Rule2022-04139
Chlorpyrifos; Final Order Denying Objections, Requests for Hearings, and Requests for a Stay of the August 2021 Tolerance Final Rule
Primary source
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Published
February 28, 2022
Effective
February 28, 2022
Issuing agencies
Environmental Protection Agency
Abstract
In response to EPA's August 2021 final rule revoking all tolerances for the insecticide chlorpyrifos under the Federal Food, Drug, and Cosmetic Act (FFDCA), several objections, hearing requests, and requests for stay were filed by numerous parties representing a wide variety of growers and pesticide users. In this Order, EPA denies all objections to, requests for hearing on those objections, as well as requests for stay of the final rule.
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[Federal Register Volume 87, Number 39 (Monday, February 28, 2022)]
[Rules and Regulations]
[Pages 11222-11273]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-04139]
[[Page 11221]]
Vol. 87
Monday,
No. 39
February 28, 2022
Part IV
Environmental Protection Agency
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40 CFR Part 180
Chlorpyrifos; Final Order Denying Objections, Requests for Hearings,
and Requests for a Stay of the August 2021 Tolerance Final Rule; Final
Rule
Federal Register / Vol. 87 , No. 39 / Monday, February 28, 2022 /
Rules and Regulations
[[Page 11222]]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2021-0523; 5993-05-OCSPP]
Chlorpyrifos; Final Order Denying Objections, Requests for
Hearings, and Requests for a Stay of the August 2021 Tolerance Final
Rule
AGENCY: Environmental Protection Agency (EPA).
ACTION: Order.
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SUMMARY: In response to EPA's August 2021 final rule revoking all
tolerances for the insecticide chlorpyrifos under the Federal Food,
Drug, and Cosmetic Act (FFDCA), several objections, hearing requests,
and requests for stay were filed by numerous parties representing a
wide variety of growers and pesticide users. In this Order, EPA denies
all objections to, requests for hearing on those objections, as well as
requests for stay of the final rule.
DATES: The Order is effective February 28, 2022.
ADDRESSES: The docket for this action, identified by docket
identification (ID) number EPA-HQ-OPP-2021-0523, is available at
<a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Office of Pesticide Programs
Regulatory Public Docket (OPP Docket) in the Environmental Protection
Agency Docket Center (EPA/DC), West William Jefferson Clinton Bldg.,
Rm. 3334, 1301 Constitution Ave. NW, Washington, DC 20460-0001.
Due to public health concerns related to COVID-19, the EPA/DC and
Reading Room is open to visitors by appointment only. For the latest
status information on EPA/DC services and docket access, visit <a href="https://www.epa.gov/dockets">https://www.epa.gov/dockets</a>.
FOR FURTHER INFORMATION CONTACT: Elissa Reaves, Pesticide Re-Evaluation
Division (7508P), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave. NW, Washington, DC 20460-
0001; telephone number: 202-566-0700; email address:
<a href="/cdn-cgi/l/email-protection#4c031c1c0f2420233e3c353e252a233f05223d39253e25293f0c293c2d622b233a"><span class="__cf_email__" data-cfemail="e1aeb1b1a2898d8e9391989388878e92a88f90948893888492a1849180cf868e97">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Executive Summary
A. Does this action apply to me?
In this document, EPA denies all objections to, requests for
hearing on those objections, and requests for stay of EPA's August 2021
final rule (Ref. 1) revoking all tolerances for the insecticide
chlorpyrifos under section 408(d) of the Federal Food, Drug, and
Cosmetic Act (FFDCA), 21 U.S.C. 346(d). This action may be of interest
to all parties filing objections, requests for hearing on those
objections, and requests for stay. This action may also be of interest
to agricultural producers, food manufacturers or pesticide
manufacturers, and others interested in food safety issues generally.
The following list of North American Industrial Classification System
(NAICS) codes is not intended to be exhaustive, but rather provides a
guide to help readers determine whether this document applies to them.
Potentially affected entities may include:
<bullet> Crop production (NAICS code 111).
<bullet> Animal production (NAICS code 112).
<bullet> Food manufacturing (NAICS code 311).
<bullet> Pesticide manufacturing (NAICS code 32532).
Other types of entities not listed in this unit could also be
affected. The NAICS codes have been provided to assist you and others
in determining whether this action might apply to certain entities. If
you have any questions regarding the applicability of this action to a
particular entity, consult the contact listed under FOR FURTHER
INFORMATION CONTACT.
B. What action is the Agency taking?
In this Order, EPA denies all objections to, requests for hearing
on those objections, as well as requests for stay of the August 2021
final rule (Ref. 1). This Order is issued under FFDCA section
408(g)(2)(C), 21 U.S.C. 346a(g)(2)(C)).
Based on information available as of August 20, 2021--the date by
which the U.S. Court of Appeals for the Ninth Circuit (Ninth Circuit)
ordered EPA to issue a final rule concerning chlorpyrifos tolerances--
EPA was unable to conclude that the tolerances for chlorpyrifos
residues were safe in accordance with the FFDCA safety standard. In
other words, EPA could not determine that there was a reasonable
certainty that no harm would result from aggregate exposure to the
pesticide chemical residue, including all anticipated dietary exposures
and all other exposures for which there is reliable information. The
Agency's analysis indicated that aggregate exposures (i.e., exposures
from food, drinking water, and residential exposures), resulting from
currently registered uses, exceeded safe levels. This decision relied
on the well-established 10% red blood cell acetylcholinesterase (RBC
AChE) inhibition as an endpoint for risk assessment and included the
default Food Quality Protection Act (FQPA) tenfold (10X) margin of
safety to account for uncertainties related to the potential for
neurodevelopmental effects to infants, children, and fetuses.
Accordingly, EPA issued a final rule revoking all tolerances for
chlorpyrifos contained in 40 CFR 180.342. (See 86 FR 48315, Aug. 30,
2021) The prepublication of the final rule was issued on August 18,
2021, the final rule was published in the Federal Register on August
30, 2021, and the final rule became effective on October 29, 2021.
Pursuant to the procedures set forth in FFDCA section 408(g)(2),
objections to, requests for evidentiary hearings on those objections,
and/or requests for stays of, the final rule were filed by the persons
listed in Unit V. (each, an Objector, and collectively, the Objectors)
on or before the close of the objections period on October 29, 2021.
(Ref. 1) The Objectors raised challenges to the final rule, including,
for example, objections relating to the scope of the revocations in the
final rule, retention of the additional FQPA Safety Factor, and use of
the 2016 drinking water assessment, as well as raising procedural or
other irrelevant concerns that do not change the basis for the final
rule itself.
Four Objectors requested a hearing on their objections. The
American Soybean Association, American Sugarbeet Growers Association
and U.S. Beet Sugar Association (collectively, ``Sugarbeet
Associations''), and Cherry Marketing Institute each submitted requests
for evidentiary hearings to dispute EPA's revocation of tolerances for
the 11 ``high-benefit'' uses identified in the ``Proposed Interim
Decision for the Registration Review of Chlorpyrifos'' (2020 PID) (Ref.
31)--including soybean uses, sugarbeet uses, and the Michigan tart
cherry industry's use. Gharda also submitted a request for an
evidentiary hearing on an issue related to the assessment of
chlorpyrifos oxon in EPA's aggregate assessment.
Finally, EPA received several written requests for EPA to stay the
effective date of the final rule due to impacts on the agricultural
industry and in order to provide more time for EPA to fully consider
the objections filed.
This Order denies all of the objections, requests for evidentiary
hearings on those objections, and requests for stays of the final rule.
EPA has undertaken a comprehensive analysis of the merits of each of
the Objectors' objections, hearing requests, and requests for stay.
That analysis shows, as set out in Units VI., VII., and VIII. of this
document, respectively, that none of the Objectors' objections support
the claims raised, none of the Objectors' requests for hearing meet the
[[Page 11223]]
regulatory standard for granting a hearing, and none of the Objectors'
requests for stay warrant staying the effective date of the final rule.
There are numerous reasons for EPA's conclusions, for which additional
detail is provided in Units VI., VII., and VIII. of this document.
C. What is the Agency's authority for taking this action?
The procedure for filing objections and requests for hearings
thereon to EPA's final rule and EPA's authority for acting on such
objections is contained in FFDCA section 408(g)(2) (21 U.S.C.
346a(g)(2)) and EPA's regulations at 40 CFR part 178.
II. Statutory and Regulatory Background
In this Unit, EPA provides background on the relevant statutes and
regulations governing pesticides and tolerances, objections, requests
for hearing, and requests for a stay, as well as on pertinent Agency
policies and practices.
Unit II.A. summarizes the requirements and procedures in FFDCA
section 408 and applicable regulations pertaining to pesticide
tolerances, including the procedures for objecting to EPA tolerance
actions and the substantive standards for evaluating the safety of
pesticide tolerances. This unit also discusses the closely-related
statute under which EPA regulates the sale, distribution, and use of
pesticides, the Federal Insecticide, Fungicide, and Rodenticide Act
(FIFRA) (7 U.S.C. 136 et seq.).
Unit II.B. provides an overview of EPA's Office of Pesticide
Programs (OPP) risk assessment process. It contains an explanation of
how EPA identifies the hazards posed by pesticides, how EPA determines
the level of exposure to pesticides that pose a concern (level of
concern), how EPA measures human exposure to pesticides, and how
hazard, level of concern conclusions, and human exposure estimates are
combined to evaluate risk. Further, this unit presents background
information on the Agency's policy on the FQPA safety factor and
acetylcholinesterase (AChE) inhibition.
A. FFDCA/FIFRA and Applicable Regulations
1. General
EPA establishes, modifies, or revokes tolerances for pesticide
residues in food under FFDCA section 408. (21 U.S.C. 346a) A
``tolerance'' represents the maximum level for residues of pesticide
chemicals legally allowed in or on raw agricultural commodities and
processed foods. Without a tolerance or exemption, pesticide residues
in or on food are considered unsafe (21 U.S.C. 346a(a)(1)), and such
food, which is then rendered ``adulterated'' under FFDCA section 402(a)
(21 U.S.C. 342(a)), may not be distributed in interstate commerce. (21
U.S.C. 331(a)) 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). FFDCA section 408 was substantially
rewritten by the Food Quality Protection Act of 1996 (FQPA), which
added the provisions establishing a detailed safety standard for
pesticides and additional protections for infants and children, among
other things. (Pub. L. 104-170, 110 Stat. 1489 (1996))
EPA also regulates pesticides under FIFRA. (7 U.S.C. 136 et seq.)
While FFDCA authorizes the establishment of legal limits for pesticide
residues in food, FIFRA requires the approval of pesticides prior to
their sale and distribution (Id. at section 136a(a)), and establishes a
registration regime for regulating the use of pesticides. In order for
a pesticide to be registered, EPA must determine that a pesticide
``will not generally cause unreasonable adverse effects on the
environment'', among other things. (Id. at section 136a(c)(5)) The term
``unreasonable adverse effects on the environment'' is defined to
include ``a human dietary risk from residues that results from a use of
a pesticide in or on any food inconsistent with the standard under
section 346a of Title 21.'' (Id. at section 136(bb)) The FFDCA safety
standard was integrated into the FIFRA registration standard in the
FQPA, which also directed that EPA coordinate, to the extent
practicable, revocations of tolerances with pesticide cancellations
under FIFRA. (21 U.S.C. 346a(l)(1))
Also under FIFRA, EPA is required to re-evaluate existing
registered pesticides every 15 years in a process called ``registration
review.'' (7 U.S.C. 136(a)(g)) The purpose of registration review is
``to ensure that each pesticide registration continues to satisfy the
FIFRA standard for registration,'' (40 CFR 155.40(a)(1)) taking into
account changes that have occurred since the last registration
decision, including any new relevant scientific information and any
changes to risk-assessment procedures, methods, and data requirements.
(40 CFR 155.53(a)) To ensure that a pesticide continues to meet the
standard for registration, EPA must determine, based on the available
data, including any additional information that has become available
since the pesticide was originally registered or re-evaluated, that the
pesticide does not cause ``unreasonable adverse effects on the
environment.'' (7 U.S.C. 136a(c)(1), (5); see also 40 CFR 152.50)
2. Safety Standard for Pesticide Tolerances
FFDCA section 408(b)(2) directs that EPA may establish or leave in
effect a tolerance for a pesticide only if it finds that the tolerance
is safe and that EPA must revoke or modify tolerances determined to be
unsafe. (21 U.S.C. 346a(b)(2)(A)(i)) FFDCA section 408(b)(2)(A)(ii)
defines ``safe'' 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.'' (Id. At section
346a(b)(2)(A)(ii)) FFDCA section 408(b)(2)(D) 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 exposure from other non-
occupational sources.'' (Id. at section 346a(b)(2)(D)(vi)) As the
language indicates, this includes exposure through food, drinking
water, and all non-occupational exposures (e.g., in residential
settings), but does not include occupational exposures to workers
(i.e., occupational).
Risks to infants and children are given special consideration.
Specifically, pursuant to FFDCA section 408(b)(2)(C), EPA must assess
the risk of the pesticide chemical based on ``available information
concerning the special susceptibility of infants and children to the
pesticide chemical residues, including neurological differences between
infants and children and adults, and effects of in utero exposure to
pesticide chemicals''; and available information concerning the
cumulative effects on infants and children of such residues and other
substances that have a common mechanism of toxicity. (21 U.S.C.
346a(b)(2)(C)(i)(II) and (III))
This provision also creates a presumption that EPA will use an
additional safety factor for the protection of infants and children.
Specifically, it directs that ``in the case of threshold effects, ...
an additional
[[Page 11224]]
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 postnatal 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.) Due to Congress's focus on both pre- and postnatal
toxicity, EPA has interpreted this additional safety factor as
pertaining to risks to infants and children that arise due to prenatal
exposure as well as to exposure during childhood years. This section
providing for the special consideration of infants and children in
section 408(b)(2)(C) was added to the FFDCA by the FQPA in 1996;
therefore, this additional margin of safety is referred to throughout
this Order as the ``FQPA safety factor (SF)''.
3. Procedures for Establishing, Amending, or Revoking Tolerances
Tolerances are established, amended, or revoked by rulemaking under
the unique procedural framework set forth in FFDCA. Generally, a
tolerance rulemaking is initiated by the party seeking to establish,
amend, or revoke a tolerance by means of filing a petition with EPA.
(See 21 U.S.C. 346a(d)(1)) EPA publishes in the Federal Register a
notice announcing the filing of a petition filing and requesting public
comment. (Id. at section 346a(d)(3)) After reviewing the petition, and
any comments received on it, EPA may issue a final rule establishing,
amending, or revoking the tolerance; issue a proposed rule subject to
public comments and then finalize a rule to do the same; or deny the
petition. (Id. at section 346a(d)(4))
Once EPA takes final action on the petition by either establishing,
amending, or revoking the tolerance or denying the petition, any person
may file objections with EPA and seek an evidentiary hearing on those
objections. (21 U.S.C. 346a(g)(2)) Objections and hearing requests must
be filed within 60 days after EPA takes that action. (Id.) The statute
provides that EPA shall ``hold a public evidentiary hearing if and to
the extent the Administrator determines that such a public hearing is
necessary to receive factual evidence relevant to material issues of
fact raised by the objections.'' (Id. at section 346a(g)(2)(B)) EPA
regulations make clear that hearings will only be granted where it is
shown that there is ``a genuine and substantial issue of fact,'' the
requestor has identified evidence ``which, if established, resolve one
or more of such issues in favor of the requestor,'' and the issue is
``determinative'' with regard to the relief requested. (40 CFR
178.32(b)) EPA's final Order on the objections and requests for hearing
is subject to judicial review. (21 U.S.C. 346a(h)(1)) The statute
directs that tolerance regulations shall take effect upon publication
unless EPA specifies otherwise. (Id. at section 346a(g)(1)) EPA is
authorized to stay the effectiveness of the tolerance if objections are
filed. (Id.) Because EPA does not have its own regulations governing
stay requests, EPA typically evaluates requests for stay under the
criteria set out in FDA's regulations at 21 CFR 10.35(e) due to the
fact that the FFDCA provisions governing EPA's objections and hearings
process were adapted from the similar parallel statutory process
governing FDA objections and hearings.
B. EPA Risk Assessment--Policy and Practice
1. The Safety Determination--Risk Assessment
To assess risk of a pesticide tolerance, EPA combines information
on pesticide toxicity with information regarding the route, magnitude,
and duration of exposure to the pesticide. The risk assessment process
involves four distinct steps, which are discussed in further detail in
this section: (1) Identification of the toxicological hazards posed by
a pesticide; (2) determination of the ``level of concern'' with respect
to human exposure to the pesticide, which includes choosing a point of
departure (PoD) that reflects the adverse health endpoint that is most
sensitive to the pesticide and uncertainty factors; (3) estimation of
human exposure to the pesticide through all applicable routes; and (4)
characterization of risk posed to humans by the pesticide based on
comparison of human exposure to the level of concern. For tolerances,
characterization of risk involves determining whether the tolerances
are safe; if aggregate exposure to humans is greater than the Agency's
determined level of concern, the Agency's determination is that the
tolerances are not safe.
a. Hazard Identification
Any risk assessment begins with an evaluation of a chemical's
potential to cause adverse effects, and whether those properties have
the potential to cause adverse effects (i.e., a hazard identification).
In evaluating toxicity or hazard, EPA reviews toxicity data, typically
from studies with laboratory animals, to identify any adverse effects
on the test subjects. Where available and appropriate, EPA will also
take into account studies involving humans, including human
epidemiological studies. For most pesticides, the animal toxicity
database usually consists of studies investigating a broad range of
endpoints including potential for carcinogenicity, mutagenicity,
developmental and reproductive toxicity, and neurotoxicity. These
studies include gross and microscopic effects on organs and tissues;
functional effects on bodily organs and systems; effects on blood
parameters (such as red blood cell count, hemoglobin concentration,
hematocrit, and a measure of clotting potential); effects on the
concentrations of normal blood chemicals (including glucose, total
cholesterol, urea nitrogen, creatinine, total protein, total bilirubin,
albumin, hormones, and enzymes such as alkaline phosphatase, alanine
aminotransferase, and cholinesterases); and behavioral or other gross
effects identified through clinical observation and measurement. EPA
examines whether adverse effects are caused by different durations of
exposure ranging from short-term (acute) to long-term (chronic)
pesticide exposure and different routes of exposure (oral, dermal,
inhalation). For chlorpyrifos, the Agency examined acute and steady-
state durations because of the potential to cause adverse effects based
on acute (single day, 24 hours) and steady-state (21-day) exposures.
The latter duration is based on the observation in the available
studies for organophosphates (OPs) indicating a consistent pattern of
AChE inhibition that reaches a steady-state (or comes to an
equilibrium) around 2-3 weeks and does not change in studies of longer
duration. (Ref. 2 at pg. 7) Further, EPA evaluates potential adverse
effects in different age groups (adults as well as fetuses and
juveniles). (Ref. 3 at pgs. 8 through 10)
EPA also considers whether the adverse effect has a threshold--a
level below which exposure has no appreciable chance of causing the
adverse effect. For effects that have no threshold, EPA assumes that
any exposure to the substance increases the risk that the adverse
effect may occur.
b. Level of Concern/Dose-Response Analysis
Once a pesticide's potential hazards are identified, EPA determines
a toxicological level of concern for evaluating the risk posed by human
exposure to the pesticide. In this step of the risk assessment process,
EPA
[[Page 11225]]
essentially evaluates the levels of exposure to the pesticide at which
effects might occur. An important aspect of this determination is
assessing the relationship between exposure (dose) and response (often
referred to as the dose-response analysis). EPA follows differing
approaches to identifying a level of concern for threshold and non-
threshold hazards.
i. Threshold effects. In examining the dose-response relationship
for a pesticide's threshold effects, EPA evaluates an array of toxicity
studies on the pesticide. In each of these studies, EPA attempts to
identify the lowest observed adverse effect level (LOAEL) and the no
observed adverse effect level (NOAEL), which by definition is the next
lower tested dose level below the LOAEL. Generally, EPA will use a
NOAEL from the available studies as a starting point (called ``the
Point of Departure'' or ``PoD'') in estimating the level of concern for
humans. At times, however, EPA will use a LOAEL from a study as the
Point of Departure when no NOAEL is identified in that study and the
LOAEL is close to, or lower than, other relevant NOAELs. PoDs are
selected to be protective of the most sensitive adverse toxic effect
for each exposure scenario and are chosen from toxicity studies that
show clearly defined NOAELs or LOAELs and dose-response relationships.
The Point of Departure is, in turn, used in choosing a level of
concern. EPA will make separate determinations as to the Points of
Departure, and corresponding levels of concern, for both short and long
exposure periods as well as for the different routes of exposure (oral,
dermal, and inhalation).
EPA has also used other approaches for choosing the Point of
Departure. One approach, called a benchmark dose, or BMD, estimates a
point along a dose-response curve that corresponds to a specific
response level. (Ref. 4) For example, a BMD<INF>10</INF> represents a
10% change from the background or typical value for the response of
concern. In contrast to the NOAEL/LOAEL approach, a BMD is calculated
using a range of dose-response data and thus better accounts for the
variability and uncertainty in the experimental results due to
characteristics of the study design, such as dose selection, dose
spacing, and sample size. In addition to a BMD, EPA generally also
calculates a ``confidence limit'' in the BMD. Confidence limits express
the uncertainty in a BMD that may be due to sampling and/or
experimental error. The lower confidence limit on the dose used as the
BMD is termed the BMDL, which the Agency often uses as the PoD. Use of
the BMDL for deriving the PoD rewards better experimental design and
procedures that provide more precise estimates of the BMD, resulting in
tighter confidence intervals. It also provides a health protective
conservative estimate of the safe dose. Numerous scientific peer review
panels have supported the Agency's application of the BMD approach as a
scientifically supportable method for deriving PoDs in human health
risk assessment, and as an improvement over the historically applied
approach of using NOAELs or LOAELs. (Refs. 5 and 6)
Another approach for deriving Points of Departure uses a
sophisticated model called a physiologically based pharmacokinetic-
pharmacodynamic (PBPK-PD) model. PBPK models are mathematical
descriptions of how a chemical enters the body (e.g., breathing,
drinking, eating); the amount of chemical that gets into the blood; how
the chemical moves between body tissues (e.g., fat, brain) and the
blood; and how the body alters (i.e., metabolizes) and eliminates the
chemical (e.g., via urine, feces). PBPK models incorporate information
about the body's anatomical and physiological structure as well as
biochemical processes into the model structure. EPA uses PBPK models to
better translate animal toxicity data to potential human risks (i.e.,
extrapolation). A PBPK model that describes a chemical in a laboratory
animal species can be used for humans by changing the physiological
parameters. In the case of chlorpyrifos assessment, the PBPK-PD model
is used to derive age-, duration-, and route-specific PoDs that would
have resulted in a maximum RBC AChE inhibition level at 10% in humans.
Rather than converting an animal BMDL to derive a human POD, the PBPK-
PD modeling approach accounts for human physiology, biochemistry, life-
stage, and exposure scenarios to derive human PODs based on predicted
AChE inhibition in humans. (Ref. 7) Numerous Federal Advisory
Committees and external review panels have encouraged the use of such a
modeling approach to reduce inherent uncertainty in the risk assessment
and facilitate more scientifically sound extrapolations across studies,
species, routes, and dose levels. The PBPK-PD model for chlorpyrifos
has undergone extensive peer review by various individual and groups,
including the FIFRA Scientific Advisory Panel (SAP) (discussed in Unit
III.A.3.) Significant improvements have been made to the model over the
years in response to recommendations from the 2008, 2011, and 2012
FIFRA SAPs and comments from both internal and external peer reviewers.
(Ref. 2 at pg. 20)
In estimating and describing the level of concern, the Point of
Departure is at times used differently depending on whether the risk
assessment addresses dietary or non-dietary exposures. For dietary
risks, EPA uses the PoD to calculate an acceptable level of exposure or
reference dose (RfD). The RfD is calculated by dividing the PoD by all
applicable safety or uncertainty factors. Typically, EPA uses a
baseline safety/uncertainty factor of 100X in assessing pesticide risk.
That value includes a factor of 10 (10X) where EPA is using data from
laboratory animals to account for the possibility that humans
potentially have greater sensitivity to the pesticide than animals
(also known as the ``inter-species factor'' or ``inter-species
extrapolation factor'') and another factor of 10X to account for
potential variations in sensitivity among members of the human
population (also known as the ``intra-species factor'' or ``intra-
species extrapolation factor''). These factors may vary if data is
available to indicate that another extrapolation factor would be
appropriate and protective. For example, where a PBPK-PD model using
human parameters is used for deriving Points of Departure, there is no
need for an interspecies factor since the model directly predicts human
Points of Departure based on human physiology and biochemistry, rather
than animal studies. Moreover, because the PBPK-PD model used for
assessing chlorpyrifos accounts for differences in metabolism and
toxicity response across the human population for some age groups and
some subpopulations, the intraspecies extrapolation factor can be
refined in accordance with EPA's 2014 Guidance for Applying
Quantitative Data to Develop Data-Derived Extrapolation Factors for
Interspecies and Intraspecies Extrapolation. (Ref. 8)
Additional safety factors may be added to address data deficiencies
or concerns raised by the existing data. Under the FQPA, an additional
safety factor of 10X is presumptively applied to protect infants and
children, unless reliable data support selection of a different factor.
This FQPA additional safety factor largely replaces EPA's pre-FQPA
practice regarding additional safety factors (e.g., LOAEL to NOAEL
factor or database uncertainty factor), but it might also account for
residual concerns related to pre- and postnatal toxicity or exposure.
(Ref. 9 at pgs. 4 through 11)
[[Page 11226]]
In implementing FFDCA section 408, EPA's Office of Pesticide
Programs, also calculates a variant of the RfD referred to as a
Population Adjusted Dose (PAD). A PAD is the RfD divided by the FQPA
safety factor. (Id. at pgs. 13 through 16) RfDs and PADs are generally
calculated for both acute and chronic dietary risks. Throughout this
document, general references to OPP's calculated safe dose are denoted
as an RfD/PAD.
For non-dietary, and combined dietary and non-dietary, risk
assessments of threshold effects, the toxicological level of concern is
not expressed as an RfD/PAD but rather in terms of an acceptable (or
target) margin of exposure (MOE) between human exposure and the Point
of Departure. The ``margin'' of interest is the ratio between human
exposure and the Point of Departure, which is calculated by dividing
human exposure into the Point of Departure. An acceptable MOE is
generally considered to be a margin at least as high as the product of
all applicable safety factors for a pesticide. For example, if a
pesticide needs a 10X factor to account for potential inter-species
differences, 10X factor for potential intra-species differences, and
10X factor for the FQPA children's safety provision, the safe or target
MOE would be an MOE of at least 1,000. What that means is that for the
pesticide in the example to meet the safety standard, human exposure to
the pesticide would generally have to be at least 1,000 times smaller
than the Point of Departure. Like RfD/PADs, specific target MOEs are
selected for exposures of different durations. For non-dietary
exposures, EPA typically examines short-term, intermediate-term, and
long-term exposures. Additionally, target MOEs may be selected based on
both the duration of exposure and the various routes of non-dietary
exposure--dermal, inhalation, and oral.
ii. Non-threshold effects. For risk assessments for non-threshold
effects, EPA does not use the RfD/PAD or MOE approach to choose a level
of concern if quantification of the risk is deemed appropriate. Rather,
EPA calculates the slope of the dose-response curve for the non-
threshold effects from relevant studies frequently using a linear, low-
dose extrapolation model that assumes that any amount of exposure will
lead to some degree of risk. This dose-response analysis will be used
in the risk characterization stage to estimate the risk to humans of
the non-threshold effect.
c. Estimating Human Exposure
Risk is a function of both hazard and exposure. Thus, equally
important to the risk assessment process as determining the hazards
posed by a pesticide and the toxicological level of concern for those
hazards is estimating human exposure. Under FFDCA section 408, EPA must
evaluate the aggregate exposure to a pesticide chemical residue. This
means that EPA is concerned not only with exposure to pesticide
residues in food but also exposure resulting from pesticide
contamination of drinking water supplies and from use of pesticides in
the home or other non-occupational settings. (See 21 U.S.C.
346a(b)(2)(D)(vi)) This statutory requirement specifically clarifies
that the assessment of dietary exposures includes exposure under the
tolerances at issue, as well as ``all other tolerances in effect for
the pesticide chemical residue''. (Id.) Additionally, EPA must take
into account exposure from ``other related substances.'' (Id.)
i. Exposure from food. There are two critical variables in
estimating exposure in food: (1) The types and amount of food that is
consumed and (2) the residue level in that food. Consumption is
estimated by EPA based on scientific surveys of individuals' food
consumption in the United States conducted by the USDA. (Ref. 3 at pg.
12) Information on residue values comes from a range of sources
including crop field trials, data on pesticide reduction (or
concentration) due to processing, cooking, and other practices,
information on the extent of usage of the pesticide, and monitoring of
the food supply. (Ref. 3 at pg. 17)
In assessing exposure from pesticide residues in food, EPA, for
efficiency's sake, follows a tiered approach in which it, in the first
instance, assesses exposure using the worst-case assumptions that 100%
of the crop or commodity in question is treated with, or exposed to,
the pesticide and 100% of the food from that crop or commodity contains
pesticide residues at the tolerance level. (Ref. 3 at pg. 11) When such
an assessment shows no risks of concern, a more refined risk assessment
is unnecessary. By using worst-case assumptions as a starting point for
risk assessment, EPA's resources are conserved, and regulated parties
are spared the cost of any additional studies that may be needed. The
risk assessments produced using the worst-case assumptions yield
conservative and health-protective outcomes; however, if 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 or
commodity actually treated with, or exposed to, the pesticide and data
on the level of residues that may be present on the treated crop or
commodity. These latter data are used to estimate what has been
traditionally referred to by EPA as ``anticipated residues''.
Use of percent crop/commodity treated data and anticipated residue
information is appropriate because EPA's worst-case assumptions of 100%
treatment and residues at tolerance value significantly overstate
residue values. There are several reasons why this is true. First, all
growers of a particular crop would rarely choose to apply the same
pesticide to that crop (some may apply no pesticide; some may apply an
alternative pesticide); generally, the proportion of the crop treated
with a particular pesticide is significantly below 100%. (70 FR 46706,
46731, August 10, 2005) (FRL-7727-4) Second, the tolerance value
represents a high-end or worst-case value. Tolerance values are chosen
only after EPA has evaluated data from experimental trials in which the
pesticide has been used in a manner, consistent with the draft FIFRA
label, that is likely to produce the highest residue in the crop or
food in question (e.g., maximum application rate, maximum number of
applications, minimum pre-harvest interval between last pesticide
application and harvest). (Refs. 3 and 10) These experimental trials
are generally conducted in several locations and involve multiple
samples. (Ref. 10 at pgs. 5 and 7 and Tables 1 and 5) The results from
such experimental trials invariably show that the residue levels for a
given pesticide use will vary from as low as non-detectable to
measurable values in the parts per million (ppm) range with the
majority of the values falling at the lower part of the range. (70 FR
46706 at 46731) EPA uses a statistical procedure to analyze the
experimental trial results and identify the upper bound of expected
residue values. This upper bound value is typically used as the
tolerance value. There may be some commodities for which pesticide
residues come close to the tolerance value where the maximum label
rates are followed, but most generally fall significantly below the
tolerance value. If less than the maximum legal rate is applied,
residues will be even lower. Third, residue values measured at the time
of treatment do not take into account the lowering of residue values
that frequently occurs as a result of degradation over time and through
food processing and cooking.
EPA uses several techniques to refine residue value estimates.
(Ref. 3 at pgs. 17 through 28) First, where appropriate, EPA will take
into account all the
[[Page 11227]]
residue values reported in the experimental trials, either through an
average of all the field trials or consideration of individual field
trials. Second, EPA will consider data showing what portion of the crop
or commodity is not treated with, or exposed to, the pesticide. Third,
data can be produced showing pesticide degradation and decline over
time, and the effect of commercial and consumer food handling and
processing practices. Finally, EPA can consult monitoring data gathered
by the FDA, the USDA, or pesticide registrants, on pesticide levels in
food at points in the food distribution chain distant from the farm,
including retail food establishments. Monitoring data, including data
gathered by USDA's Pesticide Data Program (PDP), generally provide a
characterization of pesticide residues in or on foods consumed by the
U.S. population that closely approximates real-world exposures because
they are sampled closer to the point of consumption in the chain of
commerce than field trial data, which are generated to establish the
maximum level of legal residues that could result from maximum
permissible use of the pesticide immediately after harvest.
Another critical component of the exposure assessment is how data
on consumption patterns are combined with data on pesticide residue
levels in food. Traditionally, EPA has calculated exposure by simply
multiplying average consumption by average residue values for
estimating chronic risks and high-end consumption by maximum residue
values for estimating acute risks. Using average residues is a
realistic approach for chronic risk assessment due to the fact that
variations in residue levels and consumption amounts average out over
time, especially given the nationwide market for food in the United
States. Using average values is inappropriate for acute risk
assessments, however, because in assessing acute exposure situations it
matters how much of each treated food a given consumer eats in the
short-term and what the residue levels are in the particular foods
consumed. Yet, using maximum residue values for acute risk assessment
tends to greatly overstate exposure because it is unlikely that a
person would consume at a single meal multiple food components bearing
high-end residues. To take into account the variations in short-term
consumption patterns and food residue values for acute risk
assessments, EPA uses probabilistic modeling techniques for estimating
exposure when more simplistic models appear to show risks of concerns.
In practice, EPA uses a computer program known as the Dietary
Exposure Evaluation Model and Calendex software with the Food Commodity
Intake Database (DEEM-FCID version 3.16/Calendex) to estimate dietary
exposure from pesticide residues in food by combining data on human
consumption amounts with residue values in food commodities. The model
used for assessment of chlorpyrifos in the 2020 human health risk
assessment (HHRA) incorporated 2003-2008 consumption data from USDA's
National Health and Nutrition Examination Survey/What We Eat in America
database (NHANES/WWEIA). The data are based on the reported consumption
of more than 20,000 individuals over two non-consecutive survey days.
Foods ``as consumed'' (e.g., apple pie) are linked to EPA-defined food
commodities (e.g., apples, peeled fruit--cooked; fresh or N/S (Not
Specified); baked; or wheat flour--cooked; fresh or N/S, baked) using
publicly available recipe translation files developed jointly by USDA
Agricultural Research Service (ARS) and EPA. For chronic exposure
assessment (or in the case of chlorpyrifos, for steady-state exposure
assessment), consumption data are averaged for the entire U.S.
population and within population subgroups; however, for acute exposure
assessment, consumption data are retained as individual consumption
events. Using this consumption information and residue data, the
exposure estimates are calculated for the general U.S. population and
specific subgroups based on age, sex, ethnicity, and region.
All of these refinements to the exposure assessment process, from
use of food monitoring data through probabilistic modeling, can have
dramatic effects on the level of exposure predicted, typically reducing
worst-case estimates by at least 1 or 2 orders of magnitude. (Ref. 11
at pgs. 16 through 17; 70 FR 46706 at 46732)
For chlorpyrifos, EPA has calculated potential risk by using
probabilistic techniques to combine distributions of potential
exposures in sentinel populations. The resulting probabilistic
assessments present a range of dietary exposure/risk estimates. Because
probabilistic assessments generally present a realistic range of
residue values to which the population may be exposed, EPA's starting
point for estimating exposure and risk for such assessments is the
99.9th percentile of the population under evaluation. When using a
probabilistic method of estimating acute dietary exposure, EPA
typically assumes that, when the 99.9th percentile of acute exposure is
equal to or less than the acute PAD (aPAD), the level of concern for
acute risk has not been exceeded. By contrast, where the analysis
indicates that estimated exposure at the 99.9th percentile exceeds the
aPAD, EPA would generally conduct one or more sensitivity analyses to
determine the extent to which the estimated exposures at the high-end
percentiles may be affected by unusually high food consumption or
residue values. (The same assumptions apply to estimates for steady-
state dietary exposure and the steady-state PAD (ssPAD).) To the extent
that one or a few values seem to ``drive'' the exposure estimates at
the high-end of exposure, EPA would consider whether these values are
reasonable and should be used as the primary basis for regulatory
decision making. (Ref. 11)
ii. Exposure from water. (a) Modeling and monitoring data. EPA may
use either or both field monitoring data and mathematical water
exposure models to generate pesticide exposure estimates in drinking
water. Monitoring and modeling are both important tools for estimating
pesticide concentrations in water and can provide different types of
information. Monitoring data can provide estimates of pesticide
concentrations in water that are representative of specific
agricultural or residential pesticide practices and under environmental
conditions associated with a sampling design. Although monitoring data
can provide a direct measure of the concentration of a pesticide in
water, it does not always provide a reliable estimate of exposure
because sampling may not occur in areas with the highest pesticide use,
and/or the sampling may not occur when the pesticides are being used.
When monitoring data meet certain data quantity criteria, EPA has tools
available to quantify the uncertainty in available monitoring data such
that it can be used quantitively to estimate pesticide concentrations
in drinking water. (Ref. 12) Furthermore, monitoring data can be used
in a weight of evidence (WOE) approach with model estimated
concentrations to increase confidence in the conclusions of a drinking
water assessment.
Due often to the limitations in many monitoring studies, EPA uses
mathematical water exposure models to estimate pesticide exposure
levels in drinking water. EPA's models are based on extensive
monitoring data and detailed information on soil properties, crop
characteristics, and weather patterns to estimate water concentrations
in vulnerable locations where the pesticide could be used according to
its label. (Ref. 13 at pgs. 27 and 28) (See also 69 FR 30042, 30058
[[Page 11228]]
through 30065, May 26, 2004) (FRL-7355-7) These models calculate
estimated environmental concentrations of pesticides using laboratory
data that describe how fast the pesticide breaks down to other
chemicals and how it moves in the environment. The modeling provides an
estimate of pesticide concentrations in ground water and surface water.
Depending on the modeling algorithm (e.g., surface water modeling
scenarios), daily concentrations can be estimated continuously over
long periods of time, and for places that are of most interest for any
particular pesticide. Modeling is a useful tool for characterizing
vulnerable sites and can be used to estimate peak concentrations from
infrequent, large rain events.
EPA relies on models it has developed for estimating pesticide
concentrations in both surface water and groundwater. The most common
model used to conduct drinking water assessments is the Pesticide in
Water Calculator (PWC). PWC couples the Pesticide Root Zone Model
(PRZM) and Variable Volume Water Model (VVWM) together to simulate
pesticide fate and transport from the field of application to an
adjacent reservoir. (Ref. 13 at pgs. 27 and 28) The PWC estimates
pesticide concentrations for an index reservoir that is modeled for
site-specific scenarios (i.e., weather and soil data) in different
areas of the country. A detailed description of the models routinely
used for exposure assessment is available from the EPA OPP Aquatic
Models website: <a href="https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/models-pesticide-risk-assessment#aquatic">https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/models-pesticide-risk-assessment#aquatic</a>.
In modeling potential surface water concentrations, EPA attempts to
model areas of the country that are vulnerable to surface water
contamination rather than simply model ``typical'' concentrations
occurring across the nation. EPA models exposures occurring in small
highly agricultural watersheds in different growing areas throughout
the country, over a 30-year period. The scenarios are designed to
capture residue levels in drinking water from reservoirs with small
watersheds with a large percentage of land use in agricultural
production. EPA believes these assessments are likely reflective of a
small subset of the watersheds across the country that maintain
drinking water reservoirs, representing a drinking water source
generally considered to be more vulnerable to frequent high
concentrations of pesticides than most locations that could be used for
crop production.
(b) Drinking Water Level of Comparison (DWLOC). The drinking water
level of comparison (DWLOC) is an estimate of the maximum concentration
of the pesticide (and other residues of concern) that may be in
drinking water without triggering a risk concern for human health.
(Ref. 13 at pg. 10) The DWLOC is a benchmark that can be used to guide
refinements of the drinking water assessment (DWA). This value relates
to the concept of the ``risk cup,'' which EPA developed to facilitate
risk refinement when considering aggregate human health risk to a
pesticide. (Ref. 14) The risk cup is the total exposure allowed for a
pesticide considering its toxicity and required safety factors. The
risk cup is equal to the maximum safe exposure for the duration and
population being considered. Exposures exceeding the risk cup are of
potential concern. There are risk cups for each pertinent duration of
exposure (e.g., acute, short-term, chronic). The exposure durations
most commonly of interest for acute or short-term pesticide exposure
risk assessments are 1-day, 4-day, and 21-day averages. For example,
the relevant exposure duration for AChE reversible inhibition from
exposure to N-methyl carbamate insecticides is 1-day, while AChE
irreversible inhibition resulting from exposure to OP insecticides is
usually 21-days based on steady-state kinetics. (Ref. 5)
When using the DWLOC approach, EPA calculates the total exposure
from food consumption and residential (or other non-occupational)
exposures and subtracts this value from the maximum safe exposure
level. The resulting value is the allowable remaining exposure without
the potential for adverse health effect, and this allowable remaining
exposure becomes the remaining space in the ``risk cup'' for pesticide
exposures in drinking water. Knowing this allowable remaining exposure
and the water consumption for each population subgroup (e.g., infants),
the Agency can calculate the DWLOC, which is the estimate of safe
concentrations of pesticides in drinking water. Using this process of
DWLOC calculation allows EPA to determine a target maximum safe
drinking water concentration, which makes it easier to identify
instances where drinking water estimates require refinement. (Ref. 13
at pgs. 19 and 20)
(c) Scale of drinking water assessment. Although food is
distributed nationally, and residue values are therefore not expected
to vary substantially throughout the country, drinking water is locally
derived and concentrations of pesticides in source water fluctuate over
time and location for a variety of reasons. Pesticide residues in water
fluctuate daily, seasonally, and yearly because of the timing of the
pesticide application, the vulnerability of the water supply to
pesticide loading through runoff, spray drift and/or leaching, and
changes in the weather. Concentrations are also affected by the method
of application, the location, characteristics of the sites where a
pesticide is used, the climate, and the type and degree of pest
pressure, which influences the application timing, rate used, and
number of treatments in a crop production cycle.
EPA may conduct a drinking water assessment (DWA) for a national
scale depending on the pesticide use under evaluation. A national-scale
DWA may use a single upper-end pesticide concentration as a starting
point for assessing whether additional refinements are needed or
estimated pesticide concentrations for certain site-specific scenarios
that are associated with locations in the United States vulnerable to
pesticide contamination based on pesticide use patterns. (Ref. 13 at
pg. 22)
EPA may also conduct a regional-scale DWA to focus on areas where
pesticide concentrations may be higher than the DWLOC. Under this type
of assessment, EPA estimates pesticide concentrations across different
regions in the United States that correspond with specific hydrologic
units identified by a unique hydrologic unit code (HUC). For purposes
of assessing chlorpyrifos, EPA evaluated concentrations in the 21 major
geographic areas (or regions) used that comprise the United States.
These areas contain either the drainage area of a major river or a
combined drainage of a series of rivers. This information can be found
at: <a href="https://water.usgs.gov/GIS/huc.html">https://water.usgs.gov/GIS/huc.html</a>. Estimated pesticide
concentrations under this approach would be associated with a
vulnerable pesticide use area somewhere within the evaluated region.
(Ref. 13 at pg. 23)
(d) Refinements to drinking water assessments. Much like the tiered
approach used for assessing exposures of pesticides in food, EPA has
defined four tiers for drinking water assessments. Lower-tiered
assessments are more conservative based on the defaults or upper bound
assumptions and may compound conservatisms, while higher tiers
integrate more available data and provide more realistic estimates of
environmental pesticide concentrations.
These four tiers are generally based on the level of effort, the
amount of data considered, the spatial scale, and the
[[Page 11229]]
certainty in the estimated pesticide concentration. Each successive
tier integrates more focused pesticide, spatial, temporal, agronomic,
and crop-specific information. Tier 1 requires the least amount of
effort and the least amount of data, whereas Tier 4 is resource
intensive, considers a wide range of sources and types of data, and is
spatially explicit. The order in which refinements are considered
(i.e., the order in which the assessment is refined) is pesticide-
specific and depends on the nature and quality of the available data
used to support the refinement. Additional information on the conduct
of drinking water assessments can be found in EPA's ``Framework for
Conducting Pesticide Drinking Water Assessment for Surface Water''
(Drinking Water Framework) (Ref. 13).
As discussed in the Drinking Water Framework, EPA can incorporate
several refinements in higher tiered modeling. Two such refinements are
the percent cropped area (PCA) and the percent crop treated (PCT). The
PCA refers to the amount of area in a particular community water system
that is planted with the crop of interest (e.g., the default assumption
is that the entire watershed is planted with a crop of interest). The
PCT refers to the amount of the cropped area that is treated with the
pesticide of interest (e.g., the default is that the entire cropped
area is treated with the pesticide of interest). With additional use
and usage data, EPA can refine assumptions about the application rate
and PCT for use in modeling to generate estimated drinking water
concentrations (EDWCs) that are appropriate for human health risk
assessment and more accurately account for the contribution from
individual use patterns in the estimation of drinking water
concentrations. The goal of the PCA and PCT refinements are to generate
EDWCs that are appropriate for human health risk assessment that reduce
the magnitude of overestimation due to variability in crops and actual
pesticide usage. (Ref. 15)
iii. Non-occupational (Residential) exposures. Residential
assessments examine exposure to pesticides in non-occupational or
residential settings (e.g., homes, parks, schools, athletic fields, or
any other areas frequented by the general public), based on registered
uses of the pesticide. Exposures to pesticides may occur to persons who
apply pesticides (which is referred to as residential handler exposure)
or to persons who enter areas previously treated with pesticides (which
is referred to as post-application exposure). Such exposures may occur
through oral, inhalation, or dermal routes and may occur over different
exposure durations (e.g., short-term, intermediate-term, long-term),
depending on the type of pesticide and particular use pattern.
Residential assessments are conducted through examination of
significant exposure scenarios (e.g., children playing on treated lawns
or homeowners spraying their gardens) using a combination of generic
and pesticide-specific data. To standardize this process, EPA has
prepared Standard Operating Procedures (SOPs) for conducting
residential assessments on a wide array of scenarios that are intended
to address all major possible means by which individuals could be
exposed to pesticides in a non-occupational environment. (Ref. 16) SOPs
have been developed for many common exposure scenarios including
pesticide treatment of lawns, garden plants, trees, swimming pools,
pets, and indoor surfaces including crack-and-crevice treatments.
The SOPs identify relevant generic data and construct algorithms
for calculating application and post-application exposures in a
residential or non-occupational setting using these generic data in
combination with pesticide-specific information. The generic data
typically involve survey data on behavior patterns (e.g., activities
conducted on turf and time spent on these activities) and transfer
coefficient data (i.e., data measuring the amount of pesticide that
transfers from the environment to humans during some activity).
Specific information on pesticides can include information on residue
levels as well as information on environmental fate such as degradation
data.
Once EPA assesses all the potential exposures from all applicable
residential exposure scenarios, EPA selects the highest exposure
scenario for each exposed population to calculate representative risk
estimates for use in the aggregate exposure assessment. Those specific
exposure values are then combined with the life-stage appropriate
exposure values provided for food and drinking water to determine
whether a safety finding can be made.
iv. Aggregate exposures. The aggregate exposure assessment process
considers exposure through multiple pathways or routes of exposure
(e.g., food, water, and residential) for different sub-populations
(e.g., infants, children ages 1 through 6) and exposure duration or
types of effects (e.g., acute noncancer effects (single dose), chronic
noncancer effects, and cancer). The aggregated exposure assessments can
be deterministic (levels of exposure for each pathway are point
estimates), probabilistic (levels of exposure are a distribution for a
given population), or a combination of the two and are dependent on the
level of refinement or assessment tier.
EPA evaluates aggregate exposure by comparing combined exposure
from all relevant sources to the safe level. Where exposures exceed the
safe level, those levels exceed the risk cup and are of potential
concern. There are risk cups for each pertinent duration of exposure
for a pesticide because the amount of exposure that can be incurred
without adverse health effects will vary by duration (e.g., acute,
short-term, chronic, steady-state). The size of the risk cup is
dependent on the maximum safe exposure for the different relevant
durations (e.g., acute, short-term, intermediate-term, long-term,
steady-state).
d. Risk Characterization
The final step in the risk assessment is risk characterization. In
this step, EPA combines information from the first three steps (hazard
identification, level of concern/dose-response analysis, and human
exposure assessment) to quantitatively estimate the risks posed by a
pesticide. Separate characterizations of risk are conducted for
different durations of exposure. Additionally, separate and, where
appropriate, aggregate characterizations of risk are conducted for the
different routes of exposure (dietary and non-dietary).
Whether exposures will exceed the available space in the risk cup
(i.e., whether exposures are expected to exceed safe levels) is
expressed differently, depending on the type of level of concern (i.e.,
RfD/PAD or MOE) the Agency has identified. For dietary assessments for
which EPA calculates an RfD/PAD, the risk is expressed as a percentage
of the acceptable dose (i.e., the dose which EPA has concluded will be
``safe''). Dietary exposures greater than 100% of the percentage of the
acceptable dose are generally cause for concern and would be considered
``unsafe'' within the meaning of FFDCA section 408(b)(2)(B). For non-
dietary (and combined dietary and non-dietary) risk assessments of
threshold effects, the toxicological level of concern is typically not
expressed as an RfD/PAD, but rather in terms of an acceptable (or
target) Margin of Exposure (MOE) between human exposure and the PoD.
Non-dietary (and combined) exposures that result in an MOE equal to or
exceeding the product of all applicable
[[Page 11230]]
safety factors would not generally be of concern.
As a conceptual matter, the RfD/PAD and MOE approaches are
fundamentally equivalent. For a given risk and given exposure of a
pesticide, if exposure to a pesticide were found to be acceptable under
an RfD/PAD analysis it would also pass under the MOE approach, and
vice-versa. However, for any specific pesticide, risk assessments for
different exposure durations or routes may yield different results.
This is a function not of the choice of the RfD/PAD or MOE approach but
of the fact that the levels of concern and the levels of exposure may
differ depending on the duration and route of exposure.
Where EPA has calculated a DWLOC, the Agency can assess risk by
comparing estimated pesticide concentrations in drinking water to the
DWLOC. As noted previously, an aggregate DWLOC represents the amount of
maximum safe residues of pesticide in drinking water because it
represents the room remaining in the risk cup for drinking water
exposures, after accounting for the food and residential exposures.
When the EDWC is less than the DWLOC, there are no risk concerns for
aggregate exposures because the Agency can conclude that the
contribution from drinking water, when aggregated with food and non-
occupational exposures, will not exceed safe levels of exposure.
Conversely, an EDWC at or exceeding the DWLOC would indicate a risk of
concern, as pesticide exposures in drinking water, when aggregated with
exposures from food and residential exposures, would exceed safe levels
of exposure. (Ref. 14)
For non-threshold risks (generally, cancer risks), EPA uses the
slope of the dose-response curve for a pesticide in conjunction with an
estimation of human exposure to that pesticide to estimate the
probability of occurrence of additional adverse effects. Under FFDCA
section 408, for non-threshold cancer risks, EPA generally considers
cancer risk to be negligible if the probability of increased cancer
cases falls within the range of 1 in 1 million. EPA describes this
quantitative standard as a ``range'' because it does not want to impart
a false precision to numerical cancer risk estimates. EPA seeks to
identify risks differing significantly from a 1 in 1 million risk, and
that involves both a quantitative as well as qualitative assessment of
what a risk estimate represents.
2. EPA Policy on the FQPA Children's Safety Factor
As the summary of EPA's risk assessment practice indicates, the use
of safety factors plays a critical role in the process. This is true
for traditional safety factors to account for potential differences
between animals and humans when relying on studies in animals (inter-
species factor) and potential differences among humans (intra-species
factor), as well as the FQPA's additional 10X children's safety factor.
In implementing the children's safety factor provision, EPA has
interpreted it as imposing a presumption in favor of applying a 10X
safety factor, in addition to the traditional safety factors for inter-
and intra-species extrapolation. (Ref. 9 at pgs. 4 and 11) Thus, EPA
generally refers to the FQPA 10X factor as a presumptive or default 10X
factor. EPA has also made clear, however, that this presumption or
default in favor of the FQPA 10X safety factor is only a presumption.
The presumption can be overcome if reliable data demonstrate that a
different factor is safe for children. (Id.) In determining whether a
different factor is safe for children, EPA focuses on the three factors
listed in section 408(b)(2)(C) of the FFDCA--the completeness of the
toxicity database, the completeness of the exposure database, and
potential pre- and postnatal toxicity. In examining these factors, EPA
strives to make sure that its choice of a safety factor, based on a WOE
evaluation, does not understate the risk to children. (Id. at pgs. 24
through 25 and 35)
3. Acetylcholinesterase Inhibition
Acetylcholinesterase (AChE) inhibition is a disruption of the
normal process in the body by which the nervous system chemically
communicates with muscles and glands. Communication between nerve cells
and a target cell (i.e., another nerve cell, a muscle fiber, or a
gland) is facilitated by the chemical, acetylcholine. When a nerve cell
is stimulated, it releases acetylcholine into the synapse (or space)
between the nerve cell and the target cell. The released acetylcholine
binds to receptors in the target cell, stimulating the target cell in
turn. As EPA has explained, ``the end result of the stimulation of
cholinergic pathway(s) includes, for example, the contraction of smooth
(e.g., in the gastrointestinal tract) or skeletal muscle, changes in
heart rate or glandular secretion (e.g., sweat glands) or communication
between nerve cells in the brain or in the autonomic ganglia of the
peripheral nervous system.'' (Ref. 17 at pg. 10)
AChE is an enzyme that breaks down acetylcholine and terminates its
stimulating action in the synapse between nerve cells and target cells.
When AChE is inhibited, acetylcholine builds up prolonging the
stimulation of the target cell. This excessive stimulation potentially
results in a broad range of adverse effects on many bodily functions
including muscle cramping or paralysis, excessive glandular secretions,
or effects on learning, memory, or other behavioral parameters.
Depending on the degree of inhibition, these effects can be serious or
even fatal.
EPA's cholinesterase inhibition policy statement explains EPA's
approach to evaluating the risks posed by AChE-inhibiting pesticides
such as chlorpyrifos. (Id.) The policy focuses on three types of
effects associated with AChE-inhibiting pesticides that may be assessed
in animal and human toxicological studies: (1) Physiological and
behavioral/functional effects; (2) AChE inhibition in the central and
peripheral nervous system; and (3) AChE inhibition in red blood cells
and blood plasma. The policy discusses how such data should be
integrated in deriving an acceptable dose (e.g., RfD/PAD) for an AChE-
inhibiting pesticide.
After clinical signs or symptoms, AChE inhibition in the nervous
system provides the next most important endpoint for evaluating AChE-
inhibiting pesticides. Although AChE inhibition in the nervous system
is not itself regarded as a direct adverse effect, it is ``generally
accepted as a key component of the mechanism of toxicity leading to
adverse cholinergic effects.'' (Id. at pg. 25) As such, the policy
states that it should be treated as ``direct evidence of potential
adverse effects'' and ``data showing this response provide valuable
information in assessing potential hazards posed by anticholinesterase
pesticides.'' (Id.) Unfortunately, useful data measuring AChE
inhibition in the peripheral nervous system tissues has only been
relatively rarely captured by standard toxicology testing. For central
nervous system effects, however, more recent neurotoxicity studies
``have sought to characterize the time course of inhibition in * * *
[the] brain, including brain regions, after acute and 90-day
exposures.'' (Id. at pg. 27)
AChE inhibition in the blood is one step further removed from the
direct harmful consequences of AChE-inhibiting pesticides. According to
the policy, inhibition of blood AChEs ``is not an adverse effect, but
may indicate a potential for adverse effects on the nervous system.''
(Id. at pg. 28) The policy states that ``[a]s a matter of science
policy, blood cholinesterase data are considered appropriate surrogate
measures of potential effects on peripheral nervous system
[[Page 11231]]
acetylcholinesterase activity in animals, for CNS [central nervous
system] acetylcholinesterase activity in animals when CNS data are
lacking and for both peripheral and central nervous system
acetylcholinesterase in humans.'' (Id. at pg. 29) The policy notes that
``there is often a direct relationship between a greater magnitude of
exposure [to an AChE-inhibiting pesticide] and an increase in incidence
and severity of clinical signs and symptoms as well as blood
cholinesterase inhibition.'' (Id. at pg. 30) Thus, the policy regards
blood AChE data as ``appropriate endpoints for derivation of reference
doses or concentrations when considered in a weight-of-the-evidence
analysis of the entire database * * *.'' (Id. at pg. 29) Between AChE
inhibition measured in red blood cell (``RBC'') or blood plasma, the
policy states a preference for reliance on RBC AChE measurements
because plasma cholinesterase is composed of a mixture of
acetylcholinesterase and butyrylcholinesterase, and inhibition of the
latter is less clearly tied to inhibition of acetylcholinesterase in
the nervous system. (Id. at pgs. 29 and 32)
In the Agency's analysis for chlorpyrifos, EPA used a response
level of 10% RBC AChE inhibition; this value represents the estimated
dose where AChE is inhibited by 10%, compared to untreated animals. For
the last several years EPA has used the 10% value to regulate AChE-
inhibiting pesticides, including other organophosphorous pesticides.
For a variety of toxicological and statistical reasons, EPA chose 10%
RBC AChE inhibition as the response level for use in its PBPK-PD
modeling. (Ref. 2 at pg. 7) EPA analyses have demonstrated that 10% is
a level that can be reliably measured in the majority of rat toxicity
studies; is generally at or near the limit of sensitivity for
discerning a statistically significant decrease in AChE activity across
the brain compartment; and is a response level close to the background.
III. Chlorpyrifos Background
A. Regulatory Background
1. General
a. Chlorpyrifos Uses
Chlorpyrifos (0,0-diethyl-0-3,5,6-trichloro-2-pyridyl
phosphorothioate) is a broad-spectrum, chlorinated organophosphate (OP)
insecticide that has been registered for use in the United States since
1965. (The OPs are a group of closely related pesticides that affect
functioning of the nervous system.) Pesticide products containing
chlorpyrifos are registered for use on many agricultural crops,
including, but not limited to, corn, soybeans, alfalfa, oranges, wheat,
and walnuts. Additionally, chlorpyrifos products are registered for use
on nonfood sites such as ornamental plants in nurseries, golf course
turf, and as wood treatment. There are also public health uses
including aerial and ground-based mosquito adulticide fogger
treatments, use as fire ant control in nursery stock grown in USDA-
designated quarantine areas, and for some tick species that may
transmit diseases such as Lyme disease. The majority of uses in
residential settings were voluntarily canceled over two decades ago
(e.g., 65 FR 76233, December 6, 2000 (FRL-6758-2); 66 FR 47481,
September 12, 2001 (FRL-6799-7)).
b. Chlorpyrifos Risks
i. Acetylcholinesterase (AChE) inhibition. Chlorpyrifos, like other
OP pesticides, affects the nervous system by inhibiting AChE, an enzyme
necessary for the proper functioning of the nervous system, and
ultimately leading to signs of neurotoxicity. This mode of action, in
which AChE inhibition leads to neurotoxicity, is well-established, and
thus has been used as basis for the PoD for OP human health risk
assessments, including chlorpyrifos. This science policy is based on
decades of work, which shows that AChE inhibition is the initial event
in the pathway to acute cholinergic neurotoxicity. (Ref. 17 at pg. 14)
The Agency has conducted a comprehensive review of the available
data and public literature regarding this adverse effect from
chlorpyrifos. (Ref. 18 at pgs. 25 through 27) There are many
chlorpyrifos studies evaluating RBC AChE inhibition or the brain in
multiple lifestages (gestational, fetal, postnatal, and non-pregnant
adult); multiple species (rat, mouse, rabbit, dog, human); methods of
oral administration (oral gavage with corn oil, dietary, gavage via
milk); and routes of exposure (oral, dermal, inhalation via vapor and
via aerosol). In addition, chlorpyrifos is unique in the availability
of AChE data from peripheral tissues in some studies (e.g., heart,
lung, liver). There are also literature studies comparing the in vitro
AChE response to a variety of tissues that show similar sensitivity and
intrinsic activity. Across the database, brain AChE tends to be less
sensitive than RBC AChE or peripheral AChE. In oral studies, RBC AChE
inhibition is generally similar in response to peripheral tissues.
Thus, the in vitro data and oral studies combined support the continued
use of RBC AChE inhibition as the critical effect for quantitative
dose-response assessment.
Female rats tend to be more sensitive than males to these AChE
effects. For chlorpyrifos, there are data from multiple studies which
provide robust RBC AChE data in pregnant, lactating, and non-pregnant
female rats from oral exposure (e.g., developmental neurotoxicity
(DNT), reproductive, and subchronic data).
In addition, studies are available in juvenile pups that show age-
dependent differences, particularly following acute exposures, in
sensitivity to chlorpyrifos and its oxon metabolite. This sensitivity
is not derived from differences in the AChE enzyme itself but instead
are derived largely from the immature metabolic clearance capacity in
the juveniles.
ii. Neurodevelopmental toxicity. In addition to information on the
effects of chlorpyrifos on AChE, there is an extensive body of
information (in the form of laboratory animal studies, epidemiological
studies, and mechanistic studies) studying the potential effects on
neurodevelopment in infants and children following exposure to OPs,
including chlorpyrifos.
There are numerous laboratory animal studies on chlorpyrifos in the
literature that have evaluated the impact of chlorpyrifos exposure in
pre- and postnatal dosing on the developing brain. These studies vary
substantially in their study design, but all involve gestational and/or
early postnatal dosing with behavioral evaluation from adolescence to
adulthood. The data provide qualitative support for chlorpyrifos to
potentially impact the developing mammalian brain with adverse outcomes
in several neurological domains including cognitive, anxiety and
emotion, social interactions, and neuromotor function. It is, however,
important to note that there is little consistency in patterns of
effects across studies. In addition, most of these studies use doses
that far exceed EPA's 10% benchmark response level for RBC AChE
inhibition. There are only a few studies with doses at or near the 10%
brain or RBC AChE inhibition levels; among these only studies from Carr
laboratory at Mississippi State University are considered by EPA to be
high quality. EPA has concluded that the laboratory animal studies on
neurodevelopmental outcomes are not sufficient for quantitatively
establishing a PoD. (Ref. 2 at pgs. 88 and 89)
EPA evaluated numerous epidemiological studies on chlorpyrifos and
other OP pesticides in accordance with the Agency's ``Framework for
[[Page 11232]]
Incorporating Human Epidemiologic & Incident Data in Health Risk
Assessment'' (``Epidemiologic Framework''). (Ref. 19) The most robust
epidemiologic research comes from three prospective birth cohort
studies. These include: (1) The Mothers and Newborn Study of North
Manhattan and South Bronx performed by the Columbia Children's Center
for Environmental Health (CCCEH) at Columbia University (``CCCEH
study''); (2) the Mount Sinai Inner-City Toxicants, Child Growth and
Development Study (``Mt. Sinai study''); and (3) the Center for Health
Assessment of Mothers and Children of Salinas Valley (CHAMACOS)
conducted by researchers at University of California Berkeley
(``CHAMACOS study''). (Ref. 20 at pgs. 32 through 43)
In the case of the CCCEH study, which specifically evaluated the
possible connections between chlorpyrifos levels in cord blood and
neurodevelopmental outcomes on a specific cohort, there are a number of
notable associations. (Id. at pgs. 35 through 38) Regarding infant and
toddler neurodevelopment, the CCCEH study authors reported
statistically significant deficits of 6.5 points on the Psychomotor
Development Index at three years of age when comparing high to low
exposure groups. Notably, these decrements persist even after
adjustment for group and individual level socioeconomic variables.
These investigators also observed increased odds of mental delay and
psychomotor delay at age three when comparing high to low exposure
groups. The CCCEH study authors also report strong, consistent evidence
of a positive association for attention disorders, attention deficit
hyperactivity disorder (ADHD), and pervasive development disorder (PDD)
when comparing high to low chlorpyrifos exposure groups. Moreover, it
was reported that for children in the CCCEH study cohort at age seven
for each standard deviation increase in chlorpyrifos cord blood
exposure, there is a 1.4% reduction in Full-Scale IQ and a 2.8%
reduction in Working Memory. In addition, the CCCEH study authors
evaluated the relationship between prenatal chlorpyrifos exposure and
motor development/movement and reported elevated risks of arm tremor in
children around 11 years of age in the CCCEH cohort.
Notwithstanding the observed associations, EPA and the 2012 and
2016 FIFRA SAPs identified multiple uncertainties in the CCCEH
epidemiology studies. (Refs. 21 and 22) Some of these include the
relatively modest sample sizes, which limited the statistical power;
exposure at one point in prenatal time with no additional information
regarding postnatal exposures; representativeness of a single-point
exposure where time-varying exposures or the ability to define
cumulative exposures would be preferable; lack of specificity of a
critical window of effect and the potential for misclassification of
individual exposure measures; and lack of availability of the raw data
from the studies that would allow verification of study conclusions.
One of the notable uncertainties in the CCCEH epidemiology studies
identified by EPA and the 2016 FIFRA SAP is the lack of specific
exposure information on the timing, frequency, and magnitude of
chlorpyrifos application(s) in the apartments of the women in the
study. Despite extensive effort by EPA to obtain or infer this exposure
information from various sources, the lack of specific exposure data
remains a critical uncertainty. EPA made efforts in 2014 and 2016 to
develop dose reconstruction of the exposures to these women. These dose
reconstruction activities represent the best available information and
tools but are highly uncertain. In addition, the pregnant women and
children in the CCCEH studies were exposed to multiple chemicals,
including multiple potent AChE inhibiting OPs and N-methyl carbamates.
Moreover, using EPA's dose reconstruction methods from 2014 suggest
that the pregnant women likely did not exhibit RBC AChE inhibition
above 10%. The 2012 and 2016 FIFRA SAP reports expressed concern that
it is likely that the CCCEH findings occurred at exposure levels below
those that result in 10% RBC AChE inhibition. (Refs. 21 and 22)
However, given the available CCCEH exposure information and the
exposures to multiple potent AChE inhibiting pesticides, EPA cannot
definitively attribute all AChE inhibition to chlorpyrifos. EPA remains
unable to make a causal linkage between chlorpyrifos exposure and the
outcomes reported by CCCEH investigators. (Ref. 20 at pg. 43) Moreover,
given the uncertainties, particularly in the exposure information
available from CCCEH (single timepoints, lack of time varying exposure,
lack of knowledge about application timing), uncertainties remain about
the dose-response relationships from the epidemiology studies.
Finally, there are several lines of evidence for actions of
chlorpyrifos distinct from the classical mode of action of AChE
inhibition. This information has been generated from model systems
representing different levels of biological organization and provide
support for molecular initiating events (binding to the morphogenic
site of AChE, muscarinic receptors, or tubulin), cellular responses
(alterations in neuronal proliferation, differentiation, neurite
growth, or intracellular signaling), and responses at the level of the
intact nervous system (serotonergic tone, axonal transport). Among the
many in vitro studies on endpoints relevant to the developing brain
available for chlorpyrifos, only three have identified outcomes in
picomole concentrations, including concentrations lower than those that
elicit AChE inhibition in vitro. However, as is the case for many other
developmental neurotoxicants, most of these studies have not been
designed with the specific goal of construction or testing an adverse
outcome pathway. Thus, there are not sufficient data available to test
rigorously the causal relationship between effects of chlorpyrifos at
the different levels of biological organization in the nervous system.
(Id. at pgs. 27 through 31)
Due to the complexity of nervous system development involving the
interplay of many different cell types and developmental timelines, it
is generally accepted that no single in vitro screening assay can
recapitulate all the critical processes of neurodevelopment. As a
result, there has been an international effort to develop a battery of
new approach methodologies (NAMs) to inform the DNT potential for
individual chemicals. This DNT NAM battery is comprised of in vitro
assays that assess critical processes of neurodevelopment, including
neural network formation and function, cell proliferation, apoptosis,
neurite outgrowth, synaptogenesis, migration, and differentiation. In
combination the assays in this battery provide a mechanistic
understanding of the underlying biological processes that may be
vulnerable to chemically-induced disruption. It is noteworthy, however,
that the quantitative relationship between alterations in these
neurodevelopmental processes and adverse health outcomes has, to date,
not been fully elucidated. Moreover, additional assays evaluating other
critical neurodevelopmental processes such as myelination are still
being developed. (Ref. 23)
In September 2020, EPA convened a FIFRA SAP on developing and
implementing NAMs using methods such as in vitro techniques and
computational approaches. Included in that consideration was use of the
DNT NAM battery to evaluate OP compounds as a case study. These methods
[[Page 11233]]
presented to the 2020 FIFRA SAP provide a more systematic approach to
evaluating pharmacodynamic effects on the developing brain compared to
the existing literature studies. Initial data from the NAM battery were
presented to the SAP for 27 OP compounds, including chlorpyrifos and
its metabolite, chlorpyrifos-oxon, and, when possible, compared to in
vivo results (by using in vitro to in vivo extrapolation). On December
21, 2020, the SAP released its final report and recommendations on
EPA's proposed use of the NAMs data. (Ref. 24) The advice of the SAP is
currently being taken into consideration as EPA develops a path forward
on NAMs. The Agency is continuing to explore the use of NAMs for the
OPs, including chlorpyrifos, and intends to make its findings available
as soon as it completes this work.
2. Reregistration and Registration Review
In 2006, EPA completed FIFRA section 4 (7 U.S.C. 136a-1)
reregistration (a program under which EPA reregisters older pesticides
that continue to meet the standard for registration) and FFDCA
tolerance reassessment (21 U.S.C. 346a(q)) for chlorpyrifos and the OP
class of pesticides. EPA concluded that process by determining that
those tolerances were safe and should be left in effect. That decision
relied on an endpoint based on 10% RBC AChE inhibition. (Ref. 25)
Given ongoing scientific developments in the study of the OPs
generally, in March 2009 EPA announced its decision to prioritize the
FIFRA section 3(g) (7 U.S.C. 136a(g)) registration review of
chlorpyrifos by opening a public docket and releasing a preliminary
work plan to complete the chlorpyrifos registration review by 2015.
Despite the ambitions of that original work plan, the registration
review of chlorpyrifos has proven to be far more complex than
originally anticipated, and thus, chlorpyrifos is currently still
undergoing registration review, which must be completed by October 1,
2022. (7 U.S.C. 136a(g)(1)(A)(iv)) For information about the ongoing
registration review process for chlorpyrifos, see <a href="https://www.regulations.gov/docket/EPA-HQ-OPP-2008-0850">https://www.regulations.gov/docket/EPA-HQ-OPP-2008-0850</a>.
Reflecting that complexity, the Agency has engaged in extensive and
ongoing analyses of the available science since initiating registration
review in 2009, including multiple human health risk assessments and
drinking water assessments, development of a new model for deriving
points of departure to assess risks of chlorpyrifos, development of a
framework for incorporating human epidemiology information into risk
assessments as well as conducting an in-depth epidemiology and
literature review, and in the process convening the FIFRA SAP at least
six times. The following lays out the major milestones of the
chlorpyrifos registration review process.
In 2011, EPA released its preliminary human health risk assessment
(2011 HHRA) for the registration review of chlorpyrifos. (Ref. 18) The
2011 HHRA used 10% RBC AChE inhibition from laboratory rats as the
critical effect (or PoD) for extrapolating risk. It also used the
default 10X uncertainty factors for inter- and intra-species
extrapolation. The 10X FQPA safety factor was reduced to 1X with a note
to the public that a WOE analysis evaluating available epidemiological
studies would be forthcoming. Also, in 2011, EPA released its Revised
Chlorpyrifos Preliminary Registration Review Drinking Water Assessment.
(Ref. 26) This assessment provided estimated drinking water
concentrations (EDWCs) based on Tier I groundwater and Tier II surface
water model simulations for registered uses of chlorpyrifos and
considered monitoring data from several different programs. Based on
data demonstrating the impacts of drinking water treatment on
chlorpyrifos, EPA concluded that chlorpyrifos in drinking water would
convert to chlorpyrifos-oxon, a metabolite, when going through
chlorinated drinking water treatment systems. Based on modeling
results, EDWCs for chlorpyrifos and chlorpyrifos-oxon generated from
surface water sources provided higher estimates of the potential
exposure to either of these chemicals in drinking water than those from
groundwater.
In 2014, following the development of the PBPK-PD model and 2012
SAP's review of EPA's epidemiology review, EPA released a revised human
health risk assessment (2014 HHRA). (Ref. 20) Using the chlorpyrifos
PBPK-PD model for deriving human PoDs for RBC AChE inhibition, which
obviated the need for the inter-species extrapolation factor and
allowed for data-derived intra-species extrapolation factors (as
described in Unit II.B.1.b.i.), the revised risk assessment identified
highly refined PoDs that accounted for gender, age, duration and route-
specific exposure considerations. In addition, the revised risk
assessment retained the 10X FQPA SF, based on EPA's WOE analysis
concerning the potential for neurodevelopmental outcomes that followed
a draft of EPA's Epidemiologic Framework (Ref. 19), and incorporated
recommendations from the 2012 SAP. Also in 2014, EPA released its
Updated Drinking Water Assessment for Registration Review (``2014
DWA''). (Ref. 27) As an update to the 2011 DWA, the 2014 DWA included
several additional analyses focusing on: (1) Clarifying labeled uses,
(2) evaluating volatility and spray drift, (3) revising aquatic
modeling input values, (4) comparing aquatic modeling and monitoring
data, (5) summarizing the effects of drinking water treatment, and (6)
updating model simulations using current exposure tools. The additional
analyses did not change the exposure assessment conclusions reported in
the preliminary DWA. The 2014 HHRA, taken together with the Agency's
drinking water assessment, identified estimated aggregate risks
exceeding the level of concern for chlorpyrifos.
In 2016 EPA issued a revised human health risk assessment using a
dose-reconstruction approach to derive the PoD based on the
neurodevelopmental effects observed in the CCCEH study based on advice
from the 2016 SAP. (Ref. 28) Although the 2016 HHRA found that risks
from food alone exceeded the safe level for chlorpyrifos, EPA also
issued a revised drinking water assessment (2016 DWA). (Ref. 29) This
refined drinking water assessment served to combine, update, and
complete the work presented in the 2011 and 2014 drinking water
assessments for chlorpyrifos as part of the registration review
process. Even with the additional refinements, the results were
consistent and suggested potential exposure to chlorpyrifos or
chlorpyrifos[hyphen]oxon in finished drinking water based on labeled
uses. The assessment noted that depending on the drinking water level
of concern, measured concentrations of chlorpyrifos and
chlorpyrifos[hyphen]oxon may exceed the level of concern in some
locations across the country, which warranted comparison of EDWCs to
the established drinking water level of concern. EPA issued a Notice of
Data Availability seeking public comment on the 2016 HHRA and 2016 DWA.
(81 FR 81049, November 17, 2016) (FRL-9954-65)
In September 2020, EPA issued the ``Chlorpyrifos: Third Revised
Human Health Risk Assessment for Registration Review'' (2020 HHRA)
(Ref. 2) and the ``Updated Chlorpyrifos Refined Drinking Water
Assessment for Registration Review'' (2020 DWA) (Ref. 30). In the 2020
HHRA, EPA utilizes the same endpoint and PoDs as those used in the 2014
HHRA. This was done because the Agency concluded that the
[[Page 11234]]
unresolved nature of the science addressing neurodevelopmental effects
warranted further evaluation of the science during the remaining time
for completion of registration review. Due to the uncertainties
concerning neurodevelopmental effects, the 2020 HHRA retained the
default 10X FQPA safety factor; the 2020 HHRA also presented potential
risk estimates at a reduced 1X FQPA safety factor to reflect the range
of estimates possible, although it did not adopt or explain why the 1X
FQPA safety factor would be safe for infants and children. While in the
2020 HHRA the Agency determined that risks from exposures to
chlorpyrifos residues in food combined with residential exposures were
not of concern, drinking water exposures significantly add to those
risks. The 2020 DWA built upon the analysis in the 2016 DWA but focused
on a subset of currently registered chlorpyrifos uses for high benefit
crops to growers in specific areas of the country, i.e., alfalfa,
apple, asparagus, cherry, citrus, cotton, peach, soybean, sugar beet,
strawberry, and wheat. This assessment utilized new surface water model
scenarios (i.e., soil, weather, and crop data), integrated the entire
distribution of community water system percent cropped area (PCA)
adjustment factors and state[hyphen]level percent crop treated (PCT)
data, and considered the quantitative use of available surface water
monitoring data. The 2020 DWA noted that concentrations of chlorpyrifos
and chlorpyrifos[hyphen]oxon in drinking water were not likely to
exceed the drinking water level of comparison (DWLOC) even with the
retention of the 10X FQPA safety factor for the subset of uses
considered; however, that assessment noted that adding additional uses
could change estimated drinking water concentrations, which could
ultimately result in changes to the risk conclusion relative to the
drinking water level of comparison(s).
In December 2020, EPA released the ``Proposed Interim Decision for
the Registration Review of Chlorpyrifos'' (2020 PID) for a 60-day
public comment period (85 FR 78849, December 7, 2020) (FRL-10017-1).
The 2020 PID concluded that ``[w]hen considering all currently
registered agricultural and non-agricultural uses of chlorpyrifos,
aggregate exposures are of concern.'' (Ref. 31 at pg. 19) However, the
2020 PID also noted that if one considered only the uses that result in
EDWCs below the DWLOC, then aggregate exposures would not be of
concern. (Id.) Accordingly, the 2020 PID proposed to limit applications
of chlorpyrifos in this country to only 11 uses in certain regions of
the United States; EPA had focused its review on those 11
geographically limited uses due to potential benefits from those uses
and concluded that the EDWCs for those uses alone were below the DWLOC.
This proposed path forward was intended to offer to stakeholders a way
to mitigate the aggregate risk from chlorpyrifos, although as a
proposal, it was not a final Agency determination and could be subject
to change following public comment and stakeholder interest, perhaps in
an Agency determination on a different subset of uses. Along with
comments on the 2020 PID, EPA invited comments on the benefits
assessments, the 2020 HHRA, draft ecological risk assessment, and 2020
DWA. EPA extended the 60-day comment period by 30 days, which then
closed on March 7, 2021. EPA is currently reviewing public input and
will respond to comments prior to issuing an interim decision.
3. Scientific Issues and SAPs
As noted previously, the registration review of chlorpyrifos has
proven to be far more complex than originally anticipated. The OPs have
presented EPA with numerous novel scientific issues that the Agency has
taken to multiple FIFRA Scientific Advisory Panel (SAP) meetings since
the completion of reregistration in 2006. (Note: The SAP is a federal
advisory committee created by FIFRA section 25(d), 7 U.S.C. 136w(d),
and serves as EPA's primary source of peer review for significant
regulatory and policy matters involving pesticides. EPA may convene an
SAP meeting to present significant regulatory, science, or policy
matters involving pesticides and request that the SAP provide comments,
evaluations, and recommendations on the matters submitted for its
review.)
These FIFRA SAP meetings, which have included the review of new
worker and non-occupational exposure methods, experimental toxicology
and epidemiology, and the evaluation of a chlorpyrifos-specific PBPK-PD
model, have resulted in significant developments in EPA's risk
assessments generally, and, more specifically, in the study of
chlorpyrifos's effects. In particular, and partly in response to issues
raised in the 2007 Petition (discussed in Unit III.B. of this
document), EPA has conducted extensive reviews of available data to
evaluate the possible connection between chlorpyrifos and adverse
neurodevelopmental effects and to assess whether the neurodevelopmental
effects could be used to determine PoDs for assessing chlorpyrifos. On
this particular topic, EPA has convened multiple FIFRA SAP meetings.
In 2008, the Agency presented to the FIFRA SAP a preliminary review
of available literature and research on epidemiology in mothers and
children following exposures to chlorpyrifos and other OPs, laboratory
studies on animal behavior and cognition, AChE inhibition, and
mechanisms of action. (Ref. 32) The 2008 FIFRA SAP recommended that
AChE inhibition remain as the source of data for the PoDs but noted
that despite some uncertainties, the CCCEH epidemiologic studies ``is
epidemiologically sound'' and ``provided extremely valuable
information'' for evaluating the potential neurodevelopmental effects
of chlorpyrifos.
The 2010 FIFRA SAP favorably reviewed EPA's 2010 draft epidemiology
framework. (Ref. 33) This draft framework, titled ``Framework for
Incorporating Human Epidemiologic & Incident Data in Risk Assessments
in Pesticides,'' (``Epidemiologic Framework'') described the use of the
Bradford Hill Criteria as modified in the Mode of Action Framework to
integrate epidemiology information with other lines of evidence. As
suggested by the 2010 FIFRA SAP, EPA did not immediately finalize the
draft framework but instead used it in several pesticide evaluations
prior to making revisions and finalizing it. EPA's Office of Pesticide
Program's (OPP) finalized this Epidemiologic Framework in December
2016. (Ref. 19)
In 2012, the Agency convened another meeting of the FIFRA SAP to
review the latest experimental data related to RBC AChE inhibition,
cholinergic and non-cholinergic adverse outcomes, including
neurodevelopmental studies on behavior and cognition effects. The
Agency also performed an in-depth analysis of the available
chlorpyrifos biomonitoring data and of the available epidemiologic
studies from three major children's health cohort studies in the United
States, including those from the CCCEH, Mount Sinai, and University of
California, Berkeley. The Agency explored plausible hypotheses on mode
of actions/adverse outcome pathways (MOAs/AOPs) leading to
neurodevelopmental outcomes seen in the biomonitoring and epidemiology
studies.
The 2012 FIFRA SAP described the Agency's epidemiology review as
``very clearly written, accurate'' and a ``very thorough review.''
(Ref. 21 at pgs. 50-52, 53) It went further to note that it ``believes
that the [Agency's] epidemiology review appropriately
[[Page 11235]]
concludes that the studies show some consistent associations relating
exposure measures to abnormal reflexes in the newborn, pervasive
development disorder at 24 or 36 months, mental development at 7
through 9 years, and attention and behavior problems at 3 and 5 years
of age. . . .'' The 2012 FIFRA SAP concluded that the RBC AChE
inhibition remained the most robust dose-response data, though
expressed concerns about the degree to which 10% RBC AChE inhibition is
protective for neurodevelopmental effects, pointing to evidence from
epidemiology, in vivo animal studies, and in vitro mechanistic studies,
and urged the EPA to find ways to use the CCCEH data.
Taking that recommendation into consideration, the Agency prepared
a proposal for using cord blood data from the CCCEH epidemiology
studies as the source of data for the PoDs, which it presented to the
FIFRA SAP in April 2016. The 2016 SAP did not support the ``direct
use'' of the cord blood and working memory data for deriving the
regulatory endpoint, due in part to insufficient information about
timing and magnitude of chlorpyrifos applications in relation to cord
blood concentrations at the time of birth, uncertainties about the
prenatal window(s) of exposure linked to reported effects, lack of a
second laboratory to reproduce the analytical blood concentrations, and
lack of raw data from the epidemiology study. (Ref. 22) Despite its
critiques of uncertainties in the CCCEH studies, the 2016 FIFRA SAP
stated that it ``agrees that both epidemiology and toxicology studies
suggest there is evidence for adverse health outcomes associated with
chlorpyrifos exposures below levels that result in 10% RBC AChE
inhibition (i.e., toxicity at lower doses).'' (Id. at pg. 18)
B. FFDCA Petition and Associated Litigation
1. 2007 Petition Seeking Revocation of Chlorpyrifos Tolerances
As described previously, in 2006, EPA issued the Reregistration
Eligibility Decision (RED) for chlorpyrifos, which concluded that
chlorpyrifos was eligible for reregistration as it continued to meet
the FIFRA standard for registration. In September 2007, Pesticide
Action Network North America (PANNA) and Natural Resources Defense
Council (NRDC) (collectively, the Petitioners) submitted to EPA a
petition (the Petition) seeking revocation of all chlorpyrifos
tolerances under FFDCA section 408 and cancellation of all chlorpyrifos
pesticide product registrations under FIFRA. (Ref. 34) That Petition
raised several claims regarding EPA's 2006 FIFRA reregistration
decision for chlorpyrifos and the active registrations in support of
the request for tolerance revocations and product cancellations. Those
claims are described in detail in EPA's earlier Order denying the
Petition (82 FR 16581, April 5, 2017) (FRL-9960-77).
2. Agency Responses and 2017 Order Denying Petition
Ultimately, EPA denied the Petition in full on March 29, 2017 (82
FR 16581, April 5, 2017) (FRL-9960-77). Prior to issuing that Order,
however, EPA issued two interim responses and a proposed rule in
response to the Petition.
EPA provided the Petitioners with two interim responses on July 16,
2012, and July 15, 2014, which denied six of the Petition's claims. EPA
made clear in both the 2012 and 2014 responses that, absent a request
from Petitioners, EPA's denial of those six claims would not be made
final until EPA finalized its response to the entire Petition.
Petitioners made no such request, and EPA therefore finalized its
response to those claims in the March 29, 2017 Order Denying Petition.
As background, three of the Petition's claims all related to the
same issue: Whether the potential exists for chlorpyrifos to cause
neurodevelopmental effects in children at exposure levels below EPA's
existing regulatory standard (10% RBC AChE inhibition). Because the
claims relating to the potential for neurodevelopmental effects in
children raised novel, highly complex scientific issues, EPA originally
decided it would be appropriate to address these issues in connection
with the registration review of chlorpyrifos under FIFRA section 3(g)
and decided to expedite that review, intending to finalize it in 2015,
well in advance of the October 1, 2022 registration review deadline.
(Ref. 35) EPA decided as a policy matter that it would address the
Petition claims regarding these matters on a similar timeframe. (82 FR
16581 at 16583)
As noted earlier in this Unit, the complexity of these scientific
issues precluded EPA from finishing its review according to EPA's
original timeline, and the Petitioners brought legal action in the
Ninth Circuit Court of Appeals to compel EPA to either issue an Order
denying the Petition or to grant the Petition by initiating the
tolerance revocation process. The result of that litigation was that on
August 10, 2015, the Court ordered EPA to ``issue either a proposed or
final revocation rule or a full and final response to the
administrative [P]etition by October 31, 2015.'' (In re Pesticide
Action Network N. Am., 798 F.3d 809, 815 (9th Cir. 2015))
In response to that Court's order, EPA issued a proposed rule in
2015 to revoke all tolerances for chlorpyrifos (80 FR 69080, November
6, 2015) (FRL-9935-92) (2015 proposed rule), based on its unfinished
registration review risk assessment. EPA acknowledged that it had had
insufficient time to complete its drinking water assessment and its
review of data addressing the potential for neurodevelopmental effects.
Although EPA noted that further evaluation might enable more tailored
risk mitigation, EPA was unable to conclude, based on the information
before EPA at the time, that the tolerances were safe, since the
aggregate exposure to chlorpyrifos exceeded safe levels.
On December 10, 2015, the Ninth Circuit issued a further order, in
response to additional legal challenge by Petitioners, requiring EPA to
take final action on its proposed revocation rule and issue its final
response to the Petition by December 30, 2016. In re Pesticide Action
Network N. Am., 808 F.3d 402 (9th Cir. 2015). In response to EPA's
request for an extension of the deadline in order to be able to fully
consider the July 2016 FIFRA SAP report regarding chlorpyrifos
toxicology, the Ninth Circuit ordered EPA to complete its final action
by March 31, 2017. In re Pesticide Action Network of North America v.
EPA, 840 F.3d 1014 (9th Cir. 2016). Following that Court's order, EPA
published a Notice of Data Availability (NODA), seeking comment on
EPA's revised risk assessment and water assessment and reopening the
comment period on the proposal to revoke tolerances. (81 FR 81049,
November 17, 2016) (FRL-9954-65)
On March 29, 2017, the EPA issued the 2017 Order Denying Petition.
(82 FR 16581, April 5, 2017) (FRL-9960-77) The specific responses are
described in full in that 2017 Order Denying Petition (and summarized
again in the Agency's denial of objections. (84 FR 35555, July 24,
2019) (FRL-9997-06) EPA's 2017 Order Denying Petition did not contain a
determination concerning the safety of chlorpyrifos. Rather, EPA
concluded that, despite several years of study, the science addressing
neurodevelopmental effects remained unresolved and that further
evaluation of the science on this issue during the remaining time for
completion of registration review was warranted. EPA therefore denied
the remaining Petition claims, concluding that it was not required to
complete--and would not complete--the human
[[Page 11236]]
health portion of the registration review or any associated tolerance
revocation of chlorpyrifos without resolution of those issues during
the ongoing FIFRA registration review of chlorpyrifos.
3. Objections and EPA's Denial of Objections
In June 2017, several public interest groups and states filed
objections to the 2017 Order Denying Petition pursuant to the
procedures in FFDCA section 408(g)(2). Specifically, Earthjustice
submitted objections on behalf of the following 12 public interest
groups: Petitioners PANNA and NRDC, United Farm Workers, California
Rural Legal Assistance Foundation, Farmworker Association of Florida,
Farmworker Justice, GreenLatinos, Labor Council for Latin American
Advancement, League of United Latin American Citizens (LULAC), Learning
Disabilities Association of America, National Hispanic Medical
Association and Pineros y Campesinos Unidos del Noroeste. Another
public interest group, the North Coast River Alliance, submitted
separate objections. With respect to the states, New York, Washington,
California, Massachusetts, Maine, Maryland, and Vermont submitted a
joint set of objections. (Ref. 34), These objectors asserted that EPA
erred in not making the requisite safety finding in denying the
Petition and that EPA should revoke all tolerances because the
available record supported a conclusion that the tolerances were
unsafe.
On July 18, 2019, EPA issued a final Order denying all objections
to the 2017 Order Denying Petition and thereby completing EPA's
administrative denial of the petition (2019 Order Denying Objections to
Petition Denial) (84 FR 35555, July 27, 2019) (FRL-9997-06). Again, the
2019 Order Denying Objections to Petition Denial did not issue a
determination concerning the safety of chlorpyrifos. Rather, EPA denied
the objections on the grounds that the data concerning
neurodevelopmental toxicity were not sufficiently valid, complete, and
reliable to meet the Petitioners' burden to present evidence supporting
the request for revocation.
4. Judicial Challenge to 2019 Order Denying Objections To Petition
Denial and 2021 Ninth Circuit Order
On August 7, 2019, the objectors (LULAC Petitioners) and States
petitioned the Ninth Circuit for review of the 2017 Order Denying
Petition and the 2019 Order Denying Objections to Petition Denial. The
LULAC Petitioners and States argued that EPA was compelled to grant the
2007 Petition and revoke chlorpyrifos tolerances because: (1) EPA
lacked authority to maintain chlorpyrifos tolerances without an
affirmative finding that chlorpyrifos is safe; (2) EPA's findings that
chlorpyrifos is unsafe in the Agency's 2014 and 2016 risk assessments
compel revocation of the chlorpyrifos tolerances; and (3) The Petition
provided a sufficient basis for EPA to reconsider the question of
chlorpyrifos's safety and was not required to prove that a pesticide is
unsafe.
On April 29, 2021, the Ninth Circuit issued its decision, finding
that when EPA denied the 2007 Petition to revoke chlorpyrifos
tolerances, it was essentially leaving those chlorpyrifos tolerances in
effect, which, the Court noted, the FFDCA only permits if EPA has made
an affirmative determination that such tolerances were safe. (League of
United Latin Am. Citizens (LULAC) v. Regan, 996 F.3d. 673 (9th Cir.
2021)) Although EPA argued that it was not compelled to reconsider its
safety determination because the 2007 Petition had failed to meet the
threshold requirement of providing reliable evidence that the
tolerances were unsafe, the Court found that the Petition provided the
necessary ``reasonable grounds,'' which triggered EPA's duty to ensure
the tolerances were safe. (Id. at pg. 695) Since the 2017 Order Denying
Petition and 2019 Order Denying Objections to Petition Denial failed to
make any safety determinations for chlorpyrifos, the Court concluded
that EPA violated the FFDCA by leaving those tolerances in place
without the requisite safety findings. (Id. at pgs. 678, 695 and 696
(declaring that EPA's action was a ``total abdication of EPA's
statutory duty under the FFDCA'')) Moreover, in light of the record
before the Court, including the 2016 HHRA indicating that the current
chlorpyrifos tolerances were not safe, the Court found EPA's denial of
the 2007 Petition to be arbitrary and capricious. (Id. at pg. 697)
Based on the available record, the Court concluded that EPA must grant
the Petition and issue a final rule modifying or revoking the
tolerances under FFDCA section 408(d)(4)(A)(i). (Id. at pg.701)
The Court recognized that, since the litigation had commenced, EPA
had been continuing to evaluate chlorpyrifos in registration review and
had issued the 2020 PID and convened another FIFRA SAP; the Court noted
that such information could be relevant to a safety determination. (Id.
at pg. 703) The Court allowed that if the new information could support
a safety determination, EPA might issue a final rule modifying
chlorpyrifos tolerances rather than revoking them. But the Court warned
that EPA was to act ``immediately'' and not engage in ``further
factfinding.'' (Id.) The Court chided that taking ``nearly 14 years to
publish a legally sufficient response to the 2007 Petition'' was an
``egregious delay'' and ``EPA's time is [ ] up.'' (Id.) As a result,
the Court ordered EPA to: (1) Grant the 2007 Petition; (2) Issue a
final rule within 60 days of the issuance of the mandate that either
revokes all chlorpyrifos tolerances or modifies chlorpyrifos
tolerances, provided that such modification is supported by a safety
finding, and (3) Modify or cancel related FIFRA registrations for food
use in a timely fashion. (Id. at 703 and 704) Since the mandate was
issued on June 21, 2021, the deadline for issuing the final rule was
August 20, 2021, less than four months from the date the Court issued
its decision.
IV. The Final Rule
As noted in the previous Unit, the Ninth Circuit directed EPA to
act on the 2007 Petition by granting it and issuing a final rule
concerning the chlorpyrifos tolerances. The Court allowed that that
rule could either revoke all tolerances or modify tolerances, as long
as EPA issued, concurrently with such modification, a determination
that such modified tolerances were safe. The Court, impatient with
EPA's failure to comply with the FFDCA when it left chlorpyrifos
tolerances in place without the requisite safety finding, directed EPA
to issue that final rule very quickly, i.e., 60 days after the issuance
of the mandate.
Given the limited window for issuing the rule and the Court's
directive not to engage in additional fact-finding or further delay,
the Agency focused in its rulemaking on the data and completed
assessments available at the time and whether they were adequate to
support a safety finding for the chlorpyrifos tolerances. EPA did not
conduct additional analyses or engage in any additional fact-finding or
scientific review, due to the limited time. Thus, the rule was based on
available information that EPA had already reviewed and incorporated
into risk assessments and/or regulatory documents.
The most recent risk assessments and regulatory documents were the
2020 HHRA (Ref. 2), 2020 DWA (Ref. 30), and the 2020 PID (Ref. 31).
These documents were not in the record before the Ninth Circuit,
although as noted previously, the Court allowed that the new
information could be used in support of
[[Page 11237]]
a safety finding as appropriate. Thus, the Agency considered, in
addition to other previously developed documents on chlorpyrifos as
cited in the final rule (Ref. 1), whether the 2020 documents would
support a safety finding for the chlorpyrifos tolerances.
EPA's final rule follows the Agency's practice of assessing risk
described in Unit II.B. of this document. Relying on the Agency's
existing analyses on chlorpyrifos, EPA examined the toxicological
profile of chlorpyrifos to identify potential hazards and identify PoDs
for assessing risk. The Agency considered the appropriate uncertainty
factors, including the appropriate FQPA safety factor, for setting the
level of concern. EPA also examined potential exposures of chlorpyrifos
in food and drinking water, as well as from uses that might result in
exposure to residues in residential settings. Finally, EPA aggregated
all anticipated exposures to determine if the existing tolerances would
meet the safety standard of the FFDCA. The rest of this Unit summarizes
the analysis and conclusions of the 2021 final rule. For further
detail, see Ref. 1.
In the 2021 final rule, EPA described the two primary toxicological
effects associated with chlorpyrifos: Acetylcholinesterase inhibition
and neurodevelopmental effects. These effects are discussed in greater
detail in Unit III.A.1.b. of this document. As EPA noted, the mode of
action of chlorpyrifos of affecting the nervous system through
inhibition of AChE is well-established, as well as its use as the basis
for PoD for assessing risks from chlorpyrifos as well as other OPs. In
addition, EPA acknowledged and addressed the extensive body of
information studying the potential effects on neurodevelopment in
infants and children following exposure to OPs, including chlorpyrifos.
EPA recognized that available data provide qualitative support for
chlorpyrifos to potentially impact the developing mammalian brain and
acknowledged the observed associations between prenatal chlorpyrifos
exposure and neurodevelopmental outcomes in the epidemiological data.
But EPA also noted that due to uncertainties in the data, including the
lack of specific exposure information, EPA was precluded from being
able to make a causal linkage between chlorpyrifos exposure and the
outcomes found in the epidemiological studies. As a result, while there
is a lot of information about the potential association between
chlorpyrifos and neurodevelopmental outcomes in infants and children,
there was insufficient information at the time of the final rule to
draw conclusions about the dose-response relationship between
chlorpyrifos and those outcomes.
As a result, EPA relied on the RBC AChE inhibition results from
laboratory animals to derive PoD, consistent with the 2006 chlorpyrifos
RED, the 2006 OP cumulative risk assessment, and other single chemical
OP risk assessments. To account for the unresolved scientific
uncertainties associated with the potential for neurodevelopmental
effects--and to be protective of those effects--the Agency retained the
default 10X FQPA safety factor. As noted earlier, EPA is required to
apply this tenfold margin of safety to account for potential pre- and
postnatal toxicity, unless it has reliable data to support a
determination that a different margin of safety would be protective.
(21 U.S.C. 346a(b)(2)(C)) EPA explained that the Agency's WOE analysis
indicates there is qualitative evidence of a potential effect on the
developing brain associated with chlorpyrifos exposures; however,
uncertainties remain about the levels at which those neurodevelopmental
outcomes may occur. Therefore, EPA retained the 10X FQPA safety factor
in recognition of the fact that despite extensive analysis of the
available data, the science concerning neurodevelopmental effects
remains unresolved and thus presents an uncertainty concerning the
potential pre- and postnatal toxicity. EPA did not believe it had
sufficient reliable data to determine that a lower safety factor would
be protective of infants and children.
To assess risk, EPA estimated exposures to chlorpyrifos from
approved uses. As the FFDCA requires, EPA examined exposures for
chlorpyrifos uses that resulted in residues of chlorpyrifos in or on
food, in drinking water, and in residential (or non-occupational)
settings. EPA's assessment of dietary (food only) exposures relied on
the Agency's Dietary Exposure Evaluation Model and Calendex software
with the Food Commodity Intake Database (DEEM-FCID version 3.16/
Calendex) to estimate exposure by combining data on human consumption
amounts with residue values in food commodities. These food-only
exposure assessments were highly refined, based both on field trial
data and monitoring data.
In drinking water, EPA estimated exposures of chlorpyrifos and
chlorpyrifos-oxon, a metabolite of chlorpyrifos. The most recent
drinking water assessment that examined all approved uses of
chlorpyrifos was conducted in 2016; thus, the Agency relied on that
assessment in evaluating the safety of the chlorpyrifos tolerances.
While a more recent drinking water assessment had been conducted in
2020, that newer assessment only evaluated a subset of the approved
uses and thus was incomplete for purposes of assessing the aggregate
exposures of chlorpyrifos. Based on the 2016 drinking water assessment
then, EPA evaluated estimated concentrations of chlorpyrifos and
chlorpyrifos-oxon in drinking water resulting from approved uses of
chlorpyrifos.
There are few remaining uses of chlorpyrifos that result in
residential or non-occupational exposures. EPA evaluated those uses and
used estimated exposures from use on golf courses in the overall
aggregate risk assessment since golf course uses result in the highest
estimated exposures among remaining residential (non-occupational)
uses.
In accordance with the requirements of the FFDCA, EPA considered
aggregate exposures of chlorpyrifos in all food, drinking water, and
residential settings. EPA used a DWLOC approach, in which EPA compared
estimated drinking water exposures to a DWLOC, i.e., a value
corresponding to the maximum amount of chlorpyrifos exposures that may
be present in drinking water without resulting in aggregate exposures
of chlorpyrifos that would result in unsafe exposures. Where the
estimated drinking water concentrations for chlorpyrifos exceed the
DWLOC, the Agency concluded that aggregate exposures would be unsafe
because the chlorpyrifos residues in drinking water, when combined with
food and residential exposures, would exceed safe levels of
chlorpyrifos exposure. For chlorpyrifos and chlorpyrifos-oxon, the
Agency calculated DWLOCs for acute and steady-state exposures for
several population subgroups. (Ref. 2 at pgs. 15, and 44 through 47)
As noted in the final rule, EPA's assessment concluded that
exposures to chlorpyrifos from food and residential exposures
individually or together did not exceed EPA's levels of concern.
However, the Agency found that when combined with the exposures in
drinking water from all registered uses of chlorpyrifos, the aggregate
exposure to chlorpyrifos exceeded safe levels. The estimated drinking
water concentrations calculated in the 2016 drinking water assessment
exceeded the DWLOC. The Agency recognized that the 2020 PID proposed a
subset of uses that might result in exposures below the Agency's level
of concern if uses were eliminated and significant changes to the
labels were made, including use cancellations
[[Page 11238]]
and geographic limitations, among others. However, as no registration
or label changes had been effectuated such that EPA could rely on them
at the time of the final rule, EPA assessed aggregate exposures
expected from all registered uses.
Ultimately, EPA concluded that, based on the information before the
Agency and taking into consideration all the registered uses for
chlorpyrifos at the time, it was unable to determine that the
chlorpyrifos tolerances were safe, since aggregate exposures to
chlorpyrifos exceeded safe levels. Therefore, EPA issued a final rule
revoking all tolerances for chlorpyrifos contained in 40 CFR 180.342.
The prepublication copy of the final rule was posted on the EPA website
on August 18, 2021, and the final rule published in the Federal
Register on August 30, 2021 (Ref. 1). The final rule became effective
on October 29, 2021. EPA provided a grace period of six months to ease
the transition for growers and accommodate international trade
considerations, by setting an expiration date for the chlorpyrifos
tolerances of February 28, 2022.
The final rule provided that, pursuant to FFDCA section 408(g), 21
U.S.C. 346a, any person could file an objection to any aspect of the
regulation, request a hearing on those objections, and requests for
stay of the final rule. The objections, requests for hearing, and
requests for stay received are summarized in Units V. and VI. of this
document.
V. Objections, Requests for Hearing, and Requests for Stay
The Agency received several filings of objections, four requests
for hearing on those objections, and several requests seeking a stay or
extension of the rule. EPA briefly summarizes the objections, hearing
requests, and stay requests, and responds to them in the next three
units of this document.
Individual objections were filed by the following: The Amalgamated
Sugar Company; the American Crystal Sugar Company; the American Farm
Bureau Federation; the American Soybean Association; the California
Citrus Quality Council; the Cherry Marketing Institute; the Coalition
of Organophosphate (OP) Registrants; Gharda Chemicals International,
Inc.; the Michigan Vegetable Council. Inc.; the Minor Crop Farmer
Alliance; the Republic of Colombia; the Southern Minnesota Beet Sugar
Cooperative; and 99 independent growers of soybean, corn, wheat,
cotton, rice, alfalfa, and sugarbeet. Several entities also filed
objections jointly in response to the final rule as follows: American
Sugarbeet Growers Association and U.S. Beet Sugar Association
(collectively, Sugarbeet Associations) CropLife America (CLA) and
Responsible Industry for a Sound Environment (RISE) (collectively, CLA/
RISE); two sugarbeet farmers filed a joint objection; numerous growers,
retailers, co-ops, applicators, refiners, crop consultants, and other
agricultural stakeholders signed on to a set of objections
(collectively, the Agricultural Retailers Association, et al.).
The Agency has grouped the objections submitted into the following
five categories:
(i) Objections to the scope of EPA's final rule revoking
tolerances. Several Objectors objected to the final rule revoking all
chlorpyrifos tolerances. Rather than revoke all tolerances, the
Objectors assert that EPA should have modified tolerances by retaining
the tolerances for those 11 high-benefit crops identified in the 2020
PID. Some of those objectors also argued that EPA had an obligation to
harmonize its tolerance revocations with action under FIFRA (e.g.,
canceling uses) in order to allow for the retention of the 11
tolerances identified in the PID. Finally, a number of Objectors
requested that EPA retain ``import tolerances'' for chlorpyrifos
commodities, on the grounds that those tolerances would not contribute
to drinking water exposures, which are driving risks.
(ii) Retention of the 10X FQPA safety factor. Several objectors
assert that EPA should not have retained the 10X FQPA safety factor due
to scientific uncertainties tied to epidemiological data that objectors
believe is invalid, incomplete, and unreliable. Objectors argue that
EPA should have reduced the FQPA safety factor to 1X based on the rest
of the available data for assessing the toxicity of chlorpyrifos.
(iii) Objections related to drinking water. Several objectors
assert that EPA erred in relying on the 2016 Drinking Water Assessment
(DWA), instead of the more refined 2020 DWA for assessing drinking
water exposures. Objectors believe the Agency's approach is highly
conservative and inaccurate. In addition, Gharda asserts that the
Agency erred in assessing chlorpyrifos-oxon in the aggregate assessment
of chlorpyrifos.
(iv) Procedural considerations. A number of objectors argue that
EPA has failed to provide adequate due process by not addressing
comments submitted on the 2015 proposed rule to revoke chlorpyrifos
tolerances, and in the chlorpyrifos registration review process.
Moreover, an objector raised due process concerns with the delayed
opening of the Agency's Federal eRulemaking Portal for submitting
objections electronically. Finally, some objectors argued that the
Agency failed to provide meaningful opportunity for interagency input
under Executive Order 12866.
(v) Objections that, as a matter of law, do not provide a basis for
leaving the tolerances in place. Several Objectors requested that EPA
rescind the final rule due to the impacts on growers and the
environment from the loss of the pesticide. One objector believes that
EPA improperly considered occupational exposure in the final rule based
on an Agency press statement. Other objectors assert that the final
rule is improper because it deviates from an unspecified Codex
Alimentarius international standard of 0.05 mg/kg for chlorpyrifos.
Some objectors assert that the implementation timeline specified by EPA
was too short and that the final rule should have provided guidance for
chlorpyrifos products in the channels of trade and considered the
implications for existing stocks of chlorpyrifos. Finally, Gharda
objects that the final rule violates their substantive due process
rights.
Four objectors also included requests for evidentiary hearings.
Three of these requesters--the American Soybean Association, the
Sugarbeet Associations, and the Cherry Marketing Institute--each
request evidentiary hearings to demonstrate that the best available
science, including the 2020 PID, supports a finding that chlorpyrifos
tolerances can remain in effect for soybeans, sugarbeets, and Michigan
tart cherries, respectively. Gharda submitted the fourth request for an
evidentiary hearing on its objection that the chlorpyrifos-oxon was not
relevant to the Agency's aggregate risk assessment. While Gharda
believes the Agency has all the evidence necessary to make this
determination, it still requests a hearing ``[t]o the extent that EPA
believes that a fact issue is presented by this data.''
Finally, EPA received written requests to stay the effective date
of the final rule from several objectors. The Sugarbeet Associations
and Gharda both argue that the criteria set out in the FDA's
regulations regarding stays of administrative proceedings at 21 CFR
10.35 require that EPA stay the effectiveness of the final rule.
Specifically, these Objectors argue that they will suffer irreparable
injury absent a stay, that their objections are not frivolous and are
undertaken in good faith, that the public interest favors a stay, and
the delay caused by a stay is not outweighed by the public health or
public interest. Several other Objectors
[[Page 11239]]
do not specifically address the regulatory criteria set forth at 21 CFR
10.35, but request that EPA stay the effectiveness of the final rule
until EPA can address the issues raised in their various objections.
Some objectors simply request an extension of the timeframe for
implementation of the rule.
VI. Response to Requests for Hearing
EPA denies each of the four requests for evidentiary hearing on
objections. Three objectors requested an evidentiary hearing on their
objection that EPA should have retained tolerances for certain crops
based on the conclusions of the 2020 PID; these requests are denied for
failure to make a sufficient evidentiary proffer. Gharda also requested
a hearing on its objection to EPA's assessment of chlorpyrifos-oxon
exposures in drinking water; this request is denied as unnecessary for
the purpose of receiving evidence and because the likely factual issue
has no material impact on Agency's decision to revoke tolerances. EPA's
substantive responses to the underlying objections follow in the next
Unit, i.e., Unit VII.C.1. and VII.C.3.b., respectively. Under EPA's
regulations, EPA may treat these objections as a group and rule on them
only after ruling on the request for an evidentiary hearing on that
objection. 40 CFR 178.30(c)(2) Therefore, EPA is addressing these
hearing requests before responding to objections in the next Unit.
A. The Standard for Granting an Evidentiary Hearing
EPA has established regulations governing objections to tolerance
rulemakings and tolerance petition denials and requests for hearings on
those objections. (40 CFR part 178; 55 FR 50282, December 5, 1990)
(FRL-3688-4)) Those regulations prescribe both the form and content of
hearing requests and the standard under which EPA is to evaluate
requests for an evidentiary hearing.
As to the form and content of a hearing request, the regulations
specify that a hearing request must include: (1) A statement of the
factual issues on which a hearing is requested and the requestor's
contentions on those issues; (2) A copy of any report, article, or
other written document ``upon which the objector relies to justify an
evidentiary hearing;'' (3) A summary of any other evidence relied upon
to justify a hearing; and (4) A discussion of the relationship between
the factual issues and the relief requested by the objection. (40 CFR
178.27)
The standard for granting a hearing request is set forth in 40 CFR
178.32. That section provides that a hearing will be granted if EPA
determines that the ``material submitted'' shows all of the following:
(1) There is a genuine and substantial issue of fact for resolution
at a hearing. An evidentiary hearing will not be granted on issues of
policy or law.
(2) There is a reasonable possibility that available evidence
identified by the requestor would, if established, resolve one or more
of such issues in favor of the requestor, taking into account
uncontested claims or facts to the contrary. An evidentiary hearing
will not be granted on the basis of mere allegations, denials, or
general descriptions of positions and contentions, nor if the
Administrator concludes that the data and information submitted, even
if accurate, would be insufficient to justify the factual determination
urged.
(3) Resolution of the factual issue(s) in the manner sought by the
person requesting the hearing would be adequate to justify the action
requested. An evidentiary hearing will not be granted on factual issues
that are not determinative with respect to the action requested. For
example, a hearing will not be granted if the Administrator concludes
that the action would be the same even if the factual issue were
resolved in the manner sought. (40 CFR 178.32(b))
This provision essentially imposes four requirements upon a hearing
requestor. First, the requestor must show it is raising a question of
fact, not one of law or policy. Hearings are for resolving factual
issues, not for debating law or policy questions. Second, the requestor
must demonstrate that there is a genuine dispute as to the issue of
fact. If the facts are undisputed or the record is clear that no
genuine dispute exists, there is no need for a hearing. Third, the
requestor must show that the disputed factual question is material,
i.e., that it is outcome determinative with regard to the relief
requested in the objections. Finally, the requestor must make a
sufficient evidentiary proffer to demonstrate that there is a
reasonable possibility that the issue could be resolved in favor of the
requestor. Hearings are for the purpose of providing objectors with an
opportunity to present evidence supporting their objections as the
regulation states, hearings will not be granted on the basis of ``mere
allegations, denials, or general descriptions of positions or
contentions.'' (40 CFR 178.32(b)(2))
The Court in National Corn Growers Ass'n v. EPA noted that the
FFDCA and EPA's regulations ``establish a `summary-judgment type'
standard for determining whether to hold a hearing: The EPA must hold a
hearing if it determines an objection raises a material issue of
fact.'' (613 F.2d 266, 271 (DC Cir. 2010)) In addition, the Court
applied a ``necessarily deferential'' standard of review in determining
whether an issue was material, looking to whether the agency ``has
given adequate consideration to all relevant evidence in the record.''
(Id. at pgs. 271 and 272) ``Mere difference in the weight or credence
given to particular scientific studies . . . are insufficient'' to
overturn an agency conclusion regarding whether an objection raises a
material issue of fact. (Id. at pg. 271)
EPA's hearing request requirements are based heavily on FDA
regulations establishing similar requirements for hearing requests
filed under other provisions of the FFDCA (53 FR 41126, 41129, October
19, 1988) (FRL-8372-5). FDA pioneered the use of summary judgment-type
procedures to limit hearings to disputed material factual issues and
thereby conserve agency resources. FDA's use of such procedures was
upheld by the Supreme Court in 1972, (Weinberger v. Hynson, Westcott &
Dunning, Inc., 412 U.S. 609 (1973)), and, in 1975, FDA promulgated
generic regulations establishing the standard for evaluating hearing
requests (40 FR 22950, May 27, 1975). It is these regulations upon
which EPA relied in promulgating its hearing regulations in 1990.
Unlike EPA, FDA has had numerous occasions to apply its regulations
on hearing requests. FDA's summary of the thrust of its regulations,
which has been repeatedly published in the Federal Register in Orders
ruling on hearing requests over the last 24 years, is instructive on
the proper interpretation of the regulatory requirements. That summary
states:
A party seeking a hearing is required to meet a threshold burden
of tendering evidence suggesting the need for a hearing.' [ ] An
allegation that a hearing is necessary to sharpen the issues' or
fully develop the facts' does not meet this test. If a hearing
request fails to identify any evidence that would be the subject of
a hearing, there is no point in holding one.
A hearing request must not only contain evidence, but that
evidence should raise a material issue of fact concerning which a
meaningful hearing might be held. [ ] FDA need not grant a hearing
in each case where an objection submits additional information or
posits a novel interpretation of existing information. [ ] Stated
another way, a hearing is justified only if the objections are made
in good faith and if they `draw in question in
[[Page 11240]]
a material way the underpinnings of the regulation at issue.'
Finally, courts have uniformly recognized that a hearing need not be
held to resolve questions of law or policy.
(49 FR 6672 at 6673, February 22, 1984; 72 FR 39557 at 39558, July 19,
2007 (citations omitted) EPA has been guided by FDA's application of
its regulations in this proceeding.
Congress confirmed EPA's authority to use summary judgment-type
procedures with hearing requests when it amended FFDCA section 408 in
1996. Although the statute had been silent on this issue previously,
the FQPA added language specifying that when a hearing is requested,
EPA ``shall . . . hold a public evidentiary hearing if and to the
extent the Administrator determines that such a public hearing is
necessary to receive factual evidence relevant to material issues of
fact raised by the objections'' (21 U.S.C. 346a(g)(2)(B)). This
language grants EPA broad discretion to determine whether a hearing is
``necessary to receive factual evidence'' to objections (H.R. Rep. No.
104-669, at pg. 49 (1996)).
B. American Soybean Association, Sugarbeet Associations, and Cherry
Marketing Institute Hearing Requests
1. Summary of Hearing Request
Three Objectors--the American Soybean Association, the Sugarbeet
Associations, and the Cherry Marketing Institute--requested evidentiary
hearings based on their objections that EPA erred in revoking
tolerances covering chlorpyrifos residues for their particular
commodity, i.e., soybean, sugarbeet, and cherry, respectively. (Refs.
36 through 38) These Objectors root this claim in statements made in
the 2020 PID, in which EPA proposed a subset of 11 registered uses for
retention as an option to mitigate dietary risks from uses of
chlorpyrifos. The 2020 PID noted that if uses were limited in
accordance with that proposal, EPA would be able to determine that such
uses would ``not pose potential risks of concern.'' Because, at the
time of the final rule, uses were not so limited, EPA revoked all
tolerances. These Objectors assert that such a conclusion was
inconsistent with the conclusions in the 2020 PID and thus not
supported by factual evidence. As a result, these Objectors request a
hearing on that objection to dispute the underlying factual basis for
EPA's decision to revoke all tolerances and, in particular, for their
tolerance of interest.
Specifically, the American Soybean Association notes that soybeans
were included among the 11 high-benefit crop uses of chlorpyrifos that
the 2020 PID described as ``not pos[ing] potential risks of concern
with a Food Quality Protection Act (FQPA) safety factor of 10X.'' (Ref.
36 at pg. 4) In addition, the American Soybean Association asserts that
EPA has determined ``elsewhere in its administrative record'' that it
is reasonably certain soybean uses will not pose harm from aggregate
dietary exposures. (Id.) Therefore, the American Soybean Association
challenges EPA's determination in the final rule that soybean uses of
chlorpyrifos might pose dietary risks of concern as factually
inaccurate and contrary to the finding in the 2020 PID, and requests an
evidentiary hearing ``to dispute this underlying factual inaccuracy.''
(Id.) Similarly, the Sugarbeet Associations argue that EPA's decision
to revoke tolerances for the 11 high-benefit crop uses of chlorpyrifos
identified in the 2020 PID is arbitrary and capricious and request an
evidentiary hearing ``to demonstrate that the best available science,
including the 2020 PID, supports a finding that tolerances for
sugarbeets can remain in effect.'' (Ref. 37 at pg. 6) Lastly, the
Cherry Marketing Institute argues that EPA's decision to revoke
tolerances for chlorpyrifos in the Michigan tart cherry industry due to
dietary risks is factually inaccurate, in light of EPA's identification
of tart cherries among the 11 high-benefit crop uses of chlorpyrifos
identified in the 2020 PID. (Ref. 38 at pg. 2) The Cherry Marketing
Institute allege that an unspecified ``drinking water assessment and a
dietary assessment'' provide that the Michigan tart cherry industry's
use of chlorpyrifos meets FFDCA safety standards. (Id. at pg. 1) The
Cherry Marketing Institute therefore requests an evidentiary hearing
``to further convey [its] concerns with EPA's determination'' to revoke
chlorpyrifos tolerances. (Id. at pg. 2)
2. Denial of Hearing Request
The evidentiary hearing requests submitted by the American Soybean
Association, the Sugarbeet Associations, and the Cherry Marketing
Institute do not meet the regulatory standard for granting an
evidentiary hearing request set forth in 40 CFR 178.32 and are
therefore denied.
As noted previously, the purpose for holding hearings is ``to
receive factual evidence.'' (21 U.S.C. 346a(g)(2)(B); 53 FR 41126 at
41129 (``Hearings are for the purpose of gathering evidence on disputed
factual issues . . . .'')) Therefore, at a bare minimum, a requestor
must identify evidence relied upon to justify a hearing and either
submit copies of that evidence or summarize it. (40 CFR 178.27)
None of these Objectors proffers any factual evidence to support
their request for an evidentiary hearing. Other than offering that the
Agency's determinations in the final rule were inconsistent with the
2020 PID, these Objectors refer to a hearing as an opportunity to
dispute the Agency's factual conclusions regarding the risks posed by
the use of chlorpyrifos on their particular commodity. As noted
previously, ``[a]n allegation that a hearing is necessary to sharpen
the issues' or fully develop the facts' does not meet this test. If a
hearing request fails to identify any evidence that would be the
subject of a hearing, there is no point in holding one.'' (49 FR 6672
at 6673, February 22, 1984; 72 FR 39557 at 39558, July 19, 2007)
(citing Georgia Pacific Corp v. EPA, 671 F.2d 1235, 1241 (9th Cir.
1982)) The statute requires that the objector identify actual evidence;
however, the Objectors point to no additional factual evidence that
they would offer for review in this evidentiary hearing. Failing to
identify any factual evidence that the Objectors would like to be
considered in a hearing, the Objectors' hearing request fails to
proffer the requisite evidence.
Even viewed in the most favorable light, these Objectors merely
proffer the Agency's own statements in its risk assessments and the
2020 PID and unspecified references to statements ``elsewhere in the
administrative record.'' As a result, EPA concludes that this
submission is sufficiently lacking to be considered an evidentiary
proffer. Given that the purpose of a hearing is to gather or receive
evidence, proffering evidence already considered and relied upon by EPA
is not grounds for holding a hearing. Furthermore, EPA has already
considered and found inadequate the evidence in the record to support
retaining individual tolerances without a change in registrations, and
it is difficult to understand, how, as a matter of law, this same
evidence would justify the opposite conclusion, given the same
underlying facts. At bottom, these objectors' proffer fails to
``identify'' evidence which would, if established, resolve an issue in
the objectors' favor.
Moreover, the American Soybean Association, the Sugarbeet
Associations, and the Cherry Marketing Institute have all failed to
demonstrate that there is a ``genuine and substantial issue of fact for
resolution at a hearing.'' (40 CFR 178.32(b)(1)) Whether EPA was
arbitrary and capricious in revoking the soybean, sugarbeet, and cherry
tolerances is a question of law, not of fact. Contrary to what these
objectors assert, EPA does
[[Page 11241]]
not assess safety of tolerances based upon the risks posed by use on a
single commodity. Under the FFDCA, EPA is required to assess aggregate
exposures, i.e., exposure to the pesticide from use on that particular
commodity, as well as use on all other commodities, contributions to
drinking water from all registered uses, and exposures in non-
occupational settings. Furthermore, to the extent there is a factual
question here, it is not in dispute. EPA does not dispute its own
scientific conclusions and findings in the 2020 PID that the Agency
could support a safety determination for the very limited and specific
subset of uses identified in that document. The problem is that at the
time of the final rule, the Agency did not have a basis for assuming
that uses would be limited in accordance with the 2020 PID mitigation
proposal. Thus, as a legal matter, EPA could not rely on those
scientific findings to support leaving the tolerances in place at the
time of the final rule. Ultimately, this issue comes down to whether
EPA properly interpreted its obligation under the FFDCA in assessing
aggregate exposure to chlorpyrifos, and that is ultimately a question
of law and not one of fact. Hearings are not granted on legal
questions. (40 CFR 178.32(b)(1)) Accordingly, the hearing requests of
the American Soybean Association, the Sugarbeet Associations, and the
Cherry Marketing Institute are denied.
EPA responds to the objection concerning whether EPA was justified
in revoking all chlorpyrifos tolerances in Unit VII.C.1.a. of this
document.
C. Gharda Chemicals International, Inc. Hearing Request
1. Summary of Hearing Request
In a footnote in a section of its objections alleging that EPA
failed to adequately consider certain relevant scientific information,
Gharda says, ``Gharda respectfully submits that EPA has all of the
scientific data at its disposal to find that chlorpyrifos oxon is not
relevant to EPA's aggregate exposure assessment under the FFDCA. To the
extent that EPA believes that a fact issue is presented by this data,
Gharda respectfully requests a hearing.'' (Ref. 39 at pg. 34) Although
the first sentence of Gharda's footnote indicates that Gharda does not
believe that a hearing is necessary, which should settle the matter,
the second sentence introduces some ambiguity that compels a response
as a matter of completeness. So, as discussed later in this document,
EPA considers whether an evidentiary hearing on Gharda's objection to
EPA's assessment of chlorpyrifos-oxon is warranted and determines that
it is not.
On its face, Gharda's request for a hearing fails to proffer any
evidence that Gharda believes warrants an evidentiary hearing. The
specific request refers simply to ``scientific data'', which is so
vague as to not be an evidentiary proffer at all. Nevertheless, taking
into consideration the whole of Gharda's objection concerning the
assessment of chlorpyrifos-oxon, EPA notes that Gharda references two
documents: (i) A drinking water study submitted to EPA by Corteva in
December 2020 (Study of Cholinesterase Inhibition in Peripheral Tissues
in Sprague Dawley Rats Following Exposure to Chlorpyrifos Oxon in
Drinking Water for 21 Days (MRID 51392601) (``Corteva Oxon Study''))
and (ii) A Declaration of Dr. Richard Reiss, dated October 21, 2021 and
included as an exhibit attached to Gharda's Objections to the final
rule, offering opinions on the meaning of the Corteva Oxon Study
(``Reiss Declaration''). (Id. at pg. 32) Also mentioned within the same
section of Gharda's submission as its objection relating to
chlorpyrifos-oxon are two other documents: (i) Comments filed by Dow
AgroSciences LLC (DAS) (now doing business as Corteva Agriscience) on
January 17, 2017 on the Chlorpyrifos: Tolerance Revocations; Notice of
Data Availability and Request for Comment (81 FR 81049) and its
accompanying assessments, including the 2016 DWA; and (ii) A Response
to Objections document filed by DAS on April 18, 2019 regarding
objections submitted by PANNA, NRDC, and others to EPA's March 29, 2017
Order denying the 2007 Petition. (Id. at 31) Because Gharda refers to
these documents only in the context of challenging the Agency's use of
the 2016 DWA in general and not with regard to the chlorpyrifos-oxon
objection specifically, EPA concludes that Gharda is not proffering
those documents in support of its objection on the assessment of
chlorpyrifos-oxon.
Gharda points to the Corteva Oxon Study as support for its
objection that the chlorpyrifos-oxon was not relevant to, and should
not have been included in, EPA's aggregate risk assessment. Gharda
asserts, quoting from the Reiss Declaration, that the Corteva Oxon
Study found ``(a) no detectable circulating chlorpyrifos oxon in blood,
(b) no statistically significant AChE inhibition in either RBC or
brain, and (c) an absence of clinical signs of toxicity or markers of
exposure,'' and therefore nullified EPA's assumption in the 2020 DWA
``that chlorpyrifos oxon is more toxic that the parent chlorpyrifos for
drinking water exposure purposes.'' (Id. at pg. 32) As a result, Gharda
argues that this study shows that ``drinking water risks associated
with the oxon are not a risk concern for any agricultural uses of
chlorpyrifos and should not be part of the EPA's aggregate risk
assessment or serve as a basis for limiting uses of chlorpyrifos.''
(Id. at pgs. 32 and 33) According to Gharda, EPA has received this
study but has failed to review it. Gharda argues that EPA's failure to
consider this study means that the final rule rests on incomplete
information and is arbitrary and capricious. (Id. at pgs. 33 through
34) Therefore, giving Gharda the benefit of the doubt, EPA finds that
the Corteva Oxon Study is being proffered by Gharda for the Agency's
consideration in determining whether a factual issue is raised that
warrants an evidentiary hearing. Similarly, because Gharda relies
heavily on the Reiss Declaration for its allegations concerning the
Corteva Oxon Study, EPA finds that Gharda is proffering that
declaration as evidence as well.
2. Denial of Hearing Request
EPA denies Gharda's hearing request under both its broad
discretionary authority found in FFDCA section 408(g)(2) and under the
regulatory standard in 40 CFR 178.32. As an initial matter, the
equivocating and vague nature of Gharda's hearing request makes it
difficult to discern whether Gharda has submitted a request for an
evidentiary hearing that meets even the basic form and content criteria
of EPA's regulations. (40 CFR 178.27) First, EPA's regulations require
a specific request for an evidentiary hearing and a statement of the
factual issue on which the hearing is requested. (40 CFR 178.27(a) and
(b)) While Gharda ``respectfully requests a hearing,'' it is only to
the extent EPA finds a factual issue warranting one. (Ref. 39 at pg.
34) Gharda asserts many things in this particular objection concerning
what Gharda believes is EPA's failure to consider relevant scientific
data, including failure to consider the Corteva Oxon Study, which
Gharda asserts would support a conclusion that chlorpyrifos-oxon in
drinking water is not relevant for chlorpyrifos risk assessment
purposes. That is not a clear statement of the factual issue on which
EPA should evaluate the request for a hearing. (40 CFR 178.27(b))
Moreover, as discussed previously, it is difficult to discern exactly
what evidence Gharda is proffering--``all scientific data'' in EPA's
files or just the Corteva Oxon Study. (40 CFR 178.27(c)) Finally,
Gharda makes no attempt to ``include a discussion of the relationship
between
[[Page 11242]]
the factual issues and the relief requested by the objection.'' (40 CFR
178.27(e)) Gharda seems to be arguing that if the chlorpyrifos-oxon was
not relevant to the Agency's assessment, it would somehow change the
outcome of the final rule, but Gharda fails to explain how
consideration of that study would ultimately impact the Agency's
conclusions concerning the safety of chlorpyrifos. In order to evaluate
this ``hearing request'', EPA has had to discern from context what the
factual issue is and what Gharda specifically hopes to accomplish with
this evidence. This is contrary to EPA's regulations, which place the
burden of presenting evidence upon which the objector relies to justify
an evidentiary hearing on the objector, not on EPA. (40 CFR 178.27(c)
and (d)) It appears that Gharda in its comment is trying to flip the
burden for demonstrating whether an evidentiary hearing is necessary
onto EPA; as such EPA believes that Gharda has failed to meet a
threshold burden of submitting a hearing request that meets the basic
criteria for such submissions under 40 CFR 178.27.
Significantly, by its own terms, Gharda does not believe that a
hearing is necessary for the Agency to receive factual evidence, since
the Agency already ``has all of the scientific data at its disposal''
to evaluate this objection. (Ref. 39 at pg. 34) As noted previously,
FFDCA directs EPA to ``hold a public evidentiary hearing if and to the
extent the Administrator determines that such a public hearing is
necessary to receive factual evidence relevant to material issues of
fact raised by the objections'' (21 U.S.C. 346a(g)(2)(B)) This language
was added to the FFDCA by the FQPA in 1996, after EPA promulgated its
evidentiary hearing regulations, and EPA views it as providing broad
discretion to evaluate whether a hearing is necessary, even if the
requirements in 40 CFR 178.32 are met. EPA does not interpret this
language as requiring it to hold a hearing in any instance where
factual evidence relevant to a material issue of fact is proffered
(essentially the standard set forth in 40 CFR 178.32); rather, EPA
construes the statutory language as requiring it to hold a hearing only
where it determines a hearing is necessary to receive such proffered
evidence. In other words, a party wishing to obtain a hearing must not
only satisfy the requirements of 40 CFR 178.32, it must also show that
an evidentiary hearing is necessary for the presentation of proffered
evidence to the Agency.
In this particular instance, Gharda states that EPA already has all
the scientific data necessary to evaluate this issue and thus does not
believe that a hearing is necessary to address the relevance of the
oxon issue. EPA agrees. Because EPA already has the Corteva Oxon Study
in its files, EPA has determined that a hearing is not necessary to
receive that evidence. This conclusion is bolstered by EPA's
determination that ultimately, consideration of this study would not
materially impact EPA's conclusions regarding the safety of
chlorpyrifos, since (as discussed later in this unit) EPA could not
support a safety finding for chlorpyrifos based on consideration of
only the chlorpyrifos (and not the oxon) concentrations in drinking
water.
Moreover, in examining the evidentiary proffer of the Reiss
Declaration, EPA concludes that a hearing would not be appropriate for
receiving that evidence. ``An evidentiary hearing will not be granted
on the basis of mere allegations . . . or general descriptions of
positions and contentions. . . .'' (40 CFR 178.32(b)(2)) The Reiss
Declaration contains a composite of conclusory statements of
interpretation of the Corteva Oxon Study, with no elucidation of how
Dr. Reiss arrived at those conclusions. (Ref. 39 at pgs. 113 through
132) One paragraph simply refers to a ``prior study'' to illustrate an
example of the oxon causing lower levels of brain AChE inhibition than
chlorpyrifos, but no citation to that study is provided. (Id. at pg.
120, paragraph 26) Paragraph 27, which Gharda quotes for its
objections, concludes that the Corteva Oxon Study ``found (a) no
detectable circulating chlorpyrifos oxon in blood, (b) no statistically
significant AChE inhibition in either RBC or brain, and (c) an absence
of clinical signs of toxicity or markers of exposure.'' (Id. at pg.
121, paragraph 27) But that is it. There is no explanation of how Dr.
Reiss came to those conclusions based on the study or what information
provided in the study that supports these conclusions. Therefore, with
regard to the Corteva Oxon Study, EPA finds that a hearing is not
warranted to receive the Reiss Declaration, since the statements
contained therein appear to contain mere allegations and conclusions.
In applying the criteria for granting a hearing, EPA looks first to
the question of whether there is a genuine and substantial issue of
fact. (40 CFR 178.32(b)(1)) As noted previously, Gharda has failed to
provide a clear statement of the factual issue to be resolved at an
evidentiary hearing. However, EPA recognizes Gharda's assertion that
chlorpyrifos-oxon is not relevant for risk assessment purposes due to
the lack of toxicity allegedly demonstrated in the Corteva Oxon Study
is at odds with EPA's assessment of chlorpyrifos-oxon residues in
drinking water and in the aggregate risk assessment. Whether there is
valid scientific data supporting a different conclusion about the
toxicity of chlorpyrifos-oxon is likely to be a factual question,
rather than one of law or policy.
Nevertheless, EPA's hearing regulations also require that the
``[r]esolution of the factual issue(s) in the manner sought by the
person requesting the hearing would be adequate to justify the action
request.'' (40 CFR 178.32(b)(3)) Under this prong, Gharda's request for
a hearing fails. As noted previously, Gharda has failed to provide a
discussion of how resolution of this factual issue would assist in
granting the relief of their objection. For that matter, Gharda has not
even clarified how their objection (i.e., failure to consider relevant
scientific information) supports a change to the Agency's safety
determination in the final rule.
Assuming arguendo that Gharda (and Dr. Reiss) has correctly
interpreted the Corteva Oxon Study and assuming also that chlorpyrifos-
oxon is less toxic than chlorpyrifos and is not therefore the relevant
exposure measurement for assessing risks of chlorpyrifos in drinking
water as EPA had assumed, Gharda's request for an evidentiary hearing
still fails. This is because this assumption would not ultimately
change the outcome of the final rule; EPA would still be unable to
conclude that the chlorpyrifos tolerances were safe because the
estimated concentrations of chlorpyrifos itself (rather than
chlorpyrifos-oxon) in drinking water still exceed the relevant DWLOC.
In the 2020 PID, EPA calculated a DWLOC for both chlorpyrifos and
chlorpyrifos-oxon. The DWLOCs used for comparison to residues of
chlorpyrifos in drinking water in the final rule were associated with
chlorpyrifos-oxon, as that was considered the residue of concern: 4.0
ppb for steady-state exposures and 23 ppb for acute exposures. Based on
the 2016 DWA, EPA determined that there were likely to be estimated
concentrations of chlorpyrifos-oxon in drinking water that exceeded
those DWLOCs. As indicated in Unit II.B.1.d., where the concentrations
of pesticide in drinking water exceed the DWLOC, the Agency concludes
that the aggregate exposures are not safe. If, as Gharda asserts, the
chlorpyrifos-oxon residues are not relevant, there would still be
exposures to chlorpyrifos in drinking
[[Page 11243]]
water, and EPA would need to consider whether those exposures to
chlorpyrifos would be safe. The DWLOCs calculated for chlorpyrifos were
17 ppb for steady-state exposures and 100 ppb for acute exposures.
(Ref. 31 at pg. 15) Relative to the DWLOCs for chlorpyrifos-oxon, the
DWLOCs for chlorpyrifos are larger, providing slightly more room in the
risk cup for residues of chlorpyrifos, relative to chlorpyrifos-oxon.
Nevertheless, the 2016 DWA indicates that for the majority of HUC
regions assessed, the estimated concentrations of chlorpyrifos alone in
drinking water still exceed the higher DWLOC of 17 ppb, i.e., Table 25
of the 2016 DWA indicates that the range of chlorpyrifos concentrations
in drinking water have the potential to exceed the DWLOC for all HUC
regions except one (HUC 16b). (Ref. 29 at pgs. 73-74) As long as there
are certain vulnerable watersheds where the concentrations of
chlorpyrifos exceed the maximum amount allowed for residues in drinking
water to ensure that aggregate chlorpyrifos exposures stay below safe
levels, the Agency cannot make a safety finding to support the
chlorpyrifos tolerances. Thus, Gharda has failed to raise a material
factual issue for which an evidentiary hearing would be appropriate.
``An evidentiary hearing will not be granted on factual issues that are
not determinative with respect to the action requested. For example, a
hearing will not be granted if the Administrator concludes that the
action would be the same even if the factual issue were resolved in the
manner sought.'' (40 CFR 178.32(b)(3))
The absence of a material issue of fact here is fatal to Gharda's
request for a hearing. As noted previously, the Corteva Oxon Study,
even if it supported Gharda's assertion that chlorpyrifos-oxon residues
were not relevant for EPA's risk assessment, does not ultimately
support a finding that the chlorpyrifos tolerances are safe. Therefore,
EPA concludes that a hearing is not justified to receive that evidence
for the purposes of evaluating Gharda's claim concerning the
consideration of chlorpyrifos-oxon in the Agency's risk assessment.
This conclusion also reinforces EPA's earlier determination that a
hearing is not necessary to receive the evidence since the study is
already in the Agency's files. Furthermore, because the Reiss
Declaration offers nothing more than conclusory statements about how to
interpret the Corteva Oxon Study, it also fails to provide a basis for
determining that the chlorpyrifos tolerances are safe and changing the
final rule. Conclusory statements indicating a potential difference of
scientific interpretation of a study that, even in the most favorable
light, is not outcome determinative, does not create a material issue
of fact. (See National Corn Growers Ass'n, 613 F.3d at 274 (finding
that ``[m]ere differences in the weight or credence given to particular
scientific studies'' would not be a sufficient basis to overturn an
Agency conclusion that there is no material issue of fact)) Therefore,
EPA has determined that Gharda has failed to proffer evidence
warranting an evidentiary hearing on its objection concerning the
Agency's assessment of chlorpyrifos-oxon.
D. Summary of Reasons for Denial of Hearing Requests
EPA is denying the requests for evidentiary hearing submitted by
the American Soybean Association, the Sugarbeet Associations, and the
Cherry Marketing Institute because those entities failed to proffer any
evidence for which a hearing would be appropriate. The statute clearly
states that a hearing is appropriate when ``necessary to receive
material evidence.'' (21 U.S.C. 346a(g)(2)(B)) Moreover, these
Objectors ultimately disagree with EPA's application of the FFDCA
statutory standard for assessing exposures, which is a legal question,
rather than a factual one, and thus not appropriate for a hearing. (40
CFR 178.32(b)(1))
EPA is denying Gharda's request for an evidentiary hearing for lack
of necessity since, as Gharda concedes, EPA already has the evidence
proffered and for lack of materiality, since even if Gharda's factual
assertions are correct and supported by the evidence proffered, those
issues are not determinative with regard to the Agency's conclusions in
the final rule, i.e., they would not provide a basis for leaving the
chlorpyrifos tolerances in place at this time.
VII. Response to Objections
A. Overview
EPA denies each of the objections to the final rule. As noted in
Unit V. of this document, EPA received several objections from many
different entities, including trade associations, farm bureaus,
individual growers, and registrants. EPA has grouped these objections
into five different categories, which are described later in this unit.
After a brief description of each objection or objection subissue, EPA
responds to each in this unit.
B. Denial of Objections Not Properly Filed
As a preliminary matter, EPA notes that several parties submitted
documents to the Federal eRulemaking Portal that are styled as
objections but that do not comply with the requirements of 40 CFR
178.25. As EPA noted in the final rule--and as required in EPA's
regulations--objections must be submitted in writing and filed with the
Office of the Hearing Clerk in accordance with the procedures in 40 CFR
178.25. While the regulations specify that objections are to be mailed
or hand-delivered to the Hearing Clerk, due to the pandemic the Office
of Administrative Law Judges (OALJ), where the Office of the Hearing
Clerk is housed, is directing parties to file electronically. (Ref. 40)
The final rule provided instructions for filing online as well as what
to do in the event that online filing was not available. (Ref. 1 at
pgs. 48315-16)
The following parties did not submit their objections to the Office
of the Hearing Clerk either through the OALJ e-filing system or through
mail or hand delivery as required by 40 CFR 178.25(b): The Colombia
Ministry of Trade, Industry and Tourism; Drexel Chemical Company; the
International Pepper Community; Oregonians for Food and Shelter; and
the Republic of Ecuador. (Refs. 41 through 45) EPA also notes that the
National Association of Wheat Growers submitted two sets of objections:
One as a standalone document, which was not properly filed with the
Office of the Hearing Clerk (Ref. 46), and one as a signatory to
objections submitted by numerous growers, retailers, co-ops,
applicators, refiners, crop consultants, and other agricultural
stakeholders (which EPA is referring to as the Agricultural Retailers
Association, et al. objections (Ref. 47)), which was properly filed
with the Office of the Hearing Clerk. EPA's regulations require EPA to
deny each objection that is found not to conform with 40 CFR 178.25.
(40 CFR 178.30(a)(1)) As a result, EPA denies the previously-described
objections that were not submitted to the Office of the Hearing Clerk
and will not be considering them in this Order.
C. Responses to Specific Issues Raised in Objections
1. Objections to the Scope of EPA's Final Rule Revoking Tolerances
One theme running through several objections was an assertion that
EPA's revocation of all chlorpyrifos tolerances was unlawful and
unnecessary. Some Objectors argued that EPA should have
[[Page 11244]]
retained some of the chlorpyrifos tolerances, rather than revoking them
all, based on EPA's mitigation proposal in the 2020 PID to limit uses
to 11 high-benefit crops in certain geographic locations. Relatedly,
some Objectors believed that EPA should have coordinated the tolerance
revocations with actions under FIFRA to cancel uses in order to avoid
revoking all tolerances. Finally, some Objectors asserted that EPA
should have retained import tolerances since imported commodities would
not contribute to drinking water exposures, which were driving risk
concerns. These objections and EPA's responses are discussed in further
detail in this sub-unit.
a. EPA's Proposal for Limiting Uses to 11 High-Benefit Crops in the
2020 Proposed Interim Decision (PID) for Chlorpyrifos
i. Objection. Nearly all Objectors assert that revoking all
chlorpyrifos tolerances was unlawful and unnecessary based on
statements in the 2020 PID where EPA proposed a subset of chlorpyrifos
tolerances for retention, provided certain restrictions were
implemented. (The objections, requests for hearing on objections, and
stay requests submitted in response to the final rule are available at
<a href="https://www.regulations.gov">https://www.regulations.gov</a> in docket ID number EPA-HQ-OPP-2021-0523.)
Some Objectors' claims are general, asserting that EPA should have
retained all 11 tolerances, and some are specific to their own
commodity of interest (e.g., the American Soybean Association focuses
on EPA's determination in the 2020 PID as it relates to soybeans,
specifically). (Ref. 36 at pg. 4) In each case, however, these
Objectors rely on EPA's proposed finding in the 2020 PID to demonstrate
that EPA's record contains sufficient information to determine that at
least some tolerances and uses satisfy the FFDCA safety standard. The
objectors conclude that, therefore, revocation of all tolerances was
inconsistent with the FFDCA requirement to consider aggregate exposure
from all ``anticipated dietary exposures''.
The Objectors point to the Ninth Circuit's April 29, 2021, decision
for support that EPA was not required to revoke all chlorpyrifos
tolerances. The Objectors note that the Court gave EPA the option to
``either revoke all chlorpyrifos tolerances or modify chlorpyrifos
tolerances,'' as long as the modification was supported by a safety
determination, as well as a direction to ``modify or cancel related
FIFRA registrations for food use in a timely fashion consistent with
the requirements of [FFDCA 408(a)].'' (LULAC, 996 F.3d at 703-04)
Consequently, the Objectors assert that EPA should have modified
tolerances by retaining the 11 uses rather than revoking all.
ii. Denial of objection. EPA denies this objection. The Objectors'
claim is primarily based on a misunderstanding of the FFDCA's
requirement to consider aggregate exposure, a misreading of the 2020
PID, and a disregard of the facts at the time of the final rule. When
one corrects for each of those factors, it is clear that EPA's
revocation of all chlorpyrifos tolerances was entirely consistent with
the Agency's obligations under the FFDCA.
Before diving into the rationale for why the Objectors' argument is
legally flawed, it is worth providing context for the PID, or proposed
registration review decision. Under EPA's regulations, a proposed
(interim) registration review decision lays out the Agency's proposed
findings, identifies proposed risk mitigation measures or other
remedies as needed, identifies any missing or needed data, specifies
proposed labeling changes, and identifies any anticipated deadlines.
(See 40 CFR 155.58(b)) EPA publishes notice of the availability of this
proposed decision and provides for at least a 60-day comment period.
(40 CFR 155.58(a)) After consideration of those comments, EPA will
issue an interim or final registration review decision, which can be
very similar to the proposed decision or incorporates changes based on
those comments. (40 CFR 155.58(c)) As noted in Unit II.A., the purpose
of registration review is to determine whether the registered pesticide
continues to meet the standard for registration. Where EPA identifies
potential unreasonable risks from use of a pesticide, EPA considers
whether there are any options or measures for reducing or mitigating
those risks that would enable the pesticide to meet the standard for
registration. Where such mitigation measures are available, EPA will
propose those in the proposed registration review decision in
conformance with its regulations. But consistent with the nature of any
proposal, the findings in the proposed decision are just proposals and
subject to change based upon public comment or other developments that
may occur before the final decision is issued.
For the 2020 PID for chlorpyrifos, EPA followed the process laid
out in its regulations. EPA summarized the findings of its aggregate
risk assessment and concluded that ``[w]hen considering all currently
registered agricultural and non-agricultural uses of chlorpyrifos,
aggregate exposures are of concern. If considering only the uses that
results in DWLOCs below the EDWCs, aggregate exposures are not of
concern.'' (Ref. 31 at pg. 19 (emphases added)) In other words, EPA
found that the universe of currently registered chlorpyrifos uses
presented aggregate exposures that exceeded the Agency's determined
safe level of exposure. As a result, EPA proposed mitigation to address
the dietary and aggregate risks of concern that were posed by use of
chlorpyrifos as currently registered. (Id. at pg. 40)
To mitigate these risks, EPA proposed that chlorpyrifos
applications be limited to the following 11 specific uses in only those
specific geographic areas where the estimated concentrations of
chlorpyrifos in drinking water from those uses were lower than the
DWLOC, i.e., the maximum amount of chlorpyrifos residues that could be
present in water and still ensure that aggregate exposures would be
safe: Alfalfa, apple, asparagus, tart cherry, citrus, cotton, peach,
soybean, strawberry, sugar beet, and spring and winter wheat. (Id. at
pgs. 40 and 41) For this mitigation proposal to reduce aggregate
exposures to safe levels, all other existing uses of chlorpyrifos that
contribute to aggregate exposures (i.e., food, drinking water, and
residential exposures) would need to be cancelled and the labels for
products containing the identified subset of uses would need to be
amended to ensure that applications would be limited to those
specifically identified geographic areas. Moreover, some revisions to
labeled application rates would also be required since the conclusions
in the 2020 PID that drinking water contributions were safe in these
areas from these uses was based on usage data rather than maximum
labeled application rates. It is also important to emphasize that the
act of proposing to limit chlorpyrifos applications to this subset of
uses did not, in fact, automatically result in the elimination of all
uses beyond those identified uses; that would require separate actions
under FIFRA to cancel uses and to amend labels, which has not occurred.
EPA proposed this particular list of uses as critical and high-
benefit uses of those uses currently registered for chlorpyrifos. (Ref.
30, Attachment 2) Although the ``reasonable certainty of no harm''
standard in the FFDCA, which is strictly a risk-based standard, allows
no consideration of benefits, except in one very limited circumstance
not relevant here (see 21 U.S.C. 346a(b)(2)(B)), FIFRA's ``unreasonable
adverse effects'' standard incorporates a consideration of economic
costs or benefits, which EPA took into
[[Page 11245]]
consideration when identifying this proposed list of retainable uses as
part of the FIFRA registration review process. But this is likely not
the only combination of uses that could have resulted in safe levels of
aggregate exposure. To conserve resources (and because previous
analyses had indicated risks of concern when considering all
chlorpyrifos uses), EPA's 2020 DWA focused solely on the areas where
these particular crops were grown that had the highest benefit to
growers to determine if there were areas where the EDWCs were below the
DWLOC; it is possible that a different set of crops and a different
range of geographic areas could also result in safe aggregate
exposures. The Agency expressly noted that it would ``consider
registrant and stakeholder input on the subset of crops and regions
from the public comment period and may conduct further analysis to
determine if any other limited uses may be retained.'' (Ref. 31 at pg.
40) The 2020 PID was made available for public comment, and the Agency
did, in fact, receive hundreds of comments, although none committed to
making changes to the chlorpyrifos registrations necessary to implement
the 2020 PID as proposed, nor were any requests for voluntary
cancellation of registered uses submitted under FIFRA in response to
the 2020 PID.
Turning now to the legal standard, as noted in Unit II.A., FFDCA
section 408(b)(2)(A)(i) permits EPA to leave tolerances in place only
if the Agency can determine that the tolerance is safe. If the Agency
determines that the tolerances, which must be based on aggregate
exposures, are not safe (or cannot determine that tolerances are safe),
the Agency must modify or revoke them. (21 U.S.C. 346a(b)(2)(A)(i); see
also LULAC, 996 F.3d at pgs. 693-94 (concluding that when EPA receives
a petition raising substantive questions concerning safety, FFDCA
provides no middle ground in which EPA can leave tolerances in place if
EPA is unwilling or unable to make a safety finding)) The FFDCA also
defines safe as requiring EPA to determine 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) (emphases added)) Congress understood the
phrase ``aggregate exposure'' to include dietary exposures under all
tolerances for the pesticide chemical residue, H.R. Rep. 104-669(II) at
1279, and codified that understanding among the factors EPA must
consider when establishing, modifying, leaving in effect, or revoking
tolerances. (21 U.S.C. 346a(b)(2)(D)(vi)) In FFDCA section
408(b)(2)(D)(vi), EPA must consider ``available information concerning
the aggregate exposure levels of consumers (and major identifiable
subgroups of consumers) to the pesticide chemical residue and to other
related substances, including dietary exposure under the tolerance and
all other tolerances in effect for the pesticide chemical residue, and
exposure from other non-occupational sources.'' (Id. (emphasis added))
The requirement to consider ``aggregate exposure'' was added to the
FFDCA through the FQPA amendments in 1996. (Food Quality Protection Act
of 1996, Pub. L. 104-170) Prior to the enactment of the FQPA, when
assessing risk, EPA treated exposures from different pathways as
independent events and made no concerted effort to evaluate potential
exposures simultaneously. In reality, however, exposures to pesticides
do not occur as single, isolated events, but rather as a series of
sequential or concurrent events that may overlap or be linked in time
and space. Congress, in enacting the FQPA, was concerned with ensuring
that the Agency's assessments under the FFDCA would be strictly health-
protective and risk-based, and as a result, made a number of
significant amendments to the FFDCA, including the new risk-only safety
standard, the FQPA children's safety factor, and, of most relevance
here, a new requirement for EPA to consider exposures in the aggregate
rather than independently.
Following the enactment of the FQPA, EPA developed guidance on how
to conduct aggregate exposure and risk assessment. (Ref. 14) That
guidance describes the aggregate exposure and risk assessment as
involving ``the analysis of exposure to a single chemical by multiple
pathways [food, drinking water, residential] and routes of exposure
[oral, dermal, inhalation] . . . . All potential, relevant routes of
exposure are analyzed with an aggregate exposure assessment.'' (Id. at
pg. 4) That guidance also defines aggregate risk as ``[t]he likelihood
of the occurrence of an adverse health effect resulting from all routes
of exposure to a single substance.'' (Id. at pg. 72) In describing how
EPA intends to conduct such aggregate risk assessments, EPA states that
``[t]he starting point for identifying the exposure scenarios for
inclusion in an aggregate exposure assessment is the universe of
proposed and approved uses for the pesticide,'' which are determined by
looking to labeled allowable use patterns. (Id. at pgs. 24, 44 and 45)
Moreover, the guidance directs that aggregate exposure and risk should
be estimated for major identifiable subgroups of the population, which
the Agency typically does through considerations of demographics (e.g.,
age, gender, racial/ethnic background) and temporal (season) and
spatial (geographics) characteristics of potentially exposed
individuals. (Id. at pgs. 12, 24)
The Aggregate Exposure Guidance describes an approach for assessing
aggregate exposures that recognizes such exposures to hypothetical
individuals in the population: ``(1) may occur by more than one route
(i.e., oral, dermal and/or inhalation); (2) may originate from more
than one source and/or pathway (i.e., food, drinking water, and
residential); (3) may occur within a time-frame that corresponds to the
period of exposure required in an appropriately designed toxicity study
to elicit an adverse toxicological effect; (4) should occur at a
spatially relevant set of locations that correspond to an individual's
potential exposure; and (5) should be consistent with the individual's
demographic and behavioral attributes.'' (Id. at pg. 26) In practice,
this means that the Agency might consider whether different populations
of individuals are more or less likely to eat different kinds of food
over different time periods; whether pesticide concentrations in
drinking water vary temporally due to the growing season calendar or
spatially due to the nature of applications generally being localized
or regional; and/or whether different populations are likely to use or
be exposed to pesticides in non-occupational settings. Generally, EPA
would utilize upper-end estimates to ensure protection for the most
vulnerable populations, unless other factors warranted a different
approach.
From there, the Agency assesses the aggregate exposure through
relevant routes of exposure for hypothetical individuals among these
major identifiable subgroups (including food, drinking water, and
residential exposures to which that individual is likely exposed),
taking into consideration the various factors for co-occurrence of
exposures in the various exposure pathways. (Id. at pg. 26) Where risks
from aggregate exposures exceed safe levels, EPA will examine whether
refinements can be made to the assessment. (Id. at pg. 13)
In the final rule, EPA assessed aggregate exposure based on all
currently registered uses of chlorpyrifos as required by the FFDCA and
consistent with its guidance. That
[[Page 11246]]
assessment considered exposure through oral, dermal, and inhalation
routes of exposure that could result from exposures in food, drinking
water, and residential uses. Taking into consideration the registered
use patterns for chlorpyrifos, EPA assessed the universe of potential
exposures from all currently approved uses of chlorpyrifos because no
formal steps had been taken to limit those uses.
In demanding that EPA retain tolerances for the 11 uses, the
Objectors essentially argue that EPA should have presumed that
individuals would only be exposed to chlorpyrifos from the 11 uses
because EPA proposed those 11 uses as an option for mitigation in the
2020 PID proposal. However, that argument ignores the premise in the
PID that the safety finding for those uses is contingent on all other
uses being cancelled and the remaining 11 uses being restricted both
geographically and with lowered use rates. Exposures from those uses
alone could not reasonably be considered as ``anticipated'' since they
did not yet (nor did EPA have reason to believe that they would)
reflect the exposures people would be exposed to in the real world. The
FFDCA requires EPA to determine whether tolerances are safe, requiring
consideration of aggregate exposures, including ``anticipated dietary
exposures''; it does not allow EPA to leave tolerances in place if they
would be safe at some unspecified time in the future based on certain
mitigation that may not be implemented.
At the time of the final rule, no concrete steps had been taken by
registrants under FIFRA to implement the PID proposal: No uses had been
cancelled, nor had any labels been revised to geographically limit
applications or limit maximum application rates. Although there were
discussions with registrants and indications of a willingness to
mitigate uses (see discussion in next sub-unit), the Agency had not
received prior to the issuance of the final rule from registrants any
formal requests under FIFRA for voluntary cancellation or applications
to amend labels, to which the Agency could point as directionally
supportive for a conclusion that exposures would at some future time be
limited to that subset of chlorpyrifos applications. Until such uses
cease--or at least until EPA has a reasonable basis to believe that
they will cease--the Agency could not ignore the exposures from those
uses. In sum, the 2020 PID proposal, without more, is just a proposal;
it does not support an EPA assumption that aggregate exposures would be
limited to that subset of uses instead of an assessment based on the
actual registered uses and ongoing real-world applications of
chlorpyrifos.
While the Objectors claim that EPA could have modified tolerances,
as per the Court's order, by leaving in place only those identified in
the 2020 PID, doing so, without accompanying registration actions under
FIFRA, would have put EPA in the position of picking ``winners and
losers'' among the tolerances. While, under FIFRA, EPA might be able to
make an argument that some uses contribute relatively lower risks or
higher benefits than other uses and thus meet the FIFRA standard of no
unreasonable adverse effects on the environment whereas others may not,
considerations of those relative benefits is not a factor for
consideration under the FFDCA when determining which tolerances are
safe or not. As noted previously, the 2020 PID proposal reflected one
possible subset of uses that might warrant retention based on economic
considerations. In circumstances where aggregate exposures exceed safe
levels, there are potentially multiple variations of the potential
subset of tolerances that might meet the safety standard and that EPA
did not analyze. As such, EPA's general policy is to defer to the
pesticide registrant and the public to determine which of the various
subsets of tolerances are of sufficient importance to warrant
retentions since not all parties might agree on the particular
combination that should be retained. For example, one comment submitted
on the 2020 PID requested that EPA retain tolerances on cranberries
(Ref. 48), which was not listed among the 11 uses in the PID. Without
some reasonable basis to believe that the uses would be limited as had
been proposed, EPA did not have a basis to assume anticipated exposures
would be limited to that particular subset of uses for purposes of
modifying the tolerances.
Some Objectors made this same argument but focused more
specifically on their crop of interest (e.g., cherry, citrus, soybean,
sugarbeet). These objectors assert that EPA could not have revoked the
specific commodity tolerance because that crop was included in the list
of crops EPA proposed to retain and thus EPA did not have a basis for
concluding that those tolerances themselves were unsafe. However, the
Agency does not assess tolerances for each crop in a vacuum; whether
one tolerance is safe depends on whether aggregate exposure from that
tolerance and all other tolerances in effect are safe. (21 U.S.C.
346a(b)(2)(D)(vi)) The consequence of the FFDCA requirement for EPA to
assess the safety of tolerances as an aggregate is that, when one
tolerance is unsafe, all tolerances are equally unsafe until aggregate
exposures have been reduced to acceptable levels. At the time the final
rule was issued, there were over 80 tolerances in effect, which the
Agency was required to consider in its aggregate exposure assessment,
unless there had been a reasonable basis to exclude exposures from
those tolerances. The list in the 2020 PID was only a proposed
mitigation measure, necessary because the aggregate exposures from
chlorpyrifos, which included exposures from use of chlorpyrifos on
these three commodities, exceeded safe levels.
It is also worth noting that tolerances themselves are broadly
applicable rules that regulate the amount of pesticide residues on a
food commodity. As such, they are not limited in geographic scope, and
the Agency must be able to determine that all aggregate exposures from
any registered uses (including all relevant geographic areas) that
would be covered by a particular tolerance would be safe. For example,
the tolerance covering residues of chlorpyrifos on cherry applies to
the pesticide residues on the crop regardless of the location of
application. In practice, this means that EPA needs to be able to
determine that use of chlorpyrifos in any place permitted by the FIFRA
label would be safe. For cherries, EPA's 2020 PID proposal only
concluded that use on cherry could be safe in Michigan, if the other
aforementioned mitigation measures were implemented; whether cherry use
could be safe in other areas was not assessed. In order to conclude
that cherry use was safe based on the 2020 PID proposal, the labels
would need to restrict chlorpyrifos use to cherries only in Michigan.
Since the uses on cherry were not so restricted under FIFRA at the time
of the final rule, EPA could not assume that chlorpyrifos would be used
only in the limited geographical regions without some progress being
made on the label revisions.
In conclusion, while the 2020 PID proposed that there is at least
one subset of chlorpyrifos uses that could be safe if additional
restrictions were adopted and all other uses contributing to aggregate
exposures were cancelled under FIFRA, that is not a basis for
maintaining tolerances when the Agency does not have a reasonable basis
to believe that the registrations would be so amended. Based on the
factual realities at the time of the final rule, EPA was required to
consider aggregate exposures resulting from approved labelling and all
currently registered
[[Page 11247]]
uses. The Objectors' claim incorrectly relies on the proposal in the
2020 PID as a basis for limiting the aggregate exposure assessment, and
the request to limit EPA's safety assessment to a subset of actual
exposures based on a proposal would reflect an incorrect application of
the statutory standard under the FFDCA. EPA recognizes that the
practice of identifying mitigation measures to address risks of concern
in the proposed or interim decisions in registration review is common,
and the expectation is that registrants will make adjustments to retain
registrations. However, this is not always the case; some registrants
may suggest alternative means of mitigating risks, which the Agency
then needs to evaluate, or may refuse due to a disagreement with the
Agency's underlying rationale for its decision. When mitigation
measures are not implemented (or it is unclear that such risks will be
mitigated), the risks that EPA initially identified remain. Therefore,
the objection is denied.
b. Coordination With FIFRA Under FFDCA Section 408(l)(1)
i. Objection. Objectors assert that the revocation of tolerances
should not have been undertaken without coordination of use
cancellations under FIFRA. The Sugarbeet Associations and Gharda argue
that EPA had a statutory duty under section 408(l)(1) of the FFDCA to
harmonize the chlorpyrifos tolerance revocation with necessary actions
under FIFRA. (Refs. 37 and 39) They argue that EPA offers no
explanation for why it was not practicable for EPA to cancel the FIFRA
registrations and revoke tolerances for the food uses for which EPA
would be unable to make a safety finding while maintaining the
registrations and tolerances that the 2020 PID proposed for retention.
The Sugarbeet Associations also argue that because the Ninth Circuit
also ordered EPA to ``correspondingly modify or cancel related FIFRA
registrations for food use in a timely fashion,'' EPA's failure to
harmonize its revocations with FIFRA actions is therefore also
inconsistent with the Court's order. (Ref. 37 at pg. 7) Gharda
acknowledges that EPA did engage in negotiations with registrants to
attempt this harmonization but alleges that EPA was acting in bad faith
in those negotiations and disregarded Gharda's commitment to modify its
registration. (Ref. 39 at pgs. 28 through 31) The Minor Crop Farmers
Alliance notes that EPA did not follow ``its traditional FIFRA/FQPA
sequencing of taking the necessary tolerance actions only after first
finalizing its decision in a cancellation action under Section 6 of
FIFRA.'' (Ref. 49 at pg. 4) Finally, CLA/RISE requests guidance on how
EPA intends to harmonize the tolerance revocation under FIFRA to reduce
confusion among growers and industry. (Ref. 50)
ii. Denial of objection. EPA denies this objection on the following
legal and factual grounds. FFDCA 408(l)(1) states that ``[t]o the
extent practicable . . . , in issuing a final rule under this
subsection that suspends or revokes a tolerance or exemption for a
pesticide chemical residue in or on food, the Administrator shall
coordinate such action with any related necessary action under
[FIFRA].'' (21 U.S.C. 346a(l)(1)) While the statutory language includes
the word ``shall,'' this provision clearly contemplates that there may
be circumstances in which coordination is not practicable and thus such
coordination is not required. Even when such coordination would be
practicable, the statute does not require that this coordination be
concurrent or occur in any predetermined order.
EPA has previously opined on this provision in a final rule
revoking carbofuran tolerances in which this same comment was raised.
(See 74 FR 23046, 23069-70, May 15, 2009 (FRL-8413-3)) In that rule,
EPA found that the requirement to ``coordinate'' is a direction to
ensure that the substance of actions taken under FIFRA and the FFDCA
are consistent, and that the Agency make a determination as to the
proper order of action under the two statutes. It cannot be read as a
requirement that actions under FIFRA precede actions under the FFDCA,
or that any particular order for EPA actions is necessarily required.
Accordingly, there is no support for the notion that, as a matter of
law, the Agency lacks the legal authority to revoke pesticide
tolerances under the FFDCA that do not meet the safety standard of that
statute unless the Agency has first canceled--or simultaneously
cancels--associated pesticide registrations under FIFRA.
In this instance, the Ninth Circuit itself prioritized EPA's taking
action on the chlorpyrifos tolerances above the action necessary under
FIFRA, when it set a very short and specific deadline for addressing
pesticide tolerances (i.e., within 60 days of the issuance of the
mandate) and allowed flexibility for EPA to ``modify or cancel related
FIFRA registrations for food use in a timely fashion.'' (LULAC, 996
F.3d at 703-04) Under the Court's timeframe, it was not practicable for
EPA to take action under FIFRA to cancel registered food uses of
chlorpyrifos concurrently with the final rule. Cancellation of uses
under FIFRA section 6(b) requires several steps, including drafting a
notice of intent to cancel, interagency coordination and SAP review, as
well as possible administrative hearings, and can take several years to
complete. (See 7 U.S.C. 136d(b)) Even the process to obtain and act on
voluntary cancellation requests can be a time-consuming process with
statutorily set comment periods before a cancellation can be ordered.
(7 U.S.C. 136d(f))
In any event, in this particular instance, EPA did attempt to
harmonize its tolerance revocation actions with cancellation actions
under FIFRA. As the Minor Crop Farmer Alliance pointed out, EPA
traditionally, as part of the registration review process, identifies
the relative risks and benefits of particular uses and works with
registrants to eliminate uses that no longer meet the FIFRA standard,
including for safety risks. Under that approach, EPA and the
registrant(s) can mutually agree on terms for the smooth phase-out of
the product, and the product or use cancellations can be coordinated
with tolerance revocations under the FFDCA. After the Ninth Circuit's
decision was issued, EPA engaged in discussions with the four
registrants of technical chlorpyrifos products (i.e., those that are
used to manufacture the chlorpyrifos pesticide products sold to end
users) to discuss possible voluntary use cancellations and label
restrictions, although EPA did not initiate any discussions with the
dozens of registrants of end-use products. (Ref. 51) Despite the
progress made in those discussions, no registrant submitted under FIFRA
a request for voluntary cancellation of any uses or application to
amend existing chlorpyrifos labels to reduce application rates and
geographically limit uses. One of those registrants, Gharda, asserts
that EPA acted in bad faith in the negotiations with Gharda and
disregarded a commitment from Gharda to modify its registration. EPA
disagrees with Gharda's characterization of the negotiations.
Prior to the issuance of the final rule, EPA entered into
discussions with Gharda, as well as several other registrants, in a
good-faith effort to determine if the safety issues identified in EPA's
record on chlorpyrifos by the Ninth Circuit could be resolved in a
sufficient and timely manner to allow for the modification of
tolerances by the Court's imposed timeline. EPA held several meetings
with each of the technical registrants, including Gharda, to discuss
their interests and concerns as EPA considered its response to the
Court's directive to issue a final rule. (Id.) The meetings with Gharda
occu
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This is legal information, not legal advice. Laws vary by jurisdiction and change frequently. Always verify current law with official sources and consult a licensed attorney in your jurisdiction for advice on your specific situation.