2 

### Strychnine Preliminary Work Plan – Table of Contents

OVERVIEW ...................................................................................................................... ............. 3

ANTICIPATED DATA NEEDS .................................................................................................... 3

STATUTORY AND REGULATORY AUTHORITY ................................................................... 4

CHEMICAL FACTS ................................................................................................................ ...... 4

USE AND USAGE INFORMATION ............................................................................................ 5

RECENT ACTIONS ................................................................................................................ ....... 6

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW ................................ 6

TIMELINE ...................................................................................................................... ................ 9

NEXT STEPS .................................................................................................................... ............. 9 Appendix – Additional Areas Considered in the Strychnine Regi stration Review ...................... 10

References:

This Preliminary Work Plan summarizes the En vironmental Protection Agency's current position based on the following documents:

1. Problem Formulation in Support of the Regist ration Review for Strychnine (PC Code 076901)

. Nicholas Mastrota, James Wolf, and Rosanna Louie-Juzwiak. November 13,

2015.

2. Strychnine. Human Health Assessment Scoping Document in Support of Registration

Review . Jaime D’Agostino and Matthew Crowley. December 15, 2015.

3. Strychnine: Tier I (Scoping) Review of Human Incidents and Epidemiology . Shana Recore. November 17, 2015.

4. BEAD Chemical Profile for Registration Review: Strychnine Alkaloid (076901). Colwell Cook. July 24, 2015.

5. EFED Table 1 Report. Ingredient: Strychnine (076901). June 1, 2015.

6. HED Master Label Report. Ingredient: Strychnine (076901). June 1, 2015.

These and other supporting documents for the stry chnine registration revi ew case may be found in the docket EPA-HQ-OPP-2015-0754 at http://www.regulations.gov

.3 OVERVIEW

The docket for strychnine is now open, initia ting the first public comment period for this registration review (docket number EPA-HQ- OPP-2015-0754). Strychnine is an alkaloid compound registered for use as an active ingredie nt in rodenticide baits for vertebrate pest control. There are no registered food uses for stry chnine. Strychnine products are used primarily in underground burrows on residential lawns, pastures, rangeland, and cropland. This Preliminary Work Plan (PWP) document explai ns what EPA’s Office of Pesticide Programs knows about strychnine, highlighting anticipated data and assessment needs, identifying the types of information that would be especially useful to the Agen cy in conducting the review, and providing an anticipated timeline for completi ng the registration review for strychnine.

The registration review process was designed to include a publi c participation component to solicit input from interested stak eholders. The Agency intends, by sharing this information in the docket, to inform the public of what it knows abou t strychnine and what types of new data or other information would be helpful for the Agen cy to receive as it moves toward a decision on strychnine. The Agency encourages all interested stakeholders to review the PWP and Appendix and to provide comments and additional inform ation that will help the Agency’s decisionmaking process for this chemical. In addition to general areas on which persons may wish to comment, there are some areas identified in the PWP and Appendix about which the Agency specifically seeks comments and information. Interested stakeholders could include: environmental non-profit or interest groups; pe sticide manufacturers; agricultural labor or commodity groups; commercial, institutional, reside ntial, and other users of pesticides; or the public at large.

The Preliminary Work Plan begins by listing the anticipated data needs for strychnine. Next, it discusses the statutory and regul atory authority for Registration Review. Then the document provides chemical facts, use and usage info rmation, recent actions, the anticipated risk assessments, and a projected registration review timeline for strychnine. Finally, the Appendix to

this document includes identification and discussion of some areas that ar e considered generally in Registration Review along with some a dditional chemical case-specific information.

ANTICIPATED DATA NEEDS

Table 1 below summarizes anticipa ted data needs for strychnine. For additional discussion of the anticipated data needs, see the Problem Formulation in Support of the Registration Review for Strychnine (PC Code 076901) and Strychnine. Human Health Assessment Scoping Document in Support of Registration Review

.4 Table 1: Anticipated Data Needs for the Strychnine Registration Review

Guideline

Number Study Title Test

Material Estimated Timeframe

(Months from receipt of DCI)

Non-Guideline Subacute Inhalation Toxicity Study TGAI 24
TGAI = technical grade active ingredient

STATUTORY AND REGULATORY AUTHORITY

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All pesticides distributed or sold in the United Stat es (U.S.) generally 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 re view 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 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 on EPA’s website. 1

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 regulations governing registra tion review begin at 40 CFR 155.40. 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 what it knows about the pesticide and what additional risk analyses

and data or information it believes are needed to make a registrati on review decision. After reviewing and responding to comments and data received in the docke t during this initial comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for the registration review of strychnine.

CHEMICAL FACTS

Table 2 provides a summary of th e chemical facts for strychnine.

1 http://www2.epa.gov/pesticide-reevaluation5 Table 2: Chemical Facts for Strychnine

PC code 076901

Case Number 3133

CAS Number 57-24-9 Year first registered 1947 Pesticide Type Rodenticide

Chemical class Alkaloid Reregistration Eligibility Decision (RED) 1996

Tolerance Reassessment Eligibility Decision (TRED) Not applicable – there are no estab lished tolerances for strychnine.

Cumulative group Not applicable. Strychnine has not been identified as a member of a cumulative group that shares a common mechanism of toxicity. 40 CFR Citation There are no established tolerances for strychnine. Dual-use Strychnine is registered for conventional pesticidal uses only and has no registered antimicrobial or biopesticidal uses. Non-pesticidal uses There are no identif ied non-pesticidal uses of strychnine.

Pesticide Re-evaluation Division, Chemical Review Manager Susan Bartow, bartow.susan@epa.gov, 703-603-0065

Registration Division, Product Manager Mark Suarez, Suarez.mark@epa.gov, 703-305-0120

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage information for strychnine. Please see the BEAD Chemical Profile for Registration Re view: Strychnine Alkaloid (076901) in the registration

review docket for more details.

Table 3: Strychnine Use and Usage Information

Summary of Use Strychnine is a rodenticide currently registered only for underground use to control pocket gophers, excep t in the state of Nevada where a special local need registration also allows its use to control the yellowbellied marmot and 3 species of ground squirrel. Use Sites Orchards, pastures, rangelands , agricultural crops, non-agricultural uncultivated areas, irrigation systems, and residential outdoor premises. Summary of Usage EPA has no availa ble usage data for strychnine. Formulation Type(s) Granular, pelleted/ta bleted, and ready-to-use solution/paste. Application Method(s) Products can be applied manually by spoon or bait dispensing probe or mechanically by “burrow builder” (which digs artificial tunnels) or an impinger (which “injects” bait into the animals tunnel). Technical Registrant(s) Fort Dodge Chemical Company and H Interdonati Inc. No. of Registrations 18 Section 3 products 2 and 1 section 24(c) product. Restricted Use All strychnine products, except for those products which contain strychnine at nominal concentrati ons no greater than 0.5% and which

2 Section 3 product labels can be obtained from th e Pesticide Product Label System (PPLS) website

(http://oaspub.epa.gov/pestlabl/ppls.home).6 Table 3: Strychnine Use and Usage Information

are limited by their labels to manua l below-ground applications, were classified as restricted use by the Ag ency in 1978. Currently there are 10 section 3 products and 1 section 24(c) product classified as restricted use pesticides.

Guidance for Commenters: Additional areas of use and usage related information requested for this registration review, and of part icular interest to EPA, are described below.

 Information on why strychnine is select ed rather than other rodenticides.

 Descriptions of where, when, and how strychnine is used.

 Confirmation of the following label informati on: sites of application; formulations; application methods and equipment; maxi mum application rates; frequency of application, application intervals, and maxi mum number of applica tions per season; and geographic limitations on use.

 Use distribution ( e.g. , acreage and geographical distri bution of relevant use sites).

 Median and 90 th percentile reported use rates (lbs a i/A) from usage data – national, state, and county.

 Typical application timing (date of first applic ation and application in tervals) – national, state, and county.

 Usage/use information for non-agricultural uses.

 Typical application interval (days).

 State or local use restrictions.

 Foreign technical registrants not listed above who supply tech nical strychnine to the US

market.

RECENT ACTIONS

There are no recent actions for strychnine.

ANTICIPATED RISK ASSESSMENT S FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for strychnine was completed on January 22, 1996 in preparation for the Reregistrati on Eligibility. The most recent ecological risk assessment was completed 2009 to assess risk to three species inhabiti ng California that are federally listed as threatened or endangered spec ies—California red-legged frog, California tiger salamander, and the San Joaquin kit fox. Findings and conclusions from these risk assessments

are summarized in the Problem Formulation in Support of the Registration Review for Strychnine (PC Code 076901) and Strychnine. Human Health Assessment Scoping Document in Support of Registration Review.

During registration review, the Agency antici pates the need to conduct a comprehensive ecological risk assessment, including an enda ngered species assessment, for all uses of strychnine. For human health, EPA anticipates th e need to conduct a revised occupational risk assessment during registration review. In the pr evious RED, no endpoints were set due to the lack of toxicity studies available from which to identify endpoints. Sin ce the Agency plans to7 perform a quantitative occupati onal inhalation exposure assessment, an inhalation endpoint will be chosen during Registration Review. Any cha nges to the standard operating procedures or default exposure assumptions also will be considered in the new assessment.

Table 4 below summarizes the anticipated regi stration review risk assessments based on the

EFED Problem Formulation and HED Scoping Document.8 Table 4: Anticipated Risk Assessments for the Strychnine Registration Review

Type of Risk Assessment Conduct? Notes

Ecological and Environmental Fate Comprehensive ecological (species to be assessed include terrestrial and aquatic organisms), including endangered species Yes The risk assessment will focus on risk from primary exposure to non-target wildlife that consume strychnine bait, and secondary exposure to predators and scavengers that feed on small mammals (target and non-target) which feed on strychnine bait.

Incidents Will check for updates For a discussion of reported ecological incidents for strychnine, see page 10 of the Problem Formulation.

Human Health Dietary Food No Strychnine is a non-food use rodenticide and its limited and targeted underground uses do not warrant estimation of concentrations in drinking water; therefore, a dietary exposure assessment is not applicable. Drinking water No

Occupational Handlers (mixers, loaders, applicators) Yes Registration Review will include an inhalation occupational handler exposure assessment only. Based on the estimated low dermal absorption, a dermal exposure assessment will not be conducted. Exposures are anticipated to be short-term only; intermediate-term and chronic exposures are not expected. Post-application No No post-appli cation exposure assessment will be conducted. Due to strychnine’s formulation as a solid or paste and its targeted underground use, no inhalation exposure or dermal contact with residues are expected following applications.

Residential

Handlers No Residential handler assessments will not be conducted based on existing label requirements for clothing and

PPE. Post-application No A residential pos t-application exposure assessment will not be conducted because contact with or ingestion of residues is not expected due to the underground use. Exposure via drift or volatilization is not expected due to strychnine’s formulation as solids/pastes and its underground use.

Other Aggregate No Because strychnine is a non-food use rodenticide with limited and targeted underground uses, dietary and residential exposures are not expected. Cumulative No Unlike other pestic ides for which EPA has followed a cumulative risk approach based on a common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as to strychnine and any other substances and strychnine does not appear to produce a toxic metabolite produced by other substances.

Tolerances No There are no estab lished tolerances for strychnine.9 Incidents Will check for updates For a discussion of reported human incidents for strychnine, see page 8 of the Scoping Document and Strychnine: Tier I (Scoping) Review of Human Incidents and Epidemiology

.

Guidance for Commenters: Additional ecological information requested for this registration review, and of particular interest to EPA, is described below.

 Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not alr eady reported to the Agency.

 Water quality monitoring data (s ee Appendix for further details).

TIMELINE

EPA has created the following estimated time line for the completion of the strychnine registration review in Table 5 below.

Table 5: Projected Strychnine Registration Review Timeline

Activities Estimated Date Opening the Docket Open Docket and 60-day Public Comment Period 2015 December Close Public Comment 2016 February Case Development Final Work Plan 2016 May Issue DCI 2016 July - September Data Submission 2018 July - September 60-day Public Comment Period for Draft Risk Assessments 3 2020 January - March Registration Review Decision 60-day Public Comment Period for Proposed Registration

Review Decision 2020 October - December

Registration Review Decision and Begin Post-Decision Follow-up 2021

Total (years) 6

NEXT STEPS

After the 60-day public comment period closes , the Agency will review and respond to any comments received in a timely manner and then i ssue a Final Work Plan for the registration review of strychnine.

3 The regulations governing Registration Review generally require the Agency to provide a public comment period

of at least 30 calendar days for draft risk assessments; see 40 CFR Part 155.53(c). For conventional pesticides, the Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments.10 

### Appendix – Additional Areas Considere d in the Strychnine Registration

Review

PUBLIC COMMENTS AND FEEDBACK:

Guidance for Commenters: The areas below highlight topics of special interest to the Agency where your comments, data submi ssions, or reference to sources of additional information could be of particular use.

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. The Agency will work to harmonize tolerances and international maximum residue limits (MRLs) and may modify tolerance levels to do so, when possible. Growers and other stakeholders are asked to

comment on any trade irritant issues resulting from lack of MRLs or disparities between U.S. tolerances and MRLs in key export markets, provi ding as much specificity as possible regarding the nature of the concern. Because strychnine is not registered for food/feed uses in the U.S., it has no U.S. tolerances; therefore, the Agency does not anticipate any trade irritant issues for it.

Water Quality:

Strychnine is not identified as a cause of im pairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act. 4 In addition, no Total Maximum Daily Loads (TMDL) have been developed for strychnine. 5 More information on impaired water bodies and TMDLs can be found at the Agency’s website. 6 The Agency invites submission of water quality data for this pesticide. To the extent possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedur e: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Regist ration Review Risk Assessment and Management Process 7 in order to ensure they can be us ed quantitatively or qualitatively 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 strych nine compared to the general population. Please

4 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

5 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl _pollutant_detail?p_pollutant_group_id=885&p_pollutant_

group_name=PESTICIDES

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

7 http://www2.epa.gov/pesticide-reevaluation/opp-guidance- submission-state-and-tribal-water-quality-monitoringdata11 comment if you are aware of any sub-populations that may have atypical, unusually high exposure compared to the general population.

ENDANGERED SPECIES:

A risk assessment that supports a complete endangered species determination has not been conducted for strychnine. The ecolo gical risk assessment planned dur ing registration review will allow the Agency to determine whether use of strychnine has “no effect” or “may affect” federally listed threatened or endangered specie s (listed species) or their designated critical habitats. When an assessment concludes that a pes ticide’s use “may affect” a listed species or its designated critical habitat, the Agency will c onsult with the U.S. Fish and Wildlife Service

and/or National Marine Fisheries Service (the Se rvices), as appropriate.

A previous endangered species a ssessment was conducted for strychnine in 2009 to assess risk to three species inhabiting California that are federally listed as th reatened or endangered species: the California red-legged frog ( Rana aurora draytonii ), California tiger salamander ( Ambystoma californiense ), and the San Joaquin kit fox ( Vulpes macrotis mutica ). The assessment made a “Likely to Adversely Affect” conclusion for all three species because of potential direct and indirect adverse effects from strychnine exposur e due to labeled uses to control pocket gophers.

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 rere gistration decision for strychnine, 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), strychnine 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 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.12 Under FFDCA section 408(p), the Agency must scre en all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/dat a call-ins for the firs t group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredient s. A second list of chemicals identified for EDSP screening was published on June 14, 2013 8 and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists should be

construed as a list of known or likely endocrine disruptors.

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

website. 9

8 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of

chemicals.

9 http://www2.epa.gov/endocrine-disruption