1 Kevin Sweeney Eric Bohnenblust, Ph.D. Maureen Lydon Office of Pesticide Programs 

# EPA Review of i2LResearch USA, Inc. Protocol Testing of S.C. Johnson Personal Tick Repellent Products to Support their Use of the EPA Repellency Awareness Graphic.

# Overview i2LResearch submitted a protocol for testing insect repellent products against ticks in the laboratory to determine the Complete Protection Time (CPT) of their 18 skin applied repellent products to support the use of the EPA Repellency Awareness Graphic.

2

# Overview (2) Testing will be conducted by i2L Research USA, Inc. in Baltimore, Maryland. Testing will be conducted against 3 tick species with up to 30 different human subjects per product (10 per species).

3

# Comparisons to Skin- Applied Repellent Protocols Reviewed by the HSRB In this protocol:


##  Aerosol and lotion products are proposed to be tested at 1 g/600cm 2 

##  Spritz/pump sprays are proposed to be tested at 0.5 g/600cm 2 

##  A dosimetry phase is not proposed.

• This is a departure from the design of repellent efficacy studies that that have been reviewed and approved by EPA and the HSRB in recent years, which have experimentally determined the dose. 4

# What is the Repellency Awareness

Program? **A program to raise public awareness of the health protectiveness**  **of mosquito and tick repellents applied**  **to the skin.** Purposes : 

###  Raise consumer awareness of the efficacy of skin applied insect repellents. 

###  Increase EPA and consumer confidence in the efficacy claims on labels. 

###  Improve consumer protection against vector borne diseases, such as Lyme disease and West Nile virus.

# EPA Repellency Awareness Graphic

6

# Repellency Awareness Graphic The graphic clearly informs consumers about the duration of repellent protection so that they can make informed choices about the repellent products they purchase and use.

78



# Science Assessment: Testing of S.C. Johnson Personal Tick Repellent Products to Support their Use of the EPA Repellency Awareness Graphic

**Kevin Sweeney Eric Bohnenblust,**  **Ph.D.** Registration Division Office of Pesticide Programs9



# Study Objectives To determine the complete protection time (CPT) of up to eighteen EPA registered skin applied repellent products from S.C. Johnson & Son, Inc. in the laboratory against adults of 3 tick species using volunteer human subjects to support use of the EPA Repellency Awareness Graphic on the product label.

# Study Objectives (2) The data provided from this research can be used by the EPA to support the addition of the Repellency Awareness Graphic to skin applied insect repellent labels, thereby allowing for better protection of consumers from nuisance arthropod bites and bites that lead to arthropod - borne diseases.

1011 

# Acute Toxicity of the Test Materials All test materials are S.C. Johnson Products registered by the EPA as skin applied insect repellents. 

##  Acute Dermal LD 50 

### >2,000 mg/kg body weight 

##  Minimally irritating to the skin and eyes. 

##  Not skin sensitizers.12 

# Margin of Exposure (MOE) Estimate S.C. Johnson prepared an estimate of the Margin of Exposure via the dermal route for each of the 18 products to be tested. The proposed exposures to the subjects in these tests are not of concern for the three active ingredients to be tested.

## Calculated **Margins of Exposure for DEET Products**

**Product Dose**  **(mg) 1**  **Acute**

**Product 2**  **LD 50**  **(mg /kg)**  **MOE Adj.**  **Acute Product** **6 LD**  **50 (mg** **/kg) Adj.** 

**MOE 6**  **Acute 3** 

**Active Ingredient**  **LD 50**  **(mg /kg)**  **MOE 4** 
**5% DEET**  **Spritz (4822** **- 415)**  567 >2,000 > **282** 5000 > **705** 4280 **>8161 5.6%**  **DEET Towelette**  **(4822 -** **552)** 1133 >2,000 > **141** 5000 > **353** 4280 **>3645 7%**  **DEET Spritz**  **(4822 -** **395)** 567 >2,000 **>282** 5000 > **705** 4280 **>5829 15%**  **DEET Aerosol**  **(4822 -** **380)** 1133 >2,000 > **141** 5000 > **353** 4280 **>1361 15%**  **DEET Aerosol**  **(4822 -** **543)** 1133 >2,000 > **141** 5000 > **353** 4280 **>1361 25%**  **DEET Aerosol**  **(4822 -**  **167)** 1133 >2,000 > **141** 5000 > **353** 4280 **> 817**  **25% DEET**  **Towelette (4822** **- 258)**  1133 >5,000 > **353** 4280 **> 817**  **25% DEET**  **Spritz (4822** **- 399)**  567 >5,000 > **705** 4280 **> 1632**  **25% DEET**  **Aerosol (4822** **- 572)**  1133 >5,000 > **353** 4280 **> 817**  **30% DEET**  **Aerosol (4822** **- 397)**  1133 >5,000 > **353** 4280 **> 680**  **98.25% DEET**  **Spritz (4822** **- 276** **)** 567 4280 **> 615**  13 

### Ta **ble 1:**

### Calculated Margins of Exposure for Picaridin Products

**Product Dose**  **1 (mg)**  **Acute**

**Produ ct**  **LD 02**  **(mg/kg) MOE**  **Acute Active**  **LD 03**  **(mg/kg) MOE**  **5% Picaridin**  **Spritz (4822** **- 536)**  1133 >5,020 354 >2000 **1249 4**  **5% Picaridin**  **Lotion (4822** **- 535)**  1133 >5,040 356 >2000 **2824 20%**  **Picaridin Spritz(4822** **- 556)**  1133 >5,020 354 >2000 **312 4**  **20% Picaridin**  **Aerosol (4822** **- 564**  **1133 >5,020**  **354 >2000**  **312 4** 

14 **Product Dose**  **1 (mg)**  **Acute Product** **2 LD**  **50 (** **mg/kg) MOE**  **Acute Active**  **LD 50**  **(mg/kg) 3**  **MOE 5%**  **Picaridin Spritz**  **(4822 -**  **536)** 567 >5,020 > **708** >2000 **>2497 4**  **5% Picaridin**  **Lotion (4822** **- 535)**  1133 >5,040 > **356** >2000 **>2824 20%**  **Picaridin Spritz(4822** **- 556)**  567 >5,020 > **708** >2000 **>624 4**  **20% Picaridin**  **Aerosol (** **4822 -**  **564)** 1133 >5,020 **> 354**  >2000 **>312 4**  

### Ta **ble 2:**

### Calculated Margins of Exposure for

**p -**  **Methane -** **3 , 8** **- Diol**  **(PMD) Products**

**Product Dose**  **1 (mg)**  **Acute Product** **2 LD**  **50 (mg/kg)**  **MOE Acute**  **Active 3**  **LD 50**  **(mg/kg) MOE** **4 8%**  **PMD Towelette(4822 -**  **526) 1133**  >5,000 > **353** >5000 **>4413 10%**  **PMD Lotion**  **(4822 -** **515) 1133**  >5,000 > **353** >5000 **>3529 10%**  **PMD Spritz(4822** **- 528)**  **567** >5,000 **>705** >5000 **>7055**

15 

### Ta **ble 3:**

# Dosage and Product Application i2LResearch will not include a dosimetry phase to determine “typical consumer dose.” Instead, i2LResearch proposes standardized rates of:


##  1 g/600cm 2 

### for aerosol and lotion products 

##  0.5 g/600cm 2 

### for Spritz/pump sprays

16

# Dosage and Product Application (2) A set dose can be related to known consumer behavior based on past tests reviewed by the HSRB where dosimetry was employed for skin applied insect repellent products.

17

# Dosage and Product Application (3) The HSRB determined during their April meeting that a dose of 1 g/600cm 2 was appropriate for all product types. However, based on analysis of dosimetry results from repellent studies reviewed since 2006, EPA recommends the following doses be used for studies conducted using this protocol:


###  Aerosol/lotion – 1 g/600cm 2 

###  Towelette/pump spray 0.5g/600cm 2 Data may be bridged from a pump spray to a towelette because pump spray and towelette formulations are usually similar and the pump spray is applied at a lower dose. 18

# Experimental Design For each test, 10 subjects (5 males and 5 females) will be treated with the test substance. Two additional subjects (one male and one female) will serve as alternates for each test.


###  The test subjects will be selected at random from a pool of potential subjects from the area around Baltimore, MD.

19

# Experimental Design (2) For each product there will be a total of up to 30 different treated subjects and up to 6 different alternate subjects.


###  The subjects will not be blinded to the test substances with which they are treated. 

###  If subjects participate in more than 1 test, the tests must be separated by a minimum of 2 days. Subjects are required to wash after each test. 

### A positive control substance will not be used.
20

# Experimental Design (3) Each subject will have one forearm treated with the repellent product to be tested, and the other arm will serve as the untreated control.


###  Assignment of the test substance to the subject’s arms will be randomized . 

###  The control arm will be used to qualify ticks that are active, and determine the attractiveness of the subject to ticks. 

### The data collected from the control arm will not be used to calculate the Median Complete Protection Time.

21

# Experimental Design (4) Four lines will be drawn on both of the subjects’ forearms as follows:

 ‘Release line’ 3 cm above the wrist bone towards the elbow 

###  ‘Boundary line’ 3 cm above the release line towards the elbow (this will be the edge of the treated area) 

###  ‘Crossing line’ 3 cm above the boundary line 

###  An upper boundary line 12 cm above the boundary line; this will not be used during testing and serves only to denote the boundary of the treated area. 22

# Experimental Design (5)

23 

### ‘R elease line’ ‘Upper boundary’

‘Crossing line’ ‘Boundary line’24 

### ‘R elease line’ ‘Boundary line’

‘Crossing line’ ‘Upper boundary’

# Experimental Design (6) Ticks will be trialed to make sure they will actively quest. To qualify this behavior, ticks will be placed at the ‘release line’ on the untreated control arm and then must cross the boundary line within 3 min. Treatments will be challenged with 1 tick every 15 minutes (4 ticks/h).

25

# Experimental Design (7)

 Once qualified, the ticks will be placed at the ‘release line’ on the treated arm.  After the tick begins to move up the arm, it will be given 3 minutes to cross the ‘boundary’ and ‘crossing’ lines on the treated arm.  Ticks are considered repelled if in 3 min. they do not:


###  Reach the ‘boundary’ line 

###  Reach the ‘crossing’ line  Ticks are considered not repelled if in 3 min. they reach the crossing line. 2627 

## Experimental Design (8) – DEET Products

**Repellent Product EPA Reg. No. Product Type**  **Number of Tick Species**  **Number of**

**Human Subjects per**  **Tick Species (Replicates)**  **Total**

**Replicates per**  **Product Maximum** 

**Number of Tick Exposures per**  **Species /Product**  **Test (18**  **hours) 4822** **- 415**  5% DEET Spritz 3 10 30 72/206 **4822 -**  **552** 5.6% DEET T owelette 3 10 30 72/206 **4822 -** **395** 7% DEET Spritz 3 10 30 72/206 **4822 -** **380** 15% DEET Aerosol 3 10 30 72/206 **4822 -**  **543** 15% DEET Aerosol 3 10 30 72/206 **4822 -**  **167** 25% DEET Aerosol 3 10 30 72/206 **4822 -**  **258** 25% DEET T owelette 3 10 30 72/206 **4822 -** **399** 25% DEET Spritz 3 10 30 72/206 **4822 -**  **572** 25% DEET Aerosol 3 10 30 72/206 **4822 -** **397** 30% DEET Aerosol 3 10 30 72/206 **4822 -**  **276** 98.25% DEET Spritz 3 10 30 72/20628 

## Experimental Design (9) – Picaridin Products

**Repellent Product** 

**EPA Reg.**  **No. Product**  **Type Number of**  **Tick Species**  **Number of** 

**Human Subjects per**  **Tick Species (Replicates)**  **Total**

**Replicates per**  **Product Maximum** 

**Number of Tick**  **Exposures per Species**  **/Product Test**  **(18 hours )**  **4822 -**  **536** 5% Picaridin Spritz 3 10 30 72/206 **4822 -**  **535** 5% Picaridin Lotion 3 10 30 72/206 **4822 -**  **556** 20% Picaridin

Spritz 3 10 30 72/206 **4822 -**  **564** 20% Picaridin

Aerosol 3 10 30 72/206

## Experimental Design (10) – PMD Products

29

**Repellent Product EPA**  **Reg. No.**  **Product Type**  **Number of Tick**  **Species Number of** 

**Human Subjects per**  **Tick Species (Replicates)**  **Total**

**Replicates per**  **Product Maximum** 

**Number of Tick Exposures**  **Per Species/Product**  **Test (18 hours** **) 4822** **- 526**  8% PMD T owelette 3 10 30 72/206 **4822 -**  **515** 10% PMD Lotion 3 10 30 72/206 **4822 -**  **528** 10% PMD Spritz 3 10 30 72/20630 

# Endpoints and Measures
 

## Unit of measure for determination of the repellent effects is Complete Protection Time (CPT).
 

### “The CPT for each tick species will be calculated as the time from test substance application to the time of the First Confirmed Crossing. The time in hours for each individual test subject will be used to calculate the median protection time for each species separately.”

# Endpoints and Measures (2)
 

## A‘Crossing’ occurs when a tick crosses the ‘crossing line’ within 3 min. on the treated arm of a subject.  

## A ‘First Confirmed Crossing’ is that which is followed by the subsequent tick crossing in the next exposure period, or the first subsequent tick is repelled but the second subsequent tick is recorded as not being repelled. 31

# Statistical Analysis Plan
 

## The objective of the data analysis is to estimate the Median Complete Protection Time.  

## The Median CPT of all test subjects will be calculated using the Kaplan - Meier Survival Analysis, which is advantageous since CPTs may not be normally distributed.

32

# Statistical Analysis Plan (2)

**Sample size**  **Distributional**

**position for**  **95% LCL Distributional** 

**position for**  **95% UCL Percent of** 

**values above LCL**  **10 1**  **8 90%**  **12 2**  **10 83%**  **15 3**  **11 80%**  **20 5**  **15 75%**  33 **Ta ble 1:Kaplan** **- Meier**  **Median Confidence Limits for**  **a Range of Sample Sizes.**  

### As evidenced by the table, sample sizes larger than ten would provide only marginal increases in precision relative to the increase in the number of exposed test subjects.

# Statistical Analysis Plan (3) The Kaplan- Meier Survival Analysis has been accepted by EPA and the HSRB for the Median CPT calculation in past efficacy studies using repellents and is also recommended by the World Health Organization for CPT calculation from these data sets.

34

# Statistical Analysis Plan (4) The proposed sample size of 10 subjects per study represents a reasonable compromise between increasing precision and limiting costs based on past analyses by the EPA.

3536 

# Measures to Ensure Reliability

 Good Laboratory Practices, as defined by 40 CFR part 160 will be followed throughout all studies.  Study staff will conduct a training session with the subjects on a day prior to the test date.  Study staff will treat the skin of the exposed limb with the test substance and the limb will be measured in advance.  Study staff will place ticks on the untreated and treated arms.  Study staff will monitor and record tick movement and the start and stop times for each exposure period.  Study staff and the study director will track test substance samples, closely monitor the testing, and data recording.  Alternate subjects will be enrolled to ensure adequate sample size.  A Quality Assurance Unit will be in place to monitor all study activities and data collection.  Test subjects can only take part once in any two-day testing period. If scheduled to participate in two studies within one week, there will be two calendar days in between test days.37 

# Compliance with Scientific Standards The following elements are adequately addressed:


##  Available toxicity studies with DEET, picaridin, and PMD. • Adequately characterize toxicological profile of the formulations. • Data to support estimate of acceptable Margin of Exposure (MOE).

# Compliance with Scientific Standards The following elements are generally acceptable but require refinement and clarification:
• Pre-Training
• Experimental Design
• Data Analysis
38

# Science Comments and

Recommendations 1 **1) EPA comment** : “Pre-training of subjects is barely described. More information is required. The protocol should be explicit with regard to the training outline and specific topics to be addressed.” **S.C. Johnson & i2L response**  **:** Revised section 2.2.5 with an outline providing specifics for pre-training. 39

# Science Comments and

Recommendations 2 **2) EPA comment** : “Please provide more details on the exact timing of the testing. The protocol needs to explicitly describe the amount of time the technician has to do testing and the amount of time in a 15 minute period that requires the subject to be seated and exposed to ticks .” **S.C. Johnson & i2L Research response**  : Revised protocol to include specific details regarding testing.

40

# Science Comments and

Recommendations 3 **3) EPA comment** : “Repellent sample size selection: The protocol cites one example of the effect of sample size on mean confidence interval width when changed from 10 to 20 subjects. Submit a simulation showing the impact of increasing sample size on the width of 95% confidence interval of median CPT where median CPT will be estimated using Kaplan Meier method. This can be presented in table form .” 41

# Science Comments and Recommendations 3 continued **S. C. Johnson & i2L Research**  **response :**  “Sample size is adequate and is unlikely to overestimate CPT due to selection of the lowest CPT value, and historical precedent.”

42

# Science Comments and Recommendations 3 continued **S. C. Johnson & i2L Research**  **response continued:** “The confidence limits associated with the Kaplan - Meier median are positional values in the distribution, rather than calculated values as in the case of a confidence interval around the mean .” 43

# Science Comments and Recommendations 3 continued **S.C. Johnson & i2L**  **Research response**  **continued:**

“ The table from slide 32 indicates which positions in the distribution of values constitute the lower confidence limit (LCL) and upper confidence limit (UCL) of the median for various sample sizes. The assumption is that the values are sorted in increasing order, so value “1” in the distribution refers to the smallest value (i.e., the minimum).” 44

# Science Comments and

Recommendations 4 **4) EPA Comment:** A randomization mechanism needs to be inserted into sections 2.3.8 and 2.3.9. **S.C. Johnson & i2L Research**  **response:** Will use a random number generator from a statistical software package (e.g., M initab, Excel) 4546



# Science Comments and Recommendations 5 **5) EPA Comment:**  Amend the protocol to require subjects to wait at least two calendar days (48 hours) between tests if they participate in multiple tests . **S.C. Johnson & i2L Research**  **response:** Amended the protocol to require subjects wait two days between participating in different tests

# Compliance with Scientific Standards As amended to address the concerns raised in the EPA review, the i2L Research USA protocol entitled “Testing of S.C. Johnson Personal Tick Repellent Products to Support their Use of the EPA Repellency Awareness Graphic” is likely to yield scientifically reliable information, satisfying the following scientific criteria from the framework recommended by the HSRB: 

##  It would produce important information that cannot be obtained except from research with human subjects. 

##  It has clear scientific objectives. 

##  The study design should produce adequate data to achieve those objectives. 4748



# Ethics Assessment: Testing of S.C. Johnson Personal Tick Repellent Products to Support their use of the EPA Repellency Awareness Graphic

Maureen Lydon Office of the Director Office of Pesticide Programs49



# Value to Society  

## Proposed study will determine the complete protection time (CPT) of up to 18 EPA- registered insect repellent products against ticks  

## Up to 3 different active ingredients (AIs) and variety of products, all previously registered and assessed by EPA, will be tested for duration of efficacy  

## Product-specific efficacy testing is required to support use of EPA’s Repellency Awareness Graphic on product labels.50



# Value to Society 2  

## Consumers who use tick repellents to avoid tick bites cannot readily assess the duration of repellency.  

## If EPA’s Repellency Awareness Graphic is added to the label, consumers can make informed decisions by knowing the length of time each product repels ticks.51



# Subject Selection
 

## Participants will be recruited through advertising using digital and social media.  

## Recruitment firm will also use Spanish language advertisement and on- line Spanish newspaper that advertises in the recruitment area.  

## Ad will contain link to study-specific website with prescreening qualification form.

# Subject **Selection 2** 
 

## Once completed, pre-screening qualification form will be uploaded to secure and encrypted portal, that only i2LResearch staff can access.  

## The respondents who meet the eligibility criteria will be contacted initially by the recruitment firm or i2LResearch. 52

# Subject Selection **3**
 

## The respondents will be asked some basic eligibility questions and told about the test using the telephone script.  

## Eligible/interested respondents will receive follow- up call from i2lResearch to review study steps, identify training, inclusion/exclusion factors, payment, and offer to provide consent form. 53

# Subject Selection **4**
 

## Next step is 2 hour training prior to each study.  

## As part of training, consent form will be provided and reviewed. Questions will be asked to ensure understanding.  

## Eligible interested subjects will sign consent form. 54

# Inclusion/Exclusion **Criteria**
 

## 15 inclusion/exclusion criteria are complete and appropriate, except: 

# o Add exclusion for sensitivity to tick bites or latex. 

# o Add exclusion for individuals with skin disease, skin problems such as eczema, psoriasis or atopic dermatitis.
55

# Inclusion/Exclusion **Criteria 2** 
 

## One of the inclusion criteria: 

# o Read and speak English fluently. 

## Rationale: 

# o Current repellent product labels in English 

# o Language does not affect attractiveness to ticks 56

# Inclusion/Exclusion **Criteria 3**  Rationale (continued): 

# o To target users that understand product labels, will recruit English speaking subjects with minimum 10% bilingual 

# o Research offers no benefits to subjects 

# o Limiting recruitment to English speakers with 10% bilingual, is not expected to result in equity of access issues 5758 

# Informed Consent Process  

## Proposed consent process with EPA comments included is satisfactory
• Potential subjects meet with i2LResearch for 2 hour training. Subjects given consent form, time to read it, opportunity to ask questions • As part of training, the study, subject’s role, potential length of test day, inclusion/exclusion criteria will be reviewed • Questions will be asked to ensure understanding • Pregnancy test within 48 hours prior to test day  

## Revised consent form includes all elements required by regulations59



# Informed Consent 2  

## To confirm understanding of the consent form, subjects will be asked 6 questions: 1. What will study staff place on your arm, monitor, take off & discard in order to collect study data? 2. What type of product will be applied to your arm and remain on your arm during the exposure period of the study? 3. How long could one test day last?60



# Informed Consent 3  

## To confirm understanding of the consent form, subjects will be asked 6 questions: 4. What are the potential discomforts or hazards from this study? 5. Do you have the freedom to quit or withdraw from the study at any time? 6. If you quit or withdraw from the study, for how many hours will you be paid?

# Highlights **of EPA Comments**
 

## Revise protocol to include details of training and what will occur.
• i2LResearch & SCJ: Revised accordingly 

##   

## Revise description of recruitment process and provide details. Also, include Spanish language ad and use of online Spanish newspaper • i2LResearch & SCJ: Revised accordingly 

## 
61

# EPA Comments **2**
 

## Add breaks during test day. Provide breakfast, lunch, dinner to subjects
• i2LResearch & SCJ: Revised accordingly 

##   

## Increase proposed compensation for participating in training and test day
• i2LResearch & SCJ: Revised accordingly 

## 

62

# EPA Comments **3**
 

## Reduce length of 2 hour prep time on test day
• i2LResearch & SCJ: Revised accordingly 

##   

## Pregnancy test should occur within 48 hours prior to test day instead of on test day
• i2LResearch & SCJ: Revised accordingly 

## 

63

# EPA Comments **4**
 

## Draft questions to ensure understanding of consent form
• i2LResearch & SCJ: Revised accordingly 

##   

## Clarify when and how often consent form will be signed if subject participating in more than 1 study • i2LResearch & SCJ: Revised accordingly 

## 

64

# EPA Comments **5**
 

## In consent form, include: 

# o section on Test Material 

# o detailed description of training 

# o provision of breaks 

# o provision of breakfast, lunch and dinner 

# o discomfort of and fatigue from long test day as another risk • i2LResearch & SCJ: Revised accordingly 

## 

65

# EPA Comments **6**
 

## Revise phone scripts for initial and follow- up contact to: Clarify length of test day and training, explain use of code numbers for privacy, update compensation figures, highlight freedom to withdraw
• i2LResearch & SCJ: Revised accordingly 

## 
66

# EPA Comments **7**
 

## For the follow- up contact script, also add that breaks and meals will be provided
• i2LResearch & SCJ: Revised accordingly 

##   

## Add support to help bolster subject’s arm when it’s being held at 45 degree angle during test
• i2LResearch & SCJ: Revised accordingly 

##  67

# EPA Comments **8**
 

## Add that closest hospital to lab and directions will be identified prior to test date.
• i2LResearch & SCJ: Revised accordingly 

##   

## Add that sharing new information or results with subjects will occur “in timely manner” • i2LResearch & SCJ: Revised accordingly 

## 
68

# EPA Comments **9**

 

## i2LResearch and SC Johnson agreed to address EPA’s comments.

6970 

# Risks and Risk Minimization

 

## Revisions to protocol describe appropriate measures to minimize 5 types of hazards 

## o Adverse reaction to test material 

## o Exposure to ticks 

## o Exposure to potential tick-vectored diseases 

## o Unanticipated loss of confidential information 

## o Fatigue and/or physical discomfort from length of test day71



# Benefits
 

## No direct benefit to subjects  

## Primary direct beneficiary is sponsor  

## Another beneficiary is consumer who uses tick repellents  

## If EPA’s Repellency Awareness Graphic is added to product label, consumer will know how long the tick repellent will be effective in repelling ticks72



# Risk:Benefit Balance
 

# Risks have been effectively minimized  

# Risks are reasonable in light of the expected societal benefits of the knowledge likely to be gained73 

# Independent **Ethics Review**
 

## Schulman Associates IRB (SAIRB) reviewed and conditionally approved the protocol and informed consent materials  

## Final approval is conditioned on the sponsor obtaining HSRB review  

## SAIRB has AAHRPP accreditation, is registered with OHRP, and is independent of the investigators74



# Respect for Subjects  

## Effective methods for protecting subjects’ privacy  

## Revised level of compensation is appropriate  

## Subjects will be free to withdraw at any time  

## Sponsor will reimburse subjects for cost of any medical care if research- related injuries occur75 

# Applicable **Ethical Standards** 

 

### This is a proposal for third - party research involving intentional exposure of human subjects to a pesticide, with the intention of submitting the resulting data to EPA under the pesticide laws  

### The primary ethical standards applicable to the conduct of this research are 40 CFR 26, Subparts K and L, and FIFRA 12(a)(2)(P)  

### Attachment 1 to the EPA Review contains a point- bypoint evaluation of how this protocol addresses the requirements of 40 CFR 26 Subparts K and L76 

# Findings **in EPA Ethics Review**  

## i2LResearch and SC Johnson agreed to address EPA’s comments  

## No deficiencies relative to 40 CFR 26, subparts K and L, or to FIFRA § 12(a)(2)(P)  

## Protocol meets the applicable requirements of 40 CFR part 26, subparts K and L77



# Charge Questions If the lab repellency study protocol is amended as suggested in EPA’s and the HSRB’s review and if the research is performed as described: 1. Is this protocol likely to generate scientifically reliable data, useful for estimating the complete protection time of various EPA- registered S.C. Johnson skin -applied tick repellents in the lab against three species of ticks? 2. Is the research likely to meet the applicable requirements of 40 CFR part 26, subparts K and L?