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## EPA Response to Scientific Advisory Panel Comments Related to the Proposed Repellency Awareness Graphic

Introduction

This document contains EPA’s responses to co mments made about the proposed program for use of a repellency awareness gra phic at a FIFRA Scientific Advi sory Panel (SAP) Meeting held March 19- 20, 2013, on Draft Product Performan ce Data Needs Assessment for Products Claiming Efficacy Against Invertebrate Pests. EP A thanks the SAP for their comments and will carefully consider these comments in developing the program and any future guideline or data requirement revisions. The final SAP report, m eeting minutes, the Technical Support Document, the charge questions, and other informati on about this meeting are available at http://www.epa.gov/scipoly/sap/ meetings/2013/031913meeting.html

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This document is not a complete response to all SAP comments. On ly those comments related to the effort are included in this document. In pr eparing this document, first, EPA has included the charge question given to the Panel. Only certain of the charge que stions or certain parts of the charge questions were applicable to the graphic: This include s charge questions 2b, 4a, 4c, 4d, and 10. Next, EPA included the portions of the SAP’ s response to the app licable charge question, which is categorized here as “comment.” This is then followed by EPA’s response to the

comment.



### Charge Question 2 to the Panel

Establish pest groupings and identify representa tive taxa to support su ch groups in lieu of the submission of data for every species of significant public health and economic importance on a label

The agency is considering es tablishing formal pest groupi ngs that will permit defined, generalized label claims against assemblages of pests. These groups are taxonomically and biologically based to allow repr esentative test organisms, wher e appropriate, and provide for generalized label claims against the pest grouping as a whole. Please discuss:

(b) Whether the pest groups and/or sub-groups identified [in the TSD] are appropriate and adequate? If not, how should groups be developed?

SAP COMMENT 2b-1: Ticks - Group 2 (including sub-groups 2a, b, and c)

Suggest adding Dermacentor andersoni as a test species as it is easily reared under laboratory conditions and is common.

EPA RESPONSE to COMMENT 2b-1: We are not aware of a study using Dermacentor

andersoni as the test species being submitted to EPA. Historically, we are more familiar with the09/23/2013

Page 2 of 13 American dog tick ( Dermacentor variabilis ), since we have review ed and evaluated many of

these studies. We are not aware of any unique advantages that Dermacentor andersoni offers

over Dermacentor variabilis . Additionally, it is our understanding that Dermacentor andersoni is not commonly available at testing labo ratories. Furthermore, the addition of Dermacentor

andersoni as a test species could in troduce another vari able, and thus make comparisons of Complete Protection Time (CPT) more challeng ing. However, under the current regulations and guidelines, a researcher may c onduct testing using different me thodologies and submit the data to meet EPA’s requirements. Thus, if a regi strant were to submit to EPA a well-conducted, scientifically-valid study using Dermacentor andersoni as the test species, which provided the information needed by EPA, then such a study w ould likely be considered acceptable. In the future, if EPA develops a rulemaking for produc t performance data requirements, then EPA

would consider at that time wh ether to establish a requirement regarding which test species would be acceptable.



### Charge Question 4 to the Panel

Evaluation of insect repellent efficacy data

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With regard to skin-applied insect repellent products, EPA evaluates submitted efficacy data on mosquitoes and ticks and analyzes these data to determine protection ti mes that are typically provided as claims on labels of the products. As noted in Unit VII.A of the TSD for this SAP, EPA is developing a standardized graphic for skin - applied insect repell ent products that will highlight to consumers that a product works for an estimated period of time against mosquitoes and/or ticks when the product is used as directed on the label. EPA is undertaking this initiative in order to improve and clarify pesticide pr oduct labeling for consumers and promote public health protection. EPA provides recommendations for the design and execution of repellent efficacy studies in the EPA Office of Chemi cal Safety and Pollution Prevision (OCSPP) Harmonized Product Performance Test Guideline, OPPTS 810.3700: Insect Repellents to be Applied to Human Skin ( http://www.epa.gov/ocspp/pubs/frs/public ations/Test_Guide lines/series810.htm ). Additionally, EPA has developed criteria that it believes are crit ical to analyzing submitted mosquito and tick efficacy data in such a way that consistent, reli able, informative, and health-protective estimates of Complete Protection Time (C PT) are produced. The intended criteria are as follows:

• Based in part on discussions with the Huma n Studies Review Board, EPA will be using the median CPT determined using survival analysis to evaluate product efficacy/repellency for both mosquito and tick repellents.

• The median CPT will be derived from the most conservative data set per pest (lowest CPT value among the tests performed for the pest) to calculate the hours of protection listed on a label. For mosquitoes, this woul d be the lower CPT from the typical two field study sites where testing was performed, and for ticks, this would be the lowest CPT of all the representative tick species tested.09/23/2013

Page 3 of 13 • Standard arithmetic rounding conventions will be used to round to a whole number of hours

when the calculated CPT is not a whole number. 1

• The minimum performance standard (using the raw median CPT, before rounding) as outlined in Unit IX (Table 12) will be two hours. If a product does not meet the minimum hours of protection EPA would not allow the gr aphic to be used on the label.

Given EPA’s objectives to (1) ensure the reliabili ty and consistency of claims made for skinapplied insect repellent products to keep mosqu itoes and ticks away from the typical consumer for an estimated period of time and (2) to aid consumers in their decision-making by conveying to consumers that products differ in their dur ation of efficacy towards these vector-borne, disease-carrying insects, please discuss:

Charge Question 4(a) : Should some of the testing para meters in test guideline “OPPTS 810.3700: Insect Repellents to be Applied to Human Skin” be described with greater specificity in order to derive consistent a nd reliable estimates of CPT for label claims? Please provide a supporting discussion and in clude references to any published literature

that could inform our data collection.

SAP COMMENT 4(a)-1:

[The SAP described the definition of "cro ssing" as] "A crossing may be quantified either or both by the distance the tick or chigger moves onto treated skin or by how long the tick or chigger remains on treated skin." The Panel questioned

whether the actions described in this st atement are measuring the same thing. If not, allowing both to be an outcome of a test would confound the product labeling effort. Does the individual conducting th e test decide? How does the statement account for a crossing, but then a drop off? The Panel recommended choosing one

or the other as a measurable outcome to provide greater clarity to registrants.

EPA RESPONSE to COMMENT 4(a)-1:

The agency believes the existing guideline defi nition of “crossing” (p age 5 of Guideline 810.3700) is sufficiently clear. While the definitio n may offer some flexibility for quantifying the “crossing,” the descriptions in the guideline (page 30) refer to a “rel ease point 3 cm distant from the treated area and scoring of a crossing when a tick moves at least 3 cm into the treated area.” Most of the protocols revi ewed by EPA have used “crossi ng” as the measurable outcome for tick repellency testing.

In light of this definition, once the tick has crossed the “line,” whet her the tick keeps moving forward on or over the treated skin, or remains st atic on the treated skin, or falls/drops off the treated area, the tick is not being repelled. Alth ough a “drop off” could be considered further proof of repellency, as the tick would be rem oved from the host, EPA relies on the more conservative measure of a crossing. EPA also ac knowledges that there could be circumstances

1 Based on the recommendations of the SAP, as discussed in response to comment 4(c)-1, EPA is changing this

criterion to “round down.”09/23/2013

Page 4 of 13 dependent on the chemical being tested when the use of a different measurable outcome could be more appropriate.

SAP COMMENT 4(a)-2:

In the guideline description of "dose determination," th e Panel believed use of the words "multiple applications" is rather vague. A power analysis conducted by the registrant or at least a minimum number of subjects specified by EPA was suggested. The typical dose or "dosimet ry" is the average application rate by consumers (test subjects) on themselves. Th ere may be an opportunity for bias if consumers feel they must meet a certain expectation when doing the applications. Also, an application in an efficacy study (e.g., preparing for a field trial) may not accurately reflect what someone might rea lly apply to themselves if they are anticipating an activity such as hikin g, hunting or other outdoor activity when arthropod contact might be high.

The Panel recommended that EPA establish the dose for spray-type formulations.

EPA RESPONSE to COMMENT 4(a)-2:

EPA follows recommendations from the Huma n Studies Review Board (HSRB) on dose determination by using dosimetry testing instead of establishing a standardized dose (see http://www.epa.gov/hsrb/files/ oct2006-final-report-12107.pdf ). Dosimetry testing is conducted separately from the repellency testing and seeks to estimate a “typical consumer dose.” Guideline 810.3700 (page 7) indicates that the “typical dose” s hould be calculated as the mean of multiple applications. The number of subjects would be sp ecified in the protocol reviewed by EPA and the HSRB. EPA agrees that each person applies different amounts of repe llent based on factors such as the formulation, the part of body to wh ich the repellent is applied, and their past experiences in using insect repe llents. The differences in amount of repellent applied via the individual application techniques are precisely the informa tion that EPA seeks. EPA believes that its approach to dose determination by us ing dosimetry testing is appropriate for all formulation types.

EPA does not believe that there is an opportunity fo r bias when test subjects are instructed to apply the repellent as indicated on the label. It is possible that a test subject could apply the product at a lower dose than what some consumer s could apply when they are “anticipating an activity such as hiking, hunting or other outdoor activity when arthropod contact might be high.”

If such a lower dose is determined to be effec tive, then EPA assumes that the product will be at least as effective as when applied at a higher dose.

SAP COMMENT 4(a)-3:09/23/2013

Page 5 of 13 The Panel believed that the only way that a median CPT can be estimated was with multiple study participants and, therefore, the emphasis should be on replication of study participants within each lab or field trial.

EPA RESPONSE to COMMENT 4(a)-3:

Guideline 810.3700 specifically includes inform ation on complying with the new ethical requirements for research invol ving human test subjects. (EPA ’s codification of the Common Rule is at 40 CFR part 26.) The testing methodologi es were also upgraded to ethically justify the use of human subjects, since it would be une thical to employ human subjects for unreliable testing results. The current recommendations for product performance te sting of skin-applied insect repellents, as specif ied in Guideline 810.3700, strike a balance between ethical considerations, cost of te sting, and reliable results.

The ethical considerations for conducting studies with human subjects are clear on the need to minimize human exposure when conducting needed re search as well as assu ring that there is a benefit to having such information. Guideline 810.3700 provides flexibility by not requiring a minimum sample size. Study directors must provide a rationale for the choice of sample size; however, we note that a sample size of 10 subjects is routinely used and accepted.

The CPT is derived from the first confirmed la nding and this measure is analyzed using a nonparametric survival analysis procedure, which is appropriate for right-cen sored data that is not normally distributed. The central CPT value is th e median CPT derived from such analysis. The first confirmed landing is the most protective e fficacy endpoint for human subjects exposed to mosquitoes during testing. It prevents bites and even probing since mosquitoes can transmit pathogens during probing activity. Testing para meters and study design are standardized for consistency. EPA notes that guideline recommenda tions are flexible enou gh to allow adoption of innovative technologies as they develop since th is is an evolving field. Additionally, EPA will consider SAP advice in related policy formation in the future.

SAP COMMENT 4(a)-4:

Using the EPA definition of CPT ("the time from application of a repellent until efficacy failure, as defined in the protoc ol used to conduct the study"), a repellent would fail at the point in time when one mosquito bites or one tick crosses a line, or by successive bites or crossings with in a 30 minute period. The CPT will likely underestimate repellency and use of CPT as a criterion for evaluating repellent efficacy may encourage the over-application of repellents because consumers may believe that they would be vulnerabl e to attack after the CPT period.

Measuring percent repellency with 95% as the minimum allowable in estimating protection time for repellents applied to skin would likely yield more reliable results. A requirement of 100% repellency is too rigorous because it does not take into account the size of the mosquito popul ation and intensity of activity. Using 95% reduction in landing or biting is a more appropriate measure of the response09/23/2013

Page 6 of 13 of a mosquito test populati on as a whole in comparison to CPT. CPT essentially records the activity of outli ers and provides the time wh en the first outlier lands (or bites) or the landing (biting) followed by a landing (bite) of a second outlier. What would the CPT be for a repellent that achieved 99% repellency at 1 hour, 100% at 1.5 hours, and 99% at 2 hours?

If landings were allowed (or bites or crossings), then why not use percent repellency as the measure instead? EPA allows the study design to use either landing or bites, but then goes on to strongly recommend landings. The Panel recommended not offering a choice. When would measuring "bites" be justified, according to EPA? Furthermore, use of la nding rather than biting as an endpoint in repellent tests would require formulat ors to increase the volatility of their formulations to increase the repellent ac tivity of their end us e products. Increased volatility would decrease CPT unless the c oncentration of the active ingredient was increased. Some, if not most, repellents work as a contact irritant rather than a spatial repellent (altering seeking behavi or). Therefore, land ing as an endpoint

should be defined in terms of a "touch time" such as greater than 2 seconds rather than as a simple touch with immediate lift off. Use of biting as an endpoint must be carefully considered for field studies due to risk of disease transmission to

volunteers.

The Panel agreed that from a consumer perspective, when reading a product label, it is more likely that the average cons umer would understand repellency when

stated in terms of CPT rather than as "percent repellency over time". However, duration of percent repellency could be written on a product label in a common sense way to enhance unde rstanding by a consumer.

EPA RESPONSE to COMMENT 4(a)-4:

EPA recommends the use of landings (for mosquitoes ) or crossings (for ticks ), not bites, as the measurement of repellency appr opriate to the repellency awaren ess graphic. As previously discussed, the ethical considerations for conducti ng studies with human subjects are clear on the need to minimize human exposure when conducting needed research as well as assuring that there is a benefit to having such information. Wh ile there is a clear be nefit to understanding how long and how well a skin applied insect repellen t works, exposure of the human test subjects must be minimized. Bites potentially put human subjects at risk since one bite can contain enough pathogenic material to transmit disease. T hus bites should not be used as a measurement of repellency for efficacy studies measuring e ffectiveness against mosquitoes. This also comports to advice given by the HSRB during it s review of a draft version of Guideline 810.3700. (see http://www.epa.gov/hsrb/fil es/june2006mtgreportfinal100606.pdf)

EPA agrees that the CPT may underestimate re pellency, but notes that underestimation of repellency would be more protective for consumer s than overestimation. The agency assesses the risk associated with exposure to the repellent as part of the risk a ssessment and the exposure09/23/2013

Page 7 of 13 includes re-application of the product. Any limitations to ap plication (e.g. , number of reapplications) are requ ired to be part of the product label.

EPA disagrees that using 95% repellency would be more reliable or appropriate. EPA believes that the CPT is more protectiv e since it is indicative of 100% protection, i.e., no confirmed landings. EPA has considered the use of percent repellency statements for skin-applied insect repellent products. However, we believe that a st atement such as “repels mosquitoes for up to 4 hours” is easily understandable. While there is, of course, variability from person to person on how long the repellent works, the focus groups conducted by EPA indicated that consumers do have an understanding of such variability. A stat ement such as “repels 99% of mosquitoes at 1 hour, 100% of mosquitoes at 1.5 hours, and 99% at 2 hours” offers little practical information to

consumers. EPA is concerned that such deta iled information offers a false precision to consumers because of these variability issues . Additionally, using percent repellency could require measurement of a sample of untreated negative subjects exposed to mosquitoes which makes it impossible to prevent multiple bites from happening. Given the need to minimize exposure for the test subjects, EPA does not be lieve that percent repellency is workable.

In general, EPA allows registrants the flexibilit y to define efficacy failure in a study protocol; however, specifically for skin-applied insect repe llent studies, the first confirmed landing or crossing is used to determine efficacy, thus provi ding consistency across re gistrant studies. With test species other than mosquitoes or ticks, effi cacy failure may need to be defined differently, and the guideline allows this flexibility. For instance, biting flies such as stable flies will bite immediately upon landing on skin, thus bites are more appropriate as an endpoint instead of landings. EPA will continue to consider this SAP advice in future policy discussions.

SAP COMMENT 4(a)-5:

One or two untreated persons are used to verify landing pressure in CPT tests. This is not a true negative control be cause untreated persons are not to be compared to treated persons. The Pane l recommended clarification. Further, multiple negative controls are required for studies of relative protection or percent repellency. If the Agency uses CPT as the endpoint or measure of repellency (which is not recommended), it creates c onfusion or ambiguity in the guidelines for registrants. This comment also applie s to other places in the guidelines that

describe "untreated controls".

EPA RESPONSE to COMMENT 4(a)-5:

EPA acknowledges that an untreated person used to verify landing pressure is not a true negative

control. EPA believes that it is not necessary to have a repli cated negative control group for statistical purposes.

Based on the recommendations of the HSRB, Gu ideline 810.3700 encourages the use of positive controls (page 9) and only discus ses negative controls (page 35) as part of the consideration for statistical design. As previously discussed, the et hical considerations fo r conducting studies with human subjects are clear on the need to mi nimize human exposure when conducting needed09/23/2013

Page 8 of 13 research as well as assuring that there is a benefit to having such information. Exposure to infected mosquitoes in the field is possible, a nd EPA does not want subject s to be bitten or to encourage the use of bite data to determine repellency.

The type of statistical analysis that has been us ed to estimate CPT (bas ed on the First Confirmed Landing) is a non-parametric test which is not intended to comp are treatment groups. This means that a negative control is not n eeded to determine whether there is any statistically significant

difference which demonstrates that the treatment effect is significant. The experiment is not designed for testing such hypothesis. The objective of the test is to measure time of repellency using a sample of treated subjects and having on e person, fully covered, to monitor whether there is enough mosquito activity at the site during testing.

SAP COMMENT 4(a)-6:

Guideline 810.3700 states that for testi ng DEET (N,N-diethyl-meta-toluamide) lotion formulations, the standard dose was 1 g per 600 cm 2 . The guideline stated only that this was through many tests of repellency; therefore, it was not clear

how the dose was determined. Has this been established over time, as a "typical consumer dose," using methods describe d by EPA? If so, the guideline should include a description or clar ification. Why woul d this dose not also be a standard for other active ingredients? The onl y reason given was that no comparable

standard dose had been identified. Wh en was the standard dose for DEET identified by EPA? In public comments made by the DEET Task Force, it was noted that variable dosing would have an impact on CPT. This could lead to an overestimation or underestimation of CPT, which may provide inaccurate information to the consumer for protecti on against a public health pest and could complicate EPA's efforts to begin a repe llent mark/graphic program. Data should be easily comparable across studies, registrants, etc.

EPA RESPONSE to COMMENT 4(a)-6:

The use of this DEET dose and formulation as a positive control is al so used by the World Health Organization (WHO) and is also include d in the WHO “Guidelines for Efficacy Testing of Mosquito Repellents for Human Skin.” ( http://whqlibdoc.who.int/hq/2009 /WHO_HTM_NTD_WHOPES_2009.4_eng.pdf ) For other ingredients and formulations no comparable standard dose has been identified, and it is recommended that a “typical c onsumer dose” be estimated through empirical dose-determination testing as described in the test guideline.

SAP COMMENT 4(a)-7:09/23/2013

Page 9 of 13 EPA specifies which mosquito species s hould be used for conducting laboratory studies. However, this does not agree with the recommendations proposed in Appendix 5 of the TSD. The Panel recommended that guideline 810.3700 be

revised to reflect the Panel's recommenda tions to Appendix 5 (for mosquitoes) that EPA chooses to accept (e.g., diffe rentiating between field and laboratory studies, repellent requirements vers us other types of pesticides).

EPA recommended two distinct habitats for field testing sites where the predominant mosquito species differ, but it did not provide any specific guidance on what species should be targeted for these field studies. A registrant must provide field data (which EPA prefers) to support a product label claim against mosquitoes; however, field data on some of the specific species identified in Appendix 5 of the TSD could not readily be obtained in the U.S. Any adopted "test requirements" from the TSD s hould be harmonized with preexisting published guidelines.

EPA RESPONSE to COMMENT 4(a)-7:

The Panel is correct that page 25 of Guideline 810.3700 provides specific species for laboratory studies of mosquito repellency. For field testing, EPA does not be lieve it possible to prescribe the species and genera that woul d be encountered in a given fi eld test. Instead, EPA recommends field testing at two di stinct habitats where predominant mosquito species differ and would presumably cover several different genera.

Guideline 810.3700 specifies that in sects should be aspirated or trapped, and then identified by genus and species (page 27). Field studies that have been submitted to EPA since 2006 include a complete listing of all species co llected at the field sites as we ll as the number of individual species collected. EPA evaluates the identified speci es to make sure that sufficient disease vector species were present. As appropr iate, EPA has required additional lab studies of one or more disease carrying species to supplement the field study when insufficient sp ecies were present.

If EPA develops a rulemaking for product perfor mance data requirements, then most of the

Guidelines would be revised at that time to accomm odate what is codified in the regulations (and therefore required), and what is recommended in the guidelines. At that time EPA will consider

which recommendations of the SAP are codi fied and which are placed in guidance.

SAP COMMENT 4(a)-8:

The guideline states “subjects may work in pairs.....;” however, working in pairs would likely interfere with a true measur ement on the actual test subject for many reasons. A second person acting as "co llector" would create an additional attractant (if not wearing repellent) or re pellent (if required to wear repellent to minimize risk). It is entirely possible to adequately train test subjects to use an09/23/2013

Page 10 of 13 aspirator and collecting cup prior to executi on of a field study thus eliminating the need to work in pairs.

In Unit VII, Part A of the TSD, EPA stat ed that they are planning to implement a voluntary repellency mark program and that information derived from this SAP may be used to further refine the criteri a for this voluntary program. Registrants

would have to demonstrate CPT ≥ 2 hours (the current endpoint or measurement for efficacy) in order to use a proposed graphic or repellency mark on a product

label. In Table 12 of the TS D, EPA states that a CPT ≥ 2 hours would be required for any repellent, implying a minimum st andard for registration. This does not entirely agree with th e statements in Unit VII Part A, which is likely an oversight, but should be made clear by EPA. The Panel inquired whether a CPT ≥ 2 hours is required for registration of a repellent product or me rely required to use the voluntary graphic on labels. The Panel thought that EPA's concept for the repellency mark program was a good idea since it aims to help consumers by reflecting protection times supported by data generated through performance testing and they thought that it should ultimately be a mandatory program.

A Panel member noted that there is a di scussion in the EU concerning protection times and the current line of thought is to work with average protection times because there can be large differences in responses between tested individuals. EPA's proposal to put whole hours of protection time on a product label would require calculation of the average protection time. Due to the high variability in individual protection time, the 100% cr iterion cannot be applied as the only criterion for the derivation of the protection time. If all users are to be protected at 100% during a claimed period, the protection time on the label would need to be very low. The Panel members, therefore, suggested deriving a mean value to use as the protection time on a product label. It should somehow be stated on the product label that the declared hours of protection represent a mean value (e.g., “protects on average X hours”). For the cal culation of the mean value, the EU uses only those studies which fulfill the requirements of the official guidelines (EPA, WHO) and which were conducted with at least 10 test persons. If test methods deviate from official guidelines and are less rigorous, the labeling should be adjusted, for example, by subtracti ng a certain amount of declared hours (e.g., 5 instead of 6 hours).

EPA RESPONSE to COMMENT 4(a)-8:

Guideline 810.3700 (page 29) offers the option of subj ects working in pairs to assist each other.

While EPA continues to believe that this is an acceptable me thod of collecting and reporting data, EPA also recognizes that te st subjects can be trained to accomplish this on their own. Test subjects do not need to see around their entire bodies to be able to count the number of landings (not bites) because there is only one small sec tion of the forearm or leg that is treated and exposed to mosquitoes. That is the only area th at needs supervision. Therefore, each test subject should be capable of counting/aspira ting his/her own mosquito landings.09/23/2013

Page 11 of 13 With regard to a minimum of two hours for CPT, EPA agrees that two hours should be the minimum for product registration, not just for participation in the voluntary program.

EPA continues to believe that the median CP T value from the chosen data set is more appropriate for deriving the CPT used on the graphi c. Most of the data sets submitted to EPA and reviewed by both EPA and the HSRB are right censored. This means that the data are not normally distributed and therefore the m ean is effectively meaningless.

As previously described, Guideline 810.3700 pr ovides flexibility by not requiring a minimum sample size. Study directors must provide a rationa le for the choice of samp le size; however, we note that a sample size of 10 subject s is routinely used and accepted.

EPA does not believe that it needs to consider adjusting labels by s ubtracting hours if test methods are less rigorous. Given the current proc ess used by EPA for evaluating skin applied insect repellent testing protocols, in which the draft protocol is discu ssed during a public meeting of the HSRB, EPA finds it unlikely that any submitte d study would have signifi cant deviations.



### Charge Question 4 (c) to the Panel

Given our intended criteria, would the whole number derived from the data analysis represent a realistic method of approximating protection times for the typical consumer?

COMMENT 4(c)-1:

The Panel believed that use of the whole number is realistic for expressing CPT,

but asked whether the CPT would be rounded up or down. Standard rounding

conventions would lead to an overestim ation of CPT when numbers are rounded up. Therefore, the Panel reco mmended rounding numbers down.

A typical statement on a product label might read, "This product protects for an average period of 6 hours from biting mosquitoes." One Panel member did not think such a statement provided useful info rmation to consumers. In parts of the EU, there are only Culex species, but many consumers take DEET products with them on vacations to the tropics. Therefore, the EU has adopted label instructions that say: "This product protects for an average period of 6 hours from biting mosquitoes in the Netherlands, for an average period of 3 hours against yellow fever mosquitoes and 5 hours against ma laria mosquitoes." This provides more

useful information to a consumer. A CPT would reduce the claimed protection time while in practice the product may be effective for a longer period.

It was also suggested that consumer ac tivity and behavior be part of labeling

considerations and the Panel asked if there should there be something on the product label that differen tiates between types of c onsumer activities. EPA09/23/2013

Page 12 of 13 responded that some companies are alre ady making this distinction on their product packaging.

EPA RESPONSE to COMMENT 4(c)-1:

EPA agrees that a whole number is realistic fo r expressing CPT and also agrees with the SAP recommendation to round down when estimating CP T so that overestimation does not occur.

EPA disagrees with listing multiple CPTs on the label by species and consumer activity/behavior. EP A’s registration of an insect repellent product can mean that the product can

be distributed and used nationa lly. The variation of geographic habitats and species is wideranging. Given these variations EPA believes that using the lowest CPT is protective of almost any geographic or species variation that coul d be encountered in the US. Additionally, the agency believes that most consumers are not be able to visually distinguish the difference in mosquito species and therefore providing multiple CPTs on the label could be confusing. It is more practical and effective to require that the lowest CPT be stated on the label, which will cover all species and is the most cons ervative and protective approach.



### Charge Question 4 (d)

Is [there] additional or altern ative scientific advice that EP A should consider to improve the analysis of efficacy da ta for mosquitoes and ticks?

COMMENT 4(d)-1:

One Panel member recommended using di fferent CPTs on the product label for different mosquito species. In general, Aedes are the most aggressive species, and

have a much shorter CPT than Culex species. Anopheles is between Aedes spp. and Culex spp. with regard to aggressive feeding behavior. Depending on the climatic zone and country, different mosquito species may be present and different CPTs may be relevant. Are c onsumers aware that there are different mosquito species at "home" or when tr aveling? It was suggested that a map indicating regions with different mosquito species using different colors could be

useful.

EPA RESPONSE to COMMENT 4(d)-1:

EPA agrees with the SAP comment regarding the di fferent behaviors in mo squito species but, as described in response to comment 4(c)-1, disagrees with using different CPTs on the product label. Since species can respond differently to a repellent, using the lowest CPT rather than a CPT for each species is more protective. EPA does not believe the use of a map on repellent

labels is feasible. Given that re pellent containers tend to be sma ll, a map would have to be very small and may not be understand able. In addition, a map may be limiting, as vectors may move due to climate changes or other external factors. EPA will continue to consider this advice for09/23/2013

Page 13 of 13 policy formation in other areas related to comm unicating product efficacy. The use of graphics such as maps may be more appropriate for other communication outreach activities such as

websites.



### Charge Question 10

Please provide comments on the overall clarity, accuracy a nd completeness of the agency’s consideration of product performance data that might be needed as discussed in the TSD and EPA guidelines.

COMMENT 10-1:

Pesticides registered under 25(b): As discussed earlier, efficacy data is important for minimum risk pesticides in order to avoid false or misleading statements. There is an industry demand for applying the same or similar performance standards to 25(b) products as for any other registered products to prove their efficacy as reliable products.

EPA RESPONSE to COMMENT 10-1:

As a point of clarification, EPA wishes to empha size that minimum risk products that qualify for an exemption are not registered products. EPA agrees that such produc ts should fulfill product performance testing requirements in order to us e the repellency awareness graphic. EPA intends to encourage producers of these products to apply to regist er their product under FIFRA if interested in participating in the repellency awareness program.