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EFFICACY TEST OF KBR 3023 (PICARIDIN; ICARIDIN) -
BASED PERSONAL INSECT REPELLENTS (20% CREAM
AND 20% SPRAY) WITH TICKS UNDER LABORATORY
CONDITIONS
Data Requirement: OPPTS 810.3700 US EPA
Author: Scott P. Carroll, Ph.D.
Study Initiation Date: 26 July 2009
Experimental Start Date: 15 January 2010
Experimental End Date: 24 January 2010
Study Completion Date: 5 April 2010
Performing Laboratory: Carroll-Loye Biological Research
711 Oak Avenue
Davis, CA 95616
Laboratory Project ID: LNX-003
Standards Applied:
U. S. EPA Good Laboratory Practice
Regulations (40 CFR 160); 40 CFR 26
subparts K, L and M; FTFRA § 12(a)(2)(P);
California State EPA Department of
Pesticide Regulation study monitoring
(California Code of Regulations Title 3,
Section 6710).
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Carroll-Loye Biological Research Personnel for Study LNX-003:
Scott Carroll, Ph.D.
Study Director - Oversight of the study, data analysis and interpretation, report
authoring.
William K. Johnson, M.S.
Laboratory Director - Managing the application and observation technicians,
preparing Test Materials for application, application of test materials, data
recording and entry.
Shawn B. King, M.S.
Director of Operations - Managing and assisting other staff, logistics,
communicating with QAU, application of test materials, guiding and observing
subjects' tick handling, observing tick crossing events, report editing and
production.
Andrew Fowles, B.A.
Field and Logistics Manager - Logistics, environmental control, application of
test materials, guiding and observing subjects' tick handling, observing tick
crossing events.
Crystal V. Perreira, B.S.
Application and Observation Technician - Application of test materials,
guiding and observing subjects' tick handling, observing tick crossing events.
William Donahue, Ph.D.
Quality Assurance Unit.
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TABLE OF CONTENTS
Good Laboratory Practice Compliance Statement 3
Carroll-Loye Biological Research Staff on this Study 4
Quality Assurance Unit Summary 7
Information Summary 8
Testing Objective, Materials, and Methods 10
Test Results 18
Conclusions and References Cited 25
Appendix 1. Subject Tracking Spreadsheet 26
Appendix 2. Completed Limb Measurement Forms 27
Appendix 3. Treatment Allocation and Dosing 50
Appendix 4. Efficacy 54
Repellency Data Spreadsheet 54
Completed Repellency Data Capture Forms 56
Appendix 5. Environmental Records 68
Conditions for Staff, Subjects, and Ticks 68
Conditions for Test Materials - see Appendix 7
Appendix 6. Tick Disease-Free Certification 70
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Appendix 7. Test Materials Information, including Chain of Custody
and Handling Conditions 72
Sample Labels 72
Test Materials Labels Scan 74
Test Material Identities including Certificates of Analysis 75
Chain of Custody/Handling Documentation
and information for Test Materials 79
Safety Data Sheets 82
Toxicology Profile for KBR 3023 (Picaridin) 92
Chain of Custody Documentation for Ticks 94
Notes on Tick Holding and Identification 96
Appendix 8. Study Protocol LNX-003, Informed Consent,
Amendments, and Deviations 97
Study Protocol LNX-003 as amended 97
Informed Consent Form as amended 125
CLBR Subject Training for Handling Ticks 133
Amendment 1 135
Informed Consent Form, final approved version 145
Experimental Subject's Bill of Rights 153
Deviations from the Protocol and their Consequences 154
Appendix 9. Diagram of Carroll-Loye Biological Research
Laboratory Facility 155
Appendix 10. California EPA/DPR Approval of the Protocol 156
Appendix 11. Correspondence with IRB subsequent to
HSRB and EPA Protocol review 157
Appendix 12. Staff Certifications of Human Research Subject
Protection Training 167
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OUAt ITY ASSURANCE STATEMENT
Carroll-Love Biological Research, GLP study for LANXESS Corporation. Protocol
Number LNX-003 Entitled "Efficacy Test of KBR 3023 (Picaridin;Iearidin) - Based
Personal Insect Repellents (20% Cream and 20% Spray) with Ticks under Laboratory
Conditions" was inspected during various stages of the study. The data presented in the
final report represent an accurate record of the raw data and the experimental findings.
Records of results of facility inspections, study and final report audits are kenl on file at
Sierra Research Laboratories. The phases of the study inspected, dales and the findings
were reported to the study director and management is as follows:
Phase Inspected
Date
Description
Protocol Review-
Raw Data Audit
(Dosemitry)
20 January 2010
20-22 Jan, 2010
Protocol Review-
Partial Raw Data Audit
In-Life Inspection
and Audit
23 January 20 \ 0
Test Day O - Test Substance
Application and Efficacy
H valuations in the Lab - Data
CoMeeliop
Letter to Management
& Studv Direelor
01 March 2010
Letter to C-LBR
Management & Study Director
Raw Data Audit
25-28 March, 2010
Audit of Raw Data
Final Report Audit
25 Mar - 03 Apr, 2010 Final Report Audit and QAU
Statement
fx
- ¦ i - •, • — ^^ —_____——
VViiiiaui A. Donahue, .Jr., Ph.D. -! 'Date
Oualitv Assurance Unit
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Information Summary for Final Report
This tick repellent study was commissioned by LANXESS Corporation to
provide efficacy data for purposes of US/EPA registration. The test
materials, based on the active ingredient Picaridin, were KBR 3023 All-
Family Insect Repellent Cream (20% Cream) and KBR 3023 All-Family
Insect Repellent Spray (20% Pump Spray).
KBR 3023 (Icaridin; Picaridin) is a synthetic repellent developed by the
Bayer Corporation using molecular modeling techniques. From more than
800 substances, KBR 3023 showed the best repellent efficacy against a
variety of arthropods (Boeckh, et al., 1996), along with desirable attributes
regarding safety, low skin penetration, and compatibility with skin and
plastic materials. It is now owned by Saltigo GmbH (LANXESS Group)
and is managed in the USA by LANXESS Corporation (previously a
Division of Bayer Corporation).
Nomenclature. Icaridin (US EPA Registration Name Picaridin, the current
common name), was developed under the Code Name KBR 3023 and the
registered trade name Saltidin™ (formerly Bayrepel™) and was sold under
the Brand name Autan. The chemical name for Icaridin is 1-
PIPERIDINECARBOXYLIC ACID, 2- (HYDROXY-ETHYL), 1-
METHYLPROPYLESTER. However, the International Nomenclature of
Cosmetic Ingredients (INCI) name was given as HYDROXY METHYL
ISOBUTYL PIPERIDINE CARB. The product was submitted to US EPA
under the common name Picaridin. However, the common name Picaridin
was rejected by International Organization for Standards (ISO) as it was not
considered a pesticide. The common name Picaridin was also rejected by
World Health Organization/International Non-proprietary Name
(WHO/INN), but the common name, Icaridin, was accepted by WHO/INN.
The study Protocol was reviewed and approved by Independent
Investigational Review Board, Inc., and reviewed favorably by the US
Environmental Protection Agency and its Human Studies Review Board,
and by the California Environmental Protection Agency.
The KBR 3023 All-Family Insect Repellent Spray (20% Pump Spray)
dosage rate of 0.97 //l/crrr on arms was taken from the related study LNX-
001 (MRID 47506401). The KBR 3023 All-Family Insect Repellent Cream
(20% Cream) dosage rate of 1.94 //1/cm2 on arms was determined by pooling
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dosimetry data from studies LNX-001 and LNX-002. Estimated dosing,
relative to acute dermal toxicity limit dose in Picaridin (>2000 mg/kg, see
MSDS), resulted in Margin of Exposure (MOE) values of 741 for the
repellent cream and 1429 for the repellent spray. Both MOE values were
deemed sufficient to permit prolonged dermal exposure of the subjects to the
test materials during efficacy testing.
Efficacy was measured in a laboratory setting. For each of the two Test
Materials, 5 female and 5 male subjects each exposed one treated arm to
individual ticks of two species (Dermacentor variabilis, the American dog
tick, and Ixodes scapular is, the deer tick) for one minute every 15 minutes
until the Test Material failed or until cessation of the test. All individual
ticks crossed on subjects' untreated arms immediately prior to exposure to
their treated arms, indicating that the ticks were active and suitably
challenging for the efficacy trial.
Under laboratory conditions, the repellent formulations provided substantial
and prolonged protection against the two species of ticks. The mean
Complete Protection Time (CPT)(±sd) for KBR 3023 All-Family Insect
Repellent Cream (20% Cream) was 15.3±0.3 hours (range 14.5 to 15.5
hours) against Dermacentor variabilis and 12.6±4.3 hours (range 3.4 to 15.5
hours) against Ixodes scapularis. The mean CPT for KBR 3023 All-Family
Insect Repellent Spray (20% Pump Spray) was 14.0±1.6 hours (range 11.4
to 15.5 hours) against Dermacentor variabilis and 14.1±1.8 hours (range
10.3 to 15.5 hours) against Ixodes scapularis.
In summary, the data indicate that LANXESS Corporation KBR 3023 All-
Family Insect Repellents at 20% Picaridin concentration provided unusually
long periods of Complete Protection against American dog ticks and deer
ticks, and may therefore assist in reducing personal risk from the diseases
they vector, including Rocky Mountain Spotted Fever and Lyme Disease,
respectively.
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1) Objective
The objective is to determine the duration and efficacy of the picaridin-based
LANXESS Corporation insect repellent products KBR 3023 All-Family Insect
Repellent Cream (20% Cream) and KBR 3023 All-Family Insect Repellent
Spray (20% Pump Spray) when applied at a typical consumer dose, in repelling
deer ticks (.Ixodes scapularis) and American dog ticks (Dermacentor
variabilis).
2) Protocol Reference
• Carroll-Loye protocol ID number and title: LNX-003, 'Efficacy test of
KBR 3023 (Picaridin; Icaridin)-based Personal Insect Repellents (20%
Cream and 20% Spray) with Ticks under Laboratory Conditions.'
• IRB: Independent Investigational Review Board Inc., Plantation, FL.
• IRB Approval date for protocol/Informed Consent Form: 2 Nov 2009.
• Human Studies Review Board review date for protocol: 21 Oct 2009.
• California Environmental Protection Agency approval: 16 Nov 2009.
• Amendment 1 30 October 2010, clarifies how the described experimental
procedures apply to or include one, both, or either of the two tick species
to be used in the test, how subjects are screened for attractiveness to the
target tick species, and how stopping rules apply to the cessation of tick
foraging activity. The Amendment is given in Appendix 8.
• Deviations from the protocol and their consequences are given in
Appendix 8.
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3) Test Materials
Hereinafter, the Cream 20% picaridin repellent product is referred to as 'Cream' and
the Spray 20% picaridin repellent product is referred to as 'Spray'. Table 1
summarizes information about the test material(s) relevant to this study.
Table 1: Test Materials as referred to in this Protocol:
Cream 20%
Spray 20%
Test Material name
KBR 3023 All-Family Insect
KBR 3023 All-Family Insect
(Picaridin cone.)
Repellent Cream (20%)
Repellent Spray (20%)
Manufacturer
LANXESS Corporation
LANXESS Corporation
Lot Number/Batch ID
XKOC 00736
XKOC 00738
Manufacturing
Standards Applied
Good Manufacturing Practice
standards, with records available
Good Manufacturing Practice
standards, with records
to EPA.
available to EPA.
Transport
Commercial Courier, express,
insulated container
Commercial Courier, express,
insulated container
Chain of Custody
Documented
Documented
Specific gravity
0.98
0.96
Delivery system
Lotion
Pump Spray
Active ingredient(s) (%)
Picaridin 20%
Picaridin 20%
Inert ingredients
Proprietary, available to US EPA
Proprietary, available to US
EPA
Stability
Stable
Stable
Storage conditions
specified
Room temperature, max 30° C
(86° F)
Room temperature, max
30° C (86° F)
Storage conditions
Locking, closed cabinet at room
Locking, closed cabinet at
applied
temperature (19-23°C) protected
from light and moisture sources
room temperature (19-23°C)
protected from light and
moisture sources
Cosmetic properties
White cream
Clear solution
NOAELs for Picaridin
NOAEL = 200 mg/kg
NOAEL = 200 mg/kg
(dermal); 308 mg/kg (oral)
(dermal); 308 mg/kg (oral)
Irritation and
(Picaridin) No irritant or sensitizing
(Picaridin) No irritant or
sensitization class
potential
sensitizing potential
Hazard label
Substantial but temporary eye
Moderate eye irritation, avoid
requirements
injury. Do not get in eyes. Wash
thoroughly with soap & water after
handling, returning indoors, and
before eating, drinking, chewing
gum, or using tobacco. Discontinue
use and consult a doctor if irritation
or rash occurs; Flammable.
contact with eyes or clothing,
wash thoroughly with soap &
water after handling, returning
indoors, and before eating,
drinking, chewing gum, or
using tobacco. Flammable.
Reference materials
Sample labels, Safety Data Sheets and Toxicology documents are
given in Appendix 7, page 72-93
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4) Methods
a) Test Sites and Dates
Laboratory tests of repellent efficacy were conducted at Arthropod Behavior
Laboratory at Carroll-Loye Biological Research on January 23 and 24, 2010.
b) Environmental Conditions
Ambient temperature (°C), relative humidity, and light intensity (lux) were
measured at approximately 1-hr intervals in the laboratory where the
efficacy study took place. Test Material storage temperature and humidity
range were noted, as were temperature and humidity during handling for the
test.
c) Human Study Subjects
A total of 23 subjects (20 Treated, 3 Alternates) participated in the study.
They were selected randomly from a pool of 119 subjects. Their
demographics are described in table 2.
Table 2. Demography of test subjects
Participated Participated
Pool (excluding Alternates) (including Alternates)
Male
52%
50%
48%
Female
48%
50%
52%
Caucasian
72%
55%
52%
Asian
11%
10%
9%
Hispanic
9%
10%
17%
African-American
3%
10%
9%
Middle-Eastern
5%
15%
13%
For each of the two Test Materials used for the repellent efficacy study, each
of ten human subjects (5 female and 5 male for Cream; 5 female and 5 male
for Spray) exposed a treated arm to ticks for repellent efficacy evaluation in
the laboratory. A sample size of ten subjects was chosen to give a reasonably
large statistical population size while avoiding exposing too many
individuals to the minor but present risks associated with exposure to biting
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arthropods. The subjects had the following attributes: they were 18-55 years
old, reported themselves to be in good physical condition, were not students
or employees of the Study Director, did not believe themselves to be
hypersensitive to tick bites or phobic of ticks, completed the consenting
process including signing the IRB-approved Informed Consent Form, had
not used repellents within 1 day prior to the repellency study, and refrained
from using alcoholic beverages or perfumed products or smoking beginning
at 9 PM the night before, and during, the test. Females were negative in
pregnancy tests conducted immediately before they participated in efficacy
testing, and stated that they were not lactating.
d) Ticks
Nymphal deer ticks (.Ixodes scapularis) and nymphal American dog ticks
(.Dermacentor variabilis) are appropriate study animals because they are
common and geographically widespread human pests, and are important
vectors of pathogens causing such maladies as Lyme Disease and Rocky
Mountain Spotted Fever in humans. These ticks may obtain the pathogens
during larval feeding on wildlife, and then readily pass them to a human
during the succeeding nymphal stage because their small size makes them
difficult to detect while they are feeding.
This study did not test tick biting, and the risk of disease transmission during
its conduct is judged to be extremely low. Nonetheless, to preclude the
possibility of having infected ticks present in the laboratory, laboratory-
reared, disease-free ticks were used. Nymphal ticks were obtained from the
Centers for Disease Control and Prevention in Atlanta, Georgia. They were
reared in all life stages on uninfected New Zealand white rabbits. Sera from
those rabbits are routinely tested for antibodies against a number of
rickettsial and bacterial agents after infestation with colony ticks, and
representative samples of tick colonies are tested by PCR to ensure their
uninfected status. Ticks were received on 7 January 2010 (used in subject
training and screening for attractiveness to ticks) and 20 January 2010 (used
in the repellent efficacy test) from CDC-Atlanta. The ticks were identified
by the Laboratory Manager using keys and illustrations found in Durden and
Keirans (1996) and Yunker et. al. (1986). Tick chain of custody, holding
conditions, and identification are described in Appendix 7. Tick disease-free
certification is given in Appendix 6.
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e) Dosage determination and margin of exposure
The Spray dosage rate of 0.97 //l/crrr on arms was taken from dosimetry data and
analysis reported in related study LNX-001 (MRID 47506401). The Cream dosage
rate of 1.94 //l/crrr was determined by pooling data from study LNX-001 with
additional dosimetry data collected as part of the related study LNX-002.
Estimated dosing relative to the acute dermal toxicity limit dose of Picaridin
(>2000 mg/kg, MSDS) resulted in Margin of Exposure (MOE) values that were
deemed sufficient to permit prolonged dermal exposure of the subjects to the test
materials during efficacy testing.
Despite the individual variation in dosing rate inevitable in actual consumer
use, we used the same, average dosing rate in all subjects. The chief
advantage of this approach is that it may guard against early failures in
subjects who might otherwise "under-dose" for the test conditions. In
consumer use, those who under-dose might be expected to re-apply repellent
when protection fails, and to perhaps learn about adequate dosing from
experience. That process cannot take place in standard repellent efficacy
trials. Consequently, the average values from dosimetry studies were chosen
as a reasonable approximation of sensible dosing behavior. However, a
consequence of employing values from dosimetry is that the dosing rate
differed between the products.
f) Test Materials and their application (see also Appendix 3 and Appendix 7)
Test Materials were received at CLBR on 1 October 2009, with Chain-of-
Custody documented. They were stored at the Carroll-Loye Offices in a
closed cabinet at room temperature (19-23°C, see Appendix 7) within
specifications provided by the sponsor. Test Material custody and storage
condition data, sample labels, Test Material container labels, Certificates
of Analysis, Safety Data Sheets, and the toxicology profile for KBR 3023
are given in Appendix 7.
For blinding, the two Test Materials were coded 'A' and 'B' by a designated
technician, who was then prohibited from judging crossing and repulsion
events. Sealed physical and password-protected electronic keys to the Test
Material identities were maintained for the duration of the repellency trial, to
be opened by the Study Director only after the completion of the test or if
needed for medical or legal reasons. This moderate level of blinding security
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is deemed appropriate for a test in which the performances of the test
materials are not specifically being compared with each other.
Treatments were stratified by gender and allocated at random within each
gender excepting minor adjustments needed to constrain the number of
subjects treated with each Test Material to 10. Individual doses were
prepared for each subject on the basis of the surface area of their forearm
skin. Before repellent was applied, subjects washed their forearms carefully
with a fragrance-free cleanser in tap water, rinsed them with tap water and
then rinsed them again with 35% ethanol in water, and then dried them with
clean cotton towels. Repellent was then applied by CLBR technicians and
staff, using 1 ml syringes (0.01 ml measurement increment) and one
fingertip in a surgical glove, to spread the material as evenly as possible. For
subjects with arms large enough to require doses exceeding 1 ml, the total
dose was measured into, and dispensed from, two syringes.
The treatment allocation and dosing are given in Appendix 3.
g) Subjects' Exposure to ticks
• Exposure interval: 15 min.
• Exposure duration per interval: Approximately 3 min per tick species
and per limb.
• Time between application and first exposure: up to 15 minutes
• 10 female subjects, numbers 4,33,37,45,47, 53, 60,92, 99,105
• 10 male subjects, numbers 14, 24,41,42,52, 64, 67,71, 104,117
Ticks were held in plastic vials with a moist paper substrate. Vials with ticks
had their lids removed and were placed in small trays from which ticks could
not escape. Each vile was provided with a paper "tower" that extended
beyond the top of the vial vertically, allowing ticks to move upward to the
tip and extend hooked forelegs, typical host-seeking behavior. Subjects
exploited that behavior by picking ticks up on small artist's paintbrushes and
moving the ticks to their arms. Subjects had practiced procuring ticks in this
way before the test.
In each exposure period ticks were first tested on the untreated arm to
determine if they were sufficiently active in questing. To assist subjects in
positioning ticks and in determining how far ticks walked, after application
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of the Test Material, each subject was marked on the skin with three black
dots from a Sharpie® permanent marker. On each arm, one dot was placed
at the inner wrist (i.e., at the margin of the treated area), a second dot was
placed 3 cm into the treated area in a line toward the elbow, and a third was
placed in the opposite direction, 3 cm onto the palm.
Subjects worked in groups of 3-4, and initiated exposures together. To
initiate an exposure, a subject used a paintbrush to lift a tick onto the palm
dot of the untreated arm. To be included in subsequent repellent challenge
during that exposure interval, each tick needed to be active in locomotion
and to travel at least as far as the third (elbow-most) dot within 3 min of
placement on the untreated arm. Ticks usually began walking shortly after
they were placed on the palm. While the ticks were still on the palm and
when necessary, the brush was then used very gently to guide, but not push
or force, them in the direction of the elbow. They were allowed to remain on
the hand or arm for three minutes after moving in the direction of the elbow.
Ticks meeting that criterion (all did) were scored as 'crossing' on the
untreated arm, and were immediately tested on the treated arm in like
manner. Ticks that walked away from or parallel to the treated area, after
having approached it or crossed into it less than 3 cm distance, were
occasionally repositioned with the brush near the treatment a second or third
time within an exposure period in order to clearly satisfy the scoring
criterion for repulsion. Ticks that crossed into the material for a distance of
at least 3 cm towards the elbow were scored as 'crossing' the treated arm.
Technical personnel monitored tick behavior during each exposure in each
subject group and verified suspected crossings using the criteria above.
Subjects and laboratory personnel used a large, highly visible wall clock to
measure time. Each tick was employed in only a single exposure period, on a
single subject. Discarded ticks were placed in vials in trays labeled 'Used'
and periodically removed from the lab test area by technicians. Brushes that
might have inadvertently contacted a Test Material during tick handling
were replaced with new or cleaned ones. Brushes were cleaned in 50%
ethanol in water and air-dried before re-use.
A stopping rule for exposures was invoked when a subject experienced a
crossing following another in either of the two prior exposure periods.
Subjects were withdrawn from further exposure to the crossing tick species
when such an event occurred.
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h) Data recording
Upon verification by an observing technician, a tick's apparent crossing of
the plane bisecting the arm at the point indicated by the proximal dot within
three minutes of placement on the treated limb was scored as a crossing.
Ticks that did not cross were scored as repelled. Because most observations
were unequivocal repulsions in which ticks sharply altered their direction of
travel upon approaching within a few cm or mm of the Test Material or
experiencing brief contact with the first few (less than 3 cm) of the treated
area, there was little ambiguity regarding scoring in almost all cases. The
verified scores were then recorded by the Laboratory Manager. Data from
first exposures were recorded as taking place at 15 minutes after application.
i) Data Analysis
Data were entered into an Excel 2004 (Macintosh) spreadsheet for calculations of
surface area and dosing means. Those means were double-checked with a
handheld calculator. All descriptive statistics were generated with the software
'SAS JMP' Version 5.0.1.2 (SAS Institute, Cary NC).
We calculated Complete Protection Time (CPT) as the interval between
application and the First Confirmed Crossing. The First Confirmed
Crossing was defined as the first crossing that was followed by another
crossing within one-half hour, i.e., within either of the subsequent two
exposure periods. This measure is analogous to that of First Confirmed
Landing, which is commonly used in measures of repellency to blood-
feeding flies including mosquitoes. CPT measured in this way gives a
single time value for each subject. The mean CPTs were calculated across
all 10 subjects for each tick species and Test Material, and are presented
herein with standard deviations and 95% confidence interval information.
Kaplan-Meier CPT survival plots were also generated. Kaplan-Meier
median CPT values were calculated only for Spray, due to a majority of
right-censoring of Cream data against both tick species. In addition, we
estimated the time until 25% failure for each test product against each tick
species.
Data were pooled among test days within treatment. Test day was ignored as
a variable because it was not of a priori interest; testing was conducted on
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two days for logistical reasons and to better monitor individual subjects.
Based upon environmental variables, the test days were similar.
5) Results
Margins of Exposure (MOEs) relative to the acute dermal toxicity limit dose
of Picaridin (>2000 mg/kg, see MSDS) were estimated for the chosen
dosage rates (Table 3). The model target subject was a 70 kg adult. The
resulting MOE values were deemed sufficient to permit risking prolonged
dermal exposure of subjects to the test materials during efficacy testing.
Table 3. Margin of exposure estimation for the Test Materials: mean grams
of Test Material and active ingredient to be applied based on efficacy test
subject limb surface areas, and the resulting exposure values.
Test material Test Material Picaridin Rate in 70 kg Margin of
applied (g) applied (mg) human (mg/kg) exposure
KBR 3023 All-Family 0.96 192 2.7 741
Insect Repellent
Cream (20%)
KBR 3023 All-Family 0.50 100 1.4 1429
Insect Repellent
Spray (20%)
-------
LANXESS Corporation
Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
19 of 168
b) Environmental Conditions
Efficacy data were collected under suitable environmental conditions.
Environmental conditions during laboratory exposures are summarized in
Table 4. Environmental data are detailed in Appendix 5.
Table 4. Summary of laboratory temperature, relative humidity and light
conditions on the two test days.
Date
Variable
Range
23 January 2010
Temperature
21-25°C
Relative humidity
46-52%
Light intensity
122-650 lux
24 January 2010
Temperature
22-24° C
Relative humidity
47-53%
Light intensity
57-260 lux
Test Materials were stored as specified, with measured minima and maxima
of 19°C and 23°C temperature, and 30% and 50% relative humidity (RH).
Conditions during handling for preparation of dosages were approximately
21°C / 46%RH on 23 January 2010 and 22°C / 52%RH on 24 January 2010.
Additional details are given in Appendix 7.
c) Crossing Rate on Untreated Arms
All 2274 ticks used by subjects for testing the repellents were active in
locomotion and met the questing criterion by traveling at least 6 cm toward
the elbow on the untreated arm within 3 min.
d) Efficacy: Influence of Test Material on Probability of Tick Crossing
To better understand the results presented in this section, note that no statistical
comparisons between results for the two tick species or the two Test Materials,
are made or inferred in this report.
-------
LANXESS Corporation
Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
20 of 168
Subjects collected data until a Test Material failed against both tick species, or
the test was formally concluded at 15.25 hours after the first exposure interval
(on both test days) to avoid any safety and data quality risks associated with
subjects becoming fatigued. The exception was one subject who chose to
withdraw for reasons of tiredness on Test Day 1 at 14.75 hours after her
repellent application.
In every case, ticks were strongly affected by the Test Materials, crossing in
only a minority of cases (Tables 5-8; raw data are given in temporal
sequence in Appendix 4). Repelled ticks changed their trajectory upon
approach to a Test Material, either reversing direction, or sometimes
circumambulating the wrist on untreated skin near the material, or, having
walked onto the margins of treated skin, freezing in place, revolving in tight
loops, or walking up a hair, before falling off the arm. Ticks that
unambiguously reached or passed the three cm mark inside the treated area
were scored as crossing even if they failed to traverse to the elbow, or
ultimately reversed course or fell from the arm onto the lab bench.
Despite the comparatively long duration of exposure after application in this
study, only a minority of subjects recorded failures, principally in the case of
Spray.
Cream Efficacy
Cream protected subjects from crossings by Dermacentor variabilis for at
least 14.5 hours. In testing against Ixodes scapularis, one subject
experienced a confirmed crossing by 3.4 hours, but as with Dermacentor,
most individual CPTs equaled the test's full duration. The average total
number of crossings per subject was 2.0 or less.
Cream performance statistics are given in Table 5, with individual subject
results detailed in Table 6.
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LANXESS Corporation
Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
21 of 168
Table 5. KBR 3023 All-Family Insect Repellent Cream (20%) efficacy against
the tick species Dermacentor variabilis and Ixodes scapularis: Mean CPTs
(hrs)(± sd), CPT 95% confidence intervals, times (?) to 25% failure, and mean
number of crossings per subject.
CPT
t to 25%
Mean
Tick species
mean (±sd)
95% CI
failure
crossings
D. variabilis
15.3±0.3
15.0-15.5
>15.4
1.6±2.0
I. scapularis
12.6±4.3
9.5-15.7
9.7
2.0±1.2
Table 6. KBR 3023 All-Family Insect Repellent Cream (20%) efficacy
against the tick species Dermacentor variabilis and Ixodes scapularis:
Complete Protection Times (CPTs) in hr (in descending order), whether a
confirmed crossing (CC) occurred, and number of crossings, by subject.
Subject number CPT CC? Total Crossings
Dermacentor variabilis
60
15.5
No
0
14
15.5
No
0
45
15.5
No
0
53
15.4
No
1
67
15.4
No
4
99
15.4
No
0
92
15.4
No
0
52
15.4
No
2
42
14.8
Yes
5
64
14.5
Yes
4
Ixodes scapularis
60
15.5
No
0
14
15.5
No
1
99
15.4
No
1
92
15.4
No
1
52
15.4
No
3
42
15.3
No
2
45
13.2
Yes
4
53
9.7
Yes
3
64
7.5
Yes
3
67
3.4
Yes
2
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LANXESS Corporation
Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
22 of 168
Kaplan-Meier survival plots for the repellency of KBR 3023 All-Family
Insect Repellent Cream (20%) against Dermacentor variabilis and Ixodes
scapularis are shown in Figure 1. Just two subjects received confirmed
crossings by D. variabilis, and four did so by I. scapularis.
Figure 1. Survival plot of Complete Protection Time (CPT)
for KBR 3023 All-Family Insect Repellent Cream (20%)
against the tick species Dermacentor variabilis and Ixodes
scapularis.
Spray Efficacy
Spray protected subjects from crossings by Dermacentor variabilis for a
minimum of 11.4 hours and Ixodes scapularis for a minimum of 10.2 hours.
KBR 3023 All-Family Insect Repellent Spray (20%) performance statistics
are given in Table 7, with individual subject results detailed in Table 8.
-------
LANXESS Corporation
Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
23 of 168
Table 7. KBR 3023 All-Family Insect Repellent Spray (20%) efficacy against
the tick species Dermacentor variabilis and Ixodes scapularis: Mean CPTs
(hrs)(± sd), CPT 95% confidence intervals, Kaplan-Meier (K-M) median CPTs,
times (?) to 25% failure, and mean number of crossings per subject.
CPT K-M t to 25% Mean
Tick species mean (±sd) 95% CI median failure crossings
D.variabilis 14.0±1.6 12.8-15.2 14.1 12.0 1.2±1.4
I. scapularis 14.1±1.8 12.7-15.4 15.0 13.1 2.4±2.2
Table 8. KBR 3023 All-Family Insect Repellent Spray (20%) efficacy
against the tick species Dermacentor variabilis and Ixodes scapularis:
Complete Protection Times (CPTs) in hr (in descending order), whether a
confirmed crossing (CC) occurred, and number of crossings, by subject.
Subject number
CPT
CC?
Total Crossings
Dermacentor variabilis
47
105
37
104
33*
4
41
24
117
71
Ixodes scapularis
47
105
37
104
4
33*
71
41
117
24
15.5
15.4
15.4
15.3
14.8
14.2
14.1
12.0
11.9
11.4
15.5
15.4
15.4
15.3
14.9
14.8
14.4
13.1
11.7
10.2
No
No
No
No
No
Yes
Yes
Yes
Yes
Yes
No
No
No
No
Yes
No
Yes
Yes
Yes
Yes
0
0
0
0
0
4
2
2
2
2
0
0
1
0
4
1
5
3
5
5
*Subject 33 withdrew 45 minutes before the trial was concluded.
-------
LANXESS Corporation
Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
24 of 168
Kaplan-Meier survival plots for the repellency of KBR 3023 All-Family
Insect Repellent Spray (20%) against Dermacentor variabilis and Ixodes
scapularis are shown in Figure 2. Five subjects received confirmed crossings
by each tick species.
Dermacentor^
Ixodes —
Figure 2. Survival plot of Complete Protection Time (CPT)
for KBR 3023 All-Family Insect Repellent Spray (20%)
against the tick species Dermacentor variabilis and Ixodes
scapularis.
Spray protected absolutely from crossings by either tick species for more
than 10 hours.
-------
LANXESS Corporation
Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
25 of 168
Conclusions
Under the test conditions, the repellent formulations provided substantial and
prolonged protection against two species of ticks. The mean CPT for KBR 3023
All-Family Insect Repellent Cream (20% Cream) was 15.3 hours (range 14.5 to
15.5 hours) against Dermacentor variabilis and 12.6 hours (range 3.4 to 15.5
hours) against Ixodes scapularis. The mean CPT for KBR 3023 All-Family Insect
Repellent Spray (20% Pump Spray) was 14.0 hours (range 11.4 to 15.5 hours)
against Dermacentor variabilis and 14.1 hours (range 10.2 to 15.5 hours) against
Ixodes scapularis.
In summary, the data indicate that LANXESS Corporation Picaridin insect repellents
at 20% concentration provided unusually long periods of Complete Protection
against the American dog tick and the deer tick, and may therefore assist in reducing
personal risk from the diseases they vector, including Rocky Mountain Spotted Fever
and Lyme Disease, respectively.
References Cited:
Durden, L.A. and Keirans, J.E. (1996) Nymphs of the Genus Ixodes (Acari:
Ixodidae) of the United States: Taxonomy, Identification Key, Distribution, Hosts,
and Medical/Veterinary Importance. Lanham, Maryland: Entomological Society of
America.
Yunker, C.E., Keirans, J.E., Clifford, C.M., and Easton, E.R. (1986) Dermacentor
Ticks (Acari: Ixodoidea: Ixodidae) of the New World: A Scanning Electron
Microscope Atlas. Proc. Entomol. Soc. Wash., 88 (4), 609-627.
-------
Research Subject Tracking Form
Study: LNX-003
Legend:
1 = January 15, 2010
6 = January 20, 2010
2 = January 16, 2010
7 = January 21, 2010
na = Not Applicable
3 = January 17, 2010
8 = January 22, 2010
* = Measured in previous study
4 = January 18, 2010
9 = January 23, 2010
Alt. Subj. = Alternate Subject
5 = January 19, 2010
10 = January 24, 2010
Pg. 1 ofl
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Subject Number
4
6
14
24
33
37
41
42
45
47
52
53
60
64
67
71
92
99
104
105
117
118
119
Subject Gender
F
M
M
M
F
F
M
M
F
F
M
F
F
M
M
M
F
F
M
F
M
F
F
MSD Sheet(s) Provided
6
8
7
1
2
5
4
5
8
4
9
9
6
3
8
1
5
5
1
1
1
6
6
Study Synopsis Provided
6
8
7
1
2
5
4
5
8
4
9
9
6
3
8
1
5
5
1
1
1
6
6
Experimental Subject Bill
of Rights Completed
6
8
7
1
2
5
4
5
8
4
9
9
6
3
8
1
5
5
1
1
1
6
6
Pregn ancy Test Advisory
(Females)
6
na
na
na
2
5
na
na
8
4
na
9
6
na
na
na
5
5
na
1
na
6
6
Informed Consent Form
Completed
6
8
7
1
2
5
4
5
8
4
9
9
6
3
8
1
5
5
1
1
1
6
6
Limb Measurements
Completed
*
8
7
1
*
5
*
*
*
*
9
9
6
3
8
1
*
*
*
*
1
6
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Arthropod Training
Orientation Completed
6
8
7
1
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5
4
5
8
4
9
9
6
3
8
1
5
5
1
1
1
6
6
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Attractiveness
6
8
7
1
2
5
4
5
8
4
9
9
6
3
8
1
5
5
1
1
1
6
6
Positive Dermacentor
/Attractiveness
6
8
7
1
2
5
4
5
8
4
9
9
6
3
8
1
5
5
1
1
1
6
6
Pregnancy Test Completed
10
na
na
na
9
10
na
na
9
9
na
10
9
na
na
na
10
9
na
10
na
9
10
Repellent Efficacy Test
Day 1
na
Alt.
Subj.
na
9
9
na
na
na
9
9
na
na
9
9
9
9
na
9
na
na
9
Alt.
Subj.
na
Repellent Efficacy Test
Day 2
10
Alt.
Subj.
10
na
na
10
10
10
na
na
10
10
na
na
na
na
10
na
10
10
na
na
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Limb Measurement Form
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Data recorder name: /C.
Data recorder signature: j)t-£
Note: all measurements in cm
Circumference
Limb
Length
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Lower (A)
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Upper-mid (C)
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3 Product of mean circumference and length
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Subject number: 7 /
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3 Product of mean circumference and length
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Circumference
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Length/31
Lower (A)
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circumference2
Left forearm
23
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Circumference
Limb
Length
Length/31
Lower (A)
Lower-mid (B)
Upper-mid (C)
Upper(D)
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circumference2
Left forearm
Z (
7
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22
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Right forearm
H
1
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Circumference
Limb
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circumference2
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LANXESS Corporation Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal 50 of 168
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
-------
LANXESS Corporation Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal 51 of 168
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
-------
LANXESS Corporation Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal 52 of 168
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
-------
LANXESS Corporation Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal 53 of 168
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
-------
LNX-003 Tick Crossing Data
Td-
LO
Day
Date
Subject
Se*
Product
Application
Tick
i
2
3
4
5
7
8
10
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
1
2
Hours since first exposure
3
4
5
6
7
1
January 23,2010
24
M
B
07:47
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
January 23,2010
33
F
B
07:45
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
January 23,2010
45
F
A
07:47
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
January 23,2010
47
F
B
07:45
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
January 23,2010
60
F
A
07:45
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
January 23,2010
64
M
A
07:47
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
January 23,2010
67
M
A
07:50
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
1
January 23,2010
71
M
B
07:50
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
January 23,2010
99
F
A
07:50
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
January 23,2010
117
M
B
07:50
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
January 24,2010
4
F
B
07:35
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
2
January 24,2010
14
M
A
07:32
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
January 24,2010
37
F
B
07:38
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
January 24,2010
41
M
B
07:40
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
January 24,2010
42
M
A
07:40
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
January 24,2010
52
M
A
07:39
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
2
January 24,2010
53
F
A
07:35
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
January 24,2010
92
F
A
07:37
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
January 24,2010
104
M
B
07:40
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
January 24,2010
105
F
B
07:35
Dermacentot
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
January 23,2010
24
M
B
07:47
Ixodes
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
1
January 23,2010
33
F
B
07:45
Ixodes
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
January 23,2010
45
F
A
07:47
Ixodes
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
1
January 23,2010
47
F
B
07:45
Ixodes
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
January 23,2010
60
F
A
07:45
Ixodes
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
January 23,2010
64
M
A
07:47
Ixodes
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
1
1
January 23,2010
67
M
A
07:50
Ixodes
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
1
January 23,2010
71
M
B
07:50
Ixodes
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
1
January 23,2010
99
F
A
07:50
Ixodes
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
January 23,2010
117
M
B
07:50
Ixodes
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
1
0
0
0
0
0
2
January 24,2010
4
F
B
07:35
Ixodes
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
January 24,2010
14
M
A
07:32
Ixodes
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
January 24,2010
37
F
B
07:38
Ixodes
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
2
January 24,2010
41
M
B
07:40
Ixodes
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
January 24,2010
42
M
A
07:40
Ixodes
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
January 24,2010
52
M
A
07:39
Ixodes
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
2
January 24,2010
53
F
A
07:35
Ixodes
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
2
January 24,2010
92
F
A
07:37
Ixodes
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
January 24,2010
104
M
B
07:40
Ixodes
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
January 24,2010
105
F
B
07:35
Ixodes
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
2
3
Hours since first exposure
4
5
6
7
Date
Subject
s"
Product
Application
Tick
1
2
3
4
5
6
7
8
9
10
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
First Time Interval
1
January 23,2010
08:00
2
January 24,2010
07:45
LNX-003 Tick Crossing.xls
-------
LNX-003 Tick Crossing Data
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
Subject
Product
8
9
10
11
12
13
14
15
CPT
(hours!
Total
Crossings
Confirmed
Crossing
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
1
-
-
-
-
-
-
-
-
-
-
-
-
11.97
2
1
24
B
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Wthdi
-
-
14.75
0
0
33
B
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
15.47
0
0
45
A
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
15.5
0
0
47
B
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
15.5
0
0
60
A
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
1
1
-
-
-
14.47
4
1
64
A
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
0
0
15.42
4
0
67
A
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
11.42
2
1
71
B
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
15.42
0
0
99
A
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
1
-
-
-
-
-
-
-
-
-
-
-
-
11.92
2
1
117
B
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
-
-
-
-
14.17
4
1
4
B
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
15.47
0
0
14
A
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
15.37
0
0
37
B
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
1
-
-
-
14.08
2
1
41
B
1
0
0
1
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
-
14.83
5
1
42
A
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
15.35
2
0
52
A
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
15.42
1
0
53
A
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
15.38
0
0
92
A
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
15.33
0
0
104
B
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
15.42
0
0
105
B
0
1
0
0
0
1
0
0
0
0
1
0
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
10.22
5
1
24
B
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Wthdi
-
-
14.75
1
0
33
B
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
1
-
-
-
-
-
-
-
13.22
4
1
45
A
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
15.5
0
0
47
B
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
15.5
0
0
60
A
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
7.47
3
1
64
A
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
3.42
2
1
67
A
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
1
1
-
-
-
14.42
5
1
71
B
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
15.42
1
0
99
A
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
1
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
11.67
5
1
117
B
0
0
0
0
1
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
1
14.92
4
1
4
B
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
15.47
1
0
14
A
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
15.37
1
0
37
B
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
-
-
-
-
-
-
-
-
13.08
3
1
41
B
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
15.33
2
0
42
A
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
15.35
3
0
52
A
0
0
0
0
0
0
0
0
1
0
1
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
9.67
3
1
53
A
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
15.38
1
0
92
A
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
15.33
0
0
104
B
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
15.42
0
0
105
B
8
9
10
11
12
13
14
15
CPT
(hours)
Total
Crossings
Confirmed
Crossing
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
Subject
Product
O
CO
CO
LU
X
<
Wthdr = Subject withdrew before trial ended.
LNX-003 Tick Crossing.xls
-------
Tick Crossings or Repulsions at 15 Minute Intervals
Tick species: Dermacentor variabilis
Study: L. X -coj
Date: 2* 3 / 20 / O
Application Time(s): 07. V5" - ai.'To
Time of First Exposure: oy; eo
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20
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Page 1 of 3
-------
LANXESS Corporation Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal 57 of 168
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
-------
LANXESS Corporation Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal 58 of 168
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
-------
Tick Crossings or Repulsions at 15 Minute Intervals
Tick species: Ixodes scapularis
Study:
Date: 23, 2o/s
/2.Jo
13 oa
;s./r
15 Minute
Interval:
1
2
3
4
5
6
7
8
9
10
I)
12
13
14
15
16
17
18
19
20
21
22
Subject
Number
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-------
Study: L A/X - *°3
Date: J~jtnwy
Tick Crossings or Repulsions at 15 Minute Intervals
Tick species: Ixodes scapularis
Application Time(s): 0 7 vr- c-7;s~*>
Time of First Exposure: ox 00
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Page 2 of ?
-------
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Tick species: Ixodes scapular is
Application Time(s): o 7.
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Tick Crossings or Repulsions at 15 Minute Intervals
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Tick Crossings or Repulsions at 15 Minute Intervals
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Application Time(s): 0~) : - o~>;<-fo
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Tick Crossings or Repulsions at 15 Minute Intervals
Tick species: Dermacentor variabilis
Study: LA/X - 003
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-------
Tick Crossings or Repulsions at 15 Minute Intervals
Tick species: Ixodes scapularis
Study: X - oo J
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Page 1 of_
-------
Study: 'Y-ool
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Tick species; Ixodes scapular is
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-------
LANXESS Corporation Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal 68 of 168
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
Laboratory Environmental Conditions
Study: LtJX-003 Location: clb# l
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-------
LANXESS Corporation Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
69 of 168
Laboratory Environmental Conditions
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LabEnvironCondUions.xls
-------
LANXESS Corporation
Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
70 of 168
Subject: RE: Tick shipment date; pathogen question
Date: Fri, 29 Feb 2008 10:29:40 -0500
Thread-Topic: Tick shipment date; pathogen question
From: "Levin, Michael L. (CDC/CCID/NCZVED)"
To: "Scott P Carroll"
Scott,
We always send ticks by Priority Overnight service for delivery in the morning of
the next business day. We will try and send ticks on March 10-11 and will
provide you with a Tracking Number.
All our uninfected colonies are "routinely" screened for the presence of the
following human pathogens:
Borrelia burgdorferi
Borrelia lonestari
Anaplasma phagocytophilum
Ehrlichia chaffeensis
Ehrlichia ewingii
Rickettsia conorii
Rickettsia amblyommii
Rickettsia rickettsii
"Routinely" means:
1) Females that have laid eggs are tested by PCR for the presence of bacterial
DNA in every generation - 1/generation;
2) Rabbits used for feeding of each life-stage in every tick colony, in every
generation are tested for the presence of antibodies to the above-listed
pathogens - 3/generation.
Let me know if I can be of more help.
Thank you
Michael L. Levin, Ph.D.
Medical Entomology Laboratory
Rickettsial Zoonoses Branch
Centers for Disease Control and Prevention
1600 Clifton Road, MS G-13, Atlanta, GA 30333
Phone: (404) 639-3639
Cell: (404) 542-6608
Fax: (404) 639-4436
E-mail: MLevin@cdc.gov
-------
LANXESS Corporation
Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
71 of 168
Confirming disease-free documentation for tick shipment
2 messages
Shawn King Thu, Jan 21, 2010 at 2:21 PM
To: "Levin, Michael L. (CDC/CCID/NCZVED)"
Cc: Scott P Carroll
Hi Michael,
One last detail - we would like to confirm that the details for
disease free management of source tick colony have not changed since
2008 when we last checked. At that time, you provided the following
description:
All our uninfected colonies are "routinely" screened for the presence of the
following human pathogens:
Borrelia burgdorferi
Borrelia lonestari
Anaplasma phagocytophilum
Ehrlichia chaffeensis
Ehrlichia ewingii
Rickettsia conorii
Rickettsia amblyommii
Rickettsia rickettsii
"Routinely" means:
1) Females that have laid eggs are tested by PCR for the presence
of bacterial
DNA in every generation - 1/generation;
2) Rabbits used for feeding of each life-stage in every tick
colony, in every
generation are tested for the presence of antibodies to the above-listed
pathogens - 3/generation.
Are there any changes to this description? If so, please let us know,
for our records.
Thanks again for all your assistance in providing the ticks. The
study will be conducted this weekend.
Best, Shawn King
Director of Operations
Carroll-Loye Biological Research
Levin, Michael L. (CDC/CCID/NCZVED) Thu, Jan 21, 2010 at 2:24 PM
To: Shawn King
Cc: Scott P Carroll
Yes, our routine procedures for maintenance of uninfected ticks colonies
remain unchanged.
Thank you
Michael L. Levin, Ph.D.
Medical Entomology Laboratory
Rickettsial Zoonoses Branch
Centers for Disease Control and Prevention
1600 Clifton Road, MS G-13, Atlanta, GA 30333
Phone: (404) 639-3639
Cell: (404) 542-6608
Fax: (404) 639-4436
E-mail: MLevin@cdc.gov
[Quoted text hidden]
https://mail.google.com /mail/?ui=2&ik=50e5329dce&view=pt&q=cdc&search=query&th = 12652c32d90b5a98
Page 1 of 1
-------
KBR 3023 Insect Repellent Cream
Contains Bayrepel
Long-tasting, effective protection from mosquitoes ticks, biting flies, and fleas. Not oily, greasy or sticky, it smells great, too. Repels
insects for up to 8 hours
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ACTIVE INGREDIENT
INERT INGREDIENTS-
TOTAL
Ptcartdin, 1-Methylpropyi-2-(2-hydroxyethyl)-1-piperidme carboxylase •
20%
80%
— 100.0%
"Other Ingredients: Purified watei, glycerin, denatured alcohol, thickener, emollient, fragrance
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KEEP OUT OF REACH OF CHILDREN
WARNING
STOP - Read This Entire Label Before- Use
PRECAUTIONARY STATEMENTS
WARNING HAZARDS TO HUMANS.
Causes substantial but temporary eye injury. Do not get in eyes. Wash
thoroughly with soap and water after handling, returning indoors and
before eating, drinking, chewing gum, or using tobacco. Discontinue use
and consult a doctor if irritation or rash occurs.
The information below describes the first aid procedures foi incidents involving
KBR 3023 Insect Repellent Cteam.
FIRST AID
IF IN EYES:
• Hold eye open and rinse gently with water for 15-20 minutes
• Remove contact lenses if present, after the first five minutes, then
continue rinsing,
• Call a poison control center or doctor for treatment advice.
IF SWALLOWED:
» Call a physician or poison control center immediately for treatment
advice.
• Have person sip a glass of water if able to swallow
• Do not induce vomiting unless told to do so by a Poison Control
Center or a doctor.
« Do not give anything to an unconscious person
Have the product container or label with you when calling a poison control
center or doctor or going for treatment You may also contact 1-800-410-
3063 for emergency medical information
The LANXESS Pittsburgh Emergency Response Telephone Number is 800-410-3063
PHYSICAL HAZARDS
Flammable Do not use of store near heat sources, sparks or open flame Do nol smoke while
applying,
DIRECTIONS FOR USb"
It is a violation of Federal law to use this product in a manner inconsistent with its
labeling.
for best results, read and follow all label directions.
Follow these guidelines when applying KBR 3023 Insect Repellent.
Apply evenly to skin in a thin layer
Excessive amounts or more frequent reapplication should be unnecessary,
not apply more than 2 times a day.
Repels insects and ticks for up to eight hours.
Reapply every 8 hours, Do not exceed two applications per day
Do not spray directly on face.
Avoid contact with lips, cuts, wounds, or irritated skin.
Oo not apply to excessively sunburned skin
Do not apply under clothing.
Apply sparingly around ears.
Do
STORAGE AND DISPOSAL
STORAGE: Store in a cool, dry place out of the reach of children. Keep away from
heat, sparks and open flame.
DISPOSAL. Oo not reuse empty container Discard in trash,
IF EMPTY' Do not reuse this container Place in trash or offer for recycling if available
IF PARTLY FILLED: Call your local solid waste agency or 1-800-528-9377 for disposal
instructions Never place unused product down any indoor or outdoor drain
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EPA REGISTRATION NUMBER: 39967-50
EPA ESTABLISHMENT NUMBER:
LANXESS
INTERNATIONAL 703-527-3387
Net Contents:
Lot No.:
LANXESS Coiporation
111 ft IDC Park West Drive • Pittsburgh. PA 15275-1112
LABEL TEXT DATE 12/19/06
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-------
LANXESS Corporation
Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
73 of 168
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LANXESS Corporation
Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
74 of 168
saltigo
customized competence
Dr. B-Koch
Saltigo GmbH, Leverkusen,
Germany
phone: ++49/214/30-43872
KBR 3023 ALL-FAM.INSECT REPELL. CREAM
MUS
Lot.Nr.: XKOC 00736
Auftr.Nr.: 7700011363 / 10 / 1
A company of the *
LANXESS 9ross: 168'3g net: 14°9 tare: 28/3g
Group Art.Nr.: 56154780
saltigc
Dr. B-Koch
Saltigo GmbH, Leverkusen,
Germany
phone: ++49/214/30-43872
customized competence
KBR 3023 ALL-FAM.INSECT REPELL.SPRAY MUS
Lot.Nr.: XKOC 00738
:ompany of the
Auftr.Nr.: 7700011363/ 20/1
MESS gross: 121g net: lOOg tare: 21g
°up Art.Nr.: 56115181
-------
LANXESS Corporation
Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
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Test Substance Information*
LANXESS CORPORATION
Date Shipped: 2009.09.16. Quantity Shipped: 560g
Test Substance: 56154780
Product Name: KBR 3023 All-FAMILY INSECT REPELLENT CREAM
CAS #: of the Active Ingredient 119515-38-7
Source: Saltigo GmbH. Building O 18. 51369 Leverkusen. Germany
Batch / Lot / Reference No.: XKOC 00736
Secondary Reference No.:
Appearance: white cream
% Active Ingredient (COA) / Date of Analysis: mean value:20.5% KBR 3023 / 2009-09-10
Expiration Date: 2011-07-09
Analysis Reference Number: Biogenius Mo 3830
Storage Conditions: store at temperature not more than 30°C
Room Temperature:_x Refrigerator: Freezer: Light Sensitive:
Safety Information - Attach copy of MSDS or list known information:
Hazards -
Health & Safety Data -
* This questionnaire should be completed and shipped with all materials to be used for testing. This requested
information is needed for implementation of GLP studies and to protect personnel conducting studies. The sponsor
is required to maintain this technical information / data in order to comply with the GLP regulations.
-------
LANXESS Corporation
Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
76 of 168
Test Substance Information*
LANXESS CORPORATION
Date Shipped: 2009.09.16 Quantity Shipped: 5OOg
Test Substance: 56115181
Product Name: KBR 3023 All-FAMILY INSECT REPELLENT SPRAY
CAS #: of the Active Ingredient 119515-38-7
Source: Saltigo GmbH. Building O 18. 51369 Leverkusen. Germany
Batch / Lot / Reference No.: XKOC 00738
Secondary Reference No.:
Appearance: clear solution
% Active Ingredient (COA) / Date of Analysis: mean value:21.5% KBR 3023 / 2009-09-18
Expiration Date: 2010-09-11
Analysis Reference Number: Biogenius Mo3829
Storage Conditions: store at temperature not more than 30°C
Room Temperature:_x Refrigerator: Freezer: Light Sensitive:
Safety Information - Attach copy of MSDS or list known information:
Hazards -
Health & Safety Data -
* This questionnaire should be completed and shipped with all materials to be used for testing. This requested
information is needed for implementation of GLP studies and to protect personnel conducting studies. The sponsor
is required to maintain this technical information / data in order to comply with the GLP regulations.
-------
LANXESS Corporation
CONFIDENTIAL
Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
77 of 168
BioGenius
Test Facility:
BioGenius GmbH
TeehnoiogiePark
Building 56
Fried rich-Ebert-Stra fie
51429 Bergisch Gladbach, Germany
Date : 2009-09-11
No. CoA: Mo3830 - RT - 0 weeks
Certificate of Analysis
Study No.
Sponsor
Test Item
Product No,
Batch No.
Interna! Product ID
Production Date
Date of Analysis
Storage Conditions
Test Time
Test Method
Retest Date
Mo3830
Saltigo GmbH
KBR 3023 All Family Insect Repellent Cream 20 %
56154780
XKOC 00736
SGO001 /0014#1 #1
2009-08-11
2009-09-10
room temperature
start
M01166-01
2010-09-11
Test
Requirement
Result
f%]
I%]
1.
Content (HPLC-ESTD )
1.1
Saltidin (KBR 3023)
19,0-21.0
20.5
This analysis was conducted in compliance with the Principles of Good Laboratory Practice
(GLP). A reserve sample of the test item will be retained at the test facility of BioGenius GmbH
according to GLP requirements.
Study Director: rle>o€\ - (( ~ ^
Date Maria Teresa Garcia
F-D-015 Certificate of Analysis
Page 1 /1
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LANXESS Corporation
CONFIDENTIAL
Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
78 of 168
Test Facility;
BioGenius GmbH
TechnologiePark
Building 56
F ried rich-Ebert-Stra He
51429 Bergisch Gladbach, Germany
Date : 2009-09-11
# BioGenius
No. CoA: Mo3829 - RT - 0 weeks
Certificate of Analysis
Study No.
Sponsor
Test Item
Product No,
Batch No,
Internal Product ID
Production Date
Date of Analysis
Storage Conditions
Test Time
Test Method
Retest Date
Mo3829
Saltigo GmbH
KBR 3023 All Family Insect Repellent Spray 20 %
56115181
XKOC 00738
SG0001/0013#1#1
2009-08-18
2009-09-10
room temperature
start
M01166-01
2010-09-11
Test
Requirement
Result
[%]
[%]
1.
Content (HPLC-ESTD )
1.1
Saltidin {KBR 3023)
19.0-21.0
20.5
This analysis was conducted in compliance with the Principles of Good Laboratory Practice
(GLP). A reserve sample of the test item will be retained at the test facility of BioGenius GmbH
according to GLP requirements.
Study Director: 'Zgos-oS-L
Date MartaTSrisa Garcia
F-D-015 Certificate of Analysis
Page
1
/1
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LANXESS Corporation Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
79 of 168
LANXESS CORPORATION/Saltigo GMBH
Test Material Shipment
Chain-Of-Custody
Sent To: _ Scott P. Carroll. Ph.D.
Date Sent: 16.09.2009
Address: Carroll-Loye,Biological Research, 711 Oak Avenue, Davis, CA 95616 USA
Signature:
Date:
^OOc7 - /(o
Description Of Shipment
Test Substance
Batch / Lot /
Reference No.
Amount
Number of
Containers
Container Type
KBR 3023 ALL-FAMILY INSECT
REPELLENT CREAM
XKOC00736 (batch
Nr)
56154780 (article code)
560ml
4
Plastic
container
KBR 3023 ALL-FAMILY INSECT-
REPELLENT SPRAY
XKOC00738 (batch
Nr)
56115181 (article code)
500ml
5
Plastic
container
Received By: t
£ (^'n9 r» i
J Date: '
Do ° ^
2 oof
Signature: ^>
Condition at Receipt: ^
b/e k
Comments:
Please return copy of the Chain-of-Custody to:
Stan Oslosky
LANXESS Corporation
Materials Protection Products
-------
LANXESS Corporation
Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
Carroll-Loye Biological Research
80 of 168
Oak Avenue Davis, California Tel (530) 902-8267 htto://www
CHAIN-OF-CUSTODY, MATERIALS RECEIVED
Sponsor reference (Study #): I—^ ^ ^
Date Received: i O^oLe-r 2001
Courier: (~eJ
Courier delivery information: s~ r\af)r>*ei (
¦r-ry /o
Vendor/Source: /~&/vx£*S
Vendor Shipment ID Number:
CZfyendor Packing List Received?:
(ZJ Study Monitor notified by email that materials have been received (if appl.)?:
Sight (Label) Inventory of Materials Received: ^ 1°^
Name (description): Code no. Lot fhatrh\ no Quantity
| v
(ri 7 phs-b'c
jUfci'°22 AU-Family si"5a{ X>c0C 00711 ~ S*> "I
sffiA/ Co«hi
Deviations of Sight Inventory from Packing List?:
f\fP
Other (e.g., notes on condition, references to information recorded
elsewhere):
Signature of Custodian, date:
Management Approval:
/ I (?cMer ^cOf
Da,e ft ^7 ^
Sianature
Materials check-in chain of custody v2 Page 1 of 1 5/19/09 3:08 PM
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LANXESS Corporation Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal 81 of 168
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
Carroll-Loye Biological Research
711 Oak Avenue Davis, California 95616 Tel (530)902-8267 http://www.carroll-love.com/
Research Notes
CLBR Project I.D.#i.A|X- QD^
Date: 3/ ^ 2-a D
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Signed
Q *~j$ >
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LANXESS Corporation Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
82 of 168
ouiiiuinia a if lasiccu - iuu i/so/cu - cuiupe
SAFETY DATA SHEET
KBR 3023 ALL-FAM.INSECT REPELLENT CREAM
saltigo
customized competence
A company of the LANXESS Group
56154772
1. Identification of the substance/preparation and of the
company/undertaking
Identification of the substance or preparation
Product name : KBR 3023 ALL-FAM.INSECT REPELLENT CREAM
Use of the : Repellent
substance/preparation
Company/undertaking identification
Supplier/Manufacturer : Saltigo GmbH
51369 Leverkusen, Germany
Phone: +49 214 30 65109
Fax: +49 214 30 55787
E-mail: infosds@lanxess.com
Emergency telephone number : +49 214 30 99300 (Sicherheitszentrale Chemiepark Leverkusen)
2. Composition/information on ingredients
Preparation of
sec-butyl 2-(2-hydroxyethyl)piperidine-1-carboxylate CAS No.: 119515-38-7 ELINCS No.: 423-210-8
Substance/preparation : Preparation
Ingredient name
CAS
number
%
EC Number
Classification
Perfume floral 12889G
0.5
N; R51/53
* Occupational Exposure Limit(s), if available, are listed in Section 8
3. Hazards identification
The preparation is classified as dangerous according to Directive 1999/45/EC and its amendments.
Physical/chemical hazards : Flammable.
See section 11 for more detailed information on health effects and symptoms.
4. First aid measures
First aid measures
If inhaled, remove to fresh air. If breathing is difficult, give oxygen.
If not breathing, give artificial respiration. Obtain medical attention.
Wash out mouth with water. If affected person is conscious, give a
copious amount of water to drink. Seek medical attention.
Wash skin thoroughly with soap and water or use recognised skin
cleanser.
In case of contact with eyes, rinse immediately with a copious
amount of water. Seek medical attention.
See section 11 for more detailed information on health effects and symptoms.
Date of issue : 7/19/2006 Page: 1/5
Inhalation
Ingestion
Skin Contact
Eye contact
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LANXESS Corporation Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
83 of 168
KBR 3023 ALL-FAM.INSECT REPELLENT CREAM 5615477210.02
5. Fire-fighting measures
Extinguishing media
Special exposure hazards
Hazardous thermal
decomposition products
Special protective
equipment for fire-fighters
In case of fire, use water spray (fog), foam, dry chemical or C02
extinguisher or spray.
Flammable liquid and vapour. Vapour may cause flash fire.
Vapours may accumulate in low or confined areas, travel a
considerable distance to a source of ignition and flash back. Runoff
to sewer may create fire or explosion hazard.
These products are carbon oxides (CO, C02), nitrogen oxides (NO,
N02...).
Fire fighters should wear appropriate protective equipment and self-
contained breathing apparatus (SCBA) with a full face-piece
operated in positive pressure mode.
6. Accidental release measures
Personal Precautions
Environmental precautions
Methods for cleaning up
Immediately contact emergency personnel. Eliminate all ignition
sources. Keep unnecessary personnel away. Use suitable
protective equipment (Section 8). Do not touch or walk through
spilled material.
Avoid dispersal of spilled material and runoff and contact with soil,
waterways, drains and sewers.
If emergency personnel are unavailable, contain spilled material.
For small spills add absorbent (soil may be used in the absence of
other suitable materials) and use a non-sparking or explosion proof
means to transfer material to a sealed, appropriate container for
disposal. For large spills dike spilled material or otherwise contain
material to ensure runoff does not reach a waterway. Place spilled
material in an appropriate container for disposal.
7. Handling and storage
Handling
Storage
Keep container closed. Use only with adequate ventilation. Keep
away from heat, sparks and flame. To avoid fire or explosion,
dissipate static electricity during transfer by earthing and bonding
containers and equipment before transferring material. Use
explosion-proof electrical (ventilating, lighting and material handling)
equipment.
Store in a segregated and approved area. Keep container in a cool,
well-ventilated area. Keep container tightly closed and sealed until
ready for use. Avoid all possible sources of ignition (spark or flame)
Packaging materials
Recommended
Use original container.
8. Exposure controls/personal protection
Exposure limit values
Exposure controls
Occupational exposure
controls
Respiratory protection
Hand protection
Eye protection
Skin protection
Not available.
Provide exhaust ventilation or other engineering controls to keep the
airborne concentrations of vapours below their respective
occupational exposure limits. Ensure that eyewash stations and
safety showers are close to the workstation location.
No special measures required.
No special measures required.
No special measures required.
No special measures required.
Date of issue
7/19/2006
Page: 2/5
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Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
84 of 168
KBR 3023 ALL-FAM.INSECT REPELLENT CREAM 5615477210.02
9. Physical and chemical properties
General information
Appearance
Physical state : Liquid.
Important health, safety and environmental information
Boiling point : >35°C
Flash point : Closed cup: 23 - 61 °C
Vapor pressure : <1100 hPa (20°C)
Density : 0.98 - 1 kg/I
Solubility : Soluble in cold water
10. Stability and reactivity
Stability : The product is stable.
Materials to avoid : Flammable liquid and vapour. Vapour may cause flash fire.
Vapours may accumulate in low or confined areas, travel a
considerable distance to a source of ignition and flash back. Runoff
to sewer may create fire or explosion hazard.
11. Toxicological information
Potential acute health effects
Inhalation :
No known significant effects
or
critical
hazards
Ingestion :
No known significant effects
or
critical
hazards
Skin Contact :
No known significant effects
or
critical
hazards
Eye contact :
No known significant effects
or
critical
hazards
Potential chronic health effects
Carcinogenicity :
No known significant effects
or
critical
hazards
Mutagenicity :
No known significant effects
or
critical
hazards
Reproductive toxicity :
No known significant effects
or
critical
hazards
Over-exposure sians/svmptoms
Inhalation :
No known significant effects
or
critical
hazards
Ingestion :
No known significant effects
or
critical
hazards
Skin :
No known significant effects
or
critical
hazards
Remarks :
Ames-test: negative
Micronucleus test: no clastogenic effect, (sec-butyl 2-(2-
hydroxyethyl)piperidine-1-carboxylate)
12. Ecological information
Other adverse effects : No known significant effects or critical hazards.
Other adverse effects : Not available.
Special remarks on the
products of biodegradation
13. Disposal considerations
Methods of disposal : Examine possibilities for re-utilisation. Product residues and
uncleaned empty containers should be packaged, sealed,labelled,
and disposed of or recycled according to relevant national and local
regulations. Where large quantities are concerned, consult the
supplier. When uncleaned empty containers are passed on, the
recipient must be warnedof any possible hazard that may be caused
by residues. For disposal within the EC, the appropriate code
according to the European Waste List (EWL) should be used. It is
Date of issue : 7/19/2006 Page: 3/5
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Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
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KBR 3023 ALL-FAM.INSECT REPELLENT CREAM 5615477210.02
among the tasks of the polluter to assign the waste to waste codes
specific to industrial sectors and processes according to the
European Waste List (EWL).
Hazardous waste : The classification of the product may meet the criteria for a
hazardous waste
14. Transport information
Regulation
UN
number
Proper shipping
name
Class
Packing
group
Label
Additional
Information
ADR/RID
UN1993
FLAMMABLE
LIQUID, N.O.S.
(CONTAINS
ETHANOL)
3
III
Hazard
identification
number
30
Limited guantitv
LQ7
GGVSE
UN1993
FLAMMABLE
LIQUID, N.O.S.
(CONTAINS
ETHANOL)
3
III
Hazard
identification
number
30
Limited guantitv
LQ7
ADNR
UN1993
FLAMMABLE
LIQUID, N.O.S.
(CONTAINS
ETHANOL)
3
III
Hazard
identification
number
30
Limited guantitv
LQ7
IMDG
UN1993
FLAMMABLE
LIQUID, N.O.S.
(CONTAINS
ETHANOL)
3
III
•
Emergency
schedules (EmS)
F-E, _S-E_
I ATA
UN1993
Flammable liquid,
n.o.s. (CONTAINS
ETHANOL)
3
III
¦
Passenger Aircraft
309: 60 L
Cargo Aircraft
310: 220 L
Combustible
Flash point (Closed cup): 23 - 61°C
Keep separated from
foodstuffs
15. Regulatory information
EU Regulations
Classification and labelling have been performed according to EU directives 67/548/EEC,
1999/45/EC, including amendments and the intended use.
- Industrial applications.
Risk Phrases : R10- Flammable.
Safety Phrases : S3- Keep in a cool place.
Other EU regulations
Date of issue : 7/19/2006 Page: 4/5
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Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
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KBR 3023 ALL-FAM.INSECT REPELLENT CREAM 5615477210.02
16. Other information
Full text of R phrases
referred to in sections 2 and
3 - Europe
History
Date of printing
Date of issue
Date of previous issue
Version
: R10-Flammable.
R51/53- Toxic to aquatic organisms, may cause long-term adverse
effects in the aquatic environment.
: 7/19/2006
: 7/19/2006
: 6/7/2006
: 0.02
: Not available.
Prepared by
Notice to reader
The data given here is based on current knowledge and experience. The purpose of this
Safety Data Sheet is to describe the products in terms of their safety requirements. The above
details do not imply any guarantee concerning composition, properties or performance.
Date of issue
7/19/2006
Page: 5/5
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LANXESS Corporation Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
87 of 168
ouiiiuinia a if lasiccu - iuu i/so/cu - cuiupe
SAFETY DATA SHEET
KBR 3023 ALL-FAMILY INSECT REPELLENT SPRAY
saltigo
customized competence
A company of the LANXESS Group
56115173
1. Identification of the substance/preparation and of the
company/undertaking
Identification of the substance or preparation
Product name : KBR 3023 ALL-FAMILY INSECT REPELLENT SPRAY
Use of the : Repellent
substance/preparation
Company/undertaking identification
Supplier/Manufacturer : Saltigo GmbH
51369 Leverkusen, Germany
Phone: +49 214 30 65109
Fax: +49 214 30 55787
E-mail: infosds@lanxess.com
Emergency telephone number : +49 214 30 99300 (Sicherheitszentrale Chemiepark Leverkusen)
2. Composition/information on ingredients
contains
sec-butyl 2-(2-hydroxyethyl)piperidine-1-carboxylate CAS No.: 119515-38-7 ELINCS No.: 423-210-8
Substance/preparation : Preparation
Ingredient name
CAS
number
%
EC Number
Classification
Perfume floral 12889G
1
N; R51/53
* Occupational Exposure Limit(s), if available, are listed in Section 8
3. Hazards identification
The preparation is classified as dangerous according to Directive 1999/45/EC and its amendments.
Physical/chemical hazards : Flammable.
See section 11 for more detailed information on health effects and symptoms.
4. First aid measures
First aid measures
If inhaled, remove to fresh air. If breathing is difficult, give oxygen.
If not breathing, give artificial respiration. Obtain medical attention.
Wash out mouth with water. If affected person is conscious, give a
copious amount of water to drink. Seek medical attention.
Wash skin thoroughly with soap and water or use recognised skin
cleanser.
In case of contact with eyes, rinse immediately with a copious
amount of water. Seek medical attention.
See section 11 for more detailed information on health effects and symptoms.
Date of issue : 8/29/2006 Page: 1/5
Inhalation
Ingestion
Skin Contact
Eye contact
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LANXESS Corporation Study LNX-003: Efficacy Test of KBR 3023 (Picaridin, Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
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KBR 3023 ALL-FAMILY INSECT REPELLENT SPRAY 56115173/2
5. Fire-fighting measures
Extinguishing media
Special exposure hazards
Hazardous thermal
decomposition products
Special protective
equipment for fire-fighters
In case of fire, use water spray (fog), foam, dry chemical or C02
extinguisher or spray.
Flammable liquid and vapour. Vapour may cause flash fire.
Vapours may accumulate in low or confined areas, travel a
considerable distance to a source of ignition and flash back. Runoff
to sewer may create fire or explosion hazard.
These products are carbon oxides (CO, C02), nitrogen oxides (NO,
N02...).
Fire fighters should wear appropriate protective equipment and self-
contained breathing apparatus (SCBA) with a full face-piece
operated in positive pressure mode.
6. Accidental release measures
Personal Precautions
Environmental precautions
Methods for cleaning up
Immediately contact emergency personnel. Eliminate all ignition
sources. Keep unnecessary personnel away. Use suitable
protective equipment (Section 8). Do not touch or walk through
spilled material.
Avoid dispersal of spilled material and runoff and contact with soil,
waterways, drains and sewers.
If emergency personnel are unavailable, contain spilled material.
For small spills add absorbent (soil may be used in the absence of
other suitable materials) and use a non-sparking or explosion proof
means to transfer material to a sealed, appropriate container for
disposal. For large spills dike spilled material or otherwise contain
material to ensure runoff does not reach a waterway. Place spilled
material in an appropriate container for disposal.
7. Handling and storage
Handling
Storage
Keep container closed. Use only with adequate ventilation. Keep
away from heat, sparks and flame. To avoid fire or explosion,
dissipate static electricity during transfer by earthing and bonding
containers and equipment before transferring material. Use
explosion-proof electrical (ventilating, lighting and material handling)
equipment.
Store in a segregated and approved area. Keep container in a cool,
well-ventilated area. Keep container tightly closed and sealed until
ready for use. Avoid all possible sources of ignition (spark or flame)
Packaging materials
Recommended
Use original container.
8. Exposure controls/personal protection
Exposure limit values
Exposure controls
Occupational exposure
controls
Respiratory protection
Not available.
Provide exhaust ventilation or other engineering controls to keep the
airborne concentrations of vapours below their respective
occupational exposure limits. Ensure that eyewash stations and
safety showers are close to the workstation location.
Use a properly fitted, air-purifying or air-fed respirator complying
with an approved standard if a risk assessment indicates this is
necessary.Respirator selection must be based on known or
anticipated exposure levels, the hazards of the product and the safe
working limits of the selected respirator.
Date of issue
8/29/2006
Page: 2/5
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Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
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KBR 3023 ALL-FAMIL Y INSECT REPELLENT SPRA Y
56115173/2
Hand protection
Eye protection
Skin protection
Chemical-resistant, impervious gloves or gauntlets complying with
an approved standard should be worn at all times when handling
chemical products if a risk assessment indicates this is necessary.
Safety eyewear complying with an approved standard should be
used when a risk assessment indicates this is necessary to avoid
exposure to liquid splashes, mists or dusts.
Personal protective equipment for the body should be selected
based on the task being performed and the risks involved and
should be approved by a specialist before handling this product.
9. Physical and chemical properties
General information
Appearance
Physical state : Liquid.
Important health, safety and environmental information
Boiling point
Flash point
Density
Solubility
: >35°C
: Closed cup: 26°C
: 0.96 kg/I
: Easily soluble in cold water
10. Stability and reactivity
Stability : The product is stable.
Materials to avoid : Flammable liquid and vapour. Vapour may cause flash fire.
Vapours may accumulate in low or confined areas, travel a
considerable distance to a source of ignition and flash back. Runoff
to sewer may create fire or explosion hazard.
11. Toxicological information
Potential acute health effects
Inhalation :
No
known significant effects
or
critical
hazards
Ingestion :
No
known significant effects
or
critical
hazards
Skin Contact :
No
known significant effects
or
critical
hazards
Eye contact :
No
known significant effects
or
critical
hazards
Acute toxicity
Product/inaredient name Test
Result
Route
Potential chronic health effects
Carcinogenicity :
No
known significant effects
or
critical
hazards
Mutagenicity :
No
known significant effects
or
critical
hazards
Reproductive toxicity :
No
known significant effects
or
critical
hazards
Over-exposure sians/svmptoms
Inhalation :
No
known significant effects
or
critical
hazards
Ingestion :
No
known significant effects
or
critical
hazards
Skin :
No
known significant effects
or
critical
hazards
Species
Remarks
12. Ecological information
Other adverse effects
Other adverse effects
Special remarks on the
products of biodegradation
No known significant effects or critical hazards.
Not available.
Date of issue
8/29/2006
Page: 3/5
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KBR 3023 ALL-FAMILY INSECT REPELLENT SPRAY 56115173/2
13. Disposal considerations
Methods of disposal : Examine possibilities for re-utilisation. Product residues and
uncleaned empty containers should be packaged, sealed,labelled,
and disposed of or recycled according to relevant national and local
regulations. Where large quantities are concerned, consult the
supplier. When uncleaned empty containers are passed on, the
recipient must be warnedof any possible hazard that may be caused
by residues. For disposal within the EC, the appropriate code
according to the European Waste List (EWL) should be used. It is
among the tasks of the polluter to assign the waste to waste codes
specific to industrial sectors and processes according to the
European Waste List (EWL).
Hazardous waste : The classification of the product may meet the criteria for a
hazardous waste
14. Transport information
Regulation
UN
number
Proper shipping
name
Class
Packing
group
Label
Additional
Information
ADR/RID
UN1993
FLAMMABLE
LIQUID, N.O.S.
(CONTAINS
ETHANOL)
3
III
Hazard
identification
number
30
Limited auantitv
LQ7
GGVSE
UN1993
FLAMMABLE
LIQUID, N.O.S.
(CONTAINS
ETHANOL)
3
III
Hazard
identification
number
30
Limited auantitv
LQ7
ADNR
UN1993
FLAMMABLE
LIQUID, N.O.S.
(CONTAINS
ETHANOL)
3
III
Hazard
identification
number
30
Limited auantitv
LQ7
IMDG
UN1993
FLAMMABLE
LIQUID, N.O.S.
(CONTAINS
ETHANOL)
3
III
Emeraencv
schedules (EmS)
F-E, _S-E_
I ATA
UN1993
Flammable liquid,
n.o.s. (CONTAINS
ETHANOL)
3
III
• ¦
Passenaer Aircraft
309: 60 L
Carao Aircraft
310: 220 L
Combustible
Flash point (Closed cup): 26°C
Keep separated from
foodstuffs
Date of issue : 8/29/2006 Page: 4/5
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KBR 3023 ALL-FAMILY INSECT REPELLENT SPRAY 56115173/2
15. Regulatory information
EU Regulations
Classification and labelling have been performed according to EU directives 67/548/EEC,
1999/45/EC, including amendments and the intended use.
- Industrial applications.
Risk Phrases : R10- Flammable.
Safety Phrases : S3- Keep in a cool place.
S60- This material and its container must be disposed of as
hazardous waste.
Other EU regulations
16. Other information
: R10-Flammable.
R51/53- Toxic to aquatic organisms, may cause long-term adverse
effects in the aquatic environment.
: 8/29/2006
: 8/29/2006
: No Previous Validation
: 2
: Not available.
Full text of R phrases
referred to in sections 2 and
3 - Europe
History
Date of printing
Date of issue
Date of previous issue
Version
Prepared by
Notice to reader
The data given here is based on current knowledge and experience. The purpose of this
Safety Data Sheet is to describe the products in terms of their safety requirements. The above
details do not imply any guarantee concerning composition, properties or performance.
Date of issue
8/29/2006
Page: 5/5
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TOXICOLOGY PROFILE OF KBR 3023 (page 1 of 2)
The toxicological profile of KBR 3023 is well characterized. All toxicology data were
developed using the dermal route of exposure, the most relevant route based on the use
pattern of the product (insect repellent for dermal application). The rationale of product
development using the dermal route of exposure was considered at the suggestion of the
USEPA and in agreement with USEPA and Bayer/Miles. All study protocols, scientific
issues, methodology for dermal dosing for extended periods of time and rationale for
dose selection were discussed with the EPA. Agreements regarding use of dermal route
of exposure were also made with BGA (German authorities) and Health & Welfare
Canada. A complete toxicology package required for the registration of an insecticide
including acute and subchronic neurotoxicity and metabolism studies was conducted.
Additionally, 14-day, 5-week and 14-week dietary feeding studies were conducted to
assess any hazard associated with hand-to-mouth transfer from dermal use of KBR 3023.
The highest dermal dose for long-term studies was 200mg/kg/day. Dermal absorption
studies were conducted both in rats and human volunteers to assess the human risk on the
absorbed dose analysis associated with the consumer use of the product.
KBR 3023 and its formulated products have low acute toxicity by oral, dermal or
inhalation routes of exposure. They were not irritating to the skin nor sensitizers in the
animal studies. A slight to moderate ocular irritation was observed in the animal studies.
KBR 3023 has no demonstrable neurological or developmental toxicity by dermal route
of exposure. KBR 3023 shows no evidence of genotoxicity. Subchronic dermal dosing at
500 mg/kg/day produced no clinical pathology and only slight histopathology changes in
the liver, and all changes were reversible after four weeks. Chronic dermal dosing in
mice, rat and dogs produced no evidence of adverse toxicity changes and it was not
oncogenic in mice or rats. In the oral toxicity studies (14-day, 5-weeks and 14-weeks),
only kidney effects were seen in the male rats and were attributed to Obu globulin
accumulation. The toxicology profile by oral route of exposure did not reveal any new
targets compared to the dermal route. Cumulative effects were not evident in dermal
or oral studies. The systemic NOAEL in the subchronic studies by oral route were similar
(308mg/kg/day for oral/200mg/kg/day- the highest dose tested).
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TOXICOLOGY PROFILE OF KBR 3023 (page 2 of 2)
The safety of KBR 3023 was further established by dermal absorption studies conducted
in rats and in human volunteers. The dermal absorption study in human volunteers
showed that KBR 3023 is poorly absorbed through the human skin. Only 1.66% of the
material (AI) was absorbed compared to 19 - 60% for the rat. A conservative dermal
penetration factor of 11.5 was used by the EPA for risk assessment. The excretion half-
life in humans was 8.2 hours compared to 23.3 hours in the rat. The qualitative pattern of
excretion is similar in humans and rats (primary urinary excretion) with similar
metabolites. KBR 3023 has good skin feel and is odorless. No significant complaints
have been reported over years of use.
In summary:
KBR 3023 has complete toxicology data supported by State-of-the-Art testing
KBR 3023 showed no foreseeable public health risks, including in children and is
alternative to DEET
It has no end points of concern
Low acute toxicity
No irritant or sensitizing potential
No specific effects in rats or dogs in short-term and long-term studies
NOAEL = 200 mg/kg (dermal); NOAEL = 308 mg/kg (oral)
Not mutagenic
Not tumorigenic
No effects on reproduction
No neurotoxicity
No photo-sensitisation or irritation
It is poorly absorbed through the human skin
Does not bio-accumulate and is rapidly excreted
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Carroll-Loye Biological Research
711 Oak Avenue Davis, California Tel (530) 902-8267 http://www.carroll-love.com/
CHAIN-OF-CUSTODY, MATERIALS RECEIVED
l_ fjX ' 003
Sponsor reference (Study #):
Date Received: z7 I^OtQ
Courier: pej
Courier delivery information: {f-
T 4- 7Uci 7*7
Vendor/Source: c.pc
Vendor Shipment ID Number: MA
~ Vendor Packing List Received?:
~ Study Monitor notified by email that materials have been received (if appl.)?: w
Sight (Label) Inventory of Materials Received:
Name (description): Code no. Lot (batch) no. Quantity
^ 100 1^ 5<-« pelts',-f
ua or !¦( Ay+pl}
a
Deviations of Sight Inventory from Packing List?:
yk
Other (e.g., notes on condition, references to information recorded
elsewhere):
Signature of Custodian, date:
Management Approva,:s|gna|ur8^^^ ^ ^ [
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Carroll-Loye Biological Research
711 Oak Avenue Davis, California Tel (530) 902-8267 http://www carroll-lovs mm/
CHAIN-OF-CUSTODY, MATERIALS RECEIVED
L /V> - 003
Sponsor reference (Study #):
Date Received: *2.0\0
Courier: FeJ £x
Courier delivery information: 5^4
w . lo a Hoic $frc>
Vendor/Source: opc
Vendor Shipment ID Number: a/A
~ Vendor Packing List Received?:/^-
CEfStudy Monitor notified by email that materials have been received (if appl.)?:
Sight (Label) Inventory of Materials Received:
Name (description): Code no. Lot (batch) no. Quantity
}^Q(? Xy r^Je i
/^v j 5"oo cen f
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Carroll-Loye Biological Research
711 Oak Avenue Davis, California 95616 Tel (530)902-8267 http://www.carroll-loye.com/
This note describes handling, storage conditions, and identification of ticks received from CDC-Atlanta
on January 7 and January 20, 2010.
Ticks were held at laboratory room temperature (ca. 20°C). They were kept in the screen top vials in
which they were shipped, in lightly hydrated zip-closure plastic bags (humidity ca. 80-100%).
Ticks were identified with the keys and illustrations in the following two references: Durden and
6 © T' 31 /VV*?L M
Keirani (199), Yunker et al. (1986)
Research Notes
CLBR Project I.D.# LNX-003
Date: February 28. 2010
Signed
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Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
1
2
3 EFFICACY TEST PROTOCOL LNX-003
4 ©2009 by Scott Prentice Carroll, Ph.D.
5
6
7 EFFICACY TEST OF KBR 3023 (PICARIDIN; ICARIDIN) -
8 BASED PERSONAL INSECT REPELLENTS (20% CREAM
9 AND 20% SPRAY) WITH TICKS UNDER LABORATORY
10 CONDITIONS
11
12
Original Date: 27 July 2009
Initial IRB Approval: 30 July 2009
Federal EPA/HSRB Review: Pending
California EPA Review: Pending
Ammendments: Pending
Final IRB Approval: Pending
Standards Applied U. S. EPA Good Laboratory Practice Regulations
(40 CFR 160); 40 CFR 26 subparts K, L and M;
F1FRA § 12(a)(2)(P); California State EPA
Department of Pesticide Regulation study
monitoring (California Code of Regulations Title
3, Section 6710).
13
14
15
16
17 SYNOPSIS
18
19 This tick repellent study was commissioned by the sponsor to provide efficacy
20 data for purposes of US/EPA registration. The test materials, based on the active
21 ingredient Picaridin, consist of KBR 3023 All-family Insect Repellent Cream
22 (20% Cream) and KBR 3023 All-Family Insect Repellent Spray (20% Pump
23 Spray).
24
25 KBR 3023 (Icaridin; Picaridin) is a new generation of synthetic repellent
26 developed as an alternative to DEET. It was developed by molecular modeling
1
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27 techniques. From more than 800 substances, KBR 3023 showed the best
28 performance regarding efficacy against a variety of arthropods (Boeckh, et al.,
29 1996) and had the most desired attributes regarding safety, low skin penetration,
30 and compatibility with skin, and plastic materials. It was developed by Bayer and
31 is now owned by Saltigo GmbH (Lanxess Group) and in the USA it is handled by
32 Lanxess Corporation (previously a Division of Bayer Corporation).
33
34 Icaridin (US EPA Registration Name Picaridin), the current common name, was
35 developed under the Code Name KBR 3023 and the registered trade name
36 Saltidin™ (formerly Bayrepel™) and was sold under the Brand name Autan. The
37 chemical name for Icaridin is 1-PIPERIDINECARBOXYLIC ACID, 2-
38 (HYDROXY-ETHYL), 1- METHYLPROPYLESTER. However, the INCI
39 (International Nomenclature of Cosmetic Ingredients) name was given as
40 HYDROXY METHYL ISOBUTYL PIPERIDINE CARB. The product was
41 submitted to US EPA under the common name Picaridin. However, the common
42 name, Picaridin, was rejected by ISO (International Organization for Standards) as
43 it was not considered a pesticide. The common name Picaridin was also rejected
44 by WHO/INN (World Health Organization/International Non-proprietary Name)
45 but the common name, Icaridin, was accepted by WHO/INN
46
47 The study pursuant to this insect repellent efficacy protocol is intended to provide
48 data under the Data-Call-in requirements (EPA Reg. No. 3126-LRNO) of United
49 States Environmental Protection Agency Guideline OPPTS 810.3700.
50
2
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50
51
52
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54
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Investigator (Study Director):
Dr. Scott P. Carroll
Carroll-Loye Biological Research
711 Oak Avenue
Davis, CA 95616
530-902-8267
530-297-6081 (Facsimile)
spcarroll @ ucdavis. edu
http: //www. carroll-loye.com/
CV on file with Carroll-Loye Biological Research
Sponsor:
Stanley C. Oslosky, Head of Regulatory Affairs
LANXESS Corporation
111 RIDC Park West Drive
Pittsburgh, PA 15275-1112
Study Monitor:
G. K. Sangha, Ph. D.
Toxicology and Regulatory Affairs Consultant
GKS International, Inc.
11411 Porter Ranch Drive #105
Northridge, CA 91326
913-638-3968
IRB:
Independent Investigational Review Board, INC.
6738 West Sunrise Blvd. Suite 102
Plantation Florida 33313
954-327-0778
Quality Assurance Unit:
Dr. William Donahue
Sierra Research Laboratories
5100 Parker Road
Modesto, CA 95357
209-521-6380
CV on file with Carroll-Loye Biological Research
3
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90
91
92
93
94 TABLE OF CONTENTS
95
96
97
Protocol
1
98
99
Protocol Approval Signatures
27
100
101
Appendices:
102
1)
IRB Approval, Informed Consent and Subject's Bill of Rights
28
103
2)
Sample data recording forms
39
104
3)
Subject training documents
51
105
4)
Draft product labels
52
106
5)
Test Material(s) MSDS and Toxicology Profile(s)
54
107
6)
Investigator Certificate of human subject protection
66
108
training
109
V)
Documentation of Disease-Free status of laboratory
68
110
reared tick populations
111
8)
Physical Plan for CLBR Laboratory
69
112
9)
Record of PI-IRB correspondence
70
113
114
115
116
4
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117
118
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131
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133
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149
150
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152
153
154
155
156
157
1 Justification for Research
1.1 Objective of Research and Endpoints:
The objective is to determine the duration and efficacy of the Test Material(s),
when applied at a typical consumer dose, in repelling the following tick
species:
Deer tick - Ixodes scapularis
American dog tick - Dermacentor variabilis
Ticks are certified disease-free laboratory-reared descendents of field caught
adults. Methods employed for disease exclusion are described in Appendix 7.
Ticks are reared at approximately 25°C under conditions of high humidity and
long day length. Laboratory nymphs are active in questing and feeding
between approximately 2 weeks and one year post-eclosion (molt). Ticks will
typically be between 6 and 12 weeks post-eclosion for testing.
Individual subject dosage will be determined using the standard application
rates from the dosimetiy completed for related Carroll-Loye Biological
Research (CLBR) studies with the Test Material(s).
For both species, efficacy and duration will be measured as Complete
Protection Time, or CPT, defined herein as the time between application of test
material and the First Confirmed Crossing of an actively foraging tick from the
untreated skin surface of a subject's hand 3 cm or more into the treated
forearm skin area. A 'First Confirmed Crossing' (FCC) is that which is
followed by another within 30 minutes.
The endpoint will be the time of failure expressed as the time of the FCC fbi^
each specie for each subject.
The resulting data set will be suitable for submission to US/EPA to comply
with the conditions of the registration.
Shawn King User 10/20/09 10:20 AM
Deleted: E
Shawn King User 9/10/09 9:44 AM
Deleted: first confirmed
1.2 Importance of the Research
Insect repellents are commonly used in the United State to reduce both nuisance
biting and disease risk. Traditional DEET-based repellents are highly effective, but
are cosmetically inferior and relatively more likely to produce mild to serious side
5
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158 effects. Picaridin-based repellents are cosmetically superior and have a better
159 safety profile. They have been marketed around the world for a decade, but only
160 recently in the US, where they were introduced in 2005. The US Centers for
161 Disease Control (CDC) has acknowledged the existence of substantial consumer
162 interest in new and effective insect repellent products, including the choice of a
163 variety of formulations, delivery systems, and concentrations of active ingredient.
164 Of the three DEET-alternatives currently considered by CDC to have public health
165 value, Picaridin probably has the highest broad-spectrum efficacy. However, few
166 Picaridin products are currently available to US consumers. US EPA has requested
167 new, US-based efficacy data as condition of registration for the test products. The
168 purpose of this study is to provide those efficacy data. The information will also be
169 used in product labeling.
170
171 Human subjects are required because they represent the target system for the
172 test material, and sufficiently reliable models for repellency testing have not
173 been developed. Repellent efficacy can only be measured in the presence of
174 biting arthropods. Prevention of tick bites and the reduction of the risks of
175 contracting tick-borne diseases are of substantial interest to U.S. consumers
176 and public health professionals. Thus, there is substantial merit in its further
177 study and the development of new repellent products toward unconditional
178 registration by the U.S. EPA.
179
180
181 1.3 Balance of Risks and Benefits:
182
183 The study-associated risks are of five types: exposure to the test materials
184 themselves, exposure to biting arthropods, possible exposure to vectors of
185 arthropod-borne diseases, physical stress from test conditions, and
186 psychological stress associated with a breach in confidentiality concerning
187 pregnancy test results. As described below, subject health and safety are
188 unlikely to be impacted by any study-associated risks during or after the study.
189 Subject health and safety are also safeguarded by medical monitoring,
190 assistance, and management.
191
192 1.3.1 Risks from Exposure to Test Material(s)
193 The repellent active ingredient has a low acute and chronic risk profile (§2),
194 established both through experimentation and through a history of consumer
195 use. EPA regulates use of inert ingredients (also termed "other" ingredients) by
196 toxicology profiles in animal tests and by their inclusion in EPA lists of
197 "approved" other ingredients. The insect-repellent products proposed for
198 testing have been tested on animals for potential oral and dermal toxicity (§2).
6
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199
200
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234
235
236
237
238
239
The active ingredient (Picaridin) has an extensive toxicity data file, has been
previously registered by EPA and has a positive safety record in consumer use.
Subjects with known allergic reactions to insect repellents and common
cosmetics are excluded from participating (§3.3.2). Risks associated with
inhalation and ingestion would only ensue from serious mishandling by
subjects, a scenario that the study methods preclude.
1.3.2 Risks from Exposure to Biting Arthropods
The risk of skin reactions to a bite is reduced by excluding candidate subjects
who are aware of having a history of such reaction (§3.3.2). In addition,
subjects will be trained to quickly remove any tick that attempts to bite them,
before penetration or injection of saliva. Stopping Rules (§4.7.6) and Medical
Management practices (§1.3.6) specify removing any subject from the study
when that subject has received confirming crossings for both tick species or the
subject shows signs of reacting to a bite or to contact with ticks. Subjects will
be teamed with others in a group for mutual observation and experienced
technical personnel will be present at all times for assistance.
Within 30 days before repellent efficacy testing, subjects will be trained by
technical personnel in handling ticks in the laboratory (Appendix 3). Subjects
will learn how to manipulate ticks with fine paintbrushes, place them on their
own forearms, observe and quantify tick movement on their aims, and dispose
of used ticks. This training will be documented. This 'hands-on' experience
will assist subjects in collecting data accurately and handling ticks safely
during the repellent efficacy trial.
The training procedure also serves to verify the subject's attractiveness to ticks
in the study. If during subject training any qualifying tick (as defined in $4.7.3)
per five exposures of each species fails to cross on the subject, the subject will
be asked to withdraw^
1.3.3 Risks from Exposure to Disease Vectors
Our laboratory-reared tick populations are certified disease free (Appendix 7).
There is no risk of tick-vectored diseases for subjects in our laboratory tests.
1.3.4 Physical Stress in the Test Environment
Physical stresses on subjects are minimized by careful preparation and
provisioning. Lab testing environments are temperature and humidity
controlled to remain well within human comfort zones. The testing area is
maintained free of tripping hazards, and an adjacent rest area is stocked with
Shawn King User 9/8/09 1:49 PM
Deleted: This procedure also serves to verify
the subject's attractiveness to ticks in the
study.
7
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240 food, water, and beverages. Seating is provided for all subjects. Private
241 bathroom facilities are also provided on site.
242
243 1.3.5 Maintaining Privacy of Pregnancy Test Results
244 Section 3.3.2 lists the exclusion criterion detailing pregnancy test procedures.
245 Results of a subject's test are only observed by one female CLBR staff
246 technician and never recorded to minimize stress on a female subject testing
247 positive, and minimize the possibility that other staff or subjects may become
248 aware of the results of that test.
249
250 1.3.6 Medical Monitoring. Assistance, and Management
251 Subjects are clearly and repeatedly informed that they may remove themselves
252 for any reason from the study at any time, without penalty to their
253 compensation. All subjects are asked to contact the Study Director and a
254 physician of their own choice at any time should they develop a rash (a
255 delayed hypersensitivity reaction) within 7 days of the conclusion of the test
256 day.
257
258 On the test day, staff will immediately communicate all subject concerns about
259 health, safety, or comfort to the Study Director for assessment. The Study
260 Director will also assess skin condition of affected subjects should any bites
261 inadvertently occur during efficacy testing, or any subject reports any
262 discomfort in treated areas. Subjects are instructed to inform the Study
263 Director (i.e., the 'Principal Investigator'), or any other staff member if at any
264 time during the study a subject suffers a skin reaction, such as redness, edema,
265 itching or pain, or feels ill. Such subjects will be immediately withdrawn from
266 testing and tick exposure, and medical management will be implemented.
267 When a subject completes the study or is removed for any reason, treated skin
268 areas will be gently washed with clean water and mild soap, rinsed with a 35%
269 ethanol in water solution, then gently dried with a towel to remove test
270 materials.
271
272 When medical management is implemented, the Study Director will contact
273 the On-Call physician for the study and comply with the physician's
274 instructions. On the day of testing, a physician who has read the protocol and
275 discussed the research with the Study Director will be on call. Contact
276 information for the nearest medical facilities and maps from the test site to the
277 facilities will be prepared and on file before the day of testing. In unlikely
278 event of a Type 1 allergic reaction (anaphylaxis), we will contact 9-1-1 by
279 cellular or ground-line telephone and cooperate as instructed with emergency
280 personnel. Epi-Pens will be on-site. At least one qualified researcher will
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281 remain with the other test subjects if other researchers depart with an injured or
282 ill subject. We will be prepared to instruct emergency personnel on how to
283 reach our site via multiple routes. In addition, we will personally transport
284 affected persons to the nearest hospital if so advised by emergency personnel.
285 There is sufficient redundancy in personnel that in such a case subjects
286 remaining at the study site will still receive appropriate technical, scientific and
287 safety guidance.
288
289 Subjects may also request access to standard first aid materials (such as
290 bandages, antiseptics, and mild topical and oral antihistamines) and request
291 qualified first aid assistance at any time.
292
293 As part of Medical Management, the Study Director will record all benign and
294 adverse health observations.
295
296 1.3.7 Summary of Risks and Benefits
297 The combination of technical precautions and natural factors means that the
298 chances that any subject will contract disease, suffer an injury, or suffer a
299 severe reaction from a tick bite are extremely small.
300
301 Against these slight risks are balanced substantial and reasonably likely
302 benefits. The principle beneficiary will likely be the Sponsor, for whom new
303 data and new labeling will meet current US EPA registration standards.
304 Because EPA registration requires efficacy data, a test such as that proposed
305 here is the only path toward further product development, greater availability,
306 and increased consumer acceptance of new repellent formulations in the United
307 States. For the general public, tick-borne disease is of growing significance in
308 the United States and around the world where U.S. citizens are active.
309 Moreover, discomfort associated with nuisance biting restricts many work and
310 pleasure activities
311
312
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312
313 2 Test Material(s): Description and Control
314
315 The following table summarizes all information about the test material(s)
316 relevant to this study.
Test Materials as referred to in this Protocol:
Cream 2O'v
Spray 20%
Test Material name
(Picaridin cone.)
KBR 3032 All-Family Insect
Repellent ('ream (20'v )
KBR 3023 All-Family Insect
Repellent Spray (20%)
Manufacturer
FAXXI iSS ('orporation
LANXESS Corporation
Manufacturing
Standards Applied
Good Manufacturing Practice
standards, with records available
to FPA.
Good Manufacturing Practice
standards, with records available
to EPA.
T ranspoi't
Commercial Courier, express,
insulated container
Commercial Courier, express,
insulated container
Chain of Custody
Documented
Documented
Specific grav ity
0.98
0.96
Delivery system
I .otion
Pump Spray
Active ingredient(s)
('¦<)
Picaridin 20'v
Picaridin 20%
Inert ingredients
Proprietary, available to I "S 1 il'A
Proprietary, available to US EPA
Stability
Stable
Stable
Storage conditions
specified
Room temperature, max 30° C
(86° F)
Room temperature, max 30°
C (86° F)
Storage conditions
applied
Locking, closed cabinet at room
temperature (19-24°(') protected
from light and moisture sources
Locking, closed cabinet at room
temperature (19-24°C) protected
from light and moisture sources
Description of
cosmetic properties
White cream
Clear solution
NOAELs for
Picaridin
N( ).\FI. = 200 mg kg (dermal);
308 mg kg (oral)
NOAEL = 200 mg/kg
(dermal); 308 mg/kg (oral)
Irritation and
sensitization class
(Picaridin) No irritant or sensitizing
potential
(Picaridin) No irritant or
sensitizing potential
Hazard label
requirements
Substantial but temporary eye
injury. Do not get in eyes. Wash
thoroughly with soap & water after
handling, returning indoors, and
before eating, drinking, chewing
gum, or using tobacco. Discontinue
use and consult a doctor if irritation
or rash occurs; Flammable.
Moderate eye irritation, avoid
contact with eyes or clothing,
wash thoroughly with soap &
water after handling, returning
indoors, and before eating,
drinking, chewing gum, or using
tobacco. Flammable.
Reference materials
Sample labels in Appendix 4, page 52-53
MSDS and Toxicology documents in Appendix 5, page 54-65
319
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320 The sponsor is responsible for completing all toxicological screening,
321 compositional analysis, and stability studies for the test material(s) and
322 providing the results to Carroll-Loye Biological Research prior to providing
323 the test material(s) to Carroll-Loye.
324
325
326 3 Research Subjects: Recruitment, Screening, Consent, Privacy
327
328 3.1 Candidate Recruitment: Population, Sampling Frame, Representativeness
329
330 For reasons of practicality and control, we work with people associated the
331 community in which our business is located (Davis, CA). Davis is a university-
332 dominated community, and so the population demography differs somewhat
333 from non-university communities. Compared to the Population of Concern (the
334 US population - all potential repellent users), our sampling frame tends to
335 under-represent blacks and over-represent Asians. It is also young, well
336 educated, and slanted towards life science researchers and students.
337
338 Over time, we have developed a Volunteer Database of individuals who have
339 expressed interest in participating in future repellency tests, provided contact
340 information, and asked us to contact them. Initial recruiting is from this
341 database, then from word-of-mouth of volunteers. The size and composition of
342 the database varies over time as new individuals volunteer and old volunteers
343 move out of the Davis area, but is now typically over 100 individuals, with the
344 following average ethnic (self-identified) and gender distribution (averaged
345 over 3 years):
346
Male
52%
Female
48%
Caucasian
74%
Asian
12%
Hispanic
7%
Af ri can-Am eri can
4%
Arabic
3%
347
348 In general, about three-quarters of the subjects are age 20-40, with the
349 remainder between 40 and 55. Final composition is not determined until
350 enrollment is completed. The relevant demographics of the participants will be
351 reported.
352
353 Carroll (2006) reviewed the factors that influence the performance of insect
354 repellents and concluded that there is no a priori means of predicting an
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355 individual's attractiveness to a particular ectoparasite, or likely impact on a
356 repellency trial's data set. Several studies have indicated that individuals differ
357 in attractiveness to mosquitoes, for example, but individual attractiveness
358 rankings shift substantially among parasite taxa. Skin-emanated volatiles
359 influence attractiveness, as do skin temperature and absorption properties;
360 these factors may likewise influence repellent efficacy. Studies of gender, age,
361 race, hair color, complexion, weight, skin moisture, menses (females),
362 hairiness, and sweat have shown only gender to have significant effects on
363 individual attractiveness to mosquitoes. Though studies have shown that
364 sweating increases attractiveness to at least one mosquito species, it is not clear
365 whether individuals that sweat more than others, on average, tend to be more
366 attractive to mosquitoes. Two studies with adequate sample sizes found
367 females to be 25% less attractive to Aedes mosquitoes, while the other showed
368 them to be significantly less well protected against Anopheles mosquitoes by
369 deet - the opposite pattern. That difference is consistent with further findings
370 that the type of repellent used also interacts complexly with individual subjects
371 and mosquito species in determining efficacy. Nonetheless, while comparable
372 data are not available for ticks because gender effects seem most plausible, we
373 attempt to enroll similar numbers of males and female subjects.
374
375 On the other hand, it is clear that conditions of use strongly influence repellent
376 performance. We intentionally test under conditions of light, temperature and
377 humidity conducive to tick foraging behavior. Further, we expose subject
378 individuals as uniformly as possible to the ticks, and have them handle the
379 ticks in ways that minimally disrupt tick behavior. We also monitor subjects to
380 prevent exposure of treated areas to external moisture or abrasion.
381
382 Analogous to the summation for repellency, there are few clear patterns
383 permitting us to predict which individuals might be at relatively greater risk
384 from participating in this study. Pregnant and lactating women are excluded on
385 | general medical princip , and persons over age 55 are excluded due to
386 slightly elevated health risks from arthropod-borne diseases (see above), Deleted: ais
387 though the likelihood of contracting the causal agent during a repellent test is
388 very low.
389
390 Based on review of the scientific literature regarding individual differences in
391 repellent performance and attractiveness to ticks, we conclude that this study's
392 deviations from the ideal frame will not influence the representativeness of the
393 results, or their generalizability to the greater population. Lastly, because our
394 Volunteer Database cohort is comprised by individuals who regularly spend
395 time in outdoor setting (and thereby may have relatively frequent encounters
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396 with biting arthropods), this group is probably appropriate for insect repellent
397 users in general.
398
399
400
401
402 3.2 Candidate Recruitment Procedures
403
404 Recruitment for the Repellency Phase begins as soon as the test dates are
405 determined.
406
407 Potential candidates are initially contacted by phone from our Volunteer
408 Database and queried about interest and availability. Individuals are chosen
409 using a random number table to choose subject numbers from the database and
410 contacted. During the phone interview, we also inform potential candidates
411 that they are permitted to refer others to us by having them contact us.
412 Recruitment continues until the roster of subjects and alternates is full.
413
414
415 3.3 Candidate Screening
416
417 3.3.1 Inclusion Criteria, all subjects
418 Age: 18-55 years
419 Sex: Male/female
420 Race: Any race
421 Completed Consent Process (§3.4) including providing Written Consent
422 (defined as having read, initialed, dated and signed Informed Consent
423 Form and Experimental Subject Bill of Rights)
424 Language: Speak and read English
425
426 3.3.2 Exclusion criteria, all subjects:
427 1. Known to be hypersensitive to tick bites or exhibiting
428 hypersensitivity during test
429 2. Phobic of ticks
430 3. Known to be allergic to insect repellents or common cosmetics
431 4. Known to be sensitive or showing sensitivity to any of the test product
432 ingredients after application.
433 5. Poor physical condition.
434 6. Unwilling to submit to brief query about personal condition.
435 7. Use of insect repellent within one day preceding the efficacy test.
436 8. Unwilling to refrain from use of perfumed products, alcoholic beverages
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437
438
439 9.
440
441
442
443
444
445
446
447 10.
448
449 11.
450
451 12.
452 13.
453 | ,_
454
455 3.4 Obtaining Subjects' Consent
456
457 All candidates are screened or re-screened for suitability for each test in a
458 private, one-on-one conversation with the Study Director, at which time the
459 Exclusion Criteria (§3.3.2) are exercised by asking each candidate to address
460 them. It is explained to female candidates of child bearing potential that
461 pregnancy will be assessed directly on the day of any study visit in which
462 repellent will be applied.
463
464 The Study Director encourages candidates to ask questions and ask for
465 clarification at any time during the interview and in all activities that follow.
466 To candidates that pass screening, the Study Director describes the test purpose
467 in plain language (in English), and the procedures and comportment to be
468 followed are described. Candidates are then asked if they would like to retire
469 from consideration at that point. If they wish to remain in consideration, it is
470 emphasized that they may withdraw from the test at any time during the test
471 without penalty to their compensation. This freedom is especially re-
472 emphasized in cases in which considerable effort or expense has been required
473 to include a subject (e.g., travel from a distant site), to discourage the subject
474 from believing that the considerable effort or expense creates an added
475 obligation to participate.
476
or smoking after 9 PM the evening preceding the efficacy test and
throughout that test.
Known to be pregnant or lactating. Each female volunteer of child
bearing potential will self-check for pregnancy using an OTC test kit
provided by a technician on the day of any study visit in which repellent
will be applied or in which the subject will be exposed to ticks. Results
of each such test will be immediately verified by direct inspection by a
female technician experienced in making that assessment. Information
regarding pregnancy test results will be kept in confidence. Only
volunteers scored as nonpregnant will be allowed to participate.
Unable to deliver the test materials or nymphal ticks to own left and
right arms.
Unable to see nymphal ticks on skin or otherwise effectively monitor
them on skin.
Student or employee of the Study Director.
Does not regularly spend time in outdoor settings.
Shawn King User 10/20/09 10:45 AM
Deleted: 14. _ Withdraws from testing before
receiving a confirmed crossing, when the total
exposure duration is less than 90% of the mean
of subjects who did not withdraw, and when
not more than 2 of 10 subjects have so
withdrawn. If more that 2 of 10 subjects
withdraw prematurely, those with the briefest
participation will be replaced first. This
exclusion factor is not automatically invoked if
the Study Director ends exposures due to other
factors, such as darkness; in such cases the
data collected before termination may be
sufficient to meet the study goals. .
15. - Not attractive to target species. ,
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477 If the candidate indicates he or she wishes to proceed, the Study Director
478 provides a copy of this study's IRB-approved Informed Consent Form (ICF)
479 and State of California Department of Pesticide Regulation 'Experimental
480 Subjects' Bill of Rights' (BOR) for review (Appendix 1). The candidate is also
481 offered their own copy of the protocol itself, and supporting documents
482 (MSDSs, toxicology study results, compositional analysis of the Test
483 Materials, and training documents) for review. In a private session a senior
484 CLBR staff member certified in protecting human research participants by the
485 National Institute of Health (NIH), will read the ICF and BOR documents out
486 loud with the candidate, offering to take questions and answering any that
487 arise. The amount and form of compensation is described.
488
489 Candidates are again encouraged to ask any questions they have about the test,
490 which may include understanding its purpose more fully, understanding risks
491 and discomforts more fully, and understanding treatment and compensation for
492 injury more fully. While the majority of our subjects have worked with us on
493 an occasional basis for a number of years, we encourage them to personally
494 evaluate their interests and concerns about participation seriously each time.
495 We ask them not to sign on immediately but to give the situation due
496 consideration (normally at least one day, sometimes less for those who have
497 participated in multiple prior studies). Because most of the volunteers are
498 researchers and/or have advanced degrees in life sciences, or work directly
499 with or otherwise regularly encounter biting arthropods in infested habitats, we
500 regard their motivations and decisions to participate as being well considered
501 and well informed. Accordingly, we normally accept their decisions to
502 participate if they so choose following due consideration. Nonetheless, the
503 Study Director retains the final right to refuse participation to any candidate.
504
505 When all screening procedures are complete, the candidate is asked to sign,
506 initial, and date the ICF and BOR for this study, both of which are then
507 cosigned by a NIH certified staff member of Carroll-Loye. The candidate, now
508 a subject, is then asked to complete a contact and emergency medical form
509
510
511 3.5 Protecting Subjects'Privacy
512
513 Screening interviews are conducted in private and one-on-one. All written
514 records containing names, contact information, medical information, and
515 signatures are kept in a locked, fire-proof cabinet. Access to these files is
516 restricted to Carroll-Loye staff with the Study Director's permission. All
517 subjects are assigned a unique number to identify them on all data forms and to
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518 staff and other subjects during testing activities. Although many subjects
519 interact socially during the tests, and may voluntarily share names or other
520 personal information, subjects are never asked, required, or encouraged to do
521 so. Individual data will be entered into the computer for retention and analysis
522 with reference to individual number, not name. Records relating individual
523 names to individual numbers will be retained separately. The Study Director
524 will retain records indefinitely. Subjects may obtain their own records from the
525 Study Director at any time.
526
527 We will enroll three more subjects than are required to meet our sample size. All
528 subjects will be informed during the Consent process that on the day of testing, a
529 small number of subjects may be designated as alternates and sent away after
530 being compensated for coming to the test site. Alternate subjects may return later
531 to replace subjects that initiate testing but withdraw before useful data are
532 generated. They also serve as insurance against any enrolled subjects who fail to
533 appear.
534
535 The possibility that any subject may be designated as an alternate will assist in
536 protecting the privacy of any subject who must withdraw in or near the presence
537 of other subjects at the start of the test day (i.e., before treatment and testing
538 begins), for reasons such as a positive pregnancy test result, or for any other
539 personal circumstance.
540
541
542 4 Study Design
543
544 4.1 Number of Subjects
545
546 In efficacy testing, we will use 10 subjects per treatment. Each subject is a
547 replicate. Ten subjects are two-thirds more than the historical EPA requirement
548 of six subjects. EPA is currently working on more precise guidance on sample
549 size, but that remains forthcoming.
550
551 The number of subjects is chosen as a compromise among multiple factors.
552 The goal is to meet regulatory requirements to provide an estimation of the true
553 mean CPT, and so from a scientific standpoint an appropriate response under
554 such circumstances is to increase size, but ethical and economic considerations
555 demand the opposite in the present study, particularly during the efficacy-
556 testing phase.
557
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558 Importantly, under the historical guidelines, there seem to have been few
559 problems with EPA registering repellents failing to meet their labeled
560 performance specification. Nonetheless, there are clear risks in using a very
561 small sample, and conspicuous among them in this study is that the probability
562 of over-representing subjects inherently unattractive to the target species is
563 rather large. We reduce this risk by confirming subject attractiveness to ticks
564 | before they participate in the phase of the test where efficacy data ire
565 collected. This should decrease the probability of certain sampling errors
566 substantially.
567
568 For calculating EPA-required mean and variance data, estimating the power
569 associated with a given sample size is constrained by three factors, namely,
570 little knowledge of the magnitude of individual CPT values in tick studies,
571 little information regarding the distribution of CPT values in insect repellent
572 studies in general, and, the first consideration notwithstanding, a reasonably
573 high chance that there will be a number of censored values. If a minority of
574 values is censored, and particularly if the range of values is not great (as in
575 related mosquito repellent study LNX-001, MRID 47506401), a sample size of
576 10 should give excellent estimates of mean, median, and variation around those
577 values, relative to historical standards. Still, 10 is sufficiently small, from both
578 statistical and biological perspectives, that we are confident that we are not
579 oversampling.
580
581 EPA has expressed interest in refining how CPT data are assessed and
582 analyzed. We judge that such improvements are best made in the context of a
583 further formalization of how EPA makes its labeling decisions from CPT data
584 sets. The central ideas stem from types of survival analysis. One suggestion is
585 to use, e.g., the time to 25% failure (among subjects) as the labeled protection
586 time (when censoring is not too frequent). Another would require the Agency
587 to specify acceptable Type I error probabilities for estimates of minimum CPTs
588 exceeding a specified value. With the latter approach, EPA would also have to
589 judge how to label with respect to the confidence interval around such
590 probability estimates. Like the typical estimation of means and standard
591 deviations, the soundness of such alternative statistical judgments will hinge on
592 the accuracy of assumptions regarding the nature of the population distribution.
593
594 Given the success of past practices in application, and our clear improvements
595 in sample size, it is premature for us to suggest further substantial change in
596 how the EPA assesses repellent efficacy data. The basic philosophy, and
597 therefore methodology, of how these data are analyzed should be based on a
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598 clear and stable agency strategy regarding the information content of product
599 labels.
600
601
602 4.2 Number of Controls
603
604 Each subject simultaneously serves as a treatment and control subject. Ticks
605 are placed on the untreated arm of the subject to determine foraging avidness,
606 then moved to the treated arm. The 'negative control' for efficacy data sets
607 serves to insure that each ndividua tick employed in the study is attracted to
608 the test subject before that tick is used in a repellency challenge^ Ticks that fail
609 to meet the questing criterion (§4.8.3, I) are not used against Test Materials. In
610 this way the negative control serves as a pre-screening of the ticks, such that
611 only actively questing ticks are then exposed to the treatments. Based on this
612 manipulation of a standard control design, the crossing rate on the negative
613 control is judged to be 100%.
614
615
616 4.3 Controls for Matrix Materials
617
618 There are no controls by which the formulation matrices without the repellent
619 active ingredient are tested. The study objective is to examine efficacy of the
620 end products, and there is no a priori basis for anticipating significant repellent
621 activity in the matrices. The question of whether there is interaction between
622 matrix and active is external to the objective. Accordingly, the added risk of
623 including additional subjects testing matrix-only formulations cannot be
624 justified.
625
626
627 4.4 Controls with Comparison Materials
628
629 There are no comparison materials in this study. Questions of comparison
630 between the Test Materials and other repellents are external to the objective.
631
632 4.5 Subject Measurements
633
634 We will measure length and circumference of the forearms of subjects.
635 Circumference will be measured at four points (upper forearm, lower forearm,
636 and two equally spaced points in between). This data will be averaged for
637 mean circumference, which will be multiplied by length to calculate surface
638 area. This data will be kept on file for each subject. Subjects will be re-
Shawn King User 10/20/09 10:51 AM
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Deleted: 2
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639
640
641
642
643
644
645
646
647
648
649
650
651
652
653
654
655
656
657
658
659
660
661
662
663
664
665
666
667
668
669
670
671
672
673
674
675
measured bignniallv or if. when asked, they indicate they may have gained or
lost weight or muscle mass on their limbs since their measurements were last
taken. This practice reduces the frequency of potentially invasive repeated
measurement procedures for subjects.
4.6 Standard Dose as Determined by Dosimetry
Dosimetry data are used to determine individual dosing for efficacy testing.
Dosing rates are calculated on a per square cm basis. Those rates were obtained
in a dosimetry study of each test material in 2007 during our conduct of an
earlier study reported as LNX-001 (MRID 47506401).
Dosing Rates, by Test Material
arms
Cream 20%
TBE *
Spray 20%
0.97 piVcvcc
Cre.
) 47506401)
1 be used to <
The dosing rate for each Test Material is the grand mean rate calculated from 10
subjects (converted from weight to volume by reference to the specific gravity of
each test material).
4.7 Efficacy - Components of the test
The efficacy study will consist of one laboratory trial. In each trial, each Test
Material will be tested with 10 subjects. The individual subject will be the
experimental unit.
Using a mean application rate derived from dosimetry (§4.6), individual
dosages will be prepared for each subject volumetrically such that for each
Test Material, all subjects receive the same amount of Test Material per unit
skin area exposed. Skin surfaces of both treated and untreated limbs are first
cleansed with water and a fragrance-free detergent soap, rinsed with a 35%
ethanol in water solution, and then towel-dried. Test Material is dispensed
from tuberculin (1 ml) syringes by technicians wearing surgical gloves who
apply it to treated subjects by spreading evenly over the area to be treated
using one finger in a light nibbing motion. Application of each Test Material is
r Scott Carroll 10/28/09 11:58
PM
1
Deleted: biennialy
r Shawn King User 10/26/09 S
i:55 PM
Inserted: ennialy
_J
f Shawn King User 10/26/09 S
i:55 PM
Deleted: -annually
-J
Shawn King User 10/20/09 10:53 AM
Deleted: 2.51 >d/cm;
Shawn King User 10/20/09 10:52 AM
Formatted: Font:10 pt
Shawn King User 10/20/09 10:52 AM
Formatted: Font:10 pt
Shawn King User 10/20/09 10:52 AM
Deleted: We are currently in the process of
negotiating with EPA concerning additional
dosimetry data collection for the Cream 20%
product to augment the data set. Depending on
the outcome of the negotiations, we may
amend this protocol to include augmented data
in the final dosage determination.
J
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676 considered a treatment. All treated limbs are monitored to minimize abrasion
677 with clothing or laboratory surfaces from the time of application.
678
679 | All subjects will be assigned to the treated group, which will be stratified by
680 gender. The treatments will be allocated in sequence ('A', then 'B\ then 'A',
681 etc.). Within each gender, the treatments will be allocated at random excepting
682 minor adjustments needed to constrain the numbers treated with a particular
683 Test Material to 10. The treatment each subject receives and the time of
684 application for each subject will be recorded on a data capture form (Appendix
685 2). Multiple technicians will make the applications, and each application will
686 take only about two minutes to complete, so that subjects receiving 'A', for
687 example, will not be treated on average significantly earlier than those treated
688 with 'B\
689
690 Materials will be distributed among subjects as tabulated below.
691
Shawn King User 10/26/09 8:36 PM
Deleted:
blocked
Subject
Cream 20%
Spray 20%
1
Left arm
2
Left arm
3
Left arm
4
Left arm
5
Left arm
6
Right arm
7
Right arm
8
Right arm
9
Right arm
10
Right arm
11
Left arm
12
Left arm
13
Left arm
14
Left arm
15
Left arm
16
Right arm
17
Right arm
18
Right arm
19
Right arm
20
Right arm
692
693 4.7.1 Blinding of Study
694 Because the treated condition will be evident to researchers, technicians, and
695 subjects, neither staff nor subjects will be effectively blinded. However, within
696 the treated group, the twc treatments will be indistinguishable to test subjects
697 and staff based on their physical properties. Accordingly, the wo treatments will
20
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be coded 'A' or 'B' by a technician. That technician will dispense the test
materials so labeled for efficacy test treatments. That technician will not be
involved in judging crossing events during efficacy data collection.
The treatment code key will be recorded in hardcopy by the technician and
maintained in a locked file drawer to which only he/she has the key. As a
backup, the key will also be recorded in a password protected computer file.
For backup access, two technicians will be charged with privately maintaining
the password offsite from the laboratory. Technicians will be charged not to
reveal the code or the specific identity of test materials at any time during
application or data collection, unless needed for medical or legal reasons. The
Study Director will retrieve the code key from the technician(s) after the
conclusion of data collection.
This moderate level of blinding security is deemed appropriate for a test in
which the performance difference between untreated and treated conditions is
unlikely to be ambiguous, and in which the performances of the test materials
are not specifically being compared.)
4.7.2 Target Arthropods
Species challenging the repellent in the test are listed in § 1.1. We will test
repellency against deer tick - Ixodes scapularis, and American dog tick -
Dermacentor vciriabilis.
4.7.3 Confirming Tick Foraging Activity
To be included in the test on a treated limb, each tick must first ie determined
to be a "qualifying tick" (defined as beginning walking on the hand of the
subject's untreated arm within approximately 15 seconds of being placed
there). Each tick must then alsc meet the crossing criterion on the untreated
limb, following the procedure for the treated limb in the same test period
(§4.8. .1).
4.7.4 Measuring Repulsion
For each tick species, the number of crossings on each subject's exposed
treated area will be recorded (Appendix 2) as they occur during 3-minute
exposure periods commencing once every 15 minutes, beginning at the onset
of data collection and ending when the subject receives a confirmin g rossing,
a stopping rale is invoked for the subject, or the Study Director stops the test
for all subjects. Based on repellency trials of the Test Material(s) against
mosquitoes (related study LNX-001, MRID 47506401), we expect the
repellents may remain effective for up to 12-14 hours possibly more.
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Deleted: Foraging pressure falls below
threshold needed to challenge the .
Test Material(s) ,
4.7.5 Environmental Conditions - Data
Records (Appendix 2) of presence/absence and general rate/quality data for
environmental conditions (temperature, relative humidity, light intensity) will
be made at approximately one-hour intervals throughout the course of the
laboratory trial.
4.7.6 Stop Rules
All subjects
Consented duration reached
Test site becomes unsafe for subjects for any reason
W- — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — — —
Individual subjects
Subject asks to withdraw
Subject's treated limb receives Confirming Crossings for both target species'
Medical management is invoked for the subject (§1.3.6)
Subject proves unattractive to target species
During subject training (see CLBR Training Manual §1 .b
Handling ticks and observing their movement on the skin) - if any
qualifying tick (as defined in $4.7.3) per five exposures of each
species fails to cross on the subject, the subject will be asked to
withdraw.
During repellencv trial - While we do not anticipate tick avidity as
measured by our criteria (§4.8.3.1) will change significantly during
the study, should a subject unexpectedly lose attractiveness to
either tick species (as gauged on the untreated arm, detailed in the
following paragraph) before a confirming crossing, he or she will
be replaced on a later date if it is determined that his or her total
exposure duration is less than 90% of the mean of subjects who did
not withdraw, and when not more than 2 of 10 subjects have so
withdrawn. If more than 2 of 10 subjects withdraw prematurely,
those with the briefest participation will be replaced first. This stop
rule is not automatically invoked if the Study Director ends fFormatted^^^
exposures due to other factors, such as subject exhaustion: in such
cases the data collected before termination may be sufficient to
meet the study goals.
This stop rule is invoked in part or whole if the following sequence
of events occurs: Three ticks of a species do not cross on subject's
untreated arm during a test interval, in which case subject is retired
from testing that species. The second tick species is then tested
22
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with the same failure criterion. Since each tick is given 3 minutes
to cross on the untreated arm, note that in the unlikely scenario of a
full 6 ticks (3 of each species, summing to 6 ticks for both species
combined) being tested within an interval, testing of the sixth tick
would not begin until after 15 minutes had elapsed, which would
normally be the time at which the next exposure interval would
begin. If the third tick of the second species crosses the untreated
aim at that point, its data from the treated arm will be assigned to
the prior exposure interval, and exposures for the next interval will
begin immediately. If the third tick of the second species does not
cross on the untreated arm, the subject is asked to withdraw.
4.8 Sequence of efficacy test procedures
4.8.1 Within 30 days preceding Test Day
Candidate screening and subject consenting and orientation will occur.
4.8.2 1 Day prior to test
Staff prepare laboratory, arranging space in the facility to accommodate all test
subjects and staff. A separate area for dispensing food and beverages is
prepared and provisioned for subject access throughout the test.
4.8.3 Test Day
Subjects gather at the Carroll-Loye Biological Research laboratory to clean
limbs and receive applications. The technicians and other researchers who will
assist subjects during the test will be introduced or reintroduced to the subjects.
Subjects are instructed to call on them whenever they have questions. Subjects
are also reminded of procedures for the day's test.
The following test procedures (§4.8.3.1 and §4.8.3.2) are repeated for each
species in sequence (not concurrently) by each subject within each interval,
with intervals occurring every 15 minutes. until a stop rule (§4.7.6) is invoked.
4.8.3.1 Tick screening for active foraging and repellency challenge
Three 'orientation' ink dots are arrayed longitudinally on both ventral forearms
of each subject, at 3 cm intervals. On the treated arm, the first dot is 3 cm distal
to the treated area, the second dot marks the threshold of the treated area, and the
third dot is 3 cm into the treated area. The untreated limb/limb portion has a
spatially identical array of 3 lines for tick activity screening. The first dot, used
for placement, insures that ticks are not placed within the treated area and so can
Shawn King User 10/20/09 10:41 AM
Deleted: . Subj ect' s treated lim b recei v es
Confirming Crossings for both target species ,
- Medical management is invoked for the
subject (§1.3.6),
Shawn King User 10/20/09 11:06 AM
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detect a gradient of repellent density to which to orient. The second dot serves
keep subjects aware of where the treated area begins and serves as a reorientation
point for re-marking should either the first or the third dot become obscured.
Subjects screen ticks in two steps. First, whether an individual tick is
"qualifying" (sufficiently active in general) is screened as described in §4.7.3.
Second, whether an individual tick is "actively questing" is screened by
observing whether it walks past the second marker dot in motion toward the
elbow of the untreated arm.
Subgroups of approximately three subjects are led by a technician in the
monitoring of time, ticks, and tick behavior. Each subject selects an unused tick
and screens it for active questing behavior, repeating vith the same tick species
until an actively questing tick is identified or the stopping rule for lack of active
questing is invoked (§4.7.6. stopping rule 4 for individual subjects during
repellencv trial). The subject then transfers the tick to the treated arm for a
repellent challenge.
To initiate a screening or a repellent challenge, a tick is placed on the ventral
aim or proximal palm, in the most hair-free portion, at the first (most distal line.
Ticks are manipulated with the bristles of a fine artist's paintbrush. Ticks are
placed so that they face the elbow. Ticks may be oriented to locomote toward the
margin of the treated area with the gentle action of the paintbrush. Forearms
should be held from approximately 30° to vertically above the lab bench surface
if that increases the propensity of ticks to travel toward the body.
Active questing is verified if a qualifying tick travels past the second marker dot
in motion towards the elbow on the untreated arm. On the treated arm, a crossing
is scored if a tick travels at least 3 cm in a vector toward the elbow into the
treated area (i.e., at least as far as the third line) within 3 minutes of beginning to
move up the arm from the first line. A repulsion is scored when a tick changes
its orientation away from, or parallel to, the margin of the treated area upon
approach, or does not cross more than 3 cm toward the elbow within 3 minutes
of entering the treated area.
4.8.3.2 RepeUency data collection and tick removal
The technician will assist subjects in determining crossing versus repulsion events,
and in determining whether a tick may be beginning to bite (an extremely unlikely
event), and assisting in removing a tick should a bite occur (no embedding is
anticipated, so removal should be possible with the same small paintbrush). Time
is monitored by referring to an electric chronometer with a highly visible display.
Shawn King User 10/20/09 11:10 AM
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Shawn King User 10/26/09 8:58 PM
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863 The technician will record any crossings or repulsions as they occur. Repulsions
864 are normally unambiguous reversals of direction. Subjects lift the tick off with the
865 paintbrush after each assessment is complete. Any brushes that come into contact
866 with a test material are discarded. Used ticks are immediately retired from the
867 study by being transferred from the test arm to a container labeled "used".
868
869 4.8.4 Additional efficacy data collection
870 In the event that a subject withdraws during the Test Day or the Study Director fFormattedrund~iin"
871 invokes individual subject stopping rule number 4 (§4.7.6) for that subject, his
872 or her data will be replaced by repeating the described procedures (this
873 protocol, especially §4.8.3) on a subsequent day. Subsequent testing groups
874 may consist of as few as one subject, who would work singly with a technician
875 rather than in a subject group.
876
877
878 4.9 Efficacy - Statistical design and analysis
879
880 Statistics will be computed with SAS's JMP software, Version 5.0.1.2 (SAS
881 Institute, Cary, NC).
882
883 Because all subjects use different ticks, all ticks are used only once, and neither
884 organism interacts directly with conspecifics at the level of the skin and the
885 | repellent during data collection, we will analyze data for each tick species by
886 subject as independent, replicated values. The hypothesis that the test
887 materials will significantly reduce the number of ticks Crossing treated versus
888 untreated skin is not the objective of this study. The objective is to compute,
889 for each test material, a reasonable estimate of mean and standard deviation for
890 the duration between application and sufficient repellency breakdown such that
891 for each tick specie there are two ticks crossings on a subject within a half
892 hour period. That pattern is here assessed 'or each tick species at a resolution
893 of 15 minutes.
894
895 | For each tick species on eacl treated subject, we will measure (data form
896 Appendix 2):
897 • Exposure delay (min) - time between application and first exposure
898 • Minutes to First Confirmed Crossing (FCC) or end
899 • Complete Protection Time (CPT) - time between application and FCC
900
901 Complete protection time (CPT) is measured as the length of time from initial
902 application to the First Confirmed Crossing (FCC). A FCC is a Crossing
903 | followed by another 'confirming Crossing within 30 minutes. For example, a
25
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Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
904 Crossing at 90 minutes followed by another at 135 minutes is not confirmed,
905 but a third Crossing at 150 minutes would confirm the one at 135 minutes,
906 giving a CPT of 135 minutes.
907
908 | CPT is measured as a single time value for each subject for each tick species.
909 Based on the requirements for such estimates in the EPA draft repellent
910 efficacy testing guidelines (1999; OPPTS 810.3700), we will calculate mean
911 | CPT for each tick species across all 10 subjects, with standard deviation and
912 95% confidence interval information. Data will be normalized as possible to
913 enhance the value of confidence interval calculations.
914
915 As described in §4.74, we anticipate that protection may span up to about 12
916 hours, and possibly 14 hours or more after application for some subjects. To
917 examine the temporal pattern of failure further, we will employ Kaplan-Meier
918 | survival analyses by subject within tick species. Kaplan-Meier survival
919 analysis accommodates some data censoring in the event that any subjects
920 withdraw or are withdrawn before failure. In addition, we will estimate the
921 Kaplan-Meier median, and the time until 25% failure, for each test product on
922 each tick species. In the presence of a high frequency of censoring, median
923 (and mean) values will be underestimated.
924
925 Our chosen sample size of 10 subjects will improve precision in estimating test
926 material performance. This sample, which is larger than that traditionally
927 required by US EPA, is implemented at considerable expense to the study
928 sponsor, but is consistent with suggestions from HSRB advisors to EPA. The
929 resulting data set will be provide values suitable for any additional statistical
930 characterizations of repellent performance that EPA may wish to employ in
931 developing labeling language for the Test Materials.
932
933 5 Quality Assurance
934
935 A separate, professional Quality Assurance Unit (QAU) will inspect the study.
936 The QAU will report to the Study Director. Protocol Review and Comments
937 must take place before data collection commences. In-Life Inspection must
938 include observing the measurement and recording of key variables by subjects
939 and technicians. In addition, the Final Report will be audited for completeness
940 and accuracy. A QAU Statement will address compliance and noncompliance or
941 any omissions in auditing. Findings from the In-Life Inspection and the Final
942 Report, as well as the QAU Statement will be transmitted to both the Study
943 Director and to the Sponsor Monitor.
944
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945 6 Amendments and Deviations to the Protocol
946 Protocol amendments or deviations will be reviewed by the Study Monitor and
947 the Study Director. Any changes that may affect the health or safety of study
948 | participants must be approved by the Study Director, the State of California
949 Department of Pesticide Regulation, and the approving IRB. The amendments,
950 deviations as well as any adverse events will be documented in the Study
951 Director's final report. Documentation will include a description of the change,
952 the reason for the change and the effect of the change on the conduct and
953 outcome of the study.
954
955 7. LITERATURE CITED AND SELECTED REFERENCES
956
957 Bernard, Donald R., Bernier, U. R., Posey, K. H. and Xue, Rui-De (2002).
958 Repellency of IR 3535, KBR 3023, para-menthane-3,8,-diol, and DEET to
959 Black Salt Marsh Mosquitoes (Diptera: Culicidea) in Everglades national
960 Park). J. Med. Entomology 39(6): 895-899
961 Boeckh, J.; Breer, H.; Geier, M.; Hoever, F. P.; Kruger, H. W.; Nentwig, G.;
962 Sass, H. Acylated. 1,3-aminopropanols as repellents against bloodsucking
963 arthropods. Pestic. Sci. 1996, 48, 359-373.
964 Carroll, S. P. (2006) Evaluation of topical insect repellents and factors that affect
965 their performance. Chapter 12 In Insect Repellents: Principles, Methods,
966 and Use, Debboun, M., Strickman, D. and Frances, S. P. (eds.). Boca Raton
967 Florida, CRC Press.
968 Cilek, J. E., Peterson J. L., and Hallmon, C. F. (2004) Comparative efficacy of
969 IR3535 and DEET as repellents against adult Aedes aegypti and Culex
970 quinquefasciatus. J. Amer. Mosq. Control Assoc. 20: 299-304
971 Constantini, Carlo and Ilboudo-Sanogo, Edith (200-). WHO PES Evaluation of
972 Insect Repellent KBR 3023 in Burkina Faso. Final report for WHO Project
973 V2.181.276
974 Frances, S.P., Waterson, N.W., Beebe, N.W. and Cooper, R.D. (2004). Field
975 Evaluation of Repellent Formulation Containing DEET and Picaridin
976 against Mosquitoes in Northern Territory, Australia. J. Med. Entomology
977 41(3): 414-417
978 Frances, S.P., Van dung, N., Beebe, N. W. and Debboun, M. (2002). Field
979 Evaluation of Repellent Formulations against daytime and Nighttime Biting
980 Mosquitoes in a Tropical forest in Northern Australia. J. Med. Entomology
981 39(3): 541-544
982 Luepkes, K. H. Mosquito repellent effects of various formulations based on
983 Bayrepel I KBR 3023 against yellow fever mosquito Aedes aegypti (2005).
984 Unpublished Lanxess report
27
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985 Yap, H. H., Jahangir, K„ Chong, A.C.S., Adanan, C. R., Malik, Y. A. and
986 Rohaizat, B. (1998). Field Efficacy of a New Repellent, KBR 3023, against
987 Aedes albopictus (SKUSE) and Culex quinquefasciatus In a Tropical
988 Environment. Journal of Vector Ecology 23(1): 62-68
989 Yap, H.H., Jahangir, K. and Zairi, J. (2000) Field Efficacy of Four insect
990 Repellent Products against Vector Mosquitoes in a Tropical
991 Environment. Journal of the Mosquito Control Association. 16(3): 241-
992 244
993 8 Protocol Approval Signatures
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Page 1 of 8
INFORMED CONSENT AUTHORIZATION TO
PARTICIPATE AS A RESEARCH STUDY SUBJECT
Title of Study: LNX-003 EFFICACY TEST OF KBR 3023
(PICARIDIN; ICARIDIN) - BASED PERSONAL
INSECT REPELLENTS (20% CREAM AND
20% SPRAY) WITH TICKS UNDER
LABORATORY CONDITIONS
Principal Investigator: Scott P. Carroll, Ph.D.
Carroll-Loye Biological Research
711 Oak Avenue
Davis, CA 95616
(530) 902-8267
Site of Investigation: Carroll-Loye Biological Research
711 Oak Avenue, Davis, CA 95616
Sponsor: LANXESS Corporation
Participant's Name:
INTRODUCTION
You are being asked to participate in a research study. Your participation is
voluntary. The information in this Informed Consent Form explains the study. You
will receive a copy of this form, and you may take it home to think about before
making your decision. If you request, we will also provide you with a copy of the
study Protocol, which details all the procedures of the study, and contains details
about product safety. If you have any questions or do not understand anything in
this form, please ask the Principal Investigator to explain any words or
information you do not clearly understand.
NATURE AND PURPOSE
Carroll-Loye Biological Research is conducting this research study in order to
develop effective repellents. Many people are interested in having new and better
insect repellents available to them. The insect repellents that we will study were
developed with improved formulations of the ingredient Picaridin. More studies
are needed to determine how well such new insect repellents work.
The purpose of the study is to test how well this insect repellent, in cream and
pump spray formulations, works against two types of ticks. The information
gained from the study will assist in developing these repellents for commercial
marketing. During the study, we will test the insect repellents against ticks in a
laboratory.
Version: 7/28/09
Protocol: LNX-003
APPROVED BY
Independent IRB
7/28/09
Signature
Date
Initials:
Date:
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Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions
Page 2 of 8
The sponsor, LANXESS Corporation, has contracted Carroll-Loye Biological
Research to conduct the study. Scott Carroll, Ph.D., of Carroll-Loye Biological
Research is the Principal Investigator (Study Director) in charge of the study.
SUBJECT SELECTION
You have been invited to participate in this research study because you are a
male or female, read and speak English, consider yourself to be in good physical
condition and are 18-55 years old.
If you are a female of child-bearing potential, you cannot be pregnant or
breastfeeding. Using an over-the-counter (OTC) pregnancy kit supplied by a
technician, you will perform a pregnancy test at the laboratory on the day of any
study visit in which repellent will be applied or in which you will be exposed to
biting insects. Your test results will be verified by a female technician
experienced in making that assessment. If you are pregnant, you will not be
allowed to participate in the study. Information regarding your pregnancy test
results will be kept in confidence. If you decide to withdraw from the study after
taking the pregnancy test you do not need to show a positive result.
RESTRICTIONS
• You must not be a student or employee of the Principal Investigator.
• You must not be hypersensitive (allergic) to tick bites, or phobic of ticks.
• You must not be sensitive to any of the test product ingredients, or allergic
to common cosmetics.
• You must regularly spend time in outdoor settings.
• You must be able to see and remove ticks that come in contact with your
skin.
• You must not have used repellents within a day prior to the start of the
study.
• You must not use perfumed products after 9 p.m. the night before and
throughout the tests. To meet this restriction, you may need to purchase
fragrance-free cosmetics prior to the test days. If you do, you will be
reimbursed for your expenses.
• You must refrain from smoking or consuming alcoholic beverages after 9
p.m. the night before and throughout the tests.
NUMBER OF SUBJECTS PARTICIPATING
Up to about 23 subjects will be enrolled at this single-site study. A few more
subjects will be enrolled than are needed in order to make up for anyone who is
unexpectedly unable to participate once testing begins. If more subjects are
present than are needed for any part of the test, you may be asked not to
Version: 7/28/09
Protocol: LNX-003
APPROVED BY
Independent IRB
7/28/09
Signature
Date
Initials:
Date:
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Page 3 of 8
participate, but will instead be an 'alternate subject' who may be contacted to
participate later if needed. If you are designated as an alternate, you will be
compensated for your participation up to that point and for your inconvenience.
STUDY INTRODUCTION AND DURATION
Schedule of visits and time required to participate in the study
Activity
Visit 1
Visit 2
1. Orientation visit
X
2. Lab study visit
X
Total time
2-2.5 hours
8-16 hours
Scott Carroll 10/29/09 12:35 AM
[ Deleted: Field
You will be given a training manual and will have a chance to review it and to
read along with the instructions.
Visit 1 for Orientation
Within 30 days before the second visit (in which we will test the repellents against
ticks), you will meet with a researcher to perform orientation activities for the
repellent study. The researcher will tell you more about what you will experience
while participating and what is expected of you, and you will sign this consent
form. You will also be shown how handle ticks on your skin with a small artist's
paintbrush. This training and practice will take about 1/4 hour.
The total time for Visit 1 activities will be about 2-2.5 hours.
Visit 2 for the Tick Repellent Test
The study will also require a second visit to the same laboratory. This second
visit will most likely require approximately 12 hours of your time. However, it may
require as few as about 4 hours or many as about 16 hours, depending on how
long the repellents remain effective. Bathrooms are available, and meals, drinks
and snacks will be provided.
STUDY PROCEDURES
Visit 1
At the laboratory, a researcher will measure the length and circumference of your
forearm. If you have participated in a Carroll-Loye Biological Research study
within the last two years, and were measured for that study, we will use your on-
file limb measurements unless, when asked, you indicate that you think you have
gained or lost weight or muscle mass on your limbs since the previous
measurements were taken.
You will also be given a verbal orientation to the activities of the test day, with an
opportunity to ask the researcher questions or share your concerns about any
aspect of the research activities.
Version: 7/28/09
Protocol: LNX-003
APPROVED BY
Independent IRB
7/28/09
Signature
Date
Initials:
Date:
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Page 4 of 8
At the laboratory, you will spend about 30 minutes practicing handling ticks in the
laboratory in preparation for the repellent study. A technician will show you how to
catch the ticks, place them on your skin, take them off, and place them in a container.
You will practice these tasks several times in order to familiarize yourself with how to
handle the ticks carefully and successfully. You will also be trained to recognize tick
attachment/biting behavior, which includes cessation of crawling motion and pressing
mouth parts against the subject's skin or placing head down against your skin while
lifting hindmost legs off of the your skin. If you observe this behavior during the test,
you will alert the attending technician, who will remove the tick immediately using a
paintbrush or, if needed, tweezers. You may ask the technician for advice on how to
handle the ticks at any time while you are practicing. The ticks used for this training
are reared in the laboratory and free from diseases.
The 30-minute practice also tests to make sure the types of ticks to be used in the
test will move up your arm. If either of the two types of ticks will not move up your
arm, vou will be asked to withdraw from the study.
Visit 2
This is the day of the actual repellent study. You will first be guided to wash your
lower arms with mild, low fragrance soap, rinsing them with a spray of ethyl alcohol
(mixed at 35% in water), and then drying them with a clean towel. Experienced
personnel will then apply repellent to one of your forearms to give even, complete
coverage of the skin. The amount of repellent applied on an arm is likely to be no
more than about % teaspoon. You will be randomly (like a flip of a coin) assigned to
receive either 20% Picaridin Spray or 20% Picaridin Cream. Your other arm will not
be treated, but will instead be used to determine whether each tick is active enough
to be tested on your treated arm.
Shawn King User 10/26/09 9:12 PM
Deleted: s
During the test, you will be seated at a laboratory table with about six other treated
subjects, and a researcher or technician will lead you in handling and keeping track of
the ticks, of the time, and of your tick observations. Every 15 minutes, you will test a
new tick from one species first on your untreated and then on your treated arm, and
report the results to your leader. You will then repeat that sequence with a tick of the
other species. Together testing the two ticks will usually take between 5 and 10
minutes to complete rarely longer. At times you may need to stand so that the ticks
may climb upward, which is their preference.
Every 15 minutes a researcher or technician will announce the beginning of the next
period for testing the treated skin. You will continue in this way until a tick of each
species crosses the repellent in two of three consecutive periods, as long as you are
comfortable. There will isuallv be time for brief breaks to eat and use the bathroom
between test periods. Rarely, there may be several test periods during the test that
are unusually long, leaving little or no time until the next period. In this case, vou may
need to wait until the following period to take a break.
Version: 7/28/09
Protocol: LNX-003
APPROVED BY
Independent IRB
7/28/09
Signature
Date
Initials:
Date:
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When a technician indicates you are finished with the testing activity, the technician
will direct you to discard your gloves and wash any applied skin area to make sure all
treatment residues are removed. Using a clean towel each time, wash applied areas
with cleanser, rinse with water, dry, then wash with mild alcohol solution (35% ETOH
in water) rinse with water, and dry.
RISKS / DISCOMFORTS
If at any time you feel ill, inform the Principal Investigator (or anyone else who is
assisting to direct the study) immediately. You will be taken to receive medical
attention at the nearest healthcare facility. You may also request access to
standard first-aid materials (such as bandages, antiseptics and mild
antihistamines) and request first-aid assistance at any time. You may remove
yourself for any reason from the study at any time without penalty to your
compensation. At least one qualified researcher will remain with the other test
subjects if other researchers depart with an injured or ill subject.
The cream repellent will cause substantial but temporary injury to eyes on
contact. The pump spray repellent will cause moderate irritation to eyes on
contact. Both are harmful if swallowed. You may obtain more information about
the safety of the repellents by asking a technician at any time. You will be given
the Material Safety Data Sheets, which list product safety details similar to those
found on commercial product labels.
If they bite you, ticks can transmit serious diseases, or cause tick paralysis. Ticks
require many minutes to bite through the skin, and we do not expect them to
attempt to bite you during the study. The artist's paintbrush that we will train you
to use to handle ticks will also be used to remove any ticks before they bite or
bury in the skin. The ticks have been screened for infectious diseases at the US
Centers for Disease Control and have been determined to be free of the
pathogens that cause Lyme Disease, Rocky Mountain Spotted Fever,
Ehrlichiosis, and Anaplasmosis. Contact a physician and the Principal
Investigator if you develop a rash within 7 days after the day of testing. The first-
aid kit at the laboratory contains treatments to reduce allergic symptoms. Inform
the Principal investigator if you are allergic to any nonprescription medicines. At
least one technician with current first-aid training will be present during the test.
PREGNANCY RISKS
The risks to the unborn are unknown and may be hazardous. If you are a
woman of childbearing potential, it is important that you do not participate
in this study if you are, or if you think you may be pregnant, or if you are
lactating.
Version: 7/28/09
Protocol: LNX-003
APPROVED BY
Independent IRB
7/28/09
Signature
Date
Initials:
Date:
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If you are a female subject who is tested for pregnancy, and you test positive,
there is some risk of psychological stress from the surprise of the result. Only a
single female technician will evaluate the results, and no record will be made of
the results, to maximize your privacy by minimizing the small but present risk that
other staff or subjects may become aware of the results.
UNKNOWN / UNFORESEEABLE RISKS
In addition to the risks and discomforts listed above, there may be some
unknown or infrequent and unforeseeable risks associated with using this
product, including allergic reaction or interaction with a medication. You will be
informed in a timely manner both verbally and in writing of any new information,
findings or changes to the way the research will be performed that might
influence your willingness to continue participation in this study, or change the
nature of the risks associated with participating.
RESEARCH-RELATED INJURIES
If you are injured as a result of being in this study, a consulting physician who is
aware of the study will be contacted immediately by telephone. Medical treatment
will be available from a healthcare facility. Carroll-Loye Biological Research will
cover the costs of such medical treatment that are not covered by your own
insurance or by a third party that covers you. If necessary, Carroll-Loye Biological
Research will transport you to receive medical attention and pay costs
associated with the reasonable and appropriate treatment for any injuries
incurred as a result of participation in the study. For further information about
this, volunteers should call the Carroll-Loye Biological Research office at (530)
902-8267.
You DO NOT waive any of your legal rights by signing this form.
TREATMENT ALTERNATIVE
Since this study is not intended to provide any therapeutic or other health-related
benefit, your alternative is to not participate in this study.
BENEFITS
There are no immediate benefits to you from your participation. However, by
serving as a participant, you may assist in making new insect repellent products
available to consumers.
OFFER TO ANSWER ANY QUESTIONS ABOUT THIS STUDY
If you have any questions or problems during this study, or if you think that you
may have experienced a research-related injury, you should contact Scott Carroll
of Carroll-Loye Biological Research at (530) 902-8267 at anytime.
Version: 7/28/09
Protocol: LNX-003
APPROVED BY
Independent IRB
7/28/09
Signature
Date
Initials:
Date:
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If you have any questions regarding your rights as a research participant, please
contact Kim Lerner, Chair of the Independent Investigational Review Board, Inc.
at toll free 1- (877) 888-iirb (4472) between 6:00 AM and 2:00 PM, Pacific time,
Monday through Friday. You can also contact the Independent Investigational
Review Board, Inc. if you would like to report problems in a research study,
express concerns, ask questions, request information, or provide input. The
Independent Investigational Review Board is a committee established for the
purpose of protecting the rights of participants in a research study. For more
information about your rights and role as a research participant you can visit the
Research Participant section of the IIRB, Inc. website atwww.iirb.com.
COSTS AND REIMBURSEMENT
There will be no costs to you from participating in this study.
For participation in the study, each research study participant will receive a cash
payment of $20 per hour. Payment will be made at the end of each visit or
whenever you withdraw from the study. If you are designated as an 'alternate
subject,' you will be paid $50 to compensate you for being inconvenienced.
CONFIDENTIALITY
Carroll-Loye Biological Research will retain records of this study indefinitely. You
may access your own records by contacting the Study Director. Representatives
from the sponsor (LANXESS Corporation), the U.S. Environmental Protection
Agency (EPA), the California Department of Pesticide Regulation and the
Independent Investigational Review Board, Inc. (an independent committee that
reviewed this study's ethical aspects to help protect the rights and welfare of
study participants) may have access to all non-personal information collected in
this study. Because of the need to release information to these parties, absolute
confidentiality cannot be guaranteed. Any information or reports published as a
result of this study will not identify you by name, or by any other personal
identification.
STATEMENTS OF UNDERSTANDING
Right to withdraw or removal from study
You understand that you are free to withdraw from this study at any time, and
you agree to inform the Principal Investigator immediately if you intend to
withdraw. It is understood that your decision to participate in this study or to
withdraw from this study will not influence the availability of your future medical
care and will involve no penalty or loss of compensation or benefits to which you
are otherwise entitled. You may withdraw from this study at any time.
You agree that the Principal Investigator in charge of the study can remove you
from this study without your consent for any reason, including, but not limited to:
Version: 7/28/09
Protocol: LNX-003
APPROVED BY
Independent IRB
7/28/09
Signature
Date
Initials:
Date:
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a. His/her judgment that any condition or circumstance may jeopardize your
welfare or the integrity of the study.
b. Your failure to follow the instructions of the investigator(s).
c. If the study is stopped by the sponsor and/or Principal Investigator prior to
completion.
Consent and signatures
I have read, in a language that I understand well, and understand the information
which has been stated above. I have received satisfactory answers to all of the
questions that I have asked. I hereby voluntarily consent to take part in this study
and to be a research study participant in this study. I do not waive any of my
legal rights by signing this Informed Consent Form. I shall receive a copy of the
signed Informed Consent Authorization.
Date Time Print Subject Name Sign Subject Name
(MM/DD/YY)
Date Print Carroll-Loye Sign Carroll-Loye
Biological Research Biological Research
Representative Representative
Copy of signed/dated consent form given to subject on (date) by (initials)
Independent Investigational Review Board, Inc.
Approved: 7/28/09
Version: 7/28/09
Protocol: LNX-003
APPROVED BY
Independent IRB
7/28/09
Signature
Date
Initials:
Date:
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LANXESS Corporation
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Carroll-Loye Biological Research
711 Oak Avenue Davis, California 95616 Tel (530) 902-8267 http://www.carroll-love.com/
CLBR Training Manual
§l.b. Handling ticks and observing their movement on the skin
A. Goals of exercise
1. Learn to move and handle ticks using a fine artist's paintbrush in preparation for
participating in a tick^repellent study^ _
2. Learn to observe ticks and measure their movement in preparation for collecting data on
the effectiveness of a repellent against ticks.
3. Determine if the types of ticks to be used in the study will move up your ami.
4. Learn to identify and distinguish between the two species of ticks vou will be
handling.
Scott Carroll 10/29/09 12:23 AM
Deleted: participate
Scott Carroll 10/29/09 12:23 AM
Formatted: Indent: Left: 0.25", Hanging:
[ 0.19"
R General information
1. A technician will show you how you how to remove ticks from a plastic vial using a small
paintbrush, how to avoid injuring the ticks, and how to place them on you arm and remove
them, and how to dispose of them.
2. A technician will draw three lines on your forearm, each 3 cm apart. You will practice placing
ticks on the arm and both watching and timing their movement in relation to those lines.
3. You will work one tick at one time. The ticks are reared in the laboratory and are free from
disease.
C. Materials and equipment needed
1. Fine paintbrush
2. Marking pen
3. Approximately 6 unfed ticks
4. Labeled vials for accessing and disposing of ticks
5. Shallow pans with water
6. Timer
7. Practice data sheet and pen
D. Learning the methods
Spend about 30 minutes practicing handling >vo kinds ol ticks in the laboratory in preparation for
the repellent study. Your trainer will show you how to remove ticks from vials (held in water pans in
order to keep ticks from escaping). Your trainer will draw three fine lines with removable ink across
your inner forearm, near the wrist, 3 cm apart from one another. From the vial labeled "Fresh",
gently touch the paintbrush tip near the front of a tick's body. It will climb onto the brush. Place the
tick on the line nearest your wrist, noting the time. If the tick does not begin walking within
approximately 15 seconds, the tick is considered not active enough. Remove this tick and
replace it with another, again noting the time. A tick that is active enough will usually Twalk
toward your elbow. If the tick instead walks toward your hand, elevate your elbow further above the
hand and use the brush to gently guide the tick back toward the lines. Once it passes the first line,
walking toward the elbow, note the time at that point. Observe whether the tick crosses both the
second and third lines toward your elbow within three minutes of the start time. After it has crossed
the third line, or after three minutes if not, use your brush to remove the tick and place it in the vial
labeled "Used". If it crossed that line within three minutes, record "C" on the practice data sheet;
otherwise record "R" for "repelled". You will practice these tasks :ivejimes with_each kind of tic in
order to familiarize yourself with how to handle the ticks carefully and successfully ind to
determine if both kinds of ticks will move up vour untreated arm. It is very unlikely that ticks will
attempt to bite you during this training or during the actual study. However, if you see a tick stop
Shawn King User 9/8/09 3:27 PM
Deleted: several times J
Shawn King User 9/23/09 11:23 AM
Deleted: as soon as the tick begins to J
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Carroll-Loye Biological Research
711 Oak Avenue Davis, California 95616 Tel (530) 902-8267 http://www.carroll-love.com/
moving and press it mouth against your skin for more than a minute, or you feel a tick begin to bite,
immediately remove it with the paintbrush, and alert the trainer. You may ask your trainer for advice
about any aspects of these activities at any time while you are practicing.
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Carroll-Loye Biological Research
711 Oak Avenue Davis, California 95616 Tel (530) 902-8267 http://www.carroll-love.com/
October 30, 2009
Mr. Robert Roogow
Independent Investigational Review Board
6738 W. Sunrise Blvd., Suite 102
Plantation, Florida 33313
Amendment 1, Carroll-Loye Protocol LNX-003
Please find below Amendment 1 for CLBR Protocol LNX-003: EFFICACY TEST OF
KBR 3023 (PICARIDIN; ICARIDIN) - BASED PERSONAL INSECT REPELLENTS
(20% CREAM AND 20% SPRAY) WITH TICKS UNDER LABORATORY
CONDITIONS, along with the associated Informed Consent Form and the Protocol body
as MS Word files with tracked changes showing.
The amendment is prepared in response to HSRB reviews at the October 2009 meeting at
US EPA in Crystal City, VA., and to reviews by California EPA. The amendment is
presented as a list of entries arranged in order of appearance in the Protocol. For all edits,
the location of the change in the protocol and the exact change of wording are given. The
line numbers provided refer to beginning locations in the original document, approved by
IIRB, Inc. 30 July 2009. Adjustments to Consent documents, and miscellaneous support
documents, are provided after.
This amendment clarifies how described procedures apply to or include one, both, or
either of the two tick species to be used in the test, how subjects are screened for
attractiveness to the target tick species, and how stopping rules apply to the cessation of
tick foraging activity. In addition, this amendment will correct several minor errors and
potentially confusing statements.
Please let us know if IIRB, Inc. will be providing an expedited review of this submission.
Thank you.
Sincerely,
Dr. Scott P. Carroll, Ph.D.
Study Director
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Carroll-Loye Study LNX-003 Amendment 1 Page 1 of 9
Carroll-Loye Study LNX-003 Amendment 1
Section 1.1 Objective of Research and Endpoints:
Line 139 (paragraph four first sentence), the phrase "for both species" is inserted at the
beginning of the sentence so that it now reads,
"For both species, efficacy and duration will be measured as Complete Protection
Time, or CPT, defined herein as the time between application of test material and the
First Confirmed Crossing of an actively foraging tick from the untreated skin surface of
a subject's hand 3 cm or more into the treated forearm skin area."
Line 146 (Paragraph five), the phrase "first confirmed" is deleted and the phrase "for each
species" is added after "FCC" so that the sentence now reads
"The endpoint will be the time of failure expressed as the time of the FCC for each
species for each subject."
Section 1.3.2 Risks from Exposure to Biting Arthropods
Line 212 (first paragraph, third sentence) the phrase "treated limb" is deleted and replaced
with the word "subject" and the phrase "the repellent begins failing" is deleted and
replaced with the phrase "that subject has received confirming crossings for both tick
species" such that the sentence now reads:
"Stopping Rules (§4.7.6) and Medical Management practices (§1.3.6) specify removing
any subject from the study when that subject has received confirming crossings for both
tick species or the subject shows signs of reacting to a bite or to contact with ticks.
Line 214 (first paragraph, fourth sentence). The sentence "Subjects will be exposing small
areas of treated and untreated skin for a maximum 24 minutes per hour" is deleted.
Second paragraph, last sentence (line 225) becomes the first sentence of a new paragraph,
and the word "This" is deleted and replaced with the phrase "The training procedure".
New content is added after, such that the new paragraph now reads as follows:
"The training procedure also serves to verify the subject's attractiveness to ticks in the
study. If during subject training any qualifying tick (as defined in §4.7.3) per five
exposures of each species fails to cross on the subject, the subject will be asked to
withdraw."
Section 3.1 Candidate Recruitment: Population. Sampling Frame. Representativeness
Line 368 (paragraph four, last sentence), the phrase "while comparable data are not
available for ticks," is inserted after "Nonetheless" so that the sentence now reads:
"Nonetheless, while comparable data are not available for ticks, because gender effects
seem most plausible, we will enroll similar numbers of males and female subjects."
Line 382 misspelled word "principals" is corrected to "principles"
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Carroll-Loye Study LNX-003 Amendment 1 Page 2 of 9
Section 3.3.2 Exclusion criteria, all subjects:
Line 447 (Item number 14)
Item deleted. Content is edited and moved to §4.7.6 Stop Rules (see below).
Line 455 (Item number 15)
Item deleted. Content is edited and moved to §4.7.6 Stop Rules (see below).
Section 4.1 Number of Subjects:
Line 565 (third paragraph third sentence) "is" is replaced with "are" such that the sentence
now reads:
"We reduce this risk by confirming subject attractiveness to ticks before they participate
in the phase of the test where efficacy data are collected."
Section 4.2 Number of Controls
Line 607 To clarify that each tick is screened for its attraction to a given subject in addition
to each subject being screened for his or her attractiveness to each tick species, the word
"individual" is inserted before the word "tick" and the word "it" is replaced with the phrase
"that tick" in the third sentence of the first paragraph so that the sentence now reads:
"The 'negative control' for efficacy data sets serves to insure that each individual tick
employed in the study is attracted to the test subject before that tick is used in a
repellency challenge."
Line 610, the reference to §4.8.2.1 is corrected to §4.8.3.1.
Section 4.5 Subject measurements
Line 640-641 (first paragraph, fourth sentence) the word "bi-annually" is replaced with
"biennially" so that the sentence now reads:
"Subjects will be re-measured biennially or if, when asked, they indicate they may have
gained or lost weight or muscle mass on their limbs since their measurements were last
taken."
Section 4.6 Standard Dose as Determined by Dosimetry
Line 654, table first row second column, the quantity "2.51 |il/cm2" is deleted and replaced
with the acronym "TBD"
Line 655, footnote to dosing rates table; the entire footnote is deleted and replaced with the
sentence:
"As part of Carroll-Loye study LNX-002 (MRID 47506401), additional dosimetry
data will be collected for the Cream 20% product. The augmented data set will be used
to determine final dosage."
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Carroll-Loye Study LNX-003 Amendment 1 Page 3 of 9
Section 4.7 Efficacy - Components of the test
Line 682, third paragraph, first sentence - the statistical term "blocked" is used
inappropriately in the protocol. The word "blocked" is replaced with the correct term
"stratified" so that the sentence now reads:
"All subjects will be assigned to the treated group, which will be stratified by gender."
Section 4.7.1 Blinding of Study
Line 698 and 700 (first paragraph second and third sentences), the word "three" is deleted
and replaced with "two" so the sentences now read:
"However, within the treated group, the two treatments will be indistinguishable to test
subjects and staff based on their physical properties. Accordingly, the two treatments
will be coded 'A' or 'B' by a technician."
Section 4.7.3 Confirming Tick Foraging Activity
Line 726, after the phrase "must first" the phrase "be determined to be a "qualifying tick"
(defined as beginning walking on the hand of the subject's untreated arm within
approximately 15 seconds of being placed there). Each tick must then also" is inserted so
the section it its entirety now reads:
"To be included in the test on a treated limb, each tick must first be determined to be a
"qualifying tick" (defined as beginning walking on the hand of the subject's untreated
arm within approximately 15 seconds of being placed there). Each tick must then also
meet the crossing criterion on the untreated limb, following the procedure for the treated
limb in the same test period (§4.8.3.1)."
Line 728, reference to §4.8.2.1 is corrected to §4.8.3.1.
Section 4.7.4 Measuring Repulsion
Line 731 (first sentence), the phrase "For each tick species" is inserted at the beginning and
the phrase "the First Confirmed Crossing" is deleted and replaced with "a confirming
crossing" so that the sentence now reads:
"For each tick species, the number of crossings on each subject's exposed treated area
will be recorded (Appendix 2) as they occur during 3-minute exposure periods
commencing once every 15 minutes, beginning at the onset of data collection and ending
when the subject receives a confirming crossing, a stopping rule is invoked for the
subject, or the Study Director stops the test for all subjects."
Section 4.7.6 Stop Rules
Individual rules are now numbered for ease of referencing.
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All Subjects, third statement (line 750) "Foraging pressure falls below threshold needed
to challenge the Test Material(s)" is deleted.
Individual Subjects second statement (line 755) is moved down to become the last
statement in the list (i.e. rule number 4). For the phrase "Subject proves unattractive to
target species" a colon is placed on the end, and the following content is added after:
"During subject training (see CLBR Training Manual §l.b Handling ticks and
observing their movement on the skin) - if any qualifying tick (as defined in §4.7.3) per
five exposures of each species fails to cross on the subject, the subject will be asked to
withdraw.
During repellency trial - While we do not anticipate tick avidity as measured by our
criteria (§4.8.3.1) will change significantly during the study, should a subject
unexpectedly lose attractiveness to either tick species (as gauged on the untreated arm,
detailed in the following paragraph) before a confirming crossing, he or she will be
replaced on a later date if it is determined that his or her total exposure duration is less
than 90% of the mean of subjects who did not withdraw, and when not more than 2 of
10 subjects have so withdrawn. If more than 2 of 10 subjects withdraw prematurely,
those with the briefest participation will be replaced first. This stop rule is not
automatically invoked if the Study Director ends exposures due to other factors, such as
subject exhaustion; in such cases the data collected before termination may be sufficient
to meet the study goals.
This stop rule is invoked in part or whole if the following sequence of events occurs:
Three ticks of a species do not cross on subject's untreated arm during a test interval, in
which case subject is retired from testing that species. The second tick species is then
tested with the same failure criterion. Since each tick is given 3 minutes to cross on the
untreated arm, note that in the unlikely scenario of a full 6 ticks (3 of each species,
summing to 6 ticks for both species combined) being tested within an interval, testing of
the sixth tick would not begin until after 15 minutes had elapsed, which would normally
be the time at which the next exposure interval would begin. If the third tick of the
second species crosses the untreated arm at that point, its data from the treated arm will
be assigned to the prior exposure interval, and exposures for the next interval will begin
immediately. If the third tick of the second species does not cross on the untreated arm,
the subject is asked to withdraw."
Section 4.8.3 Test Day
Line 777 (second paragraph, first sentence) the section references "(§4.8.3.1 and §4.8.3.2)"
are inserted after the word "procedures" and the phrase "for each species in sequence (not
concurrently)" is inserted after the word "repeated" and the phrase "at designated time
intervals" is deleted and replaced with the phrase "within each interval, with intervals
occurring every 15 minutes," so that the sentence now reads:
"The following test procedures (§4.8.3.1 and §4.8.3.2) are repeated for each species in
sequence (not concurrently) by each subject within each interval, with intervals
occurring every 15 minutes, until a stop rule (§4.7.6) is invoked."
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Carroll-Loye Study LNX-003 Amendment 1 Page 5 of 9
Section 4.8.3.1 Tick screening for active foraging and repellencv challenge
Line 790
The following new content is inserted:
"Subjects screen ticks in two steps. First, whether an individual tick is "qualifying"
(sufficiently active in general) is screened as described in §4.7.3. Second, whether an
individual tick is "actively questing" is screened by observing whether it walks past the
second marker dot in motion toward the elbow of the untreated arm."
Line 792 (second paragraph second sentence), the phrase "every 15 minutes" is deleted and
after the word "repeating" the phrase "with the same tick species" is inserted. After the
word "identified", the phrase ", or the stopping rule for lack of active questing is invoked
(§4. 7.6, stopping rule 4 for individual subjects during repellency trial)" is inserted. The
sentence now reads:
"Each subject selects an unused tick and screens it for active questing behavior,
repeating with the same tick species until an actively questing tick is identified, or the
stopping rule for lack of active questing is invoked (§4.7.6, stopping rule 4 for
individual subjects during repellency trial) "
Line 797-798 (third paragraph first sentence) an inappropriately placed parenthesis is
moved from after the word "line" to after the word "distal" so that the sentence now reads:
"To initiate a screening or a repellent challenge, a tick is placed on the ventral arm or
proximal palm, in the most hair-free portion, at the first (most distal) line."
Line 805 (forth paragraph first sentence), insert the word "qualifying" before the word
"tick" such that the sentence now reads:
"Active questing is verified if a qualifying tick travels past the second marker dot in
motion towards the elbow on the untreated arm."
Line 826, a new section is inserted 4.8.4 Additional efficacy data collection.
"In the event that a subject withdraws during the Test Day or the Study Director
invokes individual subject stopping rule number 4 (§4.7.6) for that subject, his or her
data will be replaced by repeating the described procedures (this protocol, especially
§4.8.3) on a subsequent day. Subsequent testing groups may consist of as few as one
subject, who would work singly with a technician rather than in a subject group."
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Carroll-Loye Study LNX-003 Amendment 1 Page 6 of 9
Section 4.9 Efficacy - Statistical design and analysis
This section requires numerous corrections as additions (inserts). They are organized by
paragraph number and sentence number here, in table format for ease of review.
Paragraph
Sentence
(line #)
Changes made
Resulting sentence
2
1 (832)
Add "for each tick
species" after
"analyze data"
Because all subjects use different ticks, all
ticks are used only once, and neither organism
interacts directly with conspecifics at the level
of the skin and the repellent during data
collection, we will analyze data for each tick
species by subject as independent, replicated
values.
2
3 (837)
Add "for each tick
species" after "such
that"
The objective is to compute, for each test
material, a reasonable estimate of mean and
standard deviation for the duration between
application and sufficient repellency
breakdown such that for each tick species
there are two ticks crossings on a subject
within a half hour period.
2
4(840)
Add "for each tick
species" after
"assessed"
That pattern is here assessed for each tick
species at a resolution of 15 minutes.
3
1 (843)
Add "tick species
on each" after "for
each"
For each tick species on each treated subject,
we will measure (data form Appendix 2):
4
2(849)
Add " 'confirming'
" after "another"
A FCC is a Crossing followed by another
"confirming" Crossing within 30 minutes.
5
1(855)
Add "for each tick
species" after
"subject"
CPT is measured as a single time value for
each subject for each tick species.
5
2 (855)
Add "for each tick
species" after
"CPT"
Based on the requirements for such estimates
in the EPA draft repellent efficacy testing
guidelines (1999; OPPTS 810.3700), we will
calculate mean CPT for each tick species
across all 10 subjects, with standard deviation
and 95% confidence interval information.
6
2(863)
Add "within tick
species" after
"subject"
To examine the temporal pattern of failure
further, we will employ Kaplan-Meier
survival analyses by subject within tick
species.
6
4 (867)
Add "on each tick
species" after
"product"
In addition, we will estimate the Kaplan-
Meier median, and the time until 25% failure,
for each test product on each tick species.
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Carroll-Loye Study LNX-003 Amendment 1 Page 7 of 9
Section 6 Amendments and Deviations to the Protocol
Line 894 (First paragraph second sentence) the missing word "by" is added to the phrase
"approved the Study Director" so the phrase now reads "approved by the Study Director".
CLBR Training Manual §l.b. Handling ticks and observing their movement on the skin
Page 51 of the Protocol
Part A. Goals of exercise
In item 1, the word "participate" is corrected to "participating".
An item 3 is added as follows "Determine if the types of ticks to be used in the study will
move up your arm."
An item 4 is added as follows "Learn to identify and distinguish between the two species of
ticks you will be handling."
Part D. Learning the methods
First sentence, after "handling" the phrase "two kinds of' is inserted so the sentence now
reads:
"Spend about 30 minutes practicing handling two kinds of ticks in the laboratory in
preparation for the repellent study."
Sixth sentence, after the phrase "noting the time" a period is added and a new sentence
begins, "If the tick does not begin walking within approximately 15 seconds, the tick is
considered not active enough. Remove this tick and replace it with another, again noting
the time." The phrase "as soon as the tick begins to" is deleted and replaced with the phrase
"A tick that is active enough will usually". In the next sentence, the word "further" is
inserted after the phrase "your elbow". The thus edited portion of the paragraph now reads:
"Place the tick on the line nearest your wrist, noting the time. If the tick does not begin
walking within approximately 15 seconds, the tick is considered not active enough.
Remove this tick and replace it with another, again noting the time. A tick that is active
enough will usually walk toward your elbow. If the tick instead walks toward your
hand, elevate your elbow further above the hand and use the brush to gently guide the
tick back toward the lines."
Fourth from last sentence, the phrase "several times" is deleted and replaced with the
phrase "five times with each kind of tick" and after the word "successfully" the phrase "and
to determine if both kinds of ticks will move up your untreated arm" is inserted so that the
sentence now reads:
"You will practice these tasks five times with each kind of tick in order to familiarize
yourself with how to handle the ticks carefully and successfully, and to determine if
both kinds of ticks will move up your untreated arm."
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Carroll-Loye Study LNX-003 Amendment 1 Page 8 of 9
Informed Consent Form
Number of Subects Participating:
Title line, add "j" into "Subects" to correct misspelling.
Study Introduction and Duration
In the table, the word "Field" is replaced with "Lab".
Study Procedures:
Visit 1 subsection, add new paragraph after the third paragraph reading as follows:
"The 30-minute practice also tests to make sure the types of ticks to be used in the test will
move up your arm. If either of the two types of ticks will not move up your arm, you will be
asked to withdraw from the study."
Visit 2 subsection,
First paragraph, third sentence - the inappropriately pluralized word "repellents" is
corrected to "repellent" such that the sentence now reads:
"Experienced personnel will then apply repellent to one of your forearms to give even,
complete coverage of the skin."
Second paragraph, fourth sentence, add the phrase ", rarely longer" so that the sentence
now reads:
"Together testing the two ticks will usually take between 5 and 10 minutes to complete,
rarely longer."
Third paragraph: In the third sentence, add the phrase "usually be" to the phrase "there will
time" and at the end of the paragraph, add a new sentence such that the third and fourth
sentences of that paragraph now read as follows:
"There will usually be time for brief breaks to eat and use the bathroom between test
periods. Rarely, there may be several test periods during the test that are unusually
long, leaving little or no time until the next period. In this case, you may need to wait
until the following period to take a break."
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aye Study LNX-003 Amendment 1 Page 9 of 9
Carroll-Loye Study LNX-003 Amendment 1 Approval
30 October 2009
Carroll, Ph. D. HDate"
>i rector
gfck&v , 'oc9
CTOskxsky-f-f— - Date
"Regulatory Affairs
SS Corporation
KJs<->
Jangha, Ph. D,
lonitor
Date
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Page 1 of 8
INFORMED CONSENT AUTHORIZATION TO
PARTICIPATE AS A RESEARCH STUDY SUBJECT
Title of Study:
LNX-003 EFFICACY TEST OF KBR 3023
(PICARIDIN; ICARIDIN) - BASED PERSONAL
INSECT REPELLENTS (20% CREAM AND
20% SPRAY) WITH TICKS UNDER
LABORATORY CONDITIONS
Principal Investigator: Scott P. Carroll, Ph.D.
Carroll-Loye Biological Research
711 Oak Avenue
Davis, CA 95616
(530) 902-8267
Site of Investigation: Carroll-Loye Biological Research
711 Oak Avenue, Davis, CA 95616
Sponsor:
LANXESS Corporation
Participant's Name:
INTRODUCTION
You are being asked to participate in a research study. Your participation is
voluntary. The information in this Informed Consent Form explains the study. You
will receive a copy of this form, and you may take it home to think about before
making your decision. If you request, we will also provide you with a copy of the
study Protocol, which details all the procedures of the study, and contains details
about product safety. If you have any questions or do not understand anything in
this form, please ask the Principal Investigator to explain any words or
information you do not clearly understand.
NATURE AND PURPOSE
Carroll-Loye Biological Research is conducting this research study in order to
develop effective repellents. Many people are interested in having new and better
insect repellents available to them. The insect repellents that we will study were
developed with improved formulations of the ingredient Picaridin. More studies
are needed to determine how well such new insect repellents work.
The purpose of the study is to test how well this insect repellent, in cream and
pump spray formulations, works against two types of ticks. The information
gained from the study will assist in developing these repellents for commercial
marketing. During the study, we will test the insect repellents against ticks in a
laboratory.
Version: 11/2/09
Protocol: LNX-003
APPROVED BY
Initials:
Date:
11/2/09
Date
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Page 2 of 8
The sponsor, LANXESS Corporation, has contracted Carroll-Loye Biological
Research to conduct the study. Scott Carroll, Ph.D., of Carroll-Loye Biological
Research is the Principal Investigator (Study Director) in charge of the study.
SUBJECT SELECTION
You have been invited to participate in this research study because you are a
male or female, read and speak English, consider yourself to be in good physical
condition and are 18-55 years old.
If you are a female of child-bearing potential, you cannot be pregnant or
breastfeeding. Using an over-the-counter (OTC) pregnancy kit supplied by a
technician, you will perform a pregnancy test at the laboratory on the day of any
study visit in which repellent will be applied or in which you will be exposed to
biting insects. Your test results will be verified by a female technician
experienced in making that assessment. If you are pregnant, you will not be
allowed to participate in the study. Information regarding your pregnancy test
results will be kept in confidence. If you decide to withdraw from the study after
taking the pregnancy test you do not need to show a positive result.
RESTRICTIONS
• You must not be a student or employee of the Principal Investigator.
• You must not be hypersensitive (allergic) to tick bites, or phobic of ticks.
• You must not be sensitive to any of the test product ingredients, or allergic
to common cosmetics.
• You must regularly spend time in outdoor settings.
• You must be able to see and remove ticks that come in contact with your
skin.
• You must not have used repellents within a day prior to the start of the
study.
• You must not use perfumed products after 9 p.m. the night before and
throughout the tests. To meet this restriction, you may need to purchase
fragrance-free cosmetics prior to the test days. If you do, you will be
reimbursed for your expenses.
• You must refrain from smoking or consuming alcoholic beverages after 9
p.m. the night before and throughout the tests.
NUMBER OF SUBJECTS PARTICIPATING
Up to about 23 subjects will be enrolled at this single-site study. A few more
subjects will be enrolled than are needed in order to make up for anyone who is
unexpectedly unable to participate once testing begins. If more subjects are
present than are needed for any part of the test, you may be asked not to
Version: 11/2/09
Protocol: LNX-003
APPROVED BY
Initials:
Date:
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Page 3 of 8
participate, but will instead be an 'alternate subject' who may be contacted to
participate later if needed. If you are designated as an alternate, you will be
compensated for your participation up to that point and for your inconvenience.
STUDY INTRODUCTION AND DURATION
Schedule of visits and time required to participate in the study
Activity
Visit 1
Visit 2
1. Orientation visit
X
2. Lab study visit
X
Total time
2-2.5 hours
8-16 hours
You will be given a training manual and will have a chance to review it and to
read along with the instructions.
Visit 1 for Orientation
Within 30 days before the second visit (in which we will test the repellents against
ticks), you will meet with a researcher to perform orientation activities for the
repellent study. The researcher will tell you more about what you will experience
while participating and what is expected of you, and you will sign this consent
form. You will also be shown how handle ticks on your skin with a small artist's
paintbrush. This training and practice will take about % hour.
The total time for Visit 1 activities will be about 2-2.5 hours.
Visit 2 for the Tick Repellent Test
The study will also require a second visit to the same laboratory. This second
visit will most likely require approximately 12 hours of your time. However, it may
require as few as about 4 hours or many as about 16 hours, depending on how
long the repellents remain effective. Bathrooms are available, and meals, drinks
and snacks will be provided.
STUDY PROCEDURES
Visit 1
At the laboratory, a researcher will measure the length and circumference of your
forearm. If you have participated in a Carroll-Loye Biological Research study
within the last two years, and were measured for that study, we will use your on-
file limb measurements unless, when asked, you indicate that you think you have
gained or lost weight or muscle mass on your limbs since the previous
measurements were taken.
You will also be given a verbal orientation to the activities of the test day, with an
opportunity to ask the researcher questions or share your concerns about any
aspect of the research activities.
Version: 11/2/09
Protocol: LNX-003
APPROVED BY
Independent IRB
11/2/09
Signature L. Date
Initials:
Date:
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Page 4 of 8
At the laboratory, you will spend about 30 minutes practicing handling ticks in the
laboratory in preparation for the repellent study. A technician will show you how to
catch the ticks, place them on your skin, take them off, and place them in a container.
You will practice these tasks several times in order to familiarize yourself with how to
handle the ticks carefully and successfully. You will also be trained to recognize tick
attachment/biting behavior, which includes cessation of crawling motion and pressing
mouth parts against the subject's skin or placing head down against your skin while
lifting hindmost legs off of the your skin. If you observe this behavior during the test,
you will alert the attending technician, who will remove the tick immediately using a
paintbrush or, if needed, tweezers. You may ask the technician for advice on how to
handle the ticks at any time while you are practicing. The ticks used for this training
are reared in the laboratory and free from diseases.
The 30-minute practice also tests to make sure the types of ticks to be used in the
test will move up your arm. If either of the two types of ticks will not move up your
arm, you will be asked to withdraw from the study.
This is the day of the actual repellent study. You will first be guided to wash your
lower arms with mild, low fragrance soap, rinsing them with a spray of ethyl alcohol
(mixed at 35% in water), and then drying them with a clean towel. Experienced
personnel will then apply repellent to one of your forearms to give even, complete
coverage of the skin. The amount of repellent applied on an arm is likely to be no
more than about % teaspoon. You will be randomly (like a flip of a coin) assigned to
receive either 20% Picaridin Spray or 20% Picaridin Cream. Your other arm will not
be treated, but will instead be used to determine whether each tick is active enough
to be tested on your treated arm.
During the test, you will be seated at a laboratory table with about six other treated
subjects, and a researcher or technician will lead you in handling and keeping track of
the ticks, of the time, and of your tick observations. Every 15 minutes, you will test a
new tick from one species first on your untreated and then on your treated arm, and
report the results to your leader. You will then repeat that sequence with a tick of the
other species. Together testing the two ticks will usually take between 5 and 10
minutes to complete, rarely longer. At times you may need to stand so that the ticks
may climb upward, which is their preference.
Every 15 minutes a researcher or technician will announce the beginning of the next
period for testing the treated skin. You will continue in this way until a tick of each
species crosses the repellent in two of three consecutive periods, as long as you are
comfortable. There will usually be time for brief breaks to eat and use the bathroom
between test periods. Rarely, there may be several test periods during the test that
are unusually long, leaving little or no time until the next period. In this case, you may
need to wait until the following period to take a break.
Visit 2
Version: 11/2/09
Protocol: LNX-003
APPROVED BY
Initials:
Date:
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149 of 168
When a technician indicates you are finished with the testing activity, the technician
will direct you to discard your gloves and wash any applied skin area to make sure all
treatment residues are removed. Using a clean towel each time, wash applied areas
with cleanser, rinse with water, dry, then wash with mild alcohol solution (35% ETOH
in water) rinse with water, and dry.
RISKS I DISCOMFORTS
If at any time you feel ill, inform the Principal Investigator (or anyone else who is
assisting to direct the study) immediately. You will be taken to receive medical
attention at the nearest healthcare facility. You may also request access to
standard first-aid materials (such as bandages, antiseptics and mild
antihistamines) and request first-aid assistance at any time. You may remove
yourself for any reason from the study at any time without penalty to your
compensation. At least one qualified researcher will remain with the other test
subjects if other researchers depart with an injured or ill subject.
The cream repellent will cause substantial but temporary injury to eyes on
contact. The pump spray repellent will cause moderate irritation to eyes on
contact. Both are harmful if swallowed. You may obtain more information about
the safety of the repellents by asking a technician at any time. You will be given
the Material Safety Data Sheets, which list product safety details similar to those
found on commercial product labels.
If they bite you, ticks can transmit serious diseases, or cause tick paralysis. Ticks
require many minutes to bite through the skin, and we do not expect them to
attempt to bite you during the study. The artist's paintbrush that we will train you
to use to handle ticks will also be used to remove any ticks before they bite or
bury in the skin. The ticks have been screened for infectious diseases at the US
Centers for Disease Control and have been determined to be free of the
pathogens that cause Lyme Disease, Rocky Mountain Spotted Fever,
Ehrlichiosis, and Anaplasmosis. Contact a physician and the Principal
Investigator if you develop a rash within 7 days after the day of testing. The first-
aid kit at the laboratory contains treatments to reduce allergic symptoms. Inform
the Principal investigator if you are allergic to any nonprescription medicines. At
least one technician with current first-aid training will be present during the test.
PREGNANCY RISKS
The risks to the unborn are unknown and may be hazardous. If you are a
woman of childbearing potential, it is important that you do not participate
in this study if you are, or if you think you may be pregnant, or if you are
lactating.
Version: 11/2/09
Protocol: LNX-003
APPROVED BY
Initials:
Date:
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LANXESS Corporation
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150 of 168
If you are a female subject who is tested for pregnancy, and you test positive,
there is some risk of psychological stress from the surprise of the result. Only a
single female technician will evaluate the results, and no record will be made of
the results, to maximize your privacy by minimizing the small but present risk that
other staff or subjects may become aware of the results.
UNKNOWN I UNFORESEEABLE RISKS
In addition to the risks and discomforts listed above, there may be some
unknown or infrequent and unforeseeable risks associated with using this
product, including allergic reaction or interaction with a medication. You will be
informed in a timely manner both verbally and in writing of any new information,
findings or changes to the way the research will be performed that might
influence your willingness to continue participation in this study, or change the
nature of the risks associated with participating.
RESEARCH-RELATED INJURIES
If you are injured as a result of being in this study, a consulting physician who is
aware of the study will be contacted immediately by telephone. Medical treatment
will be available from a healthcare facility. Carroll-Loye Biological Research will
cover the costs of such medical treatment that are not covered by your own
insurance or by a third party that covers you. If necessary, Carroll-Loye Biological
Research will transport you to receive medical attention and pay costs
associated with the reasonable and appropriate treatment for any injuries
incurred as a result of participation in the study. For further information about
this, volunteers should call the Carroll-Loye Biological Research office at (530)
902-8267.
You DO NOT waive any of your legal rights by signing this form.
TREATMENT ALTERNATIVE
Since this study is not intended to provide any therapeutic or other health-related
benefit, your alternative is to not participate in this study.
BENEFITS
There are no immediate benefits to you from your participation. However, by
serving as a participant, you may assist in making new insect repellent products
available to consumers.
OFFER TO ANSWER ANY QUESTIONS ABOUT THIS STUDY
If you have any questions or problems during this study, or if you think that you
may have experienced a research-related injury, you should contact Scott Carroll
of Carroll-Loye Biological Research at (530) 902-8267 at any time.
Version: 11/2/09
Protocol: LNX-003
APPROVED BY
initials:
Date:
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Page 7 of 8
If you have any questions regarding your rights as a research participant, please
contact Kim Lemer, Chair of the Independent Investigational Review Board, Inc.
at toll free 1- (877) 888-iirb (4472) between 6:00 AM and 2:00 PM, Pacific time,
Monday through Friday. You can also contact the Independent Investigational
Review Board, Inc. if you would like to report problems in a research study,
express concerns, ask questions, request information, or provide input. The
Independent Investigational Review Board is a committee established for the
purpose of protecting the rights of participants in a research study. For more
information about your rights and role as a research participant you can visit the
Research Participant section of the IIRB, Inc. website atwww.iirb.com.
COSTS AND REIMBURSEMENT
There will be no costs to you from participating in this study.
For participation in the study, each research study participant will receive a cash
payment of $20 per hour. Payment will be made at the end of each visit or
whenever you withdraw from the study. If you are designated as an 'alternate
subject,' you will be paid $50 to compensate you for being inconvenienced.
CONFIDENTIALITY
Carroll-Loye Biological Research will retain records of this study indefinitely. You
may access your own records by contacting the Study Director. Representatives
from the sponsor (LANXESS Corporation), the U.S. Environmental Protection
Agency (EPA), the California Department of Pesticide Regulation and the
Independent Investigational Review Board, Inc. (an independent committee that
reviewed this study's ethical aspects to help protect the rights and welfare of
study participants) may have access to all non-personal information collected in
this study. Because of the need to release information to these parties, absolute
confidentiality cannot be guaranteed. Any information or reports published as a
result of this study will not identify you by name, or by any other personal
identification.
STATEMENTS OF UNDERSTANDING
Right to withdraw or removal from study
You understand that you are free to withdraw from this study at any time, and
you agree to inform the Principal Investigator immediately if you intend to
withdraw. It is understood that your decision to participate in this study or to
withdraw from this study will not influence the availability of your future medical
care and will involve no penalty or loss of compensation or benefits to which you
are otherwise entitled. You may withdraw from this study at any time.
Version: 11/2/09
Protocol: LNX-003
APPROVED BY
Initials:
Date:
11/2/09
Date
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Page 8 of 8
You agree that the Principal Investigator in charge of the study can remove you
from this study without your consent for any reason, including, but not limited to:
a. His/her judgment that any condition or circumstance may jeopardize your
welfare or the integrity of the study.
b. Your failure to follow the instructions of the investigator(s).
c. If the study is stopped by the sponsor and/or Principal Investigator prior to
completion.
Consent and signatures
I have read, in a language that I understand well, and understand the information
which has been stated above. I have received satisfactory answers to all of the
questions that I have asked. I hereby voluntarily consent to take part in this study
and to be a research study participant in this study. I do not waive any of my
legal rights by signing this Informed Consent Form. I shall receive a copy of the
signed Informed Consent Authorization.
Date Time Print Subject Name Sign Subject Name
(MM/DD/YY)
Date Print Carroll-Loye Sign Carroll-Loye
Biological Research
Representative
Biological Research
Representative
Copy of signed/dated consent form given to subject on (date)
by (initials)
Independent Investigational Review Board, Inc.
Approved: 7/28/09; Revised: 11/2/09
Version: 11/2/09
Protocol: LNX-003
APPROVED BY
Initials:
Date:
11/2/09
Date
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Experimental Subject's Bill of Rights
Any person who is requested to consent to participate as a subject in a research study involving
an experiment, or who is requested to consent on behalf of another, has the right to:
1. Be informed of the nature and purpose of the study.
2. Be given an explanation of the procedures to be followed in the experiment, and any
drug or device to be used.
3. Be given a description of any attendant discomforts and risks reasonably to be expected
from the experiment.
4. Be given an explanation of any benefits to the subject reasonably to be expected from
the experiment, if applicable.
5. Be given a disclosure of any appropriate alternative procedures, drugs, or devices that
might be advantageous to the subject, and their relative risks and benefits.
6. Be informed of avenues of medical treatment, if any, available to the subject after the
experiment if complications should arise.
7. Be given an opportunity to ask any questions concerning the experiment or the
procedures involved.
8. Be instructed that consent to participate in the study may be withdrawn at any time, and
the subject may discontinue participation in the medical experiment without prejudice.
9. Be given a copy of a signed and dated written consent form and Experimental Subject's
Bill of Rights when one is required.
10. Be given the opportunity to decide to consent or not to consent to an experiment without
the intervention of any element of force, fraud, deceit, duress, coercion or undue
influence on the subject's decision.
If you have any questions or problems during this study, or if you think that you may have
experienced a research-related injury, you should contact Scott Carroll of Carroll-Loye
Biological Research at (530) 902-8267 at any time.
If you have any questions regarding your rights as a research volunteer, please contact Kim
Lerner, Chairman of the Independent Investigational Review Board, Inc. at toll free (877) 888-
IIRB (4472) between 6AM and 2PM, Pacific Time, Monday through Friday. The Independent
Investigational Review Board is a committee established for the purpose of protecting the rights
of volunteers in a research study.
Signature of Subject Date
Signature of Witness Date
7/28/09
Signature
Date
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Carroll-Loye Biological Research Study LNX-003
Summary of Protocol Deviations
There were no protocol deviations observed or noted for this study.
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Appendix 9. Physical plan of Carroll-Loye Biological Research Laboratory
FItli of t ;il roIl-Loyt Rhloglfal Misearsli Laboratory
111 Onl: Av*m;e. D.v.l: >' .llifmua
Iaifiici -rlimeu-iioo-. 15.5' E2 J' N'o
VerrioaZ, Jw2COfi
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Department of Pesticide Regulation
Mary-Ann Warmerdam
Director
Arnold Schwarzenegger
Governor
November 16,2009
Dr. Scott P. Carroll
711 Oak Avenue
Davis, California 95616
Dear Dr. Carroll:
In accordance with the provisions of the California Code of Regulations, Title 3 (3CCR), Chapter 3,
Section 6710, the Director of the Department of Pesticide Regulation (DPR) grants final approval of the
pesticide study protocol entitled, "Efficacy Test of KBR 3023 (Picaridin; Icaridin) - Based Personal
Insect Repellents (20% Cream and 20% Spray) with Ticks Under Laboratory Conditions" on
November 10,2009. This study protocol and associated consent form were reviewed and unanimously
approved by the Independent Investigational Review Board of Plantation, Florida on November 2,2009,
in accordance with 40 CFR Part 26. This study approval will expire on November 1,2010.
Please note that Section 6710 of 3CCR authorizes DPR staff to observe your study. Site visits may
include observing subject recruitment and the informed consent procedures. This section also authorizes
an official observer from DPR or the county agricultural commissioner's office to terminate any study
activity that jeopardizes the safety of the study subjects, the public, or the environment.
This study must be conducted according to the approved protocol and consent forms. All protocol and
consent form amendments that may impact the health of the human participants must have DPR and
Institutional Review Board approval prior to implementing such changes (3CCR 6710, subsection g).
If during the study, problems should arise related to the safety of the study subjects, please notify our
office immediately. If you have any questions, please feel free to contact Don Richmond of my staff at
(916)445-4192, or by e-mail at: drichmond@cdpr.ca.gov.
George Farnsworth, Environmental Program Manager I
Worker Health and Safety Branch
(916)445-4163
cc: Anna M. Fan, Ph.D., Chief, Pesticide and Environmental Toxicology Branch (PETB), OEHHA
Joy Wisniewski, Ph.D., Pesticide Epidemiology Section, PETB, OEHHA
Susan Edmiston, Environmental Program Manager II, WHS Branch, DPR
Joseph P. Frank, D.Sc., Senior Toxicologist, WHS Branch, DPR
Roger Cochran, Ph.D., D.A.B.T., Staff Toxicologist, WHS Branch, DPR
Don Richmond, Research Scientist II, WHS Branch, DPR
Sincerely,
10011 Street • P.O. Box 4015 • Sacramento, California 95812-4015 • www.cdpr.ca.gov
A Department of the California Environmental Protection Agency
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LNX-003 IRB <-> CLBR CORRESPONDENCE
Post-Submission of Protocol for HSRB Review
Amendment 1 submission by CLBR to IIRB, Inc. 2 November 2009
12:41 AM Documents emailed with cover letter
Enclosures:
Protocol as amended with track changes showing
ICF as amended with track changes showing
Subject training document for ticks as amended with
tracked changes showing
Amendment 1
8:09 AM IIRB, INC. email to acknowledge receipt
158
97-124
125-132
133-134
135-144
158
Amendment 1 approval by IIRB, INC. 9 November 2009
12:41 AM IIRB, INC. emails scanned approval documents 159
Enclosures:
Amendment 1 Approval Letter 160
Final Approved ICF 145-152
Request for Meeting Minutes, Current Roster, and Current HRPP Plan, 5 Februray 2010
8:29 AM CLBR makes request by email 161
9:21 and 9:24 AM IIRB, INC. responds via email 161
Enclosures 9:21 AM:
Roster 10/1/09 162-163
Roster 1/21/10 164-165
Email 9:24 AM 166
HRPP Plan 9/17/09 (eel Note: submitted as separate file)
CLBR Acknowledges receipt and readability of Roster and HRPP Plan documents, 10
February 2010
1:55 PM email to IIRB, INC. 166
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from Shawn King
to Robert Roogow
cc Yesenia Crespo ,
Scott P Carroll ,
Ghona Sangha
date Mon, Nov 2, 2009 at 12:41 AM
subject Study LNX 003 Amendment 1 submission for
review
Hi Robert,
Please find enclosed Amendment 1 and supporting documents for
Carroll-Loye Biological Research study LNX-003. If you have any
questions, please contact us at your earliest convenience. Thank you.
Ed. Note: The attachments to this email appear as follows -
Amendment 1 FINAL appears on pages 135-144 of this report
ICF amended appears on pages 125-132 of this report
Protocol amended appears on pages 97-124 of this report
Tick training v5 amended appears on pages 133-134 of this report
From Yesenia Crespo
to Shawn King
date Mon, Nov 2, 2009 at 8:09 AM
subject RE: Study LNX 003 Amendment 1 submission
for review
Thanks Shawn for your submission, we will go ahead and try to review this by this week.
Regards,
Yesenia Crespo
Project Leader
Independent Investigational Review Board INC.
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from Yesenia Crespo
to Shawn King
date Mon, Nov 9, 2009 at 9:48 AM
subject LNX Amendment
Please see attached
Regards,
Yesenia Crespo
Project Leader
Independent Investigational Review Board INC
Ed. Note: The cover letter (page one) of this attachment appears below. The remainder
of the attachment is final version of the Informed Consent Form as it appears on pages
145-152 of this submission.
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Your Advocate for Clinical Research Participants
DATE:
November 02, 2009
TO:
Scott P. Carroll, PhD
Principal Investigator
FROM:
Authorized Signatory I
Independent Investigational Review Board, fnc
SUBJECT: Protocol Amendment;
Informed Consent Form version 11/2/2009
Amendment 1 dated 10/30/2009
PROTOCOL: LNX-003
The Independent Investigational Review Board, Inc. had an opportunity to review the
above referenced Informed Consent Form and Amendment 1 for the above noted
research study. The Amendment included administrative changes to the Objective of
the Research, Risk Section, candidate recruitment and Exclusion Section. In addition
other administrative changes were made throughout the document. This submission
met the criteria for a minor change in previously approved research and was reviewed
under expedited review procedures.
The Informed Consent Form and Amendment 1 are approved. The Informed Consent
Form has been revised to accommodate the Amendment. The approved revised
Informed Consent Form is identified as Version 11/2/2009 and stamped, "Approved
11/2/2009". All current subjects and future research participants must sign the revised
consent forms.
Thank you for your cooperation.
FC/JB/yc/rr:
phone 954-327-0778 •fax 954-327-5778 • 6738 West Sunrise Blvd., Suilc 102 • Plantation, FL 33313 • info@iirb.com (email) • www.iirb.com
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from Shawn King
to Yesenia Crespo
cc Robert Roogow ,
Scott P Carroll
date Fri, Feb 5, 2010 at 8:29 AM
subject LNX 003 Meeting minutes, HRPP, Roster
Hi Yesenia,
I hope you are well. When you have a chance, could you forward the
meeting minutes for IIRB's review of Amendment 1 for our study
LNX-003? For your reference, the amendment was reviewed and approved
by IIRB the week of November 2 2009. Also, we have on file IIRB's
HRPP dated June 1 2009 and a membership roster dated August 5 2009.
If either have been updated, could you forward the new versions to us
as well? We greatly appreciate your assistance.
Best, Shawn King
Director of Operations
Carroll-Loye Biological Research
from Robert Roogow
to Shawn King
cc Yesenia Crespo
date Fri, Feb 5, 2010 at 9:21 AM
subject RE: LNX 003 Meeting minutes, HRPP, Roster
Hello Shawn,
I have attached all of our rosters since August 5, 2009.1 will need to send the newest
HRPP Plan with a different email to ensure it goes through. As for the Amendment that
was approved 11/2/2009, it was approved through expedited procedures and not at a
convened meeting; therefore, there are not meeting minutes for that transaction. Let me
know if you should need anything else.
Best regards,
Robert
Robert Roogow, MS, CIM
Chief Operating Officer
Independent Investigational Review Board, Inc.
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INOlTl NDF.N 1"
RFVI^'BOARDINC. IRB Membership Roster
1'he Hiii of f htticc H hi'n Ow * "twic e is )mtrs
• The following lists the members identified by name; earned degrees; representative capacity;
indications of experience such as board certifications, licenses, etc., sufficient to describe each
member's chief anticipated contributions to IRB deliberations.
• No member of the Independent Investigational Review Board, Inc has employment or other
relationship (for example, full-time employee, a member of governing panel or board, stockholder,
paid or unpaid consultant) of any study sponsor, or otherwise involved with the research.
I'KIMAKY MINIMUS
Frances Conway, RN
CHAIR
(Scientific) Affiliated
Member since 2008
Ms. Conway is a registered nurse with knowledge of regulatory requirements as related to
IRB compliance with FDA, DHHS, and EPA regulations.
Julie A. Blasingim, BA, MBA
VICE CHAIR
(Non-Scientific) Affiliated
Member since 2009
Ms. Blasingim comes to the IRB with extensive knowledge of human research protection
issues and regulatory compliance. She presents ongoing educational programs and
regulatory updates to the IRB members and IIRB staff.
Marcos Rejtman, DO
(Scientific) Unaffiliated
Member since 2005
Dr. Rejtman is Board Certified in Family Practice, Geriatric Medicine and Hospice &
Palliative Care. Through his experience, Dr. Rejtman is able to evaluate protocols from a
scientific perspective with a focus on risks/benefit analysis.
Rabbi Akiva D. Mann, MA
(Non-Scientific) Unaffiliated
Member since 1997
Rabbi Mann is the Director of The Institute of Jewish Knowledge and Learning and
provides moral and ethical perspectives to the review process.
Edward Wiederhorn
(Non-Scientific) Unaffiliated
Member since 1995
Mr. Wiederhorn is a community representative to the IIRB, Inc. He is a member of the
American Association of Retired Persons (AARP) and has been involved with Fraternal
and Charitable Organizations.
Shari Somerstein, RPh
(Scientific) Unaffiliated
Member since 1999
Ms. Somerstein has extensive experience in clinical pharmacology and the drug
development process through analysis of clinical and non-clinical data, with a focus on
human research protection.
George J. Garbarino
(Non-Scientific) I naffiliated
Member since 2004
Mr. Garbarino has been an advocate for Labor Union members and brings a wide range of
experience in the area of workers' rights.
Al l I.KNA I 1. M I'M HI'.US
Alternate Members seive as a voting member, when filling the role of an absent voting member. Alternate Scientific Members can
serve as a voting alternate member for !•'ranees Conway, but cannot serve as a Chair of the IRB. Alternate Son-Scientific
Members can serve as an alternate voting member for Julie Blasingim, but cannot serve as a I 'ice Chair of the IRB.
Ernest Bertha, MD, MBA
*(Scientific) Unaffiliated
Member since 2009
Dr. Bertha is a Board Certified Pediatrician specializing in emergency medicine, bringing
with him a background of pediatric acute care medicine.
David D. Wells, MD
(Scientific) Unaffiliated
Member since 1996
Dr. Wells has served as an Emergency Medicine Department Chairman. He has worked
with different ethnic populations, especially migrant workers and brings his sensitivity of
the social mores of the underprivileged to the IRB.
Glenn K. Moran, MD, FACOFP
(Scientific) Unaffiliated
Member since 2004
Dr. Moran is Board Certified in Family Practice. Through his present practice, he is able
to contribute up to date information related to the current medical world. In addition, Dr,
Moran is a Professor of Osteopathic Medicine at a local university.
Robert Lettman, Esq
(Non-Scientific) Affiliated
Member since 2004
Mr. Lettman is a practicing Attorney providing legal understanding with regard to the
rights of research participants.
Version: 10/1/09
Page 1 of 2
Replaces 6/1/09
IRB Membership Roster
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Levi G. Williams, Esq
(Non-Scientific) Unaffiliated
Member since 2007
Mr. Williams is a practicing Attorney with a focus on cultural diversity, including multi-
racial and juvenile rights.
Marijke Adams, PharmD, PhD
(Scientific) Unaffiliated
Member since 2009
Ms. Adams is an adjunct pharmacology Professor at a local University. She also has
extensive experience in pharmaceutical drugs development, protocol development,
regulatory requirements, and the conduct of clinical and nonclinical research.
CHANGES FROM PREVIOUS ROSTER (Version: 6/1/09)
Resignation of Kim Lerner as Chair, appointment of Frances Conway, RN as Chair, appointment of Julie Blasingim, BA, MBA as
Vice Chair, appointment of Marijke Adams, PharmD, PhD as an alternate IRB Member as well as other minor clarifications.
'ersion: 6/1/09
Replaces 1/6/09
Page 2 of 2
IRB Membership Roster
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KU0 INDEPENDENT
i N v E st l gat I o N A L Membershit) Roster
REVIEW BOARD INC. iViemDer^mP rosier
The IRB of Choice When the Choice is Yours
• The following lists the members identified by name; earned degrees; representative capacity;
indications of experience such as board certifications, licenses, etc., sufficient to describe each
member's chief anticipated contributions to IRB deliberations.
• No member of the Independent Investigational Review Board, Inc has employment or other
relationship (for example, full-time employee, a member of governing panel or board, stockholder,
paid or unpaid consultant) of any study sponsor, or otherwise involved with the research.
PRIMARY MEMBERS
Frances Conway, RN
CHAIR '
(Scientific) Affiliated
Member since 2008
Ms. Conway is a registered nurse with knowledge of regulatory requirements as related to IRB
compliance with FDA, DHHS, and EPA regulations.
Julie A. Blasingim, BA, MBA
VICE CHAIR
(Non-Scientific) Affiliated
Member since 2009
Ms. Blasingim comes to the IRB with extensive knowledge of human research protection issues
and regulatory compliance. She presents ongoing educational programs and regulatory updates to
the IRB members and IIRB staff.
Marcos Rejtman, DO
(Scientific) Unaffiliated
Member since 2005
Dr. Rejtman is Board Certified in Family Practice, Geriatric Medicine and Hospice & Palliative
Care. Through his experience, Dr. Rejtman is able to evaluate protocols from a scientific
perspective with a focus on risks/benefit analysis.
Rabbi Akiva D. Mann, MA
(Non-Scientific) Unaffiliated
Member since 1997
Rabbi Mann is the Director of The Institute of Jewish Knowledge and Learning and provides
moral and ethical perspectives to the review process.
Edward Wiederhorn
(Non-Scientific) Unaffiliated
Member since 1995
Mr. Wiederhorn is a community representative to the IIRB, Inc. He is a member of the
American Association of Retired Persons (AARP) and has been involved with Fraternal and
Charitable Organizations.
Shari Somerstein, RPh
(Scientific) Affiliated
Member since 1999
Ms. Somerstein has extensive experience in clinical pharmacology and the drug development
process through analysis of clinical and non-clinical data, with a focus on human research
protection.
George J. Garbarino
(Non-Scientific) Unaffiliated
Member since 2004
Mr. Garbarino has been an advocate for Labor Union members and brings a wide range of
experience in the area of workers' rights.
ALTERNATE MEMBERS
Alternate Members serve as a voting member, when filling the role of an absent voting member. Alternate Scientific Members can
serve as a voting alternate member for Frances Conway, bat cannot serve as a Chair of the IRB. Alternate Non-Scientific Members
can serve as an alternate voting member for Julie Blasingim, bat cannot serve as a Vice Chair of the IRB.
Ernest Bertha, MD, MBA
*(Scientific) Unaffiliated
Member since 2009
Dr. Bertha is a Board Certified Pediatrician specializing in emergency medicine, bringing with
him a background of pediatric acute care medicine.
David D. Wells, MD
(Scientific) Unaffiliated
Member since 1996
Dr. Wells has served as an Emergency Medicine Department Chairman. He has worked with
different ethnic populations, especially migrant workers and brings his sensitivity of the social
mores of the underprivileged to the IRB.
Glenn K. Moran, MD,
FACOFP (Scientific)
Unaffiliated
Member since 2004
Dr. Moran is Board Certified in Family Practice. Through his present practice, he is able to
contribute up to date information related to the current medical world. In addition, Dr, Moran is
a Professor of Osteopathic Medicine at a local university.
164 of 168
Version: 1/21/10
Page 1 of 2
Replaces 10/1/09
IRB Membership Roster
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Robert Lettman, Esq
(Non-Scientific) Affiliated
Member since 2004
Mr. Lettman is a practicing Attorney providing legal understanding with regard to the rights of
research participants.
Levi G. Williams, Esq
(Non-Scientific) Unaffiliated
Member since 2007
Mr. Williams is a practicing Attorney with a focus on cultural diversity, including multi-racial
and juvenile rights.
Marijke Adams, PharmD, PhD
(Scientific) Unaffiliated
Member since 2009
Dr. Adams is an adjunct pharmacology Professor at a local University. She also has extensive
experience in pharmaceutical drugs development, protocol development, regulatory requirements,
and the conduct of clinical and nonclinical research.
Rev. Pat Alessi
(Non-Scientific) Unaffiliated
Member since 2010
Rev. Pat Alessi is an ordained minister serving as an Associate Minister for more than 35 years.
Her experience allows her to provide moral and ethical perspectives to research involving
humans.
CHANGES FROM PREVIOUS ROSTER (Version: 10/1/09)
Addition of Rev. Pat Alessi, and change in affiliation status for Shari Somerstein, RPh.
'ersion: 6/1/09
Replaces 1/6/09
Page 2 of 2
IRB Membership Roster
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from Robert Roogow
to Shawn King
date Fri, Feb 5, 2010 at 9:24 AM
subject RE: LNX 003 Meeting minutes, HRPP, Roster
Shawn,
Here is the HRPP plan.
Robert Roogow, MS, CIM
Chief Operating Officer
Independent Investigational Review Board, Inc.
Ed. Note: The HRPP plan is provided as a separate electronic document bundled with
the Study Final Report submission to EPA
from Shawn King
to Robert Roogow
date Wed, Feb 10, 2010 at 1:55 PM
subject Re: LNX 003 Meeting minutes, HRPP, Roster
Robert,
Thanks for your prompt responses. Sorry to so slow in sending
confirmation -1 had no problem downloading and opening the hrpp plan
and membership roster documents.
Best, Shawn King
Director of Operations
Carroll-Loye Biological Research
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OTI Collaborative Institutional Training Initiative
Human Research Curriculum Completion Report
Printe# on Thursday, October 30,2008
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Genetics Research. Part 2
10/24/07
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Research with Protected Populations - Vulnerable Subjects: A
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Vulnerable Subjects - Prisoners, Part 2
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Human Subjects Protections at the VA, Part 1
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jHuman Subjects Protections at the VA, Part 2
04/10/08
iHIPAA and Human Subjects Research.
04/10/08
Conflicts of Interest in Research Involving Human Subjects.
04/10/08
How to Complete the CITI Refresher Course and Receive a
Completion Report
04/10/08
For this Completion Report to be valid, the learner listed above must be
affiliated with a CITI participating Institution, Falsified Information and
unauthorized use of the CITI course site is unethical, and may be considered
scientific misconduct by your institution.
Paul Braunschweiger Ph.D.
Professor, University of Miami
Director Office of Research Education
CITI Course Coordinator
Return
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Certificate of Completion
The National Institutes of Health (NIH) Office of Extramural Research
certifies that William Johnson successfully completed the NIH Web-
based training course "Protecting Human Research Participants".
Date of completion: 10/03/2008
Certification Number: 110234
Certificate of Completion
The National Institutes of Health (NIH) Office of Extramural Research
certifies that Shawn King successfully completed the NIH Web-based
training course "Protecting Human Research Participants".
Date of completion: 10/21/2008
Certification Number: 121628
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