2

Inorganic Polysulfides Preliminary Work Plan – Table of Contents

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

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

STATUTORY AND REGULATORY AUTHORITY................................................................... 5

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

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

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

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW................................ 8

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

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

Appendix – Additional Areas Considered in the Inorganic Polysulfides Registration Review13

References:

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

based on the following documents:

1. Combined Problem Formulation and Preliminary Risk Assessment in Support of the

Registration Review of Lime Sulfur. Milians, K.; Sayer, A. February 25, 2016.

2. Calcium Polysulfide. Draft Human Health Risk Assessment for Registration Review. 

Doherty, M. December 10, 2015.

3. Inorganic Polysulfides: Tier 1 (Scoping) Review of Human Incidents and Epidemiology. 

Recore, S; Evans, E. December 2, 2015.

4. BEAD Chemical Profile (BCP) for Registration Review: Inorganic Polysulfides (calcium 

polysulfide or lime sulfur) (076702). Chandgoyal, T.; Alsadek, J.; Berwald, D. February 

25, 2016.

5. Calcium Polysulfide (076702) Screening Level Usage Analysis (SLUA). July 15, 2015.
3

6. Lime Sulfur (076702) Label Data Report. July 14, 2015.

7. Lime Sulfur (076702) HED Master Label Report. July 14, 2015.

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

in the docket EPA-HQ-OPP-2016-0102 at http://www.regulations.gov.
4

OVERVIEW

The docket for inorganic polysulfides (PC code 076702, case number 4054, docket number EPAHQ-OPP-2016-0102) is now open, initiating the first public comment period for this registration 

review. The inorganic polysulfides case includes one active ingredient, calcium polysulfide. 

Calcium polysulfide is also known by various synonyms such as calcium sulfide and lime sulfur. 

Hereafter, this document will use the name lime sulfur. 

Lime sulfur is a pesticide active ingredient that primarily has fungicidal activity and also has 

secondary activity as an insecticide or acaricide. It is registered for conventional pesticide use to 

control powdery mildews, anthracnose, scab and other diseases, as well as spider mites. 

Registered use sites include almonds, apples, caneberries, cherries, citrus, hazelnuts, currants and 

gooseberries, bearing and non-bearing fruit trees, grapes, nectarines, peaches, pears, pecans,

pineapples, pistachios, plums/prunes, quince, ryegrass, red clover, and alfalfa. Lime sulfur is also 

registered for use on ornamental plants and for livestock use as an animal treatment on horses, 

cattle, sheep, and swine. There are no registered residential uses. 

This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticide Programs

knows about lime sulfur, 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 lime sulfur.

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 lime sulfur and what types of new data or 

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

lime sulfur. 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 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; 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 lime sulfur. 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 lime sulfur. 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 lime sulfur. For additional discussion of the 

anticipated data needs, please see the document titled Combined Problem Formulation and 

Preliminary Risk Assessment in Support of the Registration Review of Lime Sulfur located in 

docket EPA-HQ-OPP-2016-0102 at www.regulations.gov. No additional human health data are 

anticipated for registration review.

Table 1: Anticipated Data Needs for the Lime Sulfur Registration Review

Guideline 

Number1 Study Title Test 

Material

Estimated 

Timeframe

(Months from 

receipt of DCI)

Non-GDLN 

(OECD 213) Tier I honeybee adult acute oral toxicity TGAI 12

850.3030 Tier 1 honeybee toxicity of residues on 

foliage TEP 12

Non-GDLN Tier I honeybee adult chronic oral toxicity TGAI 12

Non-GDLN

(OECD 237) Tier I honeybee larval acute oral toxicity TGAI 12

Non-GDLN Tier I honeybee larval chronic oral toxicity TGAI 12

Non-GDLN Tier II field trial of residues in pollen and 

nectar2 TEP 24

Non-GDLN

(OECD 75)

Tier II semi-field testing for honeybee 

toxicity (tunnel/enclosure or colony feeding)2 TEP 24

850.3040 Tier III field testing for pollinator toxicity2 TEP 24

850.4100 Tier II terrestrial plant toxicity, seedling 

emergence

TEP 12

850.4150 Tier II terrestrial plant toxicity, vegetative 

vigor

TEP 12

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

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 

 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 The need for theses anticipated data requirements is contingent on results of the tier 1 bee studies (including acute 

oral toxicity to adult honey bees, acute oral toxicity to larval honey bees, chronic oral toxicity to adult honey bees, 

and chronic oral toxicity to larval honey bees).
6

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 lime sulfur.

CHEMICAL FACTS

Table 2 provides a summary of the chemical facts for lime sulfur.

Table 2: Chemical Facts for Lime Sulfur

PC code 076702

Case Number 4054

CAS Number 1344-81-6

Year first registered Lime sulfur has been used for over 150 years. It was first 

registered in the United States in 1961.

Pesticide Type Fungicide, acaricide, and insecticide

Chemical class Inorganic pesticide

Reregistration Eligibility 

Decision (RED)

2005

Tolerance Reassessment 

Eligibility Decision 

(TRED)

Not applicable

Cumulative group Not applicable; lime sulfur has not been identified as a member of 

a cumulative group that shares a common mechanism of toxicity.

40 CFR Citation This compound is currently exempt from the requirement for a 

tolerance under 40 CFR 180.1232.

Dual-use Not applicable; lime sulfur is registered for conventional 

pesticidal uses only.

Non-pesticidal uses Not applicable

 3 http://www2.epa.gov/pesticide-reevaluation
7

Table 2: Chemical Facts for Lime Sulfur

Pesticide Re-evaluation 

Division, Chemical 

Review Manager

Katherine St. Clair, stclair.katherine@epa.gov, 703-347-8778

Registration Division, 

Product Manager and 

Reviewer

Heather Garvie, garvie.heather@epa.gov, 703-308-0034

Lisa Pahel, pahel.lisa@epa.gov, 703-347-0459

USE AND USAGE INFORMATION

Table 3 summarizes the use and usage information for lime sulfur. For more details, please see 

the BEAD Chemical Profile (BCP) for Registration Review: Inorganic Polysulfides (calcium 

polysulfide or lime sulfur) (076702) located in docket EPA-HQ-OPP-2016-0102 at 

www.regulations.gov.

Table 3: Lime Sulfur Use and Usage Information

Summary of Use Lime sulfur is registered for conventional pesticide use as a 

fungicide, insecticide, or acaricide on certain agricultural crops 

and for treatment of mange on certain types of livestock.

Use Sites Lime sulfur is registered for use on almonds, apples, blueberries, 

caneberries, cherries, citrus, hazelnuts, currants and gooseberries, 

bearing and non-bearing fruit trees, grapes, nectarines, peaches, 

pears, pecans, pineapples, pistachios, plums/prunes, quince, 

ryegrass, red clover, and alfalfa. It is also registered for use on 

ornamental plants and as an animal treatment for mites and scab 

disease on horses, cattle, sheep, and swine. There are no 

registered residential uses.

Summary of Usage In the period from 2009 to 2013, approximately 2,131,000 pounds 

of active ingredient (a.i.) were applied over 187,000 acres 

annually. The top three crops by average annual usage in pounds 

of active ingredient (a.i.) per year were apples (900,000 pounds 

a.i.), grapes (500,000 pounds a.i.), and pears (300,000 pounds 

a.i.). Crops with the highest percent crop treated (PCT) included 

caneberries (45), pears (20), and apples (15).

Formulation Type(s) Lime sulfur end use products are formulated as soluble 

concentrates and emulsifiable concentrates.

Application Method(s) Lime sulfur products can be applied by hand or by ground sprayer 

equipment.

Technical Registrant(s) Lime sulfur registrants include OR-CAL and Tessenderlo Kerley, 

Inc.

No. of Registrations As of February 2016, there are four Section 3 end-use products 

registrations.

4

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

(http://oaspub.epa.gov/pestlabl/ppls.home).
8

Table 3: Lime Sulfur Use and Usage Information

Restricted Use Lime sulfur is not classified as a restricted use pesticide.

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 on the pounds a.i. applied and percent crop treated for the uses on alfalfa, 

clover, currant, filbert (hazelnut), nectarines, pineapple, pistachio, quince, and rye. 

• Information about the non-crop uses as an animal treatment for mites and scab disease 

(e.g., dairy cattle swine horses, sheep): quantity applied, frequency of use, importance,

and potential alternatives. 

• Information on the uses on ornamentals.

• 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.

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

state, and county.

• Typical application interval (days).

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

market.

RECENT ACTIONS

A new use for lime sulfur (thinning fruit in apple blossom orchards) was registered in 2015.

ANTICIPATED RISK ASSESSMENTS FOR REGISTRATION REVIEW

The most recent human health and ecological risk assessments for lime sulfur were completed in 

September 2005 in support of the RED, and in December 2015 in support of a new use, thinning 

fruit in apple blossom orchards. For registration review, EPA has completed a draft human health 

risk assessment and a partial draft ecological assessment. Findings and conclusions from these 

risk assessments are summarized in the document titled Combined Problem Formulation and 

Preliminary Risk Assessment in Support of the Registration Review of Lime Sulfur and the 

document titled Calcium Polysulfide. Human Health Risk Assessment for Registration Review

located in docket EPA-HQ-OPP-2016-0102 at www.regulations.gov.

The draft ecological risk assessment does not include a comprehensive pollinator assessment or 

complete endangered species assessment. EPA anticipates conducting these assessments during 

registration review. 

EPA anticipates requiring data to support the planned pollinator and endangered species risk 

assessments. 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 will any changes to the standard operating procedures or default exposure 

assumptions.
9

Table 4 summarizes the recently completed registration review human health and ecological 

draft risk assessments and the planned pollinator and endangered species assessments as detailed 

in the document titled Combined Problem Formulation and Preliminary Risk Assessment in 

Support of the Registration Review of Lime Sulfur and the document titled Calcium Polysulfide. 

Human Health Risk Assessment for Registration Review.

Table 4: Overview of Anticipated Ecological Risk Assessment and Conclusions from Human 

Health Draft Risk Assessment for the Lime Sulfur Registration Review

Type of Risk Assessment To Be 

Conducted? Notes

Ecological and Environmental Fate

Comprehensive ecological 

assessment, including 

endangered species

Yes The Agency anticipates conducting an updated 

comprehensive ecological risk assessment during 

registration review for all uses of lime sulfur. The new 

assessment will incorporate the most up-to-date 

modeling methodologies, updated toxicological 

endpoints, and data submitted under the anticipated 

registration review data call-in. 

The most recent risk assessments for lime sulfur found 

that acute risk quotients (RQs) exceed levels of concern 

(LOCs) for listed and non-listed freshwater fish, birds, 

and mammals; however these assessments also 

determined that the likelihood of these aquatic and 

terrestrial animals actually being exposed to residues of 

lime sulfur at levels capable of causing adverse effects is 

considered low. 

Terrestrial plant data are not available for lime sulfur; 

also, there is some uncertainty regarding the potential 

risk to terrestrial invertebrates (such as honey bees) if 

they are exposed to lime sulfur during applications made 

at bloom to pollinator-attractive trees, i.e., apples. 

Therefore, during registration review, the Agency 

anticipates conducting a more comprehensive 

evaluation of potential effects to plants and to honey 

bees. Risks to federally listed species will be 

evaluated as well.
10

Table 4: Overview of Anticipated Ecological Risk Assessment and Conclusions from Human 

Health Draft Risk Assessment for the Lime Sulfur Registration Review

Type of Risk Assessment To Be 

Conducted? Notes

Incidents Will check for 

updates

For a discussion of reported ecological incidents for 

lime sulfur, see Section 5 of the document titled

Combined Problem Formulation and Preliminary 

Risk Assessment in Support of the Registration 

Review of Lime Sulfur. A total of seven ecological 

incidents were found that possibly involved lime 

sulfur. None of the reported incidents involved 

adverse effects to terrestrial or aquatic animals; all 

involved plant damage. Most of the incidents were 

minor.

Human Health

Dietary

Dietary No The Agency does not anticipate conducting an 

updated dietary risk assessment. The previous 

assessments determined that there are no dietary risk 

concerns.

Food No

Drinking water No

Occupational

Handlers (mixers, loaders, 

applicators)

No The Agency does not anticipate conducting an 

updated occupational risk assessment. The previous 

assessments determined that there are no occupational 

risks of concern. 

Post-application No

Residential

Handlers No There are currently no registered or proposed 

Post-application No residential uses for lime sulfur.

Other

Aggregate No An aggregate risk assessment evaluates the combined 

risk from dietary and residential exposures.

The Agency does not anticipate conducting an 

updated aggregate risk assessment. The previous 

assessments determined that there are no aggregate 

human health risks of concern.

Cumulative No Not applicable; lime sulfur has not been identified as 

a member of a cumulative group that shares a 

common mechanism of toxicity.

Tolerances No This compound is currently exempt from the 

requirement for a tolerance under 40 CFR 180.1232.
11

Table 4: Overview of Anticipated Ecological Risk Assessment and Conclusions from Human 

Health Draft Risk Assessment for the Lime Sulfur Registration Review

Type of Risk Assessment To Be 

Conducted? Notes

Incidents Will check for 

updates

Based on the low frequency and low severity of 

incident cases reported for lime sulfur, there does not 

appear to be a concern at this time that would warrant 

further investigation. However, the Agency will 

continue to monitor the incident information and if a 

concern is triggered, additional analysis will be 

included in the risk assessment. 

For a discussion of reported human incidents for lime 

sulfur, see the document titled Calcium Polysulfide. 

Draft Human Health Risk Assessment for Registration 

Review and the document titled Inorganic 

Polysulfides: Tier 1 (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.

• Submission of any existing toxicity data not previously submitted to the Agency. This

would help give the Agency a more complete understanding of the effects of lime sulfur.

• Maximum annual application rates per acre (maximum lb a.i./A/year), maximum number 

of applications per season and/or year, and minimum application intervals on all labels.

• 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 lime sulfur 

registration review in Table 5.

Table 5: Projected Registration Review Timeline for Lime Sulfur

Activity Estimated Date

Opening the Docket

Open Docket and 60-day Public Comment Period March 2016

Close Public Comment Period May 2016

Case Development

Issue Final Work Plan August 2016

Issue DCI October – December 2016
12

Table 5: Projected Registration Review Timeline for Lime Sulfur

Activity Estimated Date

Data Submission5 October – December 2017

Open 60-day Public Comment Period for Draft Risk 

Assessments6

April – June 2019

Registration Review Decision

Open 60-day Public Comment Period for Proposed 

Registration Review Decision

January - March 2020

Issue Registration Review Decision and Begin PostDecision Follow-up2020

Total (years) 4

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 lime sulfur.

 5 This estimated date for data submission is based on the study timeframes for the anticipated terrestrial plant 

toxicity studies and tier 1 bee studies only (including acute oral toxicity to adult honey bees, acute oral toxicity to 

larval honey bees, chronic oral toxicity to adult honey bees, and chronic oral toxicity to larval honey bees). The need 

for the tier 2 bee studies is contingent on the results of the tier 1 bee studies. If tier 2 bee studies are required, this 

estimated timeline for data submission would need to be extended, and the estimated dates for subsequent activities 

in the estimated timeline may also change. 6 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.
13

Appendix – Additional Areas Considered in the Lime Sulfur 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:

Lime sulfur is not identified as a cause of impairment, as defined under section 303(d) of the 

Clean Water Act, based on information provided at EPA’s website.7 In addition, no Total 

Maximum Daily Loads (TMDL) have been developed for lime sulfur.

8 More information on 

impaired water bodies and TMDLs can be found at EPA’s website.

9 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 Process10 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 lime sulfur 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.

 7 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885 8

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

group_name=PESTICIDES

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

10 http://www2.epa.gov/pesticide-reevaluation/opp-guidance-submission-state-and-tribal-water-quality-monitoringdata
14

ENDANGERED SPECIES:

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

conducted for lime sulfur. The ecological risk assessment planned during registration review will 

allow the Agency to determine whether use of lime sulfur 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 and reregistration decisions for lime 

sulfur, 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), lime sulfur 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, 201311 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. 

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

chemicals.
15

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.12

HUMAN STUDIES:

Occupational

The current lime sulfur human health risk assessment in support of registration review, as well as 

past lime sulfur 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.

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