2 Introduction

This is the Environmental Protection Agency’s (EPA or the Agency) Final Work Plan (FWP) for the registration review of fluazinam. The FWP includes the expected registration

review timeline. The FWP also addresse s public comments received concerning the Preliminary

Work Plan (PWP) in the Summary Document which was posted in the fluazinam registration review docket (EPA-HQ-OPP-2009-0039) and any ot her comments concerning the initial docket postings. The Summary Document provided information on what EPA knows about the pesticide and what additional risk analyses and data or information the Agency believes are needed to make a registration review decision.

The Agency is implementing the registra tion review program and will review each registered pesticide every 15 years to determin e whether it continues to meet the Federal Insecticide, Fungicide, and Rode nticide Act (FIFRA) standard for registration. Changes in science, public policy, and pesticide use practices will occur over time. The registration review program is intended to make sure that, as the ab ility to assess risk evolves and as policies and practices change, all registered pesticides contin ue to meet that statutory standard. The public phase of registration review begins when the ini tial docket is opened for e ach case. Information on this program is provided at http://www.epa.gov/oppsrrd1/registration_review/

.

Fluazinam is a contact fungicide of the pyrid inamine class registered for agricultural use on a variety of crops, including pean uts, potatoes, and beans. Ther e are no residential or public

recreational uses of fluazinam. Since fluazinam was first registered in 1992, it was not subject to a Reregistration Eligibility Decision.

Updates Since the Summary Document

As required under the Federal Food, Drug and Cosmetic Act (FFDCA) section 408(p), EPA has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (including pesticide active an d 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 Admi nistrator may designate.” The EDSP employs a two-tiered approach to making the statutoril y required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA will dete rmine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to identify any adverse endocrine related effects caused by the substanc e, and establish a qua ntitative relationship between the dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA issu ed test orders/data call-ins for the first group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. This list of chemicals was sele cted based on the potenti al for human exposure through pathways such as food and water, resi dential activity, and cer tain post-application3 agricultural scenarios. This list should not be construed as a list of known or likely endocrine disruptors.

Fluazinam is not among the group of 58 pesticid e active ingredients on the initial list to

be screened under the EDSP. Under FFDCA sec. 408(p), the Agency must screen all pesticide chemicals. Accordingly, EPA anticipates i ssuing future EDSP orders/data call-ins for all registration review cases, in cluding those for which EPA ha s already opened a registration review docket for a pesticide active ingredient.

For further information on the status of the ED SP, the policies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening battery, plea se visit our website: http://www.epa.gov/endo/.

Comments Received on the Preliminary Work Plan

The Agency received two comments during the 60-day public comment period on the PWP, which began on September 23, 2009 and e nded on November 23, 2009. On November 12, 2009, a comment was received from the FIFRA E ndangered Species Task Force (FESTF), and on November 23, 2009, comments were submitted by th e technical registrant, ISK Biosciences Corporation (ISKBC). These comments are a ddressed in the “Summary of Comments and Agency Responses” section of this document a nd did not change the work plan or timeline

established in the PWP.

Also in the Summary Document , EPA solicited comments on the specific topics of environmental justice, water body impairment, a nd potential trade irrita nts, in addition to questions specific to fluazinam c oncerning use, usage, benefits, a nd available alternatives. No comments or information were received during the public comment period concerning these

issues.

Risk Assessment and Data Needs

The Agency will conduct a comprehensive ecol ogical risk assessment for fluazinam, including an endangered species assessment. Add itional ecological fate and effects data will be required, which are specified below. Also, a re vised human health risk assessment will be conducted to incorporate a new drinking wate r assessment and subse quent updates to the aggregate risk and dietary exposure assessments , as well as any cha nges in toxicological endpoints as a result of the newly required studies. Below is a summ ary of the issues relevant to the registration review of fluazinam:

Ecological Risk Assessment

• The most recent ecological risk assessments for fluazinam were completed in 2007. One assessment was conducted for a petition for use on edible-podded beans, shelled succulent and dried beans, Brassica leafy vegetables, bushberrie s, and ginseng (May 16, 2007). A second assessment was conducted for the proposed aerial use of fluazinam on4 potatoes (November 21, 2007). Previous ly, use on potatoes was limited to ground application methods only.

• The Agency has not conducted a risk asse ssment that supports a complete endangered species determination. The planned ecologi cal assessment will allow the Agency to

determine whether fluazinam use has “no e ffect” or “may affect” federally listed threatened or endangered species (listed specie s) or their designated critical habitats. When an assessment concludes that a pesticid e’s use “may affect” a listed species or its designated critical habitat, the Agency w ill consult with the U.S. Fish and Wildlife

Service and/or National Marine Fisheries Se rvices (the Services ), as appropriate.

• The Agency will require the following additional data in a data call-in (DCI) in order to conduct a complete ecological risk assessment, including an endangered species assessment, for all uses:

GLN 835.6100(7) - Environmental Chemis try Analytical Methods for Soil GLN 835.6200(7) - Environmental Chemistry Analytical Methods for Water and

Sediment

GLN 850.2100 - Passerine Acute Avian Oral

GLN 850.1790 - Sediment Toxici ty Test (Freshwater)

• The Agency will also include the following unfulfilled data requirements in the DCI, previously required as part of a conditi on of registration imposed by the Office of Pesticide Programs Registration Division:

GLN 850.1400 - Fish Early Life -Stage (Saltwater) Study GLN 850.1350 - Aquatic Invertebrate Life-Cycle (Saltwater) Study GLN 850.4150 - Vegetative Vi gor, Tier I/ Tier II GLN 850.4400 - Aquatic Plant Growth- Lemna gibba GLN 850.5400 - Aquatic plant toxicity test using Pseudokirchneriella subcapitata

, Navicula pelliculosa and Skeletonema costatum, Tier I

• Please refer to Problem Formulation for Ecologic al Risk Assessment for Fluazinam

, located in the docket, for a detailed disc ussion of these risk assessment needs.

Human Health Risk Assessment

• The most recent comprehensive human health assessment was completed on August 22, 2007 in support of proposed new uses (edibl e-podded beans, shelled succulent and dried beans, Brassica leafy vegetables, bushbe rries, and ginseng). An updated occupational assessment was completed on March 15, 2008 for a proposed label amendment adding aerial application of fluazinam on potatoes.5 • During registration review, the Agency will conduct a new drinking water assessment for fluazinam. Consequently, the Agency will also conduct a new acute and chronic dietary exposure assessment for fluazinam, which w ill include the new drinking water exposure estimates and any changes to toxicological endpoints.

• Since there are no registered residential or public recreational uses for fluazinam, a residential risk assessment is not required.

• An updated aggregate risk assessment will be needed to include any new estimated drinking water concentrations and any changes in toxico logical endpoints. This assessment will consider only food and drinking water, as there are no residential uses of

fluazinam.

• The occupational exposure database is adequa te to support the registration review process of fluazinam. However, during registrati on review, agricultural handler risks not previously assessed will be ev aluated for in-furrow spray applications on potato seed pieces. In addition, inhalation risks may be re-evaluated depending on the results of the 90-day inhalation toxicity study that the Agency will be requi ring. While the inhalation guideline calls for a 90-day study duration, a 28-day study duration will satisfy the Agency’s intermediate-term inhalation exposure da ta needs, and this will be noted in the data call-in (DCI) that the Agency intends to issue.

• The toxicity database is complete except fo r the following studies, which the Agency will require in order to conduct a complete human health assessment:

GLN 870.7800 - Immunotoxicity GLN 870.3465 - 90-Day Inhalation Toxicity

• Please refer to Human Health Scoping Document in Support of Registration Review for Fluazinam, located in the docket, for a detailed discussion of the human health risk

assessment needs.6 Timeline:

EPA has created the following estimated timeline for the completion of the fluazinam registration review.

Registration Review for Fluazinam – Pr ojected Registration Review Timeline

Activities Estimated

Month/Year Phase 1: Opening the docket
Open Docket and Public Comment Period September 2009

Close Public Comment November 2009
Phase 2: Case Development

Final Work Plan (FWP) February 2010

Issue Data Call-In Oct.– Dec. 2010

Data Submission Oct – Dec. 2012

Open Public Comment Period for Preliminary Risk Assessments April – June 2014

Close Public Comment Period July – Sept. 2014

Phase 3: Registration Review Decision
Open Public Comment Period for Proposed Reg. Review Decision Oct. – Dec. 2014

Close Public Comment Period Jan. – March 2015 Final Decision and Begin Post-Decision Follow-up 2015 Total (years) 6

Summary of Comments and Agency Responses

The Agency received two submissions duri ng the 60-day public comment period on the Summary Document , which began on September 23, 2009, and ended on November 23, 2009. These comments were submitted by FESTF and the technical registrant, ISK Biosciences Corporation (ISKBC). Below are summaries of the comments received and the Agency’s

responses.

In addition, comments related to ecological fa te and effects and are addressed in the

Environmental Fate and E ffects Division's document, Response to Comments to Fluazinam Registration Review Problem Formulati on (PC Code 129098; DP Barcode D373021), located in the docket, dated February 25, 2010.

Summary of Comments from FIFRA Endangered Species Task Force

Comment : In response to the Summary Document , specifically to the need for additional information to complete an assessment on fe derally-listed threatened and endangered species that may be exposed to fluazinam, FESTF stated that its data on endangered species proximity contained in the FESTF Information Management System (FESTF7 IMS) submissions (2004, 05, 07) to the Agency “fulfill the data requirements... and provide the best available data necessary for the proximity an alysis of fluazinam use and listed species locations.” FESTF stated that ISKBC is a current member of FESTF, and as such, is entitled to the FESTF data on federally-listed threat ened and endangered species.

Response: The Agency thanks FESTF for its comment and will consider this information as it conducts the registrati on review and makes its regi stration review decisions.

Summary of Comments from ISK Biosciences Corporation Regarding Data Requirements

Comment: ISKBC indicated that a study was previously submitted to satisfy GLN 830.7050- UV/Visible Absorp tion (MRID No. 44807205).

Response: This study was reviewed by the Offi ce of Pesticide Programs Registration Division and deemed acceptable to fulf ill the GLN 830.7050- UV/Visible Absorption data requirement.

Comment: ISKBC noted that the Data Evaluation Records for previously submitted studies (GDLN Nos. 850.1400, 850.1350, 850.4150, 850.4400, 850.5400) have been

received. These studies were deemed unacceptable to satisfy outstanding data requirements. Responses to the deficienci es will be submitted in response to or in

advance of the DCI.

Response: The Agency will consider all additional information relevant to these data requirements once submitted by ISKBC. In the meantime, the Agency will include the data requirements in the pending DCI.

Summary of Comments from ISK Biosciences Corporation Regarding the Human Health Scoping Document in Support of Registration Review

Comment: ISKBC commented that a waiver reques t for a 28-day inhalation toxicity study was previously submitted on January 17, 2002. An updated waiver request using the same arguments may be submitted in response to the DCI.

Response: The previously submitted waiver requ est for the 28-day inhalation toxicity study is not granted. Rather, the available 7-day range-fin ding study for fluazinam was used for the previous risk assessment (short- and intermediate-term inhalation exposure), but included an additional safety factor ( 10x) to account for the lack of histopathology and the use of the 7-day range finding study to extrapolate intermediate-term inhalation exposure. However, fluazinam is a highl y volatile compound and it is likely that significant inhalation exposure will occur to handlers during mixing/loading and applying. The most accurate way of charac terizing and quantifying fluazinam inhalation risk is through the use of inhalation toxicity studies of appropriate dur ation. As a result, a8 new inhalation study of a longer duration (28- days) is needed to accurately assess potential occupational inhalation hazard.

Comment: ISKBC questioned a reference on page 8 of the Human Health Scoping Document in Support of Registration Review for Fluazinam that discussed the need to review the signal word for the end-use produc t. ISKBC further stated the company has recently conducted new acute toxicity studies that suggest a change in the signal word from “Danger” to “Warning” for Technical Fluazinam.

Response: The Agency has reviewed the current ac ute toxicity data and found the current signal words for Technical Fluazinam (R egistration No. 71512-8) and the end-use product, Omega 500F (Registration No. 71512- 1), to be appropriate based on the corresponding acute toxicity classifications. Omega 500F has an acute toxicity classification of II for dermal toxicity, whic h requires the signal word “Warning.” The highest acute toxicity cla ssification for Technical Flua zinam is category I for eye irritation and requires the signa l word “Danger.” EPA has not yet received any new acute toxicity studies for fluazinam. However, any new acute toxicity data submitted by the technical registrant will be considered, as appropriate.

Comment: ISKBC indicated that the maximum si ngle application rate for peanuts was incorrect as listed on the currently approved labe l and as listed in Table 1 on page 9 of the Human Health Scoping Document in Support of Registration Review for Fluazinam and

in Table 2 in the Problem Formulation for Ecological Risk Assessment for Fluazinam.

Response: Use and application information for EPA registration review documents is extracted from Agency-approved product la bels. EPA has reviewed the initial registration petition (No. 9F 5079) and corresponding residue trials for fluazinam and found that the maximum allowed single applica tion rate for fluazinam is incorrectly listed on the current approved Omega 500F label. Th e correct maximum single application rate on peanuts is 0.78 lb active ingredient/acre (AI/A). ISKBC has since submitted a label amendment for the Omega 500F label to EPA th at incorporates this correction. This label was approved by the Ag ency on February 24, 2010 and the appropriate rate of 0.78 lb AI/A for peanuts will be included in registration review risk assessments.

Comment: ISKBC also noted that the maximum a pproved rate per application for potato seed pieces should be 1.56 lb AI/A, not 1.8 lb AI/A as indicated on page 9 of the Human Health Scoping Document in Support of Registration Review for Fluazinam

.

Response: EPA thanks ISKBC for noticing this t ypographical error and will ensure that

future assessments contain the correct in-fu rrow maximum single application rate of 1.56 lb AI/A for potatoes.

Comment: ISKBC pointed out a typographi cal error in on page 19 of the Human Health Scoping Document in Support of Registration Review for Fluazinam which stated that the tolerance for grape, wine was 0.02 ppm. The correct tolerance is 3.0 ppm.9 Response: EPA thanks ISKBC for noticing this error and will ensure that future documents contain the correct grap e, wine tolerance of 3.0 ppm.

Summary of Comments from ISK Bioscien ces Corporation Regarding the Problem Formulation in Support of Registration Review

Comment: ISKBC stated that it plans to utilize th e FESTF IMS and submit an analysis of the potential direct and indirect effects of th e registered uses of fluazinam on endangered species. ISKBC will submit this study when it submits data to satisfy the DCI. requirements.

Response: The Agency will consider information submitted by ISKBC, as appropriate, when it conducts its endangered species risk assessment.

Comment: ISKBC does not believe GLN 850.1790 Sedi ment Toxicity Test should be satisfied using the parent fluazinam because its half-life is less than one day. Instead, ISKBC plans to submit two sediment t oxicity tests, one using the species Chironomus

tentans and the second using Hyallela azteca to satisfy this requirement. Both tests use the fluazinam metabolite SDS-67200, the major fluazinam sediment degradate and the compound that sediment dwelling species w ould most likely be exposed to in the

environment. ISKBC will submit these studies in response to the DCI.

Response: EPA believes that the sediment toxici ty test should be conducted using the parent compound. While SDS-67200 is the ma jor product under an aerobic conditions (maximum 39.6% by day 14), other products were observed at high concentrations, such as AMPA which was a maximum of 24.2% at 0.2 day, and DAPA with a maximum of 32.7% at day 30. In the proposed degradat ion pathway, fluazinam degrades to SDS67200 and to AMPA, both of which subsequen tly degrade to DAPA. Additionally, under aerobic aquatic metabolism, CAPA, DAPA, and DC PA were also present. Because these degradates may also be present in a sedime nt system, the parent compound should be the compound used in the sediment toxicity test.

Comment: ISKBC also commented on an incorrect placement of double bonds in the pyridyl ring portion of photolys is product G-504 and the absence of an anaerobic aquatic metabolite, SDS-67200 in Table 1 on page 4-5 of the Problem Formulation for Ecological Risk Assessment for Fluazinam. The correct structures were included in the registrant’s comments.

Response: EPA acknowledges these errors and the co rrect structures will be included in the registration review ec ological risk assessment.

Comment: ISKBC believes that it is not appropriate to base model input parameters or risk assessment endpoints on the cumulative half-life values of parent + degradates, as illustrated in Table 4. Summary of Various Physicochemical and Environmental Fate Properties of Fluazinam.10 Response: In addition to the half-lives for fluazi nam, half-lives were estimated for the total fluazinam residues, because the environmen tal fate studies indicated that the parent compound forms transformation compounds, which are structurally very similar to the parent under almost all conditions. In the absence of full ecological effects information for each degradate, the Agency assumed that the transformation products were, at least, as toxic as the parent. It was observed th at fluazinam was not undergoing degradation, instead, it was undergoing transformation into a series of products, all of which resemble the parent in chemical structure. There is no real biodegradat ion, but rather, some transformation. This approach has been used in all ecological ri sk and drinking water

assessments for this chemical.

Comment: ISKBC also stated that endpoints related to foliar di ssipation of fluazinam are important in terrestrial modeling scenarios, which are not included in Table 4. Summary of Various Physiochemical and Environmental Fate Properties of Fluazinam on page 9 of

the Problem Formulation for Ecological Risk Assessment for Fluazinam. These values were obtained for two types of vegetation, p eanut leaves and potat o leaves, in studies received and reviewed by the Agency in late 2008. The half-lives of fluazinam on leaf foliar surfaces were on averag e 4 to slightly over 5 days in peanut and potato leaves.

Response: Six foliar dissipation half-lives were derived from the two studies evaluated. Despite the problems found in the studies, the ha lf-lives were judged to be adequate for risk assessment exposure calculations. The input value to be used fo r terrestrial exposure in risk assessment (using e.g. T-REX) represents the 90 th percentile of the upper

confidence bound on the mean of six half-life va lues for the total residues, which is 7.33 days. The Agency will consider this inform ation when it conducts its ecological risk

assessment.

Comment: ISKBC also indicated that the company submitted a non-guideline study measuring run-off of fluazina m from a field under controll ed conditions, and requested

that it be evaluated.

Response: This study is currently undergoing a s econdary review. S hould it be useful, it may be used in the registrati on review ecological risk assess ment, either qualitatively or quantitatively, depending on the quality and usefulness of the data.

Next Steps

As noted previously, the Agency plans to require a number of new and outstanding ecological fate and effects studies, and human h ealth toxicity studies through a DCI, which is expected to be issued in late 2010. This new information will be used to conduct a comprehensive ecological risk assessment, includi ng an endangered species assessment, as well as a full human health assessment, for all fluazinam pesticidal uses.