Docket Number: EPA-HQ-OPP-2011-0865 www.regulations.gov



## Clothianidin Summary Document Registration Review: Initial Docket

December 20113 of 15 

### TABLE OF CONTENTS

I. Preliminary Work Plan (PWP) 4

II. Fact Sheet 11

________________________________________



### Please Note

This Preliminary Work Plan (and Fact Sheet ) summarizes the Environmental Protection Agency's current position on clothian idin based on the following documents:

1. Registration Review: Problem Formulation fo r the Environmental Fate and Ecological Risk, Endangered Species, and Drinking Wate r Exposure Assessments of Clothianidin. December 13, 2011.

2. Clothianidin. Human Health Risk Scoping Docu ment in Support of Registration Review. December 8, 2011.

3. Clothianidin: Review of Hu man Incidents. July 21, 2011.

4. BEAD Chemical Profile for Registration Re view: Clothianidin (044309). December 14,

2011.

5. Screening Level Use Analysis (SL UA) for Clothianidin. April 18, 2011.

6. Appendix A for Clothianidin. June 23, 2011.

Supporting documents for clothianidin may be found in the docket (EPA-HQ-OPP-2011-0865)

located on the internet at www.regulations.gov

.4 of 15 I. Preliminary Work Plan – Clothianidin

Introduction:

The Food Quality Protection Act (FQP A) of 1996 mandated a registration review program. All pesticides sold or distributed in the United States (U.S.) generall y must be registered by the Environmental Protection Agency (EPA or the Ag ency), based on scientific data showing that they will not cause unreasonable ri sks to human health or the environment when used as directed on product labeling. The registration review program is intended to ma ke sure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory standard of no unreasonabl e adverse effects to human health or the environment. Changes in science, public policy, and pesticide use practices will occur over time. Through the registration review prog ram, the Agency periodically r eevaluates pesticides to make sure that as change occurs, products in the mark etplace can be used safely. Information on this program is provided at: http://www. epa.gov/oppsrrd1/registration_review/.

The Agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), a nd will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. The Agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the Agency’s opportunity to state whatit knows about the pesticide and what additional risk analyses and data or information it belie ves are needed to make a registration review decision. After reviewing and responding to co mments and data received in the docket during this initial comment period, the Agency will de velop and commit to a final work plan and schedule for the registration review of clothianidin.

Clothianidin is a broad-spectrum, systemic neonico tinoid insecticide registered for use to control chewing and sucking pests on a number of row and tr ee crops and turf. It is also registered for use in poultry houses and recreatio nal and residential settings. Clothianidin induces paralysis and death in insects by enhanci ng nicotinic acetylcholine receptor activity. Clothianidin is a degradate of thiamethoxam that is also going through the registration review process (Case # 7614). Products containing clothian idin were first registered in 2003 and, therefore, clothianidin was not subject to reregistration.

Anticipated Risk Assessment and Data Needs:

The Agency anticipates conducting a comprehens ive ecological risk assessment, including an endangered species assessment, and a revised hu man health risk assessment for all uses of clothianidin. The following is a summary of the issues relevant to the registration review of

clothianidin.5 of 15 Ecological Risk:

 The most recent ecological risk assessment for clothianidin was completed in 2010 in support of the registration of clothianidin for use as seed treatments on mustard and

cotton.

 The Agency has not conducted a risk asse ssment that supports a complete endangered species determination for clothianidin. Th e ecological risk assessment planned during registration review will allow the Agency to determine whether clothianidin’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 U.S. Fish and Wildlife Service and/or National Marine Fisheries Service (the Services), as appropriate.

 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, agains t the EPA for allegedly failing to undergo

consultation with the United States Fish a nd Wildlife Service and the National Marine Fisheries Service regarding th e effects of over 350 pesticides , including clothianidin, on over 200 endangered and threatened species throughout the United States (Center for Biological Diversity, et al. v. EP A, et al., No. C 11-00293 (N.D.Cal.)

.

 Previous risk assessments have assessed most major and minor degradates and the Agency concluded that they are expected to be as toxic or less toxic than parent clothianidin. Uncertainty regarding the clot hianidin degradates thiazolylmethylguanidine (TMG) and N -(2-Chloro-5-thiazolylmethyl)- N’ -nitroguanidine (TZNG) remain and the Agency anticipates requiring data on these degradates to suppor t registration review.

 The environmental fate and effects database is largely complete for clothianidin with the exception of effects data on avian and te rrestrial invertebrate species.

 Based upon the use pattern and the current avai lable database on clothianidin, the Agency anticipates requiring the following ecologica l effects data for use in conducting a complete ecological risk assessment, includ ing an endangered species assessment.

GLN 850.2100 Acute avian oral toxicity for passerines

GLN 850.3030 Honey bee toxicity of residues on foliage (TEP)

GLN 850.3040 Field testing for pollinators (TEP)

GLN 835.6200 Aquatic field dissipation (In Review)6 of 15 Non-Guideline Pollinator larval toxicity

Non-Guideline Laboratory pollinator feeding study

Non-Guideline Residues in pollen a nd nectar/field residue analysis study

Non-Guideline Chronic sediment toxicity test with midge larvae (with TGAI and the degradates TZNG and TMG) Non-Guideline Poultry litter residue study

 The Agency is interested in receiving informa tion or data that char acterizes the potential exposure that may result from drift associ ated with pesticide products containing

clothianidin. This should include informa tion on non-traditional ro utes of exposure (e.g. dust drift from seed treatment planting operati ons. The Agency is also interested in receiving information or data on drift reducing technologies or other pr actices that reduce potential drift from both spray applicati ons and seed treatments of clothianidin.

 In an attempt to address protection of pollin ators and other beneficial insects, EPA is anticipating requiring data to assess bees as a representative for all beneficial insects. In moving forward with addressing potential risk to these organisms, EPA will consider the recommendations of the Society of Envir onmental Toxicology and Chemistry (SETAC) Workshop on Pesticide Risk Assessment for Pol linators, and is working with its federal and state partners, industry, and academia to determine appropriate assessment methodology. For compounds, such as clothianid in, which (1) show acute toxicity to bees and (2) have exposure routes for b ees, EPA anticipates requiring toxicity and exposure studies to allow for evaluation of ri sks to pollinators. The registrant should

consult with EPA on the c onduct of these studies.

 Please refer to the document, Registration Review: Problem Formulation for the Environmental Fate and Ecological Risk , Endangered Species, and Drinking Water Exposure Assessments of Clothianidin , dated December 13, 2011, located in the docket for a detailed discussion of the anticip ated risk assessment and data needs.

Human Health Risk:

 The most recent comprehensive human health risk assessment for clothianidin was completed in 2009 to support new use registrations on berries, Brassica vegetables, cotton, cucurbits, fig, fruiting vegetables, l eafy vegetables, peach, pomegranate, soybean, tree nuts, and tuberous and corm vegetables.

 The human health toxicity database is la rgely complete. The Agency anticipates requiring the following data for use in th e registration review of clothianidin:

GLN 870.3465 90 day inhalation toxicity7 of 15 GLN 875.2100 Turf transferable residue study

Special Study Residue chemistry comparisons of different

formulations on select commodities

 Side-by-side trials comparing residues from the WDG and SC formulations for leafy vegetables, Brassica vegetables, non-bell peppers. Furthermore, HED determined that side-by-side trials were needed to demonstrate the effect of spray mix adjuvants on residue

levels.

 Side-by-side trials comparing residues from foliar and soil applications to leaf lettuce, mustard greens, peppers,

and cucumbers.

 For the human health risk assessment, the re sidue of concern for the dietary assessment ( i.e. , drinking water) is parent clothianidin. The Agency an ticipates updating the dietary risk assessment for clothianidin to incorporate any changes in policy.

 The Agency anticipates conducting a new resi dential exposure assessment to incorporate changes in policy and to incorporate new data fr om the turf transferab le residue study that is expected to be required.

 The Agency anticipates calculating new aggreg ate risk estimates during this registration review if residential exposure estimates are revised.

 In addition to the dermal and oral hand- to-mouth residential exposure assessments, residential bystander inhalati on exposures resulting from of f-site transport (e.g., spray drift or volatilization) may occu r as a result of applications of clothianidin. The Agency is in the process of examining its policies and processes regarding assessment of these types of residential exposures. Therefore, the potential ne ed for a bystander inhalation risk assessment for clothianidin will be examined during registration review.

 The Agency anticipates updating the occupa tional handler and pos t application risk assessment, especially for seed treatment us es, to incorporate cha nges in policy and new agricultural transfer coefficients.

 The tolerance expression for cl othianidin will be reviewed during registration review to ensure that it appropriately c overs the metabolites and degradat es of clothianidin and that it specifies the residues to be measured for each commodity.

 The Agency will modify tolerance levels as needed, and work to harmonize tolerances/maximum residue limits (MRL), wh ere possible, in key export markets during registration review.8 of 15  Please refer to the document, Clothianidin. Human Health Assessment Scoping document in Support of Registration Review, dated December 8, 2011, located in the docket for a

detailed discussion of the an ticipated risk assessment and data needs for human health.

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 e ndpoints 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 most recent registration decision for clothianidin, EPA

reviewed these data and select ed the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), clothianidin is subject to the endocrine screening part of th e Endocrine Disruptor Screening 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 screening 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 pestic ide active ingredients and 9 inert ingredients. Clothianidin is not among the group of 58 pesticide active ingredient s on the initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issu e future EDSP orders/data callins, requiring the submission of EDSP screening assays for clothianidin. For further information on the status of the EDSP, the policies and procedur es, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screen ing battery, please visit our website: http://www.epa.gov/endo/

.9 of 15 Timeline:

EPA has created the following estimated timeline for the completion of the clothianidin registration review:
Registration Review for clothianidin – Projected Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and Public Comment Period 2011 – December Close Public Comment 2012 – February Case Development Final Work Plan 2012 – May

Issue DCI 2013 – Jan. – March

Data Submission 2016 – Jan. – March Open Public Comment Period for Draft Risk Assessments 2017 – July – Sept.

Close Public Comment Period 2017 – Oct. – Dec. Registration Review Decision Open Public Comment Period for Proposed Registration Review

Decision 2018 – Jan. – March

Close Public Comment Period 2018 – April – June Registration Review Decision and Begin Post-Decision Follow-up 2018 Total (years) 7

Guidance for Commenters:

The public is invited to comment on EPA’s preliminary work plan and rationale. The Agency will carefully consider all comments as well as any additional information or data provided in a timely manner prior to issuing a fi nal work plan for clothianidin.

Trade Irritants:

Through the registration review process, the Ag ency intends to solicit information on trade irritants and, to the extent feas ible, take steps toward facilitating irritant resolution. Growers and other stakeholders are asked to comment on any tr ade irritant issues resulting from lack of Maximum Residue Limits (MRLs) or disparitie s between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible regarding the na ture of the concern.

Water Quality:

Clothianidin is not identified as a cause of impairment for an y water bodies listed as impaired under section 303(d) of the Clean Water Act 1 . No Total Maximum Daily Load (TMDL) criteria have been developed for clothianidin 2 . More information on impaired water bodies and TMDLs

1 http://iaspub.epa.gov/tmdl_waters10/attains _nation_cy.cause_detail_30 3d?p_cause_group_id=885

2 http://iaspub.epa.gov/tmdl_waters10/attain s_nation.tmdl_pollutant_detail ?p_pollutant_group_id=885&p_ pollutant_group_name=PESTIC IDES10 of 15 can be found at the Agency’s website 3 . The Agency invites submissi on of water quality data for this pesticide. To the extent possible, data s hould conform to the qual ity standards in Appendix

A of the OPP Standard Operating Procedure: Inclus ion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Re view Risk Assessment and Management Process 4 in order to ensure they can be us ed quantitatively or qua litatively in pesticide risk assessments.

Environmental Justice:

EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation, and enforcement of environmental laws, regulati ons, and policies. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a result of thei r location, cultural practices, or other factors, may have atypical, unusually high exposure to clothianid in, compared to the ge neral population. Please comment if you are aware of any sub-populatio ns that may have atypical, unusually high exposure compared to th e general population.

Other Information:

Stakeholders are also specifically asked to prov ide information and data that will assist the Agency in refining the ecological and human h ealth risk assessments, including any speciesspecific effects determinations. The Agency is interested in receiving the following information:

1. suggestions from stakeholders on ways to reduce non-target organism exposures to

clothianidin

2. confirmation on the following label information

a. maximum application rates

b. geographic limitations on use

c. label language that specifies the method of incorporation to seed

3. use or potential use distri bution (e.g., acreage and geogr aphical distribution of relevant crop)

4. use history

5. median and 90 th percentile reported use rates (lbs. a.i./acre) from usage data – national, state, and county

6. application timing (date of first applica tion and application intervals) by crop – national, state and municipality

7. sub-municipality crop location data

8. directly acquired municipali ty-level usage data (not de rived from state level data)

a. maximum reported use rate (lbs. a.i. /acre) from usage data – county

b. percent crop treated – county

c. median and 90 th percentile number of applications – county

d. total pounds per year – county

e. the year the pesticide was last us ed in the county/sub-county area

3 http://www.epa.gov/owow/tmdl/

4 http://www.epa.gov/oppsrrd1/registra tion_review/water_quality_sop.htm11 of 15 f. the years in which the pesticide was applied in the county/sub-county area

9. state or local use restrictions

10. ecological incidents (non-target plant dama ge and avian, fish, reptilian, amphibian and mammalian mortalities) not already reported to the Agency

11. monitoring data

12. seasonal application rate limits and reapplication intervals for some labeled uses

13. usage data associated with clothianidin us e on ornamental plants and turf. Requested usage data should include use site, applica tion rate on a per acre basis, application method, timing of application, acres/area treated, and regist ered alternative

insecticides

14. data that characterizes the potential exposure that may result from dust associated with seed treatment products

15. data or information that ch aracterizes either practices or technology that reduces potential exposure from spray drift or “dust off” from seed treated with clothianidin

16. data or information on re sistance to clothianidin

Next Steps:

After the 60-day comment period closes, the Ag ency will review and respond to any comments received in a timely manner, and then issue it s Final Work Plan (FWP) for the registration

review of clothianidin.12 of 15 II. FACT SHEET

Background Information :

 Clothianidin PC Code: 044309, CAS#: 210880-92-5

 Technical registrant: Valent USA Co rporation (EPA Company Number 59639)

 First registered in 2003 and therefore was not subject to reregistration.

 There are 29 active FIFRA section 3 registrati ons (technical and end use) and 2 (special local need) section 24 (c) registrations.

 Tolerances for residues of clothianidin in or on a number of vegetables, fruits, and nuts

and livestock feed and food commodities are codified in 40 CFR § 180.586.

 Pesticide Re-evaluation Divi sion Chemical Review Manager (CRM): Russell Wasem, wasem.russell@epa.gov

 Registration Division Product Ma nager (PM): Venus Eagle, eagle.venus@epa.gov

Use & Usage Information: (For additional details, please refer to the BEAD Chemical Profile for Registration R eview: Clothianidin , dated December 14, 2011, and Appendix A document, dated June 23, 2011, in the clothianidin docket.)

 Clothianidin is a broad-spectrum, systemic neonicotinoid insecticide registered for use to control chewing and sucking pests on vari ous food sites including pome fruits, stone fruits, citrus fruits, fruiting vegetables, cucurbit vegetables , cranberries, artichokes, and leafy vegetables, in poult ry houses, and on turf.

 Major usage of clothianidin is on corn with 700,000 lbs active ingredient applied annually.

 Clothianidin is formulated as an emulsifiable concentrate, ready-to-use solution, flowable concentrate, soluble concentrate, dust, water-dispersible gran ule, and granule.

 Clothianidin is applied folia rly, through soil drench, tree trunk injection, and seed

treatments.

Recent Actions:

 There are three pending new use registrations for clothianidin use as a seed treatment on leafy green vegetables and rice a nd as a foliar treatment for rice.

 In 2011, new uses were registered for mustard and cotton seed treatments and as a trunk spray on ornamental trees.

 In 2010, clothianidin was registered for use on berries, Brassica vegetables, cotton, cucurbit vegetables, fig, fruiting vegetables, leafy green vegetables, peach, pomegranate, soybean, tree nuts, and tube rous and corm vegetables.13 of 15 Ecological Risk Assessment Status:

The following are key findings of the most recent cl othianidin ecological risk assessment. Please

refer to the Registration Review: Problem Formula tion for the Environmental Fate and Ecological Risk, Endangered Species, and Dr inking Water Exposur e Assessments of
Clothianidin

, dated December 13, 2011, for additional details.

 The most recent comprehensive ecological risk assessment for clothianidin was completed in 2010 in support of the registration of clothianidin as a seed treatment for

mustard and cotton.

 The Agency concluded that risks exceeded the level of concern (LOC) for freshwater invertebrates, estuarine/marine invertebrate s, birds, and mammals. Although the Agency did not quantitatively assess risk for non-ta rget terrestrial inve rtebrates in the 2010 assessment, information from standard tests, field studies, and inci dent reports suggest the potential for long-term toxic risks to honey bees and other be neficial insects.

Human Health Risk Assessment Status:

The following are key findings of the most recent clothianidin human health risk assessment.

Please refer to the Clothianidin. Human Health Assessment Scoping Document in Support of Registration Review , dated December 8, 2011, for additional detail.

Hazard Characterization:

 The most recent human health risk assessmen t for clothianidin was completed in 2009 when clothianidin was registered for use on berries, Brassica vegetables, cotton, cucurbit vegetables, fig, fruiting vegeta bles, leafy green vegetables , peach, pomegranate, soybean, tree nuts, and tuberous and corm vegetables. Clothianidin causes decreased body weight gain, delayed sexual maturation and decreased thymus weights.

 The Agency classified clothian idin as not likely to be carcinogenic to humans and determined that clothianidin is not mutagenic.

Dietary (Food and Drinking Water):

 The Agency concluded that dietary risk es timates were below the Agency’s level of

concern for all durations and population subgroups.

Residential:

 EPA concluded that residential risk estimates were below the Agency’s level of concern

for all scenarios and all population subgroups.14 of 15 Aggregate:

 Aggregate risk estimates (combined exposure from food, drinking wate r, and residential uses) were also below the Agency’s leve l of concern for al l population subgroups.

Occupational:

 Occupational handler and post-application expos ure risks for all applicable scenarios, were below the Agency’s level of concern w ith a single layer of clothing or with the addition of personal protective equi pment or engineering controls.

Human Studies:

 Past clothianidin risk assessments rely in pa rt on data from studies in which adult human subjects were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. Many such studies, invo lving exposure to many different pesticides, comprise generic pesticide exposure database s such as the Pestic ide Handlers Exposure Database (PHED) and the Agricultural Reen try Task Force (ARTF) Database. EPA has reviewed all the studies supporting these multi- pesticide generic exposure databases, and has found no clear and convincing evidence that the conduct of any of them was either fundamentally unethical or significantly deficient relativ e to the ethical standards prevailing at the time the research was conducte d. All applicable re quirements of EPA’s

Rule for the Protection of Hu man Subjects of Research ( 40 CFR Part 26) have been satisfied, and there is no regulatory barri er to continued reli ance on these studies.

Cumulative

 The most sensitive toxicological effect in mammals differs across the neonicotinoids. There is currently no evidence to indicate th at neonicotinoids share common mechanisms of toxicity, and EPA is not following a cu mulative risk approach based on a common mechanism of toxicity for the neonicotinoids. The Agency does not have other data that

indicate clothianidin shares a common m echanism of toxicity with other chemical substances. If, in the future, new informa tion on clothianidin is available that could potentially impact a cumulative risk assessment and result in a risk of concern, the Agency will revisit the need for a cumulative risk assessment.

Incidents:

 The Office of Pesticide Programs Incident Data System (IDS) was reviewed for reports

of clothianidin human incidents. From 2006 to 2011, there were 25 incidents involving products containing clothianidin—a ll incidents were minor or of moderate severity. The Agency will continue to monitor huma n health incidents for clothianidin.

 A review of the Agency’s Ecological Incident Information System (EIIS) identified one ecological incident attributed to clothianidin. The incident occurred in 2008 in Germany15 of 15 and involved approximately 11,000 honeybee co lonies. A review of the Avian Monitoring Information System (AIMS), whic h is maintained by the American Bird Conservancy, did not identify any bird incide nts associated with clothianidin. The Agency will continue to m onitor ecological incidents fo r clothianidin. Other bee incidents were reported in aggregate format, however neither the legality of use or the probability that clothianidin caused th ese incidents has been determined.

Status of Data Call-Ins (DCIs):

 There have been no data call-in no tices issued for clothianidin.

Tolerances and International Harmonization:

 Tolerances are established under 40 CF R 180.586 for residues that result from agricultural uses. Also, tolerances for in advertent residues in/on animal feed and a temporary tolerance on rice (expires J une 23, 2012) exist for clothianidin.

 U.S. tolerances are harmonized with Canadi an MRLs but differ, in many cases, from

Codex MRLs.

Labels:

 The labels for clothianidin can be obtain ed from the Pesticide Product Label System (PPLS) website: http://oaspub.epa.gov/ pestlabl/ppls.home

.