[Federal Register Volume 70, Number 153 (Wednesday, August 10, 2005)]
[Rules and Regulations]
[Pages 46706-46740]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-15840]
[[Page 46705]]
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Part IV
Environmental Protection Agency
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40 CFR Part 180
Order Denying Objections to Issuance of Tolerances; Final Rule
Federal Register / Vol. 70, No. 153 / Wednesday, August 10, 2005 /
Rules and Regulations
[[Page 46706]]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[OPP-2005-0190; FRL-7727-4]
Order Denying Objections to Issuance of Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final Order.
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SUMMARY: On four occasions in the first half of 2002, the Natural
Resources Defense Council (NRDC) and various other parties filed
objections with EPA to final rules under section 408 of the Federal
Food, Drug, and Cosmetic Act (FFDCA), (21 U.S.C. 346a), establishing
pesticide tolerances for various pesticides. The objections apply to 14
pesticides and 112 separate pesticide tolerances. Although the
objections raise numerous pesticide-specific issues, they all focus on
the potential risks that the pesticides pose to farm children. This
Order responds to NRDC's objections as to all of the challenged
tolerances with the exception of the objections pertaining to the
imidacloprid tolerance on blueberries which were previously denied. The
objections to the other tolerances are denied for the reasons stated
herein.
FOR FURTHER INFORMATION CONTACT: Nicole Williams, Registration
Division, (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001; telephone number: (703) 308-5551; fax number: (703) 308-6920; e-
mail address: [email protected].
SUPPLEMENTARY INFORMATION: This order is outlined as follows:
I. General Information
A. Does This Action Apply to Me?
B. How Can I Get Additional Information, Including Copies of this
Document and Other Related Documents?
1. Docket
2. Electronic access
II. Introduction
A. What Action Is the Agency Taking?
B. What Is the Agency's Authority for Taking This Action?
III. Statutory and Regulatory Background
A. Statutory Background
B. Assessing Risk Under the FFDCA
C. Science Policies
1. Children's Safety Factor Policy
2. Aggregate Exposure Policies
D. NRDC Farmworker Children Petition
IV. The Challenged Tolerance Decisions
1. Halosulfuron-methyl
2. Pymetrozine
3. Mepiquat
4. Bifenazate
5. Zeta-cypermethrin
6. Diflubenzuron
7. 2,4-D
8. Isoxadifen-ethyl
9. Acetamiprid
10. Propiconazole
11. Furilazole
12. Fenhexamid
13. Fluazinam
V. NRDC Objections
A. In General
B. Generic Issues
1. Children's safety factor issue
2. Aggregate exposure issues.
3. Reliance on LOAELs and NOAELs
C. Pesticide-specific Issues
VI. Public Comment
A. In General
B. Individual Comments
1. The FQPA Implementation Working Group
2. Inter-Regional Research Project Number 4 (IR-4)
3. ISK Biosciences - Fluazinam
4. Bayer CropScience - Isoxadifen-ethyl
5. Aventis CropScience - Acetamiprid
6. FMC Corporation - Zeta-cypermethrin
7. Crompton Corporation - Diflubenzuron and Bifenazate
a. Diflubenzuron
b. Bifenazate
8. Syngenta Crop Protection - Propiconazole and Pymetrozine
a. Propiconazole
b. Pymetrozine
9. BASF Corporation - Mepiquat
10. Industry Task Force II on 2,4-D Research Data
VII. Response to Objections
A Expired Tolerances
B. Children's Exposure to Pesticides in Agricultural Areas
1. Studies Focusing on Exposure to Children in Agricultural Areas
2. Information Bearing on Exposure Levels as a Result of Spray
Drift and Post-Application Drift of Volatilized Residues
a. Pesticide Spray Drift During Application
(1) Comparison of AgDrift Model estimates with exposurefrom
residential lawn use generally.
(2)Evaluation of MOE's based on AgDrift Model for the pesticides in
the Objections
b. Volatilization of Applied Pesticides
(1) Analysis of CFPR Report and Ranking Study
(2) Vapor Pressure
c. Conclusion
C. Failed to Retain Children's 10X Safety Factor
1. Introduction
2. Lack of DNT Study Generally
a. Pesticides may cause neurological developmental effects
b. 1998 Retrospective Study on Submitted DNT Studies
c. 10X Task Force Report
d. EPA's 10X Policy
e. Conclusion
3. Other Pesticide-specific Missing Toxicity Data
a. Diflubenzuron
b. Fluazinam
c. Furilazole
d. 2,4-D
4. Missing Exposure Data - General
a. Farm Children Exposure
b. Lack of comprehensive drinking water (DW) monitoring data
5. Missing Exposure Data - Specific
a. Mepiquat
b. Bifenazate
c. Zeta-cypermethrin
d. Diflubenzuron
e. Acetamiprid
6. Missing Risk Assessments
a. Halosulfuron-methyl
b. Bifenazate
c. Isoxadifen-ethyl
d. Propiconazole
e. Fenhexamid
f. Fluazinam
g. 2,4-D
7. Conclusion on Children's Safety Factor Objections
C. LOAEL/NOAEL
1. Generic Legal Argument
2. Objections Pertaining to Specific Pesticides
a. Pymetrozine
b. Mepiquat
c. Zeta-cypermethrin
d. Fluazinam
e. Isoxadifen-ethyl, Acetamiprid, Propiconazole, Furilazole, and
Fenhexamid
D. Aggregate Exposure
1. Worker Exposure
2. Classification of Farm Children as a Major Identifiable
Population Subgroup
3. Adequacy of EPA's Assessment of the Aggregate Exposure of
Children, Including Children in Agricultural Areas
4. Residential Exposure as a Result of Use Requiring a Tolerance
5. Anticipated Residues/Exposures Due to Purchase of Food at
Farmstands
6. Population Percentile Used in Aggregate Exposure Estimates
a. In General
b. Choice of Population Percentile
7. Alleged Inadequacies Pertaining to Specific Pesticides
a. Pymetrozine
b. Bifenazate
c. Zeta-cypermethrin
d. Diflubenzuron
e. 2,4-D
f. Isoxadifen-ethyl, acetamiprid, fluazinam
E. Human Testing
F. Conclusion on Objections
VIII. Response to Comments on NRDC's Objections
IX. Regulatory Assessment Requirements
X. Submission to Congress and the Comptroller General
XI. Time and Date of Issuance of This Order
XII. References
I. General Information
A. Does This Action Apply to Me?
In this document EPA denies objections to a tolerance actions filed
by the Natural Resources Defense Council (NRDC) and the following
additional parties: Boston Women's Health Book Collective, Breast
Cancer Action, Californians for Pesticide Reform, Commonweal, Lymphoma
Foundation of America, Natural Resources Defense
[[Page 46707]]
Council, Northwest Coalition for Alternatives to Pesticides, Pesticide
Action Network, North America, Pineros y Campesinos Unidos del
Noroeste, SF-Bay Area Chapter of Physicians for Social Responsibility,
and Women's Cancer Resource Center. This action may also be of interest
to agricultural producers, food manufacturers, or other pesticide
manufacturers. Potentially affected categories and entities may
include, but are not limited to:
Industry, e.g., NAICS 111, 112, 311, 32532, Crop
production, Animal production, Food manufacturing, Pesticide
manufacturing.
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities who may be interested in today's
action.
B. How Can I Get Additional Information, Including Copies of this
Document and Other Related Documents?
1. Docket. EPA has established an official public docket for this
action under docket identification (ID) number OPP-2005-0190. The
official public docket consists of the documents specifically
referenced in this action, any public comments received, and other
information related to this action. Although a part of the official
docket, the public docket does not include Confidential Business
Information (CBI) or other information whose disclosure is restricted
by statute. The official public docket is the collection of materials
that is available for public viewing at the Public Information and
Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2,
1801 S. Bell St., Arlington, VA. This docket facility is open from 8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The
docket telephone number is (703) 305-5805.
2. Electronic access. You may access this Federal Register document
electronically through the EPA Internet under the ``Federal Register''
listings at http://www.epa.gov/fedrgstr/.
An electronic version of the public docket is available through
EPA's electronic public docket and comment system, EPA Dockets. You may
use EPA Dockets at http://www.epa.gov/edocket/ to view public comments,
access the index listing of the contents of the official public docket,
and to access those documents in the public docket that are available
electronically. Although not all docket materials may be available
electronically, you may still access any of the publicly available
docket materials through the docket facility identified in Unit I.B.1.
Once in the system, select ``search,'' then key in the appropriate
docket ID number.
II. Introduction
A. What Action Is the Agency Taking?
On four occasions in the first half of 2002, the NRDC and various
other parties filed objections with EPA to final rules under section
408 of the Federal Food, Drug, and Cosmetic Act (FFDCA), (21 U.S.C.
346a), establishing pesticide tolerances for various pesticides. [The
objectors are hereinafter collectively referred to as ``NRDC.'']. The
objections apply to 14 pesticides and 112 separate pesticide
tolerances. This Order responds to objections as to all of the
tolerances other than the objections as to the imidacloprid tolerance
on blueberries. Those objections were denied previously. (69 FR 30042,
May 26, 2004).
Although the objections raise numerous pesticide-specific issues,
they all primarily focus on the potential risks that the pesticides
pose to farm children. Further, each of the objections makes two main
assertions with regard to the pesticide tolerances in question: (1)
That EPA has not properly applied the additional 10X safety factor for
the protection of infants and children in section 408(b)(2)(C); and (2)
that EPA has not accurately assessed the aggregate exposure of farm
children to pesticide residues. NRDC did not exercise the option
provided in section 408(g)(2) to request a hearing on its objections,
but instead asked that the Agency rule on its objections on the basis
of its written objections and attached submissions.
Because the objections raised questions of broad interest, EPA
published a representative copy of the objections in the Federal
Register for comment, (67 FR 41628, June 19, 2002), and made all of the
objections available for public review on its website. On May 26, 2004,
EPA denied the objections as to one of the challenged tolerances
(imidacloprid on blueberries) because that tolerance had expired. (69
FR 30042, May 26, 2004). At the same time EPA denied the objections to
the imidacloprid tolerance on mootness grounds, EPA also established a
new imidacloprid blueberry tolerance and as part of that action
addressed the issues raised by the NRDC objections. (69 FR 30076, May
26, 2004). In the course of addressing these issues, EPA responded to a
petition concerning farm children filed in 1998 by NRDC and various
other parties. (69 FR at 30069-70, May 26, 2004). This Order relies
heavily on much of the reasoning set forth in connection with the
establishment of the new imidacloprid blueberry tolerance.
The body of this document contains the following sections. First,
there is a background section which explains the applicable statutory
and regulatory provisions, the relevant EPA science policy documents,
and prior NRDC actions with regard to farm children. Second, EPA
describes the objected-to tolerance actions. Third, there is a section
setting forth in greater detail the substance of the objections.
Fourth, a summary of the public comment is presented. Finally, EPA
announces its response to the objections and responds to public
comments.
B. What Is the Agency's Authority for Taking This Action?
The procedure for filing objections to tolerance actions and EPA's
authority for acting on such objections is contained in section 408(g)
of the FFDCA and regulations at 40 CFR part 178. (21 U.S.C. 346a(g)).
III. Statutory and Regulatory Background
A. Statutory Background
EPA establishes maximum residue limits, or ``tolerances,'' for
pesticide residues in food under section 408 of the FFDCA. (21 U.S.C.
346a). Without such a tolerance or an exemption from the requirement of
a tolerance, a food containing a pesticide residue is ``adulterated''
under section 402 of the FFDCA and may not be legally moved in
interstate commerce. (21 U.S.C. 331, 342). Monitoring and enforcement
of pesticide tolerances are carried out by the U.S. Food and Drug
Administration (FDA) and the U. S. Department of Agriculture (USDA).
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 directs EPA, in making a safety
determination, to ``consider, among other relevant factors- . . .
.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
[[Page 46708]]
exposure from other non-occupational sources.'' (21 U.S.C.
346a(b)(2)(D)(vi)). Other provisions address in greater detail exposure
considerations involving ``anticipated and actual residue levels'' and
``percent of crop actually treated.'' (See 21 U.S.C. 346a(b)(2)(E) and
(F)). Section 408(b)(2)(C) requires EPA to give special consideration
to risks posed to infants and children. This provision directs that
``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 notice as the
``children's safety factor.''] These provisions establishing the
detailed safety standard for pesticides were added to section 408 by
the Food Quality Protection Act of 1996 (FQPA), an act that
substantially rewrote this section of the statute.
Tolerances are established by rulemaking under the unique
procedural framework set forth in the FFDCA. Generally, the rulemaking
is initiated by the party seeking the 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 along with a summary
of the petition, prepared by the petitioner. (21 U.S.C. 346a(d)(3)).
After reviewing the petition, and any comments received on it, EPA may
issue a final rule establishing the tolerance, issue a proposed rule,
or deny the petition. (21 U.S.C. 346a(d)(4)). Once EPA takes final
action on the petition by either establishing 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)).
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)).
B. Assessing Risk Under the FFDCA
In assessing and quantifying non-cancer risks posed by pesticides
under the FFDCA as amended by the FQPA, EPA first determines the
toxicological level of concern and then compares 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 the lowest dose at which no adverse effects from the
pesticide are seen in relevant studies (the margin of exposure (MOE)
approach). How EPA determines the level of concern, chooses safety
factors, and assesses risk under these two approaches is explained in
more detail below. EPA's general approach to estimating exposure is
also briefly discussed.
For dietary risk assessment (for risks other than cancer), the dose
at which no adverse effects are observed (the ``NOAEL'') from the
toxicology study identified as appropriate for use in risk assessment
is used to estimate the toxicological level of concern. However, the
lowest dose at which adverse effects of concern are identified (the
``LOAEL'') is sometimes used for risk assessment if no NOAEL was
achieved in the toxicology study selected. A safety or uncertainty
factor is then applied to this toxicological level of concern to
calculate a safe dose for humans, usually referred to by EPA as an
acute or chronic reference dose (RfD). The RfD is equal to the NOAEL
divided by all applicable safety or uncertainty factors. Typically, a
safety or uncertainty factor of 100X 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. 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. To quantitatively describe risk using the RfD
approach, estimated exposure is expressed as a percentage of the RfD.
Dietary exposures lower than 100 percent of the RfD are generally not
of concern.
For non-dietary, and combined dietary and non-dietary, risk
assessments (other than cancer risk assessments) the same safety
factors are used to determine the toxicological level of concern. For
example, when 1,000X is the appropriate safety factor (10X to account
for interspecies differences, 10X for intraspecies differences, and 10X
for FQPA), the level of concern is that there be a 1,000-fold margin
between the NOAEL from the toxicology study identified as appropriate
for use in risk assessment and human exposure. To estimate risk, a
ratio of the NOAEL to aggregate exposures (margin of exposure (MOE) =
NOAEL/exposure) is calculated and compared to the level of concern. In
contrast to the RfD approach, the higher the MOE, the safer the
pesticide. Accordingly, if the level of concern for a pesticide is
1,000, MOE's exceeding 1,000 would generally not be of concern.
For cancer risk assessments, EPA generally assumes that any amount
of exposure will lead to some degree of cancer risk. Using a model
based on the slope of the cancer dose-response curve in relevant
studies, EPA estimates risk in terms of the probability of occurrence
of additional cancer cases as a result of exposure to the pesticide. An
example of how such a probability risk is expressed would be to
describe the risk as one in one hundred thousand (1 X 10-5),
one in a million (1 X 10-6), or one in ten million (1 X
10-7). Under certain specific circumstances, MOE
calculations will be used for the carcinogenic risk assessment. No
further discussion of cancer risk assessment is included here because
NRDC's objections do not relate to cancer risks.
Equally important to the risk assessment process as determining the
toxicological level of concern is estimating human exposure. As
explained in more detail in Unit VII.D.5. of this document, EPA uses a
tiering system to estimate exposure which attempts to minimize
resources expended in exposure estimates. The first tier is generally a
worst case assessment that is relatively easy to conduct because it
relies on conservative (health-protective) assumptions. Only if that
tier suggests
[[Page 46709]]
that the pesticide may pose a risk of concern are more resource-
intensive tiers triggered where the focus is on obtaining more
realistic exposure values. (Ref. 1).
C. Science Policies
As part of implementation of the major changes to FFDCA section 408
included in the FQPA, EPA has issued a number of policy guidance
documents addressing critical science issues. Of particular interest to
the NRDC objections are the science policies covering the children's
safety factor, aggregate pesticide exposure, and the population
percentile of exposure used in estimating aggregate exposure.
1. Children's safety factor policy. On January 31, 2002, EPA
released its science policy guidance on the children's safety factor.
(Ref. 2) [This policy is hereinafter referred to as the ``Children's
Safety Factor Policy'']. That policy had undergone an intensive and
extended process of public comment as well as internal and external
science peer review. An EPA-wide task force was established to consider
the children's safety factor in March 1998. Taking into account reports
issued by the task force on both toxicity and exposure issues, EPA's
Office of Pesticide Programs (OPP) released a draft children's safety
policy document in May 1999. That document was subject to an extended
public comment period as well as review by the FIFRA Scientific
Advisory Panel. (Id. at 5). Although the January 31, 2002 policy
differed in some respects from prior Agency practice, for the most part
the policy statement reflected EPA's experience in implementing the
children's safety factor provision since the passage of the FQPA.
The Children's Safety Factor Policy emphasizes throughout that EPA
interprets the children's safety factor provision as establishing a
presumption in favor of application of an additional 10X safety factor
for the protection of infants and children. (Id. at 4, 11, 47, A-6).
Further, EPA notes that the children's safety factor provision permits
a different safety factor to be substituted for this default 10X factor
only if reliable data are available to show that the different factor
will protect the safety of infants and children. (Id.). Given the
wealth of data available on pesticides, however, EPA indicates a
preference for making an individualized determination of a protective
safety factor if possible. (Id. at 11). EPA states that use of the
default factor could under- or over-protect infants and children due to
the wide variety of issues addressed by the children's safety factor.
(Id.). EPA notes that ``[i]ndividual assessments may result in the use
of additional factors greater or less than, or equal to 10X, or no
additional factor at all.'' (Id.). Concluding that individualized
assessments would be able to be made in most cases, EPA indicates that
``this guidance document focuses primarily on the considerations
relevant to determining a safety factor `different' from the default
10X that protects infants and children. Discussions in this document of
the appropriateness, adequacy, need for, or size of an additional
safety factor are premised on the fact that reliable data exist for
choosing a `different' factor than the 10X default value.'' (Id. at
12).
In making such individual assessments regarding the magnitude of
the safety factor, EPA stresses the importance of focusing on the
statutory language that ties the children's safety factor to concerns
regarding potential pre- and post-natal toxicity and the completeness
of the toxicity and exposure databases. (Id. at 11-12). As to the
completeness of the toxicity database, EPA recommends use of a weight-
of-the-evidence approach which considers not only the presence or
absence of data generally required under EPA regulations and guidelines
but also the availability of ``any other data needed to evaluate
potential risks to children.'' (Id. at 20). EPA indicates that the
principal inquiry concerning missing data would center on whether the
missing data would significantly affect calculation of a safe exposure
level (commonly referred to as the RfD). (Id. at 22; accord 67 FR
60950, 60955, September 27, 2002) (finding no additional safety factor
necessary for triticonazole despite lack of developmental neurotoxicity
(DNT) study because the ``DNT [study] is unlikely to affect the manner
in which triticonazole is regulated.'')). When the missing data are
data above and beyond general regulatory requirements, EPA indicates
that the weight of evidence would generally only support the need for
an additional safety factor where the data ``is being required for
`cause,' that is, if a significant concern is raised based upon a
review of existing information, not simply because a data requirement
has been levied to expand OPP's general knowledge.'' (Ref. 2 at 23).
Finally, with regard to the DNT study, EPA lists several important
factors addressing the weight of evidence bearing on the degree of
concern when such a study has been required but has not yet been
completed. (Id. at 24). Moreover, EPA reiterates that, like any other
missing study, the absence of the DNT study does not trigger a
mandatory requirement to retain the default 10X value, but rather
requires an individualized assessment centering on the question of
whether ``a DNT study is likely to identify a new hazard or effects at
lower dose levels of the pesticide that could significantly change the
outcome of its risk assessment . . . .'' (Id.). The extent to which the
policy stresses the need for EPA's evaluation of the completeness of
the database to focus directly on whether missing data might possibly
lower an existing RfD was a change in emphasis from past actions.
As to potential pre- and post-natal toxicity, the Children's Safety
Factor Policy lists a variety of factors that should be considered in
evaluating the degree of concern regarding any identified pre- or post-
natal toxicity. (Id. at 27-31). As with the completeness of the
toxicity database, EPA emphasizes that the analysis should focus on
whether any identified pre- or post-natal toxicity raises uncertainty
as to whether the RfD is protective of infants and children. (Id. at
31). Once again, the presence of pre- or post-natal toxicity, by
itself, is not regarded as determinative as to the children's safety
factor. Rather, EPA stresses the importance of evaluating all of the
data under a weight-of-evidence approach focusing on the safety of
infants and children. (Id.). This attention on the overall database
also indicated a shift in emphasis for EPA's implementation of the
children's safety factor provision as previous decisions had often
treated a finding of increased sensitivity in the young as almost
necessitating some additional safety factor.
In evaluating the completeness of the exposure database, EPA
explains that a weight-of-the-evidence approach should be used to
determine the confidence level EPA has as to whether the exposure
assessment ``is either highly accurate or based upon sufficiently
conservative input that it does not underestimate those exposures that
are critical for assessing the risks to infants and children.'' (Id. at
32). EPA describes why its methods for calculating exposure through
various routes and aggregating exposure over those routes generally
produce conservative exposure estimates - i.e. health-protective
estimates due to overestimation of exposure. (Id. at 40-43).
Nonetheless, EPA emphasizes the importance of verifying that the
tendency for its methods to overestimate exposure in fact were
adequately
[[Page 46710]]
protective in each individual assessment. (Id. at 44).
Given that this policy was released at roughly the same time the
challenged tolerance actions were issued and that the toxicological,
exposure, and risk assessments leading up to such actions can take
several months or even years, the challenged tolerance actions were not
evaluated prior to being finalized under this new restatement of EPA's
policy on the children's safety factor. EPA's experience in making
decisions under the 2002 policy is that while for many pesticides the
safety factor determination remains unchanged, for others the safety
factors may go up or down. To generalize, in situations where the
database is incomplete, EPA's heightened emphasis on whether the
missing data may affect the assessment of risk has tended to make it
more likely that EPA will retain the full 10X children's safety factor.
(See, e.g., 70 FR 7876, 7882, February 16, 2005) (avermectin - 10X
factor retained due to lack of DNT study and acute and subchronic
neuorotoxicity studies and residual toxicological concerns as to safety
of young); 70 FR 7886, 7891, February 16, 2005) (clothianidim - 10X
factor retained due to lack of developmental immunotoxicity study); 69
FR 58058, 58062-58063, September 29, 2004) (fenamidone - 10X factor
retained due to lack of DNT study); but see 69 FR 52182, 52187, August
25, 2004) (folpet - 10X removed despite lack of DNT study because the
DNT study is unlikely to change RfD)). On the other hand, in instances
where a study shows increased sensitivity in the young, the focus on
whether in the context of the overall database such sensitivity
indicates that EPA's risk assessment is not protective of infants and
children, has frequently resulted in the removal of the factor. (See,
e.g., 69 FR 63083, 63092-63093, October 29, 2004) (pyraclostrobin - 10X
factor removed because additional sensitivity well-characterized); 69
FR 58290, 58295, September 30, 2004) (cyazofamid - 10X factor removed
because additional sensitivity well-characterized); but see 69 FR
62602, 62610, October 27, 2004) (deltamethrin - 10X factor lowered but
not removed taking into consideration level at which additional
sensitivity was observed)). As these decisions evidence, the
determination on the children's safety factor is heavily dependent on
the results from the studies specific to the pesticide in question.
(See, e.g., 70 FR 14535, 14541-14542, March 23, 2005) (dinotefuran -
10X factor retained as to some risk assessments due to the lack of a
developmental immunotoxicity study; no additional factor on any risk
assessment found necessary to address lack of a DNT study)).
2. Aggregate exposure policies. As mentioned above, the FQPA-added
safety standard directs that the safety of pesticide residues in food
be based on ``aggregate exposure'' to the pesticide. (21 U.S.C.
346a(b)(2)(A)(ii)). Aggregate exposure to a pesticide includes all
``anticipated dietary exposure and all other exposures for which there
is reliable information.'' (Id.). The statute makes clear that in
assessing aggregate exposure pertaining to a pesticide EPA must
consider not only exposure to the pesticide in the food covered by the
tolerance in question but exposure to the pesticide as a result of
other tolerances and from ``other non-occupational sources.'' (Id.
346a(b)(2)(D)(vi)). Further, the statute directs EPA to consider
aggregate exposure to other substances related to the pesticide so long
as that exposure results from a non-occupational source. (Id.
346a(b)(2)(D)(vi)). In November 2001, EPA released a science guidance
document entitled ``General Principles for Performing Aggregate
Exposure and Risk Assessments.'' This document deals primarily with the
complex subject of integrating distributional and probabilistic
techniques into aggregate exposure analyses. (Ref. 3).
More relevant to the current objections is the science guidance
document issued in March 2000 addressing the population percentile of
exposure used in making acute exposure estimates for applying the
safety standard under section 408. (Ref. 4) [hereinafter referred to as
``Percentile Policy'']. Traditionally, EPA had used the 95th percentile
of human exposure in acute dietary exposure assessments as representing
a reasonable worst case scenario. (Id. at 15). Due to the very
conservative (health-protective) assumptions used for acute exposure
assessments, the 95th percentile was viewed as a reasonable
approximation of an exposure level not likely to be exceeded by any
individuals. (Id. at 15-17). For these assessments EPA generally
assumed that all crops for which there is a tolerance are treated with
the pesticide and all treated crops have residues at the highest level
legally permitted.
More recently, because of the availability of better data on
residue values and new risk assessment techniques, EPA has restructured
its approach to the use of population exposure percentiles in making
safety determinations for acute risks under section 408. EPA has
retained the 95th percentile as the starting point of analysis for
worst case (tolerance level) assessments. EPA, however, generally uses
higher percentiles of exposure when less conservative assumptions are
made concerning residue values. (Id.). For example, beginning in the
late 1990's, EPA has increasingly relied upon probabilistic assessment
techniques for assessing acute dietary exposure and risk. Because EPA
generally uses much more realistic exposure values (e.g., monitoring
data on pesticide levels in food) in conducting probabilistic
assessments, a higher population exposure percentile was generally
found to be necessary to ensure that exposure for the overall
population was not understated. The Percentile Policy explains and
defends EPA's choice of the 99.9th percentile as a starting point for
evaluating exposure and acute risk with probabilistic assessments.
EPA confirms in the Percentile Policy document that it will
generally continue to use the 95th percentile of exposure for non-
probabilistic, or what has been referred to as ``deterministic'' acute
risk assessments that use worst case exposure assumptions.'' (Id. at
17, 29). The conservative (health-protective) nature of this approach
is confirmed by data EPA cites showing that deterministic assessments
of exposure at the 95th percentile assuming residues at tolerance
levels regularly result in exposure predictions significantly higher
than probabilistic exposure estimates of the 99.9th percentile using
monitoring data. (Id. at 16-17).
Importantly, EPA's Percentile Policy makes clear that in choosing a
population percentile to estimate exposure, EPA is not intending to
define the portion of the population that is to be protected. The
policy explicitly states that: ``OPP's goal is to regulate pesticides
in such a manner that everyone is reasonably certain to experience no
harm as a result of dietary and other non-occupational exposures to
pesticides.'' (Id. at 28).
D. NRDC Farmworker Children Petition
On October 22, 1998, NRDC and 58 other public interest
organizations and individuals submitted a petition to EPA asking that
EPA ``find that farm children are a major identifiable subgroup and
must be protected under FQPA when setting allowable levels of pesticide
residue in food.'' (Ref. 5) [hereinafter referred to as the ``Farm
Children Petition'']. The Farm Children Petition claims that ``[a]n
increasing body of scientific evidence, including biomonitoring data
and residential exposure studies, indicates that farm children face
particularly significant
[[Page 46711]]
exposures and health risks from pesticides.'' (Id. at 3). In addition
to requesting the ``major identifiable subgroup'' designation, the
Petition also asked that EPA use the children's safety factor to
protect farm children, require additional exposure data on farm
children exposure and not issue any new tolerances until such data are
available, deny registration for any pesticide without a validated
method for detecting residues in food, increase research into issues
concerning farm children exposure to pesticides, and honor the
President's Executive Order on Environmental Justice.
EPA responded to the Farm Children Petition in the Imidacloprid
Order. EPA declined to name farm children as a separate major,
identifiable subgroup pointing out that any pesticide exposures to
children as a result of proximity to agricultural fields can be fully
taken into account as part of the consideration of EPA's already
existing major identifiable subgroups of children. (69 FR 30069, May
26, 2004). EPA agreed with most of the other aspects of NRDC's
petition. (69 FR 30076-30077, May 26, 2004).
IV. The Challenged Tolerance Decisions
Table 1 lists the tolerance actions challenged by NRDC. The
tolerance actions are grouped as they were by NRDC in NRDC's four sets
of objections.
Table 1.--Challenged Tolerance Actions
------------------------------------------------------------------------
Pesticides Involved FR Citations (respectively)
------------------------------------------------------------------------
halosulfuron-methyl, pymetrozine 66 FR 66333, December 26, 2001; 66
FR 66778, December 27, 2002; 66
FR 66786, December 27, 2001
-------------------------------------
imidacloprid, mepiquat, bifenazate, 67 FR 2580, January 18, 2002; 67
zeta-cypermethrin, diflubenzuron FR 3113, January, 23, 2002; 67 FR
4913, February 1, 2002; 67 FR
6422, February 12, 2002; 67 FR
7085, February 15, 2002
-------------------------------------
2,4-D 67 FR 10622, March 8, 2002
-------------------------------------
isoxadifen-ethyl, acetamiprid, 67 FR 12875, March 20, 2002; 67 FR
propiconazole, furilazole, 14649, March 27, 2002; 67 FR
fenhexamid, fluazinam 14866, March 28, 2002; 67 FR
15727, April 3, 2002; 67 FR
19114, April 18, 2002; 67 FR
19120, April 18, 2002
------------------------------------------------------------------------
Each of these tolerance actions, except imidacloprid, is summarized
briefly below.
1. Halosulfuron-methyl. NRDC challenged two separate tolerance
actions on halosulfuron-methyl: (1) A December 26, 2001 action
establishing tolerances on the melon subgroup; (66 FR 66333, December
26, 2001), and (2) a December 27, 2001 action establishing time-limited
tolerances in connection with an emergency exemption under FIFRA on
asparagus, (66 FR 66778, December 27, 2002). The risk assessments for
both actions yielded similar results. Given halosulfuron-methyl's
exposure pattern and toxicological characteristics, EPA determined that
halosulfuron-methyl potentially presented acute, chronic, short-term,
and intermediate-term risks and EPA quantitatively assessed these risks
in making its safety determination. (66 FR 66336-66339; 66 FR 66783-
66784). All of these risks were found to be below the Agency's level of
concern. (Id.). Although a DNT study was outstanding, EPA determined
that the additional 10X children's safety factor was not needed to
protect infants and children because the toxicological data showed no
evidence of greater sensitivity to the young and indicated that the DNT
study was unlikely to affect the risk assessment. EPA explained the
latter conclusion by noting that:
(a) The alterations in the fetal nervous system occurred in only
one species (in rats and not in rabbits); (b) the fetal effects
which will be investigated in the required developmental
neurotoxicity study were seen only at a dose of 750 mg/kg/day which
is close to the Limit-Dose (1,000 mg/kg/day); (c) there was no
evidence of clinical signs of neurotoxicity, brain weight changes,
or neuropathology in the subchronic or chronic studies in rats; (d)
the developmental neurotoxicity study is required only as
confirmatory data to understand what the effect is at a high
exposure (dose) level.
(66 FR at 66782).
2. Pymetrozine. NRDC challenged a December 27, 2001 action
establishing tolerances for pymetrozine on cotton seed, cotton gin
byproducts, the fruiting vegetables crop group, the cucurbit vegetables
crop group, the leafy vegetables crop group (except Brassica), head and
stem Brassica, leafy Brassica, turnip greens, dried hops, and pecans.
(66 FR 66786, December 27, 2001). Given pymetrozine's exposure pattern
and toxicological characteristics, EPA determined that pymetrozine
potentially presented acute, chronic, short-term, and cancer risks and
EPA quantitatively assessed these risks in making its safety
determination. (66 FR at 66791-66792). All of these risks were found to
be below the Agency's level of concern. (Id.). Although a DNT study was
outstanding, EPA determined that the additional 10X children's safety
factor could generally be reduced to 3X because the toxicological data
showed no evidence of greater sensitivity to the young and there was no
evidence of abnormalities in the development of the fetal nervous
system. (64 FR 52438, 52444, September 29, 1999). Because the endpoint
used for assessing acute dietary and short-term risk for the general
population, including infants and children, was based on a LOAEL a
second 3X safety factor was used for these risk assessments. (Id.).
3. Mepiquat. NRDC challenged a January 23, 2002 action establishing
tolerances for mepiquat on cotton gin byproducts and meat byproducts of
cattle, goats, hogs, horses and sheep. (67 FR 3113, January, 23, 2002).
Given mepiquat's exposure pattern and toxicological characteristics,
EPA determined that mepiquat potentially presented acute and chronic
risks and EPA quantitatively assessed these risks in making its safety
determination. (67 FR at 3116). All of these risks were found to be
below the Agency's level of concern. (Id.). Although a DNT study was
outstanding, EPA determined that the additional 10X children's safety
factor was not needed to protect infants and children because the
toxicological data showed no evidence of greater sensitivity to the
young and the evidence signaling a need for a DNT study did not show
``some special concern for the developing fetuses or young'' such as
``neuropathy in adult animals; [central nervous system] malformations
following prenatal exposure; brain weight or sexual maturation changes
in offspring; and/or functional changes in offspring.`` (65 FR 1790,
1794, January 12, 2000)).
[[Page 46712]]
4. Bifenazate. NRDC challenged a February 1, 2002 action
establishing tolerances for bifenazate on wet apple pomace, undelinted
cotton seed, cotton gin byproducts, the pome fruit crop group, grapes,
raisins, dried hops, nectarines, peaches, plums, strawberries and the
fat of cattle, goats, hogs, horses, and sheep. (67 FR 4913, February 1,
2002). Given bifenazate's exposure pattern and toxicological
characteristics, EPA determined that bifenazate potentially presented a
chronic risk and EPA quantitatively assessed this risk in making its
safety determination. (67 FR at 4919). As assessed, chronic risk was
below the Agency's level of concern. (Id.). Because there was no
outstanding toxicity data, the existing toxicity data showed no
evidence of increased sensitivity of the young, and exposure data were
deemed unlikely to understate exposure, EPA determined that it was safe
for infants and children to remove the children's safety factor. (67 FR
at 4918-4919).
5. Zeta-cypermethrin. NRDC challenged a February 12, 2002 action
establishing tolerances for zeta-cypermethrin on the podded legume
vegetable crop group; the succulent, shelled peas and beans crop group;
dried shelled peas and beans crop group; soybeans; the fruiting
vegetables crop group; grain sorghum; sorghum stover; sorghum forage;
wheat grain; wheat forage; wheat hay; wheat straw; aspirated grain
fractions; and meat of cattle, goats, hogs, horses and sheep. (67 FR
6422, February 12, 2002). Given zeta-cypermethrin's exposure pattern
(including the exposure pattern of a toxicologically similar pesticide,
cypermethrin) and toxicological characteristics, EPA determined that
zeta-cypermethrin potentially presented acute, chronic, short-term,
intermediate-term, and cancer risks and EPA quantitatively assessed
these risks in making its safety determination. (67 FR at 6426-6429).
All of these risks were found to be below the Agency's level of
concern. (Id.). Although a DNT study was outstanding, EPA determined
that the additional 10X children's safety factor was not needed to
protect infants and children because the toxicological data showed no
evidence of greater sensitivity to the young and the evidence signaling
a need for a DNT study did not show ``some special concern for the
developing fetuses or young'' such as ``neuropathy in adult animals;
[central nervous system] malformations following prenatal exposure;
brain weight or sexual maturation changes in offspring; and/or
functional changes in offspring.'' (Id. at 6426).
6. Diflubenzuron. NRDC challenged a February 15, 2002 action
establishing a tolerance for diflubenzuron on pears. (67 FR 7085,
February 15, 2002). Given diflubenzuron's exposure pattern and
toxicological characteristics, EPA determined that diflubenzuron
potentially presented a chronic risk and EPA quantitatively assessed
this risk in making its safety determination. (Id. at 7089-7090). As
assessed, chronic risk was below the Agency's level of concern. (Id.).
EPA determined that the additional 10X children's safety factor was not
needed to protect infants and children because the toxicological data
showed no evidence of greater sensitivity to the young, there was no
missing toxicological data, and the exposure assessments were unlikely
to understate exposure. (Id. at 7089).
7. 2,4-D. NRDC challenged a March 8, 2002, action establishing a
time-limited tolerance for 2,4-D on soybeans. (67 FR 10622, March 8,
2002). Given 2,4-D's exposure pattern and toxicological
characteristics, EPA determined that 2,4-D potentially presented acute,
chronic, and short-term risks and EPA quantitatively assessed these
risks in making its safety determination. (Id. at 10628-10629). All of
these risks were found to be below the Agency's level of concern.
(Id.). Although a DNT study was outstanding, EPA determined that the
additional 10X children's safety factor could be reduced because the
toxicological data showed no evidence of greater sensitivity to the
young and all other required toxicological data was complete. (Id. at
10627-10628). A factor of 3X was retained because the DNT study was
triggered based on a finding of neuropathology (retinal degeneration)
and was applied to all population subgroups for all durations of
exposure.
8. Isoxadifen-ethyl. NRDC challenged a March 20, 2002, action
establishing tolerances for isoxadifen-ethyl on corn commodities. (67
FR 12875, March 20, 2002). Given isoxadifen-ethyl's exposure pattern
and toxicological characteristics, EPA determined that isoxadifen-ethyl
potentially presented acute and chronic risks and EPA quantitatively
assessed these risks in making its safety determination. (Id. at 12876-
12877; 66 FR 33179, 33184-33185, June 21, 2001). All of these risks
were found to be below the Agency's level of concern. (Id.). Although
the data showed evidence of increased pre-natal sensitivity, EPA
determined that the additional 10X children's safety factor could be
reduced to 3X because the toxicological data were complete (i.e., there
were no outstanding studies such as a DNT study). (Id. at 33184). This
additional factor was applied to the acute dietary risk assessment for
females aged 13-50 because the increased sensitivity resulted from in
utero exposure. (Id.).
9. Acetamiprid. NRDC challenged a March 27, 2002, action
establishing tolerances for acetamiprid on dried citrus pulp, the
citrus fruit crop group, cotton gin byproducts, cotton undelinted seed,
grapes, the fruiting vegetable crop group, the leafy brassica vegetable
crop group, the leafy vegetable crop group, the pome fruit group,
tomato paste, as well as various animal products. (67 FR 14649, March
27, 2002). Given acetamiprid 's exposure pattern and toxicological
characteristics, EPA determined that acetamiprid potentially presented
acute, chronic, short-term, and intermediate-term risks and EPA
quantitatively assessed these risks in making its safety determination.
(Id. at 14656-14657). All of these risks were found to be below the
Agency's level of concern. (Id.). Although the data showed qualitative
evidence of increased pre-natal sensitivity and a DNT study was
outstanding, EPA determined that the additional 10X children's safety
factor could be reduced to 3X because two of the three toxicological
studies bearing on effects on the young showed no increased sensitivity
in the young, the evidence of increased sensitivity was only
qualitative and not quantitative, and the DNT study was not requested
based on evidence indicating a special concern for developing fetuses
or the young. (Id. at 14656). This additional factor was applied for
all population subgroups for all exposures other than acute dietary
exposure because the increased sensitivity resulted from chronic
exposure. (Id.).
10. Propiconazole. NRDC challenged a March 28, 2002, action re-
establishing a time-limited tolerance for propiconazole on blueberries
in connection with an emergency exemption under FIFRA. (67 FR 14866,
March 28, 2002). Given propiconazole's exposure pattern and
toxicological characteristics, EPA determined that propiconazole
potentially presented acute, chronic, short-term, intermediate-term,
and cancer risks and EPA quantitatively assessed these risks in making
its safety determination. (64 FR 2995, 2999-3001, January 20, 1999).
All of these risks were found to be below the Agency's level of
concern. (Id.). Based on the completeness of the toxicity database and
the lack of any evidence showing increased pre- or post-natal
sensitivity, EPA determined that removing the additional 10X children's
safety factor
[[Page 46713]]
would be protective of infants and children. (Id. at 3000).
11. Furilazole. NRDC challenged an April 3, 2002, action
establishing tolerances for furilazole on corn commodities. (67 FR
15727, April 3, 2002). Given furilazole's exposure pattern and
toxicological characteristics, EPA determined that furilazole
potentially presented acute, chronic, and cancer risks and EPA
quantitatively assessed these risks in making its safety determination.
(Id. at 15732-15733). All of these risks were found to be below the
Agency's level of concern. (Id.). Although EPA was lacking a chronic
toxicity study in dogs for furilazole, EPA determined that the
additional 10X children's safety factor could be removed and that a 3X
additional factor would be protective of infants and children because
otherwise the database was complete, there was no evidence of pre- or
post-natal sensitivity, and the subchronic toxicity studies in rats and
dogs show that the toxicity of furilazole is similar, both
qualitatively and quantitatively, in both species. The 3X factor was
applied to the chronic risk assessment because the missing study was a
chronic study. (Id. at 15730).
12. Fenhexamid. NRDC challenged an April 18, 2002, action
establishing tolerances for fenhexamid on the caneberry crop subgroup,
the bushberry crop subgroup, juneberry, lingonberry, salal, and
pistachio. (67 FR 19114, April 18, 2002). Given fenhexamid's exposure
pattern and toxicological characteristics, EPA determined that
fenhexamid potentially presented a chronic risk and EPA quantitatively
assessed this risk in making its safety determination. (Id. at 19118).
As assessed, chronic risk was found to be below the Agency's level of
concern. (Id.). Although the data showed qualitative evidence of
increased pre-natal sensitivity, EPA determined that the additional 10X
children's safety factor could be reduced to 3X because the
toxicological data were complete, two of the three toxicological
studies bearing on effects on the young showed no increased sensitivity
in the young, and the evidence of increased sensitivity was only
qualitative and not quantitative. (Id. at 19117).
13. Fluazinam. NRDC challenged an April 18, 2002, action
establishing a tolerance for fluazinam on the wine grapes. (67 FR
19120, April 18, 2002). Given fluazinam's exposure pattern and
toxicological characteristics, EPA determined that fluazinam
potentially presented acute and chronic risks and EPA quantitatively
assessed these risks in making its safety determination. (Id. at 19127-
19128). All of these risks were found to be below the Agency's level of
concern. (Id.). Because the data showed qualitative evidence of
increased pre-natal sensitivity and a DNT study had been required (but
not yet submitted) based on evidence of neurotoxic lesions, EPA
retained the additional 10X safety factor for acute dietary exposure to
the population subgroup females aged 13-50. For other populations and
exposures the additional 10X factor was reduced to 3X because the
increased sensitivity had only been seen with in utero exposure. (Id.
at 19126-19127).
V. NRDC Objections
A. In General
As mentioned above, NRDC submitted four separate sets of objections
on various pesticide tolerances during the first half of 2002. The
objections were received on February 25, 2002; March 19, 2002; May 7,
2002; and May 20, 2002. (Refs. 6, 7, 8, and 9). NRDC was joined in the
objections concerning 2,4-D by the following public interest and/or
advocacy organizations: Boston Women's Health Book Collective, Breast
Cancer Action, Californians for Pesticide Reform, Commonweal, Lymphoma
Foundation of America, Northwest Coalition for Alternatives to
Pesticides, Pesticide Action Network North America, Pineros y
Campesinos Unidos del Noroeste, SF-Bay Area Chapter of Physicians for
Social Responsibility, and Women's Cancer Resource Center.
B. Generic Issues
NRDC raises a myriad of claims in its objections. Most of the
claims fall fairly neatly into three categories: (1) Children's safety
factor issues; (2) aggregate exposure issues; and (3) issues regarding
use of findings from hazard studies in calculating safe exposure levels
- the``no observed effect level'' (NOEL) versus ``no observed adverse
effect level'' (NOAEL) and the ``lowest observed adverse effect level''
(LOAEL) questions.
1. Children's safety factor issues. For each of the pesticides
included in the objections, NRDC asserts that EPA used an additional
safety factor for the protection of infants and children that is
different from the default 10x value. NRDC claims that EPA erred in
doing so due to the ``significant toxicity and exposure data gaps''
corresponding to the tolerances established. (See, e.g., Ref. 7 at 3).
Three types of data gaps are cited by NRDC. First, NRDC notes that as
to certain of the pesticides EPA has required a developmental
neurotoxicity study but such study has not yet been submitted. Pointing
to various EPA documents recommending that this study be widely
required and EPA's specific finding that this study is required as to
the pesticides in question, NRDC argues that use of a factor different
than the default 10X is precluded. Second, NRDC claims EPA lacks
``pesticide-specific data on water-based exposure'' to the pesticides.
(Id. at 6). NRDC argues that exposure estimates EPA calculated through
the use of models cannot qualify as the ``reliable data'' needed to
vary from the default 10X value. (Id.). Third, NRDC claims that ``EPA
failed to consider important exposure routes for millions of infants
and children, including exposure to children living on farms and who
accompany their parents into farm fields [], and exposure from spray
drift.'' (Ref. 9 at 5).
2. Aggregate exposure issues. NRDC raises several issues relating
to whether EPA properly estimated ``aggregate exposure'' for the
pesticides in question. First, NRDC argues that farm children are a
``major identifiable subgroup'' and that EPA has failed to consider
information concerning the sensitivities and exposures of farm children
as a major identifiable subgroup'' in conducting its aggregate exposure
assessment. According to NRDC, farm children have unique exposures to
pesticides ``from their parents' clothing, dust tracked into their
homes, contaminated soil in areas where they play, food eaten directly
from the fields, drift from aerial spraying, contaminated well water,
and breast milk.'' (Ref. 7 at 12). Further, NRDC asserts farm
children's exposure is increased because they ``often accompany their
parents to work in the fields . . . .'' (Id.). NRDC cites various
studies collected in its ``Farm Children Petition'' as well as more
recent studies in support of these claims. (Ref. 7 at 12-13). Second,
NRDC argues that EPA's aggregate exposure assessment is flawed for
these pesticides because EPA did not consider the added exposure to
pesticides that farmworkers receive as a result of their occupation.
(Id. at 14). NRDC states that EPA's interpretation of the statute as
excluding occupational exposure is incorrect. (Id.). Third, NRDC claims
that EPA has underestimated aggregate exposure for several of the
pesticides because EPA used ``anticipated residues'' for estimating
exposure rather than assuming residues would be at the tolerance level.
NRDC argues that ``EPA must ensure that the legal level of pesticide
chemical residue - the established tolerance levels - are themselves
safe.'' (Ref. 9 at 20). Additionally, NRDC asserts that using
[[Page 46714]]
``anticipated residues'' does not take into account the ``significant
number of consumers who purchase produce at farmers markets, farm
stands, and `pick-your-own' farming operations.'' (Id. at 19). These
``potentially millions of consumers,'' NRDC contends, are exposed ``to
residues of these pesticides at the tolerance level.'' (Id. at 20).
Fourth, NRDC argues that for several of the pesticides EPA has, in
effect, underestimated aggregate exposure by using the 95th population
percentile of exposure instead of the 99.9th percentile in determining
whether exposure to the pesticide meets the safety standard. (Ref. 7 at
19). NRDC claims that this is inconsistent with existing Agency policy.
(Id.).
3. Reliance on LOAELs and NOAELs. NRDC asserts that, in the absence
of identifying a NOEL in relevant animal studies, EPA cannot make a
safety finding under section 408(b)(2). In support of this argument,
NRDC cites to legislative history using the term NOEL. NRDC calls
particular attention to the instances where EPA determined safety
relying on a LOAEL: Use of acute neurotoxicity LOAEL to evaluate oral
exposure for pymetrozine; (Ref. 6 at 9), use of reproductive toxicity
LOAEL for mepiquat; (Id.), use of developmental toxicity LOAEL for
zeta-cypermethrin; (Ref. 7 at 19), use of LOAEL for dermal toxicity for
fluazinam; (Ref. 9 at 18), and reliance on rat and mouse dietary
studies for fluazinam that identified only a LOAEL. (Id.). NRDC,
however, also objects to several pesticide tolerances for use of a
NOAEL in making the safety determination. (Ref. 9 at 17-18).
C. Pesticide-specific Issues
NRDC's pesticide-specific objections to some extent build upon the
more general objections described immediately above. As to each of the
pesticides, NRDC identifies allegedly missing toxicity or exposure data
and argues that these missing data necessitate retention of the default
10X children's safety factor. Additionally, for several of the
pesticides, NRDC raises specific issues regarding the aggregate
exposure estimate. One aggregate exposure issue raised repeatedly is
EPA's reliance on allegedly arbitrary processing factors for estimating
residues in processed food. These objections are addressed in detail in
Unit VIID.7.b. and f. below, respectively.
Finally, NRDC objects to the 2,4-D tolerance on soybeans arguing
that EPA relied upon a human exposure study ``in an arbitrary departure
from the Agency's stated policy on considering human tests and a
violation of international and federal law.'' (Ref. 8 at 22). Also with
regard to 2,4-D, NRDC discusses various toxicological studies that
according to NRDC show that 2,4-D is a carcinogen, an endocrine
disruptor, and a neurotoxicant. (Id. at 4-7). NRDC did not link these
toxicological claims to its specific objections.
VI. Public Comment
A. In General
On June 19, 2002, EPA published a notice in the Federal Register
calling attention to and requesting comments on the NRDC Objections.
(67 FR 41628, June 19, 2002). As part of that notice, EPA published the
full text of one set of objections in the Federal Register. A period of
60 days was initially allowed for comment but that period was extended
twice and was closed on October 16, 2002. (See 67 FR 58536, September
17, 2003; 67 FR 53505, August 16, 2002). In addition to a large number
of form letters (principally supporting the objections) and the NRDC's
comments mentioned above, EPA received roughly 20 sets of substantive
comments. These comments were for the most part from pesticide
manufacturers and each requested denial of the objections. The most
significant of these comments are summarized below. EPA has not
repeated comments in instances where they were made by more than one
commenter.
B. Individual Comments
1. The FQPA Implementation Working Group. Extensive comments were
filed by the FQPA Implementation Working Group (IWG), an organization
comprised of associations representing pesticide manufacturers,
growers, and food processors. (Ref. 10) [hereinafter cited as ``IWG
comments'']. The IWG comments provided two alternative approaches as to
why the NRDC's objections should be denied. First, the IWG asserted
that EPA has misinterpreted the concept of ``aggregate exposure'' ever
since passage of the FQPA, and once this interpretation is corrected,
it becomes clear that the objections, for the most part, are flawed.
These comments by IWG were thoroughly described and responded to in the
Imidacloprid Order. (69 FR at 30072-30073, May 26, 2004).
Second, in the alternative, the IWG, assuming the EPA's aggregate
exposure interpretation is retained, explained that the NRDC objections
are factually flawed. IWG's comments concerning pesticide exposure to
farm children and exposure to pesticides in drinking water were
discussed in the Imidacloprid Order. (69 FR at 30049, 30069). One issue
not addressed was IWG's comments on pesticide exposure from food
purchased at farm stands. The IWG challenges the NRDC's assertion that
levels of pesticide residues in foods purchased at farm stands are
higher than residue levels in food purchased at other retail outlets.
The IWG notes that ``NRDC does not provide information to support its
allegations, and we are not aware of any credible data to suggest that
this is the case.'' (Ref. 10 at 16). The IWG cites two demonstrable
reasons undermining NRDC's claim: first, label directions and
restrictions on pesticide use apply equally to food grown for sale at
farmstands and food grown for distribution through broader channels of
trade; and second, ``[t]he various circumstances (weather, pest
pressure, etc.) that affect residue levels resulting from a given
treatment regimen are the same for those who grow crops to market
through wholesale channels and for those who grow crops to sell at
retail.'' (Id.). Finally, the IWG notes that assuming residue levels
are at the tolerance value would vastly overstate exposure amounts
given that FDA data has shown ``no pesticide residues in 41 percent and
73.5 percent of fruit and vegetable samples and either no residues or
below tolerance residues in 99.5 percent and 98.9 percent of fruit and
vegetable samples.'' (Id. at 17).
2. Inter-Regional Research Project Number 4 (IR-4). The IR-4 is a
program sponsored by the US Department of Agriculture and land grant
universities and directed toward obtaining regulatory approval for
pesticide uses on minor and speciality food crops that are not likely
to be supported by private sector companies. In its comments, the IR-4
notes that several of the pesticides covered in the objections -
diflubenzuron, halosulfuron-methyl, and fenhexamid - are both
``critical to minor crop growers'' and safer, reduced risk pesticides.
(Ref. 11). The IR-4 asserts that diflubenzuron provides an alternative
to the organophosphate pesticides and that halosulfuron-methyl is a
methyl bromide alternative. (Id.).
3. ISK Biosciences - Fluazinam. ISK Biosciences is the owner of the
data used to support the fluazinam tolerance on wine grapes. (Ref. 12).
ISK Biosciences notes that this is an import tolerance for wine grapes
meaning that as to this use there will be no exposure in the United
States other than through the consumption of wine. (Id. at 4). ISK
Biosciences also points out that children do not usually consume wine.
(Id.). ISK Biosciences notes several factors that contributed to the
conservativeness of EPA's risk assessment, including (1) use
[[Page 46715]]
of tolerance level residues; (2) assumption of 100 percent crop treated
even though fluazinam can be at most used on wine imported to the
United States (22 percent of the wine); and (3) use of a default
processing factor for wine of 1.0 even though wine processing studies
show significant reductions in residue levels. (Id. at 5-7). As regards
reliance on a LOAEL, ISK Biosciences states that EPA did indicate the
21-day dermal toxicity study did not identify a NOAEL for dermal
irritation but that EPA did find a systemic NOAEL from that study which
was used for aggregate risk assessment. According to ISK Biosciences,
NOAELs were used for dietary risk. (Id. at 7).
4. Bayer CropScience - Isoxadifen-ethyl. Bayer CropScience claims
that EPA assigned a 3X children's safety factor to isoxadifen-ethyl due
to concerns regarding a rat teratology study and EPA requested
historical control information pertaining to the study. (Ref. 13).
Bayer states that that information has been submitted and should
alleviate any concerns EPA has with regard to the study regarding
potential increased sensitivity of the young. With respect to the
conservativeness of EPA drinking water exposure estimates Bayer
CropScience cites a study which it asserts demonstrates that EPA models
typically overstate exposures by 100- to 10,000-fold. (Id. at 2 (citing
Ref. 14)). Finally, as to EPA's use of default processing factors,
Bayer CropScience argues they are not arbitrary because they assume a
worst case concentration of residues in the processed food based on the
ratio of the weights of the raw and processed foods. (Ref. 13 at 6).
5. Aventis CropScience - Acetamiprid. Aventis CropScience asserts
``there was no specific concern on the part of [EPA with regard to
acetamiprid] that would give concern for the developing fetuses or
young. The developmental neurotoxicity study was required by EPA to
expand knowledge, not for reasons of specific concerns.'' (Ref. 15).
Further, Aventis CropScience claims that ``[t]here is no reason to
expect that a lower NOEL than previously determined will be found for
acetamiprid in a developmental neurotoxicity study.'' (Id.).
6. FMC Corporation - Zeta-cypermethrin. FMC Corporation argues that
no DNT study has been required for zeta-cypermethrin because no data
call-in has been issued. (Ref. 16). If a DNT study has not been
required, FMC Corporation reasons, then the absence of a DNT study
cannot make the database incomplete. Further, FMC asserts that even if
such a study was requested any decision on the children's safety factor
would have to be based on whether the data ``give rise to concerns for
potential developmental effects.'' (Id.). Challenging claims by NRDC,
FMC contends that the DCVA degradates of zeta-cypermethrin were
considered by EPA, (Id. at 3-4), and the residential exposure due to
cypermethrin was taken into account in the aggregate risk assessment
for zeta-cypermethrin. (Id. at 6). As to the DCVA metabolites, FMC
asserts that EPA considered them and decided not to include them in an
aggregate assessment due to their lack of toxicological significance.
(Id. at 3).
7. Crompton Corporation - Diflubenzuron and Bifenazate--a.
Diflubenzuron. Crompton Corporation argues that NRDC's criticisms of
the adequacy of the residential exposure assessment for diflubenzuron
are misplaced given that an exposure assessment for agricultural
workers showed minimal exposure under conditions much more likely to
result in exposure than the sole registered residential use for
diflubenzuron on trees and shrubs limited to professional application
only. (Ref. 17).
b. Bifenazate. Crompton Corporation asserts that NRDC has
misconstrued a statement in Federal Register notice establishing the
bifenazate tolerances in question. (Id. at 4). In a table summarizing
toxicological studies, EPA at one point states that ``a clear
assessment of developmental toxicity was not possible.'' (67 FR at
4915,). Crompton Corporation contends that this statement only applied
to a range-finding study and that once the main study was completed
developmental toxicity could be clearly assessed. Crompton Corporation
acknowledges that the database does not include, as NRDC has noted,
several inhalation studies; however, Crompton argues this does not
render the database incomplete because ``significant toxicity by this
exposure route would not be expected'' given data from short-term
inhalation studies and information pertaining to the particle size of
bifenazate formulations. (Ref. 17 at 4). In response to NRDC's claim
that arbitrary processing factors were used for estimating bifenazate
residues on processed apples and grapes, Crompton points out that, at
least in part, actual processing data from bifenazate-treated grapes
and apples were used to derive processing factors. (Id. at 7-8).
8. Syngenta Crop Protection - Propiconazole and Pymetrozine--a.
Propiconazole. Syngenta Crop Protection responds to NRDC's claim that
drinking water models cannot be relied upon to provide reliable data on
exposure by citing to a study done to evaluate the residue levels of
propiconazole in drinking water reservoirs. (Ref. 18). According to
Syngenta,``[i]n 312 samples of raw water, propiconazole was detected in
only one, and that at the limit of detection. Propiconazole was not
detected in ANY finished water samples analyzed. (Id.). As to exposure
to farm children, Syngenta notes that:
[m]any of the exposure scenarios depicted in the NRDC objections
are the result of poor hygiene (contaminated work clothing being
worn inside the home instead of being washed after use, . . .)
substandard living conditions due to poverty, and lack of
information on safe pesticide handling. These kinds of issues cannot
be managed within the constraints of a risk assessment based on
labeled use of a pesticide, but rather must be addressed through
appropriate stewardship, education, and outreach. Recognizing this
as an issue, particularly in the growing Latino community of North
Carolina, Syngenta has sponsored and actively participated in
projects with the Department of Family and Community Medicine at
Wake Forest University to develop safety videos in Spanish for
pesticide handlers. These modules include a discussion of proper
hygiene for pesticide handlers/field workers once inside the home.
(Id. at 3-4).
b. Pymetrozine. Syngenta defends the use of a LOAEL reduced by a
factor of 3X for assessing the acute dietary risk of pymetrozine by
noting that the effects observed at the LOAEL ``were reversible and not
of severe magnitude (for example, body temperature was decreased at the
LOEL, but only by about 2 percent compared to controls).'' (Id. at 5).
Syngenta cites to reports indicating that a very high percentage of
toxicity studies have a ratio between LOAELs and NOAELs of 5X to 6X or
less. (Id.). Syngenta notes that ``Dourson et al. (1996) conclude that
when faced with a LOEL and not a NOEL, the choice of uncertainty factor
should generally depend on the severity of the effect at the LOEL.''
(Ref. 18 at 5).
9. BASF Corporation - Mepiquat. BASF Corporation disputes NRDC's
claim that a NOEL was not identified by EPA for the mepiquat
reproductive toxicity study in rats. Citing to EPA's Reregistration
Eligibility Document for mepiquat chloride, BASF Corporation concludes
that ``this study established a NOEL for all parameters investigated,
both for parents and pups.'' (Ref. 19).
10. Industry Task Force II on 2,4-D Research Data. A good portion
of the 2,4-D Industry Task Force II's comments pertain to NRDC
statements regarding the toxicity of 2,4-D. (Ref. 20). Because NRDC did
not directly relate these statements to its objections, neither its
allegations nor the Industry Task Force's
[[Page 46716]]
rebuttal is repeated in any detail here. In sum, the Industry Task
Force disagreed with NRDC's conclusions asserting that NRDC had focused
on a few studies of questionable reliability without considering the
extensive database on 2,4-D. The Task Force noted that ``[i]t is
difficult to understand the toxicological arguments put forth by NRDC
as many are simply threads of ideas that have been only loosely woven
into a fabric.'' (Id. at 2). To the extent necessary, toxicological
issues concerning 2,4-D are discussed below in EPA's response to the
objections.
On the children's safety factor for 2,4-D, the Industry Task Force
defends EPA's selection of a 3X factor based on the assertion that it
would be ```double counting''' to ``require both a database uncertainty
factor for the lack of a DNT study and an FQPA safety factor for
neurological sensitivity.'' (Id. at 15). The Industry Task Force also
notes that the neurological sensitivity was only found at a high dose.
(Id. at 14). As to regulation of farm children as a major identifiable
subgroup, the Industry Task Force protests that ``NRDC did not define
farm children as a subgroup by their type of living situation, food
consumption, and other population characteristics that would
discriminate them from children generally.'' (Id. at 16). The Industry
Task Force also challenges NRDC's claims regarding high exposures for
farm children noting that in three recent biomonitoring studies of farm
applicators, spouses, and their children ``only a small fraction of the
spouses and children have levels of 2,4-D detectable at 1 part per
billion.'' (Id.). Studies cited by NRDC in support of its claims
regarding high exposure to farm children, the Industry Task Force
asserts, ``fail to concurrently demonstrate a measurable internal dose
of 2,4-D to the home residents.'' (Id. at 20). Finally, as to the human
testing data relied upon by EPA in evaluating the safety of 2,4-D, the
Industry Task Force points out that they were biomonitoring studies
conducted by a provincial Canadian government agency and not ``third-
party clinical trials [conducted by the pesticide industry] to
determine effects in humans.'' (Id. at 25).
VII. Response to Objections
As summarized above, NRDC's Objections can be grouped into a few
main categories and EPA has organized its response to the objections
around these categories instead of by pesticide. Further, even among
these categories, one consistent theme emphasized by NRDC is the
potential heightened exposure of ``farm children'' to pesticides. For
that reason, EPA begins its substantive response in Unit VII.B. below
with an analysis of the data bearing on children's exposure to
pesticides in agricultural areas. Then EPA turns to NRDC's specific
objections. Unit VII. C. below addresses the objections raising issues
regarding the children's safety factor. Unit VII.D. below covers
aggregate exposure questions. Unit VII.E. below responds to claims
regarding use of LOAELs and NOAELs. Finally, Unit VII.F. below
addresses the human study issue.
Prior to addressing these substantive issues, EPA responds in Unit
VII.A. below to the objections as to several tolerances which have now
expired.
A. Expired Tolerances
The following time-limited tolerances that were objected to by NRDC
have now expired and are, therefore, no longer in effect: halosulfuron-
methyl on asparagus, (66 FR 66778, December 27, 2001) (expired on
December 31, 2003); 2,4-D on soybeans, (67 FR 10622, March 8, 2002)
(expired on December 31, 2004); and propiconazole on blueberries, (67
FR 14866, March 28, 2002) (expired December 31, 2003). Because these
tolerance actions are without legal force, NRDC's objections are denied
as moot. Other halosulfuron tolerances objected to by NRDC have not
expired and are included in the response below. Additionally, because
EPA has already, or may in the future, undertake tolerance actions as
to propiconazole and 2,4-D, EPA's analysis to the specific issues
raised by propiconazole and 2,4-D are included in this notice.
B. Children's Exposure to Pesticides in Agricultural Areas
Children can be exposed to pesticides through multiple sources and
pathways. The Agency currently considers children's exposure to
pesticides by three broad pathways: food, drinking water, and
residential use. NRDC, however, has asserted that children residing in
agricultural communities also are significantly exposed to agricultural
pesticides through additional exposure pathways.
Children in agricultural areas may be exposed to agricultural
pesticides through pathways such as contact with treated fields,
roadsides and other areas; contact with residues on clothing of parents
who work in agriculture; contact with moving spray drift while near
application areas; contact with spray drift residues left by any spray
drift that may reach their homes, yards or other areas they frequent,
such as schools and schoolyards; and contact with pesticide residues
that have volatilized after application. In addition, some of these
children may also be exposed to agricultural pesticides in their homes
via other pathways.
In analyzing the potential exposure of children in agricultural
areas, EPA first focused on data from studies relied upon by NRDC or
otherwise known to EPA that attempted: To measure levels of pesticides
in the homes of children in agricultural areas; to measure levels of
pesticide metabolites in body fluids of children in agricultural areas;
and/or to compare levels of pesticide exposure of farm children to
those experienced by non-farm children, based on similar types of
measurements. In addition, EPA examined data NRDC submitted relating to
airborne levels of pesticides (stemming from spray drift or post-
application volatilization drift) in farm communities. Finally, EPA
reviewed data it has concerning the potential for pesticides to drift
offsite during application.
1. Studies focusing on exposure to children in agricultural areas.
In response to objections filed by NRDC with regard to the imidacloprid
tolerance on blueberries, EPA discussed various studies focusing on
exposure to children in agricultural areas (other than the data cited
by NRDC regarding airborne residues). In brief, EPA found that the data
concerning levels of pesticides in homes or children's bodily fluids
are limited and inconclusive, and do not demonstrate that children in
agricultural areas as a group receive more pesticide exposure than
children in non-agricultural areas. (In fact, some data suggest that
pesticide residues in houses in urban or non-agricultural areas may be
higher than those in houses in agricultural areas.) EPA incorporates
that discussion into this response. (69 FR at 30050-30054, May 26,
2004).
Since issuing its response to the imidacloprid objections, EPA has
received several additional studies bearing on exposure of farm
children. First, EPA has received a study it funded investigating,
among other things, aggregate exposure of children to persistent
pollutants, including pesticides. (Ref. 21 ). Pesticides in the study
included chlorpyrifos, diazinon, permethrin, and 2,4-D. The Pilot Study
of Children's Total Exposure to Persistent Pesticides and Other
Persistent Organic Pollutants (CTEPP) was designed to investigate the
relative contribution of various routes of exposure (dietary, indirect
oral exposure, and inhalation) and to determine if there are
differences in exposure due to such factors as income
[[Page 46717]]
level, child care location, and regional location. CTEPP was conducted
in two states, Ohio and North Carolina, and involved 257 children in
both urban and rural (farmland) areas of these states. What the results
of CTEPP show are that (1) the dietary route is the dominant route of
exposure for the pesticides and other pollutants in the study (ranging
from 55 to 95 percent for the six pesticides studied); (Id. at 9-75),
and (2) although there were some differences in exposure for some
pesticides for some routes of exposure, where differences were present
it was the urban children that received higher exposures than rural
children (e.g. exposure of urban children in North Carolina to 2,4-D
through indirect ingestion exceeded exposure of rural children to 2,4-D
by the same route by a factor of 3), (Id. at 9-66, 9-67).
A second source of information bearing on farm children exposure is
a partial report from the Agricultural Health Study (AHS), which is a
prospective epidemiologic study of pesticide applicators and their
spouses in Iowa and North Carolina. (Ref. 22). Exposure to 2,4-D was
measured in conjunction with agricultural applications for a subset of
applicators in the AHS Pesticide Exposure Study. Urinary Biomarker
levels were measured in pre-and post-application samples collected from
applicators and their spouses and children using 2,4-D in broadcast and
hand spray applications. The results indicated applicator exposure
increased approximately 3-fold between the pre- and post-application
periods. For spouses and children exposure increased but in smaller
increments, approximately 50 percent and 25 percent, respectively. The
values, however, are questionable due to the fact that one of the
spouses admitted using a 2,4-D product, there were a low number (9) of
children participating, and it is not clear whether any of the children
assisted in farm work.
The final study, the Farm Family Exposure Study (FEES), which was
funded by a group of pesticide manufacturers, was designed to quantify
real world pesticide exposures in farmers and family members around the
time of a single pesticide application. (Ref.23). Pesticides involved
in the study included 2,4-D, chlorpyrifos, and glyphosate. The farm
families were randomly selected from a public list of licensed private
pesticide applicators from Minnesota and South Carolina. Exposures were
measured in applicators, spouses and children by collection of 24 hour
urine samples on the day of and for three days following a pesticide
application. Urine samples were also collected prior to application.
With regard to children, the study concluded that exposure levels of
chlorpyrifos and glyphosate increased marginally on post-application
days and that these marginal increases were caused by children who
directly assisted in pesticide application or who were around the
application process. Greater increases were seen between pre-
application and post-application exposure levels of children in
connection with use of 2,4-D. The study found that the highest levels
of exposure were seen in children who assisted with application
although increases were seen in some children not directly involved in
the application process. Specifically, the study concluded:
Exposure related to chemical application was also higher in
children when compared to spouses. Unlike the spouses, the children
were more often present during the application process and some
assisted their parent with the application. These opportunities for
direct exposure accounted for the higher concentrations of the
chemicals in the urine. While the children did exhibit an overall
positive change from baseline, the geometric mean differences in
urine concentration were very small (2 [mu]gL for 2,4-D). Not all
children who had measurable changes in urine concentration were
directly involved with the application process, yet identifying a
potential route of exposure will be difficult as the exposures are
subtle.
(Ref. 23 at 28). Comparisons of the exposure levels in this study with
other population-based exposure data showed mixed results. To evaluate
the significance of the exposures measured in the study, EPA compared
the exposure levels for children aged 4-15 to the dose level of
concern. Children in that range were chosen because fewer children of
this age would be expected to directly assist or otherwise participate
in agricultural activities. All exposure levels for this group were
found to be well below safe levels with margins of exposure ranging
from 4,000 to 2.6 million and averaging 42,000. (Ref. 24). Thus,
although there were increases in exposure for some children, these
increases were not meaningful in terms of risk.
The CTEPP study further confirms EPA's conclusions in the
Imidacloprid Order regarding differential exposures of urban and rural
(farm) children. The other two studies suggest that some farm children
may be exposed to pesticides as a result of living in proximity to
fields treated with pesticides; however, these exposures for farm
children are generally a result of occupational-type exposures from the
children participating in the application of pesticides or otherwise
assisting in or being present in the field during agricultural
operations. Occupational source exposure to pesticides is not
appropriately considered under FFDCA section 408. 21 U.S.C.
346a(b)(2)(D)(vi). Importantly, even as to the increases in 2,4-D
exposure in the FFES, the only pesticide as to which increased exposure
could not be definitively tied to occupational-type exposures, the data
did not indicate that children were receiving any exposures that were
even close to levels of concern. Moreover, these studies did not
indicate EPA's risk assessment process was under-protective. For
example, EPA's risk assessment for 2,4-D, both as presented in the
tolerance document and as described in Unit VII.B.2.a., predicts
significantly higher risks (i.e., lower margins of exposure) for
children from exposure to 2,4-D. Thus, EPA reaffirms its earlier
finding that data concerning levels of pesticides in homes or
children's bodily fluids are limited and inconclusive, and do not
demonstrate that children in agricultural areas as a group receive
significantly more non-occupational pesticide exposure than children in
non-agricultural areas.
2. Information bearing on exposure levels as a result of spray
drift and post-application drift of volatilized residues. Although the
epidemiology data mentioned above and discussed in the Imidacloprid
Order generally do not indicate that pesticide exposures to children in
agricultural areas differ significantly from such exposures to children
in urban or suburban areas, EPA has examined whether data on the drift
of pesticide during applications (spray drift) and the transport of
volatized pesticide residues following application (post-application
drift) suggest that these sources of exposure should be included in EPA
calculations of aggregate exposure.
a. Pesticide spray drift during application. EPA defines spray
drift as the movement of droplets off-target during or shortly after
application, which is independent of the chemical properties of the
pesticide being sprayed. EPA has gathered substantial data on the
potential of pesticides, as applied, to drift offsite through the work
of the Spray Drift Task Force (SDTF). The SDTF is a group of pesticide
registrants who have worked collaboratively to develop a database to
meet the majority of their collective spray drift data requirements
under 40 CFR 158.440. The group was chartered on April 17, 1990. (Ref.
25). Since its formation, the SDTF has generated standardized data on
spray drift levels resulting from different application
[[Page 46718]]
methods under varying meteorological conditions. The data developed by
the SDTF was reviewed by EPA internally, through external peer review
workshops, and through FIFRA Scientific Advisory Panel meetings. The
reviews generally identified the data set associated with aerial
applications to be the most robust, followed by the data sets from
ground boom applications, orchard/vineyard airblasting, and
chemigation, respectively. After the spray drift data were available,
the SDTF worked with EPA's Office of Research and Development, as well
as the USDA's Agricultural Research Service and Forest Service to use
the data in the development/evaluation of the AgDRIFT model. (See
generally Refs. 26, 27, and 28).
The AgDRIFT model has been incorporated to a limited extent in EPA
exposure assessments. It is used most prominently in environmental
assessments in estimating potential exposure of offsite animals and
plant life to pesticide residues. The AgDRIFT model has also been used
in the context of FFDCA risk assessment through use of model estimates
as an input to the various models used to estimate potential exposure
in drinking water. Importantly, EPA has regarded its drinking water
models as screening models and not as realistic predictors of actual
exposure. For that reason, until recently EPA has not directly summed
exposure estimates from its drinking water models with estimates of
exposure from food in calculating aggregate exposure. Rather, EPA has
used water model estimates more indirectly by comparing them to
Drinking Water Levels of Comparison which are estimates of the amount
of safe exposure that can occur taking exposure through residues in
food into account. This indirect approach to the use of water model
estimates of pesticide exposure keeps distinct the screening nature of
water model estimates.
In estimating pesticide exposure from various pathways EPA is
careful to avoid relying on maximum values from every input because
such an approach can grossly overestimate exposure. As EPA's exposure
guidelines note: ``When constructing this [exposure] estimate from a
series of factors [environmental concentrations, intake rates,
individual activities, etc.], not all factors should be set to values
that maximize exposure or dose, since this will almost always lead to
an estimate that is much too conservative.'' (Ref. 29). Given that
EPA's approach to estimating pesticide exposure from food, water, and
residential uses already tends to be very conservative (health-
protective), EPA has been cautious about simply adding in yet another
screening level value in calculating aggregate exposure. Certainly, the
epidemiology data discussed above and in the Imidacloprid Order does
not strongly suggest that EPA exposure estimates have been ignoring a
major pathway of exposure.
That does not mean that the AgDRIFT model does not have a role to
play in considering aggregate exposure to pesticides. It may prove
useful in designing buffer zones for pesticides that otherwise have
potentially high exposures. Alternatively, as data on exposure expands
and modeling improves, some aspect of AgDRIFT modeling may be
meaningfully incorporated into probabilistic modeling of exposure.
However, as the analysis below shows, exposure as a result of spray
drift is unlikely to be a significant contributor to any substantial
number of individuals.
To evaluate potential exposures from spray drift, EPA: (1) Compared
potential spray drift exposures to exposures from residential lawn
uses; and (2) computed MOE's for each of the 13 pesticides assuming
spray drift exposure is a component of residential exposure. Both
exercises confirm EPA's view that spray drift is unlikely to be a
significant contributor to risk.
1. Comparison of AgDrift model estimates of exposure with exposure
from residential lawn use generally. AgDRIFT version 2.01 is a computer
model that can be used to estimate downwind deposition of spray drift
from aerial, ground boom, and orchard and vineyard airblast
applications. The model contains ``Toolbox'' screens that can be used
to estimate deposition levels in terrestrial and aquatic environments
and estimate concentrations in water bodies. The model contains three
tiers of increasing complexity for aerial application. In Tier 1, the
user can estimate downwind deposition resulting from each of the
application methods under several predefined scenarios. In higher tiers
more options are available. AgDRIFT only allows Tier 1 level analyses
for ground boom and airblast application methods. The aerial portion of
the model is based on a mechanistic U.S. Forest Service model, (Ref.
30). The SDTF field trial data were used to validate the aerial portion
of AgDRIFT, (Refs. 31 and 32). The ground boom and orchard airblast
portions use data collected by the Spray Drift Task Force (SDTF) to
empirically calculate spray drift deposition. AgDRIFT was developed
under a cooperative research and development agreement between EPA,
USDA, and the SDTF.
The AgDRIFT model can provide a picture for each of the three
application techniques (aerial, groundboom, and airblast) of what
amount of an agriculturally-applied pesticide may drift onto areas
ranging from 10 feet to 210 feet from the treated field. In the
following Table 2, high-end spray drift deposition as modeled by
AgDrift is presented in terms of deposition rate offsite as a
percentage of the pesticide application rate. (Ref. 33).
Table 2.--High-end Downwind Spray Drift Deposition Levels by Application Method
----------------------------------------------------------------------------------------------------------------
Spray drift deposition (percent of application rate)
-------------------------------------------------------
airblast
Lawn placement relative to application area ------------------------
aerial ground dense or granular
boom dormant tall
orchards canopies
----------------------------------------------------------------------------------------------------------------
10 to 60 ft downwind 34.1 9.3 25.0 8.4 0
---------------------------------------------------------
20 to 80 ft downwind 31.6 6.4 16.1 6.0 0
---------------------------------------------------------
40 to 90 ft downwind 27.9 4.1 8.0 3.7 0
---------------------------------------------------------
80 to 130 ft downwind 22.0 2.4 3.0 1.9 0
---------------------------------------------------------
160 to 210 ft downwind 14.9 1.3 0.8 0.9 0
----------------------------------------------------------------------------------------------------------------
[[Page 46719]]
As Table 2 shows, the highest off-target deposition levels from
agricultural applications occur adjacent to the treated area and those
levels decrease with increasing distance from the treatment area.
Importantly, in EPA's experience, application rates for residential
uses are generally equal to or greater than the levels allowed for
agricultural applications. Thus, deposition on residential lawns from
spray drift is generally a small fraction of deposition from direct
residential treatment and, unless the residential lawn is relatively
close to the treated agricultural field, the ratio of spray drift
deposition to deposition from direct treatment is exceedingly low.
2. Evaluation of MOE's based on AgDrift Model for the pesticides in
the objections. Another way of evaluating the potential significance of
application drift exposure is by calculating potential high-end
application drift for each pesticide for areas adjacent to treated
fields and combining these values with other exposure values for the
pesticide. Due to the high-end nature of the estimates from the AgDrift
model and the limited number of persons that would be exposed at the
field boundary, EPA does not believe it is reasonable to simply add
these values to other high-end exposure values in determining pesticide
safety. Nonetheless, in the context of these objections, EPA has
performed this calculation to show how even making such low probability
exposure assumptions does not result in any safety concerns.
The exposure/risk scenario deemed most appropriate for evaluating
application drift exposures is the short-term exposure scenario. Short-
term exposures are those likely to occur over a 1- to 7-day window.
This is the exposure window most commonly used with assessing exposure
from residential turf use of a pesticide and the turf use is the
residential use that most closely approximates the exposure that may
result from application drift. To estimate potential exposure to
application drift, EPA first calculated the amount of deposition that
may drift to an area 10-60 feet downwind of the application site using
the combination of permitted application technique and rate that
yielded the highest deposition. Then EPA used the predicted deposition
amount as an input in its model for estimating post-application
exposure to toddlers on turf. EPA focused on toddlers because toddlers
have the greatest post-application turf exposure to pesticides of any
population subgroup due to their behavior patterns (i.e., crawling,
rolling on turf; hand-to-mouth activity; soil ingestion). As is done
with evaluating aggregate short-term post-application exposures to turf
uses, predicted post-application exposure from drift was then summed
with background exposures to the pesticide from residue-containing food
and water. If the pesticide has residential exposures, those predicted
exposures were summed as well. After combining all of these exposures,
the overall exposure value was divided into the safety endpoint used to
evaluate short-term exposure to quantify the Margin of Exposure (MOE).
To ensure that this assessment was conservative, EPA combined oral and
dermal exposure where appropriate. Where combining oral and dermal
exposures was not supported by the data, EPA calculated separate MOEs
for dermal and oral exposures and then combined the MOEs. (Ref. 33 at
3-5).
The following Table 3 presents estimated MOEs for the 13 pesticides
for background food and water exposure, residential exposure (where
applicable), application drift exposure, and combined exposure. Table 3
also lists the Level of Concern (LOC) for each pesticide. The LOC is
the minimum level that a MOE must obtain to ensure that the MOE
includes adequate safety factors, including the children's safety
factor. As can be seen, even when assessing risk using this unrealistic
exposure approach, the MOEs for these pesticides remain above their
respective LOC.
Table 3.--Combining Application Drift Short-term Exposures with Other Exposures of Toddlers
--------------------------------------------------------------------------------------------------------------------------------------------------------
Food and Water Residential MOE Appl. Drift MOE
Background MOE ---------------------------------------------------- Combined
Pesticide -------------------------- MOE LOC
food water oral dermal oral dermal
--------------------------------------------------------------------------------------------------------------------------------------------------------
halosulfuron-methyl 140,000 300,000 60,000 3,100 2,500,000 110,000 2,800 100
-------------------------------------------------
pymetrozine 220,000 63,000 2,200 na 15,000 na 1,800 1,000
-------------------------------------------------
mepiquat 29,000 550,000 na na 180,000 27,000 13,000 100
-------------------------------------------------
bifenazate 2,500 880,000 na na 3,700 1,100 650 100
-------------------------------------------------
zeta-cypermethrin 710 22,000 4,400 na 40,000 na 570 100
-------------------------------------------------
diflubenzuron 13,000 220,000 na na 1,600 15,000 1,300 100
-------------------------------------------------
2,4-D 17,000 17,000 970 1,100 2,500 1,600 330 300
-------------------------------------------------
isoxadifen-ethyl 5,600 3,500 na na 33,000 9,100 1,600 300
-------------------------------------------------
acetamiprid 1,000 38,000 na na 12,000 1,800 610 300
-------------------------------------------------
propiconazole 18,000 3,300,000 na na 19,000 1,800 1,500 100
-------------------------------------------------
furilazole 330,000 130,000 na na 200,000 19,000 15,000 300
-------------------------------------------------
fenhexamid 3,500 300,000 na na 13,000 14,000 1,300 300
-------------------------------------------------
fluazinam 93,000 4,300 na na 3,800 370 310 300
--------------------------------------------------------------------------------------------------------------------------------------------------------
[[Page 46720]]
Table 3 has been compiled based on analyses and data in existence
at the time of the tolerance action. Since the tolerance actions, EPA
has received new information or conducted new analyses as to these
pesticides. That data and analyses has resulted in changes, or
potential changes to the assessment of the risk posed by these
pesticides. The changes come in the form of adjusted safety factors,
more realistic exposure estimates, and new toxicity endpoints. EPA has
not incorporated that information into this objection response because
consideration of this new information was not needed to address NRDC's
objections. EPA would have considered expanding its response to address
new information if NRDC's objections had convinced EPA that its prior
analysis was flawed or EPA had a completed risk assessment showing
risks of concern.
EPA cautions that it would be inappropriate to focus on any one
aspect of the underlying risk assessment variables and conclude that
based on a change in that one variable alone the risk of a particular
pesticide is unacceptable. Not only must EPA assess all of the
variables in combination, but EPA's risk assessment process is tiered
such that more elaborate techniques to predict realistic exposure
values are not used if use of worst case default exposure assumptions
suggest there is not a risk of concern. (Refs. 29 at 22922; 1 at 11).
For example, NRDC has argued that for some of the pesticides in the
objections, use of a different safety factor would demonstrate that the
objected-to tolerances are unsafe. Given, however, the very
conservative exposure assumptions for many of these pesticides, such
arguments are likely to be incorrect even if NRDC could support its
argument for a greater safety factor.
b. Volatilization of applied pesticides. On June 19, 2003, NRDC
supplemented its submission to the Agency with several pieces of
additional information. Included was a report by the Californians for
Pesticide Reform generally addressing the issue of spray drift from
pesticide applications in California. (Ref. 34) [hereinafter referred
to as the ``CFPR Report'']. Although EPA defines spray drift as the
movement of droplets off-target during or shortly after application,
which is independent of the chemical properties of the pesticide being
sprayed, the CFPR Report looked more broadly at atmospheric pesticide
transport including pesticide volatilization as a potential mechanism
by which pesticides travel beyond treated fields. Also included in
NRDC's supplemental information was a research article containing an
analysis and ranking of the degree of inhalation risk posed by certain
migrating pesticides in California, based on ambient air monitoring
data gathered, in part, by the California Air Resources Board and the
California Department of Pesticide Regulation. (Ref. 35) [hereinafter
referred to as the ``Ranking Study''].
The Ranking Study conducted screening level assessments for many of
the pesticides regarded as having the highest potential as toxic air
contaminants by the California Department of Pesticide Regulation as
well as several pesticides categorized as hazardous air pollutants by
EPA. This screening level assessment, using conservative (health-
protective) assumptions, only identified three soil fumigants (MITC,
methyl bromide, telone) and one heavily-used non-fumigant pesticide
(chlorpyrifos) as potentially presenting non-cancer acute or chronic
risks of concern. (Id. at 1179). The study concluded that ``vapor
pressure is a significant predictor of [] ranking of inhalation risks.
(Id. at 1182). The CFPR Report examined the potential health risks from
air levels of three pesticides characterized as moderate to highly
volatile (chlorpyrifos, diazinon, and molinate) measured at the field
boundary and at more distant locations. The Report concluded that in
many instances the measured air levels of these pesticides posed risks
of concern. The Report also concluded that drift due to volatilization
was not a concern for pesticides that are not highly volatile. (Ref. 34
at 40).
(1) Analysis of CFPR report and ranking study. In terms of
volatility, pesticides can be broadly grouped into three categories:
(1) Those of high volatility (vapor pressure of 10-1 to
10-3 millimeter of mercury (mmHg)); (2) those of moderate
volatility (vapor pressure of 10-4 to 10-5 mmHg);
and (3) those of low volatility (vapor pressure of 10-6 mmHg
and below). EPA and NRDC seem to be in general agreement regarding the
exposure potential from the first and third groups. Both EPA and NRDC
believe that significant airborne exposures may occur as a result of
the application of pesticides of high volatility and that exposure
through volatilization is unlikely for pesticides of low volatility.
Where EPA and NRDC differ is regarding the middle group. NRDC argues,
based on the CFPR Report, that pesticides in this group can result in
exposures that raise levels of concern. EPA believes the evidence NRDC
has presented on this point is open to question. Although there is a
greater possibility for volatilization of residues of pesticides of
moderate volatility than those of low volatility, EPA is not convinced
that volatilization exposure from the former group is likely to be
meaningful. In any event, as discussed below, there is no reason to
expect any meaningful exposure due to volatilization from any of the 13
pesticides involved in these objections.
In the CFPR Report, CARB data is presented and analyzed for two
pesticides that fall in the middle group: Diazinon and chlorpyrifos.
The CFPR Report concludes that exposure to volatilized residues alone
from these two pesticides raise risks of concern. The risks of concern
were due to acute, not chronic exposures, and occurred primarily as a
result of exposure in areas immediately adjacent to treated fields
within a day or two of treatment. EPA questions the validity of this
determination due to various assumptions made in the Report that tend
to exaggerate exposure and risk. First, the CFPR Report estimates
exposure based on the amount of air breathed in a 24-hour period. The
field studies analyzed in the report, however, show that volatilization
exposures peak in a relatively narrow time window that is significantly
shorter than 24 hours.
Second, the measured residues in the field studies were sampled in
an outdoor location just a few feet from the field. Yet, it is unlikely
that any individual would remain stationary outdoors in such a location
for a 24-hour period. Moreover, even if an individual did stay in that
same location for a 24-hour period, it is unlikely that he or she would
be outdoors the entire time. Thus, the Report's exposure estimate rests
on the assumption that indoor air concentrations are the same as
concentrations measured in outdoor air. This assumption is reportedly
based on a pilot study supporting the prospective Agricultural Health
Study of American farmers and their families. (Ref. 36). These data
suggested higher air concentrations were found inside the residences of
farmers than were measured outdoors. The outdoor measurements were
collected either on the farmer's lawn or porch. However, it is not
clear either when the actual pesticide applications were made with
respect to the timing of the air concentration data collection or their
location with respect to the distance from the treated field.
Meteorological details were not provided. In one example from this
study (lindane), indoor concentrations were traced to work clothing
while the application of lindane was made to hogs situated inside a
separate production facility.
[[Page 46721]]
In EPA's view, it is more likely that indoor levels of pesticides
would be lower in homes situated near agricultural sites or other sites
of pesticide application than levels that might be measured outdoors.
This is particularly the case in situations involving acute exposures
where airborne levels rapidly peak and dissipate. For example, Segawa
et al. reported in 1991 that, when malathion was sprayed in Southern
California for Mediterranean fruit fly control, indoor levels of
malathion were 4 to 5 times lower than outdoor air concentrations.
(Ref. 37). In a study evaluating the impact of track-in following
applications of 2,4-D to lawns (Ref. 38), it was suggested that spray
drift and particle intrusion had little effect on indoor carpet dust
concentrations. Likewise, Solomon et al. (Ref. 39) have reported
minimal impact on indoor air measurements of bystander homes adjacent
to treatment areas (2,4-D applications to lawns). Therefore, the
assumption that indoor air concentrations are equivalent to outdoor air
concentrations appears to exaggerate risk. Consistent with this view,
California DPR measurements of indoor air versus outdoor air following
methyl bromide structural fumigations indicated that, within the first
hour, outdoor air concentrations of methyl bromide (first 50 feet from
treatment site) are approximately 5 to 8 times higher than those in
indoor air, and up to 13 times higher than indoor air at distances
equal to or greater than 100 feet. Only after 24 hours, when the
majority of the plume had passed by the house, were indoor air
measurements roughly the same as outdoor measurements.
Third, the CFPR compares these exposure estimates to reference
doses from subchronic inhalation studies. With chlorpyrifos, the
reference dose is based on lack of effects in two 90-day rat inhalation
studies at the highest dose tested and incorporates a 1,000-fold safety
factor. For diazinon, the reference dose is from a LOAEL in a 21-day
inhalation study and incorporates a 300-fold safety factor. Use of
reference doses from subchronic studies to assess what, in the case of
the field trials, are at most short-term exposures (1 to 7 day
duration) - and more likely acute exposures (single event) - is a very
conservative approach. This factor should be taken into account in
characterizing any risk estimation.
Finally, an EPA report on pesticide exposure to children along the
United States/Mexico border (discussed in the Imidacloprid Order, (69
FR at 30052)) presents a vivid contrast to conclusions reached in the
CFPR report. (Ref. 40). This report concluded that both indoor and
outdoor air concentrations had a minimal impact on the exposed
population. The pesticides diazinon and chlorpyrifos are two chemicals
widely used in that region. Thus, this report casts doubt on the
conclusions in the CFPR Report.
(2) Vapor pressure. As noted, EPA is in general agreement that
vapor pressure is a key factor in predicting whether a pesticide has
the potential to volatilize and drift offsite in significant amounts.
Because soil fumigants traditionally have very high vapor pressures,
and thus are highly volatile, EPA is now accounting for potential
exposure due to volatilization of these pesticides in calculating their
aggregate exposure. The CFPR Report concludes that post-application
volatilization exposures are not of concern for pesticides with a low
vapor pressure - i.e., less than or equal to 10-6 mmHg - but
can be for pesticides with a moderate vapor pressure - i.e. between
10-4 and 10-6 mmHg. In Table 4 below, EPA has
listed, according to vapor pressure, the five non-fumigant pesticides
examined by the CFPR Report (including the CFPR's characterization of
the vapor pressure) as well as the 13 pesticides in these objections.
(Ref. 41).
Table 4. --Vapor Pressure of Selected Pesticides
------------------------------------------------------------------------
Vapor Pressure
Pesticide Reason Included (mmHg)
------------------------------------------------------------------------
molinate CFPR (high vapor 5.3 x 10-3
pressure)
---------------------------------
diazinon CFPR (moderate 1.4 x 10-4
vapor pressure)
---------------------------------
chlorpyrifos CFPR (moderate 1.87 x 10-5
vapor pressure)
---------------------------------
fluazinam Subject of 8 x 10-6
objection
---------------------------------
mepiquat Subject of 2.3 x 10-6
objection
---------------------------------
propiconazole Subject of 4.2 x 10-7
objection
---------------------------------
2,4-D Subject of 1.4 x 10-7
objection
---------------------------------
paraquat CFPR (low vapor 1 x 10-7
pressure)
---------------------------------
halosulfuron Subject of 1 x 10-7
objection
---------------------------------
bifenazate Subject of 1 x 10-7
objection
---------------------------------
pymetrozine Subject of 3 x 10-8
objection
---------------------------------
isoxadifen-ethyl Subject of 1.65 x 10-8
objection
---------------------------------
acetamiprid Subject of 7.5 x 10-9
objection
---------------------------------
fenhexamid Subject of 7 x 10-9
objection
---------------------------------
propargite CFPR (low vapor 4.4 x 10-9
pressure)
---------------------------------
zeta-cypermethrin Subject of 3.07 x 10-9
objection
---------------------------------
[[Page 46722]]
diflubenzuron Subject of 9 x 10-10
objection
---------------------------------
furilazole Subject of 6.63 x 10-10
objection
------------------------------------------------------------------------
As Table 4 illustrates, all but two of the pesticides in these
objections have a low vapor pressure and thus, on this basis alone, are
unlikely to result in significant exposures due to post-application
volatilization. Two pesticides, fluazinam and mepiquat, have vapor
pressures in the 10-5 to 10-6 mmHg range, but
nonetheless below the vapor pressure of chlorpyrifos, the pesticide
with the lowest vapor pressure that the CFPR Report concluded had
significant levels of post-application drift. (A form of 2,4-D (2,4-
D(BEE)) has a vapor pressure of 2.4 X 10-6 mmHg; however,
whatever potential to volatize exists for this form of 2,4-D is
significantly lowered by its method of application (agitation into the
water profile at aquatic sites)). Traditionally, general scientific
opinion has been that substances with a vapor pressure of between
10-4 and 10-6 mmHg are relatively non-volatile
and thus unlikely to result in significant exposures due to
volatilization. (Ref. 42). NRDC contends otherwise based on the CFPR
Report. Even assuming NRDC is correct, however, there are several
characteristics of fluazinam and mepiquat in addition to their lower
vapor pressure, that distinguish them from chlorpyrifos and make it
unlikely that they have any significant post-application drift
exposures either in the acute or chronic exposure time-frame.
In terms of acute exposure, it is first worth re-emphasizing that
EPA has substantial questions as to whether the CFPR Report overstates
the exposure that can be expected with regard to chlorpyrifos. Second,
the maximum single application rates for fluazinam (0.8 lbs/acre) and
mepiquat (0.25 lbs/acre) are much lower than chlorpyrifos (6 lbs/acre -
this rate was used in the CFPR study) - factors of 7.5 and 24,
respectively. (Refs. 43, 44 and 45). Finally, the acute inhalation
endpoints of concern, adjusted by safety factors, for fluazinam (0.0046
mg/kg/day) and mepiquat (0.584 mg/kg/day) are much higher than for
chlorpyrifos (0.0001 mg/kg/day) - factors of 46 and 5,840,
respectively. (Refs. 46, 47 and 48).
As to chronic exposure, although a high enough vapor pressure
appears to be a necessary condition to significant ambient air
concentrations, vapor pressure alone is not sufficient for such
significant chronic exposures to occur. Equally necessary, is a
substantial overall usage amount. In this regard, chlorpyrifos dwarfs
fluazinam and mepiquat. Average annual usage for chlorpyrifos for the
years 2001-2003, is estimated to have been in the range of 8 to 9
million pounds. On the other hand over the same period, mepiquat usage
is estimated to have been in the range of 250,000 to 500,000 pounds.
Fluazinam had so little usage it did not even show up in standard
pesticide usage survey reports. (Ref. 49).
Finally, it is worth considering that occupational exposure
assessments for the three pesticides as a means of comparing the
relative inhalation risk posed by these pesticides. EPA's principal
tool for assessing occupational exposure and risk is Pesticide Handlers
Exposure Database (PHED). (Ref. 50). PHED is a software system
consisting of two parts -- a database of measured exposure values for
workers involved in the handling of pesticides under actual field
conditions and a set of computer algorithms used to subset and
statistically summarize the selected data. Currently, the database
contains values for over 1,700 monitored individuals (i.e.,
replicates). One of the measured values is the level of pesticide
residue in ambient air at the time of application. This value contains
a mixture of volatized residue as well as airborne non-volatized
residue and is likely to be substantially higher than any post-
application levels even for highly volatile pesticides.
What PHED assessments for the three pesticides show is that for
inhalation risks both fluazinam and mepiquat have high MOEs that are
well above the level of concern (i.e., there is a large margin of
safety) even without any protective equipment (e.g., respirators or
enclosed cabs) but that chlorpyrifos had MOEs for some scenarios that
are below the level of concern even assuming that applicators used
enclosed cabs. (Refs. 46 at 7-8; 47 at 37 and Ref. 51).
For all of these reasons, EPA concludes the information submitted
by NRDC does not suggest that the use of fluazinam and mepiquat, which
have vapor pressures slightly above the 10-6 mmHg level,
would result in significant post-application exposures due to
volatilization of residues. As the material relied upon by NRDC notes,
post-application drift is unlikely for the other 11 pesticides in the
objections.
c. Conclusion. EPA concludes that NRDC's arguments concerning
exposure from application and post-application drift do not undermine
EPA's conclusion that it has reliable data on exposure for these
pesticides. Not only does the scientific literature not support a
finding that pesticide drift is a major source of exposure but (1)
EPA's application drift model demonstrates that exposure from
application drift is likely to be marginal everywhere other than areas
immediately adjacent to fields; (2) even combining application drift
exposures with other aggregate exposures in a manner likely to
significantly overstate exposure does not show a risk of concern for
any of the 13 pesticides; (3) the vapor pressures for 11 of the 13
challenged pesticides are sufficiently low that even NRDC appears to
concede that significant post-application drift would not be expected
from any of them; and (4) for the two pesticides that have slightly
higher vapor pressures, individual factors regarding them indicate that
siginificant post-application drift is unlikely.
C. Failed to Retain Children's 10X Safety Factor
1. Introduction. NRDC's objections concerning the children's safety
factor principally focus on an alleged lack of data that NRDC contends
does not allow EPA to conclude that the children's safety factor may be
reduced or removed. First, NRDC argues that 7 of the 13 pesticides
(halosulfuron-methyl, pymetrozine, mepiquat, zeta-cypermethrin, 2,4-D,
acetamiprid, and fluazinam) lack a required DNT study, and that this
``is a crucial data gap that by itself should prohibit EPA from
overturning the default 10X safety factor.'' (Refs. 6 at 4; 7 at 6-7; 8
at 10; and 9 at 6). In support of this argument NRDC relies on
information showing that pesticides may cause developmental neurotoxic
effects and that these effects may come at lower doses than doses
causing other adverse effects. Second, NRDC cites, on a pesticide-by-
pesticide basis, various
[[Page 46723]]
toxicological studies that NRDC claims are missing, or were not
considered. The absence or non-consideration of these data, NRDC
contends, warrants retention of the children's safety factor. Following
the same pattern with exposure data, NRDC claims that the children's
safety factor is required because EPA is lacking both generic data on
exposure and various specific pieces of exposure information with
regard to some of the individual pesticides named in the objections.
NRDC's generic exposure data objections pertain to data on the exposure
of farm children to pesticides and exposure to pesticides through
drinking water. Additionally, NRDC claims that data are missing because
EPA has allegedly failed to undertake certain, specific risk
assessments as to some of the pesticides.
Each of these objections will be addressed individually.
2. Lack of DNT study generally. NRDC contends that ``the absence of
required developmental (DNT) tests for 2,4-D is a crucial data gap that
by itself should prohibit EPA from overturning the default 10X safety
factor.'' (See, e.g., Ref. 8 at 9). NRDC cites essentially three
grounds in support of this contention. First, NRDC claims that there is
extensive evidence showing that ``pesticide exposures may disrupt the
normal development of a child's brain and nervous system.'' (Id. at 9
and fn.16 (citing studies)). Second, NRDC references a paper by EPA
staff scientist Susan Makris that NRDC asserts demonstrates that ``DNT
testing is more sensitive than other studies in measuring the effects
of exposure on proper development of the brain and nervous system . . .
.'' (Id. at 9). Third, NRDC cites the EPA's 10X Task Force Report which
recommends the DNT testing be part of the minimum toxicity data set for
pesticides requiring a tolerance for residues in or on food. (Id. at
10). NRDC further asserts that EPA's Children's Safety Factor Policy
fails in its purported attempt to justify choosing a factor other than
10X when a required DNT study has not been submitted. According to
NRDC, the Children's Safety Factor Policy ``completely reverses'' the
statutory presumption in favor of an additional 10X factor by allowing
EPA to choose a different factor not on the basis of reliable data but
on a risk assessor's ``intuition or professional judgment.'' (Id. at
11).
EPA disagrees that the mere absence of a required DNT study should,
by itself, conclusively bar EPA from applying a different additional
safety factor than the 10X default value. After all, the statute
expressly authorizes EPA to use a different additional factor if the
Agency can determine on the basis of reliable data that a different
factor ``will be safe for infants and children.'' (21 U.S.C.
346A(b)(2)(C)). In line with the statute, EPA's Children's Safety
Factor Policy calls for a careful examination of the existing database
on a case-by-case basis to determine if a reliable basis exists for
assigning a different factor. NRDC's argument here can only be
successful if it can show that reliable data to support a different
safety finding could never be available. This NRDC has not done. NRDC's
objections contain no factual contention demonstrating that a case-
specific approach cannot work or is inappropriate for the 13 pesticides
in question.
a. Pesticides may cause neurological developmental effects. NRDC
cites the National Research Council's 1993 Report on pesticides'
effects on children in support of the claim that ``pesticide exposures
may disrupt the normal development of a child's brain and nervous
system.'' (Ref. 8 at 9). EPA does not dispute that some pesticides have
that potential; however, that some pesticides have that potential does
not mean that defensible judgments about that potential cannot be made
in the absence of a DNT study. Further, EPA would note that the
National Research Council Report did not conclude that the evidence
showed that exposure to pesticides was currently resulting in
neurological developmental effects. According to the National Research
Council, ``[a]lthough the vulnerability of the developing brain to
neurotoxic exposure is of serious concern, it is entirely unclear from
the data available whether exposures at levels consistent with usual
dietary exposures would pose a substantial risk to the long-term
neurologic development of children in general or to particular
subgroups of children that are neurologically vulnerable.'' (Id. at
65.)
NRDC also cites a number of studies showing that a particular
pesticide, chlorpyrifos, does have neurological effects on the
developing brain. Again, however, EPA does not deny that pesticides can
cause such effects. The question is, however, whether in the absence of
a DNT study, EPA can make a reliable prediction concerning whether a
particular safety factor will be protective of infants and children
from potential neurological effects. Citing the general capacity of a
specific pesticide to cause neurological effects does not answer this
question. EPA has received and reviewed a DNT study for the pesticide
in question, chlorpyrifos. Although the results of the DNT study for
chlorpyrifos were confirmatory of results in other chlorpyrifos
toxicology studies, the DNT results did not alter the regulatory
endpoints chosen for that pesticide. (Ref. 52).
b. 1998 retrospective study on submitted DNT studies. The
conclusions presented in the Makris study are more relevant to the
question at hand. (Ref. 53). After reviewing nine DNT studies that had
been submitted on pesticides, Makris found that (1) for eight out of
nine pesticides the fetal NOEL from the DNT study was lower than the
fetal NOEL from the standard prenatal developmental toxicity study; (2)
for six out of nine pesticides the offspring NOEL from the DNT study
was lower than the offspring NOEL from the standard two-generation
reproduction study; (3) for two out of nine pesticides, the acute
endpoints and associated NOELs from the DNT study were selected for the
acute dietary risk assessment; and (4) the DNT study did not provide an
endpoint and associated NOEL for chronic risk assessment for any of the
nine pesticides. The first two findings provide valuable scientific
information with regard to understanding how pesticides may affect the
developing human. More relevant to a decision regarding the children's
safety factor, however, are the latter two findings because they
highlight whether a DNT study may affect how the risk posed by a
pesticide is characterized.
Some background information may be helpful in understanding the
significance of Makris' findings. In assessing the risk posed by a
pesticide, EPA examines numerous toxicological studies and identifies
from each study the LOAEL resulting from exposure to the pesticide and
the NOAEL. These NOAEL/LOAELs are then grouped by exposure scenario
taking into account both the duration of the exposure (e.g., acute,
chronic) and the route of exposure (e.g., oral, dermal). For each
exposure scenario EPA selects the lowest of the appropriate NOAELs for
the purpose of assessing risk. For evaluating acute and chronic oral
dietary exposure, EPA uses this NOAEL to derive a safe dose - this safe
dose is commonly referred to as a Reference Dose (RfD). Generally, a
RfD is calculated by dividing the selected NOAEL by one or more safety
or uncertainty factors. When more data becomes available, it may change
a RfD but only if the NOAEL from the new data is lower than all
previous NOAELs identified for the relevant exposure scenario.
What Makris found in looking at the 9 pesticides was that, out of
the 18 potential exposure scenarios examined
[[Page 46724]]
(1 acute oral and 1 chronic oral for each pesticide), in only 2
instances did the DNT study produce a NOAEL that was below all other
NOAELs for that exposure scenario for that pesticide. In other words,
in 16 out of 18 cases, the DNT study made no difference in the
calculation of the safe human dose (i.e., RfD) for the pesticide.
Although this information shows that the DNT study can be an important
study is assessing the risk of pesticides because it has the potential
to show adverse effects at levels below those previously identified,
the potential for a DNT study to change an existing RfD is hardly so
overwhelming to suggest that there is no room for exercise of the
discretion to examine the individual facts involving the safety of each
pesticide that is expressly provided by the statute.
Today, EPA has considerably more experience with the DNT study than
when the 1998 Retrospective Study was conducted. That experience has
confirmed both that the DNT study has a role to play in assessing the
hazard posed by pesticides, (Ref. 54), and that DNT studies only
infrequently affect the projection of a safe endpoint for a pesticide.
EPA is currently in the process of completing another retrospective
study of the DNT study based on the roughly 50 DNT studies it has now
received. The full retrospective study will not be completed until
later this year; however, some preliminary information is now
available. (Ref. 55). It shows that out of the 38 pesticides for which
a DNT study has been submitted and EPA's analysis completed, the DNT
study has resulted in a lowering of at least 1 endpoint for a pesticide
in 8 instances. Again, these numbers do not suggest there is no room
for judgment in evaluating the impact a DNT study may have on a risk
assessment.
c. 10X Task Force Report. NRDC also cites the recommendation in the
report of EPA's 10X Task Force that the DNT study be included in the
core toxicology database for pesticides. Although the Task Force did
note the significance of the DNT study for assessing potential risks
for children, the Task Force also concluded that any decision on the
size of any safety factor (described by the Task Force as a database
uncertainty factor) used when a DNT study had not been submitted called
for the exercise of ``good scientific judgment.'' (Ref. 56). According
to the Task Force, ``[t]he size of the database uncertainty factor
applied will depend on other information available in the database and
how much impact the missing data may have on determining the potential
toxicity of the pesticide for children.'' (Id.). As described above,
EPA's policy on evaluating the size of the safety factor when a
required DNT study has not yet been submitted is fully consistent with
this recommendation by the 10X Task Force. When a required DNT study is
absent, EPA has focused on the other information available on the
pesticide and the possible impact the DNT study may have on estimating
the risk of the pesticide.
d. EPA's 10X Policy. Finally, EPA disagrees that its Children's
Safety Factor Policy completely reverses the statutory presumption to
include an additional 10X safety factor for the protection of infants
and children. In the opening paragraph of the policy the Agency states
that ``[t]he Office of Pesticide Programs (OPP) interprets this
statutory provision [Section 408(b)(2)(C)] as establishing a
presumption in favor of applying an additional 10X safety factor.''
(Ref. 2 at 4). The presumptive aspect of the additional 10X safety
factor (also described as the ``default position'') is referenced
throughout the document. (See, e.g., Id. at 10, 11, 17, 26, 46, 47-48,
and A-6).
NRDC cites to language in the policy statement stating that in
evaluating what safety factor decision should be made for pesticides
for which a DNT study has been requested, risk assessors should
consider ``if the available information indicates that a DNT study is
likely to identify a new hazard or effects at lower dose levels of the
pesticide that could significantly change the outcome of its overall
risk assessment . . . .'' (Ref. 7 at 8-9). NRDC argues that this
language reverses the statutory presumption because it allows the
presumption to be removed not based on reliable data but upon the
''risk assessor's expectation. (Id. at 9).
NRDC, however, is mistaken in its interpretation of this language.
In directing the risk assessor to consider the likely impact of a DNT
study on a risk assessment, EPA was not asking the risk assessor to
guess at the results of the DNT study. Rather, EPA was directing the
risk assessor to consider what the reliable data available on the
pesticide told the risk assessor about the likely outcome of the DNT
study. To ensure that the policy was not misunderstood on this point,
the policy explicitly states that ``[d]iscussions in this document of
the appropriateness, adequacy, need for, or size of an additional
safety factor are premised on the fact that reliable data exist for
choosing a `different' factor than the 10X default value.'' (Ref. 2 at
12). To the extent the policy statement injects any uncertainty with
regard to this issue, EPA herein confirms that a decision to choose a
factor different than the default 10X factor must be based on reliable
data.
e. Conclusion. EPA rejects NRDC's contention that an EPA finding
that a DNT study is needed in evaluating the risks posed by the
pesticide is outcome-determinative as regards to retaining the
children's safety factor until such time as the DNT study is submitted
and reviewed. The statute specifically grants EPA discretion to apply a
different additional safety factor where EPA can conclude based on
reliable data that the different factor is safe for infants and
children. NRDC has made no argument that would justify an across-the-
board conclusion that in the absence of a DNT study an individual
examination of the existing data pertaining to a pesticide cannot
provide a reliable basis for concluding that a different safety factor
would be safe for infants and children. NRDC's claim that a DNT study
may lower EPA's RfD (which EPA does not disagree with) is not by itself
sufficient to bar EPA from making a case-by-case inquiry into the
safety of a different additional safety factor for the protection of
infants and children in the absence of such a study. Further, NRDC has
offered no pesticide-specific arguments as to the pesticides in this
proceeding as to why the absence of a DNT study requires the retention
of the default 10X additional factor.
3. Other pesticide-specific missing toxicity data--a.
Diflubenzuron. NRDC claims that EPA is missing toxicology data for two
diflubenzuron metabolites, deemed necessary by EPA to justify an
unconditional registration.
As EPA has previously noted, the toxicology database for
diflubenzuron is complete for assessment of increased susceptibility to
infants and children. (67 FR 59006, 59013, September 19, 2002; 67 FR
7085, 7089, February 15, 2002). EPA has received and reviewed all
required studies bearing on the assessment of the effects of
diflubenzuron following in utero and/or postnatal exposure. These
studies demonstrated that diflubenzuron presented a low risk to the
developing organism. For example, in the prenatal developmental
toxicity studies in rats and rabbits, no developmental toxicity was
seen at the Limit Dose (1,000 mg/kg/day) and in the two-generation
reproduction study in rats toxicity in the offspring was manifested as
decreased body weight at approximately 4,000 mg/kg/day (4 times the
Limit Dose) The Limit Dose is generally regarded as the highest dose
that could be tested in animal studies to maximize detection of
potential adverse effects of a chemical (e.g, systemic toxicity,
[[Page 46725]]
carcinogenicity) without overloading the metabolic and/or physiological
process of the animals. This upper limit dose (1,000 mg/kg/day) is
equivalent to dietary concentrations of approximately 20,000 parts per
million (ppm) in the diet of rats, 7,000 ppm in the diet of mice, and
40,000 ppm in the diet of dogs
With regard to the alleged need for additional data on the
diflubenzuron metabolites, PCA and CPU, the Federal Register notice
establishing the challenged tolerance specifically stated that ``there
are no residue chemistry or toxicology data requirements that would
preclude the establishment of a conditional registration and permanent
tolerance for the combined residues of diflubenzuron, . . . and its
metabolites 4-chloroaniline [PCA] and 4-chlorophenylurea [PCU] in/on
pears at 0.05 ppm.'' (Id. at 7090, February 15, 2002). EPA's risk
assessment for diflubenzuron noted no toxicology data needs and no
other data needs other than validation of the analytical enforcement
method (which has now been submitted, see Unit VII.C.5.d. of this
document). (Ref. 57) The diflubenzuron registration on pears was
conditional because validation of the analytical method was required.
(Id.) Further, EPA considered and rejected NRDC's claims regarding the
need for more toxicology data on the diflubenzuron metabolites in a
tolerance rulemaking in September 2002. EPA noted that ``the rate of
metabolism of diflubenzuron to PCA or CPU in plants, ruminants, and the
environment is low and, thus, exposure to these metabolites will be
minimal.'' (67 FR 59006, 59013, September 19, 2002). EPA relied upon
the fact that when PCA and CPU were evaluated using a low dose linear
model for cancer risk assessment - the most sensitive and conservative
method for evaluating risk, whether from cancer or any other endpoint -
these metabolites were found to pose a negligible risk. (Id.) EPA
concluded that ``additional hazard testing for these metabolites will
not lead to a more protective regulatory decision.'' (Id.) In these
circumstances, EPA is confident that it has adequate reliable data to
assign a factor different than the 10x default value to diflubenzuron,
taking into account its PCA and CPU metabolites.
b. Fluazinam. NRDC asserts that for fluazinam EPA is missing a 28-
day inhalation study, and a conditionally-required subchronic
neurotoxicity battery. In response, EPA notes that a subchronic
neurotoxicity study conducted with fluazinam has been received and
reviewed. No treatment-related effects were observed in males or
females at the highest dose tested in this study. (Ref. 58). EPA
reserved the right to require this study to be redone because a toxic
impurity of fluazinam was at a low level in the test material used in
the study. EPA plans to reevaluate this issue once the DNT study is
submitted and reviewed. (Id. at 39-40). Nonetheless, a clear NOAEL and
LOAEL was identified for the impurity in other studies and EPA has
``high confidence in the hazard endpoints and dose-response
assessments'' for fluazinam. (Id. at 42-44). Regarding the data
requirement for the 28-day inhalation study, this study is primarily
required to assess worker risk and is not relevant to the exposure
patterns for fluazinam examined in making the safety determination
under FFDCA section 408. Accordingly, there is reliable data to assess
the risks of fluazinam to infants and children despite the lack of a
repeat subchronic neurotoxicity study and 28-day inhalation study.
c. Furilazole. NRDC claims that EPA lacks a chronic dog study for
furilazole. NRDC is correct that EPA does not have a chronic dog study
for furilazole. EPA determined that because furilazole is an inert
ingredient (safener) with a limited use that the chronic dog study was
not needed given consideration of the rest of the toxicological data on
furilazole. Nonetheless, to be protective, EPA applied an additional
FQPA safety factor of 3X in deriving the chronic reference dose. The
chronic reference dose was calculated by dividing the NOAEL of 0.26 mg/
kg/day in the 2-year rat study (based on increased absolute and
relative liver and kidney weights in males at 5.05 mg/kg/day in rats)
by both the standard safety/uncertainty factors (10X for inter-species
variability and 10X for intra-species variability) and a 3X factor to
account for the lack of the chronic dog study (i.e, 0.26 / 300X =
0.0009 mg/kg/day). A factor of 3X was judged to be adequate because the
results from the subchronic toxicity studies in rats and dogs show that
the toxicity of furilazole is similar, both qualitatively and
quantitatively, in both species. The liver was the target organ in both
species. EPA found there to be no significant quantitative difference
in the relative responses of dogs and rats to the hepatotoxic effects
of furilazole in the subchronic studies. The NOAELs/LOAELs for both
species were based on hepatotoxicity and are effectively the same value
(5/15 and 7/34 mg/kg/day in dogs and rats, respectively). No target
organs were identified in dogs that were not also identified in rats.
(Ref. 59).
d. 2,4-D. In an introductory section to its objections that was not
linked to any specific objection, NRDC expressed concern that EPA has
not adequately considered epidemiological studies linking 2,4-D with
non-Hodgkin's lymphoma and canine malignant lymphoma which NRDC; (Ref.
8 at 5), animal studies showing potential endocrine effects of 2,4-D;
(Id. at 5-6), epidemiological data showing endocrine effects on adverse
reproductive outcomes; (Id. at 6), and animal studies evidencing 2,4-
D's affect on the developing brain and nervous system. Reference to
cancer studies does not appear relevant to objections concerning the
children's safety factor. That safety factor is designed to provide
additional protection for risks that have a safe threshold and not non-
threshold risks such as cancer. (21 U.S.C. 346a(b)(2)(C)). The
epidemiological data cited by NRDC is either weak (few subjects,
questionable controls, not performed by epidemiologists) or not
specific to 2,4-D. (See Ref. 60). As to the animal studies on brain/
nervous system effects, NRDC cites a published article involving single
dose studies (Ref. 8 at 7) that show nervous system effects at levels
consistent with the levels at which the data before EPA evidenced
effects. (Ref. 61). Accordingly, the cited data does not materially
affect EPA's analysis.
As part of the reregistration of 2,4-D, EPA is comprehensively
reviewing these issues. This review has considered a considerable
amount of new data that have become available since 2002. EPA's draft
risk assessment for 2,4-D is available in EPA's electronic docket under
the docket number OPP-2004-0167.
4. Missing exposure data - general--a. Farm children exposure. NRDC
argues that EPA is lacking data on exposure to farm children and thus
may not remove the additional 10X safety factor. EPA disagrees. As
discussed above and in the Imidacloprid Order, the epidemiological data
cited by NRDC have not shown that there are significant exposures to
farm children that occur as a result of living in close proximity to
agricultural operations. EPA concluded that the evidence presented by
NRDC is fragmentary, at best, as to whether pesticide exposure levels
in homes of children living in agricultural areas are significantly
different than levels in other homes and whether children living in
agricultural areas have significantly different exposures than non-
agricultural children.
NRDC also submitted two articles addressing pesticide spray drift
and post-application volatilization drift of pesticides. EPA's analysis
of exposure due to pesticide drift in Unit VII.B.2., however, showed
that, as to the
[[Page 46726]]
pesticides involved here, there was little basis to find that drift
could result in exposure posing a risk of concern. In fact, the recent
data from the CTEPP study suggest that dietary exposure is generally
the dominant exposure. What the CTEPP data show, therefore, is that
NRDC, by asserting that the 10X safety factor should be retained to
protect farm children from additional exposures they allegedly receive,
is essentially asking that the dominant dietary exposure and other
quantified non-dietary exposures be multiplied by 10 in estimating risk
to protect against underestimating a potential non-dietary exposure
that is likely to be, at most, a fraction of the dietary exposure
alone. This is so because retaining an additional 10X safety factor
decreases the estimated safe dose for humans by a factor of 10 making
estimated exposure 10 times greater compared to the revised safe dose.
After considering all of data bearing on exposure to the 13
pesticides in NRDC's objections, including both pesticide-specific data
and the more general data on children's exposure to pesticides, EPA
concludes it has sufficient reliable exposure data on these pesticides
to find that an additional 10X factor is not needed to protect the
safety of infants and children. Specifically, the data reviewed in this
Order, in the Imidacloprid Order, and in the individual tolerance
actions give EPA confidence that it has not underestimated exposure as
to these pesticides.
In this regard, EPA would note that, for 8 of the 13 pesticides, it
used its most conservative (health protective) method of estimating
dietary exposure assuming that all food covered by the pesticide
tolerances contained residues at the tolerance level. (66 FR at 66335,
December 26, 2001 (halosulfuron); 67 FR at 3115, January, 23, 2002
(mepiquat); 67 FR at 4917, February 1, 2002 (bifenazate); (67 FR at
6424-6425, February 12, 2002 (zeta-cypermethrin); 66 FR at 33182-33183,
June 21, 2001(isoxadifen-ethyl); 67 FR at 14653-54, March 27, 2002
(acetamiprid); 67 FR at 15731, April 3, 2002 (furilazole); 67 FR at
19116, April 18, 2002 (fenhexamid). (The reasons these assumptions
produce such large overestimates is discussed in detail in Unit
VII.D.5). Even for the other five pesticides, EPA's dietary exposure
estimate was not highly refined. In none of these exposure estimates
did EPA use a probabilistic risk assessment, the assessment technique
that produces the most realistic picture of potential risk, or rely on
food monitoring data to estimate residue levels. For all but one of the
pesticides, EPA refined exposure estimates as to only some but not all
food commodities. (See Unit VII.D.6; 66 FR at 66786, December 27, 2001
(for pymetrozine, exposure assessment refined only as to chronic
risks); 67 FR at 7087, February 15, 2002 (for diflubenzuron, exposure
assessment refined only as to chronic risks and only as to some crops);
67 FR at 10625, March 8, 2002 (for 2,4-D, exposure estimates refined
for only citrus for acute risk and for only some crops for chronic
risk); 64 FR at 2998, January 20, 1999 (for propiconazole, exposure
estimates refined for only some crops for chronic risk; no refinement
for acute risk); 67 FR at 19120, April 18, 2002, Ref. 46 at 6 (for
fluazinam, exposure estimates refined for one of three crops for
chronic risk; no refinement for acute risk)). Further, EPA's
conservative method of modeling drinking water exposure was used, at
least in part, for all of the pesticides. (See 69 FR at 30058-30065,
May 26, 2004). For those pesticides that have residential uses, EPA
relied upon its very conservative approach for estimating exposures
that can occur around the home from such uses. (See 69 FR at 30055, May
26, 2004). The conservativeness of EPA's exposure estimates is perhaps
evidenced most dramatically by a comparison between exposure estimates
for 2,4-D from a study relied upon by NRDC involving actual sampling of
2,4-D residues in homes and the EPA's exposure estimates. The 2,4-D
exposure estimate EPA prepared for this Order is almost two orders of
magnitude greater than the estimates from the cited study and the
exposure estimate for the challenged tolerance action is well over an
order of magnitude greater. (See Unit VII.D.7.e).
b. Lack of comprehensive drinking water (DW) monitoring data. NRDC
contends that, because EPA used a model for calculating drinking water
exposure, EPA does not have, as a definitional matter, ``reliable
data'' for choosing a factor different than the 10X default value.
Similar comments were made during the development of EPA's Children's
Safety Policy. This issue was addressed at length in the response to
the imidacloprid objections. (69 FR at 30058-30064, May 26, 2004). That
response is incorporated herein and is summarized below.
Although the availability of drinking water monitoring data has
increased dramatically in the last several years, EPA still finds it
necessary to rely for most pesticides upon various exposure models to
estimate exposure levels in drinking water. These models are based on
generic data regarding fate and transport of pesticides in the
environment, and they operate by combining this generic data with
pesticide-specific data on chemical properties to estimate exposure.
EPA has primarily used its drinking water models to ``screen'' those
pesticides that may pose unacceptable risks due to exposures in
drinking water from pesticides not likely to result in such exposures.
To accomplish this goal, the models are based on data from studies at
sites that are highly vulnerable to runoff of pesticides to surface
water or leaching of pesticides to ground water. If a pesticide fails
this conservative (health-protective) screen, EPA would investigate
whether the model is significantly overstating the residue levels that
actually occur.
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.
Whether EPA assesses pesticide exposure in drinking water through
monitoring data or modeling, EPA uses the higher of the two values from
surface and ground water in assessing overall exposure to the
pesticide. In most cases, pesticide residues in surface water are
significantly higher than in ground water.
In the Imidacloprid Order, EPA analyzed each of its water models
extensively. Based on the results of design characteristics of the
models, outside peer review of the models, validation of the models,
and comparison between the models' predictions and extensive water
monitoring data, EPA concluded that the models are based on reliable
data and will produce estimates that are unlikely to underestimate
exposure to pesticides in drinking water. (69 FR at 30065).
Accordingly, EPA reaffirms its earlier conclusion that its drinking
[[Page 46727]]
water models provide a reliable basis for finding that exposure to
pesticide residues in water are not underestimated.
5. Missing exposure data - specific--a. Mepiquat. NRDC asserts that
there is a data gap for side-by-side residue field trials for mepiquat.
(Ref. 7 at 5). The tolerance in question covers both mepiquat chloride
(N,N-dimethylpiperidinium chloride) and mepiquat pentaborate (N,N-
dimethylpiperidinium pentaborate) on cotton. A full toxicological and
residue database was submitted on mepiquat chloride. As to mepiquat
pentaborate, the petitioner relied on the mepiquat chloride data and a
dissociation study demonstrating that ``pentaborate salt'' of mepiquat
dissociates in water in an identical physical manner to the ``chloride
salt'' of mepiquat. Based on this data, EPA concluded that the proposed
foliar application of mepiquat pentaborate to cotton is not expected to
result in residues of mepiquat per se greater than those resulting from
the application of mepiquat chloride. (67 FR at 3114, January 23,
2002). The required residue studies are confirmatory in nature. (Ref.
62). Accordingly, EPA concludes it has reliable data on mepiquat
residues in cotton.
b. Bifenazate-assessment of drinking water exposure to bifenazate
degradates. NRDC claims that EPA has failed to complete ``an assessment
of drinking water exposure to bifenazate degradates.'' (Ref. 7 at 5).
As the Federal Register notice establishing the contested tolerances
for bifenazate reveals, however, EPA scientists considered
environmental persistence of bifenazate and its two major degradates,
D3598 (diazinecarboxylic acid, 2-(4-methoxy-[1,1'-biphenyl]-3-yl), 1-
methylethylester) and D1989 (4-methylethylester). Aqueous photolysis
and soil metabolism studies demonstrated that the parent bifenazate and
the D3598 degradate ``quickly metabolize under aerobic soil
conditions.'' (67 FR at 4918, February 1, 2002). Noting the lack of
persistence of these two compounds and the absence of any acute dietary
endpoint, EPA focused its drinking water exposure assessment for
bifenazate on the degradate that had a possibility of being present in
drinking water. (Id.). Accordingly, NRDC is incorrect to assert that
potential exposure to bifenazate degradates in drinking water was not
assessed by EPA and hence, NRDC's assertion does not call into question
EPA's decision concerning the children's safety factor for bifenazate.
c. Zeta-cypermethrin--assessment of drinking water exposure zeta-
cypermethrin degradates. NRDC claims that EPA has ``failed to address
drinking water exposure to zeta-cypermethrin degradates.'' (Ref. 7 at
5). To the contrary, EPA has determined that DCVA need not be included
in drinking water assessments for zeta-cypermethrin or other
pyrethroids.
DCVA is the hydrolysis product of several pyrethroids (permethrin,
cypermethrin, zeta-cypermethrin, cyfluthrin). It is the acid portion of
these insecticides (which are esters) and its full chemical name is 3-
(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid. Although
it is significantly more mobile than the parent pyrethroids, EPA has
not included it in drinking water assessments for the following
reasons.
(1) Based on its structure (i.e., lacking the ester function in the
parent insecticides), it would be devoid of the neurotoxic properties
of the parent and thus, it would not be of significant concern with
respect to the neurotoxicity endpoints on which the dietary risks of
the pyrethroids are assessed.
(2) Mutagenicity and acute toxicity data have been provided for
DCVA. The submitted salmonella reverse mutation assay (Ames assay)
conducted with DCVA indicated that the compound was negative in the
presence and absence of metabolic activation in all five tester
strains. The submitted acute oral toxicity study in rats conducted with
DCVA concluded that the acute oral LD50 is 1,609 mg/kg for
males and 1,192 mg/kg for females. These values are higher than those
for the parent cypermethrin compounds (cypermethrin: LD50 =
247 mg/kg for males, LD50 = 309 mg/kg for females; zeta-
cypermethrin: LD50 = 134.4 mg/kg for males, LD50
= 86.0 mg/kg for females).
(3) Although DCVA does contain the electrophilic dichlorovinyl
group which raises a potential concern with carcinogenicity, it is not
likely this compound is a carcinogen. The latter conclusion is based on
the different toxicity profiles of the parent pyrethroids which produce
DCVA in significant quantities. Cyfluthrin, permethrin, and zeta-
cypermethrin/cypermethrin are all extensively metabolized by cleavage
of the ester linkages with formation of DCVA as shown by the amount and
nature of the radioactivity appearing in urine of rats. In the case of
cypermethrin, similar metabolism and pharmacokinetics are observed in
mice and dogs. As a result, toxicological testing of the parent
compounds results in testing of DCVA at approximately one-third of the
dose of the parent on a weight basis. In spite of that fact, the parent
compounds have markedly different profiles of toxicity. For example,
using an earlier cancer classification system, cyfluthrin is a category
E carcinogen (i.e., no evidence of carcinogenicity), zeta-cypermethrin
is category C (i.e., possible human carcinogen), and permethrin is
category C(q) (i.e., possible human carcinogen with sufficient evidence
to quantify cancer risk). On this basis, the common metabolite DCVA is
not likely to be carcinogenic.
(4) Even though DCVA is more mobile than its parent compounds, it
is expected to reach groundwater in very low levels. Exposure is
further mitigated by the DCVA's high polarity and the likelihood of it
being readily excreted from the body due to the presence of the
carboxylic acid group.(Refs. 63, 64 and 65)
d. Diflubenzuron--Residue data on two metabolites. NRDC states that
there is a data gap for residue chemistry data on two diflubenzuron
metabolites. (Ref. 7 at 6). As discussed in Unit VII.C.3.a. of this
document, the only missing data at the time of the tolerance action was
Agency validation of the analytical enforcement method. The Federal
Register notice does note, however, that the analytical enforcement
methods have been successfully validated independently, (67 FR at 7090;
Ref. 66). The Agency validation has now been successfully completed.
(Ref. 67). In any event, a second validation is conducted by EPA not
for the purposes of refining its risk assessment but to insure that the
procedures for conducting enforcement monitoring are adequately
described so that accurate and reproducible results can be produced by
enforcement personnel. Accordingly, this objection is without merit.
e. Acetamiprid--oral exposure from residential uses. NRDC asserts
that EPA is missing data bearing on oral exposure to acetamiprid from
residential uses of the pesticide. (Ref. 9 at 6). The Federal Register
notice on the contested acetamiprid tolerance notes that ``incidental
oral exposure is an insignificant pathway of exposure'' for
acetamiprid. (67 FR at 14657, March 22, 2004). Little or no incidental
oral exposure is expected since acetamiprid's residential uses are
limited to ornamentals, flowers, vegetable gardens, and fruit trees.
Incidental oral exposure to pesticides can occur when young children
engage in ``mouthing'' behavior (i.e. repeatedly placing their hands or
other objects in their mouth) in a location where a pesticide is
present. EPA assumes that incidental oral exposure to a pesticide
[[Page 46728]]
may occur when a pesticide is used to treat a home lawn because young
children frequently play on home lawns. EPA, however, considers it
unlikely that young children would spend an extended time in flower,
vegetable, or ornamental gardens, and thus treatment of such gardens
with a pesticide is not likely to lead to a significant exposure to
children by the incidental oral route.
EPA would note that NRDC was mistaken in its objections when it
claimed that EPA estimated the MOE for short- and intermediate-term
residential exposure to be 189 for adults and 239 for children aged 10-
12. (Ref. 9 at 9-10). As the Federal Register notice made clear the
MOEs for these two groups are 1,858 and approximately 3,000,
respectively, for pesticide exposures in food and 18,000 and 23,000,
respectively for non-dietary pesticide exposures. (67 FR at 14657).
6. Missing risk assessments. As to several of the pesticides, NRDC
has claimed that there is a data gap for a specific type of risk
assessment (e.g., short-term residential risk assessment) and that
therefore the full 10X children's safety factor must be retained. There
are two problems with this argument. First, a risk assessment is not
data or information that is required to be submitted to EPA but rather
an analysis of the data and information that is submitted. Thus, NRDC
has mislabeled these allegedly missing risk assessments by calling them
``data gaps.''
Second, and more important, NRDC appears to have misread the
relevant Federal Register notices in reaching the conclusion that
various risk assessments are missing. In some cases, risk assessments
that are claimed to be missing were performed and were described in the
pertinent Federal Register notice. In other cases, NRDC may have been
confused by language in Federal Register notices that states a certain
risk assessment was not conducted or performed. In conducting the
safety evaluation required by section 408, EPA performs various risk
assessments depending on the types of risks posed by a pesticide and
the varieties of exposure routes related to its use. The number and
scope of risk assessments may vary considerably from pesticide to
pesticide. Language that a risk assessment was not required or
performed has been frequently used by EPA to indicate circumstances
where a quantitative risk assessment was not needed either because the
pesticide did not present a particular hazard (e.g., a quantitative
acute risk assessment is not performed for a pesticide not judged to
pose a risk due to a one-day or single exposure) or there was no
exposure (e.g., a residential risk assessment is not performed when the
pesticide does not have residential uses). As explained below, in each
instance where NRDC objected to a ``missing'' risk assessment, EPA had
either performed the risk assessment or determined that such risk
assessment was not needed.
a. Halosulfuron-methyl. NRDC claims that EPA, in evaluating
halosulfuron, failed to conduct a cancer risk assessment, and short-
term and intermediate-term residential risk assessments for children
and for adults. (Ref. 6 at 5). As an initial matter, EPA questions the
relevance of this argument to the children's safety factor given the
fact that EPA treats cancer as a non-threshold effect unless data show
otherwise, and the children's safety factor only applies to threshold
effects. (See 21 U.S.C. 346a(b)(2)(C)). NRDC has not contended that
halosulfuron-methyl is a non-threshold carcinogen. In any event, based
on its qualitative assessment of the data bearing on cancer, EPA
concluded that halosulfuron-methyl was not likely to be a human
carcinogen, and therefore did not conduct a quantitative risk
assessment. (66 FR at 66338, Dec. 26, 2001). As to the missing short-
term and intermediate-term risk assessments, those risk assessments
were performed and summarized on pages 66337 and 66338 of the Federal
Register notice to which NRDC filed objections. (Id. at 66337-66338).
b. Bifenazate. NRDC asserts there is a data gap for a developmental
toxicity assessment for bifenazate. (Ref. 7 at 5). NRDC appears to be
referring to language in the Federal Register notice establishing the
contested bifenazate tolerances that states that ``a clear assessment
of developmental toxicity was not possible'' in the range-finding study
used to choose dose levels for the main developmental toxicity study in
rabbits. (67 FR at 4915). The statement ``a clear assessment of
developmental toxicity was not possible'' in the range finding study is
an error in the Data Evaluation Record (Ref. 68) since a detailed
assessment of developmental toxicity is not performed in the range
finding study. The objective of this study is to demonstrate definite
maternal toxicity and to guide selection of dose levels for the main
study regarding development toxicity in rabbits. This main study was
submitted and considered in conducting the risk assessment for
bifenazate. (67 FR at 4914). The study showed no developmental toxicity
at 200 mg/kg/day (highest dose tested). The doses tested in this study
was judged to be adequate since abortions were seen at >=250 mg/kg/day
and decreases in body weight seen at doses >=500 mg/kg/day in the
range-finding study. This study provided a clear assessment of
developmental toxicity in rabbits for bifenazate.
c. Isoxadifen-ethyl. NRDC claims that short-term and intermediate-
term residential risk assessments are missing for isoxadifen-ethyl.
(Ref. 9 at 6). As the relevant Federal Register notice notes, however,
EPA determined these residential risk assessments were not necessary
because isoxadifen-ethyl is not approved for any residential uses. (67
FR at 33185).
d. Propiconazole. NRDC argues that there is a data gap for all
residential risk assessments for propiconazole. (Ref. 9 at 6). For
propiconazole, EPA did quantitatively assess the short-term and
intermediate-term residential risks resulting from the treatment of
wood with propiconazole. (64 FR at 2999, January 20, 1999). EPA
determined it was unnecessary to assess quantitatively short-term and
intermediate-term residential risks connected with the turf use of
propiconazole because of the unlikelihood of exposure. (Id.). EPA
considered exposure to be minimal due to a combination of a number of
factors: (1) Propiconazole is infrequently used on lawns; and (2) even
when used, it is generally applied by lawn care operators rather than
homeowners.
e. Fenhexamid. NRDC claims that short-term and intermediate-term
residential risk assessments are missing for fenhexamid. (Ref. 9 at 6).
As the relevant Federal Register notice notes, however, EPA determined
these residential risk assessments were not necessary because
fenhexamid is not approved for any residential uses. (67 FR at 19118,
April 18, 2002).
f. Fluazinam. NRDC argues there is a data gap for a cancer risk
assessment for fluazinam. (Ref. 9 at 6). As with its objection
concerning the halosulfuron-methyl cancer risk assessment, EPA
questions the relevance of this argument to the children's safety
factor decision. NRDC has not contended that fluazinam is a non-
threshold carcinogen. In any event, EPA did qualitatively assess the
cancer potential of fluazinam and found that the data showed, at most,
suggestive evidence of carcinogenicity but that the evidence was not
strong enough to warrant quantifying this risk. (67 at 19128, April 18,
2002). This decision was based on the fact that there was equivocal/
some evidence of carcinogenicity in one species and one sex. Thyroid
tumors were seen in male rats, but not in female rats, while liver
tumors were seen in male mice but not
[[Page 46729]]
in female mice. In addition, fluazinam was negative in mutagenicity
assays. (Ref. 69).
g. 2,4-D. NRDC claims that short-term and intermediate-term
residential assessments have not been completed for 2,4-D. (Ref. 8 at
8). This claim is not supported by the record. The Federal Register
notice associated with the challenged tolerances summarizes EPA's
short-term residential risk quantitative assessment, (67 FR at 10629,
March 8, 2002), and explains why no intermediate-term exposure, and
hence no intermediate-term risk, is expected, (Id. at 10627).
7. Conclusion on children's safety factor objections. After
examining each of NRDC's objections, EPA has found no basis in the
objections to revise its conclusions regarding the children's safety
factor as to the 13 pesticides.
C. LOAEL/NOAEL
NRDC argues that EPA cannot legally make the reasonable certainty
of no harm finding for pymetrozine, mepiquat, zeta-cypermethrin, and
fluazinam because EPA has relied on a LOAEL in assessing the safe level
of exposure to the pesticide. NRDC claims EPA ``cannot lawfully
establish tolerances in the absence of a no-observed-effect-level
(NOEL).'' (Ref. 7 at 18). Implicit in this argument is that EPA cannot
use a no-observed-adverse-effect-level (NOAEL) in making a safety
finding. In later objections, NRDC confirmed that in fact it was
contending that section 408's safety standard does not permit EPA to
rely on a NOAEL in concluding a tolerance is safe. Rather, according to
NRDC, EPA may only make a safety finding for a pesticide where EPA has
determined the dose in animals at which no effects, adverse or
otherwise, are elicited from exposure to the pesticide. (Ref. 7 at 17-
18). Below EPA identifies the flaws in NRDC's generic argument
concerning LOAELs and NOAELs and addresses the pesticide-specific
concerns NRDC raises with regard to use of a LOAEL as to pymetrozine,
zeta-cypermethrin, and fluazinam.
1. Generic legal argument. EPA believes that it can make a
reasonable certainty of no harm finding based on a LOAEL from an animal
study (where no NOAEL or NOEL was found) in appropriate circumstances.
Whether or not a reasonable certainty of no harm finding can be made
when only a LOAEL is identified in a study depends on whether EPA has
sufficient toxicological evidence to estimate with confidence a
projected NOAEL that is unlikely to be higher than the actual NOAEL.
Typically, when a LOAEL but not a NOAEL has been identified by a study,
EPA will, when the data support it, project a NOAEL for that study by
dividing the LOAEL by a safety factor.
There is nothing in the statutory safety standard explicitly
addressing the use of NOELs, NOAELs, or LOAELs. Moreover, nothing in
the phrase ``reasonable certainty of no harm'' legally precludes use of
NOAELs or LOAELs to make a finding regarding the likelihood that harm
will occur at a given dose. Whether a NOAEL or LOAEL provides a
sufficient basis for a reasonable certainty of no harm finding is a
question of scientific fact. EPA fully responded to the arguments
raised by NRDC in the Imidacloprid Order, (69 FR at 30066-30067, May
26, 2004), and incorporates that response herein.
2. Objections pertaining to specific pesticides--a. Pymetrozine.
NRDC asserts that EPA unlawfully relied upon a LOAEL in assessing both
short-term risk and acute risks to pymetrozine. (Ref. 6 at 9). NRDC is
correct that EPA used the LOAEL from an acute neurotoxicity study with
pymetrozine to assess both the acute dietary risk and short-term
residential risk for the general population. (Acute risk to the
developing fetus, however, was based on the developmental study in the
rabbit which had a NOAEL.) (Ref. 70). To ensure that there would be a
reasonable certainty of no harm, EPA retained two additional 3X safety
factors in assessing acute risk to the infants and children. (Id. at
18). This decision was based both on the lack of a LOAEL from the acute
neurotoxicity study and the absence of a required DNT study. The
protectiveness of this approach is demonstrated by the fact that the
LOAEL from the acute neurotoxicity study used for conducting the safety
assessment for acute risk faced by the general population is only
higher by a factor of 2 than the NOAEL from the subchronic
neurotoxicity study. Retaining what is essentially a 10X safety factor
results in a projected acute NOAEL five times lower than the NOAEL
found in a subchronic study measuring the same endpoint. Thus, this
projected NOAEL is more conservative for a single exposure than the
measured result in the repeated exposure study (i.e., 13 weeks).
Syngenta, the registrant for pymetrozine, defends EPA's reliance on
a LOAEL here noting that the effects observed at the LOAEL ``were
reversible and not of severe magnitude (for example, body temperature
was decreased at the LOEL, but only by about 2 percent compared to
controls).'' (Ref. 18 at 5). EPA agrees that the severity of the effect
at the LOAEL should be considered in the weight of the evidence
regarding a safety determination and relied on the lack of severity and
reversibility in its determination on pymetrozine. (Ref. 71).
b. Mepiquat. NRDC claims that for mepiquat EPA ``measured
reproductive toxicity only on the basis of a LOAEL.'' (Ref. 7 at 18).
NRDC was mislead, however, by the Federal Register notice's description
of the rat reproduction study which states: ``The study did not
establish a reproductive NOAEL; however, the systemic NOAEL of 1,500
ppm would also be regarded as the reproductive NOAEL.'' (65 FR at 1792,
January 12, 2000). This was an error by EPA in preparing the Federal
Register notice. In fact, in the two-generation reproduction study, the
NOAEL for reproductive toxicity was 5,000 ppm (highest dose tested); a
LOAEL was not established. (Ref. 72).
c. Zeta-cypermethrin. NRDC argues that EPA relied upon a LOAEL from
a zeta-cypermethrin developmental toxicity study. (Ref. 7 at 18). NRDC,
however, is mistaken. In the four developmental studies conducted with
cypermethrin and zeta-cypermethrin in rats and rabbits, no
developmental effects were observed at the highest dose tested. (Ref.
73). Maternal toxicity was seen in all four studies. NRDC may have been
mislead by an error in one of the data tables in the Federal Register
that lists the NOAEL for one of the four developmental studies as <35
mg/kg/day.'' (66 FR at 47981, September 17, 2001 (Table 2)). The table
should have read >= 35 mg/kg/day. (Id.)
d. Fluazinam. NRDC claims that for fluazinam EPA relied upon a
LOAEL in assessing dermal toxicity and that only a LOAEL was achieved
in dietary studies in mice and rats. (Ref. 9 at 18). NRDC is correct
that a dermal NOAEL (as distinguished from a systemic NOAEL) was not
found in the 21-day dermal toxicity study. (67 FR at 19121, April 18,
2002). Nonetheless, EPA did not rely on the LOAEL from this study in
setting the fluazinam tolerances because there are no residential uses
for fluazinam and dermal toxicity is only relevant to exposure
occurring in the residential setting. Moreover, the data were
sufficient to set a systemic NOAEL from dermal exposure, as opposed to
a NOAEL for dermal effects. (Ref. 58 at 14). A systemic NOAEL is the
information needed to conduct an aggregate risk assessment. EPA had
adequate data on oral toxicity for evaluating dietary exposure.
As to not achieving a NOAEL in dietary studies with mice and rats,
NRDC appears to be referring to a 4-week dietary range-finding study in
[[Page 46730]]
mice and a special 90-day liver study in rats. The lack of a NOAEL in
these studies is irrelevant to the fluazinam risk assessment. The lack
of a NOAEL in the mouse study is not a concern because it is a range
finding study (i.e. a preliminary study used to gauge dosing for
another study) and the LOAEL (555 mg/kg/day) is approximately 50-fold
higher than the LOAEL (10.7 mg/kg/day) and the NOAEL (1.1 mg/kg/day) in
the chronic mouse study which was used establishing the chronic RfD.
(67 at 19121, April 18, 2002 (Table 1)). The 90-day study in rats was a
special non-guideline study (not requested by EPA) that tested one
relatively high dose level (500 ppm) to evaluate the hepatotoxic
effects of fluazinam and determine their reversibility. It was not
considered for the purpose of determining a NOAEL and a RfD. Because
the study only resulted in the modest liver changes of questionable
toxicologic significance it was of marginal value. (Refs. 74 and 75)
Neither of these studies were used for overall risk assessments (Ref.
46).
e. Isoxadifen-ethyl, acetamiprid, propiconazole, furilazole, and
fenhexamid. NRDC has lodged a blanket legal objection to the use of
NOAELs in assessing the risk to isoxadifen-ethyl, acetamiprid,
propiconazole, furilazole, and fenhexamid. (Ref. 9 at 18). NRDC has
offered no factual evidence or argument as to why reliance on these
specific NOAELs invalidates EPA's safety determination. Accordingly,
EPA denies this objection for the reasons given above and in the
Imidacloprid Order, (69 FR at 30066-30067, May 26, 2004), for rejecting
the argument that EPA is barred, as a matter of law, from using NOAELs
in assessing the safety of pesticide residues.
D. Aggregate Exposure
1. Worker exposure. EPA has interpreted ``aggregate exposure'' to
pesticide residues not to extend to pesticide exposure occurring at the
workplace based on the language in section 408(b)(2)(D) explaining what
exposures are included in the term ``aggregate exposure:''
[T]he Administrator shall consider, among other relevant factors
- . . . 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 the dietary exposure under the tolerance and all other
tolerances in effect for the pesticide chemical residue, and
exposure from other non-occupational sources . . . .
This language quite plainly directs EPA to limit consideration of
aggregate exposure of pesticide residues and other related substances
to those exposures arising from non-occupational sources. NRDC's claim
that EPA erred by not considering worker risks in making tolerance
decisions under section 408 runs afoul of Congress' explicit mandate
that such exposures not be included. Although there is some ambiguity
as to precisely how the factors listed in section 408(b)(2)(D) relate
to the safety finding described in section 408(b)(2)(A)(ii), for the
reasons set forth in the Imidacloprid Order, (69 FR at 30067-30068, May
26, 2004), NRDC's interpretation of the statutory language is
unreasonable.
2. Classification of farm children as a major identifiable
population subgroup. NRDC points out that FFDCA section 408 directs EPA
to consider not just the general population in assessing aggregate
exposure but also ``major identifiable subgroups of consumers.'' (21
U.S.C. 346a(b)(2)(D)(vi)). In this regard, NRDC argues that children
living in agricultural communities should be treated as such a major
identifiable subgroup. These children are an identifiable subgroup,
according to NRDC, because of the allegedly heightened exposure to
pesticides that they receive due to their proximity to farm operations
and farm land and, for some, due to their contact with parents involved
in agriculture. (Ref. 9 at 11-12). NRDC claims these children comprise
a ``major'' subgroup citing statistics showing that ``320,000 children
under the age of six live on farms in the United States[], . . . many
hundreds of thousands of children play or attend schools on or near
agricultural land, . . . [and] [t]he nation's 2.5 million farm workers
have approximately one million children living in the United States.''
(Id.)
Whether or not EPA attaches the label ``major identifiable
subgroup'' to farm children, EPA's risk assessment approach to
children, including the major identifiable subgroups of children used
in its risk assessments, adequately takes into account any pesticide
exposures to children - whether as a result of living close to
agricultural areas or otherwise. For some time, EPA has treated infants
and children grouped by ages (e.g., infants younger than 1 year,
children 1 - 2 years) as major identifiable subgroups. These age
groupings have been chosen to reflect different eating patterns of the
age groups. In evaluating exposure to these or any other subgroup,
however, EPA considers the range of exposures across the subgroup not
just as a result of pesticide residues in food but from all non-
occupational exposures. If a significant number of any of the
population subgroups of children have higher exposures due to a non-
food source (e.g., residential uses of a pesticide, proximity to
agricultural areas), EPA believes that that exposure is appropriate to
consider in evaluating the range of exposures for the subgroup. The
fact that the children in the subgroup receiving the higher exposures
are not themselves labeled a major identifiable subgroup in no way
lessens EPA's consideration of their exposures. Further, EPA questions
whether NRDC has properly characterized farm children as a major
identifiable subgroup in that it is not at all clear that the members
of this group are readily identifiable nor does the evidence support
that this group consistently receives higher pesticide exposures. These
issues are discussed in greater depth in the Imidacloprid Order and
that discussion is incorporated herein. (69 FR at 30068-30069, May 26,
2004).
3. Adequacy of EPA's assessment of the aggregate exposure of
children, including children in agricultural areas. EPA believes that
it has adequately assessed the aggregate exposure of children to the 13
pesticides (including both farm children and non-farm children),
through its assessment of exposure through food, drinking water and
residential use pathways. In support of its objection to this
assessment, NRDC cites numerous studies for the proposition that other
pathways (e.g., track-in) increase farm children's exposures, and it
also cites information purportedly suggesting that volatilization and
spray drift lead to higher exposures among farm children. For reasons
discussed above (see Unit VII.B. and C.), and in the Imidacloprid
Order, however, EPA does not believe that the epidemiological data
relied upon demonstrate that the pathways asserted, to the extent they
exist, lead to farm children experiencing pesticide exposure levels
significantly higher than those experienced by other children. Rather,
these studies are largely inconclusive, and to the extent they show
anything, tend to suggest that farm children and non-farm children
generally receive similar levels of exposure.
Further, EPA's evaluation of the potential additional exposure to
the 13 pesticides challenged in these objections from spray or
volatilization drift showed little likelihood of significant exposure.
In any event, an overly conservative (health-protective) estimate of
overall drift, food, water, and residential exposures shows no safety
concerns for any of these pesticides.
[[Page 46731]]
4. Residential exposure as a result of use requiring a tolerance.
NRDC also argues that EPA has erred in not assuming that additional
residential exposure occurs each time an additional agricultural use is
added. The reasons explained above as to why any additional exposure to
children as a result of their proximity to farming operations is
expected to be insignificant as regards the 13 pesticides apply with
equal or more force as to this contention.
5. Anticipated residues/exposures due to purchase of food at farm
stands. NRDC claims that EPA has underestimated aggregate exposure for
several of the pesticides because EPA used ``anticipated residues'' for
estimating exposure rather than assuming residues would be at the
tolerance level. NRDC argues that ``EPA must ensure that the legal
level of pesticide chemical residue - the established tolerance levels
- are themselves safe.'' (Ref. 9 at 20). Additionally, NRDC asserts
that using ``anticipated residues'' does not take into account the
``significant number of consumers who purchase produce at farmers
markets, farm stands, and `pick-your-own' farming operations.'' (Ref. 9
at 19). NRDC cites information from the National Association of
Farmers' Market Nutrition Programs indicating that 1.9 million people
purchase food from farm stands.
NRDC is wrong in its assertion that EPA must assume all residues in
food are at tolerance levels in assessing the safety of tolerances. The
statute is quite clear that EPA may consider data on anticipated or
actual pesticide residue levels in establishing tolerances. (21 U.S.C.
346a(b)(2)(E)). This statutory provision essentially codifies EPA
practice developed and implemented over the last 20 years.
EPA's approach to estimating exposure for tolerance risk
assessments, at least as far back as the late 1980's, is to first make
a worst case assessment of the exposure, and then, only if this worst
case exposure assessment indicates that there might be risk concerns
would EPA undertake a more sophisticated assessment using more
realistic data such as data on ``anticipated residues.'' (See Ref. 76).
Worst case exposure was designated by EPA as the Theoretical Maximum
Residue Level (TMRC) and was calculated by assuming all foods covered
by tolerances had residues at the tolerance level. (See, e.g., 59 FR
54818, 54820, November 2, 1994; (metalaxyl tolerance); 50 FR 26683,
June 27, 1985; (chlorpyrifos-methyl tolerance)). When such an
assessment shows no risks of concern, EPA's resources are conserved
because a more complex risk assessment is avoided 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.'' (Ref. 76 at 1; see, e.g., 54 FR
33044, 33045, August 11, 1989) (iprodione tolerance)).
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.
For example, the 2001 USDA Agricultural Chemical Usage survey notes 14
insecticides used on tomatoes with percent crop treated values ranging
from 2 to 26 percent, including 9 insecticides used on less than 10
percent of the crop. In another example, the survey notes 39 herbicides
used on corn with percent crop treated values ranging from less than 1
to 68 percent, including 32 herbicides used on less than 10 percent of
the crop. (Refs. 77 and 78). Obviously, if a portion of a crop is not
treated, food from that portion of the crop will not contain residues.
Second, for that portion of the crop that is treated, residues on
most treated commodities are likely to be significantly lower than the
tolerance value, even when the pesticide is applied in the manner and
amount permitted by the label that is likely to yield the highest
possible residue [hereinafter referred to as a ``maximum residue
application'']. EPA's general practice is to set tolerance values just
slightly above the highest value observed in crop field trials
conducted using maximum residue applications. For example, based on the
hypothetical pesticide residue data set in Figure 1, EPA would set the
tolerance value at 4 ppm or slightly higher. As Figure 1 illustrates,
there may be some commodities from a treated crop that approach the
tolerance value where the maximum residue applications are followed,
but most commodities generally fall significantly below. In fact, EPA's
experience is that crop field trial data generally does not sort out
into a normal, bell-shaped distribution; rather, the distribution when
plotted based on frequency/probability (Y axis) and level of residues
(X axis) is generally ``log-normal'' or ``right-skewed'' - that is,
there is a clumping of values close to, or on, the Y axis (i.e.
approaching non-detectable residues) with a few higher values out
farther on the X axis (i.e. approaching the tolerance value) resulting
in a long ``tail'' stretching out to the right. (Ref. 4 at 12, Ref. 79
and Ref. 80 at 10). Figure 1 presents a hypothetical example of how
residue data generally fall in a right-skewed curve.
[[Page 46732]]
[GRAPHIC] [TIFF OMITTED] TR10AU05.066
Third, if less than the maximum residue application is followed
(e.g., lower than the maximum amount applied, applications are not as
frequent as allowed, the pre-harvest interval after the last
application exceeds thelegal minimum), residues will be even lower than
measured by crop field trials using maximum residue applications.
Essentially, the entire distribution curve illustrated in Figure 1
shifts to the left. Finally, residue levels measured 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. (Ref. 4 at 14, and Ref. 79).
EPA uses several techniques to refine residue value estimates from
worst case levels to more realistic levels. (See Ref. 1 at 10-12).
First, where appropriate, EPA may take into account all the residue
values reported in the crop field trials, either through use of an
average or individually. Second, EPA may consider data showing what
portion of the crop is not treated with the pesticide. Third, data may
be produced showing pesticide degradation and decline over time, and
the effect of commercial and consumer food handling and processing
practices. Finally, EPA may consult monitoring data gathered by FDA,
the US Department of Agriculture, or pesticide registrants, on
pesticide levels in food at points in the food distribution chain
removed from the farm, including retail food establishments. EPA's
experience has been that, even without the use of probabilistic risk
assessment techniques discussed below, reliance on these refinements,
and particularly use of food monitoring data, reduces exposure and risk
estimates by over a order of magnitude. (See 55 FR 20416, 20422, May
16, 1990) (``Earlier registrant residue monitoring studies and FDA and
State monitoring studies indicate that [EBDC] residues may be 1 to 2
orders of magnitude lower than the Agency's current residue
estimates.''); 54 FR 22558, 22565, May 24, 1989) (using a residue value
of 1 ppm from market basket survey to assess risk of daminozide on
apples; tolerance value was 20 ppm, 40 CFR 180.246(b)(1989)); (Ref.
79).
In the FQPA, Congress essentially adopted EPA's approach, including
EPA's terminology with the slight change that it labeled one category
of anticipated residue data, monitoring results, as ``actual residue
data.'' (See 21 U.S.C. 346a(b)(2)(E)(1) (designating that data on
actual residues measured in food ``includ[es] reside data collected by
the Food and Drug Administration'')).
That Congress was codifying existing practice is confirmed by the
legislative history of the FQPA. EPA's use of anticipated residue data
had been questioned by some and several bills were introduced that
essentially prohibited EPA from using its traditional risk assessment
approach. For example, H.R. 1725, a bill introduced in the 101st
Congress, directed that ``in calculating dietary exposure to the
pesticide chemical residue in or on the raw agricultural commodity or
processed food for which the tolerance is proposed or is in effect, the
Administrator shall consider the level of exposure to be the amount of
exposure that would occur if all the commodities and food for which the
pesticide chemical residue has a tolerance have amounts of pesticide
chemical residues equal to their respective tolerances. . . .'' (H.R.
1725, 101st Cong. section 4 (establishing a new section
408(b)(2)(C)(ii)) (1989) (an exception to this bar on the use of
anticipated residue data was allowed if a second tolerance was
established to insure residue levels did not exceed the levels used to
calculate dietary exposure); see S. 722, 101st Cong. section 4
(establishing a new section 408(b)(2)(C)(ii)) (1989) (same)). A similar
approach was taken in the Clinton Administration proposal in 1994.
(H.R. 4362, 103d Cong. section 3 (establishing a new section
408(b)(2)(B)(i)) (the Administrator shall assume that the food bears or
contains residues of the pesticide chemical equal to the level
established by the tolerance set at the point closest to the time the
food is purchased); see also S. 2084, 103d Cong., section 3
(establishing a new section 408(b)(2)(B)(i)) (same)). However, this
approach was not included in the bill passed in 1996 as the FQPA.
Rather, Congress specifically authorized EPA to consider ``anticipated
residues,'' terminology EPA had long regarded as describing evidence
demonstrating the residues were below tolerance levels.
NRDC is also incorrect in its claim that failure to focus on food
purchased at farm stands will vastly underestimate dietary exposure to
pesticides. This underestimation occurs, according to NRDC because EPA
does not take into account that a significant number of consumers buy
produce at farm stands. Even assuming that food consumed as a result of
purchases at farm stands
[[Page 46733]]
constitute more than a negligible amount of the diet, NRDC's claims
here are inaccurate whether EPA is relying on anticipated residues
estimated based on crop field trials or monitoring data. Crop field
trials measure residue levels at harvest after use of application rates
and procedures that will produce maximum residues under the currently-
approved pesticide label. Thus, anticipated residue values from crop
field trials, if anything, will overstate the values found at farm
stands or U-pick farms. Even where EPA uses monitoring data it is
likely to differ little from the values at farm stands or U-pick farms.
The monitoring data EPA relies upon most frequently is from the
Pesticide Data Program (PDP) run by USDA. PDP data is extensive and
covers a wide spectrum of residue values. Samples are generally
collected at wholesale and central distribution points prior to
distribution to supermarkets and grocery stores. For fresh produce, the
type of food most likely to be found at a farm stand or U-pick farm,
rapid distribution is critical and thus central food distribution
points are likely to very close to the farm in terms of time from
harvest. This would be particularly true for those commodities which
are transported quickly from farm to distribution center under
controlled-environment conditions (e.g., strawberries, blueberries).
For all of these reasons, EPA concludes that its exposure estimates are
not likely to understate exposure without use of specific data on
residue levels at farm stands and U-pick farms.
6. Population percentile used in aggregate exposure estimates--a.
In General. NRDC contends that EPA in making the reasonable certainty
of no harm finding must make such a finding as to ``all children'' --
that is, EPA must find that ``no children will be harmed'' by exposure
to the pesticide. Although EPA is somewhat uncertain as to precisely
what approach to risk assessment and safety findings NRDC is
advocating, EPA believes that its approach to implementing the
reasonable certainty of no harm standard is consistent with the
statutory framework. As specified in the statute, EPA focuses its risk
assessment and safety findings on major identifiable population
subgroups. (21 U.S.C. 346a(b)(2)(D)(vi)). For children EPA has
identified the following subgroups: nursing infants (0-6 months); non-
nursing infants (6 months - year); 1-2 year-olds; 3-5 year olds; 6-12
year olds; and 13-19 year olds. EPA evaluates each of these subgroups
to determine if it can be determined that there is a reasonable
certainty of no harm for individuals in these subgroups. (See Refs. 2
at 40; and 1 at 14).
b. Choice of population percentile. NRDC asserts that EPA erred by
allegedly making its safety decision as to the acute risk posed by
pymetrozine, mepiquat, isoxadifen-ethyl, acetamiprid, and furilazole
based on only a portion of the population, leaving the rest of the
population unprotected. According to NRDC, EPA only considered 95
percent of the affected population. This argument was rejected in the
Imidacloprid Order, and EPA incorporates the reasoning used there. (69
FR at 30070-30071, May 26, 2004).
EPA relies on population percentages as one of several inputs in
estimating the full range of exposures in each population subgroup and
not because it has concluded that a certain percentage of the
population is unworthy of protection. As EPA explained in its
Imidacloprid Order:
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. When inputs for pesticide residue values in
the exposure estimate are high end (e.g., assuming all food contains
tolerance level residues), a lower percentile of exposure (e.g., 95
percent) is thought to be representative of exposure to the overall
population as well as subgroups. As increasingly realistic residue
values are used (e.g., information from pesticide residue
monitoring), a higher percentile of exposure (e.g., 99.9 percent) is
generally necessary to be protective of the overall population and
its subgroups.
(69 FR at 30070). As EPA pointed out, a risk assessment using the 95th
population percentile and worst case residue values is likely to
estimate much higher exposure levels than an assessment using the
99.9th population percentage and residue values from monitoring
studies. (Id. at 30071).
For each of the pesticides as to which NRDC raised concerns with
the use of the 95th population percentile for estimating exposure, EPA
estimated exposure using the gross overestimate of all crops covered by
the tolerance containing residues at tolerance levels. (66 FR at 66788,
December 27, 2001 (pymetrozine); 65 FR at 1790, 1792-93, January 12,
2000 (mepiquat); 66 FR 33179, 33184, June 21, 2001 (isoxadifen-ethyl);
67 FR at 14653, March 27, 2002 (acetamiprid); 67 FR at 15731, April 3,
2002 (furilazole)). Thus, EPA concludes it reasonably estimated
exposure in making its reasonable certainty of no harm finding for
these pesticides.
7. Alleged inadequacies pertaining to specific pesticides--a.
Pymetrozine. NRDC argues the EPA has underestimated aggregate exposure
to pymetrozine because (1) ``EPA assumes that a toddler's hand-to-mouth
exposure occurs very few times per hour;'' (2) EPA fails to consider
that children put other objects in their mouths beside their hands; and
(3) EPA ignores children's consumption of ```feral' food - food that
has been dropped on the floor and which picks up residues from
contaminated surfaces.'' (Ref. 6 at 8). NRDC is incorrect. First,
several years ago EPA modified its estimate of hand-to-mouth exposures
from 1.28/hour to 20/hour, a 90th percentile value. (Ref. 81). As to
the other types of oral exposures cited by NRDC, EPA's experience has
shown that any exposures that occurs in such a manner is
inconsequential beside the non-dietary oral exposures EPA estimates
through its models. In modeling toddler exposure, EPA assumes that the
toddler plays in the treated area engaging in repeated mouthing
behavior immediately after treatment. NRDC is referencing potential
exposures that may occur occasionally in areas inside the home and thus
well-separated from the treatment area (the lawn).
b. Bifenazate. NRDC claims that EPA relied upon ``unsupported and
apparently arbitrary processing factors to reduce estimates of dietary
exposure to bifenazate on apples and grapes.'' (Ref. 7 at 16). Further,
NRDC alleges that despite the fact that bifenazate is registered for
use on landscape ornamentals, EPA ignores this source of exposure.
(Ref. 7 at 17).
EPA's default processing factors are neither unsupported nor
arbitrary. EPA uses all available data and analyzes it in a manner to
ensure that the application of default processing factors will not
understate pesticide exposure. In fact, EPA's manner of applying
default processing factors tends to exaggerate greatly exposure levels
in processed food compared to the level of residues that is actually
present.
Default processing factors are a numerical measure of the potential
of pesticide residues to concentrate in processed foods when a raw food
is partitioned into its component fractions. They are derived from the
weight-to-weight ratio of raw and processed commodities and intended to
reflect the highest potential concentration of pesticide residue that
can occur. In calculating default processing factors EPA assumes that
concentration will be inversely proportional to the reduction of weight
(mass) that occurs during processing (e.g., if processing reduces
[[Page 46734]]
the mass of processed commodity proportional to the raw commodity by 50
percent, the default processing factor would be 2X). Importantly, EPA
applies default processing factors using the worst case assumption that
all pesticide residue in the raw commodity remains in any commodity
processed from such raw commodity. Thus, if the raw food contains 2 ppm
of a pesticide and the default processing factor for a processed
commodity from such raw food is 2X, EPA will assume that the processing
commodity contains 4 ppm of the pesticide. The 4 ppm estimate should be
regarded as a theoretical upper bound level, however, because actual
processing data generally shows residues are reduced during processing,
or at least not concentrated at EPA's theoretically-derived default
level (i.e., the inverse proportion of reduction in mass of the
processed commodity). EPA's use of default processing factors further
exaggerates residue estimates in processed food because EPA assumes
that each processed commodity from a raw food contains all of the
pesticide present in the raw food (with the precise level being
estimated by the default processing factor). (Refs. 82 and 83)
Several examples will help to elucidate how EPA calculates and
applies default processing factors. Perhaps the simplest example of how
EPA calculates default processing factors involves potatoes and dried
potato flakes. The default processing factor for potatoes is calculated
by determining the weight-to-weight ratio of whole potatoes to dried
potatoes. This ratio is assumed to be the concentration factor of the
pesticide in the dried potato. USDA information indicates that it takes
6.5 pounds of fresh potatoes to produce 1 pound of dried potato flakes.
Thus, the default processing factor for potato flakes is 6.5X and this
factor is multiplied times the residue level found in fresh potatoes to
estimate residues in potato flakes. This approach produces a worst case
estimate because it assumes that the processing process does not result
in any loss or degradation of the pesticide residues in or on the
potato - i.e, that the washing, peeling, heating, and drying that
occurs in the processing of fresh potatoes into potato flakes does not
result in any reduction in total pesticide residues.
The processing of potatoes also is a good example of how EPA
applies default processing factors in a manner that will exaggerate
estimates of pesticide levels in processed food. With potato
processing, EPA assumes that all of the pesticide residue in the raw
potato not only is translocated to the dried potato flakes but also is
present in the potato peel which is a byproduct of processing dried
potato flakes and is used as an animal feed. The level of residue
assumed for the peel is based, like the level for the flakes, on the
level of residue in the raw potato multiplied by the appropriate
default processing factor. Obviously, it is physically impossible for
all of the pesticide in the raw potato to be translocated to both the
dried flakes and the peel but in the absence of more specific data on
how the pesticide is distributed in the raw potato, EPA's approach is a
reasonable, health-protective measure. Similar methodology is employed
with other commodities that have a peel that itself is an edible
commodity for animals or humans, such as citrus.
A slightly different approach is used for deriving the default
processing factor for pome fruit, such as apples. For these
commodities, the default processing factor is calculated by dividing
the mass of the commodity that constitutes the processed commodity in
question into the mass of the entire commodity. For example, USDA data
indicates that the mass of a typical apple consists of 12.5 percent
solids and 87.5 percent intrinsic (biological) water. To calculate the
processing factor for apple juice, thus, the mass of the water (juice)
portion of the apple is divided into the mass of the entire apple
yielding a processing factor of 1.14X. Performing the same operation
for dried apple commodities, yields a processing factor of 8X. Like
with other raw commodities, to estimate residues in the processed
commodities derived from apples (apple juice, dried apple pomace), EPA
assumes all residue in the raw apple is translocated to each processed
commodity and estimates residue levels by multiplying the appropriate
default processing factor times the level of residue found in the fresh
apples.
Thus, NRDC is mistaken in its conclusion that EPA uses default
processing factors to reduce exposure estimates. To the contrary, EPA's
derivation and use of default processing factors will generally
overstate residue levels in processed commodities. NRDC's objection
here is not well taken.
EPA concluded that no significant residential exposure would occur
to the homeowner and family members as a result of the landscape
ornamental use because (1) application of the pesticide at this site is
restricted to commercial applicators; and (2) post-application exposure
is unlikely where the application is limited to ornamentals (e.g.,
bushes, shrubs). EPA routinely assumes post-application exposure may
occur with residential uses in such areas as on lawns or in vegetable
gardens where there is the potential for homeowners and family members
(other than young children as concerns vegetable gardens) to have
significant contact with the treated plant. Although in the past EPA
has occasionally conducted post-application exposure assessments for
ornamental uses, EPA's current view is that any post-application
exposure from such a use is likely to be minimal.
c. Zeta-cypermethrin. As to zeta-cypermethrin, NRDC claims that EPA
``wrongly ignores indoor and outdoor residential uses of cypermethrin
(which the agency states is toxicologically identical to zeta-
cypermethrin for the purposes of these tolerances).'' (Ref. 7 at 17).
NRDC, however, is mistaken in this allegation. EPA made clear in the
Federal Register notice associated with the challenged zeta-
cypermethrin tolerances that EPA combines residential exposures from
these two pesticides. As EPA explained:
The analytical method does not distinguish cypermethrin from
zeta-cypermethrin, and the toxicological endpoints are the same.
Therefore, dietary and non-dietary residential aggregate risk
assessment is conducted by adding the uses of the two chemicals.
(67 FR at 6426, 6427, February 12, 2002).
d. Diflubenzuron. NRDC asserts that EPA has underestimated
aggregate exposure to diflubenzuron because EPA concluded that
application of diflubenzuron to tree canopies would result in
negligible residential exposure to diflubenzuron. After review,
however, EPA reaffirms that these potential exposures are expected to
be limited. The label states that ``applications should be made during
periods of minimal use'' and requires users to ``Notify persons using
recreational facilities or living in the area to be sprayed before
application.'' Diflubenzuron is only applied by commercial applicators
to the tree canopy for control of gypsy moths and mosquitoes. Generally
applied by helicopter, these sprays are not aerosols or ultra low
volume sprays designed as space sprays, but are rather directed to the
tree canopy and designed to impinge on the tree tops where they would
be effective in pest control. The sprays designed for application to
tree canopies utilize much larger droplet sizes which are essentially
nonrespirable; therefore, minimal inhalation exposure to bystanders is
expected. Additionally, due to a low dermal absorption rate (0.5
percent), the potential for dermal exposure to bystanders is expected
to be minimal.
[[Page 46735]]
In any event, EPA would note that the results of the chronic
dietary analysis indicated that the estimated chronic dietary risk
associated with the proposed use of diflubenzuron was well below the
Agency's level of concern for the general U.S. population. In fact, the
highest exposed population subgroup (all infants <1 year of age) using
a very conservative (health-protective) estimate of exposure is 5.5
percent of the safe dose. An acute dietary exposure risk assessment was
not conducted since no hazard was identified for any population,
including infants and children, following a single exposure to
diflubenzuron (i.e., no hazard was identified, therefore,
quantification of risk is not appropriate).
e. 2,4-D. NRDC claims that ``EPA deliberately ignores known
residential uses in establishing new tolerances for 2,4-D . . . [by]
fail[ing] to assess and incorporate those residential uses as a source
of aggregate exposure, in violation of the FQPA.'' (Ref. 8 at 18). NRDC
cites to several studies allegedly demonstrating that when 2,4-D is
applied to turf, residues are tracked indoors and can lead to
``significant'' exposures. Citing a rat study, NRDC also claims that
children can be exposed to 2,4-D through mother's milk.
Contrary to NRDC's assertions, however, EPA did aggregate
residential exposures with food and water exposures to 2,4-D in
assessing its safety. EPA's quantitative aggregate assessment of the
short-term risk from residential uses appears at page 10629 of the
Federal Register notice establishing the challenged tolerance. (67 FR
at 10629, March 29, 2002). EPA did not aggregate residential exposures
in conducting an intermediate-term residential risk assessment because
data showed that intermediate-term exposure as a result of residential
uses was very low. (ID. at 10626.)
As to the study cited by NRDC on track-in exposures, EPA concludes
that, at most, these data indicated some degree of elevated seasonal
exposure but such exposure was minimal. (Ref. 33). The cited study
noted that its estimate of the combined exposure for all routes for a
10 kg child, whether looking at the maximum (8.871 micrograms/day
([mu]g/day) ) or median values (2.421 [mu]g/day), was well below safe
levels. By comparison, the exposure assessment for 2,4-D described in
Unit VII.B.2.a. estimates a 10 kg child would be exposed to 503 [mu]g/
day (excluding drift) and 756 [mu]g/day (including drift). EPA's
estimated exposure for a 10 kg child due to residential uses alone is
473 [mu]g/day. (Ref. 33 at 9). Thus, the cited study does not suggest
EPA is underestimating exposure. To the contrary, it demonstrates that
EPA's asssessment approach is very conservative (health-protective).
NRDC also expressed concern that nursing infants could be exposed
to 2,4-D in breast milk. (Ref. 8 at 7) NRDC cites to a study in rats
that showed 2,4-D in breast-fed neonates. (Ref. 84). EPA is aware, as a
result of animal feeding studies using exaggerated doses, that 2,4-D
may be present in milk. It is not surprising that the study relied upon
by NRDC suggests that 2,4-D is transmitted in breast milk given the
massive doses of 2,4-D in that study of 50, 70, 700 milligrams/kilogram
of body weight/day (mg/kg/day). By comparison, EPA estimates that the
maximum dietary exposure from food to human females ages 13-50 is
0.01018 mg/kg/day and the average exposure is 0.000642 mg/kg/day. (Ref.
61). These values range from 4,900 to 1 million times lower than the
values in the cited rat study.
Further, EPA's manner of doing risk assessment for infants is
protective of any pesticide exposure to infants from human breast milk
because the exposure values EPA assumes for pesticides in cow's milk
greatly exceed the values that could be present in breast milk. The
diet of non-nursing infants less than 1 year old still contains milk as
a primary component. Importantly, dairy cows exposure to pesticides
tend to be significantly higher than humans because residues in grass
forage are generally higher than in human foods. For example, the
tolerance for pastureland grass for 2,4-D is 1,000 ppm while the 2,4-D
tolerances for various human foods are all in the single digits. (See
40 CFR 180.142). Additionally, EPA tends to use very conservative
methods for calculating tolerance values and exposure levels in meat
and milk in cattle (e.g., relying on exaggerated feeding studies, use
of worst case diets) which overstate exposure.
For the 2,4-D risk assessment, EPA assumed that 2,4-D would be
present in milk at 0.004 ppm for both acute and chronic exposure. (Ref.
85). This value represents half of the level of detection from the
analytical method used in studies monitoring milk for 2,4-D residues.
No 2,4-D residues were detected in these studies, and in that
circumstance it is common practice to estimate exposure at half of the
level of detection. (Refs. 80 and 86). The conservative (health-
protective) nature of this exposure value can be seen by considering
data from a 2,4-D feeding study in cattle and what those data suggest
regarding the levels of 2,4-D present in rat milk in the cited study
and in human breast milk. What the cattle study showed was that cattle
fed a diet of 1,500 ppm 2,4-D had residues of 2,4-D in their milk at
the level of 0.07 ppm. (Ref. 87). Extrapolating from these figures,
2,4-D levels in rat milk in the cited study would have ranged from 0.05
ppm to 0.65 ppm. Taking into account that the dose levels in the rat
study were approximately 4,900 to 70,000-fold higher (50 mg/kg/day),
and 69,000 to one million-fold higher (700 mg/kg/day) than the
estimated maximum and average female 13-50 dietary exposure (0.01018
mg/kg/day and 0.000642 mg/kg/day), it is striking that the estimated
milk residue used to estimate dietary exposure to infants (0.004 ppm)
is only approximately 12-fold lower than the rat milk residue estimated
for the 4,900 - 78,000X exaggerated dose, and 162-fold less than the
rat milk residue estimated for the 69,000 - 1,000,000X exaggerated
dose. As to human breast milk, what the cattle study shows is that
given the maximum and average exposure levels of females ages 13-50 to
2,4-D, the expected maximum and average levels in breast milk are
roughly 200 and 4,000 times lower, respectively, than the exposure
value used for cow's milk. (Ref. 88). Thus, EPA concludes that its
aggregate exposure assessment was protective for all children,
including nursing infants.
f. Isoxadifen-ethyl, acetamiprid, fluazinam. Repeating the
allegations made as to bifenazate, NRDC argues that EPA relied upon
``unsupported and apparently arbitrary processing factors to reduce
estimates of dietary exposure'' for isoxadifen-ethyl, acetamiprid, and
fluazinam. (Ref. 9 at 16). For the reasons described above in Unit
VII.D.7.b., EPA denies these objections.
E. Human Testing
NRDC claims that EPA used a human study to assess exposure to turf
use of 2,4-D in violation of EPA's policy on use of human studies as
announced in a press release on December, 14, 2001, and in violation of
``the Nuremberg Code, the Helsinki Declaration, and EPA's common
rule.'' (Ref. 8 at 21-22). NRDC states that EPA has not clarified
whether the human study in question was an epidemiology study or
involved third-party human testing. If the study falls in the latter
category, according to NRDC, EPA's consideration of it would violate
its own policy as well as the other cited authorities.
EPA disagrees with NRDC's claim that it was improper for EPA to
consider the study in question in assessing the risk posed by 2,4-D. To
clarify, the study is not an epidemiology study; rather it is a
biomonitoring study conducted by the
[[Page 46736]]
Canadian Centre for Toxicology. (Ref. 89). Because it was not conducted
or supported by a department or agency of the U.S. Government, EPA
refers to it as a ``third-party'' study. In this biomonitoring study,
adult male and female volunteers were selected from the faculty, staff,
and students of the University of Guelph. The study participants ``were
supplied with written information outlining the possible risks they
would be taking to participate in the study. . . . Consent forms were
signed before the initiation of the study.'' (Ref. 89 at 12). In
addition, ``[t]he protocol was appraised and approved by the University
of Guelph Ethical Review Board.'' (Id.) Volunteers were exposed to 2,4-
D while performing activities specified by the researchers (walking,
sitting, and lying) for one hour on turf previously treated (consistent
with product's label instructions) with 0.88 lb acid equivalent/acre
2,4-D. The product did not specify any restricted entry interval or
require that people entering treated areas wear any special personal
protective equipment. The researchers measured the amount of 2,4-D
detectable in urine collected from the human participants for a period
of 96 hours following this exposure.
NRDC's objection appears to be based on their belief that the 2,4-D
biomonitoring study was unethical and that the decision to rely on the
data violated existing international standards (the Nuremberg Code and
the Helsinki Declaration), as well as Agency regulations (the Common
Rule) and policy (presumably the position announced in a December 14,
2001 press release). Each of these is discussed below.
The Nuremberg Code contains basic, broad ethical precepts to guide
all types of scientific research with human subjects. The text of the
Code was developed in 1949 and is available at: http://ohsr.od.nih.gov/guidelines/nuremberg.html. The Code indicates that for a human study to
be considered ethical the subjects must participate voluntarily, they
should be informed of the nature and purpose of the research, and they
should be allowed to withdraw at any time. Also, the study should be
designed to produce scientifically useful information and be conducted
by appropriately qualified researchers. The Code also indicates
researchers should take measures to protect the subjects and must
terminate the research if continuation of the study would result in
injury to a participant.
The Agency has reviewed the ethical conduct of the 2,4-D
biomonitoring study using the principles in the Nuremberg Code. While
the available information on the biomonitoring study does not address
each of the paragraphs in the Code, the information does indicate that
the study complied with the broad principles of the Code. EPA is aware
of no information to indicate that any of the Code's principles was not
followed.
The international medical research community has developed and
maintains ethical standards documented in the Declaration of Helsinki,
first issued by the World Medical Association in 1964 and revised
several times since then. The latest version of the Declaration is
available at: http://www.wma.net/e/policy/b3.htm . These standards are
available to guide research on matters relating to the diagnosis and
treatment of human disease, and to research that adds to understanding
of the causes of disease and the biological mechanisms that explain the
relationships between human exposures to environmental agents and
disease. Because the 2,4-D biomonitoring study did not involve research
on matters relating to the relationship between human exposure to
environmental agents and human disease, or otherwise fall within the
scope of the Declaration of Helsinki, the Declaration does not apply to
this research.
The Agency's rules for ``Protection of Human Subjects,'' generally
referred to as the ``Common Rule,'' apply to ``all research involving
human subjects conducted [or] supported . . . by any Federal department
or agency.'' (40 CFR 26.101). Because the 2,4-D biomonitoring study was
not conducted or supported by an agency or department of the U.S.
Government, it was not subject to the Common Rule.
At the time EPA prepared its risk assessment for the 2,4-D soybean
tolerance, the Agency had a general practice of using ``third-party''
human studies, unless the studies involved intentional dosing of human
subjects for the purpose of identifying or quantifying a toxic effect.
(Ref. 90). This policy or practice (as described in the December, 2001
Press release) applied only to intentional dosing studies conducted to
identify or quantify a toxic effect and the 2,4-D biomonitoring study
was not such a study.
It should be noted that the approach described in the 2001 press
release has been set aside. In early 2002 various parties from the
pesticide industry filed a petition with the U. S. Court of Appeals for
the District of Columbia for review of EPA's December 2001 press
release. These parties argued that the Agency's interim approach
constituted a ``rule'' promulgated in violation of the procedural
requirements of the Administrative Procedure Act and the Federal Food,
Drug, and Cosmetic Act. On June 3, 2003, the Court of Appeals concluded
that:
For the reasons enumerated above, we vacate the directive
articulated in EPA's December 14, 2001 Press Release for a failure
to engage in the requisite notice and comment rulemaking. The
consequence is that the agency's previous practice of considering
third-party human studies on a case-by-case basis, applying
statutory requirements, the Common Rule, and high ethical standards
as a guide, is reinstated and remains in effect unless and until it
is replaced by a lawfully promulgated regulation.
Crop Life America v. EPA, 329 F.3d 876, 884 - 85 (D.C. Cir. 2003)).
In sum, the information available to EPA does not suggest that the
2,4-D human biomonitoring study was performed in an unethical manner
and therefore should not have been considered by the Agency. Rather,
the researchers in the 2,4-D study informed the participants of
potential risks from participating in the study and obtained their
written consent. In addition, the researchers obtained an assessment by
an independent ethical review board of the proposed study design prior
to conducting the study. While the Journal article describing the 2,4-D
biomonitoring study does not reference any applicable ethical framework
as governing its conduct, these measures - a prior ethics review by an
independent board and informed consent - are the principal protections
required by the Common Rule adopted in the United States in 1991.
Accordingly, EPA has determined that the 2,4-D biomonitoring study is
not significantly deficient relative to the ethical standards
prevailing when the study was conducted, some time prior to 1992. EPA
has also determined that the study is not fundamentally unethical.
Moreover, EPA notes that this study is not subject to the Helsinki
Declaration, EPA's Common Rule, or EPA's now overturned December 2001
policy on third-party human testing. Finally, NRDC provided no specific
information or argument to support its objection. Therefore, EPA
concludes that it properly considered the data from the 2,4-D
biomonitoring study.
F. Conclusion on Objections
For the reasons stated above, all of the NRDC's objections are
hereby denied.
VIII. Response to Comments on NRDC's Objections
EPA has responded to many of the comments that pertained
specifically to
[[Page 46737]]
the individual pesticides and pesticide tolerances in Unit VII. The
more general comments filed by the IWG, IR-4, and the public were
responded to in the Imidacloprid Order. That response is adopted
herein. (69 FR at 30072-30074, May 26, 2004). Other comments are
addressed below.
ISK Biosciences noted that the challenged fluazinam tolerance
applied to wine grapes and children do not usually consume wine.
Although this is true, section 408(b) requires EPA to consider
aggregate exposure to a pesticide and not just exposure under the
specific tolerance at issue. Further, ISK Biosciences argues that EPA's
assessment of exposure to fluazinam in wine is very conservative. EPA
generally agrees with this comment.
FMC Corporation argues that because a data call-in has not been
issued for a DNT study on zeta-cypermethrin there can be no data gap
and the database must be complete. In response, EPA would note that the
``completeness'' inquiry in the children's safety factor provision is
not a formalistic exercise turning on whether mandatory data call-ins
have been issued. As EPA stated in its Children's Safety Policy:
the ``completeness'' inquiry should be a broad one that takes
into account all data deficiencies. In other words, the risk
assessor should consider the need for traditional uncertainty
factors not only when there are inadequacies or gaps in currently
required studies on pesticides, but also when other important data
needed to evaluate potential risks to children are missing or are
inadequate.
(Ref. 2 at 20).
Bayer CropScience states that historical control information
relating to effects seen in a rat teratology study submitted to EPA
demonstrates that the young do not have increased sensitivity to
isoxadifen-ethyl. After reviewing this historical control data, EPA has
again concluded that the developmental effects seen at the mid- and
high-doses in the rat teratology study were statistically significant
and treatment-related. (Ref. 9)
IX. Regulatory Assessment Requirements
As indicated previously, this action announces the Agency's final
order regarding objections filed under section 408 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.
X. 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).
XI. Time and Date of Issuance of This Order
The time and date of the issuance of this Order shall, for purposes
of 28 U.S.C. 2112, be at 1 p.m. eastern time (daylight savings time) on
the date that is 2 weeks after the date when the document is published
in the Federal Register.
XII. References
1. Office of Pesticide Programs, U.S. EPA, Available Information on
Assessing Pesticide Exposure From Food: A User's Guide (June 21, 2000)
(available at http://www.epa.gov/ fedrgstr/EPA-PEST/2000/July/Day-12/
6061.pdf).
2. Office of Pesticide Programs, US EPA, Determination of the
Appropriate FQPA Safety Factor(s) in Tolerance Assessment [hereinafter
cited and referred to in the text as the ``Children's Safety Factor
Policy''] (January 31, 2002) (available at http://www.epa.gov/oppfead1/trac/science/determ.pdf).
3. Office of Pesticide Programs, US EPA, General Principles for
Performing Aggregate Exposure and Risk Assessments (November 28, 2001)
(available at http://www.epa.gov/pesticides/trac/science/aggregate.pdf).
4. Office of Pesticide Programs, US EPA, Choosing a Percentile of
Acute Dietary Exposure as a Threshold of Regulatory Concern
[hereinafter referred to and cited as ``Percentile Policy''] (March 16,
2000) (available at http://www.epa.gov/pesticides/trac/science/trac2b054.pdf).
5. Petition For A Directive That the Agency Designate Farm Children
as a Major Identifiable Subgroup and Population at Special Risk to Be
Protected under the Food Quality Protection Act 2 (October 22, 1998).
6. Objections to the Establishment of Tolerances for Pesticide
Chemical Residues: Halosulfuron-methyl and Pymetrozine Tolerances
(filed February 25, 2002).
7. Objections to the Establishment of Tolerances for Pesticide
Chemical Residues: Imidacloprid, Mepiquat, Bifenazate, Zeta-
cypermethrin, and Diflubenzuron Tolerances (filed March 19, 2002).
8. Objections to the Establishment of Tolerances for Pesticide
Chemical Residues: 2,4-D Tolerances (filed May 7, 2002).
9. Objections to the Establishment of Tolerances for Pesticide
Chemical Residues: Isoxadifen-ethyl, Acetamiprid, Propiconazole,
Furilazole, Fenhexamid, and Fluazinam Tolerances (filed May 20, 2002).
10. FQPA Implementation Working Group, Response to Objections of
the Natural Resources Defense Council to Regulations Establishing
Tolerances for Residues of Various Pesticide Chemicals In or On Food
Items (October 16, 2002).
11. Inter-Regional Research Project Number 4, Response to Natural
Resources Defense Council Objection to Tolerances Established for
Certain Pesticide Chemicals (October 15, 2002).
12. ISK Biosciences, NRDC Objection to the Establishment of
Tolerances for Fluazinam (October 14, 2002).
13. Bayer CropScience, Comments to the May 20, 2002 NRDC Letter to
the EPA Objecting to the Establishment of Tolerances for Isoxadifen-
ethyl (October 16, 2002).
14. Peter Hertl, et al., Poster Session, 10th IUPAC International
Congress on Chemistry of Crop Protection, Basel, Switzerland (2002).
15. Aventis CropScience, Comments to the May 20, 2002 NRDC Letter
to the EPA Objecting to the Establishment of Tolerances for Acetamiprid
2 (October 11, 2002).
16. FMC Corporation, Comments on NRDC Objections to EPA
Establishment of Certain Pesticide Tolerances 5 (October 15, 2002).
17. Crompton Corporation, Comments of Crompton Corporation to NRDC
objections to Bifenazate and Diflubenzuron Tolerances 9 (October 15,
2002).
18. Syngenta Crop Protection, Comments on Objections to Tolerances
Established for Certain Pesticide Chemicals, 2 (October 16, 2002)
(citing Dourson, M.L., Fetter, S.P., and Robinson, D., Evaluation of
Science-Based Uncertainty Factors in Non-Cancer Risk Assessment,
Regulatory Toxicoloty and Pharmacology. 24(2), 108-120 (1996)).
19. BASF Corporation, Docket Identification (ID) Number OPP-2002-
0057 (October 16, 2002).
20. Industry Task Force II on 2,4-D Research Data, Response to
Objections of the Natural Resources Defense Council to the
Establishment of a Tolerance for Pesticide Chemical Residues of 2,4-
Dichlorophenoxyacetic Acid (2,4-D) (October 16, 2002).
21. U.S. EPA, A Pilot Study of Children's Total Exposure to
Persistent Pesticides and Other Persistent Organic Pollutants (CTEPP)
(2005).
[[Page 46738]]
22. National Exposure Research Laboratory, U.S. EPA, Memorandum
from Kent Thomas to Ruth Allen, Transmittal of Agricultural Health
Study/Pesticide Exposure 2,4-D Urinary Biomarker Measurement Results in
Support of Response to Public Comments on the Draft 2,4-D Risk
Assessment (November 9, 2004).
23. Mandel, J.S., and Alexander, B.H., Measurement of Pesticide
Exposure of Farm Residents Associated With the Agricultural Use of
Pesticides Glyphosate, 2,4-D, Chlorpyrifos: The Farm Family Exposure
Study (June 18, 2004).
24. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Timothy C. Dole to Katie Hall, 2,4-D: Response to
Public Comments (December 16, 2004).
25. Pesticide Registration Notice 90-3 (April 6, 1990) (available
at http://www.epa.gov/opppmsd1/PR_Notices/pr90-3.htm).
26. Hewitt, Andrew J., Johnson, David R., Fish John D., Hermansky,
Clarence G., and Valcore, David L., Development of the Spray Drift Task
Force Database for Aerial Applications, 21(3) Environmental Toxicology
and Chemistry, 648-658 (2002).
27. Bird, Sandra L., Perry, Steven G., Ray, Scott L., and Teske,
Milton E, Evaluation of the AgDISP Aerial Spray Algorithms in the
AgDRIFT Model, Environmental Toxicology and Chemistry, Vol. 21, No.3,
pp. 672-681 (2002).
28. Teske, Milton E., Bird, Sandra L., Esterly, David M.,
Curbishley, Thomas B., Ray, Scott L., and Perry, Steven G., AgDRIFT:
AModel for Estimating Near-field Spray Drift from Aerial Applications,
21 Environmental Toxicology and Chemistry 659-671 (2002).
29. U.S. EPA, Guidelines for Exposure Assessment. 57 FR 22888
(1992).
30. Bilanin, A.J., M.E. Teske, J.W. Barry, and R.B. Ekblad (1989).
AGDISP: The aircraft dispersion model, code development and
experimental validation. Trans. A.S.A.E. 32:327-334.
31. Bird, Sandra L., Steven G. Perry, Scott L. Ray, Milton E.
Teske, Peter N. Scherer. (1996) An Evaluation of AgDRIFT 1.0 for Use in
Aerial Applications. Ecosystems Research Division, National Exposure
Research Laboratory, Office of Research and Development, USEPA, Athens
GA, 30605.
32. Bird, Sandra L., David M. Esterly, and Steven G. Perry (1996).
Off-target Deposition of Pesticide from Agricultural Aerial Spray
Applications. Journal of Environmental Quality. 25:1095-1104.
33. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Jeff Evans to Betty Shackleford, Estimates of
Residential Bystander Exposure (August 1, 2004).
34. Californians for Pesticide Reform, Secondhand Pesticides:
Airborne Pesticide Drift in California (2003).
35. See Lee, S., McLaughlin, R., Harnly, M., Gunier, R., Kreutzer,
R., Community Exposures to Airborne Agricultural Pesticides in
California: Ranking of Inhalation Risks, 110 Environmental Health
Perspectives 1175 (December 2002).
36. Camann, D.E., Geno, P.W., Harding, H, Jac, Giardino, N.J. and
Bond, A.E., Measurements to assess exposure of the farmer and family to
agricultural pesticides, U.S. EPA (Contract 68D10150). pp. 712 - 717
(1993).
37. Segawa, R.T., Sitts, J.A., White, J.H., Marade, S.J., Powel,
S.A. Environmental monitioring of malathion aerial applications used to
eradicate Mediterranean fruit flies in Southern California. EH 91-03
California Department of Pesticide Regulation, Sacramento, California.
38. Nishioka, M.G., Burkholder, H.M, Brinkman, M.C., and Lewis,
R.G., Distribution of 2,4-Dichlorophenoxyacetic Acid in Floor Dust
Throughout Homes Following Homeowner and Commercial Lawn Applications:
Quantitative Effect of Children, Pets, and Shoes, 33 Environmental
Science and Technology 1359-1365 (1999).
39. Solomon, K.R., Harris, S.A. and Stephenson, G.R., Applicator
and Bystander Exposure to Home Garden and Landscape Pesticides,
American Chemical Society, Pesticides in Urban Environments, Chapter
22, pp. 262-274 (Eds. Racke and Leslie) (1993).
40. U.S. EPA, Pesticide Exposure and Potential Health Effects in
Young Children Along the U.S.-Mexico Border (EPA 600/R-02/085,
November, 2002).
41. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Jeff Evans to Betty Shackleford, Potential
Bystander Exposure to Volatile Pesticides (August 1, 2005).
42. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Margaret J. Stasikowski to Health Effects Division
Staff, Guidance: Waiver Criteria for Multiple-Exposure Inhalation
Toxicity Studies (August 15, 2002) (citing references).
43. ISK Biosciences, Label for Omega 500F (fluazinam) (June 11,
2003)
44. BASF, Label for Pentia plant regulator (mepiquat pentaborate)
(March 17, 2005); BASF, Label for BAS 130 03W plant regulator (mepiquat
pentaborate) (January 25, 2002).
45. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Interim Reregistration Eligibility Decision for Chlorpyrifos
(February 2002).
46. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from William D. Cutchin to Cynthia Giles-Parker/CP
Moran, Addendum to Human Health Risk Assessment for the Use of
Fluazinam on Peanuts, Potatoes, and Wine Grapes. 5 (10/23/01).
47. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Margarita Collantes to Janet Whitehurst/Cynthia
Giles-Parker, PP#1F03955. Mepiquat Chloride in/on Grapes and Raisins.
Human Health Risk Assessment. 25 (11/22/1999).
48. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Deborah Smegal to Mark Hartman, Occupational/
Residential Handler and Postapplication Residential/Non-Occupational
Risk Assessment for Chlorpyrifos. DP Barcode: D266562. Case No. 818975.
PC Code: 059101. Submission: S568580. 6 (June 20, 2000).
49. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Jihad Alsadek to Jeff Evans, Usage Report in
Support of Chlorpyrifos, an Insecticide, and Mepiquat, a Plant Growth
regulator (April 25, 2005).
50. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, PHED Surrogate Exposure Guide: Estimates of Worker Exposure from
The Pesticide Handler Exposure Database Version 1.1. (August 1998).
51. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Tim Leighton to Debbie Smegal, Agricultural and
Occupational Exposure Assessment and Recommendations for the
Reregistration Eligibility Decision Document for Chlorpyrifos. 31 (June
19, 2000).
52. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Deborah Smegal to Steve Knizner, Chlorpyrifos -
Reevaluation Based on Phase 3 (Public Comments) of the TRAC Process.
Report of the Hazard Identification Assessment Review Committee (April
6, 2000) (HED Doc. No. 014088) (available at http://www.epa.gov/
oppsrrd1 /op/chlorpyrifos/ reevaluation.pdf.
53. Makris, Susan et al., A Retrospective Analysis of Twelve
Developmental Neurotoxicity Studies
[[Page 46739]]
Submitted to the USEPA Office of Prevention, Pesticides, and Toxic
Substances (draft November 12, 1998) (available at http://www.epa.gov/scipoly/sap/1998/index.htm#december8).
54. U.S. EPA, Response to Petition to Compel the U.S. EPA to Repeal
Its Test Guidelines for Developmental Neurotoxicity (January 3, 2005)
(available at http://docket.epa.gov/edkpub/do/EDKStaffCollectionDetailView?objectId=0b0007d480525f44 =0b0007d480525f44).
55. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Jess Rowland to Betty Shackleford, Effect of
Developmental Neurotoxicity Studies on Endpoint Selection - Preliminary
Results (July 28, 2005).
56. U.S. EPA, Toxicology data requirements for assessing risks of
pesticide exposure to children's health. Report of the Toxicology
Working Group of the 10X Task Force 31 (draft April 28, 1999)
(Available at http://www.epa.gov/scipoly/sap/1999/may/10xtx428.pdf).
57. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from George F. Kramer to Shaja Brothers/Robert Forrest,
PP#: 0E06167. Diflubenzuron in/on Pears (Dimilinr 2L, EPA Reg #400-461&
Dimilinr 25W, EPA Reg # 400-464). Health Effects Division (HED) Risk
Assessment. PC Code 108201. DP Barcode: D271495. Case: 293100.
Submission S590172. (September 27, 2001).
58. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Edwin R. Budd to William Cutchin, Fluazinam -
Report of the Hazard Identification Assessment Review Committee 28
(February 13, 2001).
59. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Jessica Kidwell to Jessica Kidwell, MON 13900:
Data Waiver Request - Report of the Hazard Identification Assessment
Review Committee (November 14, 2000); Memorandum from Guruva B. Reddy
to George Kramer, MON 13900 - Report of the Hazard Identification
Assessment Review Committee (December 4, 2001).
60. Garabrant DH, Philbert MA, Review of 2,4-dichlorophenoxyacetic
acid (2,4-D) epidemiology and toxicology, Crit Rev Toxicol. 2002
Jul;32(4):233-57 (``there is no convincing evidence in the literature
that 2,4-D is associated with human reproductive toxicity.``).
61. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from G. Jeffrey Herndon to Dan Kenny/Joanne Miller,
2,4-D. Extension of Time-Limited Tolerance on Soybean Seed. Request
from Registration Division (RD) for an Updated Human Health Risk
Assessment. 10-11 (January 31, 2002).
62. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from HED Chemistry Science Advisory Council to HED
Chemistry Interest Group, Minutes of 5/16/01 ChemSAC meeting (June 15,
2001).
63. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Sherrie L. Kinard to Yan Donovan, Permethrin.
Metabolism Assessment Review Committee Memorandum (July 6, 2004) (TXR
NO. 0052775).
64. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Yan Donovan to George Kramer, Cypermethrin and
Zeta-Cypermethrin -- Conclusions of the Meeting of Metabolism
Assessment Review Committee (10/10/00) (November 03, 2000)
(TXR 0050106).
65. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Richard Loranger to Yan Donovan, MARC Decision
Memo for 5/22/02 Meeting on Cyfluthrin: Residues of Concern in Drinking
Water; Chemical #128831; DP Barcode D283553; Submission #S549586 (June
13, 2002) (TXR NO. 0050805).
66. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Jennifer E. Rowell to Donald A. Marlow, PP#8F4925.
Diflubenzuron (Dimilinr 2L, EPA Reg #400-461) on Rice. Request for
Petition Method Validation (PMV). MRID # s 44399303, 44399306,
44695001, and 44695002. Chemical 108201. Barcode D251484. Case 289260.
Submission # S539585. (December 15, 1998).
67. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from George F. Kramer to Rita Kumar, PP # 8F4925.
Diflubenzuron (Dimilinr 2L, EPA Reg #400-461) on Rice. Results of
Petition Method Validation (PMV) MRID #s 443993-03 and -06. Barcode
D261060. Chemical No 108201. Case 289260. Submission S571149.
(September 6, 2002).
68. Office of Prevention, Pesticides, and Toxic Substances, Data
Evaluation Report: Bifenazate; Study Type: Developmental Toxicity-
Rabbit (83-3B) TXR No 013403 (undated).
69. Cancer Assessment Review Committee, Health Effects Division,
Office of Pesticide Programs, U.S. EPA, Evaluation of the Carcinogenic
Potential of Fluazinam (March 29, 2001).
70. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Michael Doherty to Daniel Peacock, PPs 8F4984,
8F5031, and 0F6141. Human Health Risk Assessment for the Use of
Pymetrozine on Cotton, Hops, Pecans, Leafy Vegetables (Except Brassica
Vegetables), Head and Stem Brassica, Leafy Brassica Greens, Turnip
Greens, Cucurbits, and Fruiting Vegetables 3 (December 20, 2001)
71. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from John Doherty to Mike Ioannou, Pymetrozine - Report
of the Hazard Identification Assessment Review Committee 5 (March 15,
1999).
72. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Alan Levy to Margarita Collantes, Mepiquat
Chloride: - Report of the Hazard Identification Assessment Review
Committee 16 (October 21, 1999).
73. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Yan Donovan to A. Layne/L. Deluise, PP# 4F3012,
9F6040, 8F4970, 9F6037, and 4F4399. FQPA Human Health Risk Assessment
for the Use of Z-Cypermethrin on Sweet Corn, Rice, Leafy Vegetables
(Except Brassica), Brassica Leafy Vegetables, Sugar Beets, Sugarcane,
Corn (Field, Seed, Pop), Green Onions, and Alfalfa. (July 11, 2001).
74. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Edwin Budd to Cynthia Giles-Parker/C.P. Moran,
Fluazinam. PP# 9F05079. EPA File Symbol 71512-R. New Reduced Risk
Active Ingredient. Toxicology Disciplinary Chapter for the Registration
Support Document and Data Evaluation Records (DERs) for All Recently
Submitted Toxicology Studies, Toxicology Studies Not Previously
Reviewed, and Previously Reviewed Toxicology Studies for Which Amended
DERs or Updated Executive Summaries Have Been Prepared. (June 18,
2001).
75. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Data Evaluation Report Fluazinam Study Type: Subchronic Oral Liver
Toxicity - Rat (Non-Guideline) (June 18, 2001)
76. U.S. EPA, Guidelines for the Use of Anticipated Residues in
Dietary Exposure Assessment (March 25, 1991).
77. U.S. Department of Agriculture, Agricultural Chemical Usage,
Vegetable Summary 2000(July 2001) (available at http://usda.mannlib.cornell.edu/reports/nassr/other/pcu-bb/).
78. U.S. Department of Agriculture, Agricultural Chemical Usage,
Field Crop Summary 2000 (July 2001) (available at
[[Page 46740]]
http://usda.mannlib.cornell.edu/reports/nassr/other/pcu-bb/).
79. Office of Pesticide Programs, U.S. EPA, Use of the Pesticide
Data Program (PDP) in Acute Risk Assessment (May 5, 1999-DRAFT) (citing
studies).
80. Office of Pesticide Programs, U.S. EPA, Assigning Values to
Nondetected/non-quantified Pesticide Residues in Human Health Food
Exposure Assessments (March 23, 2000) (available at http://www.epa.gov/pesticides/trac/science/trac3b012.pdf).
81. Office of Pesticide Programs, U.S. EPA, Office of Pesticide
Programs Science Advisory Council for Exposure, Policy Number 12,
Recommended Revisions to the Standard Operating Procedures (SOPs) for
Residential Exposure Assessments (Revised: February 22, 2001)
82. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Residue Chemistry Test Guidelines: OPPTS 860.1520 Processed Food/
Feed (August 1996) (available at http://www.epa.gov/OPPTS_Harmonized/
).
83. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Sheila Piper to Betty Shackleford, Information on
Default Processing Factors For Commodities Which Appear in DEEM (Draft:
July 29, 2005).
84. Sturtz N, Evangelista de Duffard AM, Duffard R., Detection of
2,4-dichlorophen oxyacetic acid (2,4-D) residues in neonates breast-fed
by 2,4-D exposed dams, Neurotoxicology. 2000 Feb-Apr;21(1-2):147-54.
85. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from William H. Donovan to PV Shah, 2,4-
Dichlorophenoxyacetic Acid - Dietary Exposure Analysis for 2,4-
Dichlorophenoxyacetic Acid in/on Hops (00WA0033). Chemical #: 030001.
DP Barcode: D266939. Case #: 293138. Submission #: S580138. 3 (July 6,
2000).
86. Office of Prevention, Pesticides, and Toxic Substances,
Memorandum from William J. Hazel to William J. Hazel, 2,4-D. Acute and
Chronic Dietary Exposure Assessments for Reregistration Eligibility
Decision 2 (March 1, 2004).
87. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, 2,4-D, PC Code No. 030001, Case No. 0073 DP Barcode D287660,
Reregistration Eligibility Decision, Residue Chemistry Considerations
15 (July 8, 2003).
88. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Elizabeth Mendez to Jonathan Fleuchaus, 2,4-D;
Exposure Issues from Breast Milk Residues (May 12, 2005).
89. Harris and Solomon, 1992, Human Exposure to 2,4-D Following
Controlled Activities on Recently Sprayed Turf, Journal of
Environmental Science and Health, B27 (1), 9-22 (1992).
90. U.S. EPA Press Release (December 14, 2001) (available at:
http://yosemite.epa.gov/opa/admpress.nsf/b1ab9f485b098972852562e7004dc686/c232a45f5473717085256b2200740ad4?OpenDocument).
91. Office of Prevention, Pesticides, and Toxic Substances, U.S.
EPA, Memorandum from Brenda Tarplee to William Donovan, Isoxadifen-
ethyl - 2nd Report of the Hazard Identification Assessment Review
Committee 4 (March 23, 2003).
List of Subjects
Environmental protection, pesticides and pest.
Dated: August 3, 2005.
James Jones,
Director, Office of Pesticide Programs.
[FR Doc. 05-15840 Filed 8-9-05; 8:45 am]
BILLING CODE 6560-50-S