Docket Number EPA-HQ-OPP-2011-0661

www.regulations.gov

Pyrithiobac Sodium Summary Document

Registration Review: Initial Docket

September 2011

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TABLE OF CONTENTS

I. Preliminary Work Plan (PWP) 4

II. Fact Sheet 11

III. Summary of Data Needs 16

__________________________________________________________________

Please Note

This Preliminary Work Plan and Fact Sheet summarize the Environmental Protection Agency's 

current position based on the following documents:

1. Registration Review: Preliminary Problem Formulation for Environmental Fate and 

Ecological Risk, Endangered Species, and Drinking Water Assessments for Pyrithiobac-Na

(case# 7239). September 19, 2011.

2. Pyrithioiobac Sodium. Human-Health Assessment Scoping Document in Support of 

Registration Review. September, 16, 2011.

3. Pyrithiobac: Review of Human Incidents. May 11, 2011. 

4. Pyrithiobac (078905) Screening Level Usage Analysis (SLUA). December 28, 2010

5. Pyrithiobac (078905) Cal. DPR Usage Data. December 28, 2010

6. BEAD Chemical Profile for Registration Review Pyrithiobac (078905). August 17, 2011.

7. Appendix A for Pyrithiobac (078905): Food/Feed & Non-Food/Non-Feed Uses Considered 

in Registration Review Work Planning. January 13, 2011

These and other supporting documents for the pyrithiobac sodium registration review case may 

be found in docket EPA-HQ-OPP-2011-0661 at http://www.regulations.gov. 
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I. Preliminary Work Plan – Pyrithiobac sodium

Introduction:

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 at: http://www.epa.gov/oppsrrd1/registration_review/. 

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 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 and commit to a final work plan and 

schedule for the registration review of pyrithiobac sodium. 

Pyrithiobac sodium is an acetolactate synthesis (ALS) inhibiting herbicide that is currently 

registered for use to control annual grasses and broadleaf weeds in cotton (the only registered 

food use). There are currently six active FIFRA Section 3 registrations (2 technical grade 

products, 4 end-use products); and three Special Local Need (SLN) registrations under FIFRA 

Section 24(c). The state of Oklahoma (OK) has a SLN registration for use on cotton. The States 

of North Carolina (NC) and Tennessee (TN) have Section 24(c) Special Local Need (SLN) 

registrations for use on kenaf (non-food). There are no registered residential uses for pyrithiobac 

sodium. Pyrithiobac sodium was first registered in 1995 and, therefore, was not subject to 

reregistration under FIFRA.

Anticipated Risk Assessment and Data Needs:

The Agency anticipates requiring data for use in conducting a comprehensive ecological risk 

assessment, including an endangered species assessment, for all uses of pyrithiobac sodium. The 

Agency also anticipates requiring data for use in conducting an updated human health risk 

assessment for registration review. A summary of the issues relevant to the registration review 

of pyrithiobac sodium is given below.
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Ecological Risk:

• The most recent ecological risk assessment for pyrithiobac sodium was completed in

1995 in support of its use on cotton. 

• The Agency has not conducted a risk assessment that supports a complete endangered 

species determination for pyrithiobac sodium. The ecological risk assessment planned 

during registration review will allow the Agency to determine whether use of pyrithiobac 

sodium 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.

• The Agency anticipates requiring the following studies in order to conduct a 

comprehensive ecological risk assessment, including an endangered species assessment,

for the registration review of pyrithiobac sodium:

o GDLN 835.4100 - Aerobic Soil Metabolism

o GDLN 835.4300 - Aerobic Aquatic Metabolism

o GDLN 835.4400 - Anaerobic Aquatic Metabolism

o GDLN 835.6100 - Environmental Chemistry Methods (ECM) and Independent 

Laboratory Validation (ILV) for Soil1

o GDLN 835.6200 - Environmental Chemistry Methods (ECM) and Independent 

Laboratory Validation (ILV) for Water1

o GDLN 850.2100 - Avian Acute Oral Toxicity, passerine species

o GDLN 850.4100 - Terrestrial Plants: Seedling Emergence, Tier II 

o GDLN 850.4150 - Terrestrial Plants: Vegetative Vigor, Tier II 

• Certain pyrithiobac sodium labels are unclear with respect to application parameters. The 

Agency identified a discrepancy, on two currently registered labels, between the number 

of applications that can be made in one year and the application interval. In the absence 

of clear label information, EPA must employ conservative assumptions to complete risk 

assessments. The Agency encourages clear and consistent label language for the sake of 

all stakeholders and encourages the technical registrants to review and update the product 

labels for clarity. 

• Please refer to the document Registration Review: Preliminary Problem Formulation for 

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

Assessments for Pyrithiobac-Na (case# 7239), September 19, 2011, located in the 

registration review docket (EPA-HQ-OPP-2011-0661) for a detailed discussion of label 

uncertainties, and the anticipated environmental risk assessment and data needs.

 1 Environmental Chemistry Methods (ECMs) in water and soil are currently in review by the Agency. Although 

data have been submitted, these studies will be considered data gaps until the data have been reviewed and found to 

be acceptable. 
6

Human Health Risk:

• A human health risk assessment was conducted in 1995 in support of pyrithiobac 

sodium’s initial registration for use on cotton; time-limited tolerances were established 

for use in/on cottonseed. A petition to revise and establish permanent tolerances for use 

of pyrithiobac sodium in/on cotton, undelinted seed and cotton gin byproducts was 

submitted; and, in 1997 permanent tolerances were established for cotton. The most 

recent comprehensive human health risk assessment for pyrithiobac sodium was 

completed in July 1997 in support of the petition to establish permanent tolerances for 

use in/on cotton.

• The Agency anticipates requiring the following data for use in reevaluating toxicological 

endpoints (points of departure), the FQPA safety factor (SF), and for updating the 

pyrithiobac sodium human health toxicity profile: 

o GDLN 870.3465 - 90-Day Inhalation Toxicity

o GDLN 870.6200 - Acute Neurotoxicity 

o GDLN 870.7800 - Immunotoxicity

• The Agency anticipates revising the dietary risk assessment (food and drinking water) to 

incorporate current food and/or drinking water exposure models, potential changes to the 

tolerances, refined estimated drinking water concentrations (EDWCs), updated 

anticipated food residues and Pesticide Data Program (PDP) data, and any changes to 

toxicological points of departure or uncertainty factors.

• The residential and occupational exposure databases for pyrithiobac sodium are adequate; 

and therefore, at this time, EPA does not anticipate the need for additional residential or 

occupational exposure data to support registration review. 

• There are currently no registered uses of pyrithiobac sodium that would result in direct 

residential exposure and therefore, residential handler assessments are not anticipated as 

being needed. However, residential bystander exposures might occur as a result of 

pyrithiobac sodium aerial applications and/or off-site transport (e.g., spray drift or 

volatilization). The Agency is examining its policies and procedures regarding inhalation 

risk assessment, and will re-evaluate the need for a residential bystander risk assessment 

based on current Agency policy at the time of the risk assessment. 

• The Agency anticipates updating the aggregate assessment to incorporate changes to the 

dietary exposure estimates from food and/or drinking water, the points of departure or the 

FQPA safety factor, and current exposure and/or risk assessment policies and procedures, 

as applicable.
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• The Agency anticipates that updated occupational handler and post-application exposure 

assessments will be needed during registration review to incorporate updated/current 

guidelines, models, standard operating procedures, and new toxicological endpoints (if 

they are established). 

• In its previous risk assessment, the Agency did not identify short- and/or intermediateterm dermal or inhalation endpoints and, therefore, short- and intermediate-term 

occupational handler exposure assessments were not conducted. However, pyrithiobac 

sodium was classified as a probable human carcinogen, and, therefore a cancer end-point 

was selected and used to evaluate chronic/lifetime exposure to occupational handlers 

(mixer/loaders and applicators); risks exceeding the Agency’s level of concern were not 

previously identified. If changes are made to the toxicological endpoint selection, 

occupational handler scenarios may need to be assessed for short- and intermediate-term 

exposure durations. In addition, an updated occupational handler cancer assessment that 

incorporates current Agency policies and procedures is anticipated as being needed. 

• Occupational post-application exposure (dermal and inhalation) have not been previously 

assessed. A post-application inhalation exposure assessment may be needed pending 

changes to Agency policies and procedures. Also, if changes are made to the 

toxicological endpoint selection, occupational post-application dermal exposure 

assessments may be needed for activities such as weeding and scouting since pyrithiobac 

sodium may be applied post-emergence, up to 60 days before harvesting. In addition, an 

occupational post-application cancer assessment is anticipated as being needed.

• The tolerance expression in 40 CFR §180.487 will be reviewed during registration review 

to ensure that it appropriately covers the metabolites and degradates of pyrithiobac 

sodium and that it specifies the residues to be measured for each commodity. 

• There are no established or proposed international Codex, Canadian, or Mexican 

Maximum Residue Limits (MRLs) for pyrithiobac sodium. However, should MRLs be 

established, the Agency will work to harmonize tolerances/MRLs, where possible, in key 

export markets during registration review. 

• Please refer to the document Pyrithioiobac Sodium. Human-Health Assessment Scoping 

Document in Support of Registration Review, September 16, 2011, located in the 

registration review docket (EPA-HQ-OPP-2011-0661) for a detailed discussion of the

anticipated human health risk assessment and data needs.

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, 

Endocrine Disruptor Screening Program:
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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 pyrithiobac sodium, 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), 

pyrithiobac sodium 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. Pyrithiobac 

sodium is not among the group of 58 pesticide active ingredients on the initial list to be screened 

under the EDSP. Accordingly, as part of registration review, EPA will issue future EDSP 

orders/data call-ins, requiring the submission of EDSP screening assays for pyrithiobac sodium. 

For further information on the status of the EDSP, the policies and procedures, the list of 67 

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

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

Timeline:

EPA has created the following estimated timeline for the completion of the pyrithiobac sodium

registration review.

Registration Review for Pyrithiobac Sodium – Projected Registration Review Timeline

Activities Estimated Date

Opening the Docket

Open Docket and Public Comment Period 2011 – September

Close Public Comment 2011 – November

Case Development

Final Work Plan 2012 – February

Issue DCI 2012 – Oct - Dec

Data Submission 2014 – Oct - Dec

Open Public Comment Period for Draft Risk Assessments 2016 – April - June

Close Public Comment Period 2016 – July - Sept
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Registration Review for Pyrithiobac Sodium – Projected Registration Review Timeline

Activities Estimated Date

Registration Review Decision

Open Public Comment Period for Proposed Registration Review Decision 2016 – Oct - Dec

Close Public Comment Period 2017 – Jan - March

Registration Review Decision and Begin Post-Decision Follow-up 2017

Total (years) 6

Guidance for Commenters:

The public is invited to comment on EPA’s preliminary work plan and rationale. The Agency 

will carefully consider all comments as well as any additional information or data provided in a 

timely manner prior to issuing a Final Work Plan for the pyrithiobac sodium case.

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. Growers and 

other stakeholders are asked to comment on any trade irritant issues resulting from lack of 

Maximum Residue Limits (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

Pyrithiobac sodium is not identified as a cause of impairment for any water bodies listed as 

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

:

2

. In addition, no Total Maximum Daily 

Loads (TMDL) have been developed for pyrithiobac sodium3. More information on impaired 

water b odies and TMDLs can be found on the Agency’s website4

. 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 Process5 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 pyrithiobac sodium 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.

:

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

3 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_group_name=PESTICIDES 4 http://www.epa.gov/owow/tmdl/

5 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm
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Additional Information

Stakeholders are also specifically asked to provide information and data that will assist the 

Agency in refining the risk assessments, including any species-specific ecological 

determinations. The Agency is interested in obtaining the following information:

:

1. confirmation on the following label information

a. sites of application

b. formulations

c. application methods and equipment

d. maximum application rates

e. frequency of application, application intervals, and maximum number of 

applications per season and per year

f. geographic limitations on use

2. use or potential use distribution (e.g., geographical distribution of relevant uses)

3. use history and reason for changes in use 

4. median and 90th percentile reported use rates (lbs ai/1000 sq ft) from usage data –

national, state, and county

5. application timing (date of first application and application intervals) by use site –

national, state, and county

6. sub-county use site location data

7. directly acquired county-level usage data (not derived from state level data)

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

b. percent use site treated – county

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

d. total pounds per year – county

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

f. the years in which the pesticide was applied in the county/sub-county area

8. typical application interval 

9. state or local use restrictions

10. ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and 

mammalian mortalities) not already reported to the Agency

11. monitoring data

12. information on target pests and efficacy of pyrithiobac to control weeds in cotton and 

kenaf crops, especially in its major use areas (TX, GA, MO, CA, AR, MS, LA)

13. information about the value or benefit of pyrithiobac as an alternative to fluometuron or 

MSMA.

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 expects to issue a Final Work Plan for pyrithiobac 

sodium.
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II. FACT SHEET

Background Information:

• Pyrithiobac sodium registration review case number: 7239

• Pyrithiobac sodium PC code: 078905

• Pyrithiobac sodium CAS No.: 123343-16-8

• Pyrithiobac sodium was first registered in the United States in 1995 and, therefore, was 

not subject to reregistration under FIFRA. 

• Technical registrants: E.I. Du Pont de Nemours and Co., Inc.; and Celsius Property B.V.,

Amsterdam (NL)

• There are currently six active FIFRA Section 3 registrations (2 technical grade products, 

4 end-use products); and three Special Local Need (SLN) registrations under FIFRA 

Section 24(c). 

• Tolerances are established for residues of pyrithiobac sodium under 40 CFR §180.437.

• Pesticide Re-evaluation Division, Chemical Review Manager (CRM): Kylie Rothwell, 

rothwell.kylie@epa.gov

• Registration Division Product Manager (PM): Kable (Bo) Davis, davis.kable@epa.gov

Use & Usage Information: For additional details on label rates and use sites, refer to Appendix 

A for Pyrithiobac (078905): Food/Feed & Non-Food/Non-Feed Uses Considered in Registration 

Review Work Planning, January 13, 2011, the Pyrithiobac (078905) Screening Level Usage 

Analysis (SLUA), December 28, 2010, and the BEAD Chemical Profile for Registration Review

Pyrithiobac (078905), August 17 2011, located in the pyrithiobac sodium registration review 

docket EPA-HQ-OPP-2011-0661.

• Pyrithiobac sodium is an acetolactate synthesis (ALS) inhibiting herbicide that is 

currently registered to control annual grasses and broadleaf weeds in cotton (the only 

registered food use). The state of Oklahoma has a SLN registration for use on cotton. 

The states of North Carolina (NC) and Tennessee (TN) have SLN registrations for use on 

kenaf (non-food). There are no registered residential uses.

• Pyrithiobac sodium is formulated as a wettable powder (packaged in water-soluble bags)

and emulsifiable concentrate. 

• The states with the most agricultural usage in terms of total pounds of active ingredient 

applied are: Texas (23%), Georgia (16%), Mississippi (13%), California (10%), Arkansas 

(10%), Missouri (6%), and Louisiana (6%).

• Pyrithiobac sodium is applied by aerial or ground spray, broadcast, band, and spot 

treatment.
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Ecological Risk Assessment Status:

Please refer to the document, Registration Review: Preliminary Problem Formulation for 

Environmental Fate and Ecological Risk, Endangered Species, and Drinking Water Assessments 

for Pyrithiobac-Na (case# 7239), September 19, 2011, in the registration review docket (EPAHQ-OPP-2011-0661) for a detailed discussion of the key findings of the most recent ecological 

risk assessment. 

• The most recent ecological risk assessment for pyrithiobac sodium was completed in 

1995 in support of its use on cotton. 

• This assessment concluded that acute risk estimates to terrestrial and aquatic animals and 

invertebrates did not exceed the Agency’s level of concern (LOC). However, due to a 

lack of data, chronic risk to birds could not be estimated at that time. Since this risk 

assessment was conducted, an acceptable avian reproduction study was submitted to the 

Agency. 

• Pyrithiobac sodium was determined to be practically non-toxic to young adult honeybees 

on an acute contact exposure basis. 

• As expected with an herbicide, pyrithiobac sodium has adverse effects on plants and risk 

estimates exceeding the Agency’s LOC were identified for terrestrial and aquatic 

vascular plants. Mitigation measures were put in place to address these risks (e.g., 

geographic restrictions on location and soil type, application rate reductions, reduction in 

the number of applications, and measures to minimize drift). 

Please refer to the document, Pyrithiobac Sodium. Human-Health Assessment Scoping Document 

in Support of Registration Review, September 16, 2011, in the registration review docket (EPAHQ-OPP-2011-0661) for a detailed discussion of the key findings of the most recent human 

health risk assessment. 

Human Health Risk Assessment Status:

• A human health risk assessment was conducted in 1995 in support of pyrithiobac 

sodium’s initial registration for use on cotton. Time-limited tolerances were established 

for use in/on cottonseed at that time. A petition to establish permanent tolerances for use 

of pyrithiobac sodium in/on cotton, undelinted seed and cotton gin byproducts was 

submitted; and in 1997 permanent tolerances were established for cotton. The most 

recent comprehensive human health risk assessment for pyrithiobac sodium was 

completed in July 1997 in support of the petition to establish permanent tolerances for 

use in/on cotton, and EPA’s conclusions are summarized below.

Hazard Characterization:

• In animal studies, pyrithiobac sodium caused toxicity in several organs with the liver

being the most prominent. Liver toxicity occurred in the mouse, rat, and dog for both 

sub-chronic and chronic durations. Kidney toxicity was also observed in the mouse, rat, 

and dog following chronic exposures. The combined sub-chronic oral/neurotoxicity/1-

generation reproductive study showed little evidence for neurotoxic effects. 
13

• Developmental toxicity studies with pyrithiobac sodium in the rat and rabbit did not show 

any increased evidence of susceptibility in offspring at doses associated with maternal 

toxicity. 

• In the 1997 risk assessment, EPA reduced the 10x FQPA safety factor to 1x because the 

toxicity database was adequate to characterize the potential for pre- and post-natal risk 

for infants and children, no developmental effects were observed in rats, and there was a 

lack of evidence of increased susceptibility. However, this FQPA safety factor decision 

preceded changes in EPA’s current science policy.

• Pyrithiobac sodium has been classified as a “group C” possible human carcinogen based 

on: (1) evidence of increased incidences of liver tumors in the CD-1 male mouse that 

were statistically significant at more than one dose and exceeded the historical control 

range, and (2) increases in rare kidney tumors in male Crl:CDBR rats. Therefore, in its 

1997 human health assessment, the Agency selected a cancer end-point, which was used 

to evaluate potential lifetime carcinogenic risks resulting from dietary and occupational 

exposure. 

• The Agency selected a chronic dietary endpoint based on the chronic rat toxicity study, 

which showed decreased total body weight and body weight gain, decreases in hematocrit 

and red blood cells and treatment-related hematuria. The Agency did not identify shortand/or intermediate-term dermal or inhalation endpoints.

Dietary (Food):

• EPA conducted an unrefined chronic dietary (food) exposure assessment for the general 

U.S. population and various subgroups. Drinking water exposure was not incorporated 

directly in the dietary assessment. Because pyrithiobac sodium was classified as a 

probable human carcinogen, a cancer endpoint was selected and the Agency conducted a 

dietary assessment to estimate potential lifetime carcinogenic risks resulting from dietary 

exposure. Both chronic and cancer dietary exposure estimates were below EPA’s levels 

of concern for all population subgroups.

Residential:

• There are no registered uses of pyrithiobac sodium that would result in direct residential 

exposure and therefore, residential handler and post-application exposure and risk 

assessments have not been conducted. 

Aggregate:

• EPA conducted an aggregate (food and drinking water) risk assessment for pyrithiobac 

sodium. Although exposure to drinking water was not incorporated directly in the 

dietary assessment, aggregate exposure to food and drinking water was estimated using 

Tier I exposure estimates for surface and ground water. The 1997 risk assessment did 

not identify any aggregate risks above the Agency’s level of concern. 
14

Occupational:

• The Agency did not identify short- and/or intermediate-term dermal or inhalation 

endpoints, and, therefore short- and intermediate-term occupational handler and postapplication exposure assessments were not conducted. However, pyrithiobac sodium was 

classified as a probable human carcinogen and, therefore, a cancer end-point was selected 

and used to evaluate chronic/lifetime exposure to occupational handlers (mixer/loaders 

and applicators); risks exceeding the Agency’s level of concern were not identified. A 

cancer assessment was not conducted to assess potential occupational post-application 

exposure. 

Human Studies:

• Past pyrithiobac sodium 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.

Cumulative:

• EPA has not yet determined whether or not pyrithiobac sodium shares a common 

mechanism of toxicity with any other chemical substances. If the Agency determines that 

new information on pyrithiobac sodium is available that could potentially affect a 

cumulative risk assessment and result in a risk of concern, the Agency will revisit the 

need for a cumulative assessment. 

Incidents:

• A summary report listing reported human incidents for pyrithiobac sodium has been 

provided in the docket item entitled Pyrithiobac: Review of Human Incidents, May 11, 

2011. The evaluation of the OPP Incident Data System (IDS) indicated that no human 

health incidents were identified in the United States from January 1, 2006 to March 23, 

2011. Based on the lack of incident cases, there does not appear to be a concern at this 

time that would warrant further investigation. 

• The Agency reviewed the Ecological Incident Information System (EIIS, version 2.1) and 

the Avian Incident Monitoring System (AIMS) on May 13, 2011 and April 6, 2011, 

respectively, for ecological incident information. One aggregate plant incident, from 

June 2006, was reported in the EIIS database. Unless additional information on this 2006 

aggregated incident report become available, the incident will be assumed to be due to a 
15

registered use of pyrithiobac sodium. No avian incidents involving pyrithiobac sodium

were reported in the AIMS database. Although only one incident associated with the use 

of pyrithiobac sodium has been reported to the EPA, the absence of reported incidents 

should not be construed as the absence of incidents.

• The Agency will continue to monitor the human health and ecological incident 

information. If a concern is identified at the time of the registration review risk 

assessments, the Agency will conduct additional analyses of that information.

Tolerances and International Harmonization:

• Tolerances are established for residues of pyrithiobac sodium under 40 CFR §180.487 for 

use on cotton, gin byproducts and cotton, undelinted seed. There are no established or 

proposed international Codex, Canadian, or Mexican MRLs for pyrithiobac sodium. 

However, should MRLs be established, the Agency will work to harmonize 

tolerances/MRLs, where possible, in key export markets during registration review. 

Data Call-In Status:

• No Data Call-Ins (DCIs) have previously been issued for pyrithiobac sodium.

Labels

• Pyrithiobac sodium Section 3 product labels can be obtained from the Pesticide Product 

Label System (PPLS) website: http://oaspub.epa.gov/pestlabl/ppls.home.
16

III. Summary of Anticipated Data Needs – Pyrithiobac Sodium 

The table below summarizes all anticipated data needs for pyrithiobac sodium in Section I, of 

this document (Preliminary Work Plan), the Registration Review: Problem Formulation for 

Environmental Fate and Ecological Risk, Endangered Species, and Drinking Water Assessment 

for Pyrithiobac-Na (case #7239), September 19, 2011, and the Pyrithiobac. Human-Health 

Assessment Scoping Document in Support of Registration Review, September 16, 2011. 

Table 1. Anticipated Data Needs for Pyrithiobac Sodium Registration Review

Guideline 

Number

Anticipated Data Requirement Test 

Material

Estimated Timeframe 

(Measured from Date 

of DCI Receipt)

Ecological Toxicity and Environmental Fate Effects

835.4100 Aerobic Soil Metabolism TGAI 24

835.4300 Aerobic Aquatic Metabolism TGAI 24

835.4400 Anaerobic Aquatic Metabolism TGAI 24

835.6100 Environmental Chemistry Methods (ECM) and 

Independent Lab rotary Validation (ILV), Soil6 TGAI 12

835.6200 ECM and ILV, Water6 TGAI 12

850.2100 Avian Acute Oral Toxicity, Passerine Species7 TGAI 12

850.4100 Terrestrial Plants: Seedling Emergence, Tier II8 TEP 12

850.4150 Terrestrial Plants: Vegetative Vigor, Tier II8 TEP 12

Human Health Effects

870.3465 90-Day Inhalation Toxicity TGAI 24

870.6200 Acute Neurotoxicity TGAI 24

870.7800 Immunotoxicity Study7 TGAI 12

 6 See footnote 7 of 40 CFR 150.1300. EPA anticipates requiring only the environmental chemistry analytical 

(ECM) methods and independent laboratory validation (ILV) portions of this guideline. 

7 The anticipated DCI will require a study protocol to be submitted for review and approval by the Agency prior to 

this study being initiated. 8 A Tier II study is expected to be required. The DCI expected to be issued will provide that a Tier I plant study 

may be conducted in lieu of a Tier II study with the understanding that any adverse effects observed by the Tier I 

study would necessitate conduct and submission of a Tier II study as well.