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### Table of Contents

I. Introduction ............................................................................................................... .................. 3 A. General Background ......................................................................................................... ..... 4

II. Scientific Assessments .................................................................................................... ........... 4
A. Human Health Assessment .................................................................................................... 5

B. Environmental Assessment ................................................................................................... . 5

C. Alternatives Assessment .................................................................................................... .. 10

D. Endocrine Disruptor Screening Program ............................................................................. 10

III. Proposed Interim Registration Review Decision .................................................................... 10 IV. Next Steps and Timeline ................................................................................................... ...... 113 I. Introduction

This document is the Environmental Prot ection Agency’s (EPA or the Agency) Proposed Interim Registration Review Decision for denatonium saccharide and is being issued pursuant to 40 CFR sections 155.56 and 155.58. A registration review decision is the Agency’s determination whether a pesticide meets, or does not meet, the standard for registration in the Federal Insecticide, Fungicide, and Rodenticid e Act (FIFRA). The Agency may issue, when it determines it to be appropriate, a proposed interim registration review decision before completing a registration review. Among other thi ngs, the proposed interim registration review decision may (1) require new risk mitigation measures; (2) impose interim risk mitigation measures; (3) identify data or information required to complete the review; and (4) include schedules for submitting the required data, c onducting new risk assessments or revising preliminary assessments, and completing the re gistration review. For further information on denatonium saccharide, additional documents can be found in EPA’s public docket (EPA-HQOPP-2008-0441) at www.regulations.gov

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FIFRA, as amended by the Food Quality Pr otection Act (FQPA) of 1996, mandated the continuous review of existing pest icides. All pesticides distributed or sold in the United States generally must be registered by the EPA based on sc ientific data showing that they will not cause

unreasonable risks to human health or to the environment when used as directed on product labeling. The registration review program is intended to make sure that, as the ability to assess and reduce risk evolves and as polic ies and practices change, all regi stered pesticides continue to meet the statutory standard of no unreasonable a dverse effects. Changes in science, public policy, and pesticide use practices will occur over time. Through the registration review program, the Agency periodically reevaluates pes ticides to make sure that as these changes occur, products in the marketplace can continue to be used safely. Information on this program is provided as www.epa.gov/oppsrrd1/registration_review/

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In 2006, the Agency implemented the regist ration review program pursuant to FIFRA section 3(g) and will review each registered pesticide every 15 years to determine whether it

continues to meet the FIFR A standard for registration.

Pursuant to 40 CFR Section 155.50, EPA forma lly initiated registration review for denatonium saccharide (case 7625). The following highlights significant events that have occurred during the registration re view of denatonium saccharide:

 June 25, 2008 – Publication of the Denatonium Saccharide Summary Document for a 60- day public comment period. The Summary Docume nt included the preliminary work plan (PWP) and was accompanied by the scoping document and problem formulation.

 November 14, 2008 - Final Work Plan (FWP) for denatonium saccharide was signed -- no public comments were received duri ng the 60-day comment period for the Denatonium Saccharide Summary Document ; thus, the FWP did not modify the Summary

Document

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 A Data Call-In (DCI) was issued in Janua ry 2010 for a number of human toxicity, ecological toxicity, and envir onmental fate studies. Although the requested studies were4 not submitted, EPA completed the risk assessment for denatonium saccharide using available data and data from a surrogate chem ical, denatonium benzoate. EPA plans to
close out this DCI. These risk asse ssments are available along with this Proposed Interim Registration Review Decision for public comment.

Additional information on denatonium saccharide, including this Proposed Interim Registration Review Decision and the following supporting documents can be found in EPA’s public docket, EPA-HQ-OPP-2008-0441, accessed at www.regulations.gov

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 Denatonium Saccharide: Qualitative Risk Assessment for Registration Review. May 2, 2013.

 Endangered Species Determination for Registration Review of Denatonium Saccharide. April 29, 2014.

 Registration Review – Ecological Risk A ssessment for Denatonium Saccharide. March 14, 2014.

 Denatonium Saccharide Alterna tive Assessment. March 28, 2014.

 Revised Application Rate Information for Uses of RO-PEL, a Ready –To-Use Liquid Bittering Agent Containing Denatonium Saccharide. April 24, 2013.

A. General Background

Denatonium saccharide is a bittering agent in a squirrel, vole, dog, and cat repellant registered for use on outdoor surfaces and structures such as trees, fences, poles, decks, planters, siding, garbage cans, and furniture. For structures, it is applied as a spray or with a paintbrush to the point of runoff. Additionally, the product is sprayed onto seeds and bulbs before planting. Although not explicitly stated on the product labe l, the product appears to be used only in outdoor residential areas. This pr oduct is for non-food uses only. There is only one registered end use product, RO-PEL, and only 110 pounds or less of denatonium saccharide active ingredient (a.i.) are sold in th e U.S. annually. Denatonium sacc haride was first registered in August of 1985 and so it was not su bject to reregistration. There ar e few chemical alternatives to denatonium saccharide for protection of outdoor surfaces, structures, tree s, seeds and bulbs.

II. Scientific Assessments

A summary of the Agency’s human health risk assessment, environmental fate and ecological risk assessment, and alternative assessment, Denatonium Saccharide: Qualitative Risk Assessment for Registration Review (May 2, 2013), Registration Review – Ecological Risk Assessment for Denatonium Saccharide (March 14, 2014), and Denatonium Saccharide Alternative Assessment (March 28, 2014) , is presented below. For the detailed risk and alternatives assessments, see the denatoni um saccharide public docket (EPA-HQ-OPP-2008- 0441) accessed at www.regulations.gov

.5 A. Human Health Assessment

Hazard Characterization
The toxicological database is considered ade quate for characterizing hazard and assessing risk from denatonium saccharide. No toxicologi cal endpoints of concern have been identified for

denatonium saccharide.

Dietary Exposure Assessment
There are no registered food uses. Based on the use pattern and the compound's extreme bitterness, dietary exposure from food and drinking water is unlikely to occur. Therefore, a dietary exposure assess ment was not conducted.

Food Tolerances

There are no US tolerances established for denatonium saccharide.

Residential and Occupational Exposure
Denatonium saccharide is only sold as a r eady-to-use liquid formulation which can be applied using a trigger pump (spray bottle), pa intbrush, or sprayer. Dermal and inhalation exposures to occupational and resi dential handlers may occur during application of this product. Post-application exposure is expected to be neg ligible due to the limited area of use. EPA concludes that risk from exposure to denatonium saccharide will not be of concern because of the targeted method of applicati on with a coarse spray or paintbrush and the low dermal and inhalation toxicity observed fr om the available studies.

B. Environmental Assessment

There were a number of uncertainties in the environmental risk assessment for denatonium saccharide. The only available dena tonium saccharide toxicity data could not be used, there were no fate data ava ilable, and the label did not specify an application rate for use on seeds and bulbs. Estimated application rates fo r seeds and bulbs were determined and used by the Agency in its assessments based on availa ble label information. Therefore, the risk assessment for denatonium saccharide assumes no degradation of the denatonium saccharide, an estimation of the application rate 1 , and uses denatonium benzoate to xicity data as a surrogate for denatonium saccharide toxicity because it is the best available information. Denatonium

benzoate and denatonium saccharide are both bitte ring agents that share the denatonium cation.

Aquatic Organisms

It was assumed that aquatic exposure may occu r primarily from run-off. Spray drift was assumed to be negligible given the small scale use and type of application equipment. A conservative screening-level scenario was consid ered given the lack of fate data. Aquatic exposure estimates were based on the assumption that all product applied e nds up in the standard water body without sorption or degradation. Even w ith this very conserva tive scenario, there is no risk concern given the large volumes of denat onium saccharide that would be needed to be

1 See EPA memo: Revised Application Rate Information for Uses of RO-PEL, a Ready –To-Use Liquid Bittering Agent Containing Denatonium Saccharide . April 24, 20136 used to trigger a risk concern. Chronic risk to aquatic organisms is assumed to be negligible given the limited and localized us e of denatonium saccharide.

Terrestrial Organisms

Plants

There is potential exposure to plants from a pplications of denatoni um saccharide due to runoff. Spray drift is expected to be negligible given the small scale use and type of application equipment. It is unlikely that there would be a ri sk concern for terrestrial plants from the use of denatonium saccharide based on the qualitative assessment of denatonium saccharide.

Bees and other terrestrial insects

There is potential exposure to denatonium saccharide for bees and other terrestrial

insects that could visit flowers that develop from treated seeds or treated bulbs, and from visiting plants that take up denatonium saccharide used to treat structures from run-off exposure. Spray drift is expected to be negligible given the sma ll scale use and type of application equipment. However, the potential for risk from these e xposures could not be assessed because while the

available data did not indicate a ny toxicity to bees, this single study did not test up to exposures that might occur from the labeled uses.

Birds

Acute risk to birds, which are also surr ogates for reptiles an d terrestrial-phase amphibians, was evaluated based on consumption of treated seed and treate d bulbs. Chronic risk to birds is assumed to be negligible given the limited and localized use of denatonium

saccharide.

Seed

The risk assessment considered possible e xposure from seven types of grass seed commonly planted on residential lawns. Grass seed s were used as representative seed because grass is the most commonly planted seed around residences and the aggr egate surface area of grass seeds is expected to be greater than any other seed planted in residential areas. EPA estimated the application rate for the treated see d. This screening-level assessment assumed that

a bird would consume treated seed from a resident ial lawn up to 100% of its daily diet and that seed is available for foraging.

Potential risk was evaluated by comparing the estimated environmental concentration (EEC) derived from estimated application rates on the seven types of seeds with the avian LD 50 value adjusted for 20 gram, 100 gram, and 1,000 gram size birds. For example, Table 1 presents all the seed type and bird size cl ass combinations that exceed the listed species level of concern (LOC =0.1) based on the maximum estimated labe led application rate a nd on a bird consuming 100% of its daily diet as treate d seed. Table 1 includes the number of seeds necessary to reach the listed species LOC of 0.1, the minimum percent of a bird’s daily diet that would need to

come from treated seed in or der to reach the LOC, and the minimum forage area to obtain7 enough seed to reach the LOC. At applicati on rates lower than the maximum estimated, the listed species LOC is exceeded for 20 gram bird s for seven out of the seven types of seeds evaluated, for 100 gram birds for three out of the seven types of seeds evaluated, and for 1,000 gram birds two out of the seven seeds evaluated exceeds the listed species LOC.

For non-listed birds, risks of concern were onl y identified for two weight classes of birds consuming a subset of the seven seed types. Fo r 20 gram birds, potential risks of concern were identified for two out of the seven types of gra ss seed. For 100 gram birds, potential risks of concern were identified for only one out of the seven types of grass seed.

Table 1. Characterization of Risk to Li sted Birds from Consuming RO-PEL Treated
Seeds 1

Seed Minimum # of treated seeds
consumed to exceed listed LOC (EEC ≥ 0.1 LD 50 ) 2 % daily diet of listed birds consuming treated seeds to exceed listed LOC (EEC ≥ 0.1

LD 50 ) 3 Minimum foraging area (ft 2 ) to obtain enough seeds to exceed the listed LOC (EEC

≥ 0.1 LD 50 ) 4 20 g
bird 100 g
bird 1000 g
bird 20 g
bird 100 g
bird 1000 g
bird 20 g
bird 100 g
bird 1000 g
bird

red

fescue 2,420 NA 5 NA 59 NA NA 2.2 NA NA

bluegrass 2,420 15,405 217,599 12 28 87 1.4 8.8 123.8

tall

fescue 2,420 NA NA 93 NA NA 1.7 NA NA

perennial

ryegrass 2,420 NA NA 80 NA NA 3.0 NA NA

chewings
fescue 2,420 NA NA 48 NA NA 1.8 NA NA

hard

fescue 2,420 15,405 NA 37 82 NA 1.4 8.7 NA

colonial bentgrass 2,420 15,405 217,599 4 8 25 0.3 1.7 23.7

1 Based on the maximum labeled application rate, maximum number of seeds/lb from BEAD report (USEPA 2013),and the dietary needs for birds (20 g bird – 5.06 g/day; 100 g bird – 14.4 g/day; 1000 g bird – 64.6 g/day) from TREX (v 1.5.2).

2 Minimum # treated seeds = (EEC (mg denatonium/kg-bw/day) x bird weight (kg)) / 0.0000833 mg denatonium per
seed. EEC = 1/10 th of the size adjusted LD 50 . Size adjusted LD 50 reported in Appendix A.

3 % daily diet to exceed LOC = minimum # seeds to ex ceed LOC/# seeds equaling 100% daily diet. # seeds equaling 100% daily diet = # seeds per g x daily dietary need for birds (g)

4 Number of seeds consumed/number of seeds per ft 2 = minimum foraging area (ft 2 ). For example (colonial bentgrass, 1000 g bird): 217599 seeds consumed/9195 seeds per ft 2 = 23.7 ft 2 foraging area. Number of seeds/ft 2 is based on seeding rates provided in BEAD report. It is assu med that the lowest seeding rate is used for seed batches with the maximum number of seeds/lb when a range is provided for both rate and seeds/lb (tall fescue, perennial ryegrass, and Kentucky bluegrass) as advised in the BEAD report.

5 NA – not applicable, EEC is less than 0.1 of the LD 50 , equivalent to the listed species LOC.

This analysis assumes that a bird will remain feeding on the treated residential area long enough to consume enough seed to obtain a dose of concern. Although in some cases a small foraging area was estimated to be sufficient to obtain a dose of concern, denatonium saccharide is expected to be used on sm all residential lawn areas.8 Bulbs

The risk assessment also evaluates the potenti al risk for birds consuming treated bulbs.

Treated bulbs will be buried after denatonium s accharide is applied, and so these bulbs must be brought back to the surface in order for there to be a complete exposure pathway. The risk assessment identified two possible sc enarios by which this could occur. First, birds that might eat bulbs could dig them up from a lawn or garden themselves. Alternatively, a mammal such as a squirrel might dig up bulbs, be repelled by the denatonium saccharide, and leave them on the surface where they could be consumed by birds.

The risk assessment assumed that bulbs typi cally treated and planted in a residential setting range in size from approximately 20 to 100 grams. This screening-level assessment assumed that a bird would consume part or all of treated bulbs from a residential lawn up to 100% of its daily diet and that bu lbs are available for foraging.

Potential risk was evaluated by comparing the estimated environmental concentration (EEC) derived from EPA estimated application rates on bulbs with the avian LD 50 value adjusted for 20 gram, 100 gram, and 1,000 gram size birds. Th ere is a potential risk concern for all size classes of listed bird species ea ting part or all of treated bulb s up to 100% of their daily diet. There is also a potential risk concern for 20 gram non-listed specie s consuming treated bulbs less than 40 grams. Smaller bulbs pose a greater poten tial risk because the estimated concentration of

denatonium saccharide increases as the bulb size decreases.

There is a high degree of uncertainty in the potential exposure because in reality the

actual concentration will be a function of th e bulb size, porosity, amount of product applied, duration of spraying, and amount of time the bul b is resident in soil, along with other considerations. The application rate estimate is a conservative peak estimate because it is based on soaking a 50 gram bulb in a solution of RO -PEL for 10 minutes. Th is method would likely result in higher concentrations on the bulb th an could be achieved from spraying bulbs as directed on the label. Also, it assumes the bulb is made available for consumption by being excavated by another animal or process and th at the denatonium saccharide on the bulb surface does not dissipate from the bulb.

Mammals

Acute risk to mammals was evaluated for cons umption of treated grass seed and treated bulbs using the same approach that was used for bi rds. As it does for birds consuming seed, the

risk assessment for mammals calculates the numbe r of treated seeds a mammal would need to consume to attain a dose equal to the listed LO C. Assuming the highest estimated application rate, and considering the daily diet of three size classes of mammals, it was determined that this dose for listed species could only be attained fo r one of the seven types of seeds evaluated, colonial bentgrass. There were no risks of c oncern identified for non-listed mammals consuming

seed. There were no risk concerns for lis ted or non-listed mammals eating bulbs.

Chronic risk to mammals is assumed to be negligible given the limited and localized use

of denatonium saccharide.9 Endangered Species Assessment

The Agency is making a Federally-listed th reatened and endangered species (hereafter referred to as “listed”) determination for th e ecological risk assessment of denatonium saccharide, as detailed in the memorandum Endangered Species Determ ination for Registration Review of Denatonium Saccharide, dated April 29, 2014. The Action Area for this assessment is

assumed to be residential and develo ped areas based on the use pattern.

The Agency is making a no effect (NE) dete rmination for all listed species except (1) birds that may be directly affected from the cons umption of seeds, birds and reptiles that may be directly affected from the consumption of bulbs, mammals that may be directly affected from the consumption of seeds, and terrestrial insects ( non-subterranean species) that may be directly affected and (2) species that are indirectly affected based on having an obligate/dependent relationship with a species that is direc tly affected by denatonium saccharide.

For all listed species, that may be affected by denatonium saccharide, EPA is making a may affect (MA) but not likely to adversely aff ect (NLAA) determination. EPA believes there is a potential for direct effects to the followi ng numbers of listed species (by taxa).

 41 birds and 7 reptiles that may consume bul bs (no listed terrestrial-phase amphibians were identified)

 28 birds, which are a subset of the 41 birds identified that may consume bulbs, that may consume seeds (no listed reptiles or terre strial-phase amphibians were identified)

 33 mammals that consume seeds

 59 terrestrial invertebrates (non-subterranean species)

The MA finding for direct effects to birds, reptiles, and mammals is based on exceedance of the listed species LOC for specific food items (treated seed and bulbs). The finding for potential direct effects to terr estrial invertebrates is based on insufficient data; exposure values are greater than the non-definitive endpoint (no effects observed) obtained in the available toxicity study. Thus, the magnitude of any potentia l effects to terrestrial invertebrates, if any
exposure were to occur, cannot be quantified. The MA finding, fo r the above species, is also based on the assumption that the geographic rang e for those listed species overlaps with the

action area and that individuals ma y visit the treatment area. The Agency notes that there are in fact 76 terrestrial invertebrate species that overlap with the action area. However, a NE determination is concluded for the 17 listed terrestrial invertebrate species categorized as subterraneous. In general, these species are un likely to be exposed to labeled applications of denatonium saccharide because they are adap ted to living in caves or similar underground

habitats.

The MA finding for indirect effects is limited to listed birds, reptil es, terrestrial-phase amphibians, mammals, terrestrial insects, and plants (terrestrial and aquati c vascular) that have an obligate relationship with a species that is di rectly affected by denatonium saccharide. A NE

determination is concluded for indirect eff ects to listed species not having an obligate relationship with a species direct ly affected by denatonium sacchar ide due to the highly localized and short-term nature of any effects.10 A NLAA determination has been made for bot h direct effects, the listed species are indicated above, and indirect effects, where th e species have an obligate relationship with a directly affected species because the probabi lity of a listed species encountering areas of treatment is expected to be highly unlikely. This finding is based on the extremely limited use of denatonium saccharide (about 100 pounds is sold annua lly nationwide) and the nature of the use. There is no expectation that large contiguous areas of treatment will occur, rather use is expected to result in very small treatment areas (less than a typical residential yard) scattered across the landscape with few treatment areas occurring an ywhere simultaneously. Given the combination of widely dispersed and limited use, it is highly unlikely that individuals of a listed species will encounter areas of treatment. Therefore, risk is expected to be discountable because potential exposure will be confined to small patc hes isolated in space and time.

C. Alternatives Assessment

There are three animal repellen t alternatives to denatonium saccharide for protection of outdoor surfaces, structures, trees, seeds and bulbs : methyl nonyl ketone, capsaicin mixture, and thiram. However, because each of these alternatives can only be used on a subset of uses, users may only have one alternative for some uses. Some of the alternatives have constraints that may limit their usefulness. Methyl nonyl ketone has a shorter period of residual activity and needs to be reapplied daily. The capsaicin/garlic oil/put rescent whole egg solid products have a strong aromatic smell that may be offensive to some us ers. Little is known a bout the efficacy of the

alternatives relative to de natonium saccharide.

D. Endocrine Disruptor Screening Program

EPA has developed the Endocri ne Disruptor Screening Progr am to determine whether certain substances (including pes ticide active and other ingredients) may have an effect in humans or wildlife similar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may desi gnate.” Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and November 2010, EPA issued test orders/data call-ins for the first group of 67 ch emicals and published a s econd list of chemicals proposed for order issuance in the future. Dena tonium saccharide was not among the group of 58 pesticide active ingredients on th e initial list nor is it proposed on the second list of chemicals to
be screened under the EDSP. Acco rdingly, as part of registratio n review, EPA will issue future EDSP orders/data call-ins for regi stration review chemicals, includi ng denatonium saccharide. For further information on the status of the EDSP, the policies and procedures, th e list of 67 chemicals, future chemical lists proposed fo r screening, the test gu idelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/

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In the interim, EPA is making no human health or environmental safety findings associated with the EDSP screening of denat onium saccharide. Before completing this Registration Review, the Agency will make an EDSP FFDCA section 408(p) determination.

III. Proposed Interim Registration Review Decision

Per the denatonium saccharide Preliminary Work Plan, EPA has completed a human health and an ecological risk assessment, as pa rt of registration review. The Agency is,11 therefore, issuing a Proposed Interim Registration Review Decision pursuant to 40 CFR sections 155.56 and 155.58. The registration review timeline in the Denatonium Saccharide Final Work

Plan projected that the Agency w ould issue the preliminary risk assessments in June of 2013 and issue the proposed registration review deci sion in December of 2013. However, since EPA decided to delay issuing the pr eliminary risk assessments and instead issue for public comment

this Proposed Interim Registration Review Decision concurrently with the preliminary risk assessments, the anticipated timeframes were re vised. The Agency now anticipates issuing an Interim Registration Review Decision in late 2014.

EPA’s denatonium saccharide ecological risk assessment has made a determination for listed species. A no effect (NE) determination has been concluded for a ll listed species except (1) birds that may be directly affected from the consumption of seeds, birds and reptiles that may be directly affected from the c onsumption of bulbs, mammals that may be directly affected from the consumption of seeds, and terrestrial insects (non-subterranean species) that may be directly affected and (2) species that are indirectly affected based on having an obligate/dependent relationship with a species that is direc tly affected by denatonium saccharide.

For all listed species, that may be affected by denatonium saccharide, EPA is making a may affect (MA) but not likely to adversely aff ect (NLAA) determination. EPA believes there is a potential for direct effects to the followi ng numbers of listed species (by taxa).

 41 birds and 7 reptiles that may consume bul bs (no listed terrestrial-phase amphibians were identified)

 28 birds, which are a subset of the 41 birds identified that may consume bulbs, that may consume seeds (no listed reptiles or terre strial-phase amphibians were identified)

 33 mammals that consume seeds

 59 terrestrial invertebrates (non-subterranean species)

Tables showing the listed species included in the NLAA determination for direct effects

from the use of denatonium saccharide are found in the memorandum Endangered Species Determination for Registration Review of Denatonium Saccharide, dated April 29, 2014. EPA plans to request the U.S. Fish & Wildlife Se rvice (USFWS) to provide concurrence on the NLAA endangered species determinations for denatonium saccharide prior to the issuance of the Registration Review Decision fo r denatonium saccharide.

In accordance with 40 CFR Sections 155.56 and 155.58, the Agency is issuing this Proposed Interim Registration Review Deci sion document. Except for the EDSP and the endangered species components of the denatoni um saccharide registration review case, the Agency has made the following interim decision: (1) no additional data are required at this time; and (2) no changes to the affected registrations or their labeling are needed at this time.

IV. Next Steps and Timeline

A Federal Register Notice will announce the availability of this Proposed Interim Registration Review Decision for denatonium s accharide and the preliminary risk assessments and allow a 60-day comment period. If there are no significant comments or additional12 information submitted to the docket during the comm ent period that leads the Agency to change its decision, EPA may issue an Interim Registra tion Review Decision for denatonium saccharide (case 7625). However, a final decision for denatonium saccharide may be issued without having previously issued an Interim Registration Revi ew decision. A final deci sion on the denatonium saccharide registration review case will occu r after an FFDCA section 408(p) EDSP

determination has been made and after rece iving concurrence from the USFWS on the NLAA endangered species determinations.