Docket Number: EPA

- HQ

- OPP

- 2010

- 0939

www.regulations.gov



## Formetanate HCl Final Work Plan for Registration Review

June 20 1 13

Introduction:

This is the Environmental Protection Agency’s (EPA or the Agency) Final Work Plan (FWP) for the registration review of formetanate HCl (“formetanate” unless otherwise specified)

. 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

, dated December 17, 2010, which was posted in the formetanate registration rev iew docket (EPA

HQ

- OPP

- 2010

- 0939) 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 a re needed to make a registration review decision.

The Agency is implementing the new registration review program and will review each registered pesticide every 15 years to determine whether it continues to meet the Federal Insecticide, Fungicide, and Rod enticide 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

p ractices change, all registered pesticides continue to meet the 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/

.

Formetanate is a n N

- methyl carbamate miticide/insecticide originally registered for use on apple, grapefruit, lemon, lime, nectarine, orange, peach, pear, tangelo , tangerin e, alfalfa grown for seed

, and non agricultural uncultivated areas/soils

. Formetanate is not registered for use in residential or public recreational areas. T he re is one technical registration and one active end

- use product registration containing formeta nate

.

As a member of the N

- methyl carbamate (NMC) class of chemicals formetanate share s a common mechanism of toxicity known to inhibit acetyl cholinesterase . The Formetanate Interim Reregistration Eligibility Decision (IRED ) was completed in March 20 06 . Based upon public

comment s received in response to the IRED, the Agency revised elements of its occupational

assessment

, and revised the Formetanate HCl IRED in April 2007. In September 2007, the Agency completed the NMC cumulative risk assessment an d finalized the F ormetanate

R eregistration E ligibility D ecision (RED)

.

T he technical registrant submitted a new comparative cholinesterase assay (CCA) study in August of 20 10 ( a study is designed to examine the effect s betwee n sexes as well as between

ages ) prompting a new dietary risk assessment which was completed on December 7

, 2010. The new dietary risk assessment identified risks of concern for some existing uses of formetanate

.

Updates Since the Summary Document: EPA is continuing to work wit h the technical registrant to mitigate dietary risks of concern identified in the December 7, 2010 dietary risk assessment. Recently, the technical registrant has submitted voluntary cancel l ation requests for use of formetanate on apple, pear and peach (f or all special local needs (SLNs) and section 3 registrations ). The technical registrant has also

submitted amended labels

, which restrict formetanate’s use on nectarines to CA, WA and OR.4

Since apple, pear and peach uses are in the process of being vol untarily cancelled

, the Agency reassessed potential dietary risk (food + drinking water) from nectarine and citrus uses, (Formetanate Hydrochloride: Revised Acute Probabilistic (Citrus, Nectarine and Drinking Water Associated with Proposed Citrus Use) Diet ary Exposure Assessment, 17

- May

- 2011)

. The analysis identified no risks of concern (49% aPAD for all infants (< 1 yr.) which is the highest exposed population subgroup). In its analysis, the Agency looked closely at the formetanate

residue monitoring dat a available for these commodities and identified s ix residue samples for

nectarines that had v i olat ive residues. In other words, these six nectarine samples contained

residues of formetanate that were higher than the established tolerances, or maximum all owed residue levels (0.4 ppm). These over

- tolerance residues were determined to be present only on imported nectarine samples (spec ifically from Chile and Mexico), and are likely to be the result

of differences between foreign and domestic use patterns

. A s a result, the technical registrant agreed to harmonize the nectarine application parameters for all formetanate products distributed internationally with the application parameters of current U.S. labels.

Comments Received on the Preliminary Work Pl an : No comments were received on the formetanate Preliminary Work Plan (PWP) during the public comment period for the docket opening (EPA

- HQ

- OPP

- 2010

- 0939). The 60

- day public comment period on the formetanate PWP began on December 22, 2010 and closed on F ebruary
22, 2010

.

In the PWP, EPA also solicited comment on the specific topics of environmental justice, water body impairment, and trade irritants. No comments were received during the public comment period concerning these issues.

Risk Assessment and Data Needs: The Agency will be requiring data to conduct an ecological risk assessment for formetanate, including an endangered species assessment. For human health, revised dietary and occupational

risk assessments will be conducted during registra tion review to incorporate any updated toxicological endpoints, and/or exposure estimates

. Below is a summary of the issues relevant to the registration review of formetanate.

Ecological Risk :

The most recent comprehensive ecological risk assessment ( Pub lic Docket: EPA

HQ

- OPP

- 2004

- 0032

- 0015 ) was completed in October of 2003 to support the

Formetanate Interim Reregistration Eligibility Decision ( I RED).

An updated ecological and endangered species risk assessment for registered uses

of formetanate will be conducted during registration review. The assessment s will incorporate up

- to

- date modeling methodologies, ecological effects and/or fate

data submitted under the anticipated registration review data call

- in.

The Agency will be requiring the following e nvironmental fate and ecological

effects data for formetanate :5

Environmental Fate:

o GLN 835. 213 0 Hydrolysis Study

o GLN 835.4100 Aerobic Soil Metabolism

o GLN 835.4200 Anaerobic Soil Metabolism

o GLN 835.6100 Ter restrial Field Dissipation Stud y (with

(Foot note 7) Environmental Chemistry Methods and Independent

Laboratory Validation

– soil )

o GLN 835.6

2 00 Aquatic Sediment Field Dissipation (with

(Footnote 7) Environmental Chemistry Methods and Independent

Laboratory Validation

– water )

Ecological Ef

fects:

o GLN 850.1350 Aquatic Invertebrate Life Cycle Toxicity (mysid shrimp)

o GLN 850.2100 Avian Acute Oral Toxicity Test (passerine species)

o GLN 850.4100 Terrestrial Plant Toxicity, Tier II (Seedling Emergence)

o GLN 850.4150 Terrestrial Plant Toxicity, Tier II (Vegetative Vigor)

o GLN 850.4400 Aquatic Vascular Plant Toxicity

, Tier II (Lemma sp.)

o GLN 850.5400 A lgal Toxicity, Tier II (algae)

The Agency has not conducted a risk assessment that supports a complete endangered species determination for fo rmetanate

. The ecological risk assessment planned during registration review will allow the Agency to determine whether the use of formetanate has “no effect” or “may affect” federally listed threatened or endangered species (listed species) or their desi gnated 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 (FWS) and/or the National Marine

Fisheries Serv ice (NMFS) (the S ervices) , as appropriate.

On January 19, 2011, the Center for Biological Diversity and the Pesticide Action

Network North America filed a lawsuit in the United States District Court for the Northern District of California, against the Env ironmental Protection Agency (EPA) for allegedly failing to undergo consultation with the United States Fish and Wildlife Service and the National Marine Fisheries Service regarding the effects of over 350 pesticides, including formetanate HCl

, on over 200 endangered and threatened species throughout the United States (Center for Biological Diversity, et al. v. EPA, et al., No. C 11

- 00293 (N.D.Cal.) ).

Please refer to the December 7, 2010 document: Environmental Fate and Ecological Risk

Assessment Problem F

ormulation In Support of Registration Review of Formetanate

HCl

, for a more detailed discussion of the anticipated ecological risk assessment and data

needs

, available in the public docket

.6

Human Health Risk :
The most recent human health risk assessment of formetanate HCl was a dietary (food + drinking water) only assessment , completed on May 17, 2011 . Previously, t he most recent comprehensive human health risk assessment (which included occupational risks)

was conducted in December of 20 05 to support th e 2006 IRED

.

The Agency will conduct a revised drinking water assessment to incorporate

environmental fate data to be required during the registr ation review of formet a nate.

A n updated formetanate acute dietary risk assessment will be conducted durin g registration review to incorporate any updates to the toxicity profile for formetanate

, or updates in Agency polic ies or methodologies

.

The Agency will be requirin g the following study , in accordance with the revised 40 CFR, Part 158, in order to condu ct a comprehensive human health risk assessment for the registration review of formetanate.

Toxicology :

o (GLN 870.7800) Immunotoxicity

Previously required d ata from the 2008 Formetanate HCl RED generic data call

- in (GDCI) are due to be submitted to the Agency by April 30, 2013 and will be incorporated into the registration review for formetanate HCl

.

Toxicology :

o (870.3465) (90

- day) Inhalation Study

Residue Chemistry:

o (860.1300) Nature of the Residue

- storage stability of peach leaves (t o supp ort the storage stability of peach extract ) *

o (860.1500) Crop Field Trials: a pple, p ear, p each, *

n ectarine, and c itrus

* Note: Formetanate data required on apple, pear and peach commodities is pending due to the anticipated cancellation of these commodi ties from formetanate product registrations . Upon completion of the cancellation notice, these data on these commodities will no longer be required.

There are no residential uses associated with formetanate registrations; therefore

, the anticipated aggre gate risk assessment will include only dietary exposure (food + drinking water).

Formetanate shares a common mode of action with other N

- methyl carbamate chemicals. Prior to a final registration review decision for formetanate, the Agency will determine if there is any new information, such as new hazard or exposure data

, or changes to the use pattern, which would affect the cumulative risk assessment. Should the Agency determine that new information on formetanate could potentially impact the cumulative7

risk assessment and result in a risk of concern, the Agency will revisit the cumulative risk

assessment.

The Agency will conduct an updated occupational handler and post

- application risk assessment during the registration review of formetanate to incorpo rate new toxicological endpoints and any revisions to current guidelines and assessment methodologies.

The tolerance expression in 40 CFR § 180.276 will be revised during registration review to ensure that it appropriately covers the metabolites and degra des of formetanate, and that it specifies the residues to be measured for each commodity.

Please refer to the December 9, 2010 document: Formetanate Hydrochloride (HCl): Registration Review Scoping Document for Human Health Assessments

, for a more deta iled discussion of the anticipated human health risk assessment and data needs,

available in the docket.

Endocrine Disruptor Screening Program:

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse outcomes from exposur e to chemicals. Collectively, these studies include acute, subchronic and chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may b e susceptible to endocrine influence, including effects on endocrine target organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessm ents, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its reregistration decision , EPA reviewed these data and selected the most sensitive endpoints for rel evant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), formetanate HCl is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).

EPA has developed the 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 des ignate.” 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 dose

- response relationship between the dose and the E, A, or T effect.

Under FFDCA section 4 08(p), the Agency must screen all pesticide chemicals. 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. F ormetanate i s8

not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data call

ins, requiring the submission of EDSP screening assays for formetanate HCl

. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/

.

Timeline: EPA has created the following estimated timeline for the completion of the registration review of

formetanate

.

Registration Review for Formetanate HCl

– Projected Registration Review Timeline

Activities Estimated Date Opening the docket
Open Public Comment Period for the Formetanate HCl Docket 2010

– December

Close Public Comment Period 201 1

– February
Case Development

Develop Final Work Plan (FWP) 201 1

– June

Issue DCI 201 2

– Jan.

– Mar.

Data S ubm ission 2014

– Jan.

– Mar.
Open Public Comment Period for Preliminary Risk Assessments 201 5

– Jul.

– Sept.

Close Public Comment Period 2015

– Oct.

– Dec.

Registration Review Decision
Open Public Comment Period for Proposed Reg. Review D ecision 2 01 6

– Jan.

– Mar.

Close Public C omment P eriod 2016

– Apr.

– June

Final D ecision and Begin P ost

- D ecision F ollow

- up 201 6
Total ( years ) 6 1

1 An assessment of the potential cumulative risk from the NMC class of insecticides may impact this time estima te.

Summary of Data Gaps

– Formetanate HCl:

The table below summarizes all anticipated data needs for the formetanate Registration Review

as listed in the Formetanate Hydrochloride (HCl): Registration Review Scoping Document for

Human Health Assessment s , dated December 9, 2010, and the Environmental Fate and Ecological Risk Assessment Problem Formulation In Support of Registration Review of Formetanate HCl , dated December 7, 2010.

Guideline

Number Anticipated Data Requirement Test Material

835.2130 Hydrolysis Study TGAI or PAIRA

835.4100 Aerobic Soil Metabolism TGAI or PAIRA

835.4200 Anaerobic Soil Metabolism TGAI or PAIRA9

Guideline

Number Anticipated Data Requirement Test Material

835.6100 Terrestrial Field Dissipation (footnote 7) TEP

835.6200 Aquatic Sediment Field Dissipation (footnote 7) TEP

850.13 50 Aquatic Invertebrate Life Cycle Toxicity (mysid shrimp) TGAI

850.2100 Avian Acute Oral Toxicity Test (passerine species) TGAI

850.4100 Terrestrial Plant Toxicity, Tier II

(Seedling Emergence) TEP

850.4150 Terrestrial Plant Toxicity, Tier II (Vegeta tive Vigor) TEP

850.4400 Aquatic Vascular Plant Toxicity, Tier II TGAI or TEP

850.5400 Algal Toxicity, Tier II TGAI or TEP

870.7800 Immunotoxicity Study TGAI

Note : T echnical E nd

- use P roduct (TEP), T echnical G rade A ctive I

ngredient (TGAI) and “ P ure” Act ive Ingredient Radio l abeled (PAIRA)

Next Steps:

The Agency plans to require the data identified herein through a data call

- in, which is expected

to be issued in early 2012 . This new information will be used to conduct human health and ecological risk as sessments for all registered uses of formetanate.