Docket Number EPA

- HQ

- OPP

- 2011

- 0661 www.regulations.gov



## Pyrithiobac S odium Summary Document Registration Review: Initial Docket September 20113 

### 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: Prelimi nary Problem Formulation for Environmental Fate and Ecological Risk , Endangered Specie s, 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 Pr ofile 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

- 0 661 at http://www.regulations.gov

.4 

### 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 envi ronment 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

s ure 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. T he Agency will consider benefits information and d ata 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 info rmation 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 a n 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 gra de 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. T he States of North Carolina (NC) and Tennessee (TN) have Section 24(c) Special Local Need (SLN) registratio ns 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

r eregistration under FIFRA

.

Anticipated Risk Assessment and Data Needs:

The Agency anticipates requi ring data for use in conduct ing a comprehensive ecological risk assessment, including an endangered species assessment, for all uses of pyrithiobac sodium . The Agency also anticipates requir ing data for use in conduct ing an updat ed human health risk

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

of pyrithiobac sodium is given below

.5 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 e cological risk assessment planned during registration review will allow the Agency to determine whether use of pyrithiobac

sodium ha s “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, t he Agency

will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Service (the Services), as appropriate.

**•** The Agency ant i cipates requir ing the following studies in order to conduct a comprehensive ecological risk assessmen t , 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 Soil 1

o GDLN 835.6200

- Environmental Chemistry Methods (ECM) and Independent Laboratory Validation (ILV) for Water 1

o GDLN 850.2100

- Avian Acute Oral Toxicity

, passerine species

o GDLN 850.4 100

- Terrestrial Plants: Seedling Emergence , Tier II

o GDLN 850.41 50

- Terrestrial Plants: Vegetative Vigor , Tier II

**•** Certain pyrithiobac sodium labels are unclear with respect to application parameters . T he Agency identified a discrepancy, on two currently registered labels, between the number of applications that can be made in one year and the application interva l

. 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 re view and update the product labels for clarity.

**•** Please refer to the document Registration Review: Prelimi nary 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 r eview 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 ; t ime

- limited tolerances were established

for use in/on cottonseed . A petition to revise and establish permanent tolerances for use of pyrithiobac s odium 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 sup port of the petition to establish permanent tolerances for

use in/on cotton.

**•** The Agency anticipates requir ing the following data for use in reevaluating toxicological endpoints (points of departure), the FQPA safety factor (SF), and for updating the pyri thiobac sodium human health toxicity profile:

o GDLN 870.3465

- 90

- Day Inhalation Toxicity

o GDLN 870.6200

- Acute N eurotoxicity

o GDLN 870.7800

- Immunotoxicity

**•** The Agency anticipates revis ing 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

to xicological 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 expos ure 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, residenti al 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 inc orporate 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 procedure s, as applicable.7 **•** 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 intermediate

term dermal or inhalation endpoints and

, therefore

, short

- and intermediate

- term occupational handler exposure assessments were not conduct ed. 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 Agen cy’s level of concern were not previously identif ied. 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 occupat ional 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 exp osure 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 re viewe d during registration review to ensure that it appropriately covers the metabolites and degradates of pyrithiobac

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

**•** There are no established or proposed international Codex, Cana dian, or Mexican

Maximum Residue Limits (MRLs) for pyrithiobac sodium. H owever, 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

- 0 66 1) 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 an d 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 tar get organ histopathology, organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, E ndocrine Disruptor Screening Program:8 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 occ urring 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 r elationship 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 c ontains 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 f uture 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

w ebsite: 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 S odium

– 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

– Apr il

- Jun e Close Public Comment Period 201 6

– July

- Sept9 Registration Review for Pyrithiobac S odium

– Projected Registration Review Timeline

Activities Estimated Date Registration Review Decision Open Public Comment Period for Proposed Registration Review D ecision 2016

– Oct

- Dec

Close Public C omment P eriod 201 7

– Jan

- March Registration Review D ecision and Begin P ost

- D ecision F ollow

- 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

ti mely manner prior to issuing a F inal W ork P lan for the pyrithiobac so dium 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, n o Total Ma ximum Daily Loads (TMDL) have been developed for pyrithiobac sodium 3 . More infor mation on impaired

water b odies and TMDLs can be found on the Agency ’ s website 4

. The Agency invites submission of water quality data for th is pesticide. To the extent possible, data should conform to the quality standards in Appendix A of the OPP Standa rd Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process 5 in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.

E nvironmental Justice

E PA 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, unusu ally 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=PEST ICIDES

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

5 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm10 Additional Information

Stakeholders are also specifically asked to provide information and data that will assist the Agency in refining the risk assessment s , 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. geogra phic 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 90 th 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 90 th 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 t he 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 p ests 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 alternativ e 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

.11 

### II. FACT SHEET

Background Information :

**•** Pyrithiobac sodium re gistration review case number: 72 39

**•** Pyrithiobac sodium PC code: 078905

**•** Pyrithiobac sodium CAS No.: 123343

- 16

- 8

**•** Pyrithiobac sodium was first registered in the United States in 19 95 and, therefore, was not subjec t to reregistration under FIFRA.

**•** T echnical registrant s : E.I. Du Pont de Nemours and Co., Inc.; and Celsius Property B.V

., Amsterdam (NL)

**•** There are c urrently 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 §180.43 7

.

**•** Pesticide Re

- evaluation Division, Chemical Review Manager (CRM) : K ylie Rothwell, rothwell.kylie@epa.gov

**•** Registration Division Product Manager (PM) : Kable (Bo) Davis

, davis.kable@epa.gov

Use & Usag e 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

Revi ew 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.

T he s tates of North Carolina (NC) a nd 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 mos t 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.12 Ecological Risk Assessment Status :

Please refer to the document, Registration Review: Prelimi nary 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 (EPA

HQ

- 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 prac tically 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

vascu lar 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 Revie w

, September 16, 2011

, in the registration review docket (EPA

HQ

- OPP

- 2011

- 0661) for a detailed discussion of the key findings of the most recent human

health risk assessment. Hu man 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 esta blished 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 Character ization:

**•** In animal studies, p yrithiobac sodium caused toxicity in several organs with the live r 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 scie nce 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 his torical 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 d ietary and occupational

exposure

.

**•** T he 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 hem a tocrit

an d red blood cells and treatment

- related hema turia

. The Agency did not identify short

and/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

p robable 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 l evels 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 handle r 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 a nd 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:

**•** T he Agency did not identify short

- and/or i ntermediate

- term dermal or inhalation endpoints

, and

, therefore short

- and intermediate

- term occupational handler and post

application 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 gen eric 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 f or 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

mech anism 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 i ncident cases, there does not appear to be a concern at this

time that would warrant further inv estigation.

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

the Avian Incident Monitor ing System (AIMS) on May 13, 2011 and April 6, 2011, respectively , for ecological incident information

. One aggregate plant inci dent

, 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 a15 registered use of pyrithiobac sodium. No avian incidents involvin g 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 . I f a concern is identified at the time of the registration review risk

assessments, the Agency will conduct additional analys e s of that information.

Tolerances and Inte rnational 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 MR Ls 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 l abels 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 S odium

The table below summarizes all anticipated data needs for pyrithiobac sodium in Section I, of this document (Preliminary Work Plan), the Registration Revi ew: 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

N umber Anticipated D ata 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) , Soil 6 TGAI 12

835.6200 ECM and ILV , Water 6 TGAI 12

850.2100 Avian Acute Oral Toxicity, Passerine S pecies 7 TGAI 12

850.4100 Terrestrial Plants: Seedling Emergence, Tier II 8 TEP 12

850.4150 Terrestrial Plants: Vegetative Vigor, Tier II 8 TEP 12
Human Health Effects

870.3465 90

- Day Inhalation Toxicity TGAI 24

870.6200 Acute Neurotoxicity TGAI 24

870.7800 Immunotoxicity Study 7 TGAI 12

6 See footnote 7 of 40 CFR 150.1300. EPA anticipates requ iring 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

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