E7-3008. Insect Repellent-Sunscreen Combination Products; Request for Information and Comments

AGENCY:

Environmental Protection Agency (EPA).

ACTION:

Notice; request for comment.

SUMMARY:

EPA is seeking information to determine how insect repellent-sunscreen combination products should be regulated in order to complete the reregistration review which was described in the Reregistration Eligibility Decision (RED) document for the insect repellent DEET. This action would consider issues such as labeling, product performance and applicable safety standards for all currently (and any future) registered insect repellent-sunscreen combination products. The sunscreen components of these products are regulated by the Food and Drug Administration (FDA). Elsewhere in this issue of the Federal Register is a companion notice in which the FDA is also requesting information and comments on these products and for which the FDA will be considering rulemaking. The decision on what if any change in the way these products are regulated will consider information and comments submitted in response to this Notice.

DATES:

Comments must be received on or before May 23, 2007.

ADDRESSES:

Submit your comments, identified by docket identification (ID) number EPA-HQ-OPP-2007-0087, by one of the following methods:

• Federal eRulemaking Portal: http://www.regulations.gov. Follow the on-line instructions for submitting comments.
• Mail: Office of Pesticide Programs (OPP) Regulatory Public Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001.
• Delivery: OPP Regulatory Public Docket (7502P), Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South Building), 2777 S. Crystal Drive, Arlington, VA. Deliveries are only accepted during the Docket's normal hours of operation (8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays). Special arrangements should be made for deliveries of boxed information. The Docket telephone number is [phone].

Instructions: Direct your comments to docket ID number EPA-HQ-OPP-2007-0087. EPA's policy is that all comments received will be included in the docket without change and may be made available on-line at http://www.regulations.gov, including any personal information provided, unless the comment includes information claimed to be Confidential Business Information (CBI) or other information whose disclosure is restricted by statute. Do not submit information that you consider to be CBI or otherwise protected through regulations.gov or e-mail. The Federal regulations.gov website is an “anonymous access” system, which means EPA will not know your identity or contact information unless you provide it in the body of your comment. If you send an e-mail comment directly to EPA without going through regulations.gov, your e-mail address will be automatically captured and included as part of the comment that is placed in the docket and made available on the Internet. If you submit an electronic comment, EPA recommends that you include your name and other contact information in the body of your comment and with any disk or CD-ROM you submit. If EPA cannot read your comment due to technical difficulties and cannot contact you for clarification, EPA may not be able to consider your comment. Electronic files should avoid the use of special characters, any form of encryption, and be free of any defects or viruses.

Docket: All documents in the docket are listed in the docket index. Although listed in the index, some information is not publicly available, e.g., CBI or other information whose disclosure is restricted by statute. Certain other material, such as copyrighted material, is not placed on the Internet and will be publicly available only in hard copy form. Publicly available docket materials are available either in the electronic docket at http://www.regulations.gov, or, if only available in hard copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac Yard (South Building), 2777 S. Crystal Drive, Arlington, VA. The hours of operation of this Docket Facility are from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal holidays. The Docket telephone number is [phone].

FOR FURTHER INFORMATION CONTACT:

Richard Gebken, Registration Division (7505P), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone number: [phone]; fax number: [phone]; e-mail address: [e-mail].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

This action is directed to the public in general. This action may, however, be of interest to those who currently have registered products or intend in the future to register any insect repellent-sunscreen combination products, as well as those individuals who use these products. Since other entities may also be interested, the Agency has not attempted to describe all the specific entities that may be affected by this action.

B. What Should I Consider as I Prepare My Comments for EPA?

1. Submitting CBI. Do not submit this information to EPA through regulations.gov or e-mail. Clearly mark the part or all of the information that you claim to be CBI. For CBI information in a disk or CD ROM that you mail to EPA, mark the outside of the disk or CD ROM as CBI and then identify electronically within the disk or CD ROM the specific information that is claimed as CBI. In addition to one complete version of the comment that includes information claimed as CBI, a copy of the comment that does not contain the information claimed as CBI must be submitted for inclusion in the public docket. Information so marked will not be disclosed except in accordance with procedures set forth in 40 CFR part 2.

2. Tips for preparing your comments. When submitting comments, remember to:

i. Identify the document by docket ID number and other identifying information (subject heading, Federal Register date, and page number).

ii. Follow directions. The Agency may ask you to respond to specific questions or organize comments by referencing a Code of Federal Regulations (CFR) part or section number.

iii. Explain why you agree or disagree; suggest alternatives and substitute language for your requested changes.

iv. Describe any assumptions and provide any technical information and/or data that you used.

v. If you estimate potential costs or burdens, explain how you arrived at your estimate in sufficient detail to allow for it to be reproduced.

vi. Provide specific examples to illustrate your concerns and suggest alternatives.

vii. Explain your views as clearly as possible, avoiding the use of profanity or personal threats.

viii. Make sure to submit your comments by the comment period deadline identified.

II. Background

A. What Action is the Agency Taking?

Currently, there are approximately 20 combination insect repellent/sunscreen products available for consumers. Each of these products contains an insect repellent component (N,N-diethyl-meta-toluamide (DEET), oil of citronella or IR3535)) and a sunscreen component. Combination products are available in lotion, cream, and spray-on formulations. These products are currently marketed for use by the entire family. These products provide consumers with the convenience of using one product as opposed to the use of multiple products. In addition, it has been suggested that these products, containing both insect repellent and sunscreen components in one formulation, preserve the efficacy of both components better than if a consumer were to apply the insect repellent product and the sunscreen product sequentially.

EPA is responsible for reevaluating previously registered pesticide products through a program called “reregistration.” In order to reregister a pesticide, EPA determines whether the product meets current scientific and statutory standards. Due to concerns about the potential conflict in labeling for the insect repellent and the sunscreen portions of the product, EPA postponed a reregistration eligibility decision (RED) on whether to reregister the combination DEET/sunscreen products until additional information could be obtained. This document solicits opinion and comment from the public to assist in determining how best to regulate these products.

These combination products are regulated by both EPA and FDA. EPA has regulatory authority over these products because of the insect repellent component and the sunscreen component is regulated by FDA. Both agencies are seeking comments to determine how these products should be regulated. (FDA's notice is located elsewhere in this issue of the Federal Register.) EPA and FDA will work together to develop a coordinated approach to the regulation of combination products.

1. Regulatory status of the insect repellent ingredients. EPA provides information to the public regarding the use of insect repellent products at the following web site: http://www.epa.gov/​pesticides/​factsheets/​chemicals/​deet.htm . Information detailed at that site provides the EPA-recommended precautions when using insect repellents, including (in part):

• Read and follow all directions and precautions on the product label.
• Do not apply over cuts, wounds, or irritated skin.
• Do not apply to hands or near eyes and mouth of young children.
• Do not allow young children to apply repellent products.
• Use just enough repellent to cover exposed skin and/or clothing.
• Do not use under clothing.
• Avoid over-application.
• After returning indoors, wash treated skin with soap and water.
• Wash treated clothing before wearing it again.
• Use may cause skin reactions in rare cases.

The following additional statements should appear on the labels of aerosol and pump spray formulation labels:

• Do not spray in enclosed areas.
• To apply to face, spray on hands first and then rub on face. Do not spray directly onto face.

There are currently three (3) insect repellent active ingredients used in combination with sunscreen (amounting to 20 currently registered combination products). These are: N,N-diethyl-meta-toluamide (DEET), oil of citronella and IR3535. Two other active ingredients are approved for use in insect repellent products, p-methane-3,8-diol and KBR 3023 (picaridin). Neither chemical, however, is currently available in a combination sunscreen formulation. Both DEET and oil of citronella have undergone reregistration which entailed an evaluation and analysis of the complete database for both chemicals. IR3535, picaridin, and p-methane-3,8-diol are newly registered chemicals which were evaluated during the registration process to ensure they met the statutory standard.

In December 1998, EPA completed reregistration and issued a Reregistration Eligibility Decision (RED) document for the pesticide DEET. DEET products, which are applied directly to skin and/or clothing, are available in numerous formulation types (e.g., aerosol sprays, non-aerosol sprays, creams, lotions, sticks, foams, and towelettes) and concentrations (products range from 4% active ingredient (a.i.) to 100% a.i.. DEET is an insect and mite repellent used in households/domestic dwellings, on the human body and on clothing, on cats, dogs and horses and in the living and sleeping quarters of pets.

Based on pesticide usage information mainly for 1990 (DEET RED), an average annual estimate of the domestic usage of DEET is 4 million pounds (active ingredient). About 30% of the U.S. population uses DEET as an insect repellent at least once a year (about 27% of adult males, 31% of adult females and 34% of children). Approximately 21% of U.S. households use DEET annually. About 19% of households use DEET on household members, and about 4% of households that have cats and/or dogs use DEET on those pets (DEET RED).

As EPA indicated in the DEET RED: “The Agency is concerned about consumer use of products that combine sunscreen and DEET, since the directions to reapply sunscreens generously and frequently may promote greater use of DEET than needed for pesticidal efficacy, and thus pose unnecessary exposure to DEET”. DEET labels currently recommend that products be used sparingly and not be reapplied too often. Sunscreen products, however, recommend frequent reapplication. No benefits attach to use of DEET more frequently than necessary to achieve its purpose. The Agency did not make a regulatory decision about whether to reregister these combination products at the time of the DEET RED because EPA believed that adequate information was not available.

In February 1997, the EPA completed its Reregistration Eligibility Decision (RED) document for oil of citronella. This decision includes a comprehensive reassessment of the required target data and the use patterns of currently registered products. Oil of citronella is a biochemical pesticide. It is registered as an animal repellent and as an insect repellent/feeding depressant. Oil of citronella is the volatile oil obtained from the steam distillation of freshly cut or partially dried grasses (Cymbopogon nardus (Rendal) and Cymbopogon winterianus (Jowitt). Two varieties of the citronella oil exist commercially - “Ceylon type” (derived from C. nardus) and “Java type” (derived from C. winterianus). (Oil of Citronella RED, 02/97)

Based on pesticide survey usage information for the years 1991 through 1992, annual citronella domestic usage ranged approximately from 33,000 to 48,000 pounds active ingredient for four sites (domestic dwelling; ornamentals; human face, skin, and clothing; and manufacturing). Oil of citronella is an insect repellent with its largest markets, in terms of total pounds active ingredient, allocated to human face, skin, and clothing (56% to 74%); domestic dwelling outdoor (22% to 41%); and ornamentals (1.5% to 2.0%). The balance is for manufacturing use. (Oil of Citronella RED)

The third currently registered insect repellent used in combination with sunscreen is IR3535. In 1997, the Agency classified IR3535 as a biochemical, based on facts that:

i. It is functionally identical to naturally occurring beta alanine;

ii. Both repel insects;

iii. The basic molecular structure is identical;

iv. The end groups are not likely to contribute to toxicity; and

v. It acts to control the target pest via a non-toxic mode of action.

The active ingredient, IR3535 is a liquid synthetic biochemical pesticide which contains 98% 3 [N Butyl N acetyl] aminopropionic acid, ethyl ester as active ingredient and 2.00% inert ingredients. (Biopesticide Registration Eligibility Document)

Two insect repellent active ingredients in registered pesticides are not currently utilized in a combination product. However, for the purposes of completeness, all currently registered insect repellents are discussed within this Notice. The first chemical is p-methane-3,8-diol, a biochemical pesticide which is chemically synthesized, although a natural oil comparable to p-methane-3,8-diol can be extracted from lemon eucalyptus leaves and twigs. It can be used in three types of consumer pesticide products: A spray, a lotion, and a towellette. p-methane-3,8-diol can be used to make products that are used for the purpose of repelling insects such as mosquitoes. (Biopesticide Registration Eligibility Document). The other insect repellent is KBR 3023, containing the active ingredient, picaridin. This chemical is currently formulated for use as a human skin applied insect repellent. Currently EPA-registered picaridin products include 15% pump spray, 10% aerosol spray, 7% cream, 7% pump spray, 5% cream, and 5% pump spray.

2. Regulatory Status of the Sunscreen Ingredients. In the Federal Register of May 21, 1999 (64 FR 27666), FDA issued a final monograph for over-the-counter (OTC) sunscreen drug products in 21 CFR part 352, establishing conditions under which these products are generally recognized as safe and effective and not misbranded. The monograph includes 16 sunscreen active ingredients in § 352.10, provides for combinations of sunscreen active ingredients in § 353.20, specifies required labeling in §§ 352.50, 352.52 and 352.60, and sets forth required testing procedures in §§ 352.70 through 352.77.

Historically, FDA has used its enforcement discretion to allow the marketing of appropriate insect repellent-sunscreen combination products. These types of products were marketed before the OTC drug review began in 1972, and FDA has not explicitly addressed them at any time in the rulemaking for OTC sunscreen drug products. Because they have always contained a pesticide, the combination insect repellent-sunscreen products have also historically been registered with and regulated by EPA. FDA has not objected to the marketing of the combination products pending the issuance of the final sunscreen monograph so long as the products contained sunscreen ingredients included in the FDA rulemaking and were registered with EPA. FDA is interested in determining whether it should amend that monograph to address these combination products before the monograph becomes effective. Any combination product containing an active drug ingredient that is not included in the final monograph after the effective date will be considered a new drug and need a new drug approval (NDA) approval to be legally marketed, even if the product is also registered with EPA.

III. Issues Related to Insect Repellent-Sunscreen Drug Products

EPA and FDA have identified three broad issues areas in connection with the regulation of these combination products:

A. Possible Manufacturing Conflicts

Any insect repellent/sunscreen combination product would have to comply with EPA's data requirements in 40 CFR part 158 and with FDA's current good manufacturing practice for finished pharmaceuticals requirements in 21 CFR part 211. The Agencies are not aware of any specific manufacturing requirements that conflict and invite specific comment and information on this subject.

B. Possible Formulation Conflicts

The EPA has solicited information from registrants of combination insect repellent/sunscreen products regarding the possibility of formulation conflicts. The Agency is aware of some limited, conflicting information, which raises the question of whether combining a sunscreen and an insect repellent component in a single product diminishes the efficacy of either the sunscreen or the insect repellent. Specific comments and information are invited on this subject.

C. Possible Labeling Conflicts

Insect repellent/sunscreen products can have labeling requirements for their individual components that could theoretically conflict. The insect repellent component of the product must be labeled in accordance with 40 CFR part 156 and should comply with directions set out in its registration notice or the RED for the appropriate active ingredient. For each registered insect repellent, these requirements are listed in the registration or reregistration documents. The sunscreen component of the product must be labeled in accord with 21 CFR 201.66, 352.50, 352.52, and 352.60. The labeling format and some of the content requirements could vary between the EPA and FDA requirements. The Agency is looking at whether it is possible for products to comply with both sets of requirements and recommendations without confusing or misleading users.

IV. Specific Topics for Comment

The EPA is particularly interested in receiving comments on the following topics:

A. Safety Issues

1. Application frequency. The EPA is concerned that the combination products could contain conflicting use instructions on product labels which compromise safe use of these products. For example, the directions for some DEET products require a 6-hour interval between applications and state “use just enough repellent to cover exposed skin and/or clothing” and “avoid over-application of this product”. The directions for sunscreen drug products in § 352.52(d)(1) and (d)(2) state to “apply (select ‘liberally', ‘generously', ‘smoothly', or ‘evenly'), before sun exposure and as needed,” and “reapply as needed or after towel drying, swimming, or (select ‘sweating' or ‘perspiring')”. EPA is soliciting suggestions on how this potential concern can be alleviated.

2. Application location. The EPA has directed that insect repellents not be used for certain areas of the body (e.g., over cuts, applied by spray directly to the face, etc.), and apply sparingly around ears. Sunscreen use directions, however, encourage consumers to apply the products, on the face and ears, “liberally, generously, smoothly, or evenly” “before sun exposure and as needed,” and “reapply as needed or after towel drying, swimming, or (select ‘sweating' or ‘perspiring').” EPA is soliciting comment on how the safety concern of a potential misapplication of the insect repellent can be reconciled with the need to provide complete coverage of exposed skin for the sunscreen component.

3. Federal Fungicide and Rodentide Act (FIFRA) registration. Given the aforementioned safety concerns and potential conflicts, the Agency would like to solicit comments on whether these insect repellent-sunscreen combination products should be registered at all.

B. Effectiveness Issues

For some products, there are effectiveness concerns because of the interval of time required between applications of the product. EPA identifies reapplication times on product labels so consumers maintain protection against insect bites, while avoiding over-exposure. This reapplication time relates to the effectiveness of the insect repellent portion of the product, not to the sunscreen protection. The sunscreen reapplication time is under the purview of the FDA. For some of the insect repellent products currently registered, the recommended reapplication time to maintain the effectiveness of the insect repellent could potentially be longer than that recommended to ensure the protectiveness of the sunscreen portion of the product. EPA is soliciting comment on the following questions:

1. Is it possible to formulate these products such that the insect repellent protection time coincides with the sunscreen protection time?

2. Are there effective concentrations of the insect repellent ingredients that could be used to allow for liberal application and frequent reapplication of the insect repellent-sunscreen combination products, as directed by the sunscreen instructions, without causing unnecessary exposure of the consumer to the insect repellent component of the product?

3. Is information available to demonstrate that there are any chemical or physical incompatibilities between insect repellents and sunscreen active ingredients when used separately? If so, how does this vary by the insect repellent component or by the sunscreen component? Please submit and/or summarize any information that you reference.

4. Are there some product performance benefits derived from the purposeful combination of the insect repellent and the sunscreen ingredients (as opposed to the sequential application of these products separately). What information is available which would help frame the advantages or disadvantages of these formulation combinations? How does this vary by insect repellent? Please submit and/or summarize any information that you reference.

C. Manufacturing, Registration and Testing Issues

1. Are manufacturers of the insect repellent/sunscreen combination products aware of any conflicts in the EPA and FDA manufacturing requirements? If yes, please identify and propose a way to resolve the conflict.

2. As it relates to potential future regulatory action taken with regard to these products, how should currently registered products be addressed? Should these products have to meet all of the requirements that result from the current EPA-FDA joint regulatory effort to retain their registrations? If not, what requirements should be retained, revised or eliminated?

D. Labeling Issues

1. There are many differences between the labeling requirements required by FDA's OTC drug labeling requirements and EPA's pesticide labeling requirements. For example, the formats and the order in which information is presented are quite different. FDA allows the use of the word “warning” on labels; however it is only allowed as an indicator of toxicity level on pesticide labels. Various required section headings are different. Please comment on how such labeling differences can be reconciled.

2. FDA ingredient statements list the “inactive or inert” ingredients more often and in greater detail than do EPA approved labels. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) does not require the listing of the identities of inert ingredients on the label. Are there ways to provide the insect repellent inert ingredients information in the product's labeling to satisfy the drug requirements of the FFDCA?

3. Is it desirable for users of these products to have a single integrated label, or would an insect repellent (EPA) and a sunscreen (FDA) section in the product's labeling be preferable?

4. Should the insect repellent/sunscreen combination products be required to have a statement on the front panel of the label specifically identifying the product as containing an insect repellent (such as, This Product Contains An Insect Repellent)? Would this be useful to help consumers distinguish between sunscreen products that contain pesticides from the typical sunscreen drug products that contain no pesticides?

List of Subjects

Environmental protection, Administrative practice and procedure, Intergovernmental relations, Pesticides, Pests.

Dated: February 13, 2007.

James B. Gulliford,

Assistant Administrator, Office of Prevention, Pesticides and Toxic Substances.