Docket Number: EPA-HQ-OPP-2006-0239

www.regulations.gov

**Fomesafen Final Work Plan (FWP)**

**For Registration Review**

**August 2007**

Approved by: \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

Peter Caulkins, Acting Director

Special Review and Reregistration Division

Date:

Docket Number: EPA-HQ-OPP-2006-0239

www.regulations.gov

**[Introduction:]{.underline}**

This is the Environmental Protection Agency's (EPA's) ***Final Work
Plan*** for the registration review of fomesafen. This work plan
includes the expected registration review timeline. The work plan also
addresses public comments received concerning the ***Preliminary Work
Plan*** in the ***Summary Document*** which was posted in the fomesafen
registration review docket, and any other comments concerning 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 new registration review program and plans
to 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/]{.underline}](http://www.epa.gov/oppsrrd1/registration_review/_)

**[Comments Received on Preliminary Work Plan:]{.underline}**

EPA received comments during the public comment period on the initial
fomesafen docket. However, these comments, which are addressed in this
document, did not change the data and risk assessment needs or the
timeline detailed in the Preliminary Work Plan. This document makes
final the work plan for the fomesafen registration review process. A
listing of the comments and responses are in the "Summary of Comments
and Agency Responses" section of this document.

**[Risk Assessment and Data Needs:]{.underline}**

The Agency does not require any additional ecological effects or
environmental fate data to support the current assessments. However, the
Agency will conduct an endangered species risk assessment for all uses.
The Agency does not require any additional human health risk assessments
or related data.

> *Ecological Risk:*

-   Ecological risk assessments for fomesafen uses were completed
    January 30, 2006 for use on soybeans, and for new uses of fomesafen
    on cotton, snap beans, and dry beans.

Docket Number: EPA-HQ-OPP-2006-0239

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-   The planned ecological risk assessment will allow the Agency to
    determine whether fomesafen use has \"no effect\" or \"may affect\"
    federally listed threatened or endangered species (listed species)
    or their designated critical habitat. If the assessment indicates
    that fomesafen \"may affect\" a listed species or its designated
    critical habitat, the assessment will be refined. The refined
    assessment will allow the Agency to determine whether use of
    fomesafen is "likely to adversely affect" the species or critical
    habitat or \"not likely to adversely affect\" the species or
    critical habitat. 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 National Marine Fisheries Service (Services), as
    appropriate.

> *Human Health Risk:*

-   The previously completed dietary assessments (2/28/06) that
    considered dietary exposure to fomesafen from food and drinking
    water are adequate and there is no dietary risk that exceeds the
    Agency's level of concern (LOC). Thus, no additional data are
    needed.

-   The occupational database is completed for the existing uses and the
    latest risk assessment (2/28/06) indicates that most of the
    occupational scenarios do not result in risk concerns, with the
    exception of inhalation risk to mixer/loaders for aerial
    application. The Agency is working with the registrant to address
    this risk.

Docket Number: EPA-HQ-OPP-2006-0239

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**[Timeline:]{.underline}**

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

  ---------------------------------------------------- ------------------
  **Activities**                                       **Estimated
                                                       Month/Year**

  Phase 1: Opening the docket                          

  Open Public Comment Period for Fomesafen Docket      Mar. 2007

  Close Public Comment Period                          June 2007

  Phase 2: Case Development                            

  Develop Final Work Plan (FWP)                        Aug. 2007

  Open Public Comment Period for Preliminary Risk      1^st^ Quarter 2009
  Assessments                                          

  Close Public Comment Period                          2^nd^ Quarter 2009

  Phase 3: Registration Review Decision                

  Open Public Comment Period for Proposed Reg. Review  3^rd^ Quarter 2009
  Decision                                             

  Close Public Comment Period                          4^th^ Quarter 2009

  Final Decision and Begin Post-Decision Follow-up     1^st^ Quarter 2010

  Total (years)                                        3.0
  ---------------------------------------------------- ------------------

**[Summary of Comments and Agency Responses:]{.underline}**

The fomesafen registration review docket was opened for a 90-day comment
period beginning on March 28, 2007. During that time, comments were
received from the technical registrant, Syngenta Crop Protection, the
FIFRA Endangered Species Task Force (FESTF), and New York State
Department of Environmental Conservation.

***Summary of Comments Regarding EPA Proposed Actions***

1\. ***Comment:*** Syngenta responded to EPA anticipating conducting an
endangered species risk assessment for all fomesafen uses. Syngenta
indicated that they submitted an endangered species assessment for
fomesafen on March 27, 2006 (MRID No. 46796201). This submission was
made in support of the addition of Cotton, Dry and Snap Beans to the
Reflex Herbicide (EPA Reg.No.100-993) label. The conclusion from this
risk assessment was that even using worst-case screening level risk
methodologies there will be no effect to threatened or endangered
terrestrial animals, aquatic animals, aquatic plants and monocot plant
species from the use of fomesafen in cotton, dry beans, or snap beans.
In addition fomesafen is not likely to adversely affect threatened or
endangered terrestrial dicot species or the habitat of listed species.

Docket Number: EPA-HQ-OPP-2006-0239

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***[Response:]{.underline}*** The Agency thanks Syngenta Crop Protection
for its comment, and will consider this information as it conducts the
registration review and makes its registration review decision.

2\. **[Comment:]{.underline}** Syngenta responded to EPA's
recommendation for requiring a respirator to mitigate inhalation
exposure risks. Syngenta does not agree with the occupational exposure
assessment that leads to the recommendation for requiring a respirator
to mitigate inhalation exposure risks. The registrant feels that the
toxicity endpoint selected for the short-term inhalation exposure from
the 90-day feeding study is not appropriate because the short-term
exposure is defined as 1 to 30 days exposure duration. A 90-day study
covers a much longer duration of exposure. Syngenta suggests the use of
a developmental toxicity study in rats for selecting the short-term
inhalation exposure assessments.

***[Response:]{.underline}*** The liver appears to be a target organ in
the rat for fomesafen, since fomesafen has been shown to consistently
affect the liver in subchronic and chronic feeding studies in rats, as
well as in the rat reproduction study. Although it is logical for the
registrant to suggest selecting the toxicity endpoint for short-term
inhalation exposure based on a developmental toxicity study in terms of
duration of exposure, liver effects are not examined in a developmental
toxicity study. Additionally, some pesticides that produce liver
toxicity demonstrate liver effects with repeated dosing for a short
duration (2 weeks to 30 days). Therefore, in the absence of a shorter
duration (e.g., 30-day) feeding study on fomesafen to show otherwise, it
is assumed that fomesafen could cause liver toxicity following
short-term exposure. Hence, for fomesafen, it is prudent to select the
toxicity endpoint for short-term inhalation exposure based on a 90-day
feeding study.

3\. ***[Comment:]{.underline}*** Syngenta responded to EPA's statement
that additional data has been previously required as a condition of
registration for certain new uses for fomesafen. Syngenta indicated that
the actions required to satisfy these conditional registration
requirements are currently underway and will be completed within the
required time frame.

***[Response:]{.underline}*** The Agency thanks Syngenta Crop Protection
for its comment.

Docket Number: EPA-HQ-OPP-2006-0239

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***Summary of Comments Regarding Toxicology Endpoints for Fomesafen***

4\. ***[Comment:]{.underline}*** Syngenta responded to EPA's use of a
90-day toxicity study in rats to set a short-term toxicity endpoint
(inhalation and incidental oral). Syngenta indicated that this is not
appropriate, because the duration of exposure is 3-fold greater than the
maximum definition of "short-term" exposure (1-30 days). The liver
effects seen in this study at 100 ppm (10 mg/kg/day) were observed at
the terminal sacrifice, after 90 days of exposure. This included an
increased liver weight and increased alkaline phosphatase in males at
week 13, plus micropathology findings of hepatocyte eosinophilia and
reduce granulation (=hepatocyte hyalinization) in males and females at
week 13. The LOAEL findings quoted in the tables of Toxicology Endpoints
(EPA, 2006; EPA, 2007) inadvertently included increases in alanine
transaminase and aspartate transaminase as effects at 10 mg/kg/day, but
in fact these were only increased at the high dose of 100 mg/kg/day
(1000 ppm) in this study. For short-term dermal toxicity, EPA has
selected the rat developmental toxicity NOAEL of 100 mg/kg/day, and this
would be an appropriate endpoint for short-term inhalation and oral
exposures as well. In support of this, there is no evidence for an
increased concern for exposures via the inhalation route compared to
other routes with fomesafen. In an acute inhalation study, fomesafen
technical had an LC50\>2.63 mg/L (Carter, 2004) placing it in EPA
Category IV. Fomesafen is not volatile, and typical agricultural
applications of the final herbicide spray dilutions do not produce
particles of respirable size. Therefore, the same study that was used
for short-term dermal toxicity risk assessment (rat development study)
is equally applicable to short-term inhalation toxicity risk assessment.

***[Response:]{.underline}*** The Agency thanks Syngenta Crop Protection
for its comment, and will consider this information as it conducts the
registration review and makes its registration review decision.

***Summary of Comments Regarding Environmental Exposure Characteristics
for Fomesafen***

5\. ***[Comment:]{.underline}*** Syngenta noted that they have conducted
an anaerobic aquatic metabolism study that will be submitted to EPA to
support the current registration review (Peters, 2002). The result of
this study was that fomesafen was found to degrade rapidly under
anaerobic conditions. The degradation of fomesafen was studied using
three US water-sediment system and found to degrade with total system
half-lives ranging from 3.93 to 7.95 days. Syngenta believes that

Docket Number: EPA-HQ-OPP-2006-0239

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the data from this study which indicated an upper 90% confidence limit
of 8.05 days should be used as the anaerobic aquatic (benthic) half-life
input to PRIZM/EXAMS.

***[Response:]{.underline}*** The Agency thanks Syngenta Crop Protection
for its comment, and will consider this information if submitted in a
timely fashion as it conducts the registration review and makes its
registration review decision.

6\. ***[Comments:]{.underline}*** Syngenta noted that the equilibrium
adsorption coefficient, the lowest non-sand K~d~ value of 0.68 mL/g was
used by the EPA for PRZM/EXAMS modeling and K~oc~ =68 mL/g was used for
SCI-GROW, using an assumed organic carbon comment of 1%. Syngenta agrees
with this approach to the SCI-GROW input, since there is considerable
scatter in the K~d~ vs. %OC correlation. However, the input to
PRZM/EXAMS that is normally used for this parameter is the average
Freundlich K~d~ or K~oc~. In MRID 00259413, the adsorption of fomesafen
to each soil is represented as the mean K~d~ value, rather than the
Freundlich coefficient.

***[Response:]{.underline}*** The Agency thanks Syngenta Crop Protection
for its comment, and will consider this information as it conducts the
registration review and makes its registration review decision.

7\. ***[Comment:]{.underline}*** Syngenta noted that the fomesafen soil
accumulation was modeled using the 90% confidence limit of the
laboratory values for half-life (428 days) with an assumption that
aerobic soil metabolism is the only degradation process. Syngenta
indicated that this approach results in exaggerated predictions of
fomesafen soil concentrations and does not believe best estimates the
potential for fomesafen residues to accumulate in the soil. Field
dissipation studies conducted under actual use conditions and that are
cited by the Agency in the Ecological Risk Assessment for use of
Fomesafen on Cotton, Snap and Dry Beans (Docket ID
EPA-HQ-OPP-2006-0239-009) resulted in half-lives ranging from 50 to 150
days in surface soils. The utilization of these points to characterize
the soil accumulation potential for fomesafen would result in more
appropriate estimates for use in modeling.

***[Response:]{.underline}*** The Agency thanks Syngenta Crop Protection
for its comment, and will consider this information as it conducts the
registration review and makes its registration review decision.

Docket Number: EPA-HQ-OPP-2006-0239

www.regulations.gov

***Summary of Comments Regarding the FIFRA Endangered Species Task
Force***

8\. ***[Comment:]{.underline}*** The FIFRA Endangered Species Task Force
(FESTF) noted that EPA stated in the Registration Review summary
document that fomesafen does not have a complete environmental risk
assessment that is in compliance with EPA's Overview Document for
Endangered and Threatened Species Effects Determinations. FESTF requests
that EPA assure that any company that is relying upon FESFT data, and
are not a member file a proper offer to pay for data compensation.

***[Response:]{.underline}*** The Agency thanks FESTF for its comment,
and will consider this information as it conducts the registration
review and makes its registration review decision.

***Summary of Comments Regarding the Aquatic Plant Risk Assessment***

9\. ***[Comment:]{.underline}*** The New York State Department of
Environmental Conservation (NYDEC) noted that the aquatic risk
assessment appeared to be based on the green algae, Selenastrum
capricornutum, and did not report any information for the macrophyte
(Lemna gibba) study. NYDEC also commented that the active ingredient
fomesafen is used in herbicides, and therefore the macrophyte study is
of great importance to determining ecological risk from use of these
products. The Department requests that USEPA add the aquatic macrophyte
acute toxicity test as part of the Information Needs Section.

> **[Response:]{.underline}** The Agency thanks the New York State
> Department of Environmental Conservation for its comment. The Agency
> does have data on the aquatic vascular plant, *Lemna gibba*, and this
> data shows that *Lemna gibba* is less sensitive to fomesafen than
> *Selenastrum capricornutum.* However, the Agency will consider the
> *Lemna gibba* data as it conducts the registration review and makes
> its registration review decision.

**[Next Steps:]{.underline}**

The Agency will conduct an endangered species risk assessment for all
uses of fomesafen.