2

Fenbuconazole Preliminary Work Plan – Table of Contents 

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

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

STATUTORY AND REGULATORY AUTHORITY ................................................................... 7

CHEMICAL FACTS ...................................................................................................................... 7

USE AND USAGE INFORMATION ............................................................................................ 8

RECENT ACTIONS ....................................................................................................................... 9

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW ................................ 9

TIMELINE .................................................................................................................................... 13

NEXT STEPS ............................................................................................................................... 13

Appendix – Additional Areas Considered in the Fenbuconazole Registration Review ........... 14

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 Environmental Fate,

Ecological Risk, Endangered Species, and Human Health Drinking Water Exposure

Assessments for Fenbuconazole. Wendel, Christina and Lin, James. December 2, 2015.

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

Review. Hansen, Linnea. December 14, 2015.

3. Fenbuconazole: Tier 1 (Scoping) Review of Human Incidents and Epidemiology. Evans,

Elizabeth and Recore, Shanna. September 1, 2015.

4. BEAD Chemical Profile (BCP) for Registration Review: Fenbuconazole (129011).

Chandgoyal, Tara; Prieto, Rafael A.; Lee, Andrew. December 3, 2015.

5. Fenbuconazole (129011) Screening level Usage Analysis (SLUA). April 28, 2015.
3

6. EFED Table 1 Report. March 18, 2015.

7. HED Master Label Report. March 18, 2015.

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

found in the docket EPA-HQ-OPP-2015-0716 at http://www.regulations.gov.
4

OVERVIEW

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

registration review (docket number EPA-HQ-OPP-2015-0716). Fenbuconazole is a broadspectrum systemic fungicide of the triazole (conazole) chemical class. It is currently registered 

for use on the following food/feed crops: almonds, apples, bananas, blueberries, citrus fruits 

(group 10), cranberries, pecans, peanuts, peppers, stone fruits (group 12), sugar beets and wheat. 

At present there are no registered residential uses. This Preliminary Work Plan (PWP) document 

explains what EPA's Office of Pesticide Programs knows about fenbuconazole, 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 fenbuconazole.

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 fenbuconazole and what types of new data or 

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

fenbuconazole. 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 fenbuconazole. 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 fenbuconazole. 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.
5

ANTICIPATED DATA NEEDS

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

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

Environmental Fate, Ecological Risk, Endangered Species, and Human Health Drinking Water 

Exposure Assessments for Fenbuconazole and Fenbuconazole. Human Health Assessment 

Scoping Document in Support of Registration Review.

Table 1: Anticipated Data Needs for the Fenbuconazole Registration Review

Guideline 

Number1 Study Title1

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

NonGuideline

Chronic Freshwater Sediment Testing 

(Hyalella azteca) TGAI 24

NonGuideline

Chronic Freshwater Sediment Testing 

(Chironomus dilutus) TGAI 24

NonGuideline

Chronic Estuarine/Marine Sediment Testing 

(Leptocheirus plumulosus)

TGAI 24

850.2100 Avian Acute Oral Toxicity with passerine 

species TGAI 12

NonGuideline 

(OECD 

TG 213) 

Adult honey bee acute oral toxicity TGAI 12

NonGuideline 

Adult honey bee chronic oral toxicity TGAI 12

NonGuideline 

(OECD 

TG 237)

Larval honey bee acute oral toxicity TGAI 12

NonGuideline 

Larval honey bee chronic oral toxicity TGAI 12

Nonguideline2Field trial measuring residues in pollen and 

nectar TEP 24

 

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 These studies are anticipated to be included in the DCI. However the need for the data will be determined by EPA 

based upon the results of the Tier 1 honey bee laboratory studies.
6

Table 1: Anticipated Data Needs for the Fenbuconazole Registration Review

Guideline 

Number1 Study Title1

Test Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

NonGuideline

OECD 

TG 752

Semi-field testing for pollinators (Tier II) TEP 24

OSCPP 

850.30402 Field testing for pollinators (Tier III) TEP 24

875.2100 Dislodgeable Foliar Residue3 TEP 24

Outstanding Data Requirements from Conditional Registration(s)4

850.4100 Terrestrial plant seedling emergence toxicity, 

cabbage only5 TEP 12

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

 

3 A dislodgeable foliar residue (DFR) study (EPA MRID 45250601) has been submitted to the Agency but has not 

yet been reviewed. Until the study has been reviewed and found to be acceptable, this will remain as an anticipated 

data requirement. 

4 The studies listed in this section were previously required as a condition of registration in July 2013 and are still 

outstanding. These studies will not be included in the anticipated Registration Review DCI because they are 

already required as a condition of registration.

5 A terrestrial plant seedling emergence toxicity study (EPA MRID 49760701) has been submitted to the Agency but 

has not yet been reviewed. Until the study has been reviewed and found to be acceptable, this will remain as an 

outstanding conditional data requirement
7

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.

6

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 fenbuconazole.

CHEMICAL FACTS

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

Table 2: Chemical Facts for Fenbuconazole

PC code 129011

Case Number 7012

CAS Number 114369-43-6

Year first registered 1995

Pesticide Type Fungicide

Chemical class Triazole

Reregistration Eligibility 

Decision (RED)

Because it was registered after November 1984, fenbuconazole 

was not subject to reregistration.

Tolerance Reassessment 

Eligibility Decision 

(TRED)

Not Applicable

 

6 http://www2.epa.gov/pesticide-reevaluation
8

Table 2: Chemical Facts for Fenbuconazole

Cumulative group Not applicable. Fenbuconazole has not been identified as a 

member of a cumulative group that shares a common mechanism 

of toxicity.

40 CFR Citation Tolerances for fenbuconazole are established in §180.480.

Dual-use Fenbuconazole 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 fenbuconazole.

Pesticide Re-evaluation 

Division, Chemical 

Review Manager

Nathan Sell, sell.nathan@epa.gov, (703) 347-8020 

Registration Division, 

Product Manager

Tony Kish, kish.tony@epa.gov, (703) 308-9443

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage information for fenbuconazole. Please see the BEAD 

Chemical Profile (BCP) for Registration Review: Fenbuconazole (129011) in the registration 

review docket for more details.

Table 3: Fenbuconazole Use and Usage Information

Summary of Use Broad-spectrum systemic fungicide of the triazole (conazole) 

chemical class. Fenbuconazole inhibits sterol demethylation in 

fungi, causing fungal cell wall collapse and inhibition of hyphal 

growth. These antifungal properties result in fungal disease 

control on various crops. 

Use Sites Agricultural: Citrus fruit (crop group 10), stone fruit (crop group 

12), almond, apple, banana, blueberry, cranberry, peanuts, pecan, 

pepper, sugar beet, and wheat. 

Not registered for non-agricultural uses. 

Summary of Usage Based on private market usage data from 2004-2008, 

fenbuconazole annual usage averaged 28,000 pounds of active 

ingredient (A.I.) treating an annual average of 300,000 acres, and 

an average application rate of 0.093 pounds A. I. per acre. 

For years 2009-2013, fenbuconazole annual usage averaged

36,000 pounds of A.I. treating an annual average of 350,000 

acres, and an overall average application rate of 0.103 pounds A. 

I. per acre.

The use of fenbuconazole, both in terms of pounds A. I. and total 

area treated (TAT), has been increasing since 2006.

Formulation Type(s) Flowable concentrate, and wettable powder in water soluble 

packets
9

Table 3: Fenbuconazole Use and Usage Information

Application Method(s) Applied by ground or aerial methods. 

Technical Registrant(s) Dow Agrosciences

No. of Registrations 4 Section 3 products7, 13 section 24(c) products

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.

 Information for its declining use on pecans since 2008 and increasing use on oranges. 

And information on its use specific to the following commodities: banana, pepper, 

blueberries, grapes and stone fruit.

 Confirmation of the following label information: sites of application; formulations;

application methods and equipment; maximum application rates; frequency of 

application, application intervals, and maximum number of applications per season; and 

geographic limitations on use.

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

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

and county.

 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).

 State or local use restrictions.

 Foreign technical registrants not listed above who supply technical fenbuconazole to the 

US market.

RECENT ACTIONS

There are no recent actions for fenbuconazole. 

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent comprehensive human health risk assessment for fenbuconazole was completed 

on January 31, 2013. The most recent ecological and environmental fate risk assessment was 

completed on April 29, 2008. Findings and conclusions from these risk assessments are 

summarized in the Registration Review: Preliminary Problem Formulation for Environmental 

Fate, Ecological Risk, Endangered Species, and Human Health Drinking Water Exposure 

Assessments for Fenbuconazole and Fenbuconazole. Human Health Assessment Scoping 

Document in Support of Registration Review.

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

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

 

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

(http://oaspub.epa.gov/pestlabl/ppls.home).
10

fenbuconazole. For human health, EPA anticipates the need to conduct revised dietary (food and 

drinking water) and occupational risk assessments during registration review. If 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 Scoping Document.
11

Table 4: Anticipated Risk Assessments for the Fenbuconazole 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

Incidents Will check for 

updates

For a discussion of reported ecological incidents for 

fenbuconazole, see page 61 of the Problem 

Formulation.

Human Health

Dietary

Food Yes The need for an updated dietary assessment for 

fenbuconazole will be considered during registration 

review and may be needed if new data are identified 

which impact dietary exposure estimates including 

those from drinking water; toxicological endpoints or 

points of departure are revised; and if there are any 

changes to the standard operating procedures or 

default exposure assumptions. 

It should be noted, that the Agency has previously 

assessed dietary risk from triazole-derived 

metabolites, 1-2,4-traizole and its conjugates 

triazolylanine and triazolyacetic acid, resulting from 

exposure to conazole fungicides (including 

fenbuconazole) as a group. The need for an updated 

dietary triazole assessment will be determined at the 

time of registration review. 

Drinking water Yes It’s anticipated that an updated drinking water 

assessment for fenbuconazole will be needed. 

It is also anticipated that an updated drinking water 

assessment will be needed for triazole-derived 

metabolites, 1-2,4-traizole and its conjugates 

triazolylanine and triazolyacetic acid.

Occupational

Handlers (mixers, loaders, 

applicators)

Yes Updated occupational handler exposure assessments 

are anticipated as being needed to reflect current 

policies, current data, and any updates to the toxicity 

database.
12

Post-application Yes Updated post-application exposure assessments are 

anticipated as being needed to reflect current 

policies, current data, and any updates to the toxicity 

database.

Residential

Handlers No Residential handler and post-application exposure 

assessments are not anticipated as being needed 

because there are currently no registered uses that 

allow for residential use or would result in residential 

exposer. 

However, the Agency will examine the need for 

spray drift and volatilization assessments based on 

potential exposure to bystanders from agricultural 

applications. 

Post-application

Other

Aggregate Y Evaluates the combined risk from food and drinking 

water. 

It’s anticipated that an updated aggregate assessment 

will be needed if a new dietary exposure assessment 

is conducted, and/or if there are changes in estimated 

drinking water concentrations.

It should be noted, that the Agency has previously 

assessed dietary risk from triazole-derived 

metabolites, 1-2,4-traizole and its conjugates 

triazolylanine and triazolyacetic acid, resulting from 

exposure to conazole fungicides (including 

fenbuconazole) as a group. The need for an updated 

aggregate triazole assessment will be determined at 

the time of registration review. 

Cumulative No Fenbuconazole has not been identified as a member 

of a cumulative group that shares a common 

mechanism of toxicity. 

There is currently no evidence to demonstrate that 

conazoles share common mechanisms of toxicity.

Tolerances Yes The Agency anticipates it will re-evaluate U.S. 

tolerances and will harmonize them with Codex 

Maximum Residue Levels (MRLs) to the extent 

possible. 

Incidents Will check for 

updates

For a discussion of reported human incidents for 

fenbuconazole, see page 11 of the Scoping 

Document and the Fenbuconazole: Tier 1 (Scoping) 

Review of Human Incidents and Epidemiology.
13

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 already reported to the Agency.

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

TIMELINE

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

registration review in Table 5 below.

Table 5: Projected Fenbuconazole 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 

Assessments8

2020 – January - March

Registration Review Decision

60-day Public Comment Period for Proposed 

Registration Review Decision

2020 – September - November

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 issue a Final Work Plan for the registration 

review of fenbuconazole.

 

8 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.
14

Appendix – Additional Areas Considered in the Fenbuconazole 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 particular 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 issues resulting from lack of MRLs 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:

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

under section 303(d) of the Clean Water Act.

9

 In addition, no Total Maximum Daily Loads 

(TMDL) have been developed for fenbuconazole.

10

 More information on impaired water bodies 

and TMDLs can be found at the Agency’s website.

11 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 Procedure: Inclusion of Impaired 

Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and 

Management Process12 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 fenbuconazole 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.

 

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

10http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant

_group_name=PESTICIDES

11 http://water.epa.gov/lawsregs/lawsguidance/cwa/tmdl/index.cfm

12 http://archive.epa.gov/pesticides/ppdc/web/pdf/session1-sop.pdf
15

ENDANGERED SPECIES:

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

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

will allow the Agency to determine whether use of fenbuconazole 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 fenbuconazole, 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), 

fenbuconazole is subject to the endocrine screening part of the Endocrine Disruptor Screening 

Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the Tier 2 tests are necessary based on the available data. Tier 2 

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between 

October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 

chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. A second list 

of chemicals identified for EDSP screening was published on June 14, 201313 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. 

 

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

chemicals.
16

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.14

HUMAN STUDIES:

Occupational

Past fenbuconazole 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) and the 

Agricultural Reentry 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 relative to the ethical standards prevailing at the time the research was conducted. All 

applicable requirements of EPA’s Rule for the Protection of Human Subjects of Research (40 

CFR Part 26) have been satisfied, and there is no regulatory barrier to continued reliance on 

these studies.

 

14 http://www.epa.gov/endocrine-disruption