Docket Number EPA-HQ-OPP-2014-0777 

www.regulations.gov 

Flonicamid Preliminary Work Plan 

Registration Review: Initial Docket 

Case Number 7436 

Approved by: 

Date: 

December 2014 

9z:.<-hcu.cl ;P "'1.-VL 1 J":> 

Richard P. Keigwin, Jr. 

Director 

Pesticide Re-evaluation Division 

... 

... 
Flonicamid Preliminary Work Plan- Table of Contents 

OVERVIEW ................................................................................................................................... 4 

ANTICIPATED DATA NEEDS .................................................................................................... 5 

STATUTORY AND REGULATORY AUTHORITY ................................................................... 6 

CHEMICAL FACTS .................... .................................................................................................. 6 

USE AND USAGE INFORMATION ............................................................................................ 7 

RECENT ACTIONS ......................................................................................... .............................. 8 

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW ....................... : ...... 10 

TIMELINE .................................................................................................................................... 11 

NEXT STEPS ............................................................................................................................... 12 

Appendix - Additional Areas Considered in the Flonicamid Registration Review ................. 13 

References: 

This Preliminary Work Plan summarizes the Environmental Protection Agency's current position 

based on the following documents: 

1. Registration Review - Preliminary Problem Formulation for the Ecological Risk 

Assessment and Drinking Water Exposure Assessment to be conducted for Flonicamid. 

Colleen M. Rossmeisl. November 24, 2014. 

2. Flonicamid Human Health Scoping Document in Support of Registration Review. Barry 

O'Keefe, Cassi Walls, Nancy Dodd, and Myron Ottley. November 25, 2014. 

3. Flonicamid: Tier I Review of Human Incidents. Sharma Recore. September 30, 2014. 

4. BEAD Chemical Profile (BCP) for Registration Review: Flonicamid. Colwell Cook, 

Rafael A. Prieto, and Elizabeth Hill. December 1, 2014. 

5. Flonicamid (128016) Screening Level Usage Analysis (SLUA). April23, 2014. 

2 
6. Flonicamid EFED Table 1 Report. June 17, 2014. 

7. Flonicamid HED Master Label Report. June 17, 2014. 

These and other supporting documents for the flonicamid registration review case may be found 

in the docket EPA-HQ-OPP-2014-0777 at http://www.regulations.gov. 

3 
OVERVIEW 

The docket for flonicamid is now open, initiating the first public comment period for this 

registration review (docket number EPA-HQ-OPP-2014-0777). Flonicamid is a systemic 

pyridinecarboxamide insecticide registered for use against many sap-feeding insects, such as 

aphids, whiteflies, leafhoppers, plant bugs, and thrips. There are numerous agricultural uses 

including pome fruits, stone fruits, tree nuts, berries, cotton, vegetables, legumes, and crops 

grown for oil: Flonicamid products are also registered for use on commercial ornamentals, 

interiorscapes, and nurseries, but are not allowed for use in residential settings. This Preliminary 

Work Plan (PWP) document explains what EPA's Office of Pesticide Programs knows about 

flonicamid, highlighting anticipated data and assessment needs, identifying the types of 

information that would be especially useful to the Agency in conducting the review, and 

providing an anticipated timeline for completing the registration review for flonicamid. 

The registration review process was designed to include a public -participation component to 

solicit input from interested stakeholders. The Agency intends, by sharing this information in the 

docket, to inform the public of what it knows about flonicamid and what types of new data or 

other information would be helpful for the Agency to receive as it moves toward a decision on 

flonicamid. The Agency encourages all interested stakeholders to review the PWP and 

Appendix and to provide comments and additional information that will help the Agency's 

decision-making 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; pesticide manufacturers; agricultural labor or 

commodity groups; commercial, institutional, residential, and other users of pesticides; or the 

public at large. 

The Preliminary Work Plan begins by listing the anticipated data needs for flonicamid. Next, it 

discusses the statutory and regulatory authority for Registration Review. Then the document 

provides chemical facts, use. and usage information, recent actions, the anticipated risk 

assessments, and a projected registration review timeline for flonicamid. Finally, the Appendix 

to this document includes identification and discussion of some areas that are considered 

generally in Registration Review along with some additional chemical case-specific information. 

4 
ANTICIPATED DATA NEEDS 

Table 1 below summarizes anticipated data needs for flonicamid. For additional discussion of 

the anticipated data needs, see the Registration Review- Preliminary Problem Formulation for 

the Ecological Risk Assessment and Drinking Water Exposure Assessment to be conducted for 

Flonicamid and the Flonicamid Human Health Scoping Document in Support of Registration 

Review which can be found in the docket EPA-HQ-OPP-2014-0777 at 

http://www.regulations.gov. 

Table 1: Anticipated Data Needs for the Flonicamid Registration Review 

Estimated 

Guideline Study Title1 Timeframe 

Number• Test Material (Months from 

receipt of DCI) 

850.6100 Environmental chemistry methods and associated TGAI 12 independent laboratory validation for water 

850.1010 Freshwater invertebrate acute toxicity2 TGAI 12 

850.1025 Acute toxicity estuarine and marine organisms TGAI 12 (oyster shell growth)2 

850.1035 Acute toxicity estuarine and marine organisms TGAI 12 (mysid)2 

850.2100 A vi an oral toxicity (passerine species) TGAI 12 

850.3020 Honey bee acute contact toxicity2 TGAI 12 

Non- Honey bee acute oral toxicity2 TGAI 12 guideline 

Non- Honey bee chronic oral toxicity2 TGAI 12 guideline 

Non- Honey bee larval acute toxicity2 TGAI 12 guideline 

Non- Honey bee larval chronic toxicity2 TGAI 12 guideline 

850.3030 Honey bee toxicity of residues on foliage2 TEP 12 

No"n- Honey bee Tier II, semi-field2 TGAI, TEP 24 

guideline 

850.4100 Terrestrial plant toxicity, seedling emergence TEP 12 

850.4150 Terrestrial plant toxicity, vegetative vigor TEP 12 

870.3465 28-day inhalation toxicity TGAI 24 

TGAI = technical grade active ingredient; TEP = typ1cal end-use product; 

1 On June 27, 2012, EPA announced certain revisions in harmonized guideline series 850 - Ecological Effects Tests 

- including renumbering and other designations or changes for some guideline studies. See "Final Test 

Guidelines; OCSPP 850 Series; Notice of Availability" 77 FR 38282, June 27, 2012. 

http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0154-0028 2 Study protocols should be submitted for evaluation, and will need to be potentially modified to capture the delayed 

mortality effects of flonicamid. 

5 
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 States (U.S.) generally must be registered by the 

Environmental Protection Agency (EPA or the Agency), based on scientific data showing that 

they will not cause unreasonable risks to human health or the environment when used as directed 

on product labeling. 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 of no unreasonable 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 program, the Agency periodically reevaluates pesticides to make 

sure that as change occurs, products in the marketplace can be used safely. Information on this 

program is provided on EPA's website.3 

The Agency is implementing the registration review program pursuant to Section 3(g) of the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review each registered 

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

registration. The regulations governing registration 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 registration review decision. After 

reviewing and responding to comments and data received in the docket during this initial 

comment period, the Agency will develop a Final Work Plan (FWP) and anticipated schedule for 

the registration review of flonicamid. 

CHEMICAL FACTS 

Table 2 provides a summary of the chemical facts for flonicamid. 

Table 2: Chemical Facts for Flonicamid 

PC code 128016 

Case Number 7436 

CAS Number 15 8062-67-0 

Year first registered 2003 

Pesticide Type Insecticide 

Chemical class pyridinecarboxamide 

Reregistration Eligibility Because it was registered after November 1984, flonicamid was 

Decision (RED) not subject to reregistration. 

Tolerance Reassessment Not applicable 

Eligibility Decision 

(TRED) 

3 http://www.epa.gov/oppsrrd 1/registration_review/ 

6 
Table 2: Chemical Facts for Flonicamid 

Cumulative group Not applicable. Flonicamid has not been identified as a member 

of a cumulative group that shares a common mechanism of 

toxicity. 

40 CFR Citation Tolerances for flonicarnid are established in 40 CFR §180.613. 

Dual-use Flonicarnid is registered for conventional pesticidal uses only and 

has no registered antimicrobial or biopesticidal uses. 

Non-pesticidal uses There are no identified non-pesticidal uses of flonicarnid. 

Pesticide Re-evaluation Ricardo Jones 

Division, Chemical J ones.ricardo@epa. gov 

Review Manager 703-347-0493 

Registration Division, Carmen Rodia 

Product Manager Rodia.carmen@epa.gov 

703-3060327 

USE AND USAGE INFORMATION 

Table 3 summarizes the use and usage information for flonicarnid. For more details please see 

the BEAD Chemical Profile (BCP) for Registration Review: Flonicamid which can be found in 

the docket EPA-HQ-OPP-2014-0777 at http://www.regulations.gov. 

Summary of Use 

Use Sites 

Summary of Usage 

Table 3: Flonicamid Use and Usage Information 

Systemic insecticide registered for use against many sap-feeding 

insects such as aphids, whiteflies, leafhoppers, plant bugs, and 

thrips. 

Flonicarnid products are often used as part of a broader integrated 

pest management strategy and can be used in rotation with other 

pesticides to reduce or delay resistance in target pests, especially 

in crops such as fruiting vegetables, leafy vegetables, celery, and 

carrots. 

Flonicarnid is registered for use on pome fruits, stone fruits, tree 

nuts, berries, hops, cot~on, vegetables (including leafy, fruiting, 

and root/tubers), legumes, and crops grown for oil. It is also 

registered for use on commercial ornamentals, interiorscapes, and 

nurseries. 

Based upon proprietary data, between 2006-2012, flonicarnid 

annual agricultural usage was approximately 19,000 pounds a.i., 

treating an average of260,000 acres. From 2004- 2012, the crop 

with the highest usage (in pounds a.i. applied per year) is cotton 

with 10,000 average pounds used per year. The next highest 

usage crops were potatoes (3,000 average pounds per year) then 

alfalfa, celery and lettuce with 1,000 pounds used each. 

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Table 3: Flonicamid Use and Usage Information 

Proprietary data available to EPA also reported about 50 pounds 

offlonicamid used on US ornamental and turf in 2012. 

Formulation. Type(s) Dry flowable, flowable concentrate, pressurized liquid, and 

emulsifiable concentrate. 

Application Method(s) Products can be applied by aerosol application, band treatment, 

broadcast, chemigation, dip treatment, directed spray, high 

volume spray (dilute), root treatment, seed treatment, soil drench 

treatment, soil in-furrow treatment, spot treatment, and spray. 

Technical Registrant(s) ISK Biosciences Corporation 

No. of Registrations 8 - Section 3 registrations and 12- 24C (Special Local Need) 

registrations4 

Restricted Use No 

Guidance for Commenters: Additional areas of use and usage related information 

requested for this registration review, and of particular interest to EPA, are described below. 

• The application rates included on the currently registered labels are on a per season/crop 

cycle basis. Information is needed on the number of applications of flonicamid that can 

be applied per calendar year, as several of the currently registered uses may result in 

multiple seasonal applications per year. 

• Site/crop specific information on the target pests, damage, economic thresholds, best time 

to treat, as well as alternatives to flonicamid. 

• Site/crop specific information on the formulation, application method, application rates, 

frequency of application, and timing of applications. . 

• Site/crop specific information on barriers of adopting chemical and non-chemical 

alternatives to flonicamid (e.g. price, efficacy, application methods, use restrictions, etc.). 

Typical application timing (date of first application and application intervals) - national, 

state, and county. 

• Usage/use information for non-agricultural uses. 

• Typical application interval (days) for non-agricultural uses offlonicamid. 

• State or local use restrictions. 

• Foreign technical registrants not listed above who supply technical flonicamid to the US 

market. 

RECENT ACTIONS 

In December 2013 new uses and tolerances were established for flonicamid inion alfalfa and 

clover grown for seed, mint, greenhouse grown tomatoes, and tree nuts (78 FR 75262). 

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW 

4 Section 3 product labels can be obtained from the Pesticide Product Label System (PPLS) website 

(http:/ /oaspub.epa.gov/pestlab 1/ppls. home). 

8 
The most recent comprehensive human health risk assessment for flonicamid was completed on 

August 20, 2013 for a new use request for alfalfa and clover grown for seed. The most recent 

ecological and environmental fate risk assessment was completed in 2013 for the same purpose. 

Findings and conclusions from these risk assessments are summarized in the Registration Review 

- Preliminary Problem Formulation for the Ecological Risk Assessment and Drinking Water 

Exposure Assessment to be conducted for Flonicamid and 2. Flonicamid Human Health Scoping 

Document in Support of Registration Review which can be found in the docket EPA-HQ-OPP2014-0777 at http://www.regulations.gov. · 

During registration review, the Agency anticipates the need to conduct a comprehensive 

ecological risk assessment, including an endangered species assessment, for all uses of 

flonicamid. For human health, EPA will examine the need for a bystander risk assessment, and 

does not anticipate the need to update or revise the post-application exposure analysis. However, 

any revision to the occupational handler assessment will be contingent upon the results from the 

subchronic inhalation study that is anticipated to be required. If other toxicological endpoints or 

points of departure are revised based on the data that are anticipated to be required for 

registration review, they will be considered in the new assessments, as well as any changes to the 

standard operating procedures or default exposure assumptions. 

Table 4 below summarizes the anticipated registration review risk assessments based on the 

EFED Problem Formulation and HED Seeping Document. 

9 
Table 4: Anticipated Risk Assessments for the Flonicamid Registration Review 

Type of Risk Assessment Conduct? Notes 

Ecolo~ical and Environmental Fate 

Comprehensive ecological y At this time, the planned ecological assessment will 

(species to be assessed focus largely on the identified uncertainties (i.e., for 

include terrestrial and aquatic passerines, terrestrial plants and terrestrial/aquatic 

organisms), including invertebrates) and the unique mechanism of action 

endangered species and delayed mortality identified with flonicamid. To 

the extent possible, the ecological risk assessment for 

registration review will rely on previous risk 

assessment analyses. A screening-level analysis of 

risk to endangered species will be completed as part 

of registration review. 

Incidents Will check for For a discussion of reported ecological incidents for 

updates flonicamid, see page 29 ofthe Problem Formulation. 

Human Health 

Dietary 

Food N An updated drinking water assessment may be 

conducted during registration review, which may 

impact the need to revise the dietary analysis. 

Drinking water y See above 

Occupational 

Handlers (mixers, loaders, N An updated or revised post-application exposure 

applicators) assessment is not anticipated at this time. However, if 

results from the subchronic inhalation ~tudy that is 

expected to be required change the endpoints and 

result in lower points of departure, then new 

occupational handler exposure and risk assessments 

may be needed. 

Post -application N See above 

Residential 

Handlers N There are no registered residential uses and no 

residential exposures are expected. 

Post-application y Residential bystander exposures resulting from offsite transport (i.e., spray drift or volatilization) may 

occur as a result of occupational applications of 

:flonicamid. The need for a bystander risk assessment 

for flonicamid will be considered during Registration 

Review. 

Other 

Aggregate N Since there are no residential uses an aggregate 

assessment for :flonicamid is not needed. 

Cumulative N EPA has not made a common mechanism of toxicity 

finding for :flonicamid. 

10 
Tolerances N There .are no CODEX MRLs, but there are several 

Canadian MRL's for flonicamid. Revisions or 

updates to flonicamid tolerances will be reviewed 

during registration review. 

Incidents Will check for For a discussion of reported human incidents for 

updates flonicamid, see page 8 of the Scoping Document and 

the Flonicamid: Tier I Review of Human Incidents. 

Guidance for Commenters: Additional ecological information requested for this 

registration review, and ofparticular interest to EPA, is described below. 

• Ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and 

mammalian mortalities) not already reported to the Agency. 

• Water quality monitoring data (see Appendix for further details). 

Guidance for Commenters: Additional human health information requested for this 

registration review, and of particular interest to EPA, is described below. 

• Human incidents not already reported to the Agency. 

TIME LINE 

EPA has created the following estimated timeline for the completion of the flonicamid 

registration review in Table 5 below. 

Table 5: Projected Flonicamid Registration Review Timeline 

Activities Estimated Date 

Opening the Docket 

Open Docket and 60-day Public Comment Period 2014 - December 

Close Public Comment 2015 - February 

Case Development 

Final Work Plan 2015- May 

Issue DCI 2015 July- Sept. 

Data Submission 2017 July - Sept. 

60-day Public Comment Period for Draft Risk 2019 Jan. - March 

Assessments5 

Registration Review Decision 

60-day Public Comment Period for Proposed 2019 Oct. - Dec. 

Registration Review Decision 

Registration Review Decision and Begin Post-Decision 2020 

Follow-up 

Total (years) 6 

5 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 l55.53(c). For conventional pesticides, the 

Agency plans to provide a 60 calendar day public comment period generally for draft risk assessments. 

11 
.. 

,, 

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 issue a Final Work Plan for the registration 

review of flonicamid . 

12 
Appendix - Additional Areas Considered in the Flonicamid Registration 

Review 

PUBLIC COMMENTS AND FEEDBACK: 

Guidance for Commenters: The areas below highlight topics of special interest to the Agency 

where your comments, data submissions, or reference to sources of additional information could 

be of partic.ular use. 

Trade Irritants: 

Through the registration review process, the Agency intends to solicit information on trade 

irritants and, to the extent feasible, 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 issu~s resulting from lack ofMRLs or disparities between U.S. 

tolerances and MRLs in key export markets, providing as much specificity as possible regarding 

the nature of the concern. 

Water Quality: 

Flonicarnid is not identified as a cause of impairment for any water bodies listed as impaired 

under section 303(d) ofthe Clean Water Act.6 In addition, no Total Maximum Daily Loads 

(TMDL) have been developed for flonicarnid.7 More information on impaired water bodies and 

TMDLs can be found at the Agency's website.8 The Agency invites submission ofwater 

quality data for this pesticide. To the extent possible, data should conform to the quality 

standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired · 

Water Body and Other Water Quality Data in OP P 's Registration Review Risk Assessment and 

Management Process9 in order to ensure they can be used quantitatively or qualitatively in 

pesticide risk assessments. 

Environmental Justice: 

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, implementation, 

and enforcement of environmental laws, regulations, 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 their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to flonicarnid compared to the general population. Please 

comment if you are aware of any sub-populations that may have atypical, unusually high 

exposure compared to the general population. 

6 http://iaspub.epa.gov/tmdl waterslO/attains nation cy.cause detail 303d?p cause group id=885 7http://iaspub.epa.gov/tmdl waters I 0/attains nation.tmdl pollutant detail?p pollutant group id=885&p pollutant 

group name=PESTICIDES 

8 http://www.epa.gov/owow/tmdl/ 9 http://www.epa.gov/oppsrrd !/registration review/water quality sop.htm 

13 
ENDANGERED SPECIES: 

A risk assessment that supports a ·complete endangered species determination has not been 

conducted for flonicamid. The ecological risk assessment planned during registration review 

will allow the Agency to determine whether use of flonicamid 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 · 

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

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 most recent registration decision for flonicamid, 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 ), flonicamid is 

subject to the endocrine screening part of the Endocrine Disrupter 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 theE, 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. A second list 

of chemicals identified for EDSP screening was published on June 14, 2013 10 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 disrupters. 

10 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-'009-0477-0074 for the final second list of 

chemicals. 

14 
For further information on the status of the EDSP, the policies and procedures, the lists of 

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website. 11 

HUMAN STUDIES: 

Past flonicamid risk assessments rely in part 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, involving exposure to many different pesticides, comprise generic pesticide 

exposure databases such as the Pesticide Handlers Exposure Database (PHED), the Agricultural 

Reentry Task Force (ARTF) Database, and the Outdoor Residential Exposure Task Force 

(ORETF) 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 relative to the ethical 

standards prevailing at the time the research was conducted. All applicable requirements of 

EPA's Rule for the Protection.ofHuman Subjects of Research (40 CFR Part 26) have been 

satisfied, and there is no regulatory barrier to continued reliance on these studies. 

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

15