrees with NRDC's contention that a LOAEL in a study that does
not identify a NOAEL provides ``virtually meaningless information.''
Depending on the severity and consistency of the effect at the LOAEL as
well as the severity and consistency at higher doses, the LOAEL can
provide substantial information bearing on the no adverse effect level.
It is for this reason that EPA and FDA, as well as other public health
agencies, have long relied on LOAELs, in appropriate circumstances, in
making safety findings. (69 FR at 30066; Ref. 28).
EPA relied upon a LOAEL in assessing the risk posed by DDVP for the
following exposure scenarios: short-term incidental oral; short-,
intermediate-, and long-term dermal; short- and intermediate-term
inhalation. The LOAEL was from a single blind, placebo controlled,
randomized study to investigate the effects of multiple oral dosing on
erythrocyte cholinesterase inhibition in healthy male volunteers and
involved a dose of 0.1 milligrams/kilogram of body weight/day (``mg/kg/
day''). This value was adjusted with a safety factor of 3X to
approximate the value of a NOAEL. The LOAEL provided sufficient
information to estimate the NOAEL (using a 3X safety factor) because
the study measured the severity of the cholinesterase inhibition
response observed. Cholinesterase inhibition is a continuous endpoint
where no fixed generic percentage of change from baseline separates
potential adverse effects from non-adverse effects. Generally,
cholinesterase inhibition of 20 percent from baseline is regarded as
showing a potential for adverse effects on the nervous system with
lower levels evaluated on a case-by-case basis. (Ref. 9 at 37-38). In
the DDVP human study, the cholinesterase inhibition fell at the very
low end of the scale (cholinesterase inhibition in individuals varied
from baseline within a range from 8 to 23 percent at the end of the
study) indicating that the NOAEL was not significantly lower.
NRDC is mistaken to claim that the mouse oncogenicity study was
invalid for failure to identify a NOAEL. Oncogenicity (carcinogenicity)
studies are not designed to produce NOAELs but rather to examine the
cancer responses at high doses. EPA relies on chronic studies in the
rodent and non-rodent (generally the rat and dog, respectively) to
evaluate and define the level of threshold chronic, non-cancer effects.
(40 CFR 158.340(a)). Acceptable chronic rat and dog studies are
available for DDVP. (Ref. 11). NRDC also errs in contending that EPA,
by examining cholinesterase effects in the mouse oncogenicity study,
indicates that it does not have valid and reliable chronic toxicity
data. As noted, EPA does not specifically require a chronic toxicity

[[Page 68674]]

study in the mouse and it has an acceptable study meeting the
requirement for a chronic study in rodents. Nonetheless, where an
oncogenicity study in the mouse does shed light on effects seen in
chronic studies, EPA certainly will consider that information in its
overall weight-of-the-evidence evaluation for the pesticide.
3. Human studies--a. NRDC's claims. NRDC asserts that none of the
DDVP human studies satisfy the standards in EPA's human testing rule
because they ``violate the Nuremburg Code and fail to satisfy the
standards in EPA's human testing rule.'' (Ref. 1 at 26.). Therefore,
NRDC petitions EPA to reject all intentional dosing human studies for
DDVP as unethical and unscientific.
NRDC raises various specific concerns as to a particular human
study commonly referred to as the Gledhill study (MRID #
44248801). Citing a draft report by EPA's Human Studies Review Board
(HSRB), NRDC claims that this study is ``statistically meaningless''
because it had too few test subjects. Further, NRDC argues that the
variability in the cholinesterase inhibition in the study demonstrates
that ``even greater than the customary numbers of test subjects would
be required to permit detection of effects caused by the test substance
above background variation.'' (Ref. 13 at 15). Other scientific defects
in the Gledhill study alleged by NRDC include failing to promptly
measure red blood cell (``RBC'') effects; failing to measure blood
plasma effects; not restricting subjects in controlled conditions for
living and eating; and failing to properly obtain informed consent.
NRDC claims the study was ethically deficient because reference in the
consent form to DDVP as a drug made it impossible to obtain informed
consent and study conductors failed to monitor the health of subjects
after the conclusion of the study. Finally, NRDC argues that if EPA
relies on the study, EPA cannot conclude that the DDVP tolerances are
safe because the LOAEL for humans in the study (reported by NRDC to be
0.01 mg/kg/day) is well below the lowest LOAEL in animal studies (0.1
mg/kg/day).
NRDC also objects to EPA's reliance on a number of other human
studies which NRDC describes as ``ethically repugnant'' due to
involvement of children as test subjects.
b. Amvac's comments. In its comments, Amvac argues that ``there is
a large body of human data from a variety of sources that provide
information directly relevant to the DDVP risk assessment process.''
(Ref. 14 at 32). According to Amvac these human studies show that the
most sensitive endpoint for DDVP is inhibition of red blood cell
cholinesterase; DDVP operates by a common mechanism in animals and
humans; DDVP inhibits RBC cholinesterase at similar levels in animals
and humans; and DDVP has similar effects no matter what the route of
exposure. (Id. at 33). As to the Gledhill study, Amvac disputes NRDC's
criticisms of its scientific value and ethics. (Id. at 37). Amvac
claims that ``[t]he number of subjects employed, six per dose, is . . .
a standard number of test subjects sufficient to provide statistical
power in human studies.'' (Id. at 38). Measuring plasma cholinesterase
was not essential, according to Amvac, because RBC cholinesterase ``is
relevant to assessing the risk of inhibition of the toxicologically
important brain cholinesterase enzyme.'' (Id. at 37).
c. EPA's response. In responding to the petition, EPA would first
note that the petition simply asks EPA not to rely on any of the DDVP
human studies but does not contend that reliance on animal studies
instead of the human studies will show the DDVP tolerances to be
unsafe. Subsequent to NRDC's petition, EPA did rely on the Gledhill
study in assessing the risk posed by DDVP. (Ref. 11 at 133). To clarify
the basis for EPA's decision to rely on the Gledhill study, EPA has
described its decision-making process below.
EPA decisions regarding the ethics and scientific value 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 Research Rule rests on the
basic principle that EPA will not, in its actions, rely on data derived
from unethical research. The rule divides human studies into two
groups: ``new'' studies--those initiated after April 7, 2006--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).
Whether the data are ``new'' or ``old,'' the Human Research Rule
forbids EPA to rely on data from any study involving intentional
exposure of pregnant women, fetuses, or children. (40 CFR 26.1704).
To aid EPA in making ethical determinations under the Human
Research Rule, the rule established an independent Human Studies Review
Board (HSRB) to review both proposals for new research and reports of
covered human research on which EPA proposes to rely. (40 CFR 26.1603).
The HSRB is 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 intends to rely on the
results from ``old'' human research, 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).
In the risk assessment for DDVP, EPA has relied upon one human
study for several exposure scenarios. The study, conducted by A.J.
Gledhill, involved a single blind, randomized placebo-controlled oral
study in which 6 healthy male volunteers were administered a daily dose
of DDVP for 21 days at approximately 0.1/mg/kg/day and 3 volunteers
were administered a placebo

[[Page 68675]]

(Ref. 11 at 133). Prior to relying on the Gledhill study in the IRED,
EPA presented this study as well as 10 other DDVP human studies to the
HSRB for review. In its presentation to the HSRB, EPA stated that it
had concluded that the Gledhill study ``is sufficiently robust for
developing a Point of Departure for estimating dermal, incidental oral,
and inhalation risk from exposure to DDVP'' for the purpose of
assessing DDVP by itself but not for conducting a cumulative assessment
of DDVP and other organophosphate pesticides. (Ref. 29 at 19). EPA
recommended that the other 10 studies should not be used. (Id. at 20).
As part of the public participation procedures that have been
adopted by the HSRB, NRDC appeared before the HSRB when DDVP was being
considered to make the points it has raised in this petition. (Ref. 30).
The HSRB agreed with EPA on the appropriateness of using the
Gledhill study after a detailed evaluation of the scientific merit of
the study as well as an evaluation of other ethical considerations.
(Ref. 31). In examining scientific merit, the HSRB identified both
strengths and weaknesses of the Gledhill study. Identified as strengths
were: the repeated dose approach which allowed examination of the
sustained nature of RBC cholinesterase inhibition; robust analysis of
RBC cholinesterase inhibition both in terms of identifying pre-
treatment levels and consistency of response within and between
subjects; and the observation of a low, but statistically significant
RBC cholinesterase inhibition response. Weaknesses seen included: use
of a single dose; preventing establishment of a dose-response
relationship; small sample size and use of males subjects only;
measurement of RBC cholinesterase inhibition at 24 hours after dosing
which may have missed peak inhibition; no analysis of plasma
cholinesterase; sampling and analysis of enzyme inhibition ended 3 days
before the end of dosing; lack of clarity as to whether steady state
inhibition was achieved; and lack of follow-up with subjects following
completion of dosing. After carefully considering these factors, the
HSRB concluded that despite the ``numerous technical difficulties''
with the study that it ``was sufficiently robust for developing a Point
of Departure for estimating dermal, incidental oral, and inhalation
risk from exposure to DDVP in a single chemical assessment.'' (Id. at
41). The HSRB's reasoning was that ``[a]lthough a study using a single
dose level is not ideal for establishing a LOAEL, there was general
consensus that RBC cholinesterase is a well-characterized endpoint for
compounds that inhibit acetylcholinesterase activity and therefore,
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.'' (Id.).
Turning to other ethical considerations, the HSRB examined whether
there was clear and convincing evidence that prevailing ethical
standards had been violated. Specifically, the HSRB considered whether
informed consent had been compromised by certain references in test
subject disclosure forms to DDVP as a ``drug,'' or by deficiencies in
the monitoring of subjects both during and after conclusion of the
study. Ultimately, the HSRB concluded that although the study ``failed
to fully meet the specific ethical standards prevalent at the time the
research was conducted, . . . [t]here was no clear and convincing
evidence that the research was fundamentally unethical--intended to
seriously harm participants or that informed consent was not
obtained.'' (Id. at 46). The HSRB reasoned that references to DDVP as a
drug did not vitiate informed consent because ``the consent materials
clearly advised subjects that this was a study involving consuming an
insecticide.'' (Id.). Deficiencies in monitoring of subjects were found
not to provide clear and convincing evidence that the study was
ethically deficient by subjecting the test subjects to the threat of
serious harm because prior studies by this researcher involving higher
doses had only invoked minimal responses. (Id.).
The HSRB also agreed with EPA that the technical difficulties
identified with the Gledhill study limited its usefulness in the
organophosphate cumulative assessment. (Id. at 41). Finally, the HSRB
agreed with EPA that there were scientific value or other ethical
considerations that precluded reliance by EPA on the other ten DDVP
human studies. (Id. at 41-42).
EPA adopts the HSRB's reasoning and finds it persuasive in
rejecting NRDC's arguments concerning why the Gledhill study should not
be relied upon. In fact, NRDC has not raised in its petition any
arguments not considered and rejected by the HSRB.
EPA would add the following further information regarding NRDC's
criticisms of the Gledhill study's use of males only, the number of
test subjects in the study, the 24-hour period between dosing and
measurement of cholinesterase inhibition, the failure to measure plasma
cholinesterase, and purported increased sensitivity in humans
demonstrated by the study.
As to the use of males only, EPA would note that no sex differences
were observed in the comparative cholinesterase studies in animals.
(Ref. 32). With regard to statistical significance of the study results
due to the number of test subjects, EPA strongly disagrees with the
claims of NRDC. The results of the repeated dose study of 9 subjects (6
DDVP and 3 placebo) in the Gledhill study were analyzed statistically
for significance in addition to being analyzed for biological
significance. Although as a general matter more subjects would provide
greater ``statistical power,'' in this case the use of 6 to 9 subjects
with the appropriate statistical methodology is acceptable to EPA
because a positive response was seen. Indeed, all of the 6 dosed
subjects exhibited statistically significant (with respect to their
pre-dose levels) RBC cholinesterase depression on one or more days. One
of the three placebo controls exhibited statistically significant
depression on one day. However, the group means of RBC cholinesterase
activity in treated subjects are statistically below the group means of
the placebo controls on days 7, 11, 14, 16 and 18 by repeated measures
analysis of variance. (Ref. 33). The statistics of the study clearly
show the ability to demonstrate a statistically significant response.
For the sake of comparison it is worth noting that use of 6 male test
subjects exceeds the long-standing EPA recommendation for 4/sex/dose
subjects in non-rodent (usually dog) animal studies. (Ref. 34). Nor
does EPA agree with NRDC that the variability in cholinesterase
inhibition for test subjects shows that more subjects are required to
detect effects above background variations. First, the variability seen
in the study (cholinesterase inhibition in individuals varied from
baseline within a range from 8 to 23 percent at the end of the study)
is not large, particularly since the percentage inhibition in all
instances was at the marginal end of the range. Second, EPA concluded,
and the HSRB agreed, that the study did identify an effect above
background. Moreover, an intra-species safety factor of 10X was applied
to the study results to address variability in human sensitivity.
As to failure of the study to assess inhibition of plasma
cholinesterase, EPA does not believe that this deficiency has much
significance. Although the study should have had measurements of both
RBC and plasma cholinesterase, the use of RBC cholinesterase findings
provides a more

[[Page 68676]]

useful regulatory estimate for assessing the effects of DDVP on brain
and peripheral cholinesterase depression in humans. In its policy on
use of data on cholinesterase inhibition in assessing the risk of
organophosphates and carbamates, EPA made clear that ``[r]ed blood cell
measures of acetylcholinesterase inhibition, if reliable, generally are
preferred over plasma data.'' (Ref. 9 at 29). EPA explained that
``[s]ince the red blood cell contains only acetylcholinesterase, the
potential for exerting effects on neural or neuroeffector
acetylcholinesterase may be better reflected by changes in red blood
cell acetylcholinesterase than by changes in plasma cholinesterases
which contain both butyrylcholinesterase and acetylcholinesterase in
varying ratios depending upon the species.'' (Id.). Although testing
for plasma inhibition may have provided additional information, given
that the study identified statistically significant effects on RBC at a
marginal level, data on a less preferred endpoint such as plasma
cholinesterase adds little meaningful information.
With regard to the study procedure of waiting 24 hours after dosing
to measure cholinesterase inhibition, the study was designed to
evaluate the cumulative effect of repeat dosing with DDVP. While a
shorter interval between dosing and measurement would have provided
more information about acute effects of DDVP, this study has not been
relied upon to assess acute risks.
Finally, NRDC is mistaken to claim that the Gledhill study showed
humans to be more sensitive than test animals. The LOAEL from the
Gledhill study is 0.1 mg/kg/day, not 0.01 mg/kg/day, as claimed by
NRDC. (Ref. 11 at 133). The correct LOAEL is similar to the LOAEL from
animal studies.
4. Mutagenicity--a. NRDC's claim. NRDC claims that EPA cannot find
the DDVP tolerances are safe because EPA has not ``reliably
establish[ed] the bounds of risk posed by the mutagenic potential of
DDVP.'' (Ref. 1 at 47). NRDC notes that EPA has found DDVP to be
mutagenic in in vitro assays and asserts EPA has not taken this
mutagenic risk into account in assessing the safety of DDVP.
b. Amvac's Comment. Amvac claims that NRDC has focused on in vitro
assays to the exclusion of the more important in vivo studies. These
later studies, Amvac asserts ``provide[] support for the lack of in
vivo carcinogenic activity seen in the DDVP animal bioassays.'' (Ref.
14 at 31). According to Amvac, ``[p]harmacokinetic data have
demonstrated that DDVP is quickly metabolized and this likely accounts
for the difference in the in vitro and in vivo response in the
mutagenicity testing.'' (Id.).
c. EPA's response. NRDC's claim that EPA has not taken mutagenic
risk into account is mistaken. EPA has fully examined the data on
DDVP's potential for mutagenic effects and concluded that these data do
not raise a safety concern.
Mutagenicity data on DDVP shows the following: (1) DDVP does
produce positive in vitro results in the absence of activation by rat
derived liver enzymes; (2) these positive results generally disappear
in the presence of activation by liver enzymes; (3) there is some
evidence that DDVP is a weak mutagen in in vivo testing; and (4) an in
vivo chromosome aberrations study requested to address the in vivo
mutagenicity study was negative. (Refs. 11, 20 at 13, 35 and 36).
Mutagenicity data are considered by EPA both as evidence bearing on
a pesticide's carcinogenic potential and on whether the pesticide can
result in heritable mutagenic effects. As described in Unit VII.A.1.c.,
EPA fully considered the mutagenicity data in its cancer evaluation. As
to DDVP's potential to cause heritable mutagenic effects, EPA
specifically requested that an in vivo chromosome aberrations study be
performed in which germ cells as well as somatic cells were examined to
address this question. This study was negative resolving any concern
with heritable mutagenic effects. (Ref. 20 at 13). One agency reviewer
suggested a further mutagenicity study at higher doses addressing
heritable effects but EPA has not required such testing because
existing testing already tests at the maximum tolerated dose. (Ref. 37).
5. Endocrine effects--a. NRDC's claim. NRDC asserts that EPA has
failed to assess the endocrine disruption effects of DDVP. NRDC notes
that the statute requires EPA to consider, in making safety
determinations as to tolerances, whether a pesticide has an effect that
mimics estrogen or has other endocrine effects, (see 21 U.S.C.
346a(b)(2)(D)(viii)), and to establish an endocrine screening program,
(see 21 U.S.C. 346a(p)), but that EPA has not collected any data under
this program. NRDC claims that ``[i]n light of [EPA's] failure to carry
out its mandatory statutory duty to investigate the potential of DDVP
to cause endocrine disruption, EPA cannot conclude that . . . the
[DDVP] tolerances are safe.'' (Ref. 1 at 49).
b. Amvac's Comment. Amvac, in its comments, notes that EPA has
already indicated that it will rely on several studies currently
required for pesticides to assess endocrine effects and that EPA has
these studies for DDVP. (Ref. 14 at 74-75).
c. EPA's response. In a prior order adjudicating a petition to
revoke tolerances, EPA has rejected the argument that data gathered
under the Endocrine Disruptor Screening Program (``EDSP'') is a
prerequisite to a safety determination under FFDCA section 408. (71 FR
43906, 43919-43921 (August 2, 2006)). There, EPA noted that the
proposed study to be used for chemicals that initial screening suggests
may have the potential to interact with the endocrine system (the two
generation reproduction study in rats) is a study that is currently
required for approval of agricultural or other food use pesticides.
(Id. at 43920). Additionally, EPA pointed out that several other
toxicological studies required for pesticides provide information
relevant to potential endocrine disruption.
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 estrous cycling in females and
sperm number, motility, and morphology in males. The study did identify
an adverse effect on estrous 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
estrous 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.
Finally, based on a comprehensive evaluation of the testicular
toxicity of dichlorvos in rats, a recent publication reported that
there were no testicular effects, except for slightly decreased

[[Page 68677]]

sperm motility, at doses causing significant inhibition of
cholinesterase. (Ref. 38). The NOAEL for dichlorvos with respect to
reproductive organ weights, sperm counts, sperm morphology, plasma
testosterone, and testes histopathology was 4 mg/kg, the highest dose
tested.
Given that EPA has (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, EPA believes it has adequate data to make a
safety finding as to DDVP's potential endocrine-related effects.
6. Neurotoxicity--a. NRDC's claim. NRDC notes that in the 2000
preliminary risk assessment, EPA imposed a 3X uncertainty factor
because there was no measurement for cholinesterase inhibition in an
acute neurotoxicity rat study. NRDC contends that in light of the
failure to measure cholinesterase inhibition, EPA should have required
the study to be redone and that in the absence such data, EPA cannot
make its FFDCA safety finding. (Ref. 1 at 47-48). NRDC also faults the
Agency for failing to explain why, in these circumstances, a 3X
uncertainty factor is safe.
b. EPA's response. Subsequent to the 2000 preliminary risk
assessment, EPA has received additional acute neurotoxicity data in the
rat which measured cholinesterase inhibition and thus the deficiency in
the prior acute neurotoxicity study has been cured. (Ref. 11 at 130).
Accordingly, the Agency has removed the 3X uncertainty factor that had
been retained due to the deficiency in the prior study.
7. Translation of oral study to dermal endpoint--a. NRDC's claim.
NRDC asserts that EPA cannot make a safety finding for DDVP because EPA
relied on a rabbit oral study to derive a safe level of acute dermal
exposure. (Ref. 1 at 48). According to NRDC, this approach is ``based
on unwarranted and unsubstantiated assumption that the toxicology and
pharmacokinetics of oral exposure are the same as for dermal
exposure.'' (Id.) Moreover, NRDC argues that even if it were
appropriate to use oral data in place of dermal data, the ``inherent''
uncertainty requires the imposition of a properly supported uncertainty
factor. (Id.). Similarly, NRDC argues that using an oral dog study for
an intermediate-term dermal toxicity scenario is legally inappropriate
and scientifically unsupportable.
b. Amvac's comments. Amvac states that ``[i]t is common practice in
risk assessments . . . to extrapolate across exposure routes if the
characteristics of the chemical being considered, and the available
data, support such extrapolation.'' (Ref. 14 at 40). Amvac argues that
extrapolation from the oral route to the dermal route is appropriate
for DDVP because the data show that both DDVP's metabolism and types of
toxicity it causes are consistent across all routes of exposure. (Id.).
Additionally, Amvac asserts that the greater absorption of DDVP in oral
studies than in dermal studies makes it more likely that oral studies
will show DDVP-related effects than dermal studies.
c. EPA's response. Initially, EPA would note that in the IRED EPA
relied upon an oral rat and oral human study for assessing dermal
risks. Presumably, however, NRDC would have similar objections to
reliance on translation of these oral data to the dermal route.
Use of oral studies to assess dermal risks is, and has been, a
common practice at EPA for some time. (Ref. 39). Data specific to DDVP
confirm that this is a reasonable approach for this pesticide. First,
numerous toxicity studies have been performed with DDVP, involving both
acute and chronic dosing and dosing by all routes of exposure. These
studies consistently show that DDVP is an inhibitor of cholinesterase,
if doses are high enough, regardless of the duration or route of
exposure. Similar results are consistently found across the class of
organophosphate pesticides. (See, e.g., Refs. 40 and 41). Second, oral
metabolism studies indicate both that DDVP is well-absorbed from the
gastro-intestinal tract and that there are no significant differences
in excretion of DDVP doses given orally and intravenously. (Refs. 42
and 43). Accordingly, an orally-administered dose is a reliable
prediction of systemic dose. Thus, it is reasonable to use a RfD
derived from an oral DDVP study to evaluate the safety of systemic
exposures occurring as a result of dermal absorption of DDVP. Moreover,
there are two reasons to believe that EPA's use of a dermal absorption
factor of 11 percent for DDVP in translating the oral RfD into dermal
RfD tends to overstate dermal absorption, exposure, and risk. (Ref.
44). First, dermal absorption studies with volatile chemicals such as
DDVP are likely to overstate the degree of absorption because such
studies attempt to minimize losses of the chemical through evaporation.
Outside of the laboratory, there are usually no such barriers to
evaporation. Second, human skin is generally less permeable than the
rat skin (largely due to species differences in epidermal anatomy, such
as skin thickness, sebaceous secretions, and the density of hair
follicles, (Ref. 45), and thus dermal absorption studies with the rat,
such as the DDVP dermal absorption study, tend to overstate absorption
in humans.
For all of these reasons, EPA concludes that using oral DDVP
studies in assessing risk from dermal DDVP exposures is a well-
supported scientific assessment technique that would not underestimate
risks from dermal DDVP exposure. Consequently, the application of an
additional safety factor to account for uncertainty of the route to
route extrapolation is not necessary.
8. Degradates--a. NRDC's claim. NRDC asserts that the Agency has an
incomplete database regarding degradates of DDVP. (Ref. 1 at 9).
Specifically, NRDC contends that degradates identified by the Agency
were never searched for ``or even detectable in the various monitoring
and metabolism studies relied upon by the Agency.'' (Id.). Further,
NRDC states that ``[t]here is no indication whether these degradates
were ever separately subjected to toxicological testing.'' (Id.). Based
upon this assumption, NRDC contends that it is impossible for EPA to
find that the DDVP tolerances are ``safe.''
b. Amvac's comments. Amvac claims that NRDC has failed to consider
whether the DDVP degradates are toxicologically significant. (Ref. 14
at 68). According to Amvac, ``[i]t is clear just from the structures of
some of these degradates that they are either not toxicologically
significant, and/or, based on structure activity relationships and
knowledge concerning mechanisms of toxicity, that these degradates have
much lower toxicity than the parent compound.'' (Id.).
c. EPA's response. NRDC's concern that EPA has not searched for
DDVP's major metabolites in magnitude of the residue studies is
misplaced because EPA has determined that these metabolites are rapidly
degraded to harmless chemicals in the normal course of plant and
mammalian metabolism. The residue of concern is DDVP and that is the
chemical identified by DDVP's analytical method.
EPA has a robust understanding of DDVP's metabolites and degradates
derived from multiple metabolism studies in several different animal and

[[Page 68678]]

plant species. (Refs. 46, 47, 48, 49, 50 and 51). In animals, DDVP's
primary metabolites are dichloroacetaldehyde or (minor pathway) des-
methyl DDVP. Des-methyl DDVP also breaks down into
dichloroacetaldehyde. Dichloroacetaldehyde is rapidly dechlorinated and
oxidized and either expelled from the body through respiration as
carbon dioxide or through excretion in the urine and feces as urea or
hippuric acid or converted into basic carbon compounds which are
incorporated in amino acids (e.g., glycine, serine) and proteins. In
metabolism studies using radioactive-labeled DDVP, little or no DDVP or
its primary metabolites were found in animal tissues and milk.
In plants, DDVP is hydrolyzed to dimethyl phosphate and
dichloroacetaldehyde. Dimethyl phosphate is sequentially degraded to
monomethyl phosphate and inorganic phosphates. Dichloroacetaldehyde is
converted to 2,2-dichloroethanol which is conjugated and/or incorporated
into naturally-occurring plant components after additional metabolism.
9. Inerts--a. NRDC's claims. NRDC asserts that the ``apparent
absence of data on the risks posed by the inert ingredients and
impurities in all DDVP end-use products compels . . . the revocation of
all DDVP tolerances.'' (Ref. 1 at 68).
b. EPA's response. If an inert ingredient that is combined with
DDVP in an end-use product poses a risk of concern, then there would be
grounds for modifying or revoking the tolerance or tolerance exemption
pertaining to the inert ingredient. It would not be grounds for
revoking the DDVP tolerance, which is evaluated based on the safety of
DDVP. All impurities in technical active ingredient DDVP, which would
be included at lower levels in DDVP end use products, were tested as
part of the technical active ingredient when the toxicology tests on
the technical active ingredient DDVP were conducted.
10. Other allegedly missing toxicity data--a. NRDC's claims. NRDC
contends that the Agency cannot make its statutory determination of
safety for DDVP dependent upon the submission of data. Specifically,
NRDC asserts that in the absence of a dermal sensitization study and a
developmental neurotoxicity test (DNT) study, EPA cannot make a safety
finding for DDVP under the FFDCA.
b. EPA's response. EPA has received and reviewed a DNT study for
DDVP. (Ref. 11 at 127). Additionally, NRDC is incorrect in asserting
that EPA does not have any dermal sensitization data for DDVP. On the
contrary, the Agency has four dermal sensitization studies for DDVP.
(Refs. 52, 53, 54 and 55). The DDVP dermal sensitization studies were
conducted with formulations, containing varying levels of technical
DDVP. All four of the studies were negative for sensitization in guinea
pigs. Although none of the studies tested DDVP in isolation, sufficient
information was obtained from the four studies to define the dermal
sensitization toxicity of DDVP.

B. Dietary Exposure Issues

1. Revised dietary exposure and risk assessment. NRDC's petition
challenges numerous aspects of EPA's 2000 proposed dietary exposure and
risk assessment of DDVP. This exposure and risk assessment was
incorporated into the 2006 DDVP IRED without major changes. In
responding to NRDC's petition, EPA has updated the DDVP dietary
exposure and risk assessment. The main changes in the revised
assessment include: (1) use of EPA's current dietary assessment
program, DEEM-FCID, instead of DEEM; (2) incorporation of residue
estimates for drinking water directly into the DEEM-FCID program; (3)
updated monitoring data (principally from the USDA-Pesticide Data
Program (``PDP'')) and percent crop treated data; and (4) incorporation
of estimated exposure from use of naled as a wide area treatment for
mosquitoes. A summary of the revised dietary risk assessment is
presented in this unit and NRDC's specific comments are responded to
individually below. (Ref. 56).
The estimated risk levels, presented in Table 1, are largely
unchanged from the 2006 IRED when both food and water are considered.
Although this risk assessment is highly refined as to some commodities
it still contains numerous conservatisms. More details concerning the
revised risk assessment are provided in responding to NRDC's specific
objections.

Table 1.--Dietary (Food and Water) Exposure and Risk for DDVP
----------------------------------------------------------------------------------------------------------------
Acute Dietary (99.9 Percentile) Chronic Dietary
-------------------------------------------------------------------------------
Population Subgroup Dietary Exposure Dietary Exposure
(mg/kg/day) % aPAD (mg/kg/day) % cPAD
----------------------------------------------------------------------------------------------------------------
General U.S. Population 0.001313 16 0.000060 *COM041*12
----------------------------------------------------------------------------------------------------------------
All Infants (< 1 year old) 0.003735 47 0.000116 23
----------------------------------------------------------------------------------------------------------------
Children 1-2 years old 0.001523 19 0.000111 22
----------------------------------------------------------------------------------------------------------------
Children 3-5 years old 0.001312 16 0.000103 21
----------------------------------------------------------------------------------------------------------------
Children 6-12 years old 0.000911 11 0.000069 14
----------------------------------------------------------------------------------------------------------------
Youth 13-19 years old 0.000967 12 0.000048 10
----------------------------------------------------------------------------------------------------------------
Adults 20-49 years old 0.001475 18 0.000057 11
----------------------------------------------------------------------------------------------------------------
Adults 50+ years old 0.000929 12 0.000051 10
----------------------------------------------------------------------------------------------------------------
Females 13-49 years old 0.001000 13 0.000050 10
----------------------------------------------------------------------------------------------------------------

2. Drinking water models--a. NRDC's claims. NRDC argues that the
DDVP tolerances are unsafe because EPA has inadequate data on DDVP
levels in drinking water. (Ref. 1 at 40). NRDC notes that EPA has
limited groundwater monitoring data and no surface water monitoring
data for DDVP, naled, and trichlorfon. In the absence of DDVP

[[Page 68679]]

water monitoring data, NRDC claims EPA cannot find the DDVP tolerances
to be safe. Further, NRDC claims that the surface water exposure model
used by EPA in the preliminary risk assessment (PRA), GENEEC, has not
been properly validated, and that ``EPA has failed to demonstrate that
the surrogate data [in the model] are properly matched to DDVP and that
the model's assumptions and parameters are justified.'' (Id. at 54).
NRDC makes similar claims regarding the matching of surrogate
groundwater data to DDVP through the operation of the SCI-GROW ground
water model. (Id. at 55). According to NRDC, ``if the SCI-GROW model
employed surrogate data [on DDVP], it cannot be assumed to be reliable
unless full disclosure of its construction and inputs is made and this
information demonstrates its reliability.'' (Id.).
In its comments on the DDVP IRED, NRDC raised similar issues. (Ref.
13 at 9). Citing a number of alleged uncertainties pertaining to the
SCI-GROW model, NRDC argues that because ``[n]one of these
uncertainties is quantitatively bounded ... the Agency has not or
cannot determine with reasonable certainty that the risks from
groundwater contamination by DDVP will not harm people.'' (Id.).
Additionally, NRDC claims the assessment for groundwater is incomplete,
because EPA has not aggregated DDVP in groundwater resulting from uses
of DDVP, naled, and trichlorfon. (Id.).
Finally, in its petition, NRDC asserts that EPA's conclusion that
DDVP will not be persistent in surface waters is mere speculation.
(Ref. 1 at 44).
b. Amvac's comments. Amvac disputes NRDC's criticism of EPA's
drinking water models stating ``NRDC appears to not understand the
underlying assumption and highly conservative nature of these models.''
(Ref. 14 at 63). Further, Amvac argues that, because of the highly
conservative nature of the models, the targeted monitoring data NRDC
calls for would show that DDVP exposure in drinking water is lower than
projected. (Id. at 70-71). Amvac further notes that targeted monitoring
data has limited applicability and would be unlikely ``to be
representative of potential exposure on a wider geographical scale.''
(Id. at 71).
c. EPA's response. NRDC's general claims regarding EPA's drinking
water models are addressed for the most part in a prior EPA order
denying NRDC objections to use of these models in making a safety
finding for a pesticide tolerance. (69 FR 30042, 30058-30065 (May 24,
2006). In that order, EPA explained in detail as to each of the models:
(1) the basic principles on which the model is based; (2) the data
underlying the models; (3) the numerous conservatisms built in to each
of the models; (4) the extensive independent peer review used in the
development of the models; and (5) the external and internal testing of
the accuracy of the models. After this extensive analysis, EPA
concluded the models ``are based on reliable data and have produced
estimates that EPA can reliably conclude will not underestimate
exposure to pesticides in drinking water.'' (Id. at 30065). Not only
does this order provide a detailed description of the models and data
underlying the models but it referenced the many SAP reviews and Agency
policy documents that further explained the models. Additionally, it
should be noted that detailed information concerning the models is
available on EPA's website. EPA has recently updated this information
to insure that the website provides not only the ability to run the
models but also a description of the how the models work and the
underlying codes included in the structure of the model. (Ref. 57)
NRDC's more specific allegations are also without merit. First, EPA
took the characteristics of DDVP, naled, and trichlorfon into account
in modeling DDVP levels in drinking water. Specific information
concerning these pesticides' mobility and persistence was combined with
information pertaining to application amounts in use of PRZM-EXAMS to
model surface water DDVP levels and SCI-GROW to model groundwater DDVP
levels. In addition, information on soil properties, cropping
characteristics, and weather appropriate to use of these pesticides was
incorporated in the PRZM-EXAMS model run. (Ref. 58). Second, EPA has
adequately addressed uncertainties in the PRZM-EXAMS model through peer
review and validation. NRDC claims that EPA has not quantified the
uncertainties in the SCI-GROW model and thus cannot rely on it;
however, NRDC's listing of uncertainties (e.g., small drinking water
reservoir, runoff prone soils) applies to considerations relative to
the surface water model PRZM-EXAMS not SCI-GROW. These apparent
criticisms of the PRZM-EXAMS model are without merit. As noted above,
while EPA has not specifically quantified each individual uncertainty
associated with the model, the overall model has been extensively peer-
reviewed and validated, and has proved very conservative in practice.
Third, EPA's estimation of surface water DDVP levels is not flawed for
failure to combine exposures from DDVP, naled, and trichlorfon. The
highest estimated surface water DDVP levels are from the naled use on
brassica and the trichlorfon use on turf ((33 parts per billion
(``ppb'') and 60 ppb, respectively, for acute exposure and 1.83 ppb and
1.56 ppb, respectively, for chronic exposure). These estimates are
based on the conservative assumption that 87 percent of the area of the
watershed is cropped to either brassica or turf and all of the brassica
or turf is treated with naled or trichlorfon, respectively. The figure
of 87 percent is based on the fact that ``87 percent cropped was the
largest cropped area in any 8-digit hydrologic unit in the continental
United States.'' (69 FR 30042, 30060 (May 26, 2004)). Thus, there is no
reason to combine these estimates. A watershed may be 87 percent turf
or 87 percent brassica but not both. Moreover, the available data
indicate that both trichlorfon and naled are used relatively
infrequently on turf and brassica, respectively; thus, the water level
estimate is overstated to begin with. (Refs. 56 and 59). In theory, the
DDVP use producing the highest estimated surface water levels (wide
area treatment for mosquitoes) could overlap somewhat with these uses
but not only is estimated water concentration from the DDVP use
insignificant compared to the levels used to assess acute and chronic
drinking water exposure (10X and 20X lower, respectively) but relevant
survey data show no report of DDVP for this use. (Ref. 60).
EPA has chosen to rely on modeling estimates of DDVP in drinking
water because the drinking water modeling data it has were not
necessarily collected in areas of DDVP, naled, or trichlorfon usage and
there is inadequate data on drinking water from shallow, groundwater
wells. Nonetheless, the sampling data give some indication of the
conservativeness of the modeling estimates. USDA's Pesticide Data
Program (``PDP'') collected finished drinking water samples from
California and New York in 2001 (214 samples) and from California,
Colorado, Kansas, New York, and Texas in 2002 and 2003 (371 and 699
samples, respectively). In 2004, PDP sampled raw and finished water
from 171 community water systems from Michigan, North Carolina, Ohio,
Oregon, Pennsylvania, and Washington (234 samples). Although the
samples were analyzed for DDVP, no detectable residues of DDVP were
found in any sample. The limits of detection for these

[[Page 68680]]

monitoring data were between 0.4 and 22.5 parts per trillion (ppt). By
comparison, the estimates from EPA's drinking water models that EPA is
using in the DDVP risk assessment are 60 ppb for acute risk and 1.83
ppb for chronic risk. (Ref. 11). In parts per trillion, these values
would be 60,000 ppt and 1,830 ppt.
As to NRDC's claims that EPA is simply speculating in stating that
DDVP is unlikely to persist in surface water, NRDC is mistaken. The
conclusion that DDVP will not be persistent in surface water is based
on the physical and chemical properties of DDVP and the results of the
suite of environmental fate and transport studies on the compound. As
EPA noted in the DDVP IRED, ``dichlorvos should not be persistent in
any surface waters due to its susceptibility to rapid hydrolysis and
volatilization.'' (Ref. 11 at 152).
2. Dietary exposure models--a. NRDC's claims. NRDC contends that
the Dietary Exposure Model (DEEM) cannot be used to demonstrate the
safety of the DDVP tolerances because ``[t]he model is secret in that
the codes, internal structure and assumptions have not been made
available to the public for scrutiny and comment.'' (Ref 1 at 44).
Additionally, NRDC argues that the model cannot be relied upon because
it has never been validated. (Id.).
b. Amvac's comments. Amvac notes that EPA has used DEEM for many
years and claims that the DEEM ``software and its use have received
many peer reviews ....'' (Ref. 14 at 57). Further, Amvac asserts that
``[t]his model and the other models that EPA uses to assess dietary
risk (i.e., LifelineTM and CARES) have all been made available to the
public and their computer codes are available for public review and
comment.'' (Id. at 57-58).
c. EPA's response. DEEM and its successor, DEEM-FCID, are not
secret models. As explained in Unit III.B.3.b.i.(B)., these dietary
assessment models use relatively simple formulas to combine consumption
information with residue levels in food to estimate exposure and risk.
In 2000, the company that developed DEEM made a detailed explanation of
the model public so that the model could be reviewed by the FIFRA SAP.
(Ref. 7). That explanatory paper documented the data included in DEEM
and the algorithms DEEM uses to manipulate that data to estimate
exposure and risk. In addition to the algorithms, the paper contained a
full delineation of underlying computer segment codes that comprise the
DEEM program. In response to the SAP's concern that the DEEM paper did
not make public the ``recipes'' used to translate the CSFII consumption
data back to the precursor agricultural commodities (e.g. translating
pizza into tomatoes, wheat, cheese, etc.), EPA contracted to have a new
set of translations produced that would not be subject to proprietary
restrictions. Those new translations have been completed and
incorporated into DEEM-FCID, DEEM's successor, and are fully available
to the public. (Ref.61).
Thus, NRDC is wrong in its assertion that DEEM is a ``secret''
model. The fundamental logic of this model is available to the public
(including both the algorithms and computer codes) and data on food
recipes is available on DEEM's successor DEEM-FCID, the model used to
run EPA's latest dietary risk assessment for DDVP. NRDC's concerns
regarding validation are misplaced as well in that DEEM and DEEM-FCID
have been reviewed by the SAP and produce similar results to other
publicly-available dietary exposure models. (See, e.g., 70 FR 77363
(December 30, 2005); 70 FR 40202 (July 13, 2005)). Accordingly, NRDC's
request that the DDVP tolerances be revoked because of reliance on DEEM
is denied.
3. Percent crop treated data--a. NRDC's claims. NRDC asserts that
EPA has used percent crop treated data in calculating aggregate
exposure for DDVP without making the findings required by section
408(b)(2)(F). (Ref. 1 at 39). That section imposes certain conditions
upon EPA's use of percent crop treated data when assessing chronic
dietary risk. Among the specified conditions are the requirements that
EPA find (1) ``the data are reliable and provide a valid basis to show
what percentage of the food derived from such crop is likely to contain
such pesticide chemical residue;'' (2) ``the exposure estimate does not
understate exposure for any significant subpopulation group;'' and (3)
``if data are available on pesticide use and consumption of food in a
particular area, the population in such area is not dietarily exposed
to residues above those estimated by [EPA].'' (21 U.S.C.
346a(b)(2)(F)). Finally, if EPA does rely on percent crop treated data
EPA must provide for the periodic reevaluation of the estimate of
anticipated dietary exposure. (Id.). NRDC claims that EPA, having
failed to make the foregoing findings cannot rely on percent crop
treated in making a safety finding for the DDVP tolerances.
b. Amvac's comments. Amvac asserts that adequate data are available
on percent crop treated referring to an EPA memorandum (Hummel, 2000).
(Ref. 14 at 47-48). According to Amvac, ``[t]hat memorandum describes
the source of the data and states that the upper end of the range was
assumed for acute dietary exposure analysis and that the typical or
average was used for the chronic dietary exposure analysis, as is
typical EPA practice.'' (Id.).
c. EPA's response. EPA conducted a comprehensive evaluation of the
usage of DDVP, naled, and trichlorfon for the DDVP IRED. That
evaluation was described in the memorandum cited by Amvac and the
memorandum was included in the docket and on EPA's website page for
DDVP. In response to NRDC's petition EPA has updated its analysis of
percent crop treated information. Specifically, in its revised analysis
EPA used percent crop treated data in estimating exposure from use of:
(1) DDVP on livestock; (2) trichlorfon on turf; (3) DDVP and naled as a
mosquito (wide area) treatment; and (4) naled on agricultural crops.
Based on the findings below, EPA concludes that its consideration
of usage or percent crop treated data to estimate percent crop treated
conforms to the requirements in section 408(b)(2)(F).
i. Reliable data. The primary source of data for estimating the
percent of a commodity treated with a pesticide is the United States
Department of Agriculture's National Agricultural Statistics Service
(``NASS''). NASS collects data on a wide variety of agricultural topics
including pesticide usage. NASS uses the Agricultural Resources
Management Survey (``ARMS'') as well as other surveys to collect data
on pesticide usage and other agricultural topics. These surveys are
designed to produce statistically representative estimates of pesticide
usage on targeted crops in the surveyed States using a
probabilistically-based sampling procedure. (See
http://www.usda.gov/nass/nassinfo/surveyprograms/index.htm
and https://arms.ers.usda.gov/GlobalDocumentation.htm).
ARMS is a multi-phase, multi-frame, stratified, probability-
weighted sampling design. There are three phases to the annual survey:
a screening phase to update data and help target sampling for phases
two and three; a second phase that collects information on agricultural
practices and chemical usage; and a third phase that collects costs and
financial information. ARMS consists of two ``frames'' collecting farms
and ranches. The main frame is the ``list frame'' that is intended to
contain the names and addresses of all farms and ranches in the
continental United States along with the acreage of the farms/ranches
and the crops grown or livestock raised. The list frame is compiled
based on the Census of Agriculture as well as numerous other

[[Page 68681]]

surveys and governmental and non-governmental sources. The list frame
is back-stopped by the ``area frame'' which is constructed from
satellite images of the continental United States broken down into
segments based upon degree and type of cultivation. Both frames are
divided into different strata such as crop type. Due to the complexity
of the sample design, ARMS uses a weighting system to adjust data
gathered in reports from sampling of the frames.
Data is gathered by a statistically-designed sampling of the list
and area frames. The sampling is done on a state basis with the focus
for any particular crop on the major production states. Generally,
samples are conducted in states representing 90 percent or better of
the production acreage. Reports are usually prepared based on face-to-
face interviews with the identified growers. Surveys for field crops
are conducted annually with the crops varying each year. (See
http://usda.mannlib.cornell.edu/MannUsda/viewDocumentInfo.do?documentID=1560)
Surveys for fruits and surveys for vegetables are conducted in
alternating years with fruits surveyed in odd years and vegetables in
even years. (See
http://usda.mannlib.cornell.edu/MannUsda/viewDocumentInfo.do?documentID=1567 and
http://usda.mannlib.cornell.edu/MannUsda/viewDocumentInfo.do?documentID=1572).
There is some variation in the crops sampled in each survey. NASS data
on pesticide use on livestock are published periodically by USDA (1999
(summary of 1997 livestock and general farm survey), 2000 (summary of
1999 swine and swine facilities survey), 2001 (summary of 2000 sheep
and sheep facilities survey), 2002 (summary of 2001 dairy cattle and
dairy cattle facilities survey), and 2006 (summary of 2005 swine and
swine facilities survey), see
http://usda.mannlib.cornell.edu/MannUsda/viewDocumentInfo.do?documentID=1569).

To estimate percent crop treated for pre-harvest pesticide uses,
EPA has created a database containing NASS data from the years 1999-
2005. Also included in this database is data from a private service,
Doane Marketing Research, Inc., now known as dmrkynetec. This database
was used for making the majority of the percent crop treated estimates
for the DDVP assessment, namely, the estimates pertaining to the use of
naled as an agricultural pesticide. The 2007 estimates show that naled
is generally used on a very small percentage of crop acreage. This is
consistent with the estimates made for the 2000 dietary risk
assessment. Most estimates from the two assessments were similar with a
few crops showing declining use over time and one crop (strawberries)
showing increased use. (Refs. 62 at 27-30; 56 at 29).
Dmrkynetec is a market research company. Originally, it focused on
providing market and tracking data to agribusiness but has expanded its
services to a wide range of industry sectors. In the agriculture area,
dmrkynetec gathers information by survey research on, among other
things, crop acres grown, pesticide active ingredients used, total
acres treated with pesticides, pesticide application rates and timing,
number of pesticide applications, and pesticide prices. For over 30
years, EPA has purchased dmrkynetec's proprietary database, which
provides pesticide usage information for over 50 crops. As part of
EPA's contract with dmrkynetec, EPA requires both a quality management
plan and a quality assurance project plan to insure that dmrkynetec's
survey practices and data compilation are well-designed and reliably
executed. Data from dmrkynetec is relied upon not only by EPA but by
other Federal agencies and private industry. (Ref.63).
For one commodity, poultry, for which sufficient NASS and
dmrkynetec data were not available, EPA followed a different approach
in estimating percent crop treated. EPA interviewed agricultural
extension agents and professors in agricultural colleges in major
poultry-producing states and reviewed crop profiles compiled by USDA
and other literature from the extension services to obtain rough
estimates of usage. Because this information was not based on
statistically-designed surveys, EPA used it in a very conservative
manner to estimate worst case percent crop treated estimates.
Information gathered on broilers indicated that, DDVP was rarely, if
ever used in broiler production in most of the major producing states.
The one exception is Georgia, the largest broiler producing state,
where approximately 1/3 of the broiler flock is treated with a product
containing DDVP. As to layers (egg producers), DDVP is also not used in
significant amounts in most of the major producing states. However, an
expert in California (fourth in egg production among states) indicated
that a product containing DDVP was used on approximately 75 percent of
the state's layers. As a very conservative estimate, EPA assumed that
75 percent of the broilers and layers nationwide are treated with DDVP.
(Ref. 64).
Estimates of the percent of crops that receive incidental treatment
with naled or DDVP as a result of these pesticides' usage as a wide
area treatment for the control of mosquitoes was based on a combination
of data from NASS and Kline and Company, Inc., a private market
research firm. Data from NASS' Census of Agriculture was used to
determine the total farm acreage in the United States. Data from Kline
provided information on the poundage of naled and dichlorvos used for
mosquito treatment. This information was combined in a very
conservative fashion with the data on total crop acreage in the United
States. EPA calculated what percentage of the total crop acreage could
have been treated with the naled and DDVP used for mosquito control and
assumed that every crop in the United States was treated to that extent
(3 percent). Although some treatment of agricultural crops will occur
from the mosquito usage, a significant part, if not most, of the
treatment area will be in wetlands, forest, urban and suburban land,
and other non-crop areas. Even where agriculture land is treated, such
treatment may occur when no crop is present or, even if a crop is
present, at such a time that all residues would be expected to degrade
prior to harvest. Estimates of percent crop treated for turf uses was
also based on data from Kline. This information was not used to
quantitatively estimate exposure but simply to qualitatively
characterize the conservativeness of the drinking water concentration
estimates from turf usage produced by EPA's drinking water model.
NASS's Census of Agriculture is as the name would suggest a
complete count of United States farms and ranches. Additionally, the
Census collects information on land use and ownership, agricultural
practices, and farm income and costs. The Census is conducted every 5
years by law and involves individual contact with all farmers and
ranchers in the United States. (See http://www.agcensus.usda.gov ).
Kline, like dmrkynetec, conducts market research through surveys on
a wide range of products. EPA has been purchasing data on non-
agricultural pesticide usage from Kline for over 20 years. As with the
dmrkynetec contract, EPA has required both a quality management plan
and a quality assurance project plan to insure that Kline's survey
practices and data compilation are well-designed and reliably executed.
Data from Kline is relied upon not only by EPA but by other federal
agencies and private industry. (Ref. 63).

[[Page 68682]]

EPA concludes these data sources provided reliable data for the
percent crop treated estimates that were used by EPA.
ii. Significant subpopulation group. EPA considered DDVP exposure
to the general population as well as 32 subpopulation groups based on
regional location, ethnicity, and age. Reliance on the estimates of
percent crop treated discussed above will not underestimate exposure
for any of these population subgroups.
iii. Data on pesticide use and consumption. EPA takes information
on regional consumption patterns into account in estimating exposure to
significant subpopulation groups. EPA's information on percent crop
treated is primarily national in scope and does not indicate that
regional groups have greater exposures to DDVP than estimated by EPA.
iv. Periodic evaluation. The statute provides that EPA shall
periodically reevaluate the estimate of anticipated dietary exposure.
This is a prospective requirement. Although it may do so sooner, EPA
expects that the exposure estimates will be reevaluated periodically
through the registration review process. (21 U.S.C. 346a(b)(2)(F); Ref. 65).
To evaluate the sensitivity of dietary risk assessment to EPA's
percent crop treated findings, EPA conducted an alternate dietary
assessment assuming 100 percent crop treated for all commodities. (Ref.
56). As Table 2 shows, even using this very conservative assumption,
dietary exposure is well below the RfD/PAD for DDVP.

Table 2.--Dietary (Food and Water) Exposure and Risk for DDVP Incorporating 100 Percent CT for All Commodities
--------------------------------------------------------------------------------------------------------------------------------------------------------
Acute Dietary(99.9 Percentile) Chronic Dietary
---------------------------------------------------------------------------------------------------
Population Subgroup Dietary Exposure (mg/kg/ Dietary Exposure (mg/kg/
day) % aPAD day) % cPAD
--------------------------------------------------------------------------------------------------------------------------------------------------------
General U.S. Population 0.002274 28 0.000112 22
--------------------------------------------------------------------------------------------------------------------------------------------------------
All Infants (< 1 year old) 0.004152 52 0.000154 31
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 1-2 years old 0.004663 58 0.000252 50
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 3-5 years old 0.003533 44 0.000214 .......................
--------------------------------------------------------------------------------------------------------------------------------------------------------
Children 6-12 years old 0.002677 33 0.000138 28
--------------------------------------------------------------------------------------------------------------------------------------------------------
Youth 13-19 years old 0.001660 21 0.000092 18
--------------------------------------------------------------------------------------------------------------------------------------------------------
Adults 20-49 years old 0.001850 23 0.000102 20
--------------------------------------------------------------------------------------------------------------------------------------------------------
Adults 50+ years old 0.001437 18 0.000088 18
--------------------------------------------------------------------------------------------------------------------------------------------------------
Females 13-49 years old 0.001603 20 0.000097 19
--------------------------------------------------------------------------------------------------------------------------------------------------------

4. Anticipated residues-- a. NRDC's claims. NRDC asserts that
because EPA relied upon anticipated residue data, EPA must issue a data
call-in to demonstrate that actual residues are not higher than the
anticipated residues relied upon by the Agency. (21 U.S.C.
346a(b)(2)(E)(ii)).
b. EPA's response. This is a prospective requirement. To the extent
that NRDC is claiming that EPA must revoke all DDVP tolerances because
the FFDCA provides that EPA must require the registrant to submit data
in the next 5 years pursuant to section 408(f), that claim is rejected.
5. Trichlorfon and naled--a. NRDC's claims. Based solely upon EPA's
statement in the prelimanry risk assessment that ``[n]on-detectable
Dichlorvos residues in livestock commodities are expected as a result
of Trichlorfon use[,]'' NRDC speculates that the method for detecting
DDVP in beef may not be sensitive enough to detect toxicologically
significant residues. (Ref. 1 at 40). Based on this speculation, NRDC
claims that the DDVP tolerances do not comply with the requirement in
section 408(b)(3) that ``a tolerance ... shall not be established at
... a level lower than the limit of detection of the method for
detecting and measuring the pesticide chemical residue ... .'' (21
U.S.C. 346a(b)(3)(B)). Further, NRDC claims that EPA has not explained
its conclusion that residues from trichlorfon use are estimated not to
increase residues from the use of DDVP. (Ref. 1 at 51). In addition,
NRDC contends that the Agency's analysis of DDVP residues from the use
of naled (which also degrades into DDVP) for mosquito control is
inadequate.
b. EPA's response-- i. Trichlorfon. Trichlorfon degrades in plants
and livestock and one of the products (metabolites) that forms is
dichlorvos. Trichlorfon livestock feeding studies did not detect
residues of dichlorvos using a level of detection (``LOD'') of 0.05
ppm. The trichlorfon RED concluded that dichlorvos was not a
significant residue in the cattle based on the feeding study and a
metabolism study. The metabolism study found DDVP in subcutaneous fat
at 4 percent of the total radioactive residue (TRR), and less than 1
percent of the TRR in loin muscle (0.006 ppm). (Ref. 66). Subcutaneous
fat is not used for human consumption, and often has residues higher
than that in fat more distal from the site of application. Thus, it is
highly unlikely that livestock will contain residues of dichlorvos from
the use of trichlorfon. In any event, the residue monitoring data on
DDVP includes DDVP as a degradate of trichlorfon and thus any DDVP in
beef from use of trichlorfon would be captured by the monitoring data.
The Agency has substantial data showing that residues of dichlorvos
as a result of trichlorfon use will be non-detectable in beef. USDA-
FSIS has sampled for trichlorfon and dichlorvos in the past. Although
there is no U.S. registration for trichlorfon on cattle, there are
tolerances so that foreign cattle can be treated and imported to the
United States. From 1993 through 1997, FSIS monitored over 12,000
samples of beef. (Ref. 67). No residues of dichlorvos

[[Page 68683]]

or trichlorfon were detected at a LOD of 0.2 ppm. However, detectable
residues of other organophosphates were found.
In addition, monitoring data from PDP were available for milk at
the time the last anticipated residues were determined for the 2000
IRED, and were used in the dietary exposure assessment for the IRED.
One detectable residue was reported at 0.003 ppm out of 1,881 samples,
with an LOD of 0.001 - 0.002 ppm (avg. 0.0014 ppm). (Ref. 62 at 12).
Since that time, PDP collected over 300 samples of beef fat, liver, and
muscle from 2001 to 2002 and found no detectable dichlorvos at a LOD of
1.0 ppb; over 300 samples of pork in 2005 and found no detectable
dichlorvos residues at an LOD of 0.9 ppb in fat; and LOD of 0.45 ppb in
pork muscle; and over 600 samples of poultry commodities in 2000-2001
with no detectable residues of dichlorvos at an LOD of 6.3 ppb. PDP
also analyzed over 100 samples of heavy cream, and found no detectable
residues of dichlorvos at a LOD of 1-2 ppb. Finally, no detects of DDVP
were found 1,485 samples of milk analyzed in 2004-2005, at an LOD of
0.06 ppb. (Refs. 56 at 13; and 68).
NRDC is mistaken to claim that the detection method for DDVP in
meat is not adequately sensitive. Generally, the Agency accounts for
non-detectable residues by using [frac12] the LOD or LOQ in its
calculations. (Ref. 69). If this calculation shows a potential risk
problem, then the limits of detection must be lowered. In the case of
dichlorvos, no risks of concern were identified for livestock
commodities when they were assessed at [frac12] the LOD. In fact, total
dietary risk from DDVP in food is just a small fraction of the RfD.
Thus, the LODs are low enough to be below the level of risk concern and
to ensure detection of toxicologically significant metabolites.
ii. Naled. DDVP exposure from use of naled to control mosquitoes
through wide area treatment is likely to be very low to non-existent
for two reasons: (1) The treatment rate is very low--0.25 lb ai naled/
Acre, compared to the usual application rate for field crops of 1.8 lb
ai naled/Acre; (2) residues from treatment degrade rapidly; and (3) the
usage rate indicates few crops will be impacted by the mosquito use.
Residue data from field trials showed most samples to be 0.03 ppm or
less. One DDVP residue from the wide area treatment with naled was as
high as 0.27 ppm, with the duplicate of this sample having a residue of
0.08 ppm (average residue 0.18 ppm DDVP). (Ref. 70). Additional data
show that residues of DDVP are formed 1-3 days after field treatment
with naled, and decline to non-detectable within 7 days of treatment
with naled. (Ref. 71). Further, PDP data showed no detectable levels of
DDVP in crops not registered to be treated with naled out of roughly
10,000 samples. (Ref. 56 at 19-20).
Despite these data suggesting there will be little to no exposure
in the diet from use of naled to control mosquitoes, EPA took a very
conservative approach to estimating exposure from the naled mosquito
use in its revised risk assessment. (Ref. 56). First, EPA examined
usage data to determine a rough estimate of the acreage treated with
naled for mosquito control. (Ref. 72). EPA assumed that all acres
treated were cropped farmland and not wetlands, woodlands, urban or
suburban areas, or other non-cropped areas. This acreage was then
expressed as a percentage of the overall farm acreage in the United
States. That percentage (3 percent) was the value used in estimating
the percent crop treated for all crops grown in the United States. If
DDVP or naled is not registered for use on a crop, EPA assumed that
three percent of that crop was treated. If DDVP or naled are registered
on a crop and EPA has data on the percent of that crop treated as an
agricultural use with DDVP or naled, EPA summed the percentages from
the agricultural use and the mosquito use in estimating percent crop
treated. Finally, if DDVP or naled are registered on a crop and EPA
does not have data on the percent of that crop treated as an
agricultural use with DDVP or naled, EPA assumed 100 percent of the
crop was treated with DDVP or naled. In the latter circumstance, EPA
considered but rejected somehow incorporating the mosquito use as an
overlapping use because, for among other reasons, exposure from crops
was based not on data from field trials but from monitoring data.
6. Translation of reside levels--a. NRDC's claims. NRDC contends
that EPA cannot make the safety finding for DDVP because EPA has
translated data from grain dust to soybean aspirated grain fractions
and data from cattle to swine based on speculation and not validated
data. Indeed, NRDC argues that every translation of data from one plant
or species to another is a major data gap that cannot be addressed
through worst case or default assumptions because plant or animal
metabolism can produce metabolites that are more toxic than the parent
compound.
b. EPA's response. EPA's translation of other residue data to
soybean aspirated grain fractions is reasonable. EPA translated
magnitude of the residue data from wheat and corn aspirated grain
fractions to soybean aspirated grain fraction. Another name for
``aspirated grain fractions'' is ``grain dust.'' This is the dust that
is removed from the grain by the rubbing of the grains together during
storage. Residues in grain dust are generally surface residues and thus
grain crops that have otherwise similar residues tend to have similar
residue levels in grain dust. This is especially the case for DDVP
given that it is applied in equal amounts to all grains post-harvest.
Post-harvest application generally results in surface residues, and
there would be no reason to expect different levels of residues across
grains. For similar reasons, metabolism of the pesticide in the crop,
which can play a role in residue levels, is unlikely to be a factor
with DDVP grain dust residues because metabolism occurs primarily when
a plant incorporates a pesticide through uptake and not when the
pesticide is applied to the crop surface post-harvest. Thus, EPA's
analysis is not based upon mere speculation, but rather a reasoned
analysis of the similarity between commodities and how DDVP is used.
EPA's treatment of potential residue levels in swine is also
reasonable. EPA requires radio-labeled metabolism studies in a few
plant and animal commodities to identify all potential metabolites.
(Ref. 73). Then magnitude of the residue studies are generally required
for each treated plant and animal commodity for the purpose of selecting
tolerance values and, in the absence of monitoring data, assessing risk.
EPA has all required animal metabolism studies for DDVP. EPA has
required an additional study on the magnitude of DDVP residues in
swine. These data are needed to verify that a proper tolerance value
has been identified for pork commodities. In the absence of those data,
EPA has relied on data on cattle and poultry products because it is
likely that the residues will be similar to those in cattle and poultry
commodities. These additional magnitude of the residue data are not
needed for risk assessment because EPA has monitoring data on swine
commodities. These data show no detectable residues.
7. Food monitoring data--a. NRDC's claims. NRDC asserts that the
FDA and USDA monitoring programs are inadequate because the number of
samples examined in these programs is too small to be representative of
the total quantity of food potentially having DDVP residues. (Ref. 1 at
49, 61-62). In addition, NRDC claims that the monitoring data are old
and, therefore,

[[Page 68684]]

do not represent current use patterns. NRDC also asserts that the
consumption data are insufficient because they have a limited number of
individuals in the age group of infants less than one year old. NRDC
further notes that samples collected from the FDA Total Diet Study were
collected in supermarkets in only four cities per year and residues in
other locations may be different and very little monitoring data are
available for fumigated commodities, requiring extensive translation
from one fumigated commodity to another. Moreover, NRDC raises the
concern that some of the FDA data were generated with an analytical
methodology that is not capable of detecting ``early eluters'' such as
DDVP and EPA has not taken this fact into account. Finally, NRDC
contends that residues potentially present at roadside produce stands
or farmer's markets are not represented and, additionally, that EPA
failed to consider such consumers major identifiable subgroup of
consumers. NRDC therefore concludes that EPA does not have reliable
food monitoring data and argues that EPA should use the default
assumption of 100 percent crop treated for all foods which may be
treated with DDVP as well as the default assumption of tolerance level
DDVP residues in all treated commodities.
In a related comment on the IRED, NRDC takes issue with EPA's
decision not to sum potential residues resulting from multiple
treatments of a food with DDVP at different stages of the food
production process. (Ref. 13 at 8). NRDC claims EPA's conclusion that
sufficient time would pass between such treatments that only the last
treatment needs to be considered in estimating exposure is arbitrary
and capricious.
b. EPA's response. In general, EPA disagrees that the monitoring
data are unreliable. To the contrary, EPA believes that the monitoring
data provide for an appropriately conservative risk assessment.
i. Adequacy of data - Age and number of samples and sample
location. Contrary to NRDC's characterization, FDA and USDA each
analyze thousands of samples per year. FDA analyzed several hundred
samples per year for DDVP, but now analyzes less than 100. USDA
analyzes most of their samples for DDVP, generally 350 to 700 samples
per commodity per year, although sometimes only about 175 samples per
commodity per year. FDA targets their monitoring toward commodities
which have historically had residue problems. USDA-PDP uses a more
random sampling plan, which is statistically designed to be
representative of the U. S. food supply.
In response to NRDC's concerns regarding the age of the monitoring
samples, EPA has updated its dietary risk assessment based almost
exclusively on USDA PDP data from the years 2000 to 2005. In the
updated assessment, FDA monitoring data was used for only one
commodity, berries (not including strawberries). The updated assessment
confirms what the earlier assessment found: DDVP residues are rarely
found in food commodities. Not including strawberries, PDP data showed
only 20 samples with detectable residues of DDVP out of more than
43,000 samples from 34 commodities which could potentially bear DDVP
residues. Even focusing on foods covered by registered agricultural
uses for DDVP or naled, there were only 20 samples with DDVP residues
out of approximately 33,000 samples (not including strawberries). In
the PDP data, strawberries were the only commodity with more than a
marginal number of detections - with 104 samples showing DDVP out of
1,986 samples. (Ref. 56 at 19-20).
ii. Infant consumption. NRDC objects to EPA's reliance on an
alleged lack of infant consumption data. In response, EPA notes that
there is no more comprehensive a consumption survey in the United
States than the CSFII surveys. Moreover, the revised dietary assessment
relies upon more recent and updated CSFII data. Specifically, the FQPA
required additional sampling of infant and children for information on
their consumption has been completed. The results of the additional
sampling were incorporated into DEEM and DEEM-FCID. These surveys are
available to the public. (Ref. 6).
iii. Fumigant monitoring data. EPA believes it has adequate data on
the fumigant use of DDVP. EPA has data from residue studies conducted
in warehouses with packaged and bagged commodities for the following
foods: flour, cocoa beans, coffee, dry beans, walnuts, and soybeans.
(Ref. 74). These studies were conducted by fumigating pallets
containing these commodities at a maximum rate and then sampling both
the outside layer and interior of the foods on the pallet. These data
were translated to other packaged and bagged commodities based on
starch and moisture content. Although translating these data to other
commodities creates some uncertainty as to the residue estimate, this
uncertainty is more than offset by other factors. First, the studies
used maximum treatment rates and sampled the commodities 6 hours after
treatment. Not only does this approach overstate residues that would
occur from lower treatment rates but it does not take into account the
rapid disappearance of DDVP that occurs due to its volatile nature.
Second, EPA assumed 100 percent of bagged and packaged commodities were
treated.
iv. Early eluter. Because DDVP is an early eluter (i.e., DDVP will
avoid detection unless samples are analyzed under low temperature
chromatographic conditions), fewer samples are analyzed by FDA for DDVP
than are typically analyzed by the Luke multiresidue method. In its
prior dietary DDVP assessment EPA relied heavily on FDA monitoring but
only used monitoring that used early eluter conditions which are known
to detect DDVP. This issue has limited relevance given EPA's revised
dietary risk assessment which relies almost entirely on PDP monitoring
data which uses analytical methods which are known to detect DDVP.
v. Farmers' markets and roadside produce stands. In an order
responding to NRDC objections to tolerances for different pesticides,
EPA has addressed NRDC's claims regarding pesticide exposure to persons
who purchase food at roadside stands or farmers' markets. (70 FR
46733). As EPA explained there, whether EPA relies on data from crop
field trials or monitoring data in estimating pesticide exposure, given
the sampling methods in field trials and food monitoring, residue
levels identified from these sources are unlikely to understate residue
levels at farm stands.
EPA also rejects NRDC's challenge to EPA's decision not to sum
residues from treatments of a commodity at different stages of the
production process. Multiple treatments are a possibility for
commodities such as grains which may be treated as a bulk commodity and
later as a bagged and packaged commodity. EPA has estimated DDVP
exposure based on the treatment of bagged and packaged commodities.
EPA's decision was based on a number of inter-related considerations.
First, there are data showing that DDVP is a volatile compound that
rapidly degrades. Second, general monitoring data consistently show
very low to non-existent residues in food with the exception of one
commodity (strawberries) that are marketed very promptly. Third, EPA
has assumed that 100 percent of all bagged and packaged foods are
treated with DDVP and EPA's estimate of residue values in these
commodities is based on a conservative value from sampling of bagged
and packaged commodities 6 hours after treatment. Finally, the latest
data from FDA's Total Diet Study, a study measuring pesticide residues
and other

[[Page 68685]]

contaminants in food as consumed, has shown zero detections of DDVP in
the time period from the survey conducted in 1991 up until the latest
survey in 2003. (Ref. 75). The Total Diet Study examines 280 foods,
including many bagged and packaged foods, that are collected from
different regions in the United States. DDVP is one of many pesticides
analyzed for in the study.
8. Cooking factors--a. NRDC's claims. NRDC takes issue with the
Agency's practice of using cooking factors to reduce estimates of
residues for particular commodities as well as the Agency's practice of
translating these factors to other commodities based upon similarity of
cooking time and temperature. In particular, NRDC asserts that in the
absence of empirical data demonstrating that each commodity will be
affected identically by cooking, EPA cannot use cooking factors in its
assessment of DDVP residues. In addition, NRDC contends that ``EPA
apparently failed to take into account vastly different cooking
practices for different commodities, including consumption of some
commodities raw.'' (Ref. 1 at 50). As such, NRDC asserts that EPA
should not assume cooking will result in any reduction in observed
residue levels.
b. EPA's response. EPA's use of cooking factors is reasonable.
Amvac submitted a cooking study which examined residue decline due to
cooking in the following commodities: cocoa beans, dry pinto beans,
tomato juice, coffee beans, hamburger meat, eggs, and raw whole milk.
(Ref. 76 at 34-37). The study showed that DDVP residue reduction was
time and temperature dependent with dramatic reductions occurring when
items were cooked at high temperatures for more than a few minutes. For
example, eggs cooked for 3 minutes at greater than 100 degrees C
resulted in a residue decline of 38 percent, hamburger cooked at a
similar temperature for six minutes showed a 70 percent decline in DDVP
residues, and cocoa beans cooked for 10 minutes at 135 degrees C
resulted in a residue decline of 99.7 percent. Residue decline factors
(i.e., cooking factors) were translated from tested items only to
similar commodities which are cooked in a similar manner. For example,
data on dry pinto beans was translated to other dried beans and peas
and to boiled peanuts; data on hamburger was translated to other meats;
and data on tomato juice was translated to celery juice. EPA believes
these cooking times and temperatures are reasonable, conservative
estimates. Although certain of these commodities may occasionally be
cooked for shorter times or at lower temperatures, EPA expects those
instances to be infrequent. Moreover, given the conservative
assumptions on cooking times any variations are very unlikely to be
``vastly different.'' As to consumption of some of these foods
uncooked, NRDC's concern about use of cooking factors is unwarranted
because EPA's consumption database differentiates between amounts of
foods consumed cooked and uncooked and only applies cooking factors as
to the former. Further, EPA concludes that its choice of translation
commodities is also reasonable given the similarity between the cooking
methods for the tested commodity and the translated commodity and the
strong relationship shown in the data between cooking time and
temperature and residue decline.
In any event, EPA disagrees that it cannot rely on cooking data
unless it has data on all varieties of cooking practices within the
United States and its cooking data take that full range of cooking
practices into account. Implicit in this argument, is the view that EPA
must adopt a cooking factor that reflects the shortest possible cooking
time, no matter how infrequently such practice is used. Section 408,
however, does not take such an extreme approach to assessing exposure.
Rather, section 408, directs EPA to focus on major, identifiable
subgroups of consumers not worst case scenarios or maximally-exposed
individuals. EPA believes that use of reasonable, conservative exposure
assumptions are consistent with this statutory mandate.
Additionally, it is important for EPA to adapt the assumptions
underlying any exposure assessment to the complexity of the assessment.
For simple assessments - a single pesticide to which a human is exposed
by a single route (e.g., oral) from a single source (e.g., apples) - a
more conservative approach to assumptions such as cooking factors may
be necessary to assure high end exposures are captured because high end
exposure may be defined by consumption of a single food. This is not
the case with complex assessments like for DDVP that involve multiple
pesticides, multiple routes of exposure, and multiple sources of
exposure within routes. In evaluating exposure to DDVP in food alone,
EPA's exposure assessment takes into account residues in hundreds of
food commodities. If EPA were to assume worst case residue values for
each of these commodities (worst case pesticide usage, worst case
potential residues on the raw crop, worst case processing values, worst
case cooking factors, etc.) and then combine that information with the
assumption of worst case consumption for each commodity, the exposure
assessment would not reflect reality. Just as no one person, and
certainly no major subgroup of consumers, is a worst-case consumer of
every commodity, no one person, or major subgroup of consumers, is
likely to be consumers of every commodity at its worst-case residue
amount. To make such assumptions when multiple commodities are involved
compounds multiple conservatisms and would produce an assessment that
overstates exposure probably by several orders of magnitude. For this
reason, EPA's exposure assessment guidance advises using a mixture of
high end and central tendency assumptions to produce a high end
exposure assessment. (Ref. 77). Accordingly, EPA's use of conservative,
but not worst case, cooking factors in the DDVP exposure assessment is
reasonable.
9. Missing data--a. NRDC's claims. NRDC claims that various data
are missing: storage stability data for meat, milk, poultry, and egg
residue studies; crop field trials on tomatoes; and tomato processing
studies. (Ref. 1 at 43).
b. EPA's response. The tomato use has been canceled so no data are
needed on tomatoes. Although the IRED stated that data are needed on
storage stability, that statement was in error. (Ref. 11 at 189). In
fact, storage stability requirements have been met. The IRED noted that
storage stability data were needed in connection with some of the
residue data used in the 1987 Registration Standard for DDVP.
Subsequent to 1987, the registrant submitted new residue data on the
commodities in question and that residue data met the requirements for
storage stability data. (See, e.g., Ref. 74 at 10).
10. Uncertainties in estimating residues in foods--a. NRDC's
claims. NRDC argues that EPA has identified uncertainties in its
dietary assessment but fails to take these uncertainties into account.
Uncertainties cited by NRDC include lack of data on residue values in
foods sold at farm stands, use of cooking data, the limited sampling
sites in the FDA Total Diet Study, the reliance on residue trial
instead of monitoring data for warehouse uses of DDVP, the extensive
translation between commodities in estimating residues from DDVP
warehouse uses, and the reliance on field trial data for some
commodities. (Refs. 1 at 52; and 13 at 8-9).
b. EPA's response. EPA does take into account any uncertainties in
its food exposure analysis in determining whether it has estimated risk
in a manner that is protective of the general

[[Page 68686]]

population and all major identifiable consumer subgroups. For DDVP
there were a number of factors that might have led to an
underestimation of exposure levels but these factors are dwarfed by
considerations indicating that EPA has overestimated exposure. Each of
the factors highlighted by NRDC as well as others are discussed below:
i. Food from farm stands. As discussed above, EPA does not believe
that farm stands are likely to sell food containing a significantly
different residue profile than found in PDP monitoring data. This
factor introduces little to no uncertainty concerning the possibility
of underestimation of residues into EPA's analysis.
ii. Use of cooking factors. As discussed above, EPA used cooking
factors in a conservative fashion in estimating exposure. For several
reasons, EPA believes its use of cooking factors did not fully take
into account the degree of reduction of DDVP residues that occurs with
cooking. First, cooking factors were only applied to a relatively small
number of commodities that may contain DDVP residues. Cooking of other
commodities containing DDVP residues (e.g., grains and vegetables) will
undoubtedly decrease residues in those commodities substantially.
Second, the manner in which EPA translated the residue reduction data
will tend to exaggerate residue levels in many commodities. For
example, data on the residue reduction that occurs from cooking
hamburger for six minutes was translated to all cooked meats. Given
that most meats are cooked substantially longer than six minutes, this
use of the cooking data will understate exposure. This factor will
overestimate exposure to DDVP.
iii. FDA Total Diet Study. In the updated risk assessment the FDA
Total Diet Study data was not relied upon to quantitatively estimate
residues in food. This factor has no bearing on the DDVP exposure
assessment.
iv. Residues from warehouse use. EPA did do extensive translation
of data between commodities for the warehouse use. There was a
reasonable basis for these translations; nonetheless, some uncertainty
attends any such translation. However, EPA's estimation of exposure
from the warehouse use will clearly overstate DDVP exposure for two
reasons. First, EPA is not relying on monitoring data from warehouses
but data from residue trials in the warehouse. Invariably, residue
trials result in findings of higher residue values than monitoring data
because residue trials involve prompt sampling after treatment whereas
monitoring can occur days or weeks later. Thus, residue trials do not
take into account the normal degradation that occurs over time. With
DDVP, this decline in residues is likely to be exaggerated given the
data showing both DDVP's volatility and rapid degradation. Monitoring
data that is available on other commodities confirms the rapid decline
of residues. Second, EPA assumed that all food in warehouses is treated
with DDVP. This is a very conservative estimate. Accordingly, this
factor will tend to significantly overstate exposure to DDVP.
v. Reliance on field trial data. For many commodities that may be
legally treated with naled, EPA relied upon field trial data or assumed
tolerance level residues rather than monitoring data. For the reasons
noted immediately above, this assumption will significantly overstate
residues on those commodities.
vi. Percent crop treated. For many commodities that may be legally
treated with DDVP or naled (other than in warehouses), EPA assumed that
100 percent of the commodity is treated. Again, this is a very
conservative estimate and will significantly overstate DDVP exposure
from those commodities.
vii. Default processing factors. For several processed commodities,
EPA relied on default processing factors in estimating DDVP residues in
the processed food. EPA's default processing factors project worst case
levels of pesticides in processed food. (70 FR at 46733-46734). Thus,
use of default processing factors instead of specific processing data
for DDVP will overestimate residues in food.
Considering all of this information, EPA's conclusion is 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.
In any event, EPA's latest dietary assessment shows that, by a
large margin, the biggest driver in the DDVP dietary risk assessment
are DDVP residues in water not food. (Ref. 56). To the extent food is a
driver, that food is food with residue estimates from its treatment as
a bagged and packaged food. As explained above, estimates of residues
in bagged and packaged foods are likely to be a significant
overestimate due to the assumption of 100 percent treatment and use of
magnitude of the residue study rather than actual monitoring data.

C. Residential Exposure

1. Aggregating Exposures. The safety standard in FFDCA section 408
for tolerances requires that there be a reasonable certainty of no harm
from ``aggregate exposure to the pesticide chemical residue, including
all dietary exposures and all other exposure for which there is
reliable information.'' (21 U.S.C. 346a(b)(2)(A)(ii)). Further, EPA in
evaluating the safety of tolerances is directed to ``consider ...
available information concerning the aggregate exposures of consumers
... to the pesticide chemical residue ... including dietary exposure
under [all] tolerance[s] ... in effect for the pesticide chemical
residue and exposure from other non-occupational sources.'' (21 U.S.C.
346a(b)(2)(D)(vi)).
Unit VII.B. discusses EPA's assessment of aggregate dietary
exposure to DDVP from residues in food and water. That assessment
showed that these aggregate exposure levels were well below the acute
and chronic RfD/PADs. Although refined, these exposure estimates still
are likely to overstate exposure and risk. This is particularly
apparent when it is considered that the commodities that drove the risk
numbers were those commodities (drinking water and bagged and packaged
goods) for which the most conservative assumptions were made. (Ref. 56).
Pesticide residues to which humans are exposed from residential
uses of pesticides must be considered as part of section 408's
aggregate exposure calculus. The concern, of course, is that pesticide
tolerances should not be established or left in effect if dietary
exposures, when combined with other sources of exposure, exceed safe
levels. As the analysis in Unit VII.D.2. shows, however, dietary
exposures are insignificant compared to residential exposures and thus
the safety determination turns on an evaluation of the exposure and
risk from the residential uses of DDVP.
2. Revised residential exposure - pest strips. In light of the
numerous issues raised by NRDC concerning EPA's assessment of the risk
posed by DDVP pest strips, EPA has substantially revised its assessment
of exposure and risk from this use. EPA first discusses that revised
assessment before turning to NRDC's specific claims. The changes in the
assessment come in three areas: (1) analysis of exposure data and
exposure assumptions used; (2) the types of durational scenarios
assessed; and (3) the endpoint used for chronic exposure. (Ref. 78).
Currently, there are four sizes of DDVP pest strips that are
registered. The largest strip (65-80 grams) may only be used in
unoccupied areas in and around the house (garage, attic, crawl space,

[[Page 68687]]

shed) where humans are present for no greater than four hours per day.
There are three smaller strips (16, 10.5, and 5.25 grams) that may be
used in the home in closets, wardrobes, or cupboards. The IRED
recommended, and Amvac has accepted, label restrictions for these
smaller strips which bars use in closets of rooms where infants or
children or sick or elderly people will be confined for an extended
period or generally in closets of rooms for which any person will be
present for extended periods. (Refs. 11 at 161; and 79 ). EPA's risk
assessments examined each of these pest strips.
a. Exposure data and assumptions. In assessing exposure from pest
strips, EPA has relied on a study (Collins and DeVries) measuring air
concentrations in 15 houses treated with multiple large DDVP pest
strips hung directly in the living areas of the houses. (Id.). In its
prior assessment, EPA averaged air concentrations measured in the study
across houses. To insure its assessment is conservative, EPA, in its
most recent assessment, estimated risk based on the air concentrations
in the individual houses. (Id.). Additionally, for chronic risk
assessment, rather than project exposure from the 91 days of the
Collins and DeVries study over a period of 120 days (the period for
which a pest strip is generally designed to be effective), EPA used the
air concentration measured over the 91 days in the study. This approach
increases exposure estimates as the data show that DDVP air
concentrations are higher in the first weeks. Finally, rather than
calculate MOEs for different time periods in the home for strips used
in occupied portions of the home, EPA calculated MOEs assuming that
people are exposed in their homes 24 hours per day and spend 24 hours
per day in a room with a pest strip. For strips used in unoccupied
portions of the home, EPA assessed the risk based on 4 hours of
exposure per day.
b. Durational scenarios. Previously, EPA focused only on chronic
exposure to DDVP from pest strips and compared that chronic exposure to
the chronic RfD/PAD. In its revised risk assessment, EPA assessed risks
for acute, short/intermediate-term, and chronic exposures. (Id.). The
acute assessment examined risk based on the air concentrations in the
15 houses in the Collins and DeVries studies for the first 24 hours
after the pest strip is installed. The short/intermediate-term
assessment examined risk based on the air concentrations for the first
two weeks after installation of a pest strip. Appropriate acute and
short/intermediate-term endpoints were used.
c. Chronic endpoint. EPA's prior risk assessment used the benchmark
dose level of 10 percent (BMDL₁₀) for RBC cholinesterase
from a chronic inhalation study in rats to assess chronic risk from
exposure to pest strips. EPA reexamined this choice in light of its
policy on the use of cholinesterase inhibition in risk assessments.
Consistent with that policy, EPA determined that it would be more
appropriate to use the BMDL₂₀ for RBC cholinesterase from
that study in assessing chronic risk (but not for acute risk). That
decision was based on the consistent and large difference in doses
between indications of RBC cholinesterase inhibition at both the
BMDL₁₀ and the BMDL₂₀ and inhibition of brain
cholinesterase and clinical signs in numerous studies when exposure was
for 90 days or greater. (Id.).
d. Revised risk assessments. EPA's revised assessment shows that
(1) for the large strips permitted only in unoccupied portions of a
home, the target MOE is exceeded (i.e., there is not a risk of concern)
for all homes for four hours of exposure for acute, short/intermediate-
term, and chronic scenarios (Table 3, Table 5, and Table 7); (2) for
the largest closet strip the target MOE is exceeded for all homes for
24 hours of exposure for the acute scenario (Table 4); (3) for the
largest closet strip the target MOE is exceeded for most homes for 24
hours of exposure for the short/intermediate-term and chronic scenarios
(Table 6 and Table 8); (4) for the smaller closet strip and the
cupboard strip the target MOE is all but met or exceeded for all homes
for acute, short/intermediate-term, and chronic scenarios (Table 9 and
Table 10); and (5) dietary exposure is insignificant compared to pest
strip exposure for all scenarios. (Id.). The MOEs for all of these
scenarios for the large pest strip and the large closet strip are
presented in the tables below.
The acute risk assessments for large pest strips (Table 3) and
closet, wardrobe, and cupboard pest strips (Table 4) use a hazard value
of 0.800 mg/kg which is the BMDL₁₀ for RBC cholinesterase
from a rat study. Exposure is based on Day 1 air concentrations in the
Collins and DeVries study. Four hours of exposure is assumed for the
large strip and 24 hours of exposure is assumed for the closet,
wardrobe, and cupboard strips. The MOE of concern is 30, as opposed to
100, because when exposure is expressed in units of air concentration
such as part per million (``ppm'') or milligrams/meter3
(``mg/m3'') (as it is in the Collins and Devries data), then
the pharmacokinetic component of the interspecies factor is decreased
from 10X to 3X to account for the different breathing rates between
species. (Id.).

Table 3.--Acute Risk from Exposure to Large (65 g) Strips for 4 hours
------------------------------------------------------------------------
Day 1
Collins and DeVries Home ID Concentration MOE
(mg/m3)
------------------------------------------------------------------------
6N 0.11 45
------------------------------------------------------------------------
7W 0.11 45
------------------------------------------------------------------------
2C 0.08 61
------------------------------------------------------------------------
14W 0.08 61
------------------------------------------------------------------------
10C 0.07 70
------------------------------------------------------------------------
13W 0.07 70
------------------------------------------------------------------------
5N 0.05 98
------------------------------------------------------------------------
11C 0.05 98
------------------------------------------------------------------------
12N 0.05 98
------------------------------------------------------------------------
3C 0.04 123
------------------------------------------------------------------------
15N 0.04 123
------------------------------------------------------------------------
1W 0.02 245
------------------------------------------------------------------------
4N 0.02 245
------------------------------------------------------------------------
8W 0.02 245
------------------------------------------------------------------------
9C 0.01 490
------------------------------------------------------------------------

Table 4.-- Acute Risk from Exposure to Large Closet (16 g) Pest Strips
for 24 hours
------------------------------------------------------------------------
Day 1
Collins and DeVries Home ID Concentration MOE
(mg/m3)
------------------------------------------------------------------------
6N 0.028 30
------------------------------------------------------------------------
7W 0.028 30
------------------------------------------------------------------------
2C 0.020 41
------------------------------------------------------------------------
14W 0.020 41
------------------------------------------------------------------------
10C 0.018 47
------------------------------------------------------------------------
13W 0.018 47
------------------------------------------------------------------------
5N 0.013 66
------------------------------------------------------------------------
11C 0.013 66
------------------------------------------------------------------------
12N 0.013 66
------------------------------------------------------------------------
3C 0.010 82
------------------------------------------------------------------------
15N 0.010 82
------------------------------------------------------------------------
1W 0.005 165
------------------------------------------------------------------------

[[Page 68688]]

4N 0.005 165
------------------------------------------------------------------------
8W 0.005 165
------------------------------------------------------------------------
9C 0.003 329
------------------------------------------------------------------------

The smaller closet strip and cupboard strip will have higher MOEs.
Background dietary DDVP exposure when expressed in mg/m3 is
0.00026 and this value is insignificant compared to the air
concentration levels in higher concentration houses.
The short/intermediate-term risk assessments for large pest strips
(Table 5) and for closet, wardrobe, and cupboard pest strips (Table 6)
use a hazard value of 0.1 mg/kg/day which is the LOAEL for the human
repeat dose oral study. Exposure is based on the average air
concentration of the first 2 weeks of exposure in the Collins and
DeVries study. Four hours of exposure is assumed for the large strip
and 24 hours of exposure is assumed for the closet, wardrobe, and
cupboard strips. The MOE of concern is 30 based on an intraspecies
safety factor of 10X and an additional safety factor of 3X for reliance
on a LOAEL.

Table 5.--Short/Intermediate-term Risk from Exposure to Large (65 g)
Strips for 4 hours/day
------------------------------------------------------------------------
2-Week
Average
Collins and DeVries Home ID Concentration MOE
(mg/m3)
------------------------------------------------------------------------
7W 0.074 29
------------------------------------------------------------------------
2C 0.073 29
------------------------------------------------------------------------
10C 0.072 29
------------------------------------------------------------------------
6N 0.066 32
------------------------------------------------------------------------
13W 0.065 32
------------------------------------------------------------------------
14W 0.059 36
------------------------------------------------------------------------
12N 0.048 43
------------------------------------------------------------------------
11C 0.038 55
------------------------------------------------------------------------
3C 0.032 65
------------------------------------------------------------------------
5N 0.030 69
------------------------------------------------------------------------
15N 0.028 74
------------------------------------------------------------------------
8W 0.019 109
------------------------------------------------------------------------
1W 0.019 112
------------------------------------------------------------------------
4N 0.017 126
------------------------------------------------------------------------
9C 0.012 177
------------------------------------------------------------------------
------------------------------------------------------------------------

Table 6.--Short/Intermediate-term Risk from Exposure to Large Closet (16
g) Pest Strips for 24 hours/day
------------------------------------------------------------------------
2-Week
Average
Collins and DeVries Home ID Concentration MOE
(mg/m3)
------------------------------------------------------------------------
7W 0.018 19
------------------------------------------------------------------------
2C 0.018 19
------------------------------------------------------------------------
10C 0.018 20
------------------------------------------------------------------------
6N 0.016 21
------------------------------------------------------------------------
13W 0.016 22
------------------------------------------------------------------------
14W 0.015 24
------------------------------------------------------------------------
12N 0.012 29
------------------------------------------------------------------------
11C 0.010 37
------------------------------------------------------------------------
3C 0.008 43
------------------------------------------------------------------------
5N 0.008 46
------------------------------------------------------------------------
15N 0.007 50
------------------------------------------------------------------------
8W 0.005 73
------------------------------------------------------------------------
1W 0.005 75
------------------------------------------------------------------------
4N 0.004 84
------------------------------------------------------------------------
9C 0.003 118
------------------------------------------------------------------------

The smaller closet strip and cupboard strip will have MOEs of 29 or
higher. Background dietary DDVP exposure when expressed in mg/
m3 is 0.00026 and this value is insignificant compared to
the air concentration levels in higher concentration houses.
For the chronic risk assessments for large pest strips (Table 7)
and closet, wardrobe, and cupboard pest strips (Table 8, Table 9, and
Table 10), EPA calculated MOEs for a range of hazard values: the
BMDL₁₀ and BMDL₂₀ for RBC cholinesterase from a
2-year chronic rat study, BMDL₁₀ for brain cholinesterase
from a 90-day rat study, and the NOAEL for clinical signs from a 7-day
rat study. Exposure is based on the average air concentration for the
91 days of the Collins and DeVries study. Four hours of exposure is
assumed for the large strip and 24 hours of exposure is assumed for the
closet, wardrobe, and cupboard strips. The MOE of concern is 30 for the
same reason as with the acute exposure assessment.

Table 7.--Chronic Risk from Exposure to Large (65 g) Strips for 4 hours/day
--------------------------------------------------------------------------------------------------------------------------------------------------------
Study Rat 2-Year Inhalation Rate 90 Day oral Rate 7 Day oral
--------------------------------------------------------------------------------------------------------------------------------------------------------
POD Type BMDL10 BMDL20 BMDL10 LOAEL
--------------------------------------------------------------------------------------------------------------------------------------------------------
POD (mg/m3) 0.078 0.41 0.196 0.4 7.3
--------------------------------------------------------------------------------------------------------------------------------------------------------
Home ID CD avg / 6 RBC Brain RBC RBC Clincal signs
--------------------------------------------------------------------------------------------------------------------------------------------------------
10C 0.00607 13 67 32 66 1200
--------------------------------------------------------------------------------------------------------------------------------------------------------
2C 0.00575 14 70 34 70 1300
--------------------------------------------------------------------------------------------------------------------------------------------------------

[[Page 68689]]

13W 0.00483 16 84 41 83 1500
--------------------------------------------------------------------------------------------------------------------------------------------------------
7W 0.00337 23 120 58 119 2200
--------------------------------------------------------------------------------------------------------------------------------------------------------
12N 0.00330 24 123 59 121 2200
--------------------------------------------------------------------------------------------------------------------------------------------------------
14W 0.00330 24 123 59 121 2200
--------------------------------------------------------------------------------------------------------------------------------------------------------
6N 0.00212 37 191 93 189 3400
--------------------------------------------------------------------------------------------------------------------------------------------------------
3C 0.00212 37 191 93 189 3400
--------------------------------------------------------------------------------------------------------------------------------------------------------
11C 0.00207 38 196 95 194 3500
--------------------------------------------------------------------------------------------------------------------------------------------------------
15N 0.00192 41 211 102 208 3800
--------------------------------------------------------------------------------------------------------------------------------------------------------
8W 0.00161 48 251 122 248 4500
--------------------------------------------------------------------------------------------------------------------------------------------------------
1W 0.00137 57 295 143 291 5300
--------------------------------------------------------------------------------------------------------------------------------------------------------
9C 0.00127 61 318 154 314 5700
--------------------------------------------------------------------------------------------------------------------------------------------------------
5N 0.00109 71 370 179 366 6700
--------------------------------------------------------------------------------------------------------------------------------------------------------
4N 0.00099 79 409 198 404 7400
--------------------------------------------------------------------------------------------------------------------------------------------------------

Table 8.--Chronic Risk from Exposure to Large (16 g) Closet Strips for 24 hours/day
----------------------------------------------------------------------------------------------------------------
Study Rat 2-Year Inhalation Rate 90 Day Rate 7 Day
------------------------------------------------------------------------------------- oral oral
POD Type BMDL10 BMDL20 ---------------------------
------------------------------------------------------------------------------------- BMDL10* LOAEL
POD (mg/m3) 0.078 0.41 0.196 ---------------------------
------------------------------------------------------------------------------------- 0.4 7.3
---------------------------
Home ID CD avg / 4 RBC Brain RBC Clinical
RBC signs
----------------------------------------------------------------------------------------------------------------
10C 0.00910 9 45 22 44 780
----------------------------------------------------------------------------------------------------------------
2C 0.00862 9 47 23 46 830
----------------------------------------------------------------------------------------------------------------
13W 0.00725 11 56 27 55 980
----------------------------------------------------------------------------------------------------------------
7W 0.00506 15 80 39 79 1400
----------------------------------------------------------------------------------------------------------------
12N 0.00495 16 82 40 81 1400
----------------------------------------------------------------------------------------------------------------
14W 0.00495 16 82 40 81 1400
----------------------------------------------------------------------------------------------------------------
6N 0.00318 25 127 62 126 2100
----------------------------------------------------------------------------------------------------------------
3C 0.00318 25 127 62 126 2200
----------------------------------------------------------------------------------------------------------------
11C 0.00310 25 131 63 129 2300
----------------------------------------------------------------------------------------------------------------
15N 0.00288 27 141 68 139 2500
----------------------------------------------------------------------------------------------------------------
8W 0.00242 32 168 81 166 3000
----------------------------------------------------------------------------------------------------------------
1W 0.00206 38 196 95 194 3400
----------------------------------------------------------------------------------------------------------------
9C 0.00191 41 212 103 209 3800
----------------------------------------------------------------------------------------------------------------
5N 0.00164 48 247 119 244 4100
----------------------------------------------------------------------------------------------------------------
4N 0.00148 53 273 132 270 4700
----------------------------------------------------------------------------------------------------------------

[[Page 68690]]

Table 9.--Chronic Risk from Exposure to Small Closet (10.5 g) Strips for 24 hours/day
----------------------------------------------------------------------------------------------------------------
Study Rat 2-Year Inhalation
----------------------------------------------------------------------------------------------------------------
POD Type BMDL10 BMDL20
----------------------------------------------------------------------------------------------------------------
POD (mg/m3) 0.078 0.41 0.196
----------------------------------------------------------------------------------------------------------------
Home ID CD avg / 6 RBC Brain RBC
----------------------------------------------------------------------------------------------------------------
10C 0.00607 13 67 32
----------------------------------------------------------------------------------------------------------------
2C 0.00575 14 70 34
----------------------------------------------------------------------------------------------------------------
13W 0.00483 16 84 41
----------------------------------------------------------------------------------------------------------------
7W 0.00337 23 120 58
----------------------------------------------------------------------------------------------------------------
12N 0.00330 24 123 59
----------------------------------------------------------------------------------------------------------------
14W 0.00330 24 123 59
----------------------------------------------------------------------------------------------------------------
6N 0.00212 37 191 93
----------------------------------------------------------------------------------------------------------------
3C 0.00212 37 191 93
----------------------------------------------------------------------------------------------------------------
11C 0.00207 38 196 95
----------------------------------------------------------------------------------------------------------------
15N 0.00192 41 211 102
----------------------------------------------------------------------------------------------------------------
8W 0.00161 48 251 122
----------------------------------------------------------------------------------------------------------------
1W 0.00137 57 295 143
----------------------------------------------------------------------------------------------------------------
9C 0.00127 61 318 154
----------------------------------------------------------------------------------------------------------------
5N 0.00109 71 370 179
----------------------------------------------------------------------------------------------------------------
4N 0.00099 79 409 198
----------------------------------------------------------------------------------------------------------------

Table 10.--Chronic Risk from Exposure to Cupboard (5.25 g) Strips for 24 hours/day
----------------------------------------------------------------------------------------------------------------
Study Rat 2-Year Inhalation
----------------------------------------------------------------------------------------------------------------
POD Type BMDL10 BMDL20
----------------------------------------------------------------------------------------------------------------
POD (mg/m3) 0.078 0.41 0.196
----------------------------------------------------------------------------------------------------------------
Home ID CD avg / 12 RBC brain RBC
----------------------------------------------------------------------------------------------------------------
10C 0.00303 26 134 65
----------------------------------------------------------------------------------------------------------------
2C 0.00287 27 141 68
----------------------------------------------------------------------------------------------------------------
13W 0.00242 32 168 81
----------------------------------------------------------------------------------------------------------------
7W 0.00169 46 240 116
----------------------------------------------------------------------------------------------------------------
12N 0.00165 47 245 119
----------------------------------------------------------------------------------------------------------------
14W 0.00165 47 245 119
----------------------------------------------------------------------------------------------------------------
6N 0.00106 74 382 185
----------------------------------------------------------------------------------------------------------------
3C 0.00106 74 382 185
----------------------------------------------------------------------------------------------------------------
11C 0.00103 75 392 190
----------------------------------------------------------------------------------------------------------------
15N 0.00096 81 422 204
----------------------------------------------------------------------------------------------------------------
8W 0.00081 97 503 243
----------------------------------------------------------------------------------------------------------------
1W 0.00069 113 589 285
----------------------------------------------------------------------------------------------------------------
9C 0.00064 123 636 308
----------------------------------------------------------------------------------------------------------------

[[Page 68691]]

5N 0.00055 143 740 358
----------------------------------------------------------------------------------------------------------------
4N 0.00049 158 819 396
----------------------------------------------------------------------------------------------------------------

Background dietary DDVP exposure when expressed in mg/m3
is 0.00026 and this value is insignificant compared to the air
concentration levels in higher concentration houses.
Despite the fact that some homes from the Collins and DeVries study
do not have acceptable MOEs for the short/intermediate-term and chronic
scenarios for the large closet strip, EPA concludes that the pest
strips do not pose a risk of concern for the following reasons. First,
use of BMDL₂₀ for RBC cholinesterase is a conservative
endpoint based on the DDVP database. As Table 7 indicates, target MOEs
are well exceeded for all homes for chronic risk if the
BMDL₁₀ for brain cholinesterase or the NOAEL for clinical
signs are used as the Point of Departure. Second, for short/
intermediate-term risk, EPA has used the results of the human oral
study in a conservative fashion. The maximum inhibition of RBC
cholinesterase from the 0.1 mg/kg/day dose used in that study was 16
percent (group mean) after 18 days of exposure. As discussed above,
however, 20 percent inhibition is a more appropriate line of
demarcation for DDVP given, among other things, the wide margin between
RBC cholinesterase inhibition and clinical effects. If that approach is
followed the one dose from that study, then 0.1 mg/kg/day would be a
NOAEL not a LOAEL and the additional 3X safety factor would be
unnecessary. Without that 3X safety factor, the MOE of concern would
drop to 10. The conservativeness of the 3X safety factor is also
supported by the HSRB's conclusion that a dose lower than 0.1 mg/kg/day
would not be expected to show a significant inhibition response.
Finally, EPA made numerous conservative assumptions regarding
interpretation of the Collins and DeVries data in using it to estimate
exposure, including that: (1) the large strips used in the Collins and
DeVries study emitted the same amount of DDVP as the largest strip
currently registered even though the current large strip (65 - 80
grams) is smaller than the strip used in the Collins and DeVries study
(100 grams); (2) placement of a strip in a closet is the same as
hanging it in the adjacent living area; (3) for closet, wardrobe, and
cupboard strips, exposure is 24 hours per day (despite label
restrictions barring use in rooms where people would be exposed for
extended periods); (4) during the 24 hours per day a person is in a
home that person is continually in a room with a pest strip; and (5)
strips are replaced every 90 days.
3. Issues raised by NRDC concerning pest strips--a. NRDC's claims.
NRDC argues that EPA's exposure assessment for pest strips ``is based
on unsupported assumptions and inadequate data'' and therefore EPA
cannot conclude that aggregate exposure to DDVP is safe. NRDC's
specific allegations are described below.
i. Reliance on an inadequate exposure study. NRDC notes that EPA
relied on a single study (Collins and DeVries) monitoring 15 homes in
one geographic area to estimate residential exposure to DDVP from pest
strips. NRDC claims this study is inadequate because (1) the number of
homes monitored is too small to be representative of the housing stock
in the United States; (2) the study was conducted in only one
geographic area and at one time of year and thus would not be
representative of weather conditions (including humidity and
temperature) in other regions of the United States; (3) sampling in the
homes was done in only one location and thus the study ``provides no
information about the movement of residues from room-to-room and []
exposure in other rooms in the homes;'' (4) homes were only treated
with three or four pest strips but homeowners with severe pest problems
may ``place pest strips in every room or most rooms in the house;'' and
(5) the study contained insufficient information to estimate exposure
levels for pest strips of different sizes. (Ref. 1 at 19, 58-59).
ii. Unsupported assumption that users will not replace pest strips
more frequently than every 120 days. NRDC claims that EPA's assumption
that homeowners will not replace pest strips until the strip has been
in use for at least 120 days is unreasonable because the label does not
prohibit more frequent replacement and EPA has no empirical data to
support this assumption. (Id. at 59). NRDC argues that ``[i]n the
absence of reliable empirical data demonstrating that consumers do not
... replace the strips more often than is assumed by EPA, at a minimum,
the labels of these products should be amended to place restrictions on
use consistent with the assumptions made in the risk assessment.''
(Ref. 13 at 10).
iii. Only considered average exposure over 120 days. NRDC argues
that EPA erred by averaging exposure levels over a 120-day period.
According to NRDC, EPA should have considered ``the higher, more
dangerous exposures that occur when a strip is first hung ....'' (Ref.
1 at 59). Instead, NRDC asserts, EPA ``should have presented the range
of risks displayed over time.'' (Id.).
iv. Failure to consider exposure from use in unoccupied spaces.
NRDC claims that EPA has not taken into account that DDVP residues
could migrate from use of the full-size pest strips in attics, crawl
spaces, and garages to the main living areas of a home. (Ref. 13 at
10). NRDC notes that EPA has found that use of chlorpyrifos in crawl
spaces leads to residues in living areas. (Id.). NRDC further contends that
attics can be part of the air exchange for the living areas in a house.
v. Estimates of exposure durations in homes are too low. While NRDC
concedes that an estimate of 16 hours/day in a home would be a high end
estimate for most people, NRDC argues that this estimate ignores
``several significant population groups'' such as ``[p]eople who work
or stay at home, retired and elderly people, and pre-school children.''
(Id.). Further, NRDC asserts that EPA's low end estimate of 2 hours/day
in the home is ``absurd on its face.'' (Id.).
vi. No consideration of incidental oral and dermal exposure. NRDC
claims that

[[Page 68692]]

EPA had insufficient data to conclude that incidental oral and dermal
exposure resulting from DDVP residues that settle on home surfaces
would be minimal. (Id. at 19.). According to NRDC, the only information
EPA relied upon was data on residues that settle on foodstuffs and such
data would not be representative of other home surfaces.
vii. Failure to collect data on consumer use practices with pest
strips. Echoing comments from the SAP that ``better knowledge of real
world use practices would serve to improve residential exposure
analyses,'' NRDC argues that the failure of EPA to collect such data
``undermines the risk analysis for pest strips.'' (Ref. 1 at 62).
viii. Failure to consider aggregation of pest strip exposure with
other residential exposures. NRDC claims that EPA does not support its
statement that pest strip exposures would not co-occur with high
dietary exposures. NRDC also argues that EPA should consider co-
occurrence of exposure between pest strips and other DDVP residential
products. (Ref. 13 at 12-13).
b. Amvac's comments. Amvac contends that the Collins and DeVries
study is adequate for assessing exposure from pest strips citing
several other studies which it states contain similar results. (Ref. 14
at 45). Further, Amvac argues that ``the estimated time-weighted
average concentration used by EPA (0.015mg/m3) is higher
than found in many other studies.'' (Id.). Amvac also defends EPA's use
of a time-weighted average in estimating risk noting that ``EPA is
assessing chronic exposure and thus it is appropriate to average over
the entire period to compare to a chronic endpoint.'' (Id.). Finally,
Amvac argues that, if EPA assessed acute risk from pest strips, it
would be appropriate for EPA to use the highest concentration from the
Collins and DeVries study (0.11 mg/m3) but that this
exposure level does not show an acute risk concern. (Id.).
c. EPA's response--adequacy of the Collins and DeVries Study. EPA
believes this study is sufficiently representative to estimate exposure
and EPA disagrees with each of NRDC's contentions. First, EPA does not
believe the study is inadequate due to being performed in a single
location on 15 houses during a single season of the year. As noted by
Amvac, there are a number of studies other than Collins and Devries
that test DDVP pest strips in houses. Specifically, data on DDVP air
concentrations from the use of pest strips are available for over 100
homes in the United States, United Kingdom, and France. (Ref. 80).
There was no major difference in the DDVP air concentration in the 100
houses and the DDVP air concentration in the study of the 15 houses
that were used for exposure estimates.
Second, EPA does not view the study as flawed because it only
sampled DDVP concentrations in one location in each home. Importantly,
the sample location in each instance was in a room with a pest strip,
pest strips were used in other rooms of the house, and EPA assumed, for
its calculation of the MOE, that the air concentration for all areas of
a house is the same as at the sampled location. Thus, EPA has assessed
MOEs in an appropriately conservative fashion given the sampling
location in the Collins and DeVries study.
Third, NRDC's suggestion that some homeowners may put a pest strip
in every room fails to take into account that (1) the label now bars
use of full-size pest strips except in infrequently-occupied spaces
(attics, crawl spaces, sheds, and garages); (2) in-home pest strips
must contain significantly less DDVP than full-size strips and are
limited to use in closets, wardrobes, and cupboards; and (3) EPA's risk
assessment assumes a person spends all of their time in a room with a
closet or cupboard that contains a pest strip. Relevantly, the largest
closet strip is only labeled as effective in a 200 cubic foot area.
Areas beyond that efficacious zone of treatment are likely to contain
significantly lower air concentrations.
Fourth, the Collins and DeVries study does provide sufficient
information to estimate exposure from different size strips. The
Collins and Devries study used a pest strip that was larger than the
largest size available today and EPA made the conservative assumption
that the currently-registered large strip would have similar exposure
to the older, larger version and extrapolated exposure levels for
smaller strips proportionately based on that conservative assumption.
Finally, to insure that EPA has the most accurate information
possible on exposure for pest strips, EPA plans to require as part of
the data call-in to be issued in connection with reregistration that an
additional study be conducted that measures DDVP air concentrations in
houses from use of pest strips.
i. Replacement of strips. EPA's risk assessment has a built-in
margin of error in the event strips are replaced more frequently than
every 120 days because it is based on an average of the first 91 days
of exposure which was the period of time air concentrations were
measured in the Collins and DeVries study.
ii. Use of time-weighted average exposure. EPA believes that use of
a time-weighted average of the DDVP concentration levels is appropriate
for chronic risk and does not understand NRDC to be contesting this
approach to assessing chronic risk. As to acute exposures that occur
during the first day after a strip is hung, EPA has now expanded its
risk assessment to address both this scenario and a short/intermediate-
term exposure scenario (exposure for the two weeks after a strip is
installed).
iii. Exposure from use in unoccupied spaces. EPA believes it
unlikely that DDVP residues will migrate from attics, crawl spaces,
garages, and sheds to living areas within a house because it would be
unusual for these spaces to be connected to the air exchange for a
house. On the other hand, basements may be included in a home's air
exchange system and, for that reason, the large pest strips may not be
used in a basement. This is likely part of the explanation for the
result in the cited chlorpyrifos study. In that study, the chlorpyrifos
was injected into the foundation and migrated to the basement of the
house. From there, it is likely that chlorpyrifos moved to other rooms
in the house through air exchange. Further, the chlorpyrifos study
cited by NRDC has little relevance to pest strips given the vastly
different amounts of active ingredient involved. (Ref. 81). In the
chlorpyrifos study, approximately 100 gallons of a solution containing
1 percent of pesticide product (Dursban TC) was injected into basement
walls. According to the label, Dursban TC contains 4 pounds per gallon
of chlorpyrifos. Thus, that study used approximately 4 pounds of
chlorpyrifos. A large pest strip contains, at most, 80 grams of
pesticide product, of which 18.6 percent is DDVP. Accordingly, the pest
strip exposure in unoccupied areas would contain roughly 15 grams of
DDVP compared to approximately 1,800 grams of chlorpyrifos in the study
cited.
iv. Exposure durations in homes. First, EPA believes it is unlikely
that a person would spend four hours per day, day in and day out for an
extended period in an attic, crawl space, garage, or shed. In any
event, the label forbids use of the large pest strips in such locations
should they be occupied that regularly. Second, as to the closet,
wardrobe, and cupboard strips, EPA has assumed 24 hours per day
exposure in calculating margins of exposure. Amvac has agreed to modify
labels on these products so that they bar use of these strips in
closets in rooms where infants or children, or sick or elderly people are
confined for extended periods. Additionally, the label prohibits use of

[[Page 68693]]

the strip in any area of the house where people are present for
extended periods.
v. Incidental oral and dermal exposure. NRDC is incorrect in its
assertion that EPA's risk assessment does not take into account
incidental oral and dermal exposure. Although dermal and incidental
oral exposure from contact with DDVP adsorbed on solid surfaces was not
assessed directly, the inhalation study used for assessing inhalation
risk includes dermal and oral exposure components because the study
involved continuous whole-body exposure resulting in adsorption of DDVP
vapors to the animal's fur and food. In other words, the inhalation
study is actually a total exposure study accounting for exposure by all
routes when DDVP is delivered as a vapor. Further, the pest strip use
is unlikely to leave significant DDVP residues on residential surfaces
leading to dermal or incidental oral exposures. DDVP is highly volatile
and degrades rapidly. Thus, even if a person repeatedly uses pest
strips in the home, significant long-term dermal exposure is unlikely.
The Collins and DeVries study showed very low concentrations of DDVP in
the air and almost all food sampled in the home had no detectable
residues. EPA reasonably concluded that any dermal exposures from
deposit of air residues on surfaces would be negligible compared to
residues inhaled directly.
vi. Data on real world use practices. Data on ``real world'' use
practices of pest strips might make it possible for EPA to determine
the extent to which EPA is likely overestimating exposure. EPA believes
its conservative projection of exposure, given the clarity and
reasonableness of the label directions, as amended, preclude the need
to require additional data on use practices.
vii. Aggregating pest strip exposure with other residential
exposures. In assessing aggregate risks, EPA believes it is unrealistic
to add high-end exposures from intermittent and unconnected pesticide
exposures which are likely to affect relatively small population
groups. Thus, in aggregating dietary exposures to pest strip exposures,
EPA has compared chronic (rather than acute) dietary exposure levels of
DDVP as a background exposure to the various pest strip durational
scenarios (acute, short/intermediate-term, chronic). It should also be
noted that the dietary exposure estimates for DDVP are driven by high-
end model estimates of residues in drinking water which is an
additional conservatism.
For similar reasons, EPA does not believe it is realistic to add
high-end acute or short-term exposures for the residential use of
trichlorfon on turf and DDVP as a spot insect treatment by aerosol
spray. Although dietary exposure to DDVP, and possibly exposure from a
DDVP pest strip, may be appropriately aggregated as a background
exposure to the turf or spot treatment uses, assuming that the windows
for high-end acute exposures from the turf use and the spot treatment
overlap is overly conservative. In any event, however, even if
exposures from turf and spot treatment uses are aggregated with each
other and with background exposures from food and water and pest
strips, the aggregate exposure still does not show a risk of concern.
Aggregating the MOEs of 100 for both the turf and spot treatment uses,
(Ref. 11 at 160, 165), with MOEs for background exposure for dietary
(900) and pest strips (93) gives an aggregate short-term MOE of 31 for
the child who simultaneously experiences outdoor exposures from the
trichlorfon turf use with indoor exposures from DDVP spot treatments
and pest strips. The target MOE here is 30. This aggregation relies
upon average dietary exposure for the most highly exposed subgroup
which may have turf post-application exposures (children aged 1-2)
compared to the short-term oral Point of Departure and average pest
strip exposure over 91 days compared to the short-term inhalation Point
of Departure. (Refs. 11 at 138, 162; 56 at 18).

D. Risk Characterization

1. 99.9th percentile--a. NRDC's claims. NRDC asserts that EPA has
failed to provide a rationale for using the 99.9th percentile in the
DDVP risk assessment for acute population effects. (Ref. 1 at 51). NRDC
further contends that some 300,000--0.1 percent of the U.S.
population--will not be considered because they ``fall below the level
of sensitivity of the calculation method.'' (Id.). NRDC therefore
argues that EPA cannot make its FFDCA safety finding.
b. EPA's response. Contrary to NRDC's assertion, EPA has not
ignored 300,000 of the U.S. population in estimating acute DDVP risks
through reliance on the 99.9th exposure percentile in the DDVP risk
assessment. As EPA has repeatedly explained in the past - in science
policy documents and in responses to NRDC's objections to tolerances -
``the use of a particular percentile of exposure is a tool to estimate
exposures for the entire population and population subgroups and not a
means to eliminate protection for a certain segment of a subgroup.''
(69 FR 30070 and 70 FR 46733).
In examining pesticide exposure, EPA does not have the capability
of measuring actual exposure to individuals across the population.
Rather, EPA uses data on factors bearing on exposure such as residue
levels in food and drinking water, food consumption patterns, and air
concentration levels and transferable surface residues to estimate
exposure to hypothetical individuals across major identifiable
subgroups in the population. These data on exposure factors can range
from highly conservative values (e.g., assumption that 100 percent of a
crop is treated with a pesticide) to highly realistic values (e.g.,
market basket monitoring data on pesticide residue levels). In
interpreting exposure estimates based on such factors, EPA makes
judgments regarding what exposure level (expressed as a percentile) is
protective of the relevant population subgroups taking into account the
relative conservativeness of the factors which are the basis of the
assessment.
Generally, EPA uses the 95th percentile exposure as a starting
point for evaluating the safety of pesticide in circumstances where EPA
has employed very conservative assumptions on residue values and risk
assessment techniques. In EPA's judgment, the 95th percentile exposure,
when calculated using such conservative assumptions, will not
underestimate exposure for any major identifiable subgroups. However,
when EPA uses more realistic residue values and refined risk assessment
techniques, it starts its evaluation of safety at the 99.9th percentile
of exposure to be sure that it is protecting the entire population and
all major, identifiable subgroups. EPA uses the 99.9th percentile as
the starting point for refined assessments rather than the 100th
percentile because generally its exposure assumptions, even when
refined, contain residual conservatisms. Thus, whether EPA is relying
on the 95th percentile, the 99.9th percentile, or some other value, the
population exposure percentile is a means to an end and not a
designation of those people worthy of protection. As EPA noted in a
science policy document on this issue: ``just as when OPP uses the 95th
percentile with non-probabilistic exposure assessments OPP is not
suggesting that OPP is leaving 5 percent of the population unprotected,
OPP is not by choosing the 99.9th percentile for probabilistic exposure
assessments concluding that only 99.9 percent of the population
deserves protection.'' (Ref. 8 at 31). Perhaps the best evidence that
use of population percentiles is not identifying those worthy of
protection but simply a tool in estimating exposure

[[Page 68694]]

is that refined assessments using the 99.9th percentile invariably
estimate exposure to be lower for a pesticide than an unrefined
assessment for that same pesticide using the 95th percentile. (69 FR
30071). Yet, under NRDC's logic the use of the 95th percentile, by
itself, would signal that fewer people are being protected than if the
99.9th percentile was used, and thus an exposure estimate based on the
95th percentile should necessarily be lower than one based on the
99.9th percentile.
2. Inappropriate use of 100% of the RfD/PAD as a ``Bright Line''
Rule--a. NRDC's claims. NRDC contends that EPA is unlawfully
disregarding significant risks by relying on a ``bright line rule''
that risks below 100 percent of the acute population adjusted does
(aPAD) are not of concern and risks above 100 percent are of concern.
(Ref. 1 at 51-52). Specifically, NRDC argues that (i) EPA treats the
100 percent threshold as a rule that has not been subject to notice and
comment rulemakings; (ii) use of a 100 percent threshold is arbitrary
and capricious; (iii) use of 100 percent threshold improperly excludes
acute risks unless they exceed 100 percent of the aPAD; and (iv) EPA
cannot reasonably explain how children aged 1 to 6, the sub-population
with the highest percentage exposure, will not be harmed.
b. EPA's response. NRDC appears to be suggesting that EPA's
approach of comparing estimated DDVP exposure to an EPA-derived safe
dose for DDVP is unlawful because (1) EPA cannot adopt an analytical
approach of comparing exposure to the safe dose without a regulation
that permits such an approach; and (2) EPA has not adequately justified
that its chosen safe dose is actually safe. Such claims are baseless.
In assessing risks posed by a pesticide, EPA first examines
toxicological studies with the pesticide and calculates a safe dose in
humans (RfD/PAD) based on the results of those studies and
incorporating appropriate safety factors. This analysis, based on well-
established risk assessment principles used both across the federal
government and internationally, is designed to establish a dose without
appreciable risk to humans. EPA then compares estimated aggregate
exposure to humans to the safe dose to make a determination on the
safety of the pesticide. EPA believes this type of case-by-case
assessment of the risk from exposure to a pesticide is precisely what
section 408 demands. Other than the statutory mandates in FFDCA section
408, EPA does not follow ``bright line'' rules in making safety
determinations but rather is guided by what the data show on a
particular pesticide. Of course, at the end of its pesticide-specific
analysis EPA must make a safety determination. EPA does not believe it
needs a rule saying so to conclude that, where it has confidence that
exposure is below the safe dose, a tolerance is safe. Further, there is
no merit to NRDC's bald claim that EPA's safe dose determination for
DDVP is arbitrary and capricious because EPA has failed to explain the
basis for its safe dose determination. EPA's safe dose determination is
supported and explained by extensive documentation including the IRED
and numerous EPA-produced data evaluation and other analytical
memoranda addressing DDVP as well as long-established and commonly-
employed risk assessment principles. (See, e.g., Ref. 11).
3. FQPA Safety Factor--a. NRDC's claims. NRDC asserts that the
Agency has no basis upon which to apply anything lower than a 10X FQPA
safety factor in the DDVP risk assessment. According to NRDC, ``[t]he
admitted potential for pre- and post-natal toxicity from exposure to
DDVP, combined with incomplete data regarding toxicity and exposure to
infants and children, compel EPA to retain the default FQPA tenfold
safety factor for DDVP.'' (Ref. 1 at 15). As to pre- and post-natal
toxicity, NRDC called particular attention to a study in the open
literature (Mehl et al (1993), which reported brain effects in guinea
pig pups. (Id. at 15-16). As to missing data, NRDC placed particular
evidence on the absence of a DNT study. NRDC also criticizes EPA's
choice of an additional safety factor of 3X arguing that ``[t]he Agency
did not explain why it chose 3X as opposed to 4X or any other factor.''
(Id. at 14).
b. EPA's response. As discussed above, under the FQPA, EPA
presumptively applies an additional tenfold margin of safety (i.e.,
safety factor) when assessing the risk of pesticide exposure to 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. FQPA, however, authorizes the Agency to use a
different margin of safety for pesticide residues if, on the basis of
reliable data, such a margin will be safe for infants and children.
When EPA issued its preliminary risk assessment for DDVP, it employed
an FQPA safety factor of 3X because the Agency lacked an acceptable DNT
study as well as an FQPA safety factor of 3X for various residential
risk assessments.
Since the preliminary risk assessment was issued for public comment
in 2000, the Agency received two Developmental Neurotoxicity Test (DNT)
studies. The NOAEL/LOAEL for the two combined DNT studies is 1.0/7.5
mg/kg/day based on increased auditory startle amplitude in male
offspring in both studies. The NOAEL is much higher than the points of
departure used for regulation of dichlorvos: 0.05 mg/kg/day from a dog
study used to assess long-term effects, and 0.1 mg/kg/day from a human
study used for short- and intermediate-term scenarios. Now that the DNT
studies have been submitted, EPA believes it has reliable data showing
it is safe for infants and children to remove the additional safety
factor for all risk assessments other than the residential assessments.
This conclusion is based on:
(1) The toxicity database is complete.
(2) There are no residual concerns for pre- and/or postnatal
toxicity resulting from exposure to dichlorvos. There was no evidence
for increased susceptibility of the rat and rabbit offspring to
prenatal or postnatal exposure to dichlorvos. In both rat and rabbit
developmental studies, no developmental effects were observed. In the
reproduction study, the parental/systemic NOAEL/LOAEL was 2.3/8.3 mg/
kg/day which was identical to the reproductive/offspring NOAEL/LOAEL.
The DNT showed evidence of susceptibility in one parameter, auditory
startle amplitude. However, there are no residual concerns for
susceptibility from this because the affects in pups were seen at a
dose well above the points of departure upon which EPA is regulating
and a clear NOAEL for the effect (again, well above the points of
departure) was identified. In addition, using a Benchmark Dose Methods
(BMD) analysis of studies with pup and adult cholinesterase depression
results did not demonstrate any substantial numerical differences in
BMDL values for either RBC or brain cholinesterase between young and
adult animals.
(3) Although the exposure estimate for DDVP in food is highly
refined as to some commodities, EPA is confident that its DDVP exposure
estimate from food, if anything overstates DDVP exposure, given the
many conservatisms retained in the exposure assessment and DDVP's
documented volatility and rapid degradation. Additionally, the very
conservative estimate on DDVP exposure through drinking water based on
the use of trichlorfon on turf and naled on brassica is likely to
significantly overstate DDVP exposure. Finally, EPA believes its
residential exposure estimates will also not underestimate exposure
given the conservative assumptions used in the

[[Page 68695]]

assessment and in EPA's residential exposure models and the data on
residential exposure.
With respect to the Mehl study, NRDC has mischaracterized the
issue. Although the Mehl study raised an initial concern for potential
developmental neurotoxicity, this concern was resolved by the
subsequent DNT studies.
EPA has retained a FQPA safety factor of 3X for various residential
risk assessments. This additional safety factor is due to these
assessments' reliance on a LOAEL rather than a NOAEL. EPA chose a
safety factor other than 10X based on its evaluation of the study in
question. EPA determined that 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. The HSRB confirmed EPA's interpretation of this study in its
review of the scientific merit of the study. Specifically, the HSRB
concluded that ``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. 31 at 41).
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. (Ref. 82). 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.
Without in any way implying that there is anything improper with
agency decisionmakers making a FQPA safety factor determination, NRDC's
comments about who made the decision on the FQPA safety factor for DDVP
can be dismissed because NRDC is referring a prior decision on the FQPA
safety factor pre-dating the submission of the DNT.

E. Conclusion

NRDC's petition to revoke all DDVP tolerances is denied. NRDC's
arguments have not convinced EPA that the DDVP tolerances are unsafe;
to the contrary, EPA finds that its risk assessments show that the DDVP
tolerances pose a reasonable certainty of no harm. EPA specifically
rejects NRDC's claims that (1) EPA has mischaracterized the hazard
posed by DDVP; (2) dietary and residential exposure to DDVP pose a risk
of concern; and (3) EPA failed to justify removal of the additional 10X
safety factor for the protection of infants and children.

VIII. Regulatory Assessment Requirements

As indicated previously, this action announces the Agency's order
denying a petition filed, in part, under section 408(d) of FFDCA. As
such, this action is an adjudication and not a rule. The regulatory
assessment requirements imposed on rulemaking do not, therefore, apply
to this action.

IX. Submission to Congress and the Comptroller General

The Congressional Review Act, (5 U.S.C. 801 et seq.), as added by
the Small Business Regulatory Enforcement Fairness Act of 1996, does not
apply because this action is not a rule for purposes of 5 U.S.C. 804(3).

X. References

1. Petition of Natural Resources Defense Council To Conclude
Special Review, Reregistration and Tolerance Reassessment Processes and
To Revoke All Tolerances and Cancel All Registrations for the Pesticide
DDVP (June 2, 2006).
2. U.S. EPA, A User's Guide to Available EPA Information on
Assessing Exposure to Pesticides in Food (June 21, 2000).
3. U.S. EPA, Residue Chemistry Test Guidelines: OPPTS 860.1500 Crop
Field Trials (August 1996).
4. Office of Pesticide Programs, U.S. EPA and Pest Regulatory
Management Agency, Health Canada, NAFTA Guidance Document for Guidance
for Setting Pesticide Tolerances Based on Field Trial Data (September
28, 2005).
5. Office of Pesticide Programs, US EPA, Office of Pesticide
Programs' Policy on the Determination of the Appropriate FQPA Safety
Factor(s) For Use in the Tolerance Setting Process (February 28, 2002).
6. Health Effects Division, Office of Pesticide Programs, U.S. EPA,
Transition to 1994-96/1998 CSFII and Modification of Age Groups of
Regulatory Interest (September 26, 2002).
7. Novigen Sciences, Inc., Dietary Exposure Evaluation Model
(DEEMTM) and DEEMTM Decompositing Procedure and
Software (February 29 - March 3, 2000) (as presented to the FIFRA
Scientific Advisory Panel).
8. Office of Pesticide Programs, U.S. EPA, Choosing a Percentile of
Acute Dietary Exposure as a Threshold of Regulatory Concern (March 16,
2000).
9. Office of Pesticide Programs, U.S. EPA, The Use of Data on
Cholinesterase Inhibition for Risk Assessments of Organophosphorous and
Carbamate Pesticides (August 18, 2000).
10. US EPA, Endocrine Disruptor Screening and Testing Advisory
Committee Final Report (August 1998).
11. Office of Prevention, Pesticides and Toxic Substances, EPA,
Interim Reregistration Eligibility Decision for Dichlorvos (DDVP) (June
2006).
12. Office of Prevention, Pesticides and Toxic Substances, EPA,
Memorandum from Debra Edwards to Jim Jones, Finalization of Interim
Reregistration Eligibility Decisions (IREDs) and Interim Tolerance
Reassessment and Risk Management Decisions (TREDs) for the
Organophosphate Pesticides, and Completion of the Tolerance
Reassessment and Reregistration Eligibility Process for the
Organophosphate Pesticides (July 31, 2006).
13. NRDC, Letter submitting comments Re: Dichlorvos Interim
Reregistration Eligibility Decision, 71 FR 37568 (June 30, 2006)
(August 28, 2006).
14. Amvac Chemical Corporation, Comments of Amvac Chemical
Corporation in Reponse to EPA's Notice of a Petition to Revoke
Tolerances Established for Dichlorvos (November 13, 2006).
15. European Food Safety Agency, Opinion of the Scientific Panel on
Plant health, Plant protection products and their Residues on a request
from EFSA related to the evaluation of dichlorvos in the context of
Council Directive 91/414/EEC, EFSA Journal (2006) (v. 343, pp. 1-45).
16. Office of Pesticide Programs, U.S. EPA, Memorandum from Judith
W. Hauswirth to George LaRocca, Peer Review of Dichlorvos (September
25, 1987).
17. Office of Pesticide Programs, U.S. EPA, Memorandum from Judith
W. Hauswirth to George LaRocca, Second

[[Page 68696]]

Peer Review of Dichlorvos -- evalution Following the September 23, 1987
Scientific Advisory Panel Review (March 16, 1988).
18. Office of Pesticide Programs, U.S. EPA, Memorandum from Judith
W. Hauswirth to George LaRocca, Third Peer Review of Dichlorvos --
Reevalution Following the April 18, 1988 Meeting of the NTP Panel of
Experts (August 17, 1988).
19. Office of Pesticide Programs, U.S. EPA, Memorandum from George
Z. Ghali to George LaRocca, Fourth Peer Review of Dichlorvos (DDVP)
(September 18, 1989).
20. Office of Pesticide Programs, U.S. EPA, Memorandum from Jocelyn
E. Stewart and William Burnam to Dennis Utterback, Fifth
Carcinogenicity Peer Review of Dichlorvos (August 28, 1996).
21. Health Effects Division, Office of Pesticide Programs, U.S.
EPA, Dichlorvos (DDVP): Risk Assessment Issues for the FIFRA Science
Advisory Panel (July 8, 1998).
22. Cancer Assessment Review Committee, Health Effects Division,
Office of Pesticide Programs, Cancer Assessment Document: Evaluation of
the Carcinogenic Potential of Dichlorvos (DDVP) (Sixth Review) (March
1, 2000).
23. An Evaluation of the Potential Carcinogenicity of Dichlorvos:
Final Report of the Expert Panel(July 27, 1998).
24. FIFRA Scientific Advisory Panel, Final Report -- Meeting of
July 30, 1998 (September 2, 1998).
25. Office of Pesticide Programs, U.S. EPA, Email Communication
from William Burnam to Karl Baetcke, Phone Call with Dr. Boorman re
DDVP and MCL.... please comment on this draft (May 14, 1999).
26. Office of Pesticides and Toxic Substances, U.S. EPA, Memorandum
from Jerome Blondell to Flora Chow, Write-up for Human Carcinogenicity
Data section of Crave review of Dichlorvos. HED Project no. INTRA --
0223 (December 3, 1991).
27. Office of Pesticide Programs, U.S. EPA, Office of Pesticide
Programs' Policy on the Determination of theAppropriate FQPA Safety
Factor(s) For Use in the Tolerance Setting Process: Response to
Comments (February 28, 2002).
28. Dourson, M., Felter, S., and Robinson, D., Evolution of
Science-based Uncertainty Factors in Noncancer Risk Assessment, 24
Regulatory Toxicology and Pharmacology 108 (1996).
29. Kent, R., Office of Pesticide Programs, U.S. EPA, Dichlorvos:
WOE Comparison of Human and Animal Studies for Single Chemical
Assessment and OP Cumulative Assessment (April 5, 2006).
30. EPA Human Studies Review Board, Minutes of the United States
Environmental Protection Agency (EPA) Human Studies Review Board (HSRB)
April 4-6, 2006 Public Meeting (May 15, 2006).
31. EPA Human Studies Review Board, Letter Report from Celia Fisher
to George Gray, Subject: April 4-6, 2006 Meeting EPA Human Studies
Review Board Report (June 26, 2006).
32. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Memorandum from William Dykstra to Eric Olson, Review of
Developmental Neurotoxicity Studies (February 8, 2005).
33. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Memorandum from Jocelyn Stewart to Christina Schletema, Review of
Toxicity Studies on Dichlorvos Using Human Volunteers(March 24, 1998)
(MRIDs 44317901, 4416201, 44248801, 44248802).
34. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Health Effects Test Guidelines: OPPTS 870.4100 Chronic Toxicity
(August 1998).
35. Office of Pesticides and Toxic Substances, U.S. EPA, Memorandum
from Kerry L. Dearfield to Judith Hauswirth, Review of in vivo
mutagenicity studies concerning Dichlorvos (August 10, 1988).
36. An Evaluation of the Potential Genotoxicity of Dichlorvos:
Final Report of the Expert Panel (July 22, 1998).
37. Office of the Administrator [sic], U.S. EPA, Memorandum from
Irving Mauer to Susan Hummel and Robert McNally/Pamela Noyes,
Dichlorvos (2,2-dichlorovinyl dimethyl phosphate; DDVP) -- Appraisal of
Mutagenicity Potential, Presented by the Blue Ribbon Panel in: An
Evaluation of the Potential Genotoxicity of Dichlorvos: Final Report of
the the Expert Panel (April 6, 1999).
38. A. Okamura et. al, A Comprehensive Evaluation of the Testicular
Toxicity of Dichlorvos in Wistar Rats, Toxicology 213, 129-137 (2005).
39. Office of Prevention, Pesticides and Toxic Substances, EPA,
Health Effects Test Guidelines: OPPTS 870.7600 Dermal Penetration
(August 1998).
40. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Reregistration Eligibility Decision (RED) for Malathion (July 2006).
41. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Reregistration Eligibility Decision for Acephate (September 2001).
42. Cheng, T. (1989) Metabolism of (Carbon 14)-DDVP in Rats:
Project ID HLA 6274-105. Unpublished study prepared by Hazleton
Laboratories America, Inc. 322 p.
43. Cheng, T. (1991) Supplement to: Metabolism of carbon 14-DDVP in
Rats (Preliminary and Definitive Phases) (...): Lab Project Number: HLA
6274-105-1. Unpublished study prepared by Hazleton Laboratories
America, Inc. 89 p.
44. Jeffcoat, A. (1990) Dermal Absorption of Dichlorvos in Rats:
Lab Project Number: 4615. Unpublished study prepared by Research
Triangle Institute. 196 p.
45. Wester RC and HI Maibach, (1993), Animal Models for
Percutaneous Absorption in Dermatology: Clinical and Basic Science ed
HI Maibach. CRC Press, Boca Raton p 89-101.
46. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Memorandum from Dennis McNeilly to Brigid Lowery, DDVP
(dichlorvos); Poultry Dermal Metabolism Study (December 17, 1993).
47. Office of Pesticides and Toxic Substances, U. S. EPA,
Memorandum from Paul Chin to Jane Talarico, EPA ID # 6274-105:
DDVP -- Review of Metabolism of DDVP in Rats (October 19, 1990).
48. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Memorandum from Dennis McNeilly to Brigid Lowery, DDVP
(dichlorvos); Goat Metabolism Study Following Dermal Application for 3
Consecutive Days (July 21, 1993).
49. Office of Pesticides and Toxic Substances, U. S. EPA,
Memorandum from Paul Chin to Larry Schnaubelt/Brigid Lowery, EPA ID
# 084001: DDVP -- Review of Metabolism of DDVP in Rats (March 25, 1992).
50. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Memorandum from Susan Hummel to Dennis Utterback and Christina
Scheltema, Dichlorvos (084001) Product and Residue Chemistry Chapters
for the Reregistration Eligibility Document (April 27, 1998).
51. Office of Pesticides and Toxic Substances, U.S. EPA, Memorandum
to Amy Rispin and William Miller, Registration Standard for Naled (June
8, 1983).
52. Hunter, C.; Brown, V. (1969) Studies on the Skin Irritant
Effects Observed with Shellgard Dogbands: Technical Service Report
TLTR.0002.69. Interim rept. (Unpublished study received Jul 14, 1969
under 201-215; prepared by Shell Research, Ltd., Eng., submitted by
Shell Chemical Co., Washington, DC; CDL:000935-B).

[[Page 68697]]

53. Rosenfeld, G. (1984) Guinea Pig Sensitization Study (Buehler):
Study #1097F. Unpublished study prepared by Cosmopolitan Safety
Evaluation, Inc. 17 p.
54. Shapiro, R. (1993) EPA Guinea Pig Sensitization Test (Buehler):
Prentox Fish Management Bait--Formula 1: Lab Project Number: T--2525:
P328: E30628-2. Unpublished study prepared by Product Safety Labs. 26 p.
55. Rosenfeld, G. (1984) Guinea Pig Sensitization Study (Buehler):
Study #1110F. Unpublished study prepared by Cosmopolitan Safety
Evaluation, Inc. 18 p.
56. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Memorandum from Thurston G. Morton to Susan Bartow, Dichlorvos
Acute, Probabilistic and Chronic Aggregate Dietary (Food and Drinking
Water) Exposure and Risk Assessments for the Reregistration Eligibility
Decision (November 8, 2007).
57. http://www.epa.gov/oppefed1/models/water/
58. Office of Prevention, Pesticides and Toxic Substances, U.S.
EPA, Memorandum from Ibrahim Abdel-Saheb to Eric Olson and Susan
Hummel, Revised Drinking Water Assessment for DDVP (PC Code 084001),
from Naled (PC Code 034401), and from Trichlorfon (PC Code 057901); DP
Barcode: D288834 (March 16, 2003).
59. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Memorandum from Jenna Carter to Susan Bartow, Usage Report in
Support of Reregistration for Trichlorfon (November 15, 2007).
60. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Memorandum from Jenna Carter to Susan Hummel, Refined Non-
agricultural Usage Report in Support of Refined Risk Assessment and
Risk Management for Naled (November 16, 2007).
61. EPA/USDA, Revised Food Commodity Intake Databse (FCID) dated 3/
8/04.
62. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Memorandum from Susan V. Hummel to Kimberly Lowe, Dichlorvos
(084001). Refined Anticipated Residues and Acute and Chronic Dietary
exposure and Risk Analyses for Residues of Dichlorvos resulting from
use of Dichlorvos, Trichlorfon and Naled (June 7, 2000).
63. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Memorandum from Cynthia Doucore to Susan Bartow, BEAD's Commercial
Sources for Usage Information: Doane (dmrkynetec) and Kline and
Company, Inc. (November 15, 2007).
64. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Memorandum from Don Atwood to Eric Olson, Dichlovor (DDVP) Usage
on Dairy Cattle, Beef Cattle, Swine, and Poultry (Animals and
Facilities) (November 15, 2007).
65. EPA, Process for Reviewing Tolerance Decisions Based on the Use
of Anticipated or Actual Residue Data (available at http://www.epa.gov/
pesticides/regulating/anticipated_residue/process_review.htm).
66. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Memorandum from Thurston G. Morton to Kylie Rothwell/Betty
Shackleford, Trichlorfon; Chemical No. 057901. HED's Revised
Preliminary Human Health Risk Assessment for Trichlorfon, Case # 0104
(April 18, 2000).
67. S. Hummel. Summary of USDA-FSIS Monitoring Data for Chlorinated
Organophosphates from 1993 through 1997: carbophenothion (Trithion,
058102), chlorpyrifos (059101), chlorfenvinphos (084101), coumaphos
(036501), coumaphos oxon, dichlorvos (DDVP, 084001), ethion (058401),
phosalone (097701), ronnel (058301), tetrachlorvinphos (Gardona, or
stirophos, 083701), trichlorfon (057901) (6/2/1998).
68. All PDP reports are available at http://www.ams.usda.gov/science/pdp.
69. Office of Pesticide Programs, U.S. EPA, Assigning Values To
Nondetected/Non-Quantified Pesticide Residues In Human Health Food
Exposure Assessments (March 23, 2000).
70. Office of Pesticides and Toxic Substances, U. S. EPA,
Memorandum from Debra Edwards to William H. Miller, Chevron Chemical
Co. Followup to the Naled Registration Standard -- Residue Data for Fly
and Mosquito Label Uses (April 5, 1988).
71. Office of Pesticides and Toxic Substances, U. S. EPA,
Memorandum from Francis B. Suhre to Anita Schmidt, NALED/TRICHLORFON:
Potential for metabolism/conversion of naled and trichlorfon to DDVP;
No MRID No., RCB No. 3728, 3729, and 3730 (April 28, 1988).
72. Office of Pesticides and Toxic Substances, U. S. EPA,
Memorandum from Jenna Carter to Susan Hummel, Refined Non-Agricultural
Usage Report in Support of the Revised Risk Assessment and Risk
Management for Naled (034401) (November 16, 2007).
73. OPPTS Harmonized Test Guidelines, Series 860, Guideline
860.1300 Nature of the Residue -- Plants, Livestock (August 1996).
74. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Memorandum from Susan V. Hummel and Dennis McNeilly to Bridgid
Lowery, Dichlorvos (DDVP; 084001): Reregistration Case No. 0310
Magnitude of the residue/decline of dichlorvos residues in/on
nonperishable raw agricultural commodities and processed commodities,
bulk stored commodities; mushroom storage interval data (June 2, 1994).
75. Center for Food Safety and Nutrition, U.S. Food and Drug
Administration, Total Diet Study (last updated March 2007) (available
at www.cfsan.fda.gov/comm/tds-toc.html).
76. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Memorandum from Susan V. Hummel and Dennis McNeilly to Bridgid
Lowery Dichlorvos (084001) Reregistration Case No. 0310 Processing
studies on field corn, wheat, rice, cottonseed and soybeans. [MRID
42993501, CB No. 13296; DP Barcode D199979] (July 18, 1994).
77. U.S. EPA, Interim Report:Dermal Exposure Assessment: Principles
and Applications (January 1992). EPA/600/8-91/011B.
78. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Memorandum from Ray Kent to Robert McNally, Dichlorvos (PC
084001). Additional characterization of inhalation risk posed by use of
dichlorvos-containing resin strips. DP332823. (November 16, 2007).
79. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Letter from George LaRocca to Jon C. Wood, Application to Amend
Dichlorvos Labeling (November 15, 2007).
80. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Memorandum from David Jaquith to Kimberly Lowe, Examination of
Recent Submissions from Amvac regarding Dichlorvos (DDVP) and Rationale
for Not Including Them in the Exposure/Risk Assessment (May 27, 1999).
81. Office of Prevention, Pesticides and Toxic Substances, U. S.
EPA, Memorandum from Deborah Smegal to Mark Hartman, Update: Exposure
Assessment for Chlorpyrifos Post-Construction Termiticide Use DP
Barcode D266827, Case 818975, PC Code 059101) (June 20, 2000).
82. Environmental Criteria and Assessment Office, Office of Health
and Environmental Assessment, Office of Research and Development, U.S.
EPA, Methods for Derivation of Inhalation Reference Concentrations and
Application of Inhalation Dosimetry. EPA/600/8-90/066F. Environmental
Criteria and Assessment Office, Office of Health and Environmental
Assessment, (October 1994).

[[Page 68698]]

List of Subjects

Environmental protection, pesticides and pest.

Dated: November 16, 2007
Debra Edwards,
Director, Office of Pesticide Programs.
[FR Doc. E7-23571 Filed 12-4-07; 8:45 a.m.]
BILLING CODE 6560-50-S

Notices For
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2008
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2006
2005
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2003
2002
2001
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Dichlorvos (DDVP); Order Denying NRDC's Petition to Revoke All Tolerances

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