Docket Number: EPA-HQ-OPP-2009-0308
www.regulations.gov
!* \ UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
| | WASHINGTON, D.C. 20460
OFFICE OF CHEMICAL SAFETY
AND POLLUTION PREVENTION
Agency Response to the Natural Resources Defense Council's (NRDC)
April 2009 Tetrachlorvinphos Petition
October 2022
Digitally signed by
EDWARD MESSINA
Date: 2022.10.0611:54:28
-04'00'
Ed Messina, Esq.
Office Director
Office of Pesticide Programs
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Table of Contents
I. Executive Summary 5
II. Background 7
A. Registration Review of TCVP 8
B. Summary of NRDC's Petition to Cancel All Pet Uses 11
C. EPA's Review of NRDC's Issue Paper 12
D. EPA's Initial Response to NRDC's Petition and Subsequent Litigation 13
III. EPA's Revised Residential Exposure and Risk Assessment 17
A. Toxicology and Uncertainty Factors 19
B. Residential Handler Exposures 21
1. Residential Handler Assumptions and Inputs 21
2. Residential Handler Risk Estimates and Conclusions 25
C. Residential Post-Application Exposure 26
1. Residential Post-application Assumptions and Inputs 26
2. Residential Post-application Risk Estimates and Conclusions 34
IV. Benefits and Impact Assessment of Cancellation of Dust Products and Select Collars.... 37
V. EPA's Responses to NRDC's Petition Claims 40
A. Statutory Background 40
1. Pesticide Registration and Registration Review 40
2. Pesticide Cancellation Process 41
B. Rationale for Granting Petition for Remaining TCVP Pet Collars 42
C. Rationale for Denying Remainder of Petition 43
1. Liquid Spray Pet Uses 44
2. Dust and Powder Pet Uses 44
VI. Next Steps 44
VII. Conclusion 45
VIII. References 45
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List of Acronyms and Abbreviations
AChE
Acetylcholinesterase
A.I.
Active Ingredient
ALJ
Administrative Law Judge
APA
Administrative Procedure Act
BEAD
Biological and Economic Analysis Division
DAF
Dermal Absorption Factor
DCI
Data Call-In
EPA
Environmental Protection Agency
ET
Exposure Time
Far
Fraction Application Rate
FIFRA
Federal Insecticide, Fungicide, and Rodenticide Act
HEC
Human Equivalent Concentration
HED
Health Effects Division
LOC
Level of Concern
MOA
Mode of Action
MOE
Margin of Exposure
NOIC
Notice of Intent to Cancel
NRDC
Natural Resources Defense Council
OP
Organophosphate
ORE
Occupational and Residential Exposure
POD
Point of Departure
RBC
Red Blood Cell
RfC
Reference Concentration
RED
Reregi strati on Eligibility Decision
SAP
FIFRA Scientific Advisory Panel
SOP
Standard Operating Procedure
TC
Transfer Coefficients
TCVP
Tetrachlorvinphos
TR
Transferable Residue Measure
TRED
Tolerance Reassessment Eligibility Decision
UE
Unit Exposure
UFdb
Database Uncertainty Factor
USD A
United States Department of Agriculture
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Table of Authorities
Statutes
5 U.S.C. § 551. et seq 11
7 U.S.C. § 136(bb) 14
7 U.S.C. §§ 136-136y 40
21 U.S.C. § 346a(b)(2)(c) 14
FIFRA section 2(bb) 8
FIFRA section 2(uu) 14
FIFRA section 3(a) 40
FIFRA section 3(c) 40
FIFRA section 3(c)(2)(B) 15
FIFRA section 3(c)(5) 40
FIFRA section 3(g) 6, 7, 15, 18, 20, 40
FIFRA section 3(g)(l)(A)(v) 41
FIFRA section 6(a) 42
FIFRA section 6(b) 41, 42
FIFRA section 6(d) 41
FIFRA section 6(f) 5, 42
FIFRA section 16(a) 42
FIFRA section 25(d) 41
Regulations
40 CFR 152.44 40
40 CFR 26 13
40 CFR 26.1303 13
40 CFR 26.1703 9
40 CFR Part 155 7, 45
40 CFR Part 164 41
70 Fed. Reg. at 40,252 40
74 FR 27035 12
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I. Executive Summary
This document constitutes the Environmental Protection Agency's (EPA or the Agency)
response to the Natural Resources Defense Council's (NRDC) petition dated April 23, 2009
(Petition) requesting that EPA cancel all pet uses of the pesticide tetrachlorvinphos (TCVP). The
Agency previously denied the 2009 NRDC Petition to cancel all pet uses for TCVP in 2020.
NRDC challenged that denial in the Ninth Circuit Court of Appeals, which issued an Order on
April 20, 2022 vacating EPA's denial of NRDC's petition and remanding to EPA to issue a
revised response within 120 days of the court's June 13 mandate {i.e., by October 11, 2022).
The factual background relevant to NRDC's petition and recent litigation is discussed in
Section II of this document. Section III explains EPA's initial rationale and conclusions from the
2020 risk assessment leading to EPA's 2020 petition denial. Section III also explains EPA's
rationale and conclusions from a new October 2022 risk assessment, which includes a more
robust analysis of previously submitted data underlying EPA's current petition response. Section
IV discusses the benefits TCVP pet products provide their users and the potential impacts
associated with the changes necessary to address any risks of concern, while section V provides
specific information on how EPA has identified risks of concern. For the reasons discussed
below, EPA is granting NRDC's petition to cancel the Federal Insecticide, Fungicide, and
Rodenticide (FIFRA) registrations for all six remaining pet collars containing TCVP and denying
the remainder of NRDC's petition to cancel all pet uses of TCVP1. Should the Agency receive
data that bears upon the conclusions as described in this response, the Agency will review that
data, make its review publicly available, update the TCVP risk assessment as appropriate, and
make this information available for public comment. Hartz is currently working on two studies
and plans to submit the data for EPA review.
As discussed in Section III, in 2020, in response to NRDC's petition, EPA completed a
revised residential exposure and risk assessment of registered TCVP pet product uses at the time
(dust/powders, liquid sprays and collars) and an addendum to that assessment to account for
proposed mitigation. In addition to the proposed mitigation, the 2020 collar assessment had been
refined based on data from a dust torsion study that was conducted to inform the liquid-to-dust
ratio of TCVP used in the exposure calculations and to account for trimming of the collar when
applied to the animal. In 2020, based on performed mitigation (as discussed below, including
voluntary cancellation of the only two dust/powder products, voluntary cancellation of one cat
collar, one use deletion of a dust product, and label amendments and product redesign for the
remaining collars), EPA found no risks of concern for liquid spray products and the remaining
collars, as amended, and all dust products had been voluntarily cancelled.
In 2020, the Hartz Mountain Corporation (Hartz) and Chem-Tech Ltd. (Chem-Tech),
submitted requests under FIFRA section 6(f)2 to either terminate uses on cats and dogs from
1 This applies to all pet collar products containing TCVP, including those products sold by supplemental
distributors.
2 In this document EPA often uses the more commonly known FIFRA sections rather than the U.S. Code citations.
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their dust products or request voluntary cancellation of their dust products, and EPA has
processed those requests. Hartz also submitted a request under FIFRA section 6(f) to voluntarily
cancel EPA Registration No. 2596-63 (a cat collar) and Hartz requested label and registration
(design) amendments for the remaining pet collars. These amendments included restricting use
to cats or dogs at least 12 weeks of age and weighing at least 5 pounds, and redesign of certain
collars to reduce their size/weight to reduce the total amount of TCVP being applied. The final
cancellation of the cancelled Hartz products became effective on December 30, 2020 (85 FR
86557). The Hartz label amendments for the following collar registrations were approved
between October 20 and October 21, 2020:
- HARTZ 2 IN 1 COLLAR FOR CATS, EPA Reg. No. 2596-49
- HARTZ 2 IN 1 COLLAR FOR DOGS, EPA Reg. No. 2596-50
- HARTZ 2 IN 1 LONG LASTING COLLAR FOR DOGS, EPA Reg. No. 2596-62
- HARTZ 2 IN 1 SEVEN MONTH COLLAR FOR CATS, EPA Reg. No. 2596-83
- HARTZ 2 IN 1 SEVEN MONTH COLLAR FOR DOGS, EPA Reg. No. 2596-84
- HARTZ RABON COLLAR WITH METHOPRENE, EPA Reg. No. 2596-139
EPA did not find risks of concerns with these changes in 2020. As a result of that
assessment, only the liquid sprays and collars (as amended) remained as currently registered
uses.
As part of developing this revised petition response, EPA reevaluated whether the
methodology used in the 2019 torsion study provided adequate information to determine a liquid
to dust ratio for use in the collar exposure calculations. EPA concluded that the 2019 torsion
study only provided a measure of total release of material from the collar and does not appear to
distinguish between liquid and dust fractions. Since EPA determined the liquid-to-dust ratio in
TCVP in pet collars could not be determined based on the available data, EPA returned to the
approach used in the 2016 human health risk assessment, Tetrachlorvinphos (TCVP) Revised
Human Health Risk Assessment for Registration Review3, which provided three risk estimates,
based on three different liquid-to-dust ratios, to bracket the potential liquid-to-dust ratio. In
addition, as part of developing the revised petition response, EPA identified additional collar
trimming information in studies submitted for registration of pet collars and used these data to
provide updated factors to account for trimming of pet collars after application as a refinement
for the pet collar post-application assessment in cases where the product label directs users to
trim the collar.
This updated risk assessment (the October 2022 draft4 risk assessment (DRA)) is fully
discussed in Section III of this document. All three liquid-to-dust ratios result in risk estimates
3 Available at https://www.regulations.gov/document/EPA-HO-OPP-20Q8- 55.
4 Because this response was prepared at the same time EPA was preparing a risk assessment for the entire TCVP
case for registration review, EPA is relying on the 2022 registration review risk assessment as support for this
response. That risk assessment is broader in scope than required for this response and is titled as a Draft Risk
Assessment in line with how EPA has implemented its registration review program. The risk assessment is a "draft"
only in the sense that it will be made available for comment for purposes of the TCVP registration review case under
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for pet collars that exceed EPA's level of concern. However, EPA still did not find risks of
concern resulting from liquid spray pet uses of TCVP.
EPA's October 2022 DRA for TCVP addresses the arguments raised in NRDC's petition
regarding whether TCVP pet uses pose unacceptable risks. The October 2022 assessment and
the registration review currently underway will address the issues noted by NRDC as they relate
to the 2006 TCVP Reregi strati on Eligibility Decision (RED). To the extent that NRDC suggests
that EPA perform a new organophosphate (OP) cumulative risk assessment, EPA is currently
reviewing the organophosphates as a whole (including TCVP) in registration review pursuant to
FIFRA section 3(g), and 40 CFR Part 155, which will include a new OP cumulative risk
assessment. As noted previously in this document, should the Agency receive data that bears
upon the conclusions for TCVP pet collars, the Agency will review that data, make its review
publicly available, update the TCVP risk assessment as appropriate, and make this information
available for public comment. Any relevant data and conclusions associated with TCVP pet
collars included in the single chemical assessment would be included in the OP cumulative as
applicable. Hartz is currently working on two studies and plans to submit the data for EPA
review.
II. Background
TCVP is a member of the organophosphate (OP) class of pesticides. Like other OPs,
TCVP's mode of action (MO A) involves the inhibition of the enzyme acetylcholinesterase
(AChE). TCVP was first registered as a pesticide in 1966 and is an insecticide used to control
fleas, ticks, various flies, lice, and insect larvae on livestock and domestic animals and their
premises. TCVP is also applied as a perimeter treatment. All crop uses of TCVP were
voluntarily cancelled by 1987.
The Reregi strati on Eligibility Decision (RED) for TCVP was initially completed in
September 1995. An interim Tolerance Reassessment and Risk Management Decision (TRED)5
for TCVP was completed in July 2002. A residential exposure assessment was originally
completed in 19996 in support of the TRED, which concluded that there were no residential risks
of concern resulting from handler and post-application exposure. The residential assessment was
refined in 2002. Both the TRED and 1999 assessment can be found at www.regulations.gov in
public docket numbers EPA-HQ-OPP-2002-0295 and EPA-HQ-OPP-2008-0316. The Agency
completed the updates to the OP cumulative risk assessment (considering all OPs, including
TCVP, sometimes referred to as the "OP Cumulative") in July 20067, and, as a result, the TCVP
TRED and RED were considered final at that time and can be found in public docket number
EPA-HQ-OPP-2006-0618. There were no risks of concern identified in the residential
FIFRA § 3(g). The DRA represents EPA's current view on the human health risks associated with TCVP's pet uses.
EPA's risk assessments, be they titled draft or final, are subject to change based on new information.
5 Available at htlps://www.regiilations.gov/docnment?D=EPA-HO-OPP-2002-0295-00.1.2.
6 Available at https://www.regulations.gov/document?D=EPA-HO-OPP-2008-03.1.6-00.1.0.
7 Available at fattps://www. re giilatlons.gov/doeiiinent?D=EPA-HQ~OPP-2006-06.1.8-0002.
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assessment portion of the OP Cumulative, which considered exposure from the pet uses of TCVP
along with all other OP uses.
A. Registration Review of TCVP
The registration review program is intended to make sure that, as the ability to assess and
reduce risk evolves and as policies and practices change, all registered pesticides continue to
meet the statutory standard of no unreasonable adverse effects. Changes in science, public
policy, and pesticide use practices will occur over time. Through the registration review
program, the Agency periodically re-evaluates pesticides to make sure that as these changes
occur, products in the marketplace can continue to be used without causing unreasonable adverse
effects on human health and the environment taking into account the risks and benefits
associated with the use of the product.8
The TCVP registration review docket opened in June 2008 with the TCVP Summary
Document and supporting documents9 stating what EPA knew about TCVP at that time and what
additional risk analyses and data were needed to make a registration review decision. A Generic
Data Call-In (GDCI) was issued December 29, 2009, requiring the submission of studies to
inform the Agency's evaluation of risk from all TCVP exposure pathways, including those
related to pet uses. The TCVP Task Force, comprised of the TCVP registrants, committed to
conducting the studies, and anticipated submission beginning March 2012.
Concurrent with the TCVP Task Force's data development for registration review, the
Agency focused on its review of the risk from pet uses to address NRDC's petition. The Agency
began with a summary of pet collar risk estimates from the RED in order to frame the path
forward for updating the pet use risk assessment in the February 2010 memorandum,
Tetrachlorovinphos, PC Code 083701, DP Barcode 346880: Summary of Pet Collar Risk
Estimates. This memorandum outlined the risk assessment methods that changed since the
previous assessment for the TCVP RED and identified significant uncertainties that needed to be
addressed in a new risk assessment. EPA completed an updated TCVP assessment on the pet
uses on November 5, 2014, Residential Exposure Assessment in Response to the Natural
Resources Defense Council Petition to Cancel All Pet Uses for Tetrachlorvinphos, in advance of
the Agency's comprehensive December 21, 2015 TCVP Draft Human Health Risk Assessment
for registration review, in continued efforts to respond to NRDC's petition.
On November 6, 2014, EPA denied NRDC's petition on the basis of the November 5,
2014 risk assessment.10 In January 2015, NRDC filed suit in the U.S. Court of Appeals for the
Ninth Circuit on the merits of EPA's denial. Then, in its August 5, 2015, Opening Brief, NRDC
raised for the first time the issue of whether the TCVP in pet collars should be considered a
liquid or solid formulation, pointing out that one particular TCVP pet collar's label stated that
8 See FIFRA section 2(bb).
9 Available at fattps://www.regiilations.gov/doeket?D=EPA~HQ~OPP~2008~Q316.
10 Available at https://www.regulations.gov/document/EPA-HO-OPP-2009-0308-001Q.
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"[a]s the collar begins to work, a fine white powder will appear on the surface." The brief also
argued that the Agency "failed to consider the Davis study for the estimation of post-application
risks for exposures to the TCVP pet collar."
The issue that NRDC raised as to whether TCVP pet collars should be considered a liquid
or solid formulation stems from the fact that there are no exposure data specific to pet collars,
meaning there are no data available that provide information on potential exposures for people
while putting pet collars on animals nor are there any data available on potential exposures for
people while contacting their pets after a collar has been applied. Therefore, in order to assess
pet collars, EPA has to use the pet product exposure data that is available which is representative
of liquid formulations (e.g., shampoo products, spot-on products) and dust formulations. These
data indicate that there is higher potential exposure from dust products than liquid products. In
its 2012 Residential SOPs11, EPA chose to use the liquid formulation data as representative of
pet collars in lieu of product-specific exposure data. NRDC argued in its brief that EPA was
underestimating exposure by grounding its risk assessment on a liquid-formulation exposure
model and not a dust-formulation exposure model for pet collars. In response to the liquid/solid
formulation issue, the 2015 DRA included separate assessments for pet collars where the liquid
and dust/solid pet product exposure data were used separately (i.e., assuming pet collars are
entirely liquid formulations and assuming pet collars are entirely dust/solid formulations) to
provide a range of potential exposures/risks.
The study identified by NRDC (the Davis study12) is a literature study that includes glove
residue data collected by adult volunteers petting TCVP treated dogs, plasma cholinesterase
(ChE) measures from treated dogs, tee shirt samples collected from children exposed to TCVP
treated dogs, and urinary biomonitoring for adults and children exposure to TCVP treated dogs.
In EPA's 2015 memorandum, the Agency acknowledged consideration of the potential effect of
using the Davis study as the basis for residential post-application assessment of exposures from
TCVP pet collars, the study was reviewed, an OPP ethics review was conducted, and preliminary
risk estimates were presented with use of these data. However, formal use of the Davis study
was put on hold pending review by EPA's Human Studies Review Board (HSRB) in January
2016.
In January 2016, EPA took the Davis study to the HSRB to determine if the Agency
could rely on the study. 40 CFR 26.1703 prohibits EPA from relying on data from any research
involving intentional exposure of any pregnant human subject (and therefore her fetus), nursing
woman, or child, unless the EPA has: (a) obtained the views of the HSRB; (b) provided an
opportunity for public comment on the proposal to rely on the otherwise unacceptable data; (c)
determined that relying on the data is crucial to a decision that would impose a more stringent
regulatory restriction to protect public health than could be justified without the data; and
11 https://www.epa.gov/sites/prodiiction/files/2015-08/doaHnents/iisepa-opp-hed residential sops oct2012.pdf.
12 Assessing Intermittent Pesticide Exposure from Flea Control Collars Containing the Organophosphorus
Insecticide Tetrachlorvinphos", Journal of Exposure Science and Environmental Epidemiology, Davis, M. et al.,
v.18, 564-570 (2008).
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(d) published a full explanation of the decision to rely on the data, including a thorough
discussion of the ethical deficiencies of the underlying research and the full rationale for finding
that the standard in item (c) was met. The HSRB concluded that: "The research is scientifically
sound and, if used appropriately, the pet fur transferable residue data from the rubbing protocol
used in the study can provide useful information for evaluating potential exposures of adults and
children from contact with dogs treated with tetrachlorvinphos containing pet collars."13
EPA subsequently completed the TCVP Revised Human Health Risk Assessment for
Registration Review, dated December 21, 2016, in which post-application risks were assessed
using the Davis Study data. The December 21, 2016 risk assessment also assessed pet collars
using assumptions of varying liquid-to-dust ratios of active ingredient (a.i.) in the exposure
calculations to determine the impact on the outcome of the assessment.
At the time, EPA was uncertain as to whether the pet collar risk assessment should be
based on a liquid-formulation exposure model or a dust-formulation exposure model, or some
combination. This risk assessment was posted in the docket14 on December 29, 2016.
EPA issued a Data Call-In (DCI)15 to Hartz on June 3, 2019 requiring a mechanical
torsion study in order to resolve the remaining uncertainty regarding the collar formulation.
Hartz submitted the study on August 28, 2019. Following EPA's initial review in 2019, the data
were considered acceptable. EPA incorporated the 2019 mechanical torsion data (using a value
of 0.38% dust in the exposure calculations for pet collars), and an assumption for collar trimming
when applied to an animal (20% based on available data), in its July 2020 revised residential
exposure and risk assessment" Tetrachlorvinphos: Revised Residential Exposure and Risk
Assessment for the Registered Pet Product Uses. "16 The registrants mitigated risks identified in
the revised residential pet product assessment, so EPA also completed an addendum,
"Tetrachlorvinphos: Addendum to the Revised Residential Exposure and Risk Assessment for the
Registered Pet Product Uses17, " which reflects the amendments to those registrations. In
January 2022, EPA completed a revised comprehensive DRA for registration review,
"Tetrachlorvinphos (TCVP). Second Revision: Human Health Risk Assessment for Registration
Reviewwhich covered all registered uses of TCVP, and included the updated residential
assessment for pet uses as presented in the 2020 assessments.
Since January 2022, EPA has re-evaluated the torsion study data and has identified
concerns related to the methodology used in the study and whether it adequately provides
information about the liquid-to-dust ratio of TCVP flea and tick collars. EPA has outlined these
concerns in "Addendum to the Data Evaluation Recordfor the Study "Determination of TCVP
13 See https://www.epa.gov/sites/production/files/2016-04/documents/hsrb final report ianuary 201.6 meeting - 3-30-
2016.pdf
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and DC A Residues Releasedfrom Hartz Flea and Tick Collars by Torsion Stressing''18 and has
re-classified the study as unacceptable for the purpose of providing information on the liquid-to-
dust ratio of TCVP flea and tick collars. As a result, EPA is no longer confident with using a
value of 0.38% dust derived from the 2019 mechanical torsion study for pet collar exposure
calculations. Hartz provided preliminary new torsion data in September 2022 and anticipates
formally submitting the study for Agency review in October 2022, so EPA was unable to
incorporate it into the DRA in the time ordered by the Ninth Circuit Court of Appeals on April
20, 2022. In light of the Court's April 20, 2022 Opinion and Order remanding this Petition
Response to EPA, the Agency has also updated its recommendations related to the adjustment
factor for trimming of pet collars based on a review of additional collar trimming information in
studies submitted for pet collar registrations. EPA has revised the January 2022 DRA
("Tetrachlorvinphos (TCVP). Third Revision: Human Health Draft Risk Assessment for
Registration Reviewreferred to as the October 2022 risk assessment19) such that the residential
assessment for pet collars returns to the approach taken in the 2016 risk assessment, using three
ratios of liquid-to-dust (e.g., 99%/l%, l%/99%, 50%/50%) to assess pet collar exposure, and
also incorporates the updated assumptions for collar trimming. In addition, the October 2022
assessment incorporates new dermal absorption in vitro data (MRID 51890001), submitted in
April 2022, to refine the dermal absorption factor used in the risk assessment.
The October 2022 DRA identifies risks of concern for all remaining pet collar products
and confirms EPA's decision to grant NRDC's petition for pet collars. The October 2022 DRA
also confirms that risk estimates for three pet spray products containing TCVP result in no risks
of concern.
TCVP remains under registration review per FIFRA section 3(g), and per the Agency's
standard practice, it will open a public comment period on the TCVP risk assessment as well as
the Proposed Interim Decision (PID) once completed. Hartz is currently working on two studies
and plans to submit the data for EPA review. Through registration review, EPA will consider
any new data submitted, update the TCVP risk assessment as appropriate, and specify any
changes in our conclusions on TCVP pet collars in the TCVP PID, which is currently expected to
be completed in early 2023. EPA will open a public comment period for an updated risk
assessment concurrently with the TCVP PID.
B. Summary of NRDC's Petition to Cancel All Pet Uses
On April 24, 2009, EPA received a petition under the Administrative Procedure Act
(APA), 5U.S.C. § 551, e/ seq., from NRDC, dated April 23, 2009, to cancel all pet uses of
TCVP, as well as an April 2009 "Issue Paper" issued by NRDC entitled "Poisons on Pets II:
Toxic Chemicals in Flea and Tick Collars." The Petition raised the following issues:
18 Available at https://www.reguiations.gov/docket/EPA-HO-OPP-2009-03Q8.
19 Available at https://www.regiilations.gov/docket/EPA-HO-OPP-2009-0308.
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• NRDC argued that EPA failed to consider pet collar exposures in the 2002 revised human
health risk assessment underlying the 2006 RED. NRDC argued that despite finding that
pet collar uses provided the highest exposure levels for adults, EPA still chose not to
conduct a risk assessment for pet collars, and that EPA ignored the possibility that the pet
collar uses could expose infants and children to unsafe levels of TCVP.
• NRDC argued that EPA used faulty exposure assumptions in the 2006 organophosphate
cumulative risk assessment. NRDC argued that the EPA's organophosphate cumulative
risk assessment for pet products significantly underestimated toddlers' exposure to
pesticide residue on a pet from TCVP pet products, particularly flea collars.
• NRDC argued that use of TCVP pet collars results in unacceptably high exposures,
pointing to NRDC's April 2009 "Issue Paper" entitled "Poisons on Pets II: Toxic
Chemicals in Flea and Tick Collars," and to a 2008 study entitled "Assessing Intermittent
Pesticide Exposure from Flea Control Collars Containing the Organophosphate
Insecticide Tetrachlorvinphos," Journal of Exposure Science and Environmental
Epidemiology, Davis, M. et al., v. 18, 564-570 (2008) (the "Davis Study").
The Petition concluded that EPA's 2006 RED for TCVP is "arbitrary and capricious, and
contrary to law," and that "EPA must... cancel all pet uses of [TCVP]." Petition at 6.
On June 5, 2009, EPA announced receipt of NRDC's petition and "Issue Paper" in the
Federal Register (74 FR 27035) and posted the Petition in public docket number EPA-HQ-OPP-
2009-0308 in regulations.gov for a 60-day public comment period, during which time interested
stakeholders could review and comment on the Petition.
During the comment period, EPA received approximately 8,600 form letters as part of a
mass campaign supporting NRDC's petition. The Agency also received a comment from The
Humane Society of the United States (HSUS) that supported NRDC's petition, and a comment
from Hartz, which opposed NRDC's petition. In addition, Hartz provided additional
information, including a dislodgeable residue study, to help refine the Agency's pet use risk
assessment. EPA considered the substantive comments received during that public comment
period in 2009 and released a Response to Comments document20 concurrently with the
Agency's initial response to the NRDC Petition in 2014, as discussed in further detail in section
II.D. of this document below. Consistent with EPA's Response to Comments document, the
Agency has continued to review new information and this response to NRDC's petition includes
updated risk and benefit assessments.
C. EPA's Review of NRDC's Issue Paper
As mentioned above, along with the Petition, NRDC submitted an April 2009 NRDC
"Issue Paper" entitled "Poisons on Pets II: Toxic Chemicals in Flea and Tick Collars"
(hereinafter "Poison on Pets II") for EPA's consideration of potential exposures from TCVP pet
20 Available at fattps://www.regiilations.gov/doeiiment?D=EPA~HQ~OPP~2009~0308~0Q12.
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collars. This "Issue Paper" consisted of a study overview and summarized findings along with a
methodological appendix but did not include the full study report including all the raw data. In a
letter dated May 28, 2009, the Agency requested additional scientific information from NRDC so
that EPA could fully analyze and independently verify the results of the study report, including
all raw data and the protocol for the pet residue study. EPA also requested information on the
ethical conduct of the study regarding the use of human subjects, as required by 40 CFR §
26.1303 under Subpart M - "Requirements for Submission of Information on the Ethical
Conduct of Completed Human Research."
On June 25, 2009, NRDC submitted a response letter.21 Although NRDC's June 25,
2009 letter included a copy of the original protocol intended to support NRDC's argument that
the studies underlying the "Poison on Pets II" report were not "human studies" under 40 CFR
Part 26, the letter did not include either the scientific information to enable EPA to verify the
results of the study report or the information on the ethical conduct of the studies required by 40
CFR §26.1303. NRDC's letter stated:
"... NRDC will await EPA's final determination that the study does not constitute
research with human subjects and that the Agency will include it as part of its assessment
of our Petitions. Once EPA makes that final determination, then we will provide the
underlying data supporting our report." NRDC Letter, June 25, 2009, at 3.
In a letter dated August 7, 2009, EPA informed NRDC that the Agency (EPA's Office of
Pesticide Programs, in consultation with EPA's Human Subjects Research Review Officer in the
Office of the Science Advisor) still regarded the two studies described in the "Poison on Pets II'
report as research with human subjects covered by EPA's rules in 40 CFR Part 26, "Protection of
Human Subjects."22
To date, NRDC has not submitted the necessary raw data to allow EPA to verify the
"Poisons on Pets II" study report findings. Without the raw scientific data, this information was
not considered in EPA's evaluation of NRDC's petition.
D. EPA's Initial Response to NRDC's Petition and Subsequent Litigation
On April 23, 2009, NRDC filed a petition under the APA asking EPA to cancel all
pesticide registrations for the use of TCVP to control fleas and ticks on pets ("pet uses").
As of February 2014, EPA had not responded to NRDC's 2009 petition and NRDC filed
a mandamus petition in the U.S. Court of Appeals for the D.C. Circuit to compel a response. In
November 2014, EPA completed a new risk assessment in response to NRDC's 2009 petition
and, on the basis of that risk assessment, denied NRDC's petition. NRDC's 2014 mandamus
petition was therefore dismissed as moot in December 2014.
21 Available at https://www.regulations.gov/document?D=EPA-HO-C)PP-2009-0308-0006.
22 Available at https://www.regulations.gov/document?D=EPA-HO-OPP-2009-0308-00Q7.
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In January 2015, NRDC filed suit in the U.S. Court of Appeals for the Ninth Circuit on
the merits of EPA's denial of its APA petition. In its August 5, 2015 Opening Brief, NRDC
raised for the first time the issue of whether the TCVP in pet collars should be considered a
liquid or solid formulation. While EPA had previously categorized the a.i. in all pet collar
products as liquid formulations as supported by the best available science at the time of
development of the relevant SOP,23 NRDC's August 5, 2015 Opening Brief pointed out that the
label for Hartz UltraGuard Flea and Tick Collar for Dogs (EPA Reg. No. 2596-84) at the time
stated that "as the collar begins to work, a fine white powder will appear on the surface." This
statement on the label came after the instructions for the user to unroll and stretch the collar to
activate the insecticide generator.
In 2015, while the Ninth Circuit litigation was ongoing, and as scientific methodologies
and understanding had evolved, EPA reconsidered its position for purposes of developing the
TCVP Revised Human Health Risk Assessment for Registration Review (which would
ultimately be issued December 21, 2016, and posted to the docket on December 29, 2016)24 by
(re)assessing pet collars containing TCVP using assumptions of varying liquid-to-dust ratios
(99%/l%, l%/99%, 50%/50%) in the collar, knowing that the collars were not likely 100% dust
or 100% liquid given the label language. These varied assumptions were incorporated into the
exposure calculation to account for the uncertainty in the liquid-to-dust ratio. Without having
chemical-specific composition information related to TCVP pet collars, this approach was taken
to account for a range of possibilities which could occur. EPA also determined that the Food
Quality Protection Act (FQPA) safety factor should be retained for TCVP to address
uncertainties in the dose-response relationship for neurodevelopmental effects for the OPs in
infants, children, and women of childbearing age for all residential exposure scenarios.25 In
23 Available at https://www.epa.gov/sites/prodiiction/files/2015-08/documents/iisepa~opp~
hed residential sops oct2012.pdf.
24 Available in regulations.gov at https://www.regulations.gov/doeument?D=EPA~HQ~OPP~2008~Q3.1.6-0055.
25Section 408(b)(2)(C), 21 U.S.C. 346a(b)(2)(C), was added to the FFDCA through the Food Quality Protection Act
of 1996 (FQPA), and provided heightened protections for infants and children. Among other things, that provision
directs EPA to apply, "[i]n the case of threshold effects. ... an additional tenfold margin of safety for the pesticide
chemical residue and other sources of exposure ...to take into account potential pre- and post-natal toxicity and
completeness of the data with respect to exposure and toxicity to infants and children." (Emphasis added). This
additional tenfold margin of safety is referred to as the "FQPA 10X safety factor." This provision applies when
EPA is establishing, modifying, leaving in effect, or revoking tolerances - which are rules that set maximum amount
of pesticide residues that can be present in or on food - and is applied when assessing pesticides that bear labeling
for use on food (i.e., food use pesticides) as a result of the definition of "unreasonable adverse effects on the
environment" at section 2(uu) of FIFRA, 7 U.S.C. 136(bb). That definition states in relevant part: "The term
'unreasonable adverse effects on the environment' means (1) any unreasonable risk to man or the environment,
taking into account the economic, social, and environmental costs and benefits of the use of any pesticide, or (2) a
human dietary risk from residues that result from a use of a pesticide in or on any food inconsistent with the
standard under section 346a of Title 21." (Emphasis added).
As noted in footnote 4, supra, the DRA that supports this Response to NRDC's Petition to cancel "pet
uses" was drafted for the broader purposes of "registration review" of TCVP, which includes all uses of TCVP
including food uses. When assessing pesticides resulting in residues in or on food under FIFRA 2(bb) consistent
with the safety standard in the FFDCA, the FFDCA requires EPA to apply the "FQPA 10X safety factof' for the
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September 2015, EPA therefore sought a voluntary remand of its 2014 denial of NRDC's 2009
APA petition. In arguing for remand without vacatur, EPA informed the court and parties that it
intended to issue a new risk assessment before the end of 2016 and respond to the Petition within
90 days after the final risk assessment was issued. In June 2016, the court granted EPA's motion
for remand and denied NRDC's motion for vacatur.
In addition, as mentioned above, in January 2016 EPA took the Davis Study to the
HSRB, which concluded that the study was scientifically valid and met the appropriate human
ethics requirements. EPA therefore relied on the Davis Study in developing the December 21,
2016 TCVP Revised Human Health Risk Assessment for Registration Review, as the Davis
Study provided transferable residue data for pet fur and resulted in greater potential risks than
those estimated using the pet collar residue transfer study EPA had relied upon in previous
assessments.
As also mentioned above, EPA completed a new TCVP Human Health Risk Assessment
on December 21, 2016 (posted to the docket on December 29, 2016).26 While that risk
assessment identified some potential risks of concern, the risk assessment left some key
questions unresolved, such as whether the TCVP in the pet collars should be considered "liquid"
or "solid" (which, in turn, could affect the assessment of risk). With the remaining uncertainty
around the physical form of TCVP present in the collars, the Agency was unable to fully respond
to NRDC's petition. Therefore, on March 21, 2017 (90 days after finalizing the new TCVP risk
assessment), EPA informed NRDC that EPA intended to merge the Petition response with its
TCVP registration review decision under FIFRA section 3(g) that was then scheduled to be
issued in the fall of 2017.
EPA's assessment of the pet collars hinged on the uncertainty regarding the physical
form of TCVP released from collars, and the Agency determined that the best solution would be
to require a study from the registrant of the pet collars, Hartz, assessing the percentage of the
collars' total mass available for release as dust. Therefore, EPA issued a DCI to Hartz on June 3,
2019, pursuant to FIFRA section 3(c)(2)(B), requiring a mechanical torsion study.27 That DCI
requested that a protocol be submitted to EPA for review prior to the conduct of the study.
protection of infants and children, unless there is reliable data to show that a different margin of safety would be
safe. 21 U.S.C. 346a(b)(2)(C). Due to the uncertainty surrounding the potential for neurodevelopmental outcomes
associated with exposures to TCVP, including from exposures associated with the pet uses, EPA retained the FQPA
10X safety factor for assessing the risk of those uses as part of its DRA. The FQPA 10X safety factor, in this case,
is equivalent to the traditional uncertainty factor applied in situations of a database uncertainty. See USEPA,
Determination of the Appropriate FQPA Safety Factor(s) in Tolerance Assessment. Feb. 28, 2002 (FQPA safety
factor incorporates other traditional uncertainty factors to account for data deficiencies that raise concern for infants
and children, including database uncertainty factor). That same database uncertainty exists regardless of whether
EPA assesses all uses of TCVP together or if EPA assesses the pet uses alone, and thus the additional 10X
uncertainty factor for assessing pet uses is appropriate.
26 Available in regulations.gov at https://www.regiilations.gov/document?D=EPA-HQ-OPP-2008-Q3.1.6-0055.
27 Available in regulations.gov at https://www.regulations.gov/document?D=EPA-HQ-QPP-2008-0316-0078.
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Five days before EPA issued the DCI, on May 29, 2019, NRDC filed a mandamus
petition with the Ninth Circuit Court of Appeals asking the court to order EPA to respond to
NRDC's 2009 petition. The torsion study, along with additional transfer residue data, were
submitted to the Agency on August 28, 2019; however, a protocol for the torsion study had not
been submitted prior for EPA review as requested. On April 22, 2020, the court issued an Order
directing EPA to either initiate cancellation of the TCVP pet use registrations or deny NRDC's
2009 petition within 90 days of the court's order (i.e., by July 21, 2020). The Agency completed
the review of the submitted data in December 2019 and the Agency incorporated these data into
the July 2020 revised residential exposure and risk assessment.
In its initial review of the torsion study, EPA had focused on the change in collar weight
from the study and assumed it could provide an approximation of dust released from the collar.
The study found that 0.38% of the collars' mass was lost as a result of mechanical torsion, and
EPA used that figure as a percentage dust value in the pet collar exposure calculations, which
assumed that the remaining portion of exposure was attributable to liquid TCVP. This
assumption was incorporated into EPA's 2020 revised risk assessment and 2020 petition
response.28
On July 21, 2020, in compliance with the court's order, the Agency responded to
NRDC's 2009 petition by denying the Petition, concluding risk estimates for TCVP liquid spray
products do not exceed the Agency's level of concern; therefore, those products remain
registered. Based on EPA's initial assessment of the 2019 mechanical torsion study and
incorporation of the 0.38% value, risk estimates for some pet collars did not exceed the Agency's
level of concern while others did. Risk estimates for all pet dust products exceeded EPA's level
of concern. The primary pet product registrant, Hartz, voluntarily cancelled all dust powders and
one pet collar and redesigned and/or relabeled the remaining collar registrations to reduce risk
estimates below levels of concern. Additionally, Chem-tech Ltd. voluntarily submitted a request
to terminate pet uses from CLEAN CROP LIVESTOCK 1% RABON DUST (EPA Registration
No. 47000-123).
On September 18, 2020, NRDC filed a petition for review in the Ninth Circuit Court of
Appeals, seeking judicial review on the merits of EPA's July 21, 2020 denial of NRDC's petition
to cancel pet uses of TCVP. In the briefing and oral argument regarding this litigation, the
Agency provided detailed explanation regarding the data and calculations used in the revised
residential exposure and risk assessment for all TCVP pet product uses, entitled
"Tetrachlorvinphos: Revised Residential Exposure and Risk Assessment for the Registered Pet
Product Uses''
On April 20, 2022, the court issued an opinion holding that the EPA's denial of NRDC's
petition was not supported by substantial evidence and did not provide a "reasoned explanation"
for its denial of NRDC's petition in the written record. The court held that the Agency relied on
28 Available at https://www.regiilations.gov/docnment/EPA-HO-OPP-2009-0308-0018
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"mistaken calculations" central to the denial of NRDC's petition. The court vacated the 2020
Petition denial citing a lack of substantial evidence on the amount of TCVP dust released by the
pet collars, and the assumption that pet owners will trim the collars by at least 20%. The
decision was remanded to the Agency for a revised response.
As noted above, as part of developing this revised petition response, EPA re-evaluated
the data provided in the 2019 torsion study and, as a result, identified concerns about whether the
methodology used {i.e., collar weight and wipe measurements) could really distinguish between
dust and liquid fractions. The material measured via wiping could potentially represent total
release (both liquid and dust) and not necessarily just dust. The study therefore does not help
determine the percentage of the collars' overall mass available for release as dust. The original
and revised data evaluation records (DERs) for these data are available in public docket EPA-
HQ-OPP-2008-0316 at www.regulations.gov.29
III. EPA's Revised Residential Exposure and Risk Assessment
There is one risk assessment pertinent to this petition response:
• An October 2022 comprehensive draft risk assessment (DRA) for registration review:
"Tetrachlorvinphos (TCVP). Third Revision: Human Health Draft Risk Assessment for
Registration Reviewwhich includes an updated residential exposure and risk
assessment for pet product uses.
EPA risk assessments rely on the most recent guidance and risk assessment
methodologies available at the time they are completed. The human health risk assessments that
NRDC's petition alleges failed to properly identify risks were originally completed in 1999 and
2006 and utilized exposure assumptions and methodologies based on Standard Operating
Procedures (SOPs) for pet product risk assessments in place at that time. Since 2012, TCVP
residential pet product assessments assessed residential handler and post-application risk from
exposure to TCVP pet products using the Agency's 2012 SOPs for Residential Pesticide
Exposure Assessment30. Development of the 2012 SOPs included external peer review,
including the Agency presenting a draft of the SOPs to the FIFRA Scientific Advisory Panel
(SAP) for comment in 2009.
In developing the 2020 risk assessments and petition response, EPA considered, among
other things, the information contained in the Petition, new data relevant to the assessment of
exposure from pet collars {i.e., additional Hartz studies: MRID 50881801/ D453149 and MRID
50931601/ D454190), an efficacy study to inform assumptions on collar trimming (MRID
51079501) and updated residential exposure assessment methodologies and reevaluation of
29 Available at https://www.regulations.gov/document?D=EPA-HO-OPP-2008-Q31.6-0083 and
https://www.regulations.gov/document?D=EPA-HO-OPP-2008-Q31.6-0084.
30 https://www.epa.gov/sites/production/fLles/2015-08/docunientsAisepa-opp-hed_residential sops oct2012.pdf
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existing data {i.e., the Davis Study). As mentioned above, EPA incorporated the 2019
mechanical torsion data, and an assumption for collar trimming when applied to a cat or dog
(based on available data), in its July 2020 revised residential exposure and risk assessment
"Tetrachlorvinphos: Revised Residential Exposure and Risk Assessment for the Registered Pet
Product Uses31. " The registrants mitigated risks identified in the revised residential pet product
assessment, so EPA also completed an addendum, "Tetrachlorvinphos: Addendum to the Revised
Residential Exposure and Risk Assessment for the Registered Pet Product Uses32, " which
reflects the amendments to those registrations. In briefings for NRDC's September 18, 2020
petition for review, NRDC claimed that EPA's assumption that owners would trim 20% of
collars conflicts with its 2012 Standard Operating Procedures for Residential Pesticide Exposure
Assessment. The court found that EPA did not provide an adequate justification for its reliance
on the efficacy study used to support the 20% collar trimming assumption. NRDC also claimed
that EPA miscalculated the liquid-to-dust ratio from the raw data from the torsion study.
Additional data has been incorporated since the 2020 petition response into the October
2022 updated risk assessment and this current petition response, including additional efficacy
and transferable residue studies from Hartz and registrants of other pet collar products to further
inform the assumptions on collar trimming (MRIDs 51025813, 48987301, 51169106, 51160711,
51079501, 51025814, 50881801, 48646602, and 43722809) and new in vitro dermal absorption
data (MRID 51890001). In addition, EPA reevaluated the 2019 mechanical torsion study and
updated its review of a previously submitted transferable residue study and has updated the pet
collar assessment to reflect these changes.
The October 2022 DRA addresses all currently registered uses of TCVP, including pet
products {i.e., collars and liquid sprays). Like reregi strati on, registration review considers all the
uses of an a.i. along with new data and other information to ensure that the pesticide continues to
meet the standard for registration under FIFRA. To the extent that NRDC's 2009 petition may
be suggesting that EPA perform a new cumulative risk assessment, EPA is currently reviewing
the organophosphates (OP) as a whole (including TCVP) in registration review pursuant to
section 3(g) of FIFRA, which includes a new OP cumulative risk assessment. EPA has
determined it is unnecessary to update the cumulative risk assessment to respond to NRDC's
requests to cancel all TCVP pet uses and will continue to pursue an updated OP cumulative risk
assessment along the appropriate registration review timeline. EPA intends to update the
cumulative assessment following the completion of registration review for all organophosphates.
The Agency completed a revised residential exposure and risk assessment for all
currently registered TCVP pet product uses as part of its October 2022 draft risk assessment for
registration review, "Tetrachlorvinphos (TCVP). Third Revision: Human Health Draft Risk
Assessment for Registration ReviewBased on the data and updates noted above, that risk
assessment incorporated an updated dermal absorption factor, a slight change to the transfer
factor (Far), use of a range of liquid-to-dust ratios to assess pet collars, and updated
31 Available at fattps://www.regiitations.gov/doeket?D=EPA~HQ~OPP~2008~Q316.
32 Available at https://www.regiilations.gOv/docnment/EPA-HO-OPP-2008-03.l.6-0086.
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recommendations for an adjustment factor to account for trimming of pet collars, all of which are
discussed in more detail in the following sections. In the October 2022 DRA, the risk estimates
for currently registered pet collars containing TCVP exceed EPA's level of concern, while the
risk estimates for the currently registered liquid sprays containing TCVP do not exceed EPA's
level of concern.
Hartz is currently conducting two studies to address the pet collar risk issues and
formulation question. The first is a new torsion study conducted using a different methodology
than the originally submitted torsion study, which will allow the Agency to better estimate risks
from pet collars by allowing more accurate determination of the relative amounts of TCVP
coming from the collar in solid (dust) versus liquid form. The second study is a unique pet fur
clipping study which is designed to determine the relative amounts of solid (dust) vs. liquid
TCVP on pet fur at different locations on a pet wearing a TCVP collar. If the pet fur study
shows different relative amounts of solid vs. liquid on different areas of the pet (for example,
neck vs. base of the tail), a better estimation of exposure to people contacting treated pets after
application may be possible. The results of these studies will be used to reassess risks to people
applying pet collars, and to people exposed through contact with the pet after the collar has been
applied.
The following is a summary of the analysis and conclusions found in the revised
residential exposure assessment for pet uses, included in the comprehensive "Tetrachlorvinphos
(TCVP). Third Revision: Human Health Draft Risk Assessment for Registration Review."
A. Toxicology and Uncertainty Factors
Like other OPs, the MOA for TCVP involves inhibition of the enzyme AChE via
phosphorylation of the serine residue at the active site of the enzyme. This inhibition leads to
accumulation of acetylcholine and ultimately to neurotoxicity in the central and/or peripheral
nervous system.
TCVP has low acute toxicity by the oral, dermal, and inhalation routes of exposure. It is
a slight dermal irritant, a moderate eye irritant, and a dermal sensitizer. TCVP is classified as a
possible human carcinogen (Group C) based on statistically significant increases in combined
hepatocellular adenoma/carcinomas in mice, and suggestive evidence of thyroid c-cell adenomas
and adrenal pheochromocytomas in rats. The mutagenicity database for TCVP suggests that this
chemical was not mutagenic in either the gene mutation assay or the primary rat hepatocyte
unscheduled DNA synthesis assay. This chemical was positive for inducing chromosomal
aberrations in Chinese hamster ovary (CHO) cells in the absence of metabolic activation but was
negative in the presence of metabolic activation. Immunotoxicity was not observed at dose
levels that exceed the limit dose.
As with other OPs, TCVP exhibits a phenomenon known as steady state AChE
inhibition. After repeated dosing at the same dose level, the degree of inhibition comes into
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equilibrium with the production of new, uninhibited enzyme. At this point, the amount of AChE
inhibition at a given dose remains consistent across duration. In general, OPs reach steady state
within 2-3 weeks; a pattern that is observed for most OPs, but not every OP, like TCVP, which
shows no difference in response across duration. For TCVP, the steady state is reached after a
single day of exposure. As such, the endpoint selection for TCVP considers data available for all
durations of dosing when choosing the most protective point of departure. AChE data from the
comparative cholinesterase assays (CCA) suggest that the fetus is not more sensitive than the
pregnant dam and that pregnant females are not more sensitive than non-pregnant females with
respect to cholinesterase inhibition. When comparing red blood cell (RBC) BMDio (benchmark
dose) estimates from across the acute (single dose) CCA and repeat dose CCA studies, it is
apparent that there are no age-related (or duration-related) differences. The acute, steady state,
and incidental oral Points of Departure (PODs) selected for oral exposure risk assessment are
based on RBC AChE inhibition in the postnatal day 11 (PND 11) and postnatal day 21 (PND 21)
pups in the acute CCA since they provide the most robust dose-responses and are protective of
all life stages as well as brain AChE inhibition. Although the steady state dietary POD was
selected from an acute CCA, the acute study is considered appropriate for longer term durations
since AChE data across the TCVP database demonstrate that there is no progression of AChE
inhibition over exposure duration, and steady state inhibition occurs essentially after a single
dose. A route-specific inhalation study was used to assess inhalation risks based on RBC
cholinesterase inhibition and is the most appropriate and protective POD based on the route and
duration of exposure.
No quantification of dermal non-cancer risk is required for TCVP since there were: (1) no
treatment-related effects (no clinical signs) at doses up to and including the limit dose of 1000
mg/kg/day in the dermal toxicity study; (2) both RBC and brain cholinesterase activity were
assessed in the dermal study and neither compartment was affected at the limit dose; and (3) no
quantitative susceptibility was observed for juvenile or gestational life stages in the
developmental, reproductive, or CCA toxicity studies. Despite the determination of the lack of
non-cancer dermal hazard for TCVP, dermal exposures from TCVP must be quantified for the
purpose of cancer risk assessment. Because the cancer assessment is based on an oral study, a
dermal absorption factor (DAF) of 3% was used in the route-to-route extrapolation. The DAF is
based on the results of human in vitro data.
For assessing all TCVP uses, which include food uses for which tolerances are necessary,
EPA has determined that the FQPA safety factor (SF) of 10X should be retained to address
uncertainties in the dose-response relationship for neurodevelopmental effects for the OPs in
infants, children, and women of childbearing age for all residential exposure scenarios. The
FQPA safety factor does not apply when assessing pet uses on their own, but EPA is applying an
equivalent 10X uncertainty factor for pet uses alone for the same reasons as the Agency is
applying the FQPA safety factor for the consideration of all uses - including food uses - for
TCVP registration review under FIFRA § 3(g). As the current assessment of pet uses for the
purposes of this Petition Response was done in conjunction with all other uses of TCVP in the
DRA for the purposes of registration review of TCVP, the DRA (and thus the current assessment
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of pet uses) uses the terminology of the "FQPA SF " See also footnotes 4 and 25 of this
document.
For the non-cancer residential incidental oral exposures, the level of concern (LOC) is
1000 (i.e., risk estimates are not of concern when the margin of exposure (MOE) is > the LOC)
which includes a 10X uncertainty factor for interspecies extrapolation, a 10X uncertainty factor
for intraspecies variation, and a 10X FQPA Safety Factor. For the non-cancer residential
inhalation exposures, the LOC is 300 which includes a 3X uncertainty factor for interspecies
extrapolation, a 10X uncertainty factor for intraspecies variation, and a 10X FQPA safety factor.
The interspecies extrapolation factor for the inhalation route has been reduced from 10X to 3X
because the reference concentration (RfC) methodology for inhalation has been used to
determine a human equivalent concentration (HEC) and takes into consideration the
pharmacokinetic differences between animals and humans.
B. Residential Handler Exposures
In the October 2022 revised residential exposure assessment, EPA identified that there is
the potential for residential exposures from the use of TCVP pet products. Residential handler
exposures to TCVP pet products may occur via the dermal or inhalation routes while the product
is placed on a cat or dog. A steady-state non-cancer residential handler exposure assessment
(inhalation only; no non-cancer dermal endpoint) was performed for homeowners applying
TCVP products to cats and dogs. In addition, a residential handler cancer assessment was
conducted due to TCVP being classified as a Group C possible human carcinogen with a linear
low-dose approach for quantification of risk using the oral slope factor (Ql*) of 1.83 x 10"3
(mg/kg/day)"1.
1. Residential Handler Assumptions and Inputs
Application Rates for All Pet Uses: The following provides a summary of the application
rates per type of TCVP pet use.
For TCVP liquid sprays (trigger and pump spray products), all registered products direct
the user to apply a specific number of "strokes" per animal size (i.e., how many times should the
product be sprayed over the animal). In order to determine the amount of a.i. applied per
treatment as specified by number of strokes, EPA requested additional information and received
data from Hartz. Hartz provided information regarding the total volume of product released per
stroke for pump and trigger spray products: 0.19 and 0.93 grams, respectively. Only trigger
spray products are available for dogs; however, both pump and trigger spray products are
available for cats. Additionally, in 2014, EPA approved an amendment for the Hartz's product
label of EPA Registration No. 2596-140 that now includes a recommended number of strokes
per animal size. Previously, the label did not specify a number of strokes per cat/dog. The
recommendation of strokes provided a range for the assessment, assuming that the user follows
the label.
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For pet collars, the application rates used in risk assessments typically represent the
maximum amount of a.i. that could be applied by weight of the treated animal (small, medium,
and large). This is only possible when the product is manufactured for use, or is labeled
specifically, for different animal weight ranges. If EPA does not have this information, a number
of assumptions are used (as described in HED's 2012 Residential SOPs (Treated Pets SOP)).
The majority of pet collar formulations are registered as a single collar for use on all animal
weight ranges; this is the case for TCVP (i.e., the collars being assessed do not have separate
registrations for different animal sizes). These collars have been assumed for use on different
weight ranges as specified in the Residential SOPs which include:
• Cats - Small (up to 5 lbs), Medium (6 to 12 lbs), Large (13 lbs and up).
• Dogs - Small (up to 20 pounds), Medium (21 to 50 lbs) and Large (51 lbs and up).
While the pet collar product labels recommend trimming of the pet collar after it is
applied to the animal, this would not apply to a handler since they would be exposed to the full
length of the collar during application. Therefore, while the product label directions for
trimming of the collar was accounted for in the residential post-application exposure calculations
as described in Section C below, it was not accounted for in the residential handler exposure
calculations.
Pet Collar Formulation'. As already noted, there are no exposure data specific to pet
collars. EPA has exposure data representative of either liquid formulations or dust formulations.
These data indicate that there is higher potential exposure from dust products than liquids
products. Per EPA's 2012 Residential SOPs33, pet collar products are assessed as a liquid
formulation (i.e., using inputs and assumptions reflective of liquid formulations) because collar-
specific exposure data are not available. However, in NRDC's opening brief on its Petition for
Review of EPA's 2014 denial of NRDC's 2009 petition, the NRDC asserted that EPA
incorrectly considered the TCVP pet collar formulation to be a liquid formulated product noting
that a label for a TCVP pet collar product states that "as the collar begins to work, a fine white
powder will appear on the surface." This statement on the label came after the instructions for
the user to unroll and stretch the collar to activate the insecticide generator. HED reviewed this
information and agreed that exposure to the a.i. as a dust/solid formulation could occur. Due to
the uncertainty associated with pet collar formulation type, and without chemical- or product-
specific data, HED's standard approach is to assess a range of ratios to cover the range of
potential exposures (e.g., 99%/l%, l%/99%, 50%/50% dust to liquid). This is consistent with
the approach taken for TCVP in the 2016 DRA.34
In order to determine the maximum amount of dust that could be released from collars,
HED requested a "dust torsion" study for TCVP pet collars to refine those ratio assumptions. In
33 Available at http://www.epa.gov/pesticide-science-and-assessiiig-pesticide-risks/standard-operatiiig-procedures-residential-
pesticide.
34 Available at https://www.regulations.gov/document?D=EPA-HO-OPP-2008-Q31.6-0054.
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dust torsion studies, pieces of the pet collar are subjected to mechanical torsion and stress by
twisting and pulling multiple times at 180° angles to maximize any potential release of solids
from the collar. The torsion of the collar is meant to exaggerate the typical or expected
movement of the collar during activation and during use in order to give an upper bound estimate
of the amount of dust that could be produced.
EPA issued a DCI35 to Hartz on June 3, 2019, requiring a mechanical torsion study in
order to resolve the remaining uncertainty regarding the collar formulation. The DCI specified
that "A protocol must be submitted to the Agency for review and approval prior to study
inception." However, Hartz did not submit a protocol for review before conducting the torsion
study and instead only submitted the final study report on August 28, 2019 (MRID 50931601).
The study was conducted by measuring the "mass lost" from the collar by gravimetric
measurement of the collar weight before and after torsion, as well as measuring TCVP via
chemical analysis of wipe samples taken after each of three torsion cycles of ten twists. HED
had initially focused on the change in collar weight from the study and assumed it could provide
an approximation of dust released from the collar that could be used in the pet collar exposure
calculations, which assume some portion of exposure is attributable to liquid TCVP and some
portion of exposure is attributable to dust TCVP. This study was originally reviewed in 2019.36
The study was initially found to be acceptable for use in risk assessment and a value of 0.38%
dust was used in the TCVP pet collar exposure calculations based on the change in collar weight
before and after the three torsion cycles.
Upon re-evaluation, HED identified concerns with the methodology used in the torsion
study and whether it adequately provides information about the dust/liquid ratios that should be
used to assess the collars. HED prepared a revised DER37 which provides a detailed explanation
of those concerns and reclassifies the study as unacceptable for the purpose of providing
information on the liquid-to-dust ratio of TCVP flea and tick collars. As a result, the current
assessment continues to use the approach taken in the 2016 risk assessment, using three ratios of
liquid- to-dust (99%/1 %, l%/99%, 50%/50% dust to liquid) to assess the pet collar uses. As
noted above, Hartz is currently working on two studies that EPA will review when they are made
available. These data are being submitted to address the dust/liquid formulation uncertainty and
will be used to reassess risks to people applying pet collars, and to people exposed through
contact with the pet after the collar has been applied.
Unit Exposures for all Pet Uses: Unit exposures (UEs) are a ratio, for a given formulation
and application equipment, of an individual's exposure to the amount of a.i. handled, expressed
as mass a.i. exposure per mass a.i. handled (e.g., mg exposure/lb a.i. handled).
35 Available at https://www.regulations.gov/document?D=EPA-HO-OPP-2008-031.6-0078.
36 Available at https://www.regulations.gov/docket/EPA-HQ-OPP-2009-0308.
37 Available at https://www.regulations.gov/docket/EPA-HQ-OPP-2009-03Q8.
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For TCVP liquid spray products, chemical-specific UE data are not available. In the
absence of that, the Agency used UE values from the 2012 Residential SOPs as a surrogate to
estimate handler exposures. Surrogate UE data for a groomer trigger pump spray application to
dogs was used to estimate handler exposures from TCVP pump spray products.
For TCVP pet collars, chemical- and collar-specific UE data are not available. In order
to assess exposure to a liquid formulation, exposure data for spot-on applications (as provided in
the 2012 Residential SOPs) were used as surrogate data. Using the available spot-on data, the
dermal UE is 120 mg/lb a.i. and there is no inhalation UE as inhalation exposure from the
application of spot-on products is considered to be negligible. In order to assess exposure to a
dust formulation, EPA used a TCVP-specific dust/powder applicator study (MRID 45519601).
For the dust data, the dermal UE is 1,700 mg/lb a.i. and the inhalation UE is 3.1 mg/lb a.i.
Incorporation of exposure to a dust in the pet collar handler calculations results in a higher
potential exposure due to the higher UEs associated with dusts vs. liquids.
As noted earlier, for pet collars, HED has been conducting assessments assuming the a.i.
is present as both solid and liquid forms concurrently, using both the liquid and dust UEs for
handlers. Due to the uncertainty associated with pet collar formulation type, and without
chemical-specific data, HED typically assumes a range of ratios to cover a range of potential
exposures (e.g., 99%/l%, 50%/50%, and l%/99% dust/liquid). This approach was taken for
TCVP in the 2016 ORE assessment. The current assessment continues to use the approach taken
in the 2016 risk assessment, using three ratios of liquid-to-dust (e.g., 99%/l%, l%/99%,
50%/50%) to assess the pet collar uses.
Amount Handled: Per the Agency's 2012 Standard Operating Procedures (SOPs) for
Residential Pesticide Exposure Assessment,38 it is assumed that residential handlers of pet
treatment products will treat two animals per application.
Exposure Duration: Residential handler exposure is expected to be short-term in
duration. Intermediate- and long-term exposures are not likely because of the intermittent nature
of applications by homeowners. However, because of the steady state AchE inhibition exhibited
by the OPs, steady state exposures (typically 21 days and longer for OPs, but 1 day for TCVP)
were assessed and presented for residential exposures to TCVP pet products.
Days per Year of Exposure: For the purpose of assessing residential handler cancer
exposure/risk from TCVP product application, EPA has assumed four days per year for collars,
and six days per year for dusts/powders and liquid sprays. The collar is based on a worst-case
assumption of a single application every three months. Collar re-treatment intervals range from
three to seven months. EPA assumed a bi-monthly re-treatment interval for dusts/powders and
liquid sprays.
38 Available at https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-procedures-residential-
pesticide.
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Years per Lifetime of Exposure and Lifetime Expectancy: It is assumed that residential
handler exposure would occur for 50 years out of a 78-year lifespan. This factor is routinely
used as a conservative estimate of the number of years an individual could continually use a
single pesticide product. Life expectancy values are from the Exposure Factors Handbook 2011
Edition Table 18-1.39 The table shows that the overall life expectancy is 78 years based on life
expectancy data from 2007. In 2007, the average life expectancy for males was 75 years and 80
years for females. Based on the available data, the recommended value for use in cancer risk
assessments is 78 years.
2. Residential Handler Risk Estimates and Conclusions
Liquid Sprays: No non-cancer inhalation risk estimates of concern were identified for
residential handlers for the TCVP pet liquid spray formulations (all MOEs > level of concern
(LOC) of 300). Inhalation MOEs range from 8,900 to 120,000 (LOC = 300). Residential
handler cancer risk estimates for TCVP liquid sprays range from 10"8 to 10"9 which are not of
concern.
Pet Collars: No non-cancer inhalation risks of concern were identified for residential
handlers for any liquid-to-dust ratio assumption (all MOEs > level of concern (LOC) of 300). As
noted above, incorporation of exposure to a dust in the pet collar handler calculations results in a
higher exposure and ultimately a higher risk; therefore, the risk estimates when assuming a
higher percentage of dust are higher (i.e., have lower MOEs) than the risk estimates when
assuming a lower percentage of dust. When assuming a ratio of 99%/l% dust/liquid, MOEs
range from 1,900 to 4,700; when assuming a ratio of 50%/50% dust/liquid, MOEs range from
3,800 to 9,400; and when assuming a ratio of l%/99% dust/liquid, MOEs range from 190,000 to
470,000.
Similar to the non-cancer risk estimates, for the pet collar cancer risk estimates,
incorporation of exposure to a dust in the handler cancer calculations results in a higher exposure
and ultimately a higher cancer risk; therefore, the cancer risk estimates when assuming a higher
percentage of dust are higher than the cancer risk estimates when assuming a lower percentage of
dust. Residential handler cancer risks (combined dermal and inhalation) estimated for TCVP pet
collars assuming a ratio of 99%/l% dust/liquid range from 10"7 to 10"8; assuming a ratio of
50%/50% dust/liquid are all 10"8; and when assuming a ratio of l%/99% dust/liquid range from
10"8 to 10"9, which are not of concern.
A complete listing of all MOEs can be found in Tables G.lc and G.2 of the October 2022
revised human health risk assessment. A complete listing of all residential handler cancer
exposure and risk estimates can be found in Tables H.l and H.2 in the October 2022 revised
human health risk assessment.
39 Available at https://www.epa.gov/sites/production/files/2015-09/documents/efh-chapterl8.pdf.
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C. Residential Post-Application Exposure
In the October 2022 revised human health risk assessment, EPA identified that there is
the potential for post-application exposure for individuals exposed as a result of contacting a cat
or dog previously treated with TCVP pet products. A steady state non-cancer residential post-
application exposure assessment (incidental oral only {{i.e., hand-to-mouth exposure); no dermal
POD selected)) was performed for individuals coming into contact with treated cats and dogs.
Since there is no non-cancer dermal hazard for TCVP, a quantitative non-cancer post-application
dermal exposure assessment was not performed for adults or children. Residential post-
application inhalation exposure is expected to be negligible from TCVP pet products and, thus, a
quantitative assessment was not performed. Per the Residential SOPs, the combination of low
vapor pressure (2.6 xlO"7 mmHg at 25°C) and the small amounts of pesticide applied to pets is
expected to result in negligible levels of chemical in the air, and therefore negligible inhalation
exposures. In addition, a residential post-application cancer assessment was conducted due to
TCVP being classified as a Group C possible human carcinogen by the Agency with a linear
low-dose approach for quantification of risk using the oral slope factor (Ql*) of 1.83 x 10"3
(mg/kg/day)"1.
1. Residential Post-application Assumptions and Inputs
Application Rate for all Pet Uses: The application rates used in the assessment of pet
products typically represent the maximum amount of a.i. that could be applied by weight of the
treated animal (small, medium, and large). However, this is only possible when the product is
manufactured for use, or is labeled specifically, for different animal weight ranges. If this
information is not provided, a number of assumptions are used which are described in HED's
2012 Residential SOPs (Treated Pets SOP).
For pet collars, the maximum amount of a.i. that could be applied is more complicated to
determine since all of the a.i. in a collar is not available immediately for post-application
exposure. Collars are designed to provide a slow release of the a.i. In many cases, however,
when doing a post-application assessment, the amount of a.i. released is unknown; therefore, the
application rate is assumed to be the total a.i. in the collar. This does not overestimate exposure,
however, because when calculating post-application exposure, EPA adjusts the application rate
by a transfer factor to account for the fraction of the application rate that is available to transfer
to a person (this factor is described in more detail below). This transfer factor is determined by
dividing the amount of residue on a gloved hand after petting or stroking a treated animal and
comparing it to the total amount of a.i. applied. Therefore, when calculating exposure, the
assumption is that a person is potentially exposed to a fraction of the total a.i. This fraction is
discussed in more detail below {Transfer Data for Non-Cancer and Cancer Assessment).
For TCVP pet collars, the labels direct users to cut off and dispose of any excess length
once the product is fit and buckled into place. Since the application rate for pet collars is
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calculated as the total amount of a.i. in the collar (which is the total weight of the collar
multiplied by the % a.i.), a trimmed collar would represent a lower amount of a.i. applied to the
animal, and therefore, a lower potential for exposure. In the 2012 Treated Pet SOP, it is
recommended that the full length of the collar be assumed in pet collar post-application
assessments, since, at the time, data were not available to inform the exact length that is cut off;
therefore, the corresponding a.i. loss could not be quantified. However, the 2012 Residential
SOPs allow for use of other relevant information pertinent to the pesticide under examination
when assessing risks. In the 2016 assessment, HED assessed post-application exposure to the
TCVP pet collars assuming the full collar length. In 2020, Hartz informed HED that a submitted
efficacy study could provide information on collar trimming (MRID 5107950140) and HED used
this information to refine the post-application pet collar assessment41. In the efficacy study, a
total of 63 dogs (range in weight of 11 to 22 kg) and 16 cats (range in weight of 2.35 to 3.87 kg)
were included in the data summary. The weights of the collars were provided, including the pre-
cut weight, the weight of the cut-off piece, and the weight of the fitted collar. The percent of
collar removed was calculated by taking the weight of the cut-off piece and dividing by the
weight of the pre-cut collar. The percent of the collar removed ranged from 20% to 43% for
dogs, and from 18% to 38% for cats. In order to provide a conservative assumption of how
much collar might be removed during use, HED chose a value of 20% to adjust the post-
application application rate for pet collars.
Since the 2020 assessment, HED has identified additional collar trimming information in
studies submitted for registration of pet collars. This new information comes from eight
additional studies and provides 237 data points for dogs and 123 data points for cats, covering a
wide range of animal breeds and weight ranges, as well as various types of collars representing
multiple active ingredients, including TCVP. The studies include information on the collar
weight before use, and the collar weight after it is trimmed to fit the animals in the studies,
thereby providing information on the total amount of the collar that is typically trimmed during
use. It is acknowledged that these are laboratory studies; however, this information is still
considered relevant to residential post-application exposure assessment since the studies are
meant to mimic typical use to provide relevant data for product registration. The product label
directions are closely followed in these studies to ensure the data are representative of expected
real-world usage. In addition, while laboratory studies can typically be conducted using similar
sized animals (e.g., beagles are typically chosen for laboratory studies), the studies included in
this analysis provide a wider range of animal breeds (for both dogs and cats) and size ranges to
ensure the data are as representative as possible.
These data have been reviewed, and updated factors to account for trimming of pet
collars after application have been identified as a refinement for the pet collar post-application
assessment in cases where the product label directs users to trim the collar. A review of these
40 MRID 51079501. Efficacy and Repellence ofEctoparsiticidal Treatments Against Ticks (Dermacentor Variabilis, Ixodes
Scapularis, Rhipicephaslus Sanguineus), Fleas (Ctenocephalides Felis) andMosquitos (Aedes Aegypti) onDogs. May 7, 2019.
Table 4 (p. 37 - 39).
41 Available at https://www.regulations.gov/docket/EPA-HO-OPP-2009-03Q8
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data is provided in "Pet Collar Trimming Factor for Use in Exposure and Risk Assessments: A
Refinement of the Treated Pet SOP" 42 and a summary of the recommendations is provided
below. The range in weights of the dogs in the studies ranged from 13 to 75 pounds, and there
was a clear difference in the amount of collar trimmed for small (up to 20 pounds), medium (21
to 50 pounds) and large (greater than 50 pounds) dogs. For small dogs more collar was trimmed
than for medium dogs, and more collar was trimmed for medium dogs than for large dogs. For
this reason, different trimming assumptions are recommended for different sized dogs based on
an analysis of the data for each size range. A value that would be protective of the trimming data
for that specific size range was chosen. For cats, the range in weight of the animals in the studies
was smaller and only ranged from five to around 13 pounds. Across the different cat
weights/sizes, there was not a clear difference in the amount of collar trimmed; therefore, a
single trimming assumption is recommended for all size cats that is protective of all the cat
trimming data for all the cat sizes. In addition, it is acknowledged that for some larger dogs and
cats, it may be the case that the collar cannot, or does not need to be, trimmed (i.e., the entire
collar is applied to the dog or cat). This may be the case for larger breeds (e.g., dogs weighing
more than 80 pounds and cats weighing more than 20 pounds). For those larger breeds, the
recommendation is to conduct an assessment using an appropriate surface area for that animal
weight range and assume no trimming of the collar.
Dogs:
o For small dogs (up to 20 pounds according to the 2012 Residential SOPs):
assume 30% of the collar is trimmed
o For medium dogs (21 to 50 pounds according to the 2012 Residential SOPs):
assume 20% of the collar is trimmed
o For large dogs (51 pounds and up according to the 2012 Residential SOPs):
assume 15% of the collar is trimmed
o For extra-large dogs (80 pounds and up), assume no trimming of the collar
Cats:
o For all sizes: assume 5% of the collar is trimmed
o For extra-large cats (20 pounds and up), assume no trimming of the collar
Accounting for the percentage of the pet collar removed is believed to better represent
typical usage of the product as it is fit to the treated animal. These assumptions are protective of
the majority of the cat and dog collar data, and provide reasonable, conservative assumptions for
how much of the collar may be trimmed during typical use.
Pet Contact/Transfer Coefficients: For the purpose of determining exposure to treated
pets, the 2012 Residential SOPs make use of transfer coefficients (TCs). TC is an exposure rate
for a selected activity which involves contact with a source, such as adults or children playing
with treated pets or on treated turf. The TC concept is a long-standing established approach used
to estimate residential, as well as occupational, exposures after treatment has occurred (i.e., post-
42 Available at https://www.regulations.gov/docket/EPA-HO-OPP-2009-0308.
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application) and is the basis for the Agency's post-application exposure guidelines.43 A TC, with
units of cm2/hour, is derived by taking the ratio of a study volunteer's dermal exposure per unit
time (mg/hr), and the concurrent measure of residue available for transfer (mg/cm2). Ideally,
dermal exposure is based on activities representative of the use pattern, and residue transfer is
determined concurrently by use of an established method specific to the use pattern. For pet
product exposure assessments, TCs can be defined as animal surface area contact per unit time
(cm2/hour).
Currently, there is no exposure study available representing typical adult and child
activities with pets and a concurrent transferable residue (TR) measure {i.e., there are no TC
studies available that represent pet owner activities with a treated pet). As noted in the 2012
Residential SOPs44, there are groomer studies available conducted to monitor exposure during
pet grooming activities. These studies are likely to result in a highly protective estimate of
exposure per hour relative to exposure per hour associated with petting, hugging, or sleeping
with a pesticide-treated pet since groomers directly handle pesticide products and have direct
contact with treated pets. These pet grooming exposure studies have been submitted to the
Agency, reviewed and determined to be acceptable for risk assessment.
In the groomer studies, human volunteers applied dust/powders or shampoo products to
various dogs of differing sizes and fur lengths. As noted above, since the groomers extensively
handled the dogs, it is expected that their resulting exposures are higher than would be
reasonably anticipated from routine contact with treated pets by pet owners. The volunteers in
the shampoo study, who were professional groomers, shampooed eight dogs for five minutes
each, rinsed, and lifted them to counters for drying and combing. In the dust study, volunteers
applied dust via shaker can to eight dogs each and then rubbed the dusts into the dogs' coats.
Both of these studies provide a measure of exposure (mg/hour), but do not provide a
measure of concurrent TR (mg/cm2) which is necessary to determine a TC. Therefore, in order
to calculate a TC, the TR had to be estimated for the groomer studies. This can be done by
multiplying the application rate in the studies by the fraction of a.i. available for transfer (i.e.,
Far). The Far value comes from available transferable residue studies that measure how much
residue is available for transfer and compare that to the application rate. An Far for pet products
was calculated using eight available pet residue transfer studies for a variety of liquid pet
products. The Far in these studies was determined by measuring the amount of residue on a
gloved hand after petting or stroking the treated animal and comparing it to the total amount of
a.i. applied. The average Far from all available studies was 0.0096 (i.e., an average of 0.96% of
the application rate applied is expected to transfer). Therefore, to estimate the transferable
residue in the groomer studies, the application rate in those studies was multiplied by 0.0096.
The resulting value was assumed to be the residue available for transfer and was used with the
exposure value to calculate a TC for liquid and solid formulations.
43 Available at littp://www, ecfr. gov/cgi-biii/text-
idx?SID=6bfd453976 Ibe8d5b20dfbf6bc 19b9d0&node=40:25.0.1.. 1. ,9.9&rgn=div6
44 https://www.epa.gov/sites/production/fLles/2015-08/docunients/usepa-opp-hed_residential sops oct2012.pdf
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The 2012 SOPs recommend use of two different TCs dependent on the pet product
formulation. One set of TCs are for liquid formulations [5,200 cm2/hour for adults and 1,400
cm2/hour for children (1 to <2 years old)] and the other set of TCs are for dust formulations
[140,000 cm2/hour for adults and 38,000 cm2/hour for children (1 to <2 years old)].
For the liquid spray formulations, the liquid TCs were used to estimate post-application
exposure.
For the pet collars, both the liquid and dust-specific pet product TCs were used to assess
post-application exposure. As was mentioned above, due to the uncertainty as to the ratio of
liquid-to-dust in the formulated pet collars, residential post-application exposures were evaluated
assuming TCVP is simultaneously released at varying ratios of liquid-to-dust (e.g., 99%/1 %,
50%/50%, and l%/99% dust/liquid), using both the liquid and dust TCs. Similar to handlers,
incorporation of exposure to a dust in the pet collar post-application calculations results in much
higher potential exposure due to the higher TCs associated with dusts vs liquids. In addition, for
calculation of incidental oral (i.e., hand to mouth exposures), the fraction of a.i. on the hands
from the formulation-specific transfer coefficient studies are used (e.g., 4% for liquid
formulations and 37% for dust formulations) as recommended in the 2012 Residential SOPs.
Exposure Time: The exposure time (ET) assumption used to assess residential post-
application exposure to TCVP pet products is based on the 2012 Residential SOPs. The value is
derived from a study which sought to evaluate the times that individuals spend performing
different activities around the home. Based upon the 2012 Residential SOPs, the point estimates
recommended for adult and child ET with pets are 0.77 and 1 hours, respectively. In the study,
animal care is defined as "care of household pets including activities with pets, playing with the
dog, walking the dog and caring for pets of relatives, and friends." The data identified the time
spent with an animal while performing household activities as recorded in 24-hour diaries by
study volunteers. While the activities defined do not necessarily represent the time volunteers
were actively engaged in constant contact with the animal as is implicit in the post-application
dermal and incidental oral algorithms, the data are the most accurate representation of time spent
with pets available and, therefore, it is assumed that contact is continual throughout the timed
activity. The Agency assumes the ET value reflects a reasonable high-end estimate of time spent
in contact with a dog treated with TCVP pet products.
When use of the study data is coupled with high-end assumptions of pet contact, the
result is an exposure assessment that inherently implies vigorous, continual contact for the entire
duration of contact. While it is possible that an adult or child may be in close contact with a pet
intermittently throughout the day, they would not be actively engaged in the highly vigorous
contact implied by use of the TCs based on the applicator exposure data for the full exposure
duration assumed. Further, it is possible that adults or children may be exposed from sleeping
with a treated pet; however, they are not actively engaged in a high level of contact, or the
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repeated mouthing behaviors exhibited by children during waking hours, which are inherently
assumed in the assessment conducted.
Transfer Data for the Non-Cancer Assessment: Chemical-specific residue transfer studies
were used for assessment of post-application exposures from registered TCVP pet products. As
noted above, residue transfer studies provide an estimate of the fraction of the a.i. available for
transfer (i.e., Far), also referred to as the transfer factor. The transfer factor is determined by
measuring the amount of residue on a gloved hand after petting or stroking the treated animal
and comparing it to the total amount of a.i. applied.
For liquid sprays, HED relied on a TCVP-specific residue transfer study (MRID
45485501). In 2014, in support of the Agency's response to the NRDC Petition, the study was
reevaluated based on current standards of conduct for pet residue transfer studies45. For the
purposes of the non-cancer assessment for liquid sprays, a transfer factor of 0.81% (maximum
observed) was used to estimate the transferable residue on the day of application (Day 0).
For pet collars, HED has relied on two TCVP-specific residue transfer studies. The first
is a literature study46 (Davis et al.), which was originally used in the December 2016 risk
assessment, and the second is a TCVP pet collar residue transfer study submitted by Hartz in
2019 (MRID 5088180147). In the 2016 TCVP risk assessment, a transfer factor of 0.3% (based
on a study conducted for 12 days) was used from the Davis study for the non-cancer assessment,
which reflected the potential transfer of residues to gloved hands after individuals continuously
rubbed for five minutes over the neck of a dog including across the collar and along the tail
region. After subsequent review of the methodology used to collect the residues, HED
determined that this approach (rubbing continuously over the neck/collar) would likely result in
an overestimate of transferable residue because of the repeated intentional high level of contact
with the collars. As a result, the transfer factor was revised to reflect the potential transfer of
residues after individuals continuously rubbed for five minutes over the neck of the dog with the
collar removed for sampling (see further description below) and along the tail region which
reduced the factor to 0.17%. This value closely aligns with the value identified from the 2019
TCVP pet collar residue transfer study which was conducted according to current practice for
generating these types of data {i.e., with petting strokes conducted on the right side, on the left
side, and along the back line of the dog).
Davis Study Residue Transfer Factor: In the 2016 risk assessment for TCVP, it was
noted that the petting/rubbing method used in this study was not conducted based entirely upon
current practice for studies of this type; however, the methodology was relevant for the time at
which it was conducted, and it was deemed adequate for risk quantitation. Upon comparison of
45 Britton, W. 2014. Tetrachlorvinphos: Reevaluation of "HED's Review of Determination of the Dislodgeability of
Tetrachlorvinphos (TCVP) from the Fur of Doss Following the Application of an Insecticide Powder, Pump Spray or Aerosol,
MRID 45485501. 5/16/14. D420285.
46 Davis, M. et. al., Assessing Intermittent Pesticide Exposure from Flea Control Collars Containing the Organophosphorus
Insecticide Tetrachlorvinphos. Journal of Exposure Science and Environmental Epidemiology. (2008) 18, 564-57). D430707
47 D453149. TCVP: Review and Summary of Residue Transfer Studies Submitted. MRID 50881801.
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the Davis study data and the submitted TCVP transfer study (which was conducted according to
current practice), HED reevaluated the methodology used in the Davis study; specifically, the
information provided in the literature study regarding how the petting simulations were
conducted. The study authors describe that dogs were petted by volunteers continuously for a
five-minute period with cotton gloves. Transferable residue (petting/rubbing) samples were
collected 1) from the fur of the neck (after application of the collar and rubbing over the collar),
2) from the fur of the neck (after application of the collar and then removal of the collar for
sampling), and 3) along the back in the tail region after application of the collar, during two
studies; the first study was conducted for 112 days and the second study was conducted for 12
days. Dogs wore the collars continuously throughout the study, but on sampling days, residue
transfer was determined with continuous petting over the neck with the collars present for 5
minutes, and then continuous petting over the neck with the collars removed for 5 minutes.
Collars were placed back on the dogs after each sampling event.
In the 2016 risk assessment, HED had relied on residues collected in the Davis Study
from the fur of the neck (after application of the collar and rubbing over the collar) and from the
tail region. The transferable residues collected from the fur of the neck (after application of the
collar and then removal of the collar for sampling) were not included since it was thought that
the collection of those residues was not consistent with the current practice for pet fur transfer
residue studies. Current practice involves petting over the pet collar, assuming that the pet collar
is secured in place as directed by product labeling. However, while the petting strokes should
not take into account the location of the collar (i.e., the petting should not intentionally avoid the
collar), they should begin from the head/neck and end at the tail (i.e., the petting stroke should
not be limited to just over the neck and collar in the head/neck area). Therefore, it has been
determined that the sampling in the Davis Study that involved continuous rubbing over the neck
and collar for five minutes likely overestimated the potential transferable residue from typical
contact with a pet or what would be expected to be measured following current practice. HED
has determined that the residues collected from the fur of the neck (after application and then
removal of the collar for sampling) likely do not underestimate exposure considering the
continuous rubbing methodology that was followed. Therefore, for the current exposure
assessment for pet collars, HED has updated the calculation of the fraction transferred value by
dividing the sum of the residues measured from the fur of the neck (after application of the collar
and then removal of the collar for sampling) and from the back in the tail region by the amount
of a.i. in the pet collar (as reported in the Davis Study), 4,800 mg. The fraction transferred
proposed for non-cancer post-application risk assessment, therefore, is 0.0017 (0.17%), and is
based on the mean residues reported from the 12-day study [where (8 mg + 0.08 mg)/ 4,800 mg
= 0.0017], Upon reevaluation, HED has determined that the Davis Study fraction transferred and
the fraction transferred determined from MRID 50881801 transfer study (described below) are
similar.
MRID 50881801 Residue Transfer Factor: The Hartz Mountain Corporation submitted a
TCVP-specific residue transfer study for pet collars in 2019 (MRID 50881801). The purpose of
the study was to measure the transferability of the test substance, TCVP, from the hair of a dog
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wearing a TCVP-impregnated collar. Each collar contained 14.55% TCVP (TCVP weight/collar
weight). A total of 9 dogs were used in the study, randomly assigned to 3 groups. Dogs in Group
1 were petted for 5 simulations, dogs in Group 2 received 10 petting simulations, and dogs in
Group 3 received 25 petting simulations. Each simulation consisted of three strokes conducted
using a mannequin hand fitted with three cotton gloves. The first stroke was on the right side,
the second on the left side, and the third was along the back line. Percent transferable residues of
TCVP were calculated by either taking (1) the ratio of the residues of TCVP observed on the
glove to the total amount of TCVP in the collar at application or (2) the ratio of the residues of
TCVP observed on the glove to the applied TCVP dose. In the current TCVP pet collar post-
application calculations, as noted above, the application rate is calculated as the total amount of
a.i. in the collar. Therefore, the percent transferable residue relative to the total amount of TCVP
in the collar (option #1 above) was used in the calculations. The average percent transferable
residues of TCVP relative to the total amount of TCVP in the collar at application were 0.098%
for Group 1 (5 petting simulations), 0.086%) for Group 2 (10 petting simulations), and 0.20% for
Group 3 (25 petting simulations). For the purpose of non-cancer post-application risk
assessment, only the results from group 3 were used since that group used 25 petting simulations,
which most closely compares with the current methodology recommendation, which is 20
petting simulations.
Since both studies are representative of potential exposure to currently registered TCVP
pet collars and provide similar estimates of fraction transfer (0.17% and 0.20%), the higher value
of 0.20%) was used in the risk assessment.
Exposure Duration: Residential post-application exposure is expected to be short- and
intermediate-term for liquid sprays. For pet collars, post-application exposures are expected to
be long-term (greater than 6 months) due to the potential for extended usage in more temperate
parts of the country, and the longer active lifetime of pet collar products. Again, because of the
steady state AChE inhibition exhibited by the OPs, steady state exposures (typically 21 days and
longer for OPs, but 1 day for TCVP) were assessed and presented for residential exposures to
TCVP pet products.
Transfer Data for the Cancer Assessment: For purpose of quantification of estimated
TCVP post-application cancer exposures/risks, HED used an average transfer factor from the
TCVP liquid spray studies. HED used an average of the maximum observed percent residue
transfer for each day tested for calculation of cancer exposures/risks resulting in a fraction
transferred of 0.18%> for liquid sprays.
For the assessment of pet collar cancer post-application risks, longer-term residue transfer
values from the Davis study (112 days) were used to best represent the assumption of 180
days/year exposure for cancer assessment. As noted above for the non-cancer estimate, HED
had previously included the residues from the fur of the neck with the collar present in the
calculation of the fraction transferred. Updated calculations of the fraction transferred used for
cancer post-application risk assessment was also conducted, resulting in a revised fraction
Page 33 of 47
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transferred of 0.00092 (0.09%), which is based on the mean residues (112 days) reported from
the Davis study [where (4.3 mg + 0.13)/ 4,800 mg = 0.00092],
Days per Year of Exposure: For the purpose of estimating adult dermal cancer risks,
exposure was assumed for 180 of 365 total days per year, approximately representing contact
with pets every other day. This factor is used as a health protective estimate of the number of
days that an individual could be exposed to a treated animal per year of product use. The
recommendation of 6 months exposure is conservative, particularly when (1) paired with the
assumption that this exposure duration is repeated for 50 years during an adult's lifetime
knowing that pet products change over the years and whether someone owns a pet may also
change over the years and (2) paired with the conservative transfer coefficients based on
groomer/applicator studies.
Years Per Lifetime of Exposure and Lifetime Expectancy: It is assumed that residential
post-application exposure would occur for 50 years out of a 78-year lifespan. This factor is
routinely used as a conservative estimate of the number of years an individual could continually
use a single pesticide product. Life expectancy values are from the Exposure Factors Handbook
2011 Edition Table 18-148. The table shows that the overall life expectancy is 78 years based on
life expectancy data from 2007. In 2007, the average life expectancy for males was 75 years and
80 years for females. Based on the available data, the recommended value for use in cancer risk
assessments is 78 years.
2. Residential Post-application Risk Estimates and Conclusions
Liquid Spray Products: EPA has determined that all residential post-application
exposures resulting from liquid spray products are not of concern because the MOEs range from
1,600 to 15,000, well above the LOC of 1000. Residential post-application cancer risks
estimated for TCVP liquid sprays range from 10"7 to 10"8 and are not of concern.
Pet Collars: For all three assumed liquid-to-dust ratios, residential non-cancer post-
application incidental oral risks for children 1 to <2 years old are of concern (MOEs < LOC of
1000). When assuming a ratio of 99%/l% dust/liquid, MOEs range from 7 to 20; when
assuming a ratio of 50%/50% dust/liquid, MOEs range from 14 to 40; and when assuming a ratio
of l%/99% dust/liquid, MOEs range from 500 to 1,500. Residential post-application cancer
risks (adult dermal only) were also identified for all three assumed liquid-to-dust ratios;
estimated cancer risks assuming a ratio of 99%/l% dust/liquid range from 10"5 to 10"6; assuming
a ratio of 50%/50% dust/liquid from 10"5 to 10"6, which are risks of concern. When assuming a
ratio of l%/99% dust/liquid are all 10"7, which are not of concern.
A complete listing of all MOEs can be found in Tables I.lb and 1.2 in the October 2022
residential assessment. A complete listing of all residential post-application cancer exposure and
48 Available at https://www.epa.gov/sites/production/files/2015-09/documents/efh-chapterl8.pdf
Page 34 of 47
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risk estimates can be found in Tables J. lb and J.2 in the 2022 revised residential exposure
assessment.
A summary of the October 2022 residential risk estimates resulting from the registered
TCVP pet products is provided in the table below. For a more detailed explanation of residential
exposure from the use of pet products containing TCVP and the Agency's conclusions, please
refer to the October 2022 assessment, entitled "Tetrachlorvinphos (TCVP) Third Revision:
Human Health Draft Risk Assessment for Registration Reviews'".
Tabic 1: Summary of TCVP Pet Product Residential Risk Estimates (from October 2022 assessment)1
Reg. No.
(Target Animal)
Size of Animal
Residential Handler
Non-cancer MOEs
(LOC = 300)
Residential Handler
Cancer Risk
Estimates
Residential Post-
application
MOEs2
(LOC = 1000)
Residential Post-
application Cancer
Risk Estimates
Pet Collars - 99% Dust/1 % Liquid
2596-49 (Cat)
Medium
4,100
7E-08
7
2E-05
Large
11
1E-05
Extra Large
13
8E-06
2596-50, 62
(Dog)
Small
3,500
8E-08
10
1E-05
Large
1,900
2E-07
17
7E-06
Extra Large
20
5E-06
2596-83 (Cat)
Medium
4,700
6E-08
8
2E-05
Large
3,500
8E-08
10
1E-05
Extra Large
11
1E-05
2596-84 (Dog)
Small
3,500
8E-08
10
1E-05
Large
1,900
2E-07
17
7E-06
Extra Large
20
5E-06
2596-139 (Cat)
Medium
4,700
6E-08
8
2E-05
Large
3,500
8E-08
10
1E-05
11
1E-05
2596-139 (Dog)
Small
3,500
8E-08
10
1E-05
Medium
2,500
1E-07
14
8E-06
Large
1,900
2E-07
17
7E-06
Extra Large
20
5E-06
Pet Collars - 50% Dust /50% Liquid
2596-49 (Cat)
Medium
8,000
4E-08
14
8E-06
Large
22
5E-06
Extra Large
26
4E-06
2596-50, 62
(Dog)
Small
6,900
5E-08
19
6E-06
Large
3,800
8E-08
33
3E-06
40
3E-06
2596-83 (Cat)
Medium
9,400
3E-08
16
1E-05
Large
6,900
5E-08
19
6E-06
Extra Large
23
5E-06
2596-84 (Dog)
Small
6,900
5E-08
19
6E-06
Large
3,800
8E-08
33
3E-06
Extra Large
40
3E-06
2596-139 (Cat)
Medium
9,400
3E-08
16
1E-05
Page 35 of 47
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Tabic 1: Summary of TCVP Pet Product Residential Risk Estimates (from October 2022 assessment)1
Reg. No.
(Target Animal)
Size of Animal
Residential Handler
Non-cancer MOEs
(LOC = 300)
Residential Handler
Cancer Risk
Estimates
Residential Post-
application
MOEs2
(LOC = 1000)
Residential Post-
application Cancer
Risk Estimates
Large
6,900
5E-08
19
6E-06
Extra Large
23
5E-06
2596-139 (Dog)
Small
6,900
5E-08
19
6E-06
Medium
4,900
6E-08
28
4E-06
Large
3,800
8E-08
33
3E-06
Extra Large
40
3E-06
Pet Collars - 1% Dust /99% Liquid
2596-49 (Cat)
Medium
400,000
6E-09
500
7E-07
Large
800
5E-07
Extra Large
950
4E-07
2596-50, 62
(Dog)
Small
340,000
6E-09
700
5E-07
Large
190,000
1E-08
1,200
3E-07
Extra Large
1,500
3E-07
2596-83 (Cat)
Medium
470,000
5E-09
580
7E-07
Large
340,000
6E-09
690
5E-07
Extra Large
810
4E-07
2596-84 (Dog)
Small
340,000
7E-09
700
5E-07
Large
190,000
1E-08
1,200
3E-07
Extra Large
1,500
3E-07
2596-139 (Cat)
Medium
470,000
5E-09
580
7E-07
Large
340,000
6E-09
690
5E-07
Extra Large
810
4E-07
2596-139 (Dog)
Small
340,000
6E-09
700
5E-07
Medium
250,000
9E-09
1,000
4E-07
Large
190,000
1E-08
1,200
3E-07
Extra Large
1,500
3E-07
Application of TCVP Liquid Sprays
2596-126, -140
(Cat) (Trigger)
Small
25,000
8.6E-09
1,600
3.0E-07
Large
18,000
1.2E-08
3,100
1.6E-07
2596-140 (Cat)
(Pump)
Small
120,000
1.8E-09
8,000
6.2E-08
Large
87,000
2.5E-09
15,000
3.2E-08
2596-125, -140
(Dog) (Trigger)
Small
18,000
1.2E-08
2,300
2.1E-07
Medium
16,000
1.4E-08
4,800
1.0E-07
Large
8,900
2.4E-08
4,300
1.2E-07
As indicated throughout section III, the evaluation of the potential residential post-
application health risks from exposures to cats and dogs treated with TCVP pet products is
conservative, as it incorporates a number of conservative exposure assumptions in the calculation
of risk estimates. For pet collars, exposure data reflective of adults and/or kids playing with a
pet treated with a pet collar are not available. The only exposure data available for pets
represents 1) contact with either a liquid (shampoo product) or a dust (shaker can product); not a
pet collar, and 2) commercial pet grooming, not routine at-home playing with the treated pet.
Commercial pet groomers directly handle the pesticide product and have direct contact with the
Page 36 of 47
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treated pet as they are making the applications; therefore, their exposure potential is much
greater than someone at home handling a pet after treatment, particularly with a collar which is
specifically designed to be a slow release of the a.i. The exposure calculations also assume an
adult and/or child is sustaining that high level of contact with their pet (e.g., shampooing their
pet or rubbing a dust product into their pet's fur) for up to an hour per day.
IV. Benefits and Impact Assessment of Cancellation of Dust Products and Select Collars
In considering the Petition to cancel TCVP pet products (dusts, collars, and liquid
sprays), EPA assessed the benefits of TCVP pet collars, considering the availability of other pet
products49. EPA also considered the importance of TCVP dust and powder products in the
control of pests that infest pets.
Pet Insecticide Usage
Table 2 below provides information on the sales of consumer market pet insecticides in
2011 and 2016. Based on available private market research, sales of consumer market pet
insecticides in 2016 were approximately $1.5 billion, a 25 percent increase over sales in 2011 of
$1.2 billion, unadjusted for inflation.50 In 2016, the top pet insecticide formulation, in terms of
sales, was liquid products, which represented more than 80 percent of the market, followed by
tablets for veterinary use with 12.7 percent of sales.51 As a proportion of sales, collars have
remained similar over time. As discussed below, collars tend to be cheaper and provide longer-
lasting control than liquid sprays and dusts and powders. Therefore, the proportion of sales does
not represent the proportion of usage. Expenditures on dust and powder formulations declined in
nominal terms from 2011 to 2016, which likely indicates a decrease in usage.
T;ihlc 2. Siilos of Pel Products. b\ l- ormu In I ion
hudllCl I'lH'lll
| |
S million
1 VIVO 111
S million
pcivcnl
Liquids1
949.7
78.0
1,188.9
80.7
Tablets2
182.6
15.0
187.1
12.7
Collars
60.9
5.0
98.7
4.6
Dusts and Powders
12.2
1.0
7.3
0.5
Other (aerosols, foggers, soaps, combs, & traps)
12.2
1.0
21.5
1.5
Total
1,217.5
100
1,473.4
100
Source: Kline and Company. 2012. Consumer Markets for Pesticides and Fertilizers 2011.
Accessed June 2020.];
Non-Agricultural Market Research Proprietary Data. 2016. Studies conducted and sold by a consulting and research
firm. Report on consumer pesticide usage. [Accessed June 2020.]
1 Includes shampoos, dips, and topical spot-ons.
2 Veterinary supplied oral treatments.
49 Atwood, D., and S. Smearman. 2017. Alternatives Assessment for Tetrachlorvinphos (TCVP) (PC Code 083702)
Impregnated Flea and Tick Collars on Dogs and Cats. Available at https://www.re giilations.gov/doeket?D=EPA~
HO-QPP-2008-03.1.6.
50 Non-Agricultural Market Research (Proprietary) Data. 2016. Studies conducted and sold by a consulting and
research firm. Report on consumer pesticide usage. [Accessed June 2020.]
51 Ibid
Page 37 of 47
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Based on preliminary private market research of sales of brands carrying the TCVP flea
collars, sales were estimated to be slightly more than 50 percent of the total pet collar sales in the
U.S. in 2018 (NMRD, 2019; Personal communication with C. Doucoure, Email dated 6/11/2020,
may contain CBI). During the same period, TCVP flea powder sales based on the Hartz Flea and
Tick Powder were estimated to be between $3 to $5 million. Thus, based on 2016 sales figures,
TCVP products likely account for a majority of the usage of powder and dust products.
Collars
TCVP pet collars are a relatively low cost means of controlling fleas and ticks on
companion animals. Alternative control mechanisms include collars formulated with other
insecticides; liquid insecticides such as shampoos, sprays, and topical spot-ons; dusts; and
veterinary medicines. Most of these products can provide similar levels of control of both fleas
and ticks as the TCVP collars, although shampoos may not provide long-term control of ticks.52
Alternative pet collars for dogs and cats mostly contain a combination of flumethrin and
imidacloprid. Deltamethrin collars are also available for dogs. There are also several liquid
products that would provide similar efficacy, although retreatment is necessary to achieve the
duration of control provided by a collar. These products often combine a pyrethroid, or similar
chemical, with imidacloprid, indoxacarb, or pyriproxyfen.53
Collars tend to provide six to seven months of control. Treatment with liquid products or
veterinary medicines may need to be done monthly. A check of prices at several major pest
supply stores in 2017 suggests that, when converted to unit cost per month, TCVP collars tend to
be lower cost relative to other products.54 However, several topical spot-on products containing
etofenprox are available that may be within two or three dollars of the TCVP collars and would
probably be the most likely alternatives. Spot-on products are less convenient because they must
be reapplied about every month. Collars containing other insecticides would be as convenient as
TCVP collars but may be $30 to $60 more expensive per collar or five or six dollars more
expensive on a monthly basis. Veterinary medicines, which require a prescription, tend to be
substantially more expensive as well as less convenient to obtain and use.55
There could also be some short-term costs to consumers who rely on known brands and
will have to research other products. These costs may be modest. According to the American
52 Atwood, D., and S. Smearman. 2017. Alternatives Assessment for Tetrachlorvinphos (TCVP) (PC Code 083702)
Impregnated Flea and Tick Collars on Dogs and Cats. Biological and Economic Analysis Division, Office of
Pesticide Programs, U.S. EPA. 27 pp. Sept 15. Available at https://www.regulations.gov/docket?D=EPA-HO-
QPP-2008-03.1.6.
53 Ibid
54 Atwood, D., and S. Smearman. 2017. Alternatives Assessment for Tetrachlorvinphos (TCVP) (PC Code 083702)
Impregnated Flea and Tick Collars on Dogs and Cats. Biological and Economic Analysis Division, Office of
Pesticide Programs, U.S. EPA. 27 pp. Sept 15. Available at https://www.regulations.gov/docket?D=EPA-HO-
QPP-2008-03.1.6.
55 Ibid
Page 38 of 47
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Veterinary Medical Association (AVMA, 2012), over 80 percent of dog owners and nearly 45
percent of cat owners take their pets to the veterinarian at least once per year and the veterinarian
would be a ready source of information about pet insecticide products. More than 30 percent of
pet owners purchase pet insecticide products from a veterinarian.56
If EPA were to cancel all TCVP pet collars, there would likely be some increased costs
for consumers, either monetarily due to the higher cost of alternative collars or through
additional time and effort required for topical spot-on products or veterinary visits.
Impacts on Low Income Consumers
BEAD also assessed whether the lower cost in effort and money of TCVP pet collars and
dust products could suggest that, if EPA were to cancel these products, their unavailability could
disproportionally affect low-income pet owners. BEAD finds that this does not appear to be the
case. Usage of pet collars may be somewhat more common among low-income households;
about 30 percent of pet owners with a family income of less than $25,000 per year used pet
collars compared to about 25 percent of pet owners in other income categories57. However, the
usage of dust/powders is somewhat lower in low-income household compared to higher income
groups.
Usage of topical spot-ons was similar across income categories with 48 percent of pet
owners with income less than $25,000 using spot-ons compared to rates of 47 to 57 percent for
other income groups. Overall, usage of pet insecticides is similar for pet owners regardless of
income.
If EPA were to remove TCVP pet collars, there may be some increase in costs for
consumers, which could affect low-income pet owners. However, removal of TCVP pet collars
would be unlikely to disproportionately impact low-income pet owners as usage of pet
insecticide products is similar, regardless of income level. For example, seventy-two percent of
low-income pet owners reported having used pet insecticides compared to 70 percent of all
households58. Within these economic groups, usage of pet collars is relatively similar, with
about 30% of low-income households using pet collars compared to 25 percent of pet owners in
other income categories. Other pet pest control options are available across a range of prices that
perform comparably to TCVP.
Market Impacts
As noted in the Pet Insecticide Usage section above, TCVP pet collars account for a
majority of current sales in those particular segments of the market. Demand for flea and tick
56 Kline and Company. 2012. Consumer Markets for Pesticides and Fertilizers 2011. [Accessed June 2020.]
57 Ibid
58 Ibid
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products may be greatest in the spring and summer months because pests are more active in
warmer temperatures when people and their pets may spend more time outdoors.
V. EPA's Responses to NRDC's Petition Claims
A. Statutory Background
1. Pesticide Registration and Registration Review
FIFRA, 7 U.S.C. §§ 136-136y, in general, requires EPA approval of pesticides prior to
their distribution or sale, and establishes a registration regime for regulating the use of pesticides.
Id. FIFRA sections 3(a), 3(c). EPA must approve an application for pesticide registration if,
among other things, the pesticide will not cause unreasonable adverse effects on the
environment. Id. FIFRA section 3(c)(5); see also id. FIFRA section 2(bb). When determining
whether a pesticide will cause unreasonable adverse effects on human health or the environment,
EPA must balance the risks of the pesticide against the benefits of its use. See Sections III and
IV. Specifically, FIFRA section 2(bb) requires EPA to "[take] into account the economic, social,
and environmental costs and benefits of the use of any pesticide." FIFRA section 2(bb). Once a
pesticide is registered, EPA cannot unilaterally change the registration without either the
registrant requesting an amendment to their registration or EPA taking action under FIFRA
section 6 (e.g., initiating cancellation). See 40 CFR 152.44.
FIFRA also requires that EPA periodically review registered pesticides. FIFRA section
3(g). The purpose behind registration review is to account for "the rapid development of science
and the subsequent application of that knowledge in how it impacts human health and the
environment." 70 Fed. Reg. at 40,252. Registration review therefore "establishes] ongoing
scientific look-back procedures" to account for this "continually evolving" landscape. Id. at
40,253.
The process EPA uses for evaluating the potential for health and ecological effects of a
pesticide is called risk assessment, which is part of a risk management process. In registration
review, that risk assessment typically includes an ecological risk assessment, a human health risk
assessment, and, when appropriate, a cumulative risk assessment (evaluating the risk of a
common toxic effect associated with concurrent exposure by all relevant pathways and routes of
exposure to a group of chemicals that share a common mechanism of toxicity). EPA separately
assesses the benefits the chemical provides the users (impacts of the loss of the chemical) and/or
the impacts of potential mitigation.
The initial registration review cycle must be completed within 15 years after the first
pesticide containing a new a.i. is registered, but not later than October 1, 2022.
Id. Registration review does not result in the cancellation of a particular registration. Id. FIFRA
section 3(g)(l)(A)(v). Instead, if EPA determines that a pesticide does not meet the standard for
Page 40 of 47
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registration, EPA must comply with the requirements of FIFRA section 6 to proceed to seek
cancellation. Id. As noted earlier in this response, registration review is currently underway for
all TCVP uses.
2. Pesticide Cancellation Process
In relevant part, FIFRA section 6(b) authorizes EPA to initiate cancellation proceedings
"[i]f it appears to the [Agency] that a pesticide . . . generally causes unreasonable effects on the
environment." EPA can issue a notice of intent to either: (1) cancel the registration; or (2) hold a
hearing to decide whether the registration should be cancelled. Id. Before issuing such a notice,
EPA must consider a series of factors identified in the statute and complete a prescribed process
for allowing the Secretary of the Department of Agriculture (USD A) and the FIFRA Scientific
Advisory Panel (SAP) (a group of scientists charged with providing EPA with advice related to
pesticide actions) to comment on the proposed notice at least 60 days prior to publication. M;
see also, id. FIFRA section 25(d)59. Additionally, when a public health use is involved (e.g., flea
and tick protection), section 6(b) states that the Department of Health and Human Services
(HHS) should also provide information on the benefits and use or an analysis thereof. Unless
they waive review, USD A, HHS, and the SAP may comment during those 60 days. FIFRA
sections 6(b) and 25(d). When a draft Notice of Intent to Cancel (NOIC) is based on scientific
issues, the EPA may also convene a public meeting of the SAP following the procedures of the
Federal Advisory Committee Act60. EPA needs to address any comments it receives from the
SAP or USDA before moving forward to publish the NOIC.
EPA must publish in the Federal Register the proposed NOIC; any comments from the
USDA; and EPA's response to such comments. Id. FIFRA section 6(b). After the NOIC is
issued, the registrant may, within 30 days, request an evidentiary hearing before a hearing
examiner (i.e., Administrative Law Judge (ALJ)). FIFRA section 6(d). Once a hearing is
requested and an ALJ is appointed, control of the pace of the cancellation proceeding moves
from the program office to the Office of the Administrative Law Judges. FIFRA implementing
regulations set forth in 40 CFR Part 164 provide specifics on the cancellation process. The ALJ
makes an initial decision based upon the record. Any order to cancel or revise the registration
must be "based only on substantial evidence of record of such hearing and shall set forth detailed
findings of fact upon which the order is based." Id. FIFRA section 6(d).
Given the many steps of the cancellation process, arriving at an initial order from the ALJ
can take a significant amount of time. After the ALJ's decision is issued, the cancellation
proceeding may take additional time as it can be appealed by any party to the Environmental
Appeals Board (EAB), which, on behalf of the Administrator, issues the final decision for the
Agency. A final cancellation order following a public hearing is subject to judicial review within
60 days after entry of the order. Judicial review is only available to those adversely affected by
59 The SAP must follow procedures set out in the Federal Advisory Committee Act. See 5 U.S.C. Appendix 2
(1972).
60 Id.
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the order and who participated as a party in the hearing (EPA cannot appeal an adverse
decision). Products would remain on the market throughout the proceeding.
Alternatively, a registrant can request the voluntary cancellation of a registration pursuant
to the procedures in FIFRA section 6(f). EPA must provide notice and a period for public
comment before granting such a request. FIFRA section 6(f)(1). This process takes much less
time and fewer resources than the adversarial cancellation process under FIFRA section 6(b).
To cancel pesticide registrations (or terminate uses) by any method under FIFRA section
6, EPA issues a cancellation order. In such cancellation order, EPA has the authority under
FIFRA section 6(a) to allow for the sale, distribution, and use of existing stocks of the pesticide
product despite it or its terminated use no longer being registered. EPA's issuance of a
cancellation order is a separate final Agency action under FIFRA. If there is no public hearing
(i.e., public comment period) on the cancellation order, judicial review in in the U.S. district
courts as set forth in FIFRA section 16(a).
B. Rationale for Granting Petition for Remaining TCVP Pet Collars
EPA has determined that all TCVP pet collar products have potential risks of concern as
the non-cancer post-application MOEs are below the Agency's LOC (MOEs < 1000).
As previously described, EPA requested a "dust torsion" study for TCVP pet collars to
refine liquid-to-dust ratio assumptions in 2019. The study was conducted by measuring the
"mass lost" from the collar by gravimetric measurement of the collar weight before and after
torsion, as well as measuring TCVP via chemical analysis of wipe samples taken after each
torsion cycle. This study was originally reviewed in 2019 and found to be acceptable. Upon re-
evaluation, HED identified concerns that the measurement of releases via wipe samples could
potentially represent both liquid and dust rather than solely dust (particularly "dislodgeable"
dust), as EPA had previously assumed. The study was re-classified as unacceptable due to these
concerns. As a result, the current assessment uses the approach from the 2016 risk assessment,
using three ratios of liquid-to-dust to cover a range of potential exposures from pet collar use
(e.g., 99%/l%, 50%/50%, and l%/99% dust/liquid).
Under the approach from the 2016 risk assessment, EPA has determined that all TCVP
pet collar product registration have potential risks of concern as the non-cancer post-application
MOEs are below the Agency's LOC (MOEs < 1000). EPA has also considered the number of
alternatives for TCVP pet collars, the costs of those alternative, and the impacts of removing
these products from the market, including a consideration of the impacts of lower income users.
The EPA had determined that these benefits do not offset the identified unreasonable adverse
effects for children exposed to pets with collars containing TCVP.
In particular, the benefits do not offset the potential unreasonable adverse effects for
children exposed to pets with collars containing TCVP. Therefore, EPA is moving to draft a
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proposed NOIC, as described above under "Pesticide Cancellation Process" as to the remaining
collars. In August 2022, Hartz began conducting a new torsion study to define the liquid-to-dust
ratio in TCVP pet collars, as well as a novel fur clipping study. Hartz is working on two studies
and plans to submit the data for EPA review. EPA intends to incorporate into the drafting of the
NOIC review of any data received in a timeframe that allows for such incorporation. Should the
new data result in a change to the Agency's conclusions, those conclusions will be captured in an
updated risk assessment as well as the PID, both of which will be open for public comment. The
Agency would not further pursue an NOIC if the updated data demonstrates that there is no
longer a risk concern for any TCVP pet collars.
C. Rationale for Denying Remainder of Petition
As summarized above, NRDC's petition raised several issues, and ultimately requested
that EPA cancel all TCVP pet uses. EPA has considered that request to be the true thrust of the
Petition and to the extent that the request was for EPA to initiate cancellation proceedings under
section 6(b) of FIFRA, although EPA is moving to draft a proposed NOIC for the remaining pet
collars, that request is denied for the non-collar products, as explained below. But as a
preliminary matter, EPA briefly addresses the other issues raised in the petition:
• To the extent NRDC's claimed flaws to the 2002 human health risk assessment was a
request to revisit EPA's reregi strati on decision, EPA declines to do so and notes that
reregi strati on has been superseded by registration review. EPA will consider exposures
to adults and children from any remaining TCVP pet uses as part of the full TCVP
registration review human health risk assessment which is anticipated early 2023.
• As to NRDC's claims that any EPA risk assessment underestimated exposures to
children, including toddlers who are exposed through hand-to-mouth activity, as
described above in Section III, EPA has completed a new non-occupational residential
exposure assessment for all TCVP pet uses. The assessment addresses potential
exposures from hand-to-mouth activity and incorporates new information regarding
transferable residues, formulation types, and a refined dermal absorption factor. The
assessment also provides a detailed description of the methodologies EPA used to
calculate the appropriate assumption for collar trimming and liquid-to-dust ratio for use
in the pet collar assessment61.
• To the extent NRDC was requesting that EPA rely on NRDC's April 2009 Issue Paper,
the Agency continues to not consider this due to the unavailability of the underlying data
as described in Section II.C. To the extent NRDC was requesting that EPA rely on the
Davis Study, the Agency notes that this study was considered in the new non-
occupational residential exposure assessment for all TCVP pet uses as described in
Section III.
61 Available at https://www.reguiations.gov/docket/EPA-HO-OPP-2009-03Q8.
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1. Liquid Spray Pet Uses
Taking into consideration all of the information submitted to EPA by the Petitioner and
the registrants, and described above in more detail, EPA determined that all of the liquid spray
products are not of concern. For these products, the MOEs range from 1,600 to 120,000, which
are well above EPA's level of concern of 1000. Because EPA did not find any risks of concern
related to these uses, EPA did not assess the benefits of these products. Therefore, EPA finds that
HARTZ 2 IN 1 FLEA AND TICK PUMP FOR DOGS II (EPA Registration No. 2596-125),
HARTZ 2 IN 1 FLEA AND TICK PUMP FOR CATS II (EPA Registration No. 2596-126), and
HARTZ RABON SPRAY WITH METHOPRENE PUMP FORMULATION (EPA Registration
No. 2596-140) and the pet uses they include meet the FIFRA standard for registration, and EPA
denies Petitioner's request to cancel these uses.
2. Dust and Powder Pet Uses
EPA had in the 2020 response determined that all of the dust/powder TCVP pet products
have potential risks of concern because the residential post-application MOEs range from 98 to
640 (MOE < the LOC of 1000). The registrants agreed to voluntarily cancel their dust and
powder pet products or terminate pet uses. On July 10, 2020, Hartz submitted requests to
voluntarily cancel HARTZ 2 IN 1 FLEA AND TICK POWDER FOR CATS (EPA Registration
No. 2596-78) and HARTZ 2 IN 1 FLEA AND TICK POWDER FOR DOGS (EPA Registration
No. 2596-79). On June 19, 2020, Chem-Tech Ltd. voluntarily submitted a request to terminate
cat and dog uses from CLEAN CROP LIVESTOCK 1% RABON DUST (EPA Registration No.
47000-123), and this cancellation went into effect on December 30, 2020.62 Hartz was allowed
production of these products until July 31, 2020, and sale and distribution of existing stocks until
March 31, 2021.
VI. Next Steps
EPA is moving to draft a proposed NOIC, as described above under "Pesticide
Cancellation Process" as to the remaining collars. Hartz is working on two studies and plans to
submit the data for EPA review. EPA intends to incorporate into the drafting of the NOIC
review of any data received in a timeframe that allows for such incorporation. Should the new
data result in a change to the Agency's conclusions, those conclusions will be captured in an
updated risk assessment as well as the PID, which will be open for public comment. The
Agency would not further pursue an NOIC if the data demonstrates that there is no longer a risk
concern for any TCVP pet collars.
62 Available at https://www.federalregister.gov/documents/2020/12/30/2020-28827/product-canceilation-order-for-
certain-pesticide-registrations-of-tetrachlorvinphos.
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VII. Conclusion
The October 2022 revised residential exposure and risk assessment supports EPA's
responses to NRDC's petition regarding whether TCVP pet uses pose unacceptable risks. EPA
declines to revisit the 2006 RED or to perform a new cumulative risk assessment for
organophosphates at this time, and notes that registration review of TCVP, along with the other
organophosphates, is currently underway, pursuant to FIFRA § 3(g) and 40 CFRPart 155.
The October 2022 revised residential exposure and risk assessment discussed above uses
appropriate, validated methodologies to calculate potential exposure to TCVP pet products. EPA
will take appropriate regulatory action to address these registrations.
Therefore, NRDC's petition to cancel all pet uses for TCVP is hereby GRANTED for all
six remaining pet collars containing TCVP and DENIED for the remainder of the pet uses of
TCVP.
VIII. References
Assessing Intermittent Pesticide Exposure from Flea Control Collars Containing the
Organophosphorus Insecticide Tetrachlorvinphos, Journal of Exposure Science and
Environmental Epidemiology, Davis, M. et al., v. 18, 564-570 (2008). D430707.
Atwood, D., and S. Smearman. 2017. Alternatives Assessment for Tetrachlorvinphos (TCVP)
(PC Code 083702) Impregnated Flea and Tick Collars on Dogs and Cats. Biological and
Economic Analysis Division, Office of Pesticide Programs, U.S. EPA. 27 pp. Sept 15.
Available at https://www.regulations.gov/docket?D=EPA-HQ-OPP-2008-Q316.
Britton, W. 2014. Tetrachlorvinphos: Reevaluation of "HED's Review of Determination of the
Dislodgeability of Tetrachlorvinphos (TCVP) from the Fur of Dogs Following the Application of
an Insecticide Powder, Pump Spray or Aerosol', MRID 45485501. 5/16/14. D420285.
Dobreniecki, S. 2022. Review oV'The in vitro percutaneous absorption of radiolabeled
tetrachlorvinphos (TCVP) at three concentrations in aqueous and lipid vehicles through human
and rat split-thickness skin." D465603.
Dryden, M. 2015. Mange in Dogs and Cats, In Merck Veterinary Manual. Available at:
https://www.merckvetmaniial.com/inteeiimentary-SYStem/manee/manee4n-does-and-cats
Hanley, S. 2002. HED's Review of Determination of Dermal and Inhalation Exposures to
Tetrachlorvinphos (TCVP) During the Application of an Insecticide Powder to a Dog. D278626.
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Kline and Company. 2012. Consumer Markets for Pesticides and Fertilizers 2011. [Accessed
June 2020.]
Lowe, K. 2019. TCVP: Data Evaluation Recordfor the Study "Determination of TCVP and
DCA Residues Releasedfrom Hartz Flea and Tick Collars by Torsion Stressing" D454190.
Lowe, K. 2022. TCVP: Addendum to the Data Evaluation Recordfor the Study
"Determination of TCVP and DCA Residues Releasedfrom Hartz Flea and Tick Collars by
Torsion Stressing" D466273.
Lowe, K. 2022. TCVP: Addendum to Review and Summary of Residue Transfer Studies
Submitted. D466274.
Lowe, K. 2022. Pet Collar Trimming Factor for Use in Exposure and Risk Assessments: A
Refinement of the Treated Pet SOP. D465605.
Non-Agricultural Market Research (Proprietary) Data. 2016. Studies conducted and sold by a
consulting and research firm. Report on consumer pesticide usage. [Accessed June 2020.]
Non-Agricultural Market Research (Proprietary) Data. 2019. Personal communication with C.
Doucoure. Email dated 6/11/2020.
U.S. EPA. 2011. Exposure Factors Handbook: 2011 Edition, Table 18-1. Available at
https://www.epa.eov/sites/prodiiction/files/2015-09/documents/efh-chapt f
U.S. EPA. 2012. Standard Operating Procedures for Residential Pesticide Exposure Assessment.
Available at https://www.epa.gov/sites/production/files/2015-08/documents/usepa-opp-
hed residential sops oct2012.pdf.
U.S. EPA. 2015. Tetrachlorvinphos (TCVP): Responses to Arguments Presented in the Natural
Resources Defense Council, Inc. 's (NRDC) Aug. 5, 2015 Opening Brief in NRDC v. EPA, Case
No. 15-70025 (9th Cir.)
U.S. EPA. 2016. Tetrachlorvinphos: Final Occupational and Residential Exposure Assessment
for Registration Review. Available at https://www.regulations.gov/document?D=EPA-HQ-OPP-
2008-0316-0054
U.S. EPA. 2017. Tetrachlorvinphos (TCVP) Revised Human Health Risk Assessment for
Registration Review. Available at https://www.regulations.gov/document?D=EPA-HQ-OPP-
2008-0316-0055
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U.S. EPA 2020. Tetrachlorvinphos: Addendum to the Revised Residential Exposure and Risk
Assessment for the Registered Pet Product Uses. Available at
https://www.regulations.gov/docket?D=EPA-HQ-OPP-2008-Q316
U.S. EPA. 2020. Tetrachlorvinphos: Revised Residential Exposure and Risk Assessment for the
Registered Pet Product Uses and the addendum " Tetrachlorvinphos: Addendum to the Revised
Residential Exposure and Risk Assessment for the Registered Pet Product Uses. Available at
https://www.regulations.gov/docket?D=EPA-HQ-OPP-2008-Q316
U.S. EPA. 2022. Tetrachlorvinphos (TCVP). Second Revision: Human Health Risk Assessment
for Registration Review. Available at
U.S. EPA. 2022. Tetrachlorvinphos (TCVP). Third Revision: Human Health Draft Risk
Assessment for Registration Review. Available at
Ward, E. and A. Panning, 2018. "Sarcoptic Mange in Dogs." Veterinary Centers of America
(VCA) Hospitals, 2018. Available at: https://vcahospitals.com/know-your-pet/mange-sarcoptic-
in-dogs
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