[Federal Register Volume 72, Number 35 (Thursday, February 22, 2007)]
[Proposed Rules]
[Pages 7941-7945]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-2890]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 352
[Docket No. 2006N-0479]
RIN 0910-AF43
Insect Repellent-Sunscreen Drug Products for Over-the-Counter
Human Use; Request for Information and Comments
AGENCY: Food and Drug Administration, HHS.
ACTION: Request for data and information.
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SUMMARY: The Food and Drug Administration (FDA) is seeking information
to formulate a regulatory position on insect repellent products that
contain over-the-counter (OTC) sunscreen ingredients. FDA is
considering amending its monograph for OTC sunscreen drug products (the
regulation that establishes conditions under which these drug products
are generally recognized as safe and effective and not misbranded) to
add conditions for marketing insect repellent-sunscreen drug products.
The insect repellent ingredients in these products are regulated by the
Environmental Protection Agency (EPA). Elsewhere in this issue of the
Federal Register is a companion document in which EPA is also
requesting information and comments on these products. The decision on
what regulations, if any, to propose will be based, in part, on
information and comments submitted in response to this request for data
and information.
DATES: Submit written or electronic comments by May 23, 2007.
ADDRESSES: You may submit comments, identified by Docket No. 2006N-0479
or RIN 0910-AF43, by any of the following methods:
Electronic Submissions
Submit electronic comments in the following ways:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.
Agency Web site: http://www.fda.gov/dockets/ecomments.
Follow the instructions for submitting comments on the agency Web site.
Written Submissions
Submit written submissions in the following ways:
FAX: 301-827-6870.
Mail/Hand delivery/Courier [For paper, disk, or CD-ROM
submissions]: Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
To ensure more timely processing of comments, FDA is no longer
accepting comments submitted to the agency by e-mail. FDA encourages
you to continue to submit electronic comments by using the Federal
eRulemaking Portal or the agency Web site, as described in the
Electronic Submissions portion of this paragraph.
Instructions: All submissions received must include the agency name
and Docket No. and Regulatory Information Number (RIN) for this
rulemaking. All comments received will be posted without change to
http://www.fda.gov/ohrms/dockets/default.htm, including any personal
information provided. For additional information on submitting
comments, see the ``Comments'' heading of the SUPPLEMENTARY INFORMATION
section of this document.
Docket: For access to the docket to read background documents or
comments received, go to http://www.fda.gov/ohrms/dockets/default.htm
and insert the docket number, found in brackets in the heading of this
document, into the ``Search'' box and follow the prompts and/or go to
the Division of Dockets Management, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Matthew R. Holman, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, MS 5411, Silver Spring, MD 20993, 301-796-
2090.
SUPPLEMENTARY INFORMATION:
I. Background
A. Description of Insect Repellent-Sunscreen Drug Products
FDA and EPA are seeking information to formulate a regulatory
position for combination insect repellent-sunscreen drug products for
use on human skin. Because sunscreen drug products are regulated by FDA
and the insect repellent components of these products are separately
regulated by EPA, both agencies are seeking comments to
[[Page 7942]]
determine how these combination products should be regulated.
Currently, approximately 20 combination insect repellent-sunscreen
drug products are available for consumers. These products consist of
one of three insect repellents (N,N-diethyl-meta-toluamide (DEET), oil
of citronella, or IR3535) and a sunscreen component (one or more
sunscreen ingredients). Combination insect repellent-sunscreen drug
products are available in lotion, cream, and spray-on formulations and
are currently marketed for use by the entire family. Due to concerns
about the potential conflict in the directions for use and other
labeling requirements for the insect repellent and the sunscreen
components of the product, EPA postponed a regulatory decision on
combination DEET/sunscreen products in its Reregistration Eligibility
Decision (RED) for DEET (December 1998) until additional information
could be obtained. This document solicits opinion and comment from the
public to assist both agencies in regulating these products.
B. Regulatory Status of the Insect Repellent Ingredients
EPA regulates insect repellents under the Federal Insecticide,
Fungicide, and Rodenticide Act (FIFRA). Three insect repellent active
ingredients are currently used in combination with sunscreens: DEET,
oil of citronella, and IR3535. EPA recently registered two other insect
repellents, p-menthane-3,8-diol and picaridin. However, neither is
currently available in combination with a sunscreen. Both DEET and oil
of citronella have undergone reregistration, which entailed an
evaluation and analysis of the complete database for each ingredient by
EPA. IR3535, p-menthane-3,8-diol, and picaridin are registered
chemicals evaluated by the registration process, which involves a
similar analysis by EPA. They have not yet undergone the reregistration
analysis.
1. DEET
In December 1998, EPA completed its RED for DEET (Ref. 1), which
includes the active ingredient N,N-diethyl-meta-toluamide and its
isomers. DEET products, which are applied directly to skin and/or
clothing, are available in numerous formulations (e.g., aerosol and
non-aerosol sprays, creams, lotions, sticks, foams, and towelettes) and
concentrations (products range from about 4 percent to 100 percent
active ingredient). DEET is an insect and mite repellent labeled for
use in households/domestic dwellings, on the human body and clothing,
on cats, dogs, and horses, and in pet living/sleeping quarters.
Based on pesticide usage information mainly for 1990 (Ref. 1), an
average annual estimate of the domestic usage of DEET is 4 million
pounds (active ingredient). About 30 percent of the U.S. population
uses DEET annually as an insect repellent (this figure includes about
27 percent of adult males, 31 percent of adult females, and 34 percent
of children). Approximately 21 percent of U.S. households use DEET
annually. About 19 percent of households use DEET on household members,
and about 4 percent of households that have cats and/or dogs use DEET
on those pets.
EPA indicated in its DEET RED (Ref. 1):
The Agency is concerned about consumer use of products that
combine sunscreen and DEET, since 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.
EPA did not make a regulatory decision regarding these DEET-
sunscreen products at that time because it believed that it had not yet
obtained adequate information.
2. Oil of Citronella
In February 1997, EPA completed its RED for Oil of Citronella (Ref.
2). This decision includes a comprehensive reassessment of the required
target data and the use patterns of currently registered oil of
citronella 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 citronella oil exist commercially: ``Ceylon type''
(derived from C. nardus) and ``Java type'' (derived from C.
winterianus).
Based on pesticide survey usage information for 1991 and 1992 (Ref.
2), annual oil of citronella domestic usage ranged approximately from
33,000 to 48,000 pounds active ingredient for four sites: Domestic
dwellings; ornamentals; human face, skin, and clothing; and
manufacturing. The largest markets, in terms of total pounds active
ingredient, for oil of citronella as an insect repellent are: Human
face, skin, and clothing (56 to 74 percent); domestic dwelling
[outdoor] (22 to 41 percent); and ornamentals (1.5 to 2.0 percent). The
balance is used for manufacturing.
In the RED (Ref. 2), EPA required all oil of citronella products
with label claims for repelling mosquitoes, fleas, and ticks to have a
minimum protection time of 1 hour. The directions for use must also
contain the following statement pertaining to maintenance of repellent
activity: ``For maximum repellent effectiveness of this product, repeat
applications at 1 hour intervals.'' The RED allows the labeling to
claim a protection time longer than 1 hour so long as it can be
supported by product performance data showing an acceptable level of
repellent activity. Because the principal uses of oil of citronella are
dermal, special precautionary labeling related to dermal sensitization
and irritation is required for all products with use directions for
dermal application. EPA (Ref. 2) requires oil of citronella-sunscreen
products for dermal application to bear the following precautionary
statements regarding dermal sensitivity: ``For external use only. Avoid
contact with eyes. Discontinue if irritation or rash appears. Use on
children under 6 months of age only with the advice of a physician.''
These precautionary statements are consistent with the warnings and
directions (regarding use on children under 6 months of age) that
appear in FDA's stayed monograph for OTC sunscreen drug products (part
352 (21 CFR part 352)).
3. IR3535
The third currently registered insect repellent used in combination
with a sunscreen is IR3535 (CAS number 52304-36-6). In 1997, EPA
classified IR3535 as a biochemical for the following reasons (Ref. 3):
(1) It is functionally identical to naturally occurring beta-alanine,
(2) both ingredients repel insects, (3) their basic molecular structure
is identical, (4) the end groups are not likely to contribute to
toxicity, and (5) IR3535 acts to control the target pest via a nontoxic
mode of action. IR3535 is a technical grade synthetic biochemical
pesticide that is produced by an integrated process. It is a liquid
containing 98 percent 3-[N-Butyl-N-acetyl]-aminopropionic acid, ethyl
ester as the active ingredient and 2 percent inert ingredients.
4. p-menthane-3,8-diol and KBR 3023
There are two insect repellent active ingredients that are not
currently used in a combination insect repellent-sunscreen drug
product. However, for the purposes of completeness, all
[[Page 7943]]
currently registered insect repellents are discussed within this
document.
The first ingredient is p-menthane-3,8-diol, a biochemical
pesticide that is chemically synthesized, although the natural oil can
be extracted from lemon eucalyptus leaves and twigs (Ref. 4). It can be
used in spray and lotion products to repel insects such as mosquitoes.
The other insect repellent is KBR 3023, which contains the active
ingredient picaridin. This chemical is currently formulated only for
application to human skin. In December 2000, EPA registered a 15
percent pump-spray, 10 percent aerosol spray, 7 percent cream, 7
percent pump-spray, 5 percent cream, and 5 percent pump-spray (Ref. 5).
C. Regulatory Status of the Sunscreen Ingredients
In the Federal Register of May 21, 1999 (64 FR 27666), FDA issued a
final monograph for OTC sunscreen drug products in 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 Sec. 352.10; provides for
combinations of sunscreen active ingredients in Sec. 352.20; specifies
required labeling in Sec. Sec. 352.50, 352.52, and 352.60; and sets
forth required testing procedures in Sec. Sec. 352.70 through 352.77.
Once the monograph becomes effective, any drug product (including any
combination insect repellent-sunscreen drug product) that contains
unsuitable inactive ingredients or active drug ingredients that do not
comply with the monograph will be considered a new drug and require an
approved new drug application (NDA) before it may be legally marketed
in the United States.
Initially, the final monograph was to become effective on May 21,
2001, but FDA subsequently extended that date to December 31, 2002 (65
FR 36319, June 8, 2000). FDA then stayed the effective date of the
monograph until further notice (66 FR 67485, December 31, 2001). FDA
has delayed this effective date as it prepares an amendment to part 352
to address formulation, labeling, and testing requirements for
ultraviolet A (UVA) radiation protection and to revise some of the
requirements for ultraviolet B (UVB) radiation protection in a more
comprehensive final monograph.
Historically, FDA has used its enforcement discretion to allow the
marketing of insect repellent-sunscreen drug 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. These types of products were first 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 is now interested in determining whether it should further
amend that monograph to address these combination products. Once the
final monograph for sunscreen drug products becomes effective, any
combination product containing an unsuitable inactive ingredient or an
active drug ingredient that is not included in the final monograph will
be considered a new drug and need an NDA to be legally marketed, even
if the product is also registered with EPA. Thus, one purpose of this
document is to gather information to help FDA formulate its regulatory
position toward these combination products.
D. Regulatory Jurisdiction Over Insect Repellent-Sunscreen Drug
Products
In the Federal Register of December 22, 1971 (36 FR 24234), the
Department of Health, Education, and Welfare (DHEW) and EPA published a
Memorandum of Agreement (the Agreement) regarding matters of mutual
responsibility under the Federal Food, Drug, and Cosmetic Act (FFDCA)
and the FIFRA. The Agreement was amended in the Federal Register of
September 6, 1973 (38 FR 24233). This Agreement does not explicitly
address products that combine sunscreen and insect repellent active
ingredients. As noted, one purpose of this document is to solicit
comments regarding the complexities of joint jurisdiction of these
combination products.
II. Information Requested and Specific Topics for Comment
Interested persons are asked to review and comment upon all aspects
of both FDA's and EPA's documents. Interested persons should submit all
comments to both agencies. Both agencies have potential safety and
effectiveness concerns for some of these products because of the
different intervals of time required or recommended between
applications of sunscreens versus insect repellents. FDA is
particularly interested in receiving comments on the following topics:
A. Possible Manufacturing Conflicts
Because they contain ingredients regulated by EPA and FDA, all
insect repellent-sunscreen drug products currently need to comply with
both EPA's testing and laboratory requirements in 40 CFR part 158 and
FDA's current good manufacturing practice for finished pharmaceuticals
requirements in part 211 (21 CFR part 211). The products will also have
to meet the testing procedures for OTC sunscreen drug products in part
352, subpart D, when that monograph becomes effective. The agencies are
not aware of any specific manufacturing requirements that conflict and
invite specific comment and information on this subject.
1. Are manufacturers of insect repellent-sunscreen drug products or
others aware of any conflicts between the EPA and FDA manufacturing
requirements for these products? If yes, is there any way to resolve
the conflict(s)?
2. Approximately 20 insect repellent-sunscreen drug products are
currently registered with EPA. If there is a future FDA rulemaking for
all combination insect repellent-sunscreen drug products, how should
these currently registered products be addressed in the sunscreen
monograph? What requirements should be retained, revised, or eliminated
from the sunscreen monograph?
3. Have manufacturers of currently marketed insect repellent-
sunscreen drug products conducted any of the testing described in part
352, subpart D, for their combination product(s), notwithstanding that
the effective date of part 352 has been stayed? If yes, what problems,
if any, have they encountered?
B. Possible Formulation Conflicts
During completion of its DEET RED, EPA solicited information from
registrants of insect repellent-sunscreen drug products on the
possibility of formulation conflicts. At that time, EPA received
information that suggests a potential formulation conflict is
encountered when sunscreen and insect repellent are used separately (or
sequentially applied) (Ref. 6). It is unclear whether this formulation
issue poses a similar or related problem when these ingredients are
combined into a single product. The agencies invite specific comment
and information on this subject.
C. Possible Labeling Conflicts
Insect repellent and sunscreen products each have different
labeling
[[Page 7944]]
requirements that may conflict when both are combined and packaged in
one product. The insect repellent component is subject to the labeling
requirements in 40 CFR 156.10 entitled ``labeling requirements and the
active ingredient specific requirements.'' For each registered insect
repellent, these requirements are listed in the registration or
reregistration documents. The sunscreen component of the product is
subject to the labeling requirements in Sec. 201.66 (21 CFR 201.66)
and part 352. However, FDA has stayed these regulations for OTC
sunscreen drug products until we issue a sunscreen final rule (69 FR
53801 (September 3, 2004) and 66 FR 67485).
The agencies are concerned that the labeling format and some of the
content requirements vary between the EPA and FDA requirements. For
example, FDA uses the word ``warning'' on labels, while EPA uses the
word ``caution'' and only uses the word ``warning'' as an indicator of
toxicity level on pesticide labels. Many of the required warning
section headings are also different. In addition, the application
directions for the sunscreen and the insect repellent components may be
significantly different. For example, the application directions for
sunscreens state to ``apply liberally (or generously) * * * as needed''
and provide for application to more areas of the body than do the
application instructions for insect repellents, which tend to restrict
the frequency of application and where and how the product can be
applied.
EPA requirements for DEET include labeling that states: ``Apply
sparingly around ears.'' and ``Do not apply to children's hands.'' 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.''
Also, a currently marketed insect repellent (DEET)-sunscreen drug
product states in its labeling ``frequent reapplication and saturation
is unnecessary for effectiveness.'' While frequent reapplication may
not be necessary for the effectiveness of the DEET in this product,
frequent reapplication may be necessary for the effectiveness of the
sunscreen.
Hence, there are many differences between the labeling required by
FDA for OTC drugs and EPA for pesticides. The labeling formats,
labeling content, and the order in which information is presented are
quite different. FDA and EPA are exploring whether they can reconcile
these differences, safeguard the public health, and still adequately
meet the requirements of FFDCA and FIFRA.
1. Concerning an integrated label, can the different instructions
for the two components (regarding frequency of application and where
the product can be applied) be reconciled into a single direction that
does not lead to improper application (i.e., incorrect location), over-
application of the insect repellent, or under-application of the
sunscreen? Is there labeling that would reflect the differences in
reapplication intervals for DEET when combined with sunscreen
ingredients? Oil of citronella when combined with sunscreen
ingredients? IR3535 when combined with sunscreen ingredients?
2. The FFDCA requires that all OTC drug products list the
established name of each inactive ingredient on the outside container
of the retail package (see section 502(e)(1)(A)(iii) of FFDCA (21
U.S.C. 352(e)(1)(A)(iii)); also see Sec. 201.66(c)(8)). EPA does not
require a complete declaration of ``inactive or inert'' ingredients and
normally does not require insect repellent manufacturers to list the
identities of inert ingredients on product labels. However, under
FIFRA, if one inert ingredient is disclosed in product labeling, then
all inert ingredients must be disclosed. EPA is currently discussing,
with a wide spectrum of stakeholders, how to make information
concerning inert ingredients more widely available. The results of
those discussions will affect combination insect repellent-sunscreen
drug products as well as other pesticide products. Failure to list all
of the inactive ingredients in the product's labeling, including all
such ingredients in the insect repellent, would cause a combination
insect repellent-sunscreen drug product to be misbranded under the
FFDCA (see section 502(e)(1)(A)(iii) of FFDCA). Is there a way to label
combination sunscreen-insect repellent drug products that satisfies
FFDCA's requirements under section 502(e)(1)(A) of FFDCA but does not
violate FIFRA? Are those ingredients that are ``inert'' under FIFRA
also necessarily ``inactive'' under FFDCA?
D. Safety Issues
FDA is aware of only two studies examining percutaneous absorption
when combining an insect repellent with a sunscreen. One study involved
hairless mice (Ref. 6) and the other study involved piglets (Ref. 7).
Both studies demonstrate increased absorption of the insect repellent
DEET and different sunscreens when the components were combined. Thus,
FDA would like more information concerning the safety of insect
repellent-sunscreen drug products:
1. Is there data available to show whether increased absorption of
the sunscreen ingredients(s) does or does not occur as a result of
being combined with an insect repellent ingredient? If so, please
provide. For example, is there any evidence that absorption increases
as the particle size of titanium dioxide and zinc oxide decreases (down
to a few nanometers) in insect repellent-sunscreen products? If so, is
there evidence regarding the health or safety effects associated with
the increased absorption?
2. Are there reports or other information relating to skin
irritation resulting from use of a combination insect repellent-
sunscreen drug product are manufacturers of these products or others
aware of? Provide a summary of the types of events reported and, if
possible, estimate an incidence of occurrence.
E. Effectiveness Issues
For some insect repellent-sunscreen products, FDA has effectiveness
concerns because of the interval of time required or recommended
between applications of the product. EPA identifies reapplication times
on insect repellent labels so consumers can maintain the maximum
protection against insect bites but avoid over-exposure. This
reapplication time relates to the effectiveness of the insect repellent
portion of the product and not to the sunscreen protection. The
directions for sunscreen products, which encourage frequent
reapplication of the drug, relate to the effectiveness of the sunscreen
component of the product and not to the insect repellent component.
The differences in directions for use for the insect repellent
component and the sunscreen component need to be resolved to ensure
safety and effectiveness of both components and the combination product
as a whole. For example, the directions for some products containing
DEET 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.'' In contrast, the directions
for sunscreen drug products in Sec. 352.52(d)(1) and (d)(2) state to
``apply 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').'' Section
352.60(d) of the sunscreen monograph also states that ``when the time
intervals or age limitations for administration of
[[Page 7945]]
the individual ingredients differ, the directions for the combination
product may not contain any dosage that exceeds those established for
any individual ingredient in the applicable OTC drug monograph(s), and
may not provide for use by any age group lower than the highest minimum
age limit established for any individual ingredient.''
Concerns about effectiveness also stem from a study (Ref. 8)
indicating that separate application of sunscreen followed by DEET
resulted in a decrease in sun protection factor (SPF) after application
of the insect repellent. Thus, FDA is soliciting comment on the
following questions:
1. Is there additional evidence suggesting that application of a
sunscreen product followed by application of a separate insect
repellent product results in a decrease in the sunscreen's SPF? Is
there evidence suggesting that sequential application of the products
has no adverse effect on the sunscreen?
2. Is there evidence suggesting that combining a sunscreen and
insect repellent in a single formulation adversely impacts the
effectiveness of the sunscreen? Is there evidence suggesting that such
a combination has no adverse impact on the sunscreen component?
3. 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 drug products,
as directed by the sunscreen directions, without jeopardizing the
safety of the consumer? How does this vary by insect repellent
ingredient? Would any of the insect repellent ingredients be effective
at such concentrations?
4. Is there information available to show whether there are any
chemical or physical incompatibilities between insect repellent and
sunscreen active ingredients when used in combination products or when
used separately? Are there any sunscreen ingredients that should not be
used with a specific insect repellent ingredient?
5. If an insect repellent ingredient (e.g., DEET) is labeled for 6-
hour intervals between applications, can the effectiveness of the
sunscreen be assured if the product cannot be applied more often than
every 6 hours? Is there a need for a minimal SPF to assure the
effectiveness of the combination product considering the wide variation
in minimal erythemal dose (MED) between individuals and the need for
reapplication due to physical stress such as toweling or rubbing of the
skin? If the answer is yes, what minimal SPF value should be required,
and what is the basis for that SPF value?
6. Is there information available to demonstrate that there are
product performance benefits [other than the convenience of using one
product instead of two] derived from the concurrent application of the
insect repellent and the sunscreen (as opposed to sequential
application of these products separately)? Please submit any data that
you reference.
7. Oil of Citronella products are labeled to repeat applications at
1 hour intervals for maximum repellent effectiveness. Is it possible
that insect repellent-sunscreen drug products can be formulated in such
a way that the insect repellent reapplication intervals coincide more
closely with the sunscreen reapplication intervals? Can this be done
without jeopardizing the safety or effectiveness of these products?
III. Request for Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments on this document. Three
copies of all written comments are to be submitted. Individuals
submitting written comments or anyone submitting electronic comments
may submit one copy. Comments are to be identified with the docket
number found in brackets in the heading of this document and may be
accompanied by a supporting memorandum or brief. Received comments may
be seen in the Division of Dockets Management between 9 a.m. and 4
p.m., Monday through Friday.
IV. References
The following references are on display in the Division of Dockets
Management (see ADDRESSES) and may be seen by interested persons
between 9 a.m. and 4 p.m., Monday through Friday.
1. EPA Reregistration Eligibility Decision for DEET, 1998.
2. EPA Reregistration Eligibility Decision for Oil of
Citronella, 1997.
3. EPA Biopesticide Registration Eligibility Document for
IR3535, 1999.
4. EPA Biopesticide Registration Eligibility Document for p-
menthane-3,8-diol, 2000.
5. EPA Decision Memorandum on KBR 3023, 2000.
6. Ross, E. A. et al., ``Insect Repellent Interactions:
Sunscreens Enhance DEET (N,N-Diethyl-M-Toluamide) Absorption,'' Drug
Metabolism and Disposition, 32:783-785, 2004.
7. Gu, X. et al., ``In Vitro Evaluation of Concurrent Use of
Commercially Available Insect Repellent and Sunscreen
Preparations,'' British Journal of Dermatology, 152: 1263-1267,
2005.
8. Montemarano, A. D. et al., ``Insect Repellents and the
Efficacy of Sunscreens,'' The Lancet, 349:1670-1671, 1997.
This request for information and comment is issued under sections
201, 501, 502, 503, 505, 510, and 701 of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 321, 351, 352, 353, 355, 360, and 371) and
under authority of the Commissioner of Food and Drugs.
Dated: December 5, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-2890 Filed 2-21-07; 8:45 am]
BILLING CODE 4160-01-S