Docket Number: EPA-HQ-OPP-2010-0939

www.regulations.gov

Formetanate HCl Final Work Plan for

Registration Review

June 2011

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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 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 review docket (EPAHQ-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 are 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 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 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 an N-methyl carbamate miticide/insecticide originally registered for use on apple, 

grapefruit, lemon, lime, nectarine, orange, peach, pear, tangelo, tangerine, alfalfa grown for seed,

and nonagricultural uncultivated areas/soils. Formetanate is not registered for use in residential 

or public recreational areas. There is one technical registration and one active end-use product 

registration containing formetanate. 

As a member of the N-methyl carbamate (NMC) class of chemicals formetanate shares a 

common mechanism of toxicity known to inhibit acetyl cholinesterase. The Formetanate Interim 

Reregistration Eligibility Decision (IRED) was completed in March 2006. Based upon public 

comments 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 and finalized the Formetanate 

Reregistration Eligibility Decision (RED). 

The technical registrant submitted a new comparative cholinesterase assay (CCA) study in

August of 2010 (a study is designed to examine the effects between 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 with 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 cancellation requests for use of formetanate on apple, pear and peach (for 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. 
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Since apple, pear and peach uses are in the process of being voluntarily 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) Dietary 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 data available for these commodities and identified six residue samples for 

nectarines that had violative residues. In other words, these six nectarine samples contained 

residues of formetanate that were higher than the established tolerances, or maximum allowed 

residue levels (0.4 ppm). These over-tolerance residues were determined to be present only on

imported nectarine samples (specifically from Chile and Mexico), and are likely to be the result 

of differences between foreign and domestic use patterns. As 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 Plan:

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 February 

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 registration 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 (Public Docket: EPAHQ-OPP-2004-0032-0015) was completed in October of 2003 to support the 

Formetanate Interim Reregistration Eligibility Decision (IRED).

An updated ecological and endangered species risk assessment for registered uses 

of formetanate will be conducted during registration review. The assessments

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 environmental fate and ecological 

effects data for formetanate:
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Environmental Fate:

o GLN 835.2130 Hydrolysis Study

o GLN 835.4100 Aerobic Soil Metabolism

o GLN 835.4200 Anaerobic Soil Metabolism

o GLN 835.6100 Terrestrial Field Dissipation Study (with

(Footnote 7) Environmental Chemistry Methods and Independent 

Laboratory Validation – soil)

o GLN 835.6200 Aquatic Sediment Field Dissipation (with 

(Footnote 7) Environmental Chemistry Methods and Independent 

Laboratory Validation – water)

Ecological Effects:

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 Algal Toxicity, Tier II (algae)

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

species determination for formetanate. 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 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 (FWS) and/or the National Marine 

Fisheries Service (NMFS) (the Services), 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 Environmental 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 Formulation 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.
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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, the most 

recent comprehensive human health risk assessment (which included occupational risks) 

was conducted in December of 2005 to support the 2006 IRED. 

The Agency will conduct a revised drinking water assessment to incorporate 

environmental fate data to be required during the registration review of formetanate.

An updated formetanate acute dietary risk assessment will be conducted during 

registration review to incorporate any updates to the toxicity profile for formetanate, or 

updates in Agency policies or methodologies.

The Agency will be requiring the following study, in accordance with the revised 40 

CFR, Part 158, in order to conduct a comprehensive human health risk assessment for the 

registration review of formetanate.

Toxicology:

o (GLN 870.7800) Immunotoxicity

Previously required data 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 (to support the storage stability 

of peach extract)*

o (860.1500) Crop Field Trials: apple, pear, peach,*

nectarine, and citrus

*Note: Formetanate data required on apple, pear and peach commodities is pending due to the anticipated cancellation of these commodities 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 aggregate 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 cumulative
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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 incorporate 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 degrades 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 

detailed 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 exposure 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 be 

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

Under FFDCA section 408(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. Formetanate is 
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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 callins, 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 2011 – February

Case Development

Develop Final Work Plan (FWP) 2011– June

Issue DCI 2012 – Jan. – Mar. 

Data Submission 2014 – Jan. – Mar. 

Open Public Comment Period for Preliminary Risk Assessments 2015 – Jul. – Sept.

Close Public Comment Period 2015 – Oct. – Dec.

Registration Review Decision

Open Public Comment Period for Proposed Reg. Review Decision 2016 – Jan. – Mar. 

Close Public Comment Period 2016 – Apr. – June

Final Decision and Begin Post-Decision Follow-up 2016

Total (years) 61

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

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 Assessments, 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 PAIRA
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Guideline 

Number

Anticipated Data Requirement Test Material

835.6100 Terrestrial Field Dissipation (footnote 7) TEP

835.6200 Aquatic Sediment Field Dissipation (footnote 7) TEP

850.1350 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 (Vegetative 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: Technical End-use Product (TEP), Technical Grade Active Ingredient (TGAI) and “Pure” Active Ingredient Radiolabeled (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 assessments for all registered uses of formetanate.