[Federal Register Volume 83, Number 208 (Friday, October 26, 2018)]
[Notices]
[Pages 54108-54110]
[FR Doc No: 2018-23438]

-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket Nos. FDA-2017-E-4274; FDA-2016-E-3887]

Determination of Regulatory Review Period for Purposes of Patent
Extension; TALTZ

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA or the Agency) has
determined the regulatory review period for TALTZ and is publishing
this notice of that determination as required by law. FDA has made the
determination because of the submission of applications to the Director
of the U.S. Patent and Trademark Office (USPTO), Department of
Commerce, for the extension of a patent which claims that human
biological product.

DATES: Anyone with knowledge that any of the dates as published (in the
SUPPLEMENTARY INFORMATION section) are incorrect may submit either
electronic or written comments and ask for a redetermination by
December 26, 2018. Furthermore, any interested person may petition FDA
for a determination regarding whether the applicant for extension acted
with due diligence during the regulatory review period by April 24,
2019. See ``Petitions'' in the SUPPLEMENTARY INFORMATION section for
more information.

ADDRESSES: You may submit comments as follows. Please note that late,
untimely filed comments will not be considered. Electronic comments
must be submitted on or before December 26, 2018. The https://www.regulations.gov electronic filing system will accept comments until
11:59 p.m. Eastern Time at the end of December 26, 2018. Comments
received by mail/hand delivery/courier (for written/paper submissions)
will be considered timely if they are postmarked or the delivery
service acceptance receipt is on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:

     Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket Nos.
FDA-2017-E-4274 and FDA-2016-E-3887 for ``Determination of Regulatory
Review Period for Purposes of Patent Extension; TALTZ.'' Received
comments, those filed in a timely manner (see ADDRESSES), will be
placed in the docket and, except for those submitted as ``Confidential
Submissions,'' publicly viewable at https://www.regulations.gov or at
the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through
Friday.
     Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on https://www.regulations.gov.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with Sec.  10.20 (21 CFR 10.20) and
other applicable disclosure law. For more information about FDA's
posting of comments to public dockets, see 80 FR 56469, September 18,
2015, or access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://www.regulations.gov 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 Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Beverly Friedman, Office of Regulatory
Policy, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
51, Rm. 6250, Silver Spring, MD 20993,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

I. Background

    The Drug Price Competition and Patent Term Restoration Act of 1984
(Pub. L. 98-417) and the Generic Animal Drug and Patent Term
Restoration Act (Pub. L. 100-670) generally provide that a patent may
be extended for a period of up to 5 years so long as the patented item
(human drug product, animal drug product, medical device, food
additive, or color additive) was subject to regulatory review by FDA
before the item was marketed. Under these acts, a product's regulatory
review period forms the basis for determining the amount of extension
an applicant may receive.
    A regulatory review period consists of two periods of time: a
testing phase and an approval phase. For human biological products, the
testing phase begins when the exemption to permit the clinical
investigations of the biological product becomes effective and runs
until the approval phase begins. The approval phase starts with the
initial submission of an application to market the human biological
product and continues until FDA grants permission to market the
biological product. Although only a portion of a regulatory review
period may count toward the actual amount of extension that the
Director of USPTO may award (for example, half the testing phase must
be subtracted as well as any time that may have occurred before the
patent was issued), FDA's determination of the length of a regulatory
review period for a human biological product will include all the
testing phase and approval phase as specified in 35 U.S.C.
156(g)(1)(B).
    FDA has approved for marketing the human biologic product TALTZ
(ixekizumab). TALTZ is indicated for treatment of adults with moderate-
to-severe plaque psoriasis who are candidates for systemic therapy or
phototherapy. Subsequent to this approval, the USPTO received patent
term restoration applications for TALTZ (U.S. Patent Nos. 7,838,638 and
8,110,191) from Eli Lilly and Company, and the USPTO requested FDA's
assistance in determining the patents' eligibility for patent term
restoration. In a letter dated September 20, 2017, FDA advised the
USPTO that this human biological product had undergone a regulatory
review period and that the approval of TALTZ represented the first
permitted commercial marketing or use of the product. Thereafter, the
USPTO requested that FDA determine the product's regulatory review
period.

II. Determination of Regulatory Review Period

    FDA has determined that the applicable regulatory review period for
TALTZ is 3,036 days. Of this time, 2,670 days occurred during the
testing phase of the regulatory review period, while 366 days occurred
during the approval phase. These periods of time were derived from the
following dates:
    1. The date an exemption under section 505(i) of the Federal Food,
Drug, and Cosmetic Act (21 U.S.C. 355(i)) became effective: December 1,
2007. The applicant claims December 2, 2007, as the date the
investigational new drug application (IND) became effective. However,
FDA records indicate that the IND effective date was December 1, 2007,
which was 30 days after FDA receipt of the IND.
    2. The date the application was initially submitted with respect to
the human biological product under section 351 of the Public Health
Service Act (42

U.S.C. 262): March 23, 2015. FDA has verified the applicant's claim
that the biologics license application (BLA) for TALTZ (BLA 125521) was
initially submitted on March 23, 2015.
    3. The date the application was approved: March 22, 2016. FDA has
verified the applicant's claim that BLA 125521 was approved on March
22, 2016.
    This determination of the regulatory review period establishes the
maximum potential length of a patent extension. However, the USPTO
applies several statutory limitations in its calculations of the actual
period for patent extension. In its applications for patent extension,
this applicant seeks 1,156 days or 935 days of patent term extension.

III. Petitions

    Anyone with knowledge that any of the dates as published are
incorrect may submit either electronic or written comments and, under
21 CFR 60.24, ask for a redetermination (see DATES). Furthermore, as
specified in Sec.  60.30 (21 CFR 60.30), any interested person may
petition FDA for a determination regarding whether the applicant for
extension acted with due diligence during the regulatory review period.
To meet its burden, the petition must comply with all the requirements
of Sec.  60.30, including but not limited to: Must be timely (see
DATES), must be filed in accordance with Sec.  10.20, must contain
sufficient facts to merit an FDA investigation, and must certify that a
true and complete copy of the petition has been served upon the patent
applicant. (See H. Rept. 857, part 1, 98th Cong., 2d sess., pp. 41-42,
1984.) Petitions should be in the format specified in 21 CFR 10.30.
    Submit petitions electronically to https://www.regulations.gov at
Docket No. FDA-2013-S-0610. Submit written petitions (two copies are
required) to the Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

    Dated: October 22, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-23438 Filed 10-25-18; 8:45 am]
 BILLING CODE 4164-01-P


September 14, 2000

Mr. Michael Trutna

Information Transfer and Program Integration Division

U.S. Environmental Protection Agency MD-12

Research Triangle Park, North Carolina  27711

Dear Mr. Trutna:

The Minnesota Pollution Control Agency (MPCA) appreciates the
opportunity to provide comments on the Environmental Protection
Agency’s (EPA’s) draft White Paper Number 3, Operational Flexibility
in Facilities Subject to Title V Permitting (65 FR 49803;

August 15, 2000).  The MPCA supports EPA’s efforts to promote
flexibility for facilities regulated under Part 70 permits, and urges
EPA to consider our comments.

Neither “advanced approval” nor “alternative operating scenario”
has been defined in White Paper Number 3 (WP3) or in Part 70.
“Replicable operating procedures” is a term not defined in WP3 nor
mentioned or defined in Part 70.  Unambiguous definitions could lend
clarity to WP3 and discussions on flexibility.

The MPCA’s permitting program appears to conflict with WP3 regarding
the need for notifications for changes between differing alternative
operating scenarios, including installing new equipment under an
advanced approval.  While our EPA-approved program requires that the
facility keep a log of such changes, it does not require facilities to
provide a seven day advanced notice for changes between differing
alternative operating scenarios, as indicated by WP3.  The MPCA wants to
retain its discretion not to require these notices.

The requirement for seven day advance notices is burdensome and
unnecessary, and diminishes the usefulness and flexibility otherwise
offered by alternative operating scenarios.  While there may
occasionally be a need for the frequent scrutiny provided by seven day
notices, contemporaneous recordkeeping would be sufficient and
appropriate in many (if not most) cases.  In addition, it is unlikely
that state and local permitting authorities have adequate resources to
conduct a timely and appropriate review of the advance notices as they
are submitted.

Furthermore, such advance notices are likely to provide no additional
information on an approved project’s environmental impacts than those
considered during the drafting of the permit that authorizes the various
alternative operating scenarios.  In the preamble to its Part 70
proposal, EPA promoted flexible permits, noting, “Processing
unnecessary permit modifications for routine changes takes time and
provides little environmental benefit.”  Similarly, processing
unnecessary advance notices takes time and provides little environmental
benefit.

A permit that provides the opportunity for a variety of alternative
operating scenarios emanates from an application that fully contemplates
those scenarios.  The appropriate time to review the potential impacts
from a facility’s actions takes place prior to permit issuance, not
seven (or fewer) days prior to the commencement of the action.

All alternative operating scenarios must be proposed in permit
applications and approved by permitting authorities.  Permitting
authorities should carefully scrutinize these proposals to ensure the
practical enforceability of each scenario, and this review should be on
a case-by-case basis.

A summary report, collected quarterly, semiannually, or annually
(depending on the projected rate of change at the facility), provides
sufficient information to the permitting authority and the public for
documenting the status of the facility.

In Section III, the WP3 discusses the concept of the “smart permit”
in Section III.  The section describes a methodology that would allow a
facility to move away from general limitations on the volatile content
of coating and solvents and rates of application or production.  In its
place, the facility would accept a more flexible set of limitations that
relies on an overall emission-based limit and a calculation method that
takes the physical properties into consideration.

The MPCA believes that this guidance must be applied carefully depending
on the facility.  In the past, permitting authorities have introduced
limitations on the volatile organic compounds (VOC) content of coatings
or solvents as means to promote pollution prevention at facilities that
have not adopted or moved toward alternative coating technologies.  In
the future, such facilities will continue to exist; encouraging
pollution prevention is more likely to generate a significant
environmental benefit (in the near term) than providing flexibility.
WP3 could point out that flexibility in the form of the replacement
conditions may best fit

facilities farther up the alternative technology learning curve to have
increased flexibility.  In particular, increased flexibility may be
appropriate for facilities that have already implemented low or no VOC
coating alternatives in some areas and now need the flexibility to
extend the use of that technology quickly and easily to other or new
areas of operation.

While the concept of limiting emissions rather than material usage
provides increased flexibility, the capacity and the willingness of the
permittee to perform the expanded recordkeeping must also be considered.
 The permitting authority must be clear that as flexibility increases,
so does the recordkeeping burden.  Some sources may still be willing to
have less flexibility as a trade off for less recordkeeping.

(The example provided in this section includes an example in which a
calculation method is provided for a lithographic printer.  Since the
volatile content of some materials may be recycled in this or a similar
situation, it would be helpful to know how a “recycled material”
term can be included in the equation provided.)

Also, when calculating emissions, it is difficult to obtain reliable
emission factors for certain processes (though this is usually for
non-VOC pollutants such as particulate matter (PM) and nitrogen oxides
[NOx]).

The MPCA is concerned that WP3 will become a de facto rule, rather than
being guidance.  The permitting authority may deem this guidance
inappropriate for a given circumstance permit.  Our fear is that the
regional EPA office would use WP3 to override the permitting
authority’s judgement in such a situation.  In addition, the use of
WP3 as a regulatory yardstick could inhibit the development of other
innovative approaches to permitting.

We appreciate the examples that were provided at the end of WP3.
However, additional examples are needed to more fully illustrate the
concepts being presented.  Language from existing permits could be
displayed, or sample language could be developed.  Examples are sorely
needed to show how advance approvals and alternative operating scenarios
can work for pollutants other than volatile organic compounds including,
in particular, fine particulate matter.  Such examples could include the
routine change-out of (identical or similar) combustion turbines at
pipeline pumping stations.  (This situation would address emissions of
NOX and perhaps particulate matter less than 10 micron in size [PM10]
and sulfur dioxide.)  Another possible example would be the installation
and removal of temporary reciprocating internal combustion engines and
boilers.

Section IV.A. includes the statement that “… advanced approved
changes … require neither a notice nor a log entry when they do not
shift the sources from its current operating scenario.”  It would be
helpful to be able to review examples illustrating advanced approved
changes that require a log entry; a notice and a log entry; or no notice
and no log entry.

Thank you again for the opportunity to comment.

Sincerely,

J. David Thornton

Section Manager

Major Facilities Section

Policy and Planning Division

JDT/RC:lmg

cc:	Peggy Bartz, MPCA, MD/MF

	Dave Beil, MPCA, MD/MF

	Marshall Cole, MPCA, SD/MF

	Dick Cordes, MPCA, PP/MF

	Cindy Hilmoe, MPCA, PP/RF

	Al Innes, MPCA, PP/OP

 	For that matter, a reading of Part 70 itself does not lead us to
believe that changes among alternative operating scenarios requires a
7-day advance notification.

 	September 24, 1992.

Mr. Michael Trutna

Page   PAGE  4

September 13, 2000

 PAGE


1 of 17 UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D. C. 20460 OFFICE OF PREVENTION, PESTICIDES AND TOXIC SUBSTANCES April 13, 2006 MEMORANDUM SUBJECT: Environmental Fate Assessment of Didecyl dimethyl ammonium chloride ( DDAC) for the Reregistration Eligibility Decision ( RED) Document Case No.: 3003 DP Barcode: 323303 FROM: Srinivas Gowda, Microbiologist/ Chemist Risk Assessment and Science Support Branch ( RASSB) Antimicrobials Division ( 7510C)

TO: Mark Hartman, Branch Chief Benjamin Chambliss, Team Leader Najm Shamim, Risk Assessor Regulatory Management Branch II Antimicrobials Division ( 7510C)

Tracy Lantz, Chemical Review Manager Regulatory Management Branch I Antimicrobials Division ( 7510C)

THRU: Siroos Mostaghimi, Acting Team Leader, Team one Risk Assessment and Science Support Branch ( RASSB) Antimicrobials Division ( 7510C)

Norman Cook, Branch Chief Risk Assessment and Science Support Branch ( RASSB) Antimicrobials Division ( 7510C)

Chemical Name PC Code CAS# Common Name Didecyl dimethyl ammonium chloride 069149 7173 51 5 DDAC Environmental Fate Science Chapter and Fate Assessment on DDAC is submitted for Reregistration Eligibility Decision ( RED). 2 of 17 1 DECANAMINIUM, N DECYL N, N DIMETHYL, CHLORIDE ( DDAC) ENVIRONMENTAL FATE SCIENCE CHAPTER EXECUTIVE SUMMARY DDAC is used primarily as a disinfectant, sanitizer, or as a microbiocide/ microbiostat. It also serves as an algaecide, bacteriocide/ bacteriostat, fungicide/ fungistat, insecticide, miticide, virucide, and tuberculocide. Use sites for DDAC include agricultural premises and equipment, food handling, commercial, industrial and institutional settings, residential areas or areas of public access, pets and kennels, medical facilities, swimming pools, aquatic areas, and industrial water systems. DDAC is also used as a wood preservative. As an agricultural pesticide, DDAC is used for ornamental plants, shrubs, and vines. Some of the required guideline studies for an environmental fate assessment have been submitted. The Agency is using these environmental fate studies for fate assessment of DDAC to fulfill the reregistration requirements. However, field dissipation and aquatic field dissipation studies as well as a long term study on accumulation on soils are still needed.

DDAC has been shown to be hydrolytically stable under abiotic and buffered conditions over the pH 5 9 range. DDAC is stable to photodegradation in pH 7 buffered aqueous solutions; even in the presence of a photosensitizer ( acetone), degradation is minimal. DDAC is not subject to photodegradation in soil.

Aquatic metabolism studies under aerobic and anaerobic conditions indicate that DDAC is stable to microbial degradation. The calculated aerobic and anaerobic half lives of 14C DDAC in flooded river water are 180 days and 261 days, respectively. Similarly, DDAC was found to be stable with very little degradation in aerobic soils during a year long metabolism study. However, a report on the biodegradability of DDAC prepared by the Registrant concluded that the degree of DDAC biodegradability is variable and is influenced by the chemical concentration, alkyl chain length, the presence of anionic moieties and the quantity and characteristics of the microbial population. According to this report, DDAC is biodegradable and environmentally acceptable. This report was based on information from the open literature, unpublished sources, and meeting proceedings and has not been reviewed by the Agency.

DDAC is immobile in soil. A soil mobility study reviewed by the Agency shows that DDAC has a strong tendency to bind to sediment/ soil with Freundlich Kads values of 1,095, 8,179, 32,791, and 30,851 in sand, sandy loam, silty clay loam, and silt loam soils, respectively. Because of its strong adsorption to soils, DDAC is not expected to contaminate surface and ground waters.

Bioaccumulation of DDAC in freshwater fish is not likely to occur. Mean steady state bioconcentration factors for DDAC were determined to be 38X, 140X, and 81X in the edible, nonedible, and whole body fish tissue, respectively. DDAC is not expected to pose a concern for bioconcentration in aquatic organisms. 3 of 17 Information on the aqueous availability of DDAC from wood indicates that the use of DDAC as a wood preservative may result in minimal releases to the environment.

I. Environmental Fate Assessment A. Abiotic In a hydrolysis study conducted under abiotic and buffered conditions, methyl labeled 14C didecyl dimethyl ammonium chloride ( DDAC), at concentrations of 8.47 to 8.69 µ g/ ml, was stable in sterile aqueous buffer solutions adjusted to pH 5 ( 0.2 M acetate), pH 7 [ tris( hydroxymethyl) aminomethane ( TRIS)], pH 7 [ N 2 hydroxyethyl piperazine N' 2 ethanesulfonic acid ( HEPES)], and pH 9 ( 0.2 M borate) that were incubated in darkness at 25EC ± 1EC for 30 days. Of the recovered radioactivity throughout the 30 day monitoring period, DDAC residues comprised 92.0 to 95.9% ( pH 5), 89.9 to 94.5% ( pH 7, HEPES), 93.1 to 97.9% ( pH 7, TRIS), and 92.0 to 96.7% ( pH 9). The calculated half lives for DDAC ( extrapolated beyond the experimental timeframe) were 368 days at pH 5, 194 days at pH 7 ( TRIS), 175 days at pH 7 ( HEPES), and 506 days at pH 9. The hydrolysis guideline requirements ( OPP 161 1) have been fulfilled by this study ( MRID No. 411758 01).

The photodegradation potential of DDAC was investigated in sensitized and nonsensitized buffer solutions adjusted to pH 7 ( 0.2 M TRIS). Methyl labeled 14C didecyl dimethyl ammonium chloride ( DDAC), at a concentration of 8.58 µ g/ ml, was relatively stable in nonsensitized sterile aqueous buffer solutions that were continuously irradiated with a xenon light source at 25EC ± 1EC for 30 days. DDAC concentrations ranged from 91.2 to 103% of the applied radioactivity with no discernible pattern of decline. In the dark controls, DDAC concentrations ranged from 93.5 to 100% of the applied radioactivity throughout the 30 day monitoring period. In a similar experiment using acetone sensitized buffer solutions, DDAC was also found to be relatively stable. DDAC declined from 100% of the applied radioactivity immediately post treatment to 93.1% at the end of 30 day monitoring period. DDAC concentrations ranged from 96.2 to 102 percent of the applied radioactivity with no discernible pattern of decline in the dark sensitized controls. The calculated half life of DDAC ( extrapolated beyond the experimental timeframe) was 227 days based on results for the sensitized irradiated solutions. The photodegradation in water guideline requirements ( OPP 161 2) have been fulfilled by this study ( MRID 411758 02). 4 of 17 B. Biotic The aerobic aquatic biotransformation of DDAC was studied in a pond water/ sediment system ( water  pH of 8.7, sediment  pH of 8, sandy loam texture, organic carbon content of 1.6%) from Northwood, North Dakota treated with methyl labeled [ 14C] DDAC at a nominal concentration of 10 parts per million ( ppm). The treated water/ sediment system was incubated in the dark for 365 days at 25EC. The calculated half lives of 14C DDAC in water, sediment, and in the entire system were 180 days, 22,706 days ( 60.5 years), and 8,366 days ( 22.9 years), respectively. At test termination, 101% of the applied radioactivity was partitioned from water to sediment. Transformation products were not present in any significant amounts in the water or sediment. The aerobic aquatic metabolism guideline requirements ( OPP 162 4) have been fulfilled by this study ( MRID 422538 03).

A study of the anaerobic aquatic metabolism of DDAC in lake water and sediment was also conducted. Samples of lake water and sediment were incubated at 25 EC in a dark environment for 365 days. In this study, DDAC was shown to be stable to microbial degradation. The calculated half lives, based on first order degradations of 14C DDAC in anaerobic water, sediment and in the entire system were 261, 4,594, and 6,217 days, respectively. Transformation products were not present in any significant amounts in the water or sediment. This study satisfies the anaerobic aquatic metabolism guideline requirements ( OPP 162 3) ( MRID No. 422538 02).

The aerobic soil metabolism of DDAC was investigated in a sandy loam soil, which is a representative agricultural soil. The soil was treated with [ 14C] DDAC to achieve a concentration of 10 ppm and incubated in darkness at 25EC for up to 365 days. DDAC was found to be stable with very little degradation during the year long study. Transformation products were not present in any significant amounts. The calculated half life for degradation was 1,048 days. This study is acceptable and satisfies guidelines ( OPP 162 1) for aerobic soil metabolism ( MRID No 422538 01).

A review of information from the open literature, unpublished sources and meeting proceedings prepared by the Registrant indicates that DDAC is aerobically biodegradable. The report author noted that the aerobic and anaerobic aquatic metabolism studies conducted on DDAC were designed to assess the environmental fate of DDAC based on outdoor applications of agricultural chemicals but not the direct biodegradability potential of DDAC as a result of its use as an antimicrobial. Other limitations of the tests were noted such as loss of microbial activity during air drying of soil material, limited gas exchange in the aerobic test, and the use of unacclimated microbial systems. According to this report, the degree of DDAC's biodegradability is variable and is influenced by the chemical concentration, alkyl chain length, the presence of anionic moieties and the quantity and characteristics of the microbial population. A mechanism of biodegradation for DDAC in which several bacterial species are needed for ultimate biodegradation of this compound is also described.

In an adsorption/ desorption study reviewed by the Agency, DDAC was found to be immobile in four representative agricultural soils ( sand, sandy loam, silt clay loam, and silt 5 of 17 loam). Freundlich Kads values were 1,095 for the sand, 8,179 for the sandy loam, 32,791 for the silty clay loam, and 30,851 for the silt loam soils. Respective Koc values were 437,805, 908,757, 1,599,564, and 1,469,081. Freundlich Kdes values were 591 for the sand soil, 2,074 for the sandy loam soil, 8,309 for the silty clay loam soil, and 7,714 for the silt loam soil. Respective Koc values were 236,473, 230,498, 405,328, and 367334. This study ( MRID No. 413853 01) partially fulfills the adsorption/ desorption data requirements for DDAC ( OPP 163 1) by providing information on the mobility ( batch equilibrium) of unaged 14C DDAC in sodium azide sterilized sand, sandy loam, silty clay loam, and silt loam soils. However, additional data are required on the mobility of aged 14C DDAC residues in soil.

A 46 day study ( 28 day bioconcentration and 18 day depuration period) was conducted to evaluate the bioconcentration of DDAC in bluegill sunfish under flow through aquarium conditions ( MRID No. 458341 01). In this study, the levels of 14C residues in the edible, nonedible and whole body fish tissue reached steady state by day 10 of exposure. Mean steady state bioconcentration factors for DDAC were 38X, 81X, and 140X in the edible tissue, whole body fish tissue, and nonedible tissue, respectively. These bioconcentration factors are considered relatively low and indicate that DDAC would not be expected to bioaccumulate in fish tissue. By day 14 of the depuration period, 57%, 67%, and 71% of the 14C residues present on the last day of exposure in the edible, whole body, and nonedible tissue, respectively, had been eliminated. DDAC was found to bind significantly to the non edible segments of the bluegill, especially the skin and scales. 14C residue levels were approximately 2 to 6 times higher in skin tissue than those observed for the corresponding edible tissue. The half life of DDAC was determined to be between 7 and 14 days of depuration. Study results also indicated that the half life of DDAC in edible tissue is significantly shorter than that of the nonedible segments. The Agency noted that the concentration of DDAC in the treatment aquarium was continuously above nominal and was not consistently maintained within ± 20% of the mean measured value. In addition, the temperatures ranged between 17 18 ° C, which is below the recommended temperature of 20 25 ° C. However, the study was found by the Agency to be acceptable and provided useful information on the bioaccumulation of DDAC residues in bluegill sunfish. It satisfies the bioaccumulation in fish data requirements for DDAC ( OPP 165 4/ 850.1730).

A photolysis study was conducted with DDAC on soil treated at a nominal concentration of 10 ppm. The study consisted of two test systems: an exposed test system that was continuously irradiated with a xenon arc light source for 30 days and a non exposed test system. In the exposed system, the photolysis rate constant and half life of DDAC were reported as 5.26 x 10 3 days 1 and 132 days, respectively. The photolysis rate constant and half life of DDAC in the non exposed system were determined to be 4.11 x 10 3 days 1 and 169 days, respectively. This study is acceptable and meets guidelines for the fulfillment of data requirements for DDAC on photodegradation on soil ( OPP 161 3) ( MRID No. 424807 01).

An aqueous availability study ( MRID No. 455243 05), performed according to the American Wood Preservers' Association Standard, Method E11 97, evaluated the leachability of didecylmethyl ammonium carbonate ( DDACarb), a related compound, from treated wood. Wood samples were vacuum treated with 0.85 percent ( 0.5X retention level), 1.7 percent ( 1X), 6 of 17 and 3.4 percent ( 2X) of DDACarb, and placed in deionized water for 14 days. Leachate was collected from the sampling unit at intervals of 6, 24, and 48 hours, and 4, 6, 8, 10, 12, and 14 days following the start of the leaching period. The corrected amount of DDACarb recovered from the leachate ranged from 186.1 µ g to 764.7 µ g ( 0.5X retention level), from 218.9 µ g to 1152.9 µ g ( 1X), and from 446.2 µ g to 2101.1 µ g ( 2X). The total recovery from the leachate over the 14 day period was 3464.7 µ g, 4483.0 µ g and 7444.7 µ g for the 0.5X, 1X and 2X retention levels, respectively. 7 of 17 APPENDIX Environmental Fate Data for DDAC A. Environmental Fate Guideline Studies 1. Hydrolysis ( OPP Guideline Number 161 1, MRID No. 411758 01)

This hydrolysis study was reviewed by the Agency and was found acceptable. The hydrolysis data requirements for DDAC have been fulfilled.

In this study, methyl labeled [ 14C] DDAC ( didecyldimethylammonium chloride, radiochemical purity 99.2%, specific activity 9.01 mCi/ mmol), in deionized, sterile filtered water, was added to sterile pH 5 ( acetate), pH 7 ( TRIS), pH 7 ( HEPES) and pH 9 ( borate) aqueous buffer solutions at concentrations of 8.47 8.69 µ g/ ml. Aliquots of the treated buffer solutions were added to sterile, foil covered culture tubes and incubated in the dark at 25 ± 1EC for 30 days. Samples were removed for analysis at 0, 4, 7, 14, 22, and 30 days post treatment.

At each sampling interval, duplicate aliquots of the buffer solutions were analyzed for total radioactivity by liquid scintillation counting ( LSC). An additional aliquot of the test solution was analyzed by one dimensional TLC on silica gel plates developed in chloroform: methanol: formic acid ( 60: 40: 2, v: v: v). Radioscanning was used to locate and quantify radioactive areas. TLC plates from the 0 and 30 day sampling intervals were analyzed by autoradiography.

Study results indicate that methyl labeled [ 14C] DDAC was relatively stable in sterile pH 5, pH 7 ( TRIS and HEPES), and pH 9 buffer solutions incubated in the dark at 25 ± 1EC for 30 days. In the pH 5 buffer solution, the parent was present at 92.0% of the recovered radioactivity at 30 days posttreatment ( range during the study: 92.0  95.9% of the recovered radioactivity); total [ 14C] DDAC residues during the study ranged from 8.22 µ g/ mL to 8.95 µ g / ml with no discernible pattern. The parent comprised 89.9  94.5% and 93.1  97.9% of the recovered radioactivity in the pH 7( HEPES) and pH 7 ( TRIS) buffer solutions, respectively. Total [ 14C] DDAC residues during the study ranged from 7.93 µ g / ml to 9.02 µ g / ml in the pH 7 ( HEPES) buffer solution and from 7.83 µ g / ml to 8.90 µ g / ml in the pH 7 ( TRIS) buffer solution . In the pH 9 buffer solution, total [ 14C] DDAC residues ranged from 8.00 µ g / ml to 8.67 µ g / ml with no discernible pattern; parent [ 14C] DDAC comprised 92.0  96.7% of the recovered radioactivity. The material balances were 95.6  104% for the pH 5 solution, 93.6  106% for the pH 7 ( HEPES) solution, 90.1  102% for the pH 7 ( TRIS) solution, and 92.3  100% for the pH 9 solution.

The calculated half lives for [ 14C] DDAC were 368 days at pH 5, 194 days at pH 7 ( TRIS), 175 days at pH 7 ( HEPES), and 506 days at pH 9. It was noted that these statistical estimates are of limited value because the calculations involve extrapolation considerably beyond the experimental time limits of the study. 8 of 17 TLC analysis of the pH 7 ( HEPES) solution at day 30 indicated a slight decrease ( approximately 10%) in the size of the parent peak; the material appeared to form a shoulder on the parent peak. However, given the apparent half life of 175 days and a low correlation coefficient ( r2 = 0.575), the authors concluded that this observation did not indicate significant degradation.

2. Photodegradation in Water ( OPP Guideline No. 161 2, MRID No. 411758 02)

This photodegradation study was reviewed by the Agency and was found to be acceptable. The photodegradation in water data requirements for DDAC have been satisfied.

In this study, methyl labeled [ 14C] DDAC ( didecyldimethylammonium chloride, radiochemical purity   98.5%, specific activity 9.01 mCi/ mmol), in deionized water, was added to sterile pH 7 ( TRIS) buffer solution at a concentration of 8.58 µ g/ ml. [ 14C] DDAC was also added at a concentration of 8.59 µ g / ml to a sterile pH 7 ( TRIS) buffer solution that had been photosensitized with 1% acetone. Aliquots of the treated solutions were transferred to borosilicate glass culture tubes with Teflon lined screw tops. Some of the vials containing the test solutions were covered with aluminum foil and stored inside a closed box ( dark control samples). The box was placed along with unwrapped tubes ( 12) in a photolysis apparatus. A xenon lamp was used to continuously irradiate the samples for 30 days. The temperature in the photolysis chamber was maintained at 25 ± 1EC.

Aliquots of the test solutions were analyzed immediately post treatment and duplicate samples of irradiated and dark control solutions were removed for analysis at 1.03, 2.02, 7.03, 14.0, 21.0, and 29.9 days post treatment. At each sampling interval, duplicate aliquots of irradiated and dark control solutions were analyzed for total radioactivity by liquid scintillation counting ( LSC). Additional aliquots of each test solution were analyzed by one dimensional TLC on silica gel plates developed in chloroform: methanol: formic acid ( 60: 40: 2, v: v: v). Radioactive areas were located and quantified by radioscanning. In addition, TLC plates from the 0 and 30 day sampling intervals were autoradiographed. The volatilization of [ 14C] residues from the irradiated and dark control samples was also measured.

Methyl labeled [ 14C] DDAC, at a concentration of 8.58 µ g/ ml, was relatively stable in nonsensitized aqueous buffer solution ( pH 7) that was continuously irradiated with a xenon light source at 25EC ± 1EC for 30 days. In the irradiated samples, [ 14C] DDAC was present at 100% of the applied radioactivity immediately post treatment and ranged from 91.2 to 103% of the applied radioactivity throughout the study period ( 1.03   29.9 days). [ 14C] DDAC was 93.5 98.9% of the applied radioactivity from 1.03   29.9 days and was present at 100% of the applied radioactivity immediately post treatment in the dark control samples.

In the irradiated sensitized samples, [ 14C] DDAC was present at 100% of the applied radioactivity immediately post treatment and declined to 93.1% at 29.9 days. An unidentified degradate was detected, but not quantified. In the dark controls, [ 14C] DDAC was 100% of the applied radioactivity immediately post treatment and 96.2 102% of the applied radioactivity from 1.03   29.9 days. The calculated photolytic half life was 227 days. 9 of 17 Material balance ranged from 90.4 to 102%. Results of the volatility experiments indicated little or no volatilization of [ 14C] DDAC from the test solutions.

3. Aerobic Soil Metabolism ( OPP Guideline No. 162 1, MRID No. 422538 01)

This aerobic soil metabolism study was reviewed by the Agency and found to be acceptable. The study meets guidelines for the fulfillment of data requirements for DDAC on aerobic soil metabolism. However, the Agency stated that the Registrant must provide evidence that aerobic conditions were maintained throughout the experiment.

In this study, samples of sandy loam soil ( collected from Northwood, North Dakota, 78% sand, 10% silt, 12% clay, 1.8% organic carbon, pH 6.3, CEC 0.7 meq/ 100 g) were treated with methyl labeled [ 14C] DDAC ( didecyldimethylammonium chloride, radiochemical purity 90%, specific activity 9.01 mCi/ mmol), at a nominal concentration of 10 parts per million ( ppm). The treated soil samples were incubated in darkness at 24 26EC for up to 365 days; soil moisture levels were maintained between 70% and 75% of field moisture capacity by the addition of water as needed. The test system consisted of a standard tall form 3,000 ml resin pot as the incubation vessel and included an ethylene glycol trap, a sulfuric acid trap and two potassium hydroxide traps vessels for trapping CO2 and volatile organics. Samples were analysed at 0, 1, 3, 7, 14, 31, 61, 92, 123, 182, 273, and 365 days of incubation. The soil samples were extracted with 30 ml of 80: 20 ( v: v) dimethylformamide: acetic acid and then shaken for 1 hour, followed by centrifugation for 10 minutes. Total radioactivity in the samples was determined by liquid scintillation counting ( LSC). Quantification and identification of the 14C DDAC residues was performed using TLC and/ or HPLC.

Material balance averaged 100.5 ± 4.1% of the applied amount. The concentration of the parent compound decreased from a mean of 93.7% of the applied amount at day 0, to a mean of 72.85% of the applied amount at the end of the study period. However, no biotransformation of the parent compound was reported. The calculated half life of 14C DDAC in aerobic soil was 1,048 days.

Extractable 14C residues decreased from a mean of 98.55% of the applied amount at day 0 to a mean of 74.87% of the applied amount at the end of study period. Non extractable 14Cresidues increased from a mean of 1.45% of the applied amount at day 0 to a mean of 17.74% of the applied at the end of the incubation period. At study termination, an average of 1.95% of the applied radioactivity was present as volatile organics. CO2 was not present in any significant amount. Transformation products were not present in any significant amounts in the water or sediment.

4. Anaerobic Aquatic Metabolism ( OPP Guideline No. 162 3, MRID No. 422538 02)

This anaerobic aquatic metabolism study was reviewed by the Agency and was found acceptable. It fulfills the anaerobic aquatic metabolism data requirement for DDAC; however 10 of 17 the Agency noted that the Registrant must submit information describing how anaerobic conditions were assured and maintained.

The anaerobic aquatic metabolism of DDAC was studied using subsamples ( 10 g dry weight) of sieved ( 2 mm) sandy loam sediment from Northwood, ND ( 62% sand, 22% silt, 16% clay, pH 8, CEC 16.3 meq/ 100g, organic carbon 1.6%) flooded with 20 ml of lake water from the same site ( pH 8.1). The sediment water samples were treated with a sufficient amount of methyl labeled [ 14C] DDAC ( didecyldimethylammonium chloride, radiochemical purity 90%, specific activity 9.01 mCi/ mmol), to achieve a nominal concentration of 10 parts per million ( ppm). The test tubes were incubated in the dark at a temperature of 25 ° C for 365 days; the test system consisted of a standard tall form 3000 ml resin pot as the metabolism vessel. An ethylene glycol trap, a sulfuric acid trap and two potassium hydroxide traps were attached for the collection of carbon dioxide ( CO2) and volatile organic compounds. Sediment, water and volatile traps were sampled at 0, 1, 3, 7, 14, 31, 61, 92, 123, 182, 273, and 365 days of incubation. Volatile traps were also sampled at 151, 212, 243, 304 and 335 days of incubation.

At each sampling interval, sediment: water samples were centrifuged and the aqueous phase decanted. The water samples were extracted via mixing with an equal volume of 80: 20 ( v: v) dimethylformamide: acetic acid and then run through a 0.2 F filter to remove any suspended solids. The sediment samples were extracted with 30 ml of 80: 20 ( v: v) dimethylformamide: acetic acid and then shaken for 1 hour, followed by centrifugation for 10 minutes. Quantification and identification of the 14C DDAC residues was performed using TLC and/ or HLPC.

Material balance averaged 103.1 ± 3.5 % of the applied amount for the year long study. The test conditions outlined in the study protocol were maintained throughout the study. Extractable [ 14C] residues in sediment increased from a mean of 84.87 % at day 0, to a mean of 92.22 % of the applied amount, at study termination. Non extractable [ 14C] residues in sediment decreased from a mean of 12.21 % at day 0, to a mean of 10.39 % of the applied amount, at study termination. At the end of the study, 0.30 % of the applied radioactivity was present as volatile compounds, and this activity was later confirmed to be 14C carbon dioxide via precipitation with barium chloride.

The concentration of 14C DDAC in water decreased from a mean of 100 % at day 0 to a mean of 68.65 % of the applied amount, at study termination. The concentration of 14C DDAC in the sediment increased from a mean of 93.85 % at day 0 to a mean of 97.45 % of the applied amount, at the end of the study period. The study authors noted that transformation products were not present in any significant amounts in the water or sediment.

The calculated half life of 14C DDAC ( for the entire system), based on a first order degradation, was 6,218 days. The Agency's calculated half lives, based on first order degradations of 14C DDAC in anaerobic water, sediment and in the entire system were 261, 4,594, and 6,217 days, respectively. No biotransformation of the parent compound was reported. 11 of 17 5. Aerobic Aquatic Metabolism ( OPP Guideline No. 162 4, MRID No. 422538 03)

This aerobic aquatic metabolism study was reviewed by the Agency and was found to be acceptable. It satisfies the aerobic aquatic metabolism data requirements for DDAC. However, the Agency noted that the Registrant must submit information describing how aerobic conditions were assured and maintained.

In this study, subsamples ( 10 g dry weight) of sieved ( 2 mm) sandy loam sediment from Northwood, ND ( 62% sand, 22% silt, 16% clay, pH 8, CEC 16.3 meq/ 100g, organic carbon 1.6%) were weighed into culture tubes and flooded with 20 ml of lake water from the same site ( pH 8.7). The sediment was treated with a sufficient amount of methyl labeled [ 14C] DDAC ( didecyldimethylammonium chloride, radiochemical purity 98.5 ± 0.04%, specific activity 9.01 mCi/ mmol), to achieve a nominal concentration of 10 parts per million ( ppm). The test tubes were incubated in the dark at 25EC for 365 days; the test system consisted of a standard tall form 3000 ml resin pot as the metabolism vessel. An ethylene glycol trap, a sulfuric acid trap and two potassium hydroxide traps were attached for the collection of carbon dioxide ( CO2) and volatile organic compounds. Sediment, water and volatile traps were sampled for analysis at 0, 1, 3, 7, 14, 31, 61, 92, 123, 182, 273, and 365 days of incubation. Volatile traps were also sampled at 151, 212, 243, 304 and 335 days of incubation.

At each sampling interval, sediment: water samples were centrifuged and the aqueous phase decanted. Before analysis by thin layer chromatography ( TLC), the 6, 9, and 12 month water samples were concentrated by evaporating aliquots to dryness and redissolving in methanol. The other water samples were not concentrated prior to analysis. The sediment samples were extracted with 30 ml of 80: 20 ( v: v) dimethylfomamide ( DMF): acetic acid and then shaken for 1 hour, followed by centrifugation for 10 minutes. Quantification and identification of the 14C DDAC residues was performed using TLC and/ or high performance liquid chromatography ( HLPC).

The material balance averaged 105 ± 2.8 % of the applied amount for the year long study. The mean total recovery of the radiolabelled material applied was 1.5 ± 0.9% for water and 101.9 % for sediment ( 93.0 ± 4.4% for extractable residues and 8.9 ± 3.3% non extractable residues). The concentration of 14C DDAC in water decreased from 2.20 % at day 0, to 0.83% of the applied at study termination. The concentration of 14C DDAC in the sediment increased from 86.0% at day 0 to 87.8% of the applied, at the end of the study period. At test termination, 101% of the applied radioactivity was partitioned from water to sediment. Transformation products were not present in any significant amounts in the water or sediment.

Extractable [ 14C] residues in sediment decreased from an average of 90.0 % at day 0, to 89.9 % of the applied amount at the end of incubation period. Non extractable [ 14C] residues in sediment increased from 7.8% at day 0, to 11.3% of the applied amount, at study termination. At the end of the study, 4.5 % of the recovered radioactivity was present as volatiles. The volatiles were determined to be 14C carbon dioxide via precipitation with barium chloride. 12 of 17 As determined by the Agency, the half lives of 14C DDAC in water, sediment, and in the entire system were 180 days, 22,706 days ( 60.5 years), and 8,366 days ( 22.9 years), respectively. The Registrant calculated a half life of 8,365 days for 14C DDAC in the entire system. The pathway of aerobic biotransformation of 14C DDAC in water sediment system was not described.

6. Adsorption/ Desorption ( OPP Guideline No. 163 1, MRID No. 413853 01)

This adsorption/ desorption study was reviewed by the Agency and found scientifically valid. This study partially fulfills the adsorption/ desorption data requirements for DDAC by providing information on the mobility ( batch equilibrium) of unaged 14C DDAC in sodium azide sterilized sand, sandy loam, silty clay loam, and silt loam soils. Additional data are required on the mobility of aged 14C DDAC residues in soil.

Based on the results of preliminary batch equilibrium studies, an equilibration period of 24 hours and a soil: solution ratio of 1: 200 ( w: v) were chosen for this study. For the adsorption phase of the study, aliquots ( 200 ml) of 0.1 N CaCl2 solution containing methyl labeled [ 14C] DDAC ( didecyldimethylammonium chloride, radiochemical purity 97.5%, specific activity 9.01 mCi/ mmol), at nominal concentrations of 0.70, 3.50, 5.25, and 7.0 µ g/ ml, were added to sterile Nalgene screw cap bottles containing subsamples ( 1 g) of sand, sandy loam, silty clay loam, or silt loam soils. The soil samples had been air dried, sieved ( 2 mm) and sterilized by addition of 1% sodium azide ( w: w) prior to the experiment. Triplicate tubes were prepared for each soil type/ treatment rate combination. After the adsorption equilibration period of 24 hours in a dark environmentally controlled chamber at approximately 25 ± 1EC, the soil: solution slurries were centrifuged and triplicate aliquots of the supernatant were analyzed for total radioactivity by liquid scintillation counting ( LSC).

For the desorption phase of the study, pesticide free 0.01N CaCl2 solution ( equal to the volume removed in the adsorption phase) was added to the soil pellets from the adsorption phase of the study. The soil: solution slurries were again equilibrated for 24 hours at approximately 25 ± 1EC in the dark. Following equilibration, the soil: solution slurries were centrifuged and triplicate aliquots of the supernatant were analyzed for total radioactivity by LSC.

The sandy loam, silty clay, and silt loam samples were dried and analyzed for total radioactivity by LSC following combustion. The sand soil samples were extracted three times with dimethylformamide: acetic acid ( 80: 20). Following extraction, the samples were centrifuged and aliquots of the supernatant were analyzed by LSC. Subsamples of the extracted soil were analyzed by LSC following combustion.

14C didecyl dimethyl ammonium chloride ( DDAC), at nominal concentrations of 0.70 7.0 µ g/ ml, was determined to be immobile in sodium azide sterilized sand, sandy loam, silty clay loam, and silt loam soil: solution slurries ( 1: 200) that were equilibrated in darkness at 25EC ± 1EC for 24 hours. Freundlich Kads values were 1,095 for sand, 8,179 for the sandy loam, 32,791 for the silty clay loam, and 30,851 for the silt loam soils. Respective Koc values were 437,805, 908,757, 1,599,564, and 1469081. 13 of 17 Study results for the desorption phase indicate that 16.26 to 39.33% of the absorbed radioactivity was desorbed from the sand soil, 2.20 to 12.60% was desorbed from the sandy loam soil, 0.20 to 1.40% was desorbed from the silty clay loam soil, and 0.20 to 1.66% was desorbed from the silt loam soil. Freundlich Kdes values were 591 for the sand soil, 2,074 for the sandy loam soil, 8,309 for the silty clay loam soil, and 7,714 for the silt loam soil. Respective Koc values were 236,473, 230,498, 405,328, and 367334.

Material balances were 88.5  108.1% for the sand soil, 91.6  108.5% for the sandy loam soil, 78.3  106.5% for the silty clay loam soil, and 80.8  118.0% for the silt loam soil.

7. Field dissipation study on soil ( OPP Guideline No. 164 1)

A field dissipation study on soil is required for DDAC. No data have been submitted to the Agency.

8. Aquatic field dissipation study ( OPP Guideline No. 164 2)

An aquatic field dissipation study is required for DDAC. No data have been submitted to the Agency.

9. Long term study on accumulation on soil ( OPP Guideline No. 164 5).

A long term study on accumulation on soil is required for DDAC if pesticide residues do not readily dissipate in soil. No data have been submitted to the Agency. . 10. Bioaccumulation in Fish ( OPP Guideline No. 165 4, MRID No. 458341 01)

This bioaccumulation study was reviewed by the Agency and found scientifically valid. It satisfies the bioaccumulation in fish data requirements for DDAC.

In this study, Bluegill ( 220) were continuously exposed to a nominal concentration of 59 µ g/ L of DDAC for 28 days in an exposure aquarium. A control aquarium was also used which had the same conditions as the treatment aquarium. Water samples were collected from a central point in the treatment aquarium on days 0, 3, 4, 10, 11, 17, and 24 of exposure. Five fish were collected for tissue analysis from the treatment aquarium on days 4, 10, 17, 24, and 28 of exposure. Water samples and fish were collected from the control aquarium for 14C residues on days 0 and 28 of exposure.

Following a 28 day exposure period, 40 of the fish remaining in the exposure aquarium were transferred to an aquarium containing untreated dilution water for an 18 day depuration period. Water samples were collected during the depuration period on days 3, 7, 12, and 18. Five fish were collected on days 3, 7, 14, and 18 of the depuration phase. Water samples and fish were collected from the control aquarium on day 18 of depuration for 14C residues. 14 of 17 The aqueous 14C residues measured in the exposure system during the 28 days were consistently above nominal, at a mean measured concentration of 93 µ g/ L ( ± 32) DDAC. Concentrations of 14C residues present in the depuration aquarium remained at < 11 µ g / L throughout the 18 days. The levels of 14C residues in the edible, non edible, and whole tissue of bluegill exposed to DDAC reached steady state by day 10. The mean steady state bioconcentration factor for DDAC in the edible, nonedible and whole body tissue of the bluegill were determined by the authors to be 38X, 140X and 81X, respectively. The half life of the 14Cresidues present in all tissue portions of the bluegill were found to be between 7 and 14 days. The elimination of 14C residues for edible, nonedible and whole body tissue was 38%, 66% and 56%, respectively. Of the accumulated 14C residues in the edible tissue of bluegill exposed 28 days to DDAC, 65.5% was extractable with a polar solvent ( methanol), 8.1% was extractable with a non polar solvent ( hexane), and 25.9% was not extractable with either solvent. Analysis of skin tissue after 28 days of exposure displayed that 14C residue levels were approximately 2 to 6 times higher than those observed for the corresponding edible tissue. Analytical results for QA samples analyzed concurrently with water samples during the exposure and depuration period resulted in a mean recovery ( standard deviation) of 91 ± 5.93 percent. Analyses of the QA samples analyzed with the tissue samples during exposure and depuration resulted in a mean recovery ( standard deviation) of 88.7 ± 6.29 percent.

The concentration of DDAC in the treatment aquarium was continuously above nominal concentration and was not consistently maintained within ± 20 percent of the mean of the measured values ( 93 µ g / L). The temperature recommended for testing bluegill is 20 25 ° C. In this study, the temperatures ranged between 17 18 ° C.

The study authors concluded that 14C residues reached steady state by day 10 of exposure. They found that the bioconcentration factor of 14C residues in edible tissue of bluegill was much lower ( 38X) than that of the nonedible tissues ( 140X) and also found that DDAC binds significantly to the non edible segments of bluegill, and especially to the skin and scales. The study results indicated that the half life of DDAC in the edible tissue of the bluegill is significantly shorter than that of the nonedible segments.

11. Photolysis Rate on Surface of Soil ( OPP Guideline No. 161 3, MRID No. 424807 01)

This study was reviewed by the Agency and was found to be scientifically valid and acceptable. The study meets guidelines for the fulfillment of data requirements for DDAC on photodegradation on soil.

In this study, aliquots ( 1 g dry weight) of sandy loam soil were placed in silanized glass vials and treated with [ 14C] DDAC at a nominal concentration of 10 ppm. Half of the vials were placed in a photolysis chamber where they were exposed to a xenon arc light source for 30 days in an environmentally controlled chamber at 25 ± 1EC. The rest of the vials were not exposed to the xenon arc light source. One exposed and one non exposed test sample were removed from the photolysis chamber on days 1, 3, 7, 14, 21, and 30. Each vial was extracted with aliquots of 80: 20 ( v: v) dimethylformamide: acetic acid. Thin layer chromatography 15 of 17 ( TLC)/ autoradiography/ liquid scintillation counting ( LSC) were used to measure 14C DDAC and potential photolysis products.

For both exposed and non exposed test systems, the mean 14C mass balance was 104%. The parent compound was the only radioactive component obtained in the test samples when analyzed by TLC and HPLC. In the exposed system, the photolysis rate constant and half life of DDAC were reported by the study authors as 5.26 x 10 3 days 1 and 132 days, respectively. The photolysis rate constant and half life of DDAC in the non exposed system were determined to be 4.11 x 10 3 days 1 and 169 days, respectively.

Soil bound residues increased from 9.48% of the dose at day 0 to 25.5 and 20.9% in the exposed and non exposed test systems, respectively. The nature of these bound residues was investigated by HPLC analysis of the extracts from composites of reserve day 30 soil samples from both systems. The analytical results indicated the presence of the parent compound and no significant degradation products.

12. Biodegradability of DDAC ( No MRID Number)

This report is an assessment of the biodegradability of DDAC based on the review of information from the open literature, unpublished sources and meeting proceedings. It also provides a summary of the current information available on the environmental fate of DDAC. The report was submitted by the Registrant to EPA, but has not been reviewed by the Agency.

Based on the review of the studies in the report, Lee ( 1992) concluded that:

" Results of studies published in the open literature, literature reviews, conference proceedings and information obtained from unpublished sources indicate that ADBAC and DDAC are biodegradable with the rate and extent of degradation influenced by quat concentration, alkyl chain length, the presence of anionic moieties, and the type of microbes. These factors and the design of the test system are important in interpreting the reliability of biodegradability test results.

After release of ADBAC and DDAC to domestic waste streams or in the open environment, a combination of physical and chemical properties, in addition to biodegradability, influence their fate through the environmental compartments of air, water, soil/ sediment and biota. Important properties for evaluating the environmental fate of these materials include solubility, vapor pressure, surface activity and adsorptive properties."

13. Aqueous Availability ( Leachability) ( American Wood Preservers' Association Standard Method E11 97 " Standard Method for Determining the Leachability of Wood Preservatives, MRID No. 455243 05)

This study was reviewed by the Agency based on the standards specified by the American Wood Preservers' Association Standard Method E11 97 and found to be acceptable. The study was submitted by Lonza Inc. to fulfill the requirements for registration of the product, 16 of 17 Bardac 22C50, EPA File Symbol 6836 EGA. Bardac 22C50 consists of two active ingredients: didecylmethyl ammonium carbonate ( DDACarb) and didecyl ammonium bicarbonate, both of which are similar in structure to DDAC.

The test material used in the study was Bardac 22C, which contained 51.7% of the active ingredient DDACarb. The purpose of this study was to determine the leach rate of DDACarb from a sample of treated wood in deionized water using high performance liquid chromatography ( HPLC).

Southern pine wood blocks ( 19.0 ± 0.2 mm) were vacuum treated with 0.85 percent, 1.7 percent, and 3.4 percent of Bardac 22C ( based on the active ingredient DDACarb). After treatment, the blocks were subjected to a post treatment fixation for 7 days followed by conditioning for 28 days in an environment producing a moisture content of 9 to 10 percent. After conditioning, the blocks were vacuum treated with deionized water and placed in additional deionized water for 14 days.

Leach rates of DDACarb from wood blocks were determined by removing the leachate from the sampling unit at intervals of 6, 24, and 48 hours, and 4, 6, 8, 10, 12, and 14 days following the start of the leaching period. The leachate was extracted with aqueous tetramethylammonium chloride ( TMAC) and methylene chloride and analyzed by HPLC. After 14 days of leaching, the wooden blocks were extracted with acetonitrile and aqueous TMAC and analyzed by HPLC.

The corrected amount of DDACarb recovered from the leachate ranged from 186.1 µ g to 764.7 µ g ( 0.5X retention level), from 218.9 µ g to 1152.9 µ g ( 1X), and from 446.2 µ g to 2101.1 µ g ( 2X). The total recovery from the leachate over the 14 day period was 3464.7 µ g, 4483.0 µ g and 7444.7 µ g for the 0.5X, 1X and 2X retention levels, respectively. For all three retention levels, the leachability of DDACarb declined continuously over the 14 day period with the exception of the leaching rate of the 2X retention level, which began lower than the other two retention levels ( 160.4 µ g), significantly increased at Day 1 ( 2101.1 µ g), and decline gradually through Day 14 ( 496.8 µ g). The total amount of DDACarb recovered from the leachate and the wood blocks combined were 176,983.0 µ g ( 101.8%), 286,606.6 µ g ( 99.5%), and 542,370.3 µ g ( 104.9%) for the 0.5X, 1X and 2X retention levels, respectively.

American Wood Preservers' Association Standard, Method E11 97: " Standard Method of Determining the Leachability of Wood Preservatives was generally followed; however, an issue of concern was that the study did not report running spike samples along with the test samples during HPLC analysis. Rather, the samples were corrected using average validated extraction recoveries of 92.1 percent from three different fortification levels with seven replicates per level. 17 of 17 BIBLIOGRAPHY MRID Citation 411758 01 Dykes, J. and M. Fennessy. 1989. Hydrolysis of Didecyldimethylammonium chloride ( DDAC) as a function of pH at 25 ° C. Final Report # 37004. Unpublished study prepared by Analytical Bio chemistry Laboratories, Inc.

411758 02 Dykes, J. and M. Fennessy. 1989. Determination of the Photolysis Rate of Didecyldimethylammonium chloride ( DDAC) in pH 7 Buffered solution at 25 ° C. Final Report # 37005. Unpublished study prepared by Analytical Bio chemistry Laboratories, Inc.

413853 01 Daly, D. 1989. Soil/ Sediment Adsorption desorption of [ 14C] Didecyldimethylammonium chloride ( 14C DDAC). Lab Project Number 37009. Unpublished study prepared by Analytical Bio Chemistry Laboratories.

422538 01 Cranor, W. 1991. Aerobic Soil Metabolism of [ 14C] Didecyldimethylammonium chloride ( 14C DDAC). Final Report. Lab Project Number 37006. Unpublished study prepared by ABC Laboratories.

422538 02 Cranor, W. 1991. Anaerobic Aquatic Metabolism of [ 14C] Didecyldimethylammonium chloride ( 14C DDAC). Final Report. Lab Project Number 37007. Unpublished study prepared by ABC Laboratories.

422538 03 Cranor, W. 1991. Aerobic Aquatic Metabolism of [ 14C] Didecyldimethylammonium chloride ( 14C DDAC). Final Report. Lab Project Number 37008. Unpublished study prepared by ABC Laboratories.

424807 01 1992. Schmidt, J. Determination of the Photolysis Rate of Didecyldimethylammoniumchloride on the Surface of the Soil. Final Report # 39505. Unpublished study prepared by ABC Laboratories.

455243 05 2001. Bestari, K. Determination of the Leachability of Bardac 22C from Treated Wood. Centre for Toxicology, University of Guelph, Guelph, Ontario N1G 2W1, Canada.

458341 01 1990. Fackler, P. H., E. Dionne, D. A. Hartley, and S. P. Shepherd. Bioconcentration and Elimination of 14C Residues by Bluegill ( Lepomis macrochirus) Exposed to Didecyldimethylammonium Chloride ( DDAC). Final Report. Study No. 11696.0887.6104.140. Unpublished study prepared by Springborn Laboratories, Inc.

Lee, C. 1992. Assessment of the Biodegradability of ADBAC and DDAC. Unpublished report prepared by Roy F. Weston, Inc. Contractor's Fate Summary