Docket Number EPA-HQ-OPP-2010-0028 www.regulations.gov



## Oxamyl Final Work Plan for Registration Review

February 20113 Introduction:

This is the Environmental Protection Agency’s (EPA or the Agency) Final Work Plan (FWP) for the registration review of oxamyl. The Fina l Work Plan includes the expected registration review timeline. The FWP also addresses public comments received on the Preliminary Work

Plan (PWP) in the Summary Document which was posted in the oxamyl registration review docket (EPA-HQ-OPP-2010-0028). The Summary Document, dated September 17, 2010, provided information on what EPA knows about the pesticide and what additional risk analyses and data or information the Agency believes are n eeded to make a registra tion review decision.

The Agency’s implementation of the registrati on review program requi res review of 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 pestic ide use practices 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/

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Oxamyl is a restricted use N -methyl carbamate insecticide, acaricide, miticide, nematicide, and plant growth regulator regi stered for use on a variety of fruits, vegetables, and field crops. There are currently no residential uses for oxamyl. It is a member of the N -methyl carbamate (NMC)

class of chemicals that share a common mechanism of toxicity and inhib it acetylcholinesterase.

The Interim Reregistration Eligibil ity Decision (IRED) for Oxamyl was completed in October 2000, and the Reregistration Eligibility Decision (RED) for Oxamyl was finalized in September 2007 upon completion of the Revised N-Methyl Carbamate Cumulative Risk Assessment.

In 2007 and 2008, EPA received several new a nd expanded use request s from DuPont Crop Protection (DuPont), the technical registrant of oxamyl. Risk assessments were conducted in 2009 and 2010 to evaluate these amendment requests and to incorporate updated toxicological data and modeling methodologies into assessments for the currently labeled uses of oxamyl. Due to the recent improvements in EPA’s risk modeling methodologies, the new risk

assessments identified risks of concern for some existing uses of oxamyl. All of the new and expanded use amendment requests were w ithdrawn by DuPont in December 2009.

Updates Since the Summary Document:

EPA is continuing to work with DuPont to mitigate dietary and occupational risks of concern identified in the 2010 dietary and occupational risk assessments. Mitigation may result in a number of crop-specific regi onal labeling changes (e.g., lowe ring individual and annual application rates, reducing number of applications), longer restri cted entry intervals for some crops, or other measures. EPA is working to refine the risk assessment and will mitigate where necessary to resolve risk concerns in advance of the draft risk asse ssments for registration

review.4 Comments Received on the Preliminary Work Plan:

The Agency received four submissions during the 60-day public comment period on the PWP, which began on September 22, 2010 and ende d on November 22, 2010 (EPA-HQ-OPP-2010- 0028). Comments were submitted by the Physicia ns Committee for Responsible Medicine, the American Bird Conservancy, DuPont, and a member of the public. The comments do not address the timeline described in the PWP, but they do address the planned ecological data requirements and risk assessments. The submitte d comments and EPA’s responses are presented in the “Summary of Comments and Agency Responses” section of this document.

In the PWP, EPA also solicited comment on the sp ecific topics of environmental justice, water body impairment, and trade irritants. No commen ts or information were received during the public comment period concerning these issues.

Risk Assessment and Data Needs:

The Agency will require data and conduct an ecol ogical risk assessment for oxamyl, including an endangered species assessment. For human h ealth, revised dietary and occupational risk assessments may be needed during registration review to incorporat e updated toxicological endpoints, exposure estimates, and data require d through a registration re view data call-in. Below is a summary of the issues relevant to the registration review of oxamyl.

Ecological Risk:

• The most recent comprehensive ( i.e. , all use patterns) ecological risk assessment was completed in November 1999 and amended in March 2000 in support of the 2000 Oxamyl IRED.

• In 2007 and 2009, crop-specific eco logical risk assessments were conducted for oxamyl to evaluate FIFRA Section 3 proposed new uses on sugar beets and on dry bulb onions, shallots, and garlic. The requests for new uses were later withdrawn by the technical registrant.

• The Agency completed an endangered species risk assessment for the California redlegged frog (CRLF) in February 2009, and is cu rrently in consultation with the U.S. Fish and Wildlife Service (USFWS).

• Although the Agency has completed a speci es-specific determination for the CRLF relative to oxamyl use, a risk assessment that supports a complete endangered species

determination has not been conducted. The ecological risk assessment planned during registration review will allow the Agency to determine whether oxamyl’s use has “no effect” or “may affect” federally listed threat ened or endangered sp ecies (listed species) or their designated critical ha bitats. When an assessment c oncludes that a pesticide’s use “may affect” a listed species or its designate d critical habitat, the Agency will consult

with the USFWS and/or National Marine Fisher ies Service (the Services), as appropriate.5 • On January 19, 2011, the Center for Biologi cal Diversity and the Pesticide Action

Network North America filed a lawsuit in th e United States District Court for the Northern District of California, against EP A for allegedly failing to undergo consultation with the Services regarding the effects of over 350 pesticides, including oxamyl, on over 200 endangered and threatened species throughout the Un ited States (Center for Biological Diversity, et al. v. EPA, et al., No. C 11-00293 (N.D.Cal.).

• An updated ecological risk assessment of all registered uses of oxamyl will be conducted during registration review. The new assessment will incorporate the most up-to-date modeling methodologies, updated toxicological endpoints, and data submitted under the registration review data call-in.

• Data gaps exist in the environmental fate and ecological effects databases for oxamyl. EPA will require the following guideline st udies in order to conduct a complete ecological risk assessment, including an endangered species assessment, for the registration review of oxamyl.

835.4400 – Anaerobic aquatic metabolism 850.1025 – Acute toxicity es tuarine and marine or ganisms (oyster shell deposition) 850.1035 – Acute toxicity estuarine and marine organisms (mysid) 850.1350 – Aquatic invertebrate life cycle, saltwater (mysid) 850.1400 – Fish early life stage, saltwater fish 1
850.2100 – Avian oral toxicity (passerine species) 850.3040 – Field testing for pollinators 850.4100 – Seedling emergence, terrestri al plant toxicity (Tier II) 850.4150 – Vegetative vigor, terrestr ial plant toxicity (Tier II) 850.4400 – Aquatic plant growth, va scular plants (Tier II)

• Please refer to the July 28, 2010 document Registration Review: Preliminary Problem Formulation for Environmental Fate, Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments for Oxamyl in the registration review docket (EPA-HQ-OPP-2010-0028-0005) for a detailed di scussion of the risk assessment and

data needs.

Human Health Risk:

• A refined acute dietary (food plus drinking water) risk assessment for all registered uses of oxamyl was conducted in July 2010 to in corporate updated toxi cological data and modeling methodologies into assessments for th e currently labeled uses of oxamyl. In addition, the Agency further refined th e acute aggregate dietary assessment by incorporating the time and amounts consumed for each eating occasion from the United States Department of Agricu lture’s (USDA’s) Continuing Surveys of Food Intakes by

Individuals food diaries to estimate e xposures and risks on each eating occasion

1 The Oxamyl Summary Document for Registration Review in correctly stated that Guid eline 850.4100 was required for freshwater fish. That was in error, and EPA is requiri ng the fish early life stage st udy for the saltwater species.6 throughout the day and factoring in the cholines terase (ChE) inhibition half-life related to oxamyl exposure.

• The drinking water assessment may be updated as a result of mitigation implemented to address risks of concern identified in the most recent oxamyl dietary assessment. Additionally, the Agency may update the drinking water assessment during registration review if new environmental fate data are submitted, labeled use patterns are altered, residues of concern in drinking water are redefined, or the Agency’s drinking water assessment methodology is refined.

• The oxamyl dietary risk assessment may be updated as a result of mitigation implemented to address risks of concern identified in the July 2010 oxamyl aggregate (food plus drinking water) acute dietary ri sk assessment. Additionally, an updated oxamyl acute dietary risk assessment may be required during registration review if there are changes to residues in food or concentratio ns in drinking water, points of departure, or uncertainty factors.

• EPA will not conduct an oxamyl chronic dietar y assessment during registration review. Acute exposure from oxamyl is the only dur ation of concern because of the rapid recovery of ChE activity.

• A revised occupational and residential e xposure (ORE) assessment for oxamyl was completed in July 2010 to incorpor ate updated toxicological data.

• The ORE risk assessment may be updated as a result of mitigation implemented to address occupational risks of concern identi fied in the most recent assessment. Additionally, the Agen cy may update the a ssessments of oxamyl occupational handler and post-application activities during regi stration review if t oxicological endpoints change, revisions to current policies and procedures for c onducting these assessments are accepted, or new poisoning incident data are received.

• Because there are no currently registered uses of oxamyl at residentia l sites, residential handler and post-application assessments will not be conducted during registration

review.

• The current label restriction against feedi ng cotton gin byproduct to livestock can be deleted from oxamyl labels once a tolerance of 120 ppm is established for residues of oxamyl on cotton gin byproduct.

• The toxicity database for oxamyl is nearly complete. However, EPA will require Guideline 870.7800, Immunotoxicity study, in orde r to conduct a complete human health risk assessment for the regi stration review of oxamyl.

• Oxamyl shares a common mode of action with other NMCs and was included in the Revised N-methyl Carbamate Cumulative Risk Assessment completed in 2007. Over time as new use requests, new data, or other in formation are submitted to the Agency for7 individual chemicals within the cumulative group, single chemical risk assessments are updated. In the case of oxamyl, recent reque sts for new uses required updated risk assessments that indicated poten tial risks of concern for a number of existing uses. The Agency is working to address risk concer ns for the individual chemical first. Subsequently, the Agency will consider any changes to the use patterns for oxamyl, as appropriate, for the NMC cumulative assessment in order to reach a determination for the cumulative group as a whole.

• Please refer to the August 18, 2010 document Oxamyl: Registration Review Scoping Document for Human Health Assessments in the registration review docket (EPA-HQOPP-2010-0028-0004) for a detailed discussion of the risk assessment and data needs.

Endocrine Disruptor Screening Program:

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its oxamyl reregistration decision

, EPA reviewed these data and selected the most sensitive endpoi nts for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), oxamyl is subject to the endocrine screening part of the Endocri ne Disruptor Screen ing Program (EDSP).

EPA has developed the EDSP to determine whet her 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 ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e statutorily required

determinations. Tier 1 consists of a battery of 11 scr eening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects 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. Oxamyl was included on that list and has been issued an orde r to conduct the Tier 1 testing. Once all required

Tier 1 and Tier 2 data have been received and reviewed, the endpoints and safety factors used for risk assessment purposes will be examined and a new risk assessment performed if necessary.

For further information on the status of the ED SP, the policies and procedures, the list of 678 chemicals, future lists, the test guidelines and the Tier 1 screening ba ttery, please visit our

website: http://www.epa.gov/endo/

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Timeline:

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

Registration Review for Oxamyl – Projected Regist ration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and Public Comment Period Completed – Sept. 22, 2010

Close Public Comment Completed – Nov. 22, 2010 Case Development

Final Work Plan Completed – February 2011

Issue DCI 2011 – Oct – Dec

Data Submission 2013 – Oct – Dec Open Public Comment Period for Draft Risk Assessments 2015 – April – June Close Public Comment Period 2015 – July – Sept Registration Review Decision Open Public Comment Period for Proposed Registration Review

Decision 2015 – Oct – Dec.

Close Public Comment Period 2016 – Jan. – March Registration Review Decision and Begin Post-Decision Follow-up 2016 Total (years) 2 6

Summary of Comments and Agency Responses:

During the public comment period on the Oxam yl Summary Document, the Agency received comments from the Physicians Committee for Responsible Medicine, the American Bird Conservancy, DuPont, and a member of the publ ic. The following is a summary of the comments and the Agency’s responses.

Comments submitted by the American Bird Conservancy (ABC) in EPA-HQ-OPP-2010-

0028-0015.1.

For additional details regarding EPA’s response, please refer to the document “EFED Response to Comments on Preliminary Work Plan for Oxamyl,” dated January 20, 2011, included in the oxamyl registration review docket (EPA-OPP-2010-0028).

1. Comment: ABC noted that although relatively few incidents involving oxamyl have been reported to ABC or EPA, the absen ce of incident reports cannot be construed as the absence of incidents. This is because poisoned birds ma y fly far from the site of pesticide application or be consumed by scavengers.

2 An assessment of the potential cumulative risk from the NMC class of insecticides may impact this time estimate.9 Response: EPA agrees with this statement and incl udes a similar disclaimer in the discussion of incidents within our preliminary problem formulation document for oxamyl. Additionally, when EPA is ready to conduct the ecological ri sk assessment for oxamyl, we will review the Environmental Incident Information System, Am erican Bird Conservancy database, and the aggregate incident reporting system for any addi tional incidents reported between the time of

the EFED Problem Formulation and the risk assessment.

2. Comment: “ABC suggests substitution of effective insecticides with much lower avian toxicity as alternatives to oxamyl, unless effecti ve mitigation measures can be developed... Because the registration review process is so prolonged, we request that EPA mitigate uses of oxamyl that are found to pose high risks to migratory birds or th reatened or endangered species.”

Response: In the 2000 Interim Reregistration Elig ibility Decision for Oxamyl, the Agency concluded that potential risks to the environment, including to birds, from oxamyl would be mitigated with the incorporati on of additional use restrictions on oxamyl product labels. All current product labels have been amended to reflect these measures. At this time, the Agency believes the current uses of oxam yl do not pose unreasonable adverse effects to birds, and therefore, no additional risk mitigat ion is required. Additionally, the Agency will perform an endangered species assessment for oxamyl as part of the registration review process, and will consult with the Services, as appropriate, if the assessment concludes that oxamyl’s use may affect a listed species or its designated cr itical habitat.

3. Comment: “ABC requests an avian oral toxicity test using a passerine species.”

Response: The Oxamyl Summary Document for Re gistration Review and this Final Work Plan both list Guideline 850.2100, avian oral toxici ty for passerine species as a data gap, for

which EPA intends to issue a data call-in.

4. Comment: “ABC strongly supports oxamyl to be test ed under the EDSP, specifically the Tier II avian 2-generation tests.”

Response: Oxamyl is among the group of 58 pestic ide active ingredients for which test

orders were issued under Tier 1 of the E ndocrine Disruptor Scr eening Program between October 2009 and February 2010. Oxamyl orde rs were issued on November 12, 2009. The Agency reviewed the “Other Scientifically Re levant Information” submitted by DuPont and

determined that DuPont needs to conduct all Tier 1 assays. Once the Agency has received and reviewed all relevant data, including the Tier 1 results, the Agency will determine which, if any, of the Tier 2 tests are required.

5. Comment: “ABC requests an avian reproductive and de velopmental study using a passerine species... Passerine species are altricial birds, and hatch at a very di fferent developmental stage than precocial mallards and bobwhite quail... The differences in embryonic development between altricial and precocial bird s could potentially lead to differences in sensitivity to pesticides...”10 Response: EPA is not aware of any data to show that oxamyl is more toxic to passerine species than it is to the bobw hite quail or mallard ducks on an acute or chronic exposure basis as it relates to reproduc tive endpoints. The Agency be lieves that the data from reproductive studies in the bobwhite quail and mallard duck studies will be adequate for assessing potential risks to bird s from chronic oxamyl exposure. Further, EPA does not have a validated protocol for a chroni c reproduction study in passerines.

Comments submitted by the Physicians Comm ittee for Responsible Medicine (PCRM) in EPA-HQ-OPP-2010-0028-0013.1.

For additional details regarding EPA’s response, please refer to the document “EFED Response to Comments on Preliminary Work Plan for Oxamyl,” dated January 20, 2011, included in the oxamyl registration review docket (EPA-OPP-2010-0028).

6. Comment: “We strongly support the use of the newl y revised OECD Test Guideline 223 for the acute avian oral toxicity test, which has been adopted by the OECD.”

Response: At this time, EPA is actively evaluati ng the results of the OECD validation report

to determine if the OECD TG 223 effect s endpoints and dose/response information adequately address the purposes of the avian ac ute oral data requireme nt as described in 40

CFR Part 158. Until EPA’s evaluation of that validation report is complete, EPA will not classify avian toxicity studies conducted us ing the TG 223 protocol, and the studies cannot be used to fulfill data requirements.

Comments submitted by DuPont Crop Protection in EPA-HQ-OPP-2010-0028-0014.1.

7. Comment: DuPont indicated that they intend to address the data requirements that EPA plans to call-in through the registration review pr ocess. DuPont also stated that they will provide the most current and relevant info rmation to EPA on topics such as label information, mode of action, or use and us age data to allow the Agency to conduct human health and ecological risk assessments.

Response: EPA thanks DuPont for stating their inte ntion with regard to the data call-in and

additional useful information.

8. Comment: “DuPont is working with the Agency to address the concerns raised in the occupational exposure assessment.”

Response: As was stated in the “Updates Sin ce the Summary Document” section of this Final Work Plan, EPA is working with DuPont to mitigate dietary and occupational risks of concern identified in the 2010 dietary and occupational risk assessments.

9. Comment: “DuPont’s Guideline 830.7050 UV/Visib le Absorption study (MRID 45510101) has been reviewed by the Agency (DP Barcode 382386), found to be acceptable, and fulfills this data requirement.”11 Response: EPA agrees with this statement and transmitted the Data Evaluation Record to DuPont on October 20, 2010.

Summary of Data Gaps – Oxamyl:

The table below summarizes all data needs for oxamyl as listed in the Registration Review: Preliminary Problem Formula tion for Environmental Fate , Ecological Risk, Endangered Species, and Drinking Water Exposure Assessments for Oxamyl , dated July 28, 2010, and the Oxamyl: Registration Review Scoping Do cument for Human Health Assessments , dated August 18, 2010.

Guideline

Number Data Requirement Test

Material Estimated

Timeframe

(months)

835.4400 Anaerobic aquatic metabolism TGAI 24
850.1025 Acute toxicity estuarin e and marine organisms 3 TGAI 12
850.1035 Acute toxicity estuarin e and marine organisms 4 TGAI 12
850.1350 Aquatic invertebrate life cycle, saltwater 5 TGAI 12
850.1400 Fish early life stage, saltwater fish 6 TGAI 12
850.2100 Avian oral toxicity 7 TGAI 12
850.3040 Field testing for pollinators TEP 24

850.4100 Seedling emergence, terrestri al plant toxicity (Tier II) TEP 12

850.4150 Vegetative vigor, terrestrial plant toxicity (Tier II) TEP 12
850.4400 Aquatic plant growth, vascul ar plants (Tier II) TEP 12
870.7800 Immunotoxicity Study TGAI 12

Next Steps:

As noted previously, the Agency plans to requ ire several ecological e ffects and human health studies through a data call-in, expected to be issu ed in late 2011. This new information will be used to conduct complete risk assessme nts for all registered uses of oxamyl.

Additionally, EPA will continue to work with Du Pont to mitigate dietary and occupational risks of concern identified in the 2010 dietary and occupational risk assessments.

3 Acute toxicity data should be submitted where Eastern oysters are exposed to TGAI oxamyl.

4 Acute toxicity data should be submitted where mysid shrimp are exposed to TGAI oxamyl.

5 Life cycle toxicity data should be submitted for the mysid shrimp.

6 The Oxamyl Summary Document for Registration Review in correctly stated that Guid eline 850.4100 was required for freshwater fish. That was in error, and EPA is requiri ng the fish early life stage st udy for the saltwater species.

7 A passerine study protocol must be submitted for revi ew by the Agency prior to initiation of this study.