EP A-HSRB-21 -2
Dr. Jennifer Orme-Zavaleta
EPA Science Advisor
Office of the Science Advisor
1200 Pennsylvania Avenue, NW
Washington, DC 20460
Subject: April 20-21, 2021 EPA Human Studies Review Board Meeting Report
Dear Dr. Orme-Zavaleta,
The United States Environmental Protection Agency (EPA) requested that the Human
Studies Review Board (HSRB) provide scientific and ethics review of two study protocols
involving human participants. On April 20, 2021, the HSRB considered a study protocol for field
evaluation of skin-applied mosquito repellent product containing Oil of Lemon Eucalyptus and
Methyl Nonyl Ketone. Briefly, the goal of the proposed study is to determine the duration of
efficacy of protection of the skin-applied product in repelling mosquitoes. On April 21, 2021, the
HSRB considered a study protocol for evaluation of a skin-applied tick repellent product
containing Oil of Lemon Eucalyptus and Methyl Nonyl Ketone. Briefly, the goal of the proposed
study is to determine the duration of efficacy of protection of the skin-applied products in
repelling ticks.
The HSRB's responses to the charge questions presented at the meetings on April 20 and
21, 2021 along with detailed rationale and recommendations for their conclusions are provided in
the enclosed final meeting report.
Signed,
Jennifer Cavallari, ScD, CIH
Chair, EPA Human Studies Review Board

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INTRODUCTION
On April 20 and 21, 2021, the United States Environmental Protection Agency (EPA or
Agency) Human Studies Review Board (HSRB or Board) met to address the scientific and
ethical charge questions related to a study protocol "Field Efficacy Test of an Oil of Lemon
Eucalyptus and Methyl Nonyl Ketone-based Repellent Spray Against Mosquitoes" (Protocol No.
MIM-006) and a study protocol "Efficacy Test of an Oil of Lemon Eucalyptus and Methyl Nonyl
Ketone-based Repellent Spray with Ticks under Laboratory Conditions" (Protocol No. MIM-
007). In accordance with 40 CFR 26.1603, EPA sought HSRB review of the study protocol.
REVIEW PROCESS
The Board conducted a public meeting on April 20 and 21, 2021. Advance notice of the
meeting was published in the Federal Register as "Human Studies Review Board; Notification
of a Public Meeting" (EPA, FRL- 10017-40-ORD). This Final Report of the meeting describes
the HSRB's discussion, recommendations, rationale and consensus in response to the charge
questions on ethical and scientific aspects of the completed and proposed research.
For each agenda item, the Agency staff presented their review of the scientific and ethical
aspects of the proposed research, with each presentation followed by clarifying questions from
the Board. The HSRB solicited public comments and next proceeded to address the charge
questions under consideration. The Board discussed the science and ethics charge questions and
developed a consensus response to each question. For each of the charge questions, the Chair
called for the Board to vote to confirm concurrence on a summary statement reflecting the
Board's response.
For their evaluation and discussion, the Board considered materials presented at the
meeting, study protocol, related materials and documents provided by the study sponsors, the
Agency's science and ethics reviews of the study protocol, as well as oral comments from
Agency staff and the investigators during the HSRB meeting discussions. A comprehensive list
of background documents is available https://www.epa.gov/osa/april-20-21-2021-meeting-
human-studies-review-board.

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"Field Efficacy Test of an Oil of Lemon Eucalyptus and Methyl Nonyl Ketone-based
Repellent Spray Against Mosquitoes." Protocol No. MIM-006
Charge to the Board- Science:
Is the protocol "Field Efficacy Test of an Oil of Lemon Eucalyptus and Methyl Nonyl Ketone-
based Repellent Spray Against Mosquitoes" likely to generate scientifically reliable data, useful
for estimating the amount of time each of the product tested repels mosquitoes?
HSRB Response:
The research proposed in the protocol "Field Efficacy Test of an Oil of Lemon
Eucalyptus and Methyl Nonyl Ketone-based Repellent Spray Against Mosquitoes" is likely to
generate scientifically reliable data, useful for estimating the amount of time the product tested
repels mosquitoes provided that the comments and recommendations provided by the EPA and
HSRB are adequately addressed.
The HSRB also has specific comments, recommendations and additional minor points
which are described in the discussion below.
HSRB detailed response and rationale:
The HSRB reviewed the protocol and related documentation for the evaluation of a skin-
applied insect repellent product containing 11% Oil of Lemon Eucalyptus (OLE, also known as
Citriodiol; CAS 1245629-80-4) and 7.75% 2-undecanone (methyl nonyl ketone or MNK; CAS
112-12-9) for use against three genera of mosquitoes in a field- based setting. Lab-based study
procedures will occur before the field testing to evaluate subjects' attractiveness to mosquitoes
and to train them on how to use an aspirator. The study was designed to establish the median
complete protection time, or mCPT, to support the registration and labeling of the product. The
protocol was submitted by Carroll-Loye Biological Research and is sponsored by Mimikai. The
review assessed the scientific aspects of the proposed research according to the EPA guideline
OPPTS 810.3700 - Insect Repellents to be Applied to Human Skin, as well as the
recommendations from the EPA and HSRB.

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The first protocol dated February 17, 2020, submitted to the EPA was reviewed and
deficiencies were identified. Subsequently, a revised protocol was submitted on December 23,
2020, to the institutional review board (IRB). After IRB approval, the revised protocol was
submitted to the EPA. For the HSRB's review, the EPA provided both the February 17 and
December 23, 2020, protocols for review; however, the EPA's and the HSRB's reviews only
cover the December 23, 2020, protocol.
Study Overview
Briefly, the protocol describes the recruitment of 40 study participants1 to take part in a
field-based study. The study plan includes one laboratory visit prior to field-testing to take
measurements for skin surface area, evaluate attractiveness to mosquitoes, and train participants
on using aspirators. On the study day, participants will be transported to one of two field-study
test sites. There will be two ecologically-distinct test sites with a diversity and abundance of
target mosquitoes. Potential locations for test sites include northern and southern California,
Minnesota, Louisiana, Arizona, and Florida.
Two untreated control subjects will be used to monitor adequate landing pressure five
minutes before the study begins, and every 30 minutes thereafter for the duration of testing.
Adequate landing pressure is five landings within five minutes or less on each control subject.
After the 5 minute period to measure landing pressure is completed, each treated subject will
undergo five-minute exposures at 30 minute intervals until CPT occurs for that subject, signaling
repellent failure, or the end of study period is reached, whatever occurs first. The First
Confirmed Landing (FCL) is a landing followed by a second landing within 30 minutes of the
first. CPT is the measurement for residual repellency or time to product failure from time of
product application. CPT is measured as a single value for each subject. The testing may take up
to 12 hours, with up to 16 hours including transport to the field-study test site.
The product will be applied at the standard dose of 0.5g/600 cm2 for testing repellency to
either the non-dominant arm or a leg that was previously washed with unscented soap and 70%
alcohol. The dose will be applied to the skin using a tuberculin syringe and spread over the
surface by a gloved researcher.
1 At each of 2 sites, there will be 13 treated subjects, 2 control subjects, and 5 alternates.

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The risk assessment for OLE is based on the EPA risk assessment for p-menthane-3,8-
diol (PMD), which is the active component in OLE. OLE contains 65% PMD according to
EPA's risk assessment [EPA Memorandum Feb. 4, 1999; Biopesticide Registration of Citriodiol
(a mixture of chemicals, containing 65 % PMD as the key ingredient)]. Mimikai Lilly Pilly is
categorized as Toxicity Category IV for all route of exposures (MRIDs 510641-03 through
510641-08 in Protocol Appendix 6).
We agree with and support the EPA recommendations as presented in their scientific
review and report and would like to suggest some additional recommendations for consideration.
Recommendations:
•	The HSRB recommends monitoring field sites prior to testing to confirm the presence
and sufficient numbers of a diversity of mosquito species.
•	The HSRB recommends adding additional information to the study protocol clarifying
how the application of the material ".. .dispensed from tuberculin (1 ml) syringes by
researchers wearing surgical gloves who apply it to treated subjects by spreading evenly
over the area to be treated using one finger in a light rubbing motion" represents (or is
consistent with) the end-user application of pump spray. EPA noted this method of
application is consistent with the dosage and distribution on skin with the bag-in-valve
applicator of the product. This justification for using the study application should be
explicitly stated in the protocol.
•	The protocol states:
Given that we consider end user safety essential for the fundamental ethics of
conducting this study, the Sponsor proposes generating and providing dermal
absorption data for MNK as applied in the form of end product we will be testing,
if feasible, or of the active ingredient. No subject recruitment will begin until the
dermal absorption study is completed and reviewed by EPA, and the study shows
that the dermal absorption rate of MNK is such that the estimated MOE will be at
an acceptable level.
Based on information provided by the EPA, it appears that a dermal absorption study will
not be occurring. The information about this proposed study should be removed from the
protocol.

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•	Field testing is proposed in several states (i.e., California, Arizona, Florida, Minnesota,
and Louisiana). The protocol states
There will be 40 total subjects (20 male and 20 female). We will assign subjects
to the first trial by randomly choosing one of the two genders, randomly choosing
10 subjects from that gender, and then repeating the process for the other gender.
This will give us a list of 20 subjects (10 males and 10 females). We will assign
the remaining 20 subjects to the second trial.
The HSRB recommends the protocol discuss how the recruitment and randomization
strategy will work if the test sites are geographically remote (Page 14, Sampling Frame in
Section 3.2 of the protocol). This information could also be included or referenced earlier
in the protocol to further avoid confusion regarding recruitment strategy and study
conduct across disparate geographical locations.
•	Section 1.2 of the protocol makes a number of factual assertions (e.g., CDC notes
substantial consumer interest in new and effective insect repellent products) but provides
no citations for these statements. This should be corrected to be consistent with other
parts of the protocol where analogous statements are backed up with citations.
•	Page 17, line 30. Please indicate if there are any dietary restrictions, e.g., avoid spicy
foods or garlic.
•	Page 20, line 889. It is stated that "Alternate subjects may return later to replace subjects
that initiate testing but withdraw before useful data are generated." It is unclear if this is
feasible for testing done in remote locations. If this procedure is used, please indicate
how alternate subjects be notified that they are serving as a replacement.
Statistical Review
The sample size for this study was appropriately computed using EPA guidance and
calculations. There will be 13 individuals enrolled in the study with 2 untreated controls for each
field trial. Five alternates will be included for a total of 20 participants per field trial or 40 total
participants. The participants will be randomized to treatment or control maintaining a 50:50
male to female ratio in the sample; the 2 untreated control individuals will be one from each
gender. Treatment will be applied to the non-dominant arm; no randomization description is
provided for treatment application to lower legs.

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"If subject withdraws during the field test and before the withdrawing subject has
received a confirming landing, the subject's data will be retained if his or her total exposure
duration is > 90% of the mean of subjects who did not withdraw, provided that not more than 3
of 13 subjects have so withdrawn" (§4.7.7; p. 29). "If more than 3 of 13 subjects withdraw
prematurely, those with the briefest participation will be replaced first" (4.7.7; p. 30).
The design of the two experiments is that of a completely randomized design with
randomization of treatment conditions to subjects within males and within females. Kaplan-
Meier survival functions are appropriate to estimate the mCPT and 95% confidence intervals.
Recommendations:
In addition to the EPA Science Comments, please consider the following recommendations.
•	On page 32, please clarify that the "number of mosquitoes that attempted to bite their
own treated skin during that five-minute period" is the actual number of landings on
treated skin in that five-minute period. Additionally, the note "in a typical test of a
reasonably effective repellent, dozens of '0' landing values will be recorded for each ' 1'
or '2'" is unclear (line 1587). The recording of a ' 1' or '2' is unclear; please clarify which
will be recorded and under what circumstance.
•	On page 32, please clarify that if at least 50% of subjects have data that are right-
censored, the mCPT will not be computed. This is appropriate on line 1613. 'm' could be
clarified to be 'median'.
•	Clarification should be added that the analyses will be conducted for each of the field
studies separately. This clarification can be added to line 1612 in the study protocol on
page 32.
•	On page 33 (line 1641), please clarify how long of a pause will be considered for a
second landing to be confirming for the first landing. EPA has indicated that there should
not be a reason for pause based on their recommendations to the study protocol.
Charge to the Board - Ethics:

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Is the research likely to meet the applicable requirements of 40 CFR part 26, subparts
K and L?
Response:
The research proposed in the protocol "Field Efficacy Test of an Oil of Lemon
Eucalyptus and Methyl Nonyl Ketone-based Repellent Spray Against Mosquitoes" is likely to
meet the applicable requirements of 40 CFR part 26, subparts K and L, if the recommendations
made by the EPA and HSRB are adequately addressed.
Ethics review:
40 CFR Part 26, Subparts K and L
Subpart K—Basic Ethical Requirements for Third-Party Human Research for Pesticides
Involving Intentional Exposure of Non-pregnant. Non-nursing Adults
Basic ethical requirements for third-party human research for pesticides involving
intentional exposure of non-pregnant, non-nursing adults include inter alia:
IRB Approval. As per EPA Science Ethics Review of MIM-006, approval from a registered and
accredited IRB was solicited and granted:
On December 24, 2020, Advarra IRB approved the protocol dated December 23, 2020,
informed consent form, and recruitment materials. Advarra's IRB is registered with FDA
and OHRP, and has a Federal wide Assurance approved by OHRP (00023875). Advarra
is fully accredited by the Association for the Accreditation of Human Research Protection
Programs (AAHRPP). Satisfactory documentation of the IRB procedures and
membership is on file with the Agency. Documentation regarding IRB approval of the
protocol, consent and recruitment materials has been provided to the HSRB members
with the background materials for this review.

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Informed Consent, with Documentation. The process for informed consent to participation in the
study is as follows:
•	Interested candidates contact study staff via phone or email to learn more about the study
and to determine whether they meet the eligibility criteria.
•	Those who meet study criteria and remain interested in participating will then meet with
the study staff.
•	Study staff will review eligibility criteria with potential participants and inform female
subjects about the requirement for pregnancy testing.
•	Those whose eligibility is again confirmed will then be orally provided with information
about the study, including a step-by-step description of what the study requires of
participants.
•	Participants will be told that they can ask questions and meet privately with the Study
Director at any time and that they are free to withdraw from the study at any time without
forfeiting any benefits to which they are entitled.
•	Prospective participants will then be provided with the consent form, the Experimental
Subjects' Bill of Rights, a copy of the protocol, and any supporting documents.
•	Staff will read aloud the consent form and Bill of Rights, and answer any questions from
the prospective participant.
•	Prospective participants will be again reminded that they are not obligated to consent to
enroll and that they are free to withdraw from participation at any time without penalty.
•	Should prospective participants then decide to enroll, they will sign the consent form and
the Experimental Subjects' Bill of Rights.
•	Study participants will then be given copies of their signed consent form and
Experimental Subjects' Bill of Rights.
Subpart L—Prohibition of Third-Party Research for Pesticides Involving Intentional Exposure
of Human Subjects who are Children or Pregnant or Nursing Women
§ 26.1203 Prohibition of research involving intentional exposure of any human subject
who is a pregnant woman (and therefore her fetus), a nursing woman, or a child.

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All subjects who will participate in this study will be at least 18 years old. An equal
number of adult male and female participants will be enrolled (20 and 20) and female subjects
will be given pregnancy tests so that those with positive results can be excluded. Testing will be
done in private and a single female member of the research team will discuss results with
prospective participants.
Recommendations:
In summary, we agree and support the EPA Ethics comments and suggestions. We
emphasize and suggest consideration of the following recommendations:
Prevention of heat stress
•	Further clarification on what participants will wear (light clothes vs. Tyvek) during
testing periods is required; otherwise, the study forms need to be harmonized and reflect
the final proposed design. The HRSB recommends that no Tyvek suits be used; it is our
understanding that Tyvek suits have not been utilized in other studies and present a heat
stress risk. Due to heat related concerns, add a question and exclusion criteria for
potential volunteers concerning previous history of heat related injury (e.g. heat
exhaustion, heat stroke, etc). Individuals that have experienced this in the past are more
prone to future events. Excluding them from the volunteer pool could reduce overall risk
to subjects. Furthermore, the HRSB recommends that fans be used in the enclosure for
the comfort of the participants.
COVID-19 precautions
•	Ensure that any special additional steps that need to be put into place for COVID19
precautions, e.g., masks, social distancing at the lab during testing, etc. are in the
protocol.
Minor clarifications
•	The protocol indicates that subjects are to be offered latex, nitrile or vinyl gloves. Use of
latex gloves should be reconsidered because they pose a greater allergenic risk than the
other options.

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•	The protocol indicates that subjects in 'poor physical health' will be excluded from
participating. We recommend indicating the criteria and justification for how participants
will be 'judged to be in poor physical health'.
•	Page 12, line 511. Recommend specifying that standard first aid materials are commonly
acquired OTC (over the counter) materials.

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"Efficacy Test of an Oil of Lemon Eucalyptus and Methyl Nonyl Ketone-based Repellent
Spray with Ticks under Laboratory Conditions." Protocol No. MIM-007
Charge to the Board- Science:
Is the protocol "Efficacy Test of an Oil of Lemon Eucalyptus and Methyl Nonyl Ketone-based
Repellent Spray with Ticks under Laboratory Conditions" likely to generate scientifically
reliable data, useful for estimating the amount of time each of the product tested repels ticks?
HSRB Response:
The research proposed in the protocol "Efficacy Test of an Oil of Lemon Eucalyptus and
Methyl Nonyl Ketone-based Repellent Spray with Ticks under Laboratory Conditions" is likely
to generate scientifically reliable data, useful for estimating the amount of time the product tested
repels ticks provided that the comments and recommendations provided by the EPA and HSRB
are adequately addressed.
The HSRB also has specific comments, recommendations and additional minor points
which are described in the discussion below.
HSRB detailed response and rationale:
The HSRB reviewed the protocol and related documentation for the evaluation of a skin-
applied insect repellent product containing 11% Oil of Lemon Eucalyptus (OLE, also known as
Citriodiol; CAS 1245629-80-4) and 7.75% 2-undecanone (methyl nonyl ketone or MNK; CAS
112-12-9) for use against three species of ticks in a lab-based setting. The study was designed to
establish the median complete protection time, or CPT, to support the registration of the product.
The protocol was submitted by Carroll-Loye Biological Research and is sponsored by Mimikai.
The review assessed the scientific aspects of the proposed research according to the EPA
guideline OPPTS 810.3700 - Insect Repellents to be Applied to Human Skin, as well as the
recommendations from the EPA and HSRB.
The first protocol dated February 17, 2020, submitted to the EPA was reviewed and
deficiencies were identified. Subsequently, a revised protocol was submitted on December 23,
2020, to the institutional review board (IRB). After IRB approval, the revised protocol was

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submitted to the EPA. For the HSRB's review, the EPA provided both the February 17 and
December 23, 2020, protocols for review; however, the EPA's and the HSRB's review only
cover the December 23, 2020, protocol.
Study Overview
Briefly, the protocol describes the recruitment of at least 33 study participants2 to take
part in a lab-based study. The study plan includes up to four study days. The first laboratory visit
includes orientation, consent, measurements for skin surface area, evaluation of attractiveness to
ticks, and training and practice on tick manipulation. Repellency testing occurs on the second
day and may extend to three or more days.
Briefly, a new tick is exposed to the repellent treated forearm for three minutes at 15
minute intervals. The First Confirmed Crossing (FCC) is a crossing followed by a second
crossing within 30 minutes of the first. Complete Protection Time (CPT) is the measurement for
residual repellency or time to product failure from time of product application. Each subject
serves as his or her own control through the screening of actively questing ticks on the untreated
forearm prior to exposure to the repellant on the treated forearm. CPT is measured as a single
value for each subject. The testing may take up to 14 hours.
The product will be applied at the standard dose of 0.5g/600 cm2 for testing repellency to
the non-dominant arm that was previously washed with soap and 70% alcohol. Both control and
treated forearms will be arranged identically. The dose will be applied to the skin using a
tuberculin syringe and spread over the surface by a gloved researcher.
The researchers are using an external quality assurance organization.
We agree with and support the EPA recommendations as presented in their scientific
review and report and would like to suggest some additional recommendations for consideration.
Recommendations:
• The HSRB agree with the recommendation of the EPA that additional clarification is
needed to indicate how many tick species will be tested on each day and how the tick
species will be allocated per subject. The HSRB would like to emphasize that only one
2 There will be 25 treated subjects per tick species and 8 alternates.

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species of tick should be used on a subject on any given test day. Furthermore, tick
species should be randomly allocated to subjects as appropriate.
•	Occasionally language refers to the fact that ticks will only be used once on any subject.
While a tick is only used on one subject, the tick is placed or used within that subject "up
to twice", given that ticks are first tested for "questing" and then they are used in the
study if "questing" is successful. The HSRB recommends clarifying this language.
•	The HSRB recommends clarifying and minimizing the number of researchers who will
be applying the test material. The HSRB also suggests indicating the amount of test
material that is anticipated to be left on the glove and any differences in application
versus when the material is sprayed on.
Statistical Review
The purpose of this study is to examine the CPT of an insect repellent, Mimikai Lilly
Pilly, containing 11.0% OLE and 7.75% MNK as its active ingredients, against three tick
species, Ixodes scapularis, Dermacentor variabilis, and Amblyomma americanum. The product
will be tested in the laboratory on 25 subjects per species at the standard dose of 0.5g/600cm2 for
up to 14 hours.
The sample size is 25 subjects per species based on the EPA's recommended sample size
of 25 test subjects for testing repellency a single tick species (p. 16). Therefore, a sample size of
25 per species is appropriate for producing reliable and valid results. Male and female subjects
will be randomly selected from a pool of 44 candidates. Randomization will be limited to treated
and alternate subjects. Subjects proved unattractive to ticks during pre-test training will not be
chosen.
One arm from each subject will not be treated with the test product and serve as the
control for screening ticks so actively questing ticks can be used in the testing. The other arm
will be treated with the test product and serve as the treatment group (§4.2, p. 16). Each subject
will be his or her control. Treatment application to right or left arm will not be randomized.
Treatment will be applied to non-dominant arm of subject. Participants will be randomly
assigned as test or alternate subjects (p. 17).
Kaplan-Meier survival analysis will be used to calculate the median CPT from the CPT
for each participant per tick species (p. 17). The Kaplan-Meier procedure is a nonparametric

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method used to estimate the probability of survival past given time points. Kaplan-Meier
Survival Analysis is advantageous since CPTs data may not be normally distributed. The
Kaplan-Meier procedure does not assume that the data should follow a specific parametric
distribution. The Kaplan-Meier procedure accounts for censored observations. Therefore,
Kaplan-Meier estimator is most appropriate for calculating the median CPT. Thus, Kaplan-Meier
estimator is appropriate to answer the research question.
In the study, proposed statistical methods are appropriate to answer the research question.
In addition, the proposed design has adequate statistical power to answer the research question.
Therefore, the protocol "Efficacy Test of an Oil of Lemon Eucalyptus and Methyl Nonyl Ketone
based Repellent Spray with Ticks under Laboratory Conditions" is likely to generate
scientifically reliable data, useful for estimating the amount of time each of the product tested
repels ticks.
Recommendations
We agree and support the EPA comments and suggestions. Our recommendation is as
follows:
• The HSRB recommends thatthe time to an event or censorship (known as the "survival
time") should be clearly defined and precisely measured. The Kaplan-Meier method
requires the survival time to be recorded precisely.
Charge to the Board - Ethics:
Is the research likely to meet the applicable requirements of 40 CFR part 26, subparts
K and L?
Response:
The research proposed in the protocol "Efficacy Test of an Oil of Lemon Eucalyptus and Methyl
Nonyl Ketone-based Repellent Spray with Ticks under Laboratory Conditions" is likely to meet
the applicable requirements of 40 CFR part 26, subparts K and L, if the recommendations made
by the EPA and HSRB are adequately addressed.
Ethics review:

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The research objective of the study is to determine the duration and efficacy of the test
material [Mimikai Lilly Pilly Repellent containing 11% Oil of Lemon Eucalyptus (OLE or
Citriodiol) and 7.75% 2-undecanone (methyl nonyl ketone or MNK)], when applied at a typical
consumer dose to skin, in repelling the following tick species: Deer tick (blacklegged tick) -
Ixodes scapularis; American dog tick - Dermacentor variabilis; and Lone star tick -
Amblyomma Americanum. The measure of efficacy is the CPT.
Study procedures for recruiting, screening, selecting, training, and (if needed)
withdrawing and replacing study participants are described in the protocol and in the EPA
scientific review. The conditions under which participants will participate in testing, including
actions taken to minimize risks to participants where possible, and procedures for measuring
CPT for ticks (including analysis) are also adequately described in the protocol. Both OLE and
MNK are registered with the EPA for use in skin-applied repellents at or above the
concentrations used in Mimikai Lilly Pilly Repellent and the EPA scientific review found the
risks due to exposure to be low. These are lowed further via several exclusion criteria described
in the EPA review.
Five risks to participants are discussed in the protocol: exposure to test material, exposure
to ticks and tick-borne illness, physical stress of test conditions, and psychological risks
associated with disclosure of pregnancy testing results. These risks and actions taken to
minimize them are outlined in the EPA scientific and ethics review.
The protocol excludes pregnant and lactating women and individuals under 18 years of
age. The consent has been reviewed and approved by Advarra IRB and appears generally
appropriate, with the exceptions noted in the EPA ethics review.
Recommendations:
In summary, we agree and support the EPA ethics comments and suggestions. We
emphasize and suggest consideration of the following recommendations:
1. COVID-19 Precautions. The HSRB would like to emphasize the need to revise the
protocol and consent to acknowledge the risks associated with COVID-19 and to describe
precautions that will be followed. HSRB recommends that researchers should consider all
available prevention and assessment methods for COVID-19 including but not limited to
rapid testing, temperature checks, and other suggested guidelines (e.g., symptom

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questionnaires) recommended by national, state, county, and city guidelines at the time of
the study. Ensure that any special additional steps that need to be put into place for
COVID19 precautions, e.g., masks, social distancing at the lab during testing, etc. are in
the protocol.
2.	Exclusion criteria. The HSRB recommends that spending a significant amount of time
outdoors is not an appropriate inclusion criteria.
3.	Diversity and Representation: The protocol indicates that biological ethnicity may relate
to the attractiveness to biting arthropods and therefore will recruit subjects with a breadth
of ethnicities. The HSRB recommends that additional information be provided on how
subjects from a variety of ethnicities will be recruited either be recruiting within targeted
communities or other methods.

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