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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 addresses 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 other 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 registration review program and will review each 

registered pesticide every 15 years to determine whether it continues to meet the Federal 

Insecticide, Fungicide, and Rodenticide 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 ability to assess risk evolves and as policies and 

practices change, all registered pesticides continue to meet that statutory standard. The public 

phase of registration review begins when the initial docket is opened for each case. Information 

on this program is provided at http://www.epa.gov/oppsrrd1/registration_review/. 

Fluazinam is a contact fungicide of the pyridinamine class registered for agricultural use 

on a variety of crops, including peanuts, potatoes, and beans. There 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 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 designate.” The EDSP employs a two-tiered 

approach to making the statutorily 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 determine 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 substance, and establish a quantitative relationship 

between the dose and the E, A, or T effect. 

 

Between October 2009 and February 2010, EPA issued 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 selected based on the potential for human exposure 

through pathways such as food and water, residential activity, and certain post-application 
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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 pesticide 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 issuing future EDSP orders/data call-ins for all 

registration review cases, including those for which EPA has already opened a registration 

review docket for a pesticide active ingredient. 

For further information on the status of the EDSP, the policies and procedures, the list of 

67 chemicals, the test guidelines and the Tier 1 screening battery, please 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 ended on November 23, 2009. On November 12, 

2009, a comment was received from the FIFRA Endangered Species Task Force (FESTF), and 

on November 23, 2009, comments were submitted by the technical registrant, ISK Biosciences 

Corporation (ISKBC). These comments are addressed in the “Summary of Comments and 

Agency Responses” section of this document and 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, and potential trade irritants, in addition to 

questions specific to fluazinam concerning use, usage, benefits, and 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 ecological risk assessment for fluazinam, 

including an endangered species assessment. Additional ecological fate and effects data will be 

required, which are specified below. Also, a revised human health risk assessment will be 

conducted to incorporate a new drinking water assessment and subsequent updates to the 

aggregate risk and dietary exposure assessments, as well as any changes in toxicological 

endpoints as a result of the newly required studies. Below is a summary 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, bushberries, and ginseng (May 16, 

2007). A second assessment was conducted for the proposed aerial use of fluazinam on 
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potatoes (November 21, 2007). Previously, use on potatoes was limited to ground 

application methods only. 

• The Agency has not conducted a risk assessment that supports a complete endangered 

species determination. The planned ecological assessment will allow the Agency to 

determine whether fluazinam use has “no effect” or “may affect” federally listed 

threatened or endangered species (listed species) or their designated critical habitats. 

When an assessment concludes that a pesticide’s use “may affect” a listed species or its 

designated critical habitat, the Agency will consult with the U.S. Fish and Wildlife 

Service and/or National Marine Fisheries Services (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 Chemistry 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 Toxicity Test (Freshwater) 

• The Agency will also include the following unfulfilled data requirements in the DCI, 

previously required as part of a condition 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 Vigor, 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 Ecological Risk Assessment for Fluazinam, 

located in the docket, for a detailed discussion 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 (edible-podded beans, shelled succulent and dried 

beans, Brassica leafy vegetables, bushberries, and ginseng). An updated occupational 

assessment was completed on March 15, 2008 for a proposed label amendment adding 

aerial application of fluazinam on potatoes. 
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• 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 will 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 toxicological endpoints. This 

assessment will consider only food and drinking water, as there are no residential uses of 

fluazinam. 

• The occupational exposure database is adequate to support the registration review process 

of fluazinam. However, during registration review, agricultural handler risks not 

previously assessed will be evaluated 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 requiring. 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 data needs, and this will be noted in the 

data call-in (DCI) that the Agency intends to issue. 

• The toxicity database is complete except for 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. 
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Timeline:

EPA has created the following estimated timeline for the completion of the fluazinam 

registration review. 

Registration Review for Fluazinam – Projected 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 during 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 fate and effects and are addressed in the 

Environmental Fate and Effects Division's document, Response to Comments to Fluazinam 

Registration Review Problem Formulation (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 federally-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 (FESTF 
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IMS) submissions (2004, 05, 07) to the Agency “fulfill the data requirements... and 

provide the best available data necessary for the proximity analysis 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 threatened and endangered 

species. 

Response: The Agency thanks FESTF for its comment and will consider this information 

as it conducts the registration review and makes its registration 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 Absorption (MRID No. 44807205). 

Response: This study was reviewed by the Office of Pesticide Programs Registration 

Division and deemed acceptable to fulfill 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 deficiencies 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 request 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 request for the 28-day inhalation toxicity 

study is not granted. Rather, the available 7-day range-finding 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 highly volatile compound and it is likely that 

significant inhalation exposure will occur to handlers during mixing/loading and 

applying. The most accurate way of characterizing and quantifying fluazinam inhalation 

risk is through the use of inhalation toxicity studies of appropriate duration. As a result, a 
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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 product. 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 acute toxicity data and found the current 

signal words for Technical Fluazinam (Registration 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, which requires the signal word “Warning.” The 

highest acute toxicity classification for Technical Fluazinam is category I for eye 

irritation and requires the signal 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 single application rate for peanuts was 

incorrect as listed on the currently approved label 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 labels. EPA has reviewed the initial 

registration petition (No. 9F5079) and corresponding residue trials for fluazinam and 

found that the maximum allowed single application rate for fluazinam is incorrectly listed 

on the current approved Omega 500F label. The 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 that incorporates this correction. This 

label was approved by the Agency 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 approved 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 typographical error and will ensure that 

future assessments contain the correct in-furrow maximum single application rate of 1.56 

lb AI/A for potatoes.

Comment: ISKBC pointed out a typographical 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. 
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Response: EPA thanks ISKBC for noticing this error and will ensure that future 

documents contain the correct grape, wine tolerance of 3.0 ppm. 

Summary of Comments from ISK Biosciences Corporation Regarding the Problem 

Formulation in Support of Registration Review 

Comment: ISKBC stated that it plans to utilize the FESTF IMS and submit an analysis of 

the potential direct and indirect effects of the 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 Sediment 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 toxicity 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 would most likely be exposed to in the 

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

Response: EPA believes that the sediment toxicity test should be conducted using the 

parent compound. While SDS-67200 is the major product under anaerobic 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 degradation pathway, fluazinam degrades to SDS67200 and to AMPA, both of which subsequently degrade to DAPA. Additionally, under 

aerobic aquatic metabolism, CAPA, DAPA, and DCPA were also present. Because these 

degradates may also be present in a sediment 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 photolysis 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 correct structures will be included in 

the registration review ecological 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. 
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Response: In addition to the half-lives for fluazinam, half-lives were estimated for the 

total fluazinam residues, because the environmental 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 that 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 biodegradation, but rather, some 

transformation. This approach has been used in all ecological risk and drinking water 

assessments for this chemical. 

Comment: ISKBC also stated that endpoints related to foliar dissipation 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, peanut leaves and potato leaves, in studies 

received and reviewed by the Agency in late 2008. The half-lives of fluazinam on leaf 

foliar surfaces were on average 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 half-lives were judged to be adequate for 

risk assessment exposure calculations. The input value to be used for terrestrial exposure 

in risk assessment (using e.g. T-REX) represents the 90th percentile of the upper 

confidence bound on the mean of six half-life values for the total residues, which is 7.33 

days. The Agency will consider this information when it conducts its ecological risk 

assessment. 

Comment: ISKBC also indicated that the company submitted a non-guideline study 

measuring run-off of fluazinam from a field under controlled conditions, and requested 

that it be evaluated. 

Response: This study is currently undergoing a secondary review. Should it be useful, it 

may be used in the registration review ecological risk assessment, 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 health 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, including an endangered species assessment, as well 

as a full human health assessment, for all fluazinam pesticidal uses.