2

Table of Contents

I. INTRODUCTION .................................................................................................................. 3

A. Summary of Propoxycarbazone-sodium Registration Review ........................................ 4

B. Public Comments............................................................................................................. 5

II. USE AND USAGE................................................................................................................. 6

III. SCIENTIFIC ASSESSMENTS ........................................................................................... 7

A. Human Health Risk Assessment ...................................................................................... 7

1. Risk Conclusions.......................................................................................................... 7

2. Human Incidents........................................................................................................... 7

3. Tolerances..................................................................................................................... 7

B. Ecological Risk Assessment............................................................................................. 8

1. Risk Conclusions.......................................................................................................... 8

2. Ecological Incidents ................................................................................................... 10

3. Characterization of Ecological Risk........................................................................... 10

C. Benefits Assessment....................................................................................................... 11

D. Endangered Species Assessment.................................................................................... 12

E. Endocrine Disruptor Screening Program ....................................................................... 13

IV. PROPOSED INTERIM REGISTRATION REVIEW DECISION ................................... 14

A. Risk Mitigation and Regulatory Rationale..................................................................... 14

1. Spray Drift Reduction................................................................................................. 14

2. Herbicide Resistance Management ............................................................................ 15

B. Tolerance Amendments.................................................................................................. 17

C. Proposed Interim Registration Review Decision ........................................................... 17

D. Data Requirements......................................................................................................... 17

V. NEXT STEPS AND TIMELINE.......................................................................................... 18

A. Interim Registration Review Decision ........................................................................... 18

B. Implementation of Mitigation Measures........................................................................ 18

Appendix A: Summary of Proposed Actions Taken for Propoxycarbazone-sodium1..............18

Appendix B: Propoxycarbazone-sodium Label Tabl....................................................18
3

I. INTRODUCTION

This document is the Environmental Protection Agency’s (EPA or the Agency) Proposed Interim 

Registration Review Decision for propoxycarbazone-sodium (case 7264, PC code 122019) and is 

being issued pursuant to 40 CFR Sections 155.56 and 155.58. A registration review decision is 

the Agency's determination whether a pesticide meets, or does not meet, the standard for 

registration under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). The Agency 

may issue, when it determines it to be appropriate, an Interim Registration Review Decision 

before completing a registration review. Among other things, the Interim Registration Review 

Decision may: 1) require new risk mitigation measures; 2) impose interim risk mitigation 

measures; 3) identify additional data or other information required to complete the review; and 4) 

include schedules for submitting the required data, conducting the new risk assessment, and 

completing the registration review. For further information on propoxycarbazone-sodium, 

additional documents can be found in EPA’s public docket (EPA-HQ-OPP-2015-0095) at 

www.regulations.gov.

FIFRA, as amended by the Food Quality Protection Act (FQPA) of 1996, mandated the 

continuous review of existing pesticides. All pesticides distributed or sold in the United States 

generally must be registered by the EPA based on scientific data showing that they will not cause 

unreasonable risks to human health or to the environment when used as directed on product 

labeling. The registration review program is intended to make sure that, as the ability to assess 

and reduce risk evolves and as policies and practices change, all registered pesticides continue to 

meet the statutory standard of no unreasonable adverse effects. Changes in science, public 

policy, and pesticide use practices will occur over time. Through the registration review 

program, the Agency periodically re-evaluates pesticides to make sure that as these changes 

occur, products in the marketplace can continue to be used safely. Information on this program is 

provided at http://www.epa.gov/pesticide-reevaluation/registration-review-process. 

In 2006, the Agency implemented the registration review program pursuant to FIFRA section 

3(g) and will review each registered pesticide every 15 years to determine whether it continues to 

meet the FIFRA standard for registration.

EPA is issuing a proposed interim registration review decision for propoxycarbazone-sodium so 

that it can (1) move forward with aspects of the registration review that are complete and (2) 

implement interim risk mitigation. The Agency is currently working with the U.S. Fish and 

Wildlife Service and the National Marine Fisheries Service to develop methodologies for 

conducting national endangered species assessments for pesticides. Therefore, although EPA 

has not yet fully evaluated risks to threatened and endangered species, the Agency will complete 

its endangered species assessment and any necessary consultation with the Services for 

propoxycarbazone-sodium prior to completing the propoxycarbazone-sodium registration 

review. Likewise, the Agency will complete endocrine screening for propoxycarbazone-sodium, 

pursuant to the Federal Food, Drug, and Cosmetic Act (FFDCA) section 408(p), before 

completing this registration review. Lastly, EPA will determine whether additional pollinator 

exposure and effects data are necessary to make a final registration review decision for 

propoxycarbazone-sodium and, if so, issue a data call-in (DCI) to obtain any such data prior to 

completing the propoxycarbazone-sodium registration review. 
4

Propoxycarbazone-sodium is a selective, predominately post-emergence herbicide belonging to 

the sulfonamide class of herbicides. It is formulated as a water dispersible granule, and is 

currently registered for use in control of certain grasses and broadleaf weeds in wheat, triticale, 

pastureland, rangeland, and the United States Department of Agriculture (USDA) Conservation 

Reserve Program lands. There are no registered residential uses. Application equipment and 

methods for propoxycarbazone-sodium include ground application, aerial application, backpack, 

manually pressurized hand wand, and mechanically-pressurized handgun. Because 

propoxycarbazone-sodium was first registered in 2004, it was not subject to reregistration. 

A. Summary of Propoxycarbazone-sodium Registration Review

Pursuant to 40 CFR Section 155.50, EPA formally initiated registration review for 

propoxycarbazone-sodium (case 7264) in March 2015. The following timeline highlights 

significant events that have occurred during the registration review of propoxycarbazonesodium. Documentation of these events can be found in EPA’s propoxycarbazone public docket, 

EPA-HQ-OPP-2015-0095, accessed at www.regulations.gov:

• March 27, 2015 – The EPA published for a 60-day public comment period the 

Propoxycarbazone-sodium: Combined Preliminary Work Plan and Summary of Draft 

Human Health and Environmental Risk Assessments; Propoxycarbazone-sodium Human 

Health Assessment Scoping Document and Preliminary Human Health Risk Assessment; 

and the Preliminary Environmental Fate and Ecological Risk Assessment for the 

Registration Review of Propoxycarbazone-sodium.

• May 2015 – The Agency received two public comments on the Propoxycarbazonesodium Combined Preliminary Work Plan and Summary of Risk Assessments and the 

Human Health and Ecological Risk Assessments. These comments and the Agency’s 

responses are summarized in Section B. and in the Response to Comments on the 

Preliminary Environmental Fate and Ecological Risk Assessment for the Registration 

Review of Propoxycarbazone-sodium document. The comments received by the Agency 

did not cause any substantive changes to the risk assessments or registration review 

timeline.

• March 2016 – EPA is now publishing the Propoxycarbazone-sodium Proposed Interim 

Registration Review Decision in the propoxycarbazone-sodium registration review docket 

for a 60-day public comment period. In addition to this document, the Agency is 

publishing the following supporting documents:

o Response to Comments on the Preliminary Environmental Fate and Ecological 

Risk Assessment for the Registration Review of Propoxycarbazone-sodium,

August 17, 2015

o Propoxycarbazone: Usage on Wheat and Proposed Herbicide Resistance 

Management Measures (PC #122019), March 10, 2016
5

B. Public Comments

EPA received two public comments during the 60-day comment period on the 

propoxycarbazone-sodium Combined Preliminary Work Plan and Summary of Draft Human 

Health and Environmental Risk Assessments, which opened on March 27, 2015 and closed on 

May 26, 2015. Comments were submitted by Bayer CropScience (Bayer), the technical 

registrant for propoxycarbazone-sodium, and by the Center for Biologic Diversity (CBD), an 

environmental public interest group. Comments from Bayer focused on various technical 

aspects of the Combined Work Plan, Preliminary Human Health and Preliminary Ecological and 

Environmental Fate Risk Assessments. Comments from CBD focused on the EPA’s duty to 

consult with the U.S. Fish and Wildlife Services and the National Marine Fisheries Service on 

the registration review of propoxycarbazone-sodium in accordance with the Endangered Species 

Act. The comments did not affect the risk assessment conclusions. This Proposed Interim 

Decision document does not capture every comment submitted by Bayer nor all of the responses. 

Comments that are of a broader regulatory nature are summarized below. Comments that are of

technical nature on the Preliminary Ecological and Environmental Fate Risk Assessment and the 

Agency’s responses are addressed in the Response to Comments on the Preliminary 

Environmental Fate and Ecological Risk Assessment for the Registration Review of 

Propoxycarbazone-sodium, August 17, 2015. Public comments and the EPA Response to 

Comments document are located in the Registration Review Docket for propoxycarbazonesodium (EPA-HQ-OPP-2015-0095)

COMMENTS RECEIVED FROM BAYER CROPSCIENCE (EPA-HQ-OPP-2015-0095-0012)

Comment: Bayer commented that the schedule for propoxycarbazone-sodium registration review 

is atypical and requested an opportunity to comment once the DCI data have been submitted to 

the Agency. 

EPA Response: The Agency acknowledges that the schedule for propoxycarbazone-sodium 

registration review is atypical. The Agency determined that additional data were not required to 

complete the Preliminary Human Health and Ecological Risk Assessments and consequently 

proceeded to the risk assessment phase of Registration Review, expediting the process. The 

Agency notes that there will be no DCI issued for propoxycarbazone-sodium at this time, but 

there is an opportunity for the public to comment on this Proposed Interim Registration Review 

Decision.

Comment: Bayer provided clarification on propoxycarbazone-sodium usage and use patterns 

listed in the Propoxycarbazone-sodium (122019) EFED and HED Label Data Reports.

EPA Response: The EPA thanks Bayer for clarification of the propoxycarbazone-sodium usage 

and use patterns and has considered this information in this Registration Review Proposed 

Interim Decision.
6

COMMENTS RECEIVED FROM THE CENTER FOR BIOLOGIC DIVERSITY (EPA-HQ-OPP-2015-0095-

0011)

Comment: The CBD comments focus on the EPA’s duty to consult with the U.S. Fish and 

Wildlife Service and the National Marine Fisheries Service (the Services) on the registration 

review of propoxycarbazone-sodium in accordance with the Endangered Species Act (ESA).

The CBD comments mention various aspects of the risk assessment process, including use of the 

best available data to develop threatened and endangered (listed) species risk assessments, and 

evaluation of effects on listed species and their designated critical habitat. CBD also expresses 

concern regarding the rigor of the Agency’s preliminary determinations regarding the effects of 

propoxycarbazone-sodium on listed species and their designated critical habitat for the 

propoxycarbazone-sodium registration review. 

EPA Response: EPA has reviewed the comments from CBD and plans to address many of the 

concerns raised by CBD as part of the implementation plan for assessing the risks of pesticides to 

listed species based on the recommendations of the April 2013 National Academy of Sciences 

(NAS) report. EPA will address concerns specific to propoxycarbazone-sodium in connection 

with the development of its final registration review decision for this pesticide. 

For further information on the registration review of propoxycarbazone-sodium, including the 

Agency’s Response to Comment document, see the propoxycarbazone-sodium public docket 

(EPA-HQ-OPP-2015-0095) at www.regulations.gov. 

II. USE AND USAGE

Propoxycarbazone-sodium is an herbicide registered for use to control certain post-emergent 

grasses and broadleaf weeds including cheat grass, downy brome, jointed goatgrass, pigweed, 

and wild oat or mustard. Propoxycarbazone-sodium is registered for the following agricultural 

uses: rangeland, pastures, Conservation Reserve Program lands, wheat, and triticale. There are 

no residential use sites registered for propoxycarbazone-sodium. Much of the 

propoxycarbazone-sodium use is in the Northeastern United States. Propoxycarbazone-sodium 

is formulated as a water dispersible granule and is applied via ground, aerial, and/or handheld 

equipment. The predominant use of propoxycarbazone sodium is on winter wheat with an 

average of 30,000 pounds a.i. applied to winter wheat on an annual basis between 2005 and 

2012. 

For additional information on propoxycarbazone use and usage, see the October 22, 2014 BEAD

Chemical Profile (BCP) for Registration Review: Propoxycarbazone-sodium (122019) and the 

March 10, 2016 Propoxycarbazone: Usage on Wheat and Proposed Herbicide Resistance 

Management Measures (PC #122019) in the propoxycarbazone-sodium registration review 

docket (EPA-HQ-OPP-2015-0095). 
7

III. SCIENTIFIC ASSESSMENTS

A. Human Health Risk Assessment

A summary of the Agency’s human health risk assessment is presented below. The Agency used 

the most updated EPA science policies and risk assessment methodologies to prepare a 

quantitative risk assessment in support of propoxycarbazone-sodium registration review. For 

more information, see Propoxycarbazone-sodium. Human Health Assessment Scoping Document 

and Preliminary Human Health Risk Assessment in Support of Registration Review, February 25, 

2015, in the registration review docket (EPA-HQ-OPP-2015-0095) at www.regulations.gov. 

1. Risk Conclusions

EPA has found no dietary risks of concern for propoxycarbazone-sodium from exposure to 

residues in either food or drinking water. The Agency did not conduct a residential risk 

assessment because there are no registered residential uses for propoxycarbazone-sodium. 

Therefore, the aggregate exposure assessment is equivalent to the dietary assessment and not of 

concern. EPA has not made a common mechanism of toxicity finding for propoxycarbazonesodium and any other substance for this assessment. 

EPA has found no risks of concern for occupational handler or occupational post-application 

exposure scenarios. Since no dermal hazard was identified in the toxicological database, only 

inhalation exposures were quantitatively assessed. In addition, EPA evaluated off-target 

exposure of adults and children to spray drift and no risk estimates of concern were identified.

2. Human Incidents

On January 21, 2015, EPA completed a review of propoxycarbazone-sodium incidents in the 

OPP Incident Data System (IDS) and Centers for Disease Control and Prevention/National 

Institute for Occupational Safety and Health (CDC/NIOSH) Sentinel Event Notification System 

for Occupational Risk-Pesticides (SENSOR) databases. Two incident cases were reported. One 

incident case was reported as minor in the IDS (between the years 2009 and 2014), and one case 

was identified in the SENSOR/NIOSH database (between the years 1998-2010), which involved 

multiple active ingredients. Based on the low frequency and low severity of incident cases 

reported, there does not appear to be a concern at this time that would warrant further 

investigation. 

3. Tolerances

In order to be consistent with current Agency SOPs, the propoxycarbazone-sodium tolerances on 

meat products will be updated to include the recommended number of significant figures as 

indicated below. In addition, the tolerance expression will be updated as recommended in 

Section 2.2.3 of the Propoxycarbazone-sodium. Human Health Assessment Scoping Document 

and Preliminary Human Health Risk Assessment in Support of Registration Review. No Codex 
8

maximum residue limits (MRLs) have been established for propoxycarbazone-sodium except for 

wheat grain. The Canadian MRL for residues of propoxycarbazone-sodium and its metabolite 

in/on wheat grain (0.2 ppm) is equivalent to the U.S. tolerance expression level. Therefore, 

harmonization is not an issue at this time. 

Commodity Established Tolerance 

(ppm)

Recommended Tolerance 

(ppm)

Cattle, meat byproducts 0.3 0.30

Goat, meat byproducts 0.3 0.30

Horse, meat byproducts 0.3 0.30

Sheep, meat byproducts 0.3 0.30

B. Ecological Risk Assessment

A summary of the Agency’s ecological risk assessment is presented below. EPA used the most 

updated Agency science policies and risk assessment methodologies to prepare a quantitative 

ecological risk assessment in support of the registration review of propoxycarbazone-sodium. 

For a detailed discussion of the ecological risk assessment for propoxycarbazone-sodium, see the 

Preliminary Environmental Fate and Ecological Risk Assessment for the Registration Review of 

Propoxycarbazone-sodium, dated March 3, 2015 in the propoxycarbazone-sodium registration 

review docket EPA-HQ-OPP-2015-0095, which can be accessed at www.regulations.gov. 

EPA is currently working with its federal partners and other stakeholders to implement an 

interim approach for assessing potential risk to listed species and their designated critical 

habitats. Once the scientific methods necessary to complete risk assessments for listed species 

and their designated critical habitats are finalized, the Agency will complete its endangered 

species assessment for propoxycarbazone-sodium. As such, the risk conclusions described 

below pertain to non-listed species.

1. Risk Conclusions

The preliminary risk assessment showed that propoxycarbazone-sodium is practically non-toxic 

to all animal taxa including birds, mammals, terrestrial invertebrates, fish, and aquatic 

invertebrates on an acute exposure basis. Consistent with the herbicidal mode of action, 

terrestrial plants are sensitive to propoxycarbazone-sodium exposure. Propoxycarbazone-sodium 

is very highly toxic to the vascular aquatic plant duckweed. 

Aquatic Assessment

Fish, Amphibians, and Aquatic Invertebrates - Propoxycarbazone-sodium was not found 

to be toxic to any fish or aquatic invertebrate species studied at tested concentrations. 

Risk quotients (RQs) did not exceed the Agency’s Level of Concern (LOC) for listed and

non-listed species. Freshwater fish are assumed to be representative of aquatic-phase 

amphibians in this assessment. 
9

Aquatic Plants - Propoxycarbazone-sodium is toxic to vascular and non-vascular aquatic 

plants; however, RQs (highest RQ = 0.74) do not exceed the LOC of 1 for listed or nonlisted vascular or non-vascular plants for any registered uses. 

Terrestrial Assessment 

Terrestrial Plants - Consistent with its herbicidal mode of action propoxycarbazonesodium is toxic to terrestrial plant species. The RQs for listed and non-listed terrestrial 

plants exceed the LOC of 1 for almost all modeled scenarios with an RQ range of 0.81 to 

5.8 for non-listed species and 1.9-849 for listed species. Non-target terrestrial plants 

species in areas adjacent to treated fields could be impacted by exposure to 

propoxycarbazone-sodium.

Birds and Mammals - Propoxycarbazone-sodium is practically non-toxic to birds. Birds 

are assumed to be representative of terrestrial-phase amphibians and reptiles in this 

assessment. Propoxycarbazone-sodium was found to be non-toxic to mammals. Acute 

RQ values were not calculated for birds or mammals due to non-definitive toxicity 

endpoints, but even if the non-definitive endpoint was conservatively equated to an LD50, 

the RQs would be below the Agency’s LOC of 0.1 for listed birds and mammals. 

Additionally, inhalation and spray drift are not exposure routes of concern for birds or 

mammals.

Terrestrial Invertebrates - Honeybee acute adult contact toxicity and acute adult oral 

toxicity data for propoxycarbazone-sodium suggest that propoxycarbazone-sodium is 

practically non-toxic to honeybees on an acute exposure basis. RQs were not calculated 

due to non-definitive endpoints, but even if EECs for honeybees were compared to the 

highest concentrations tested in the submitted honeybee acute contact and oral studies, 

the RQs would not exceed the LOC of 0.4 for bees. 

However, there is uncertainty regarding potential acute and chronic effects of 

propoxycarbazone-sodium on honey bee larval development and survival. Therefore, 

additional data on pollinators are required to understand the risk associated with 

propoxycarbazone-sodium use to the developmental stages of honeybees because 

sensitivity may vary according to life-stage and length (adult vs. larval and acute vs. 

chronic, respectively). EPA intends to issue a DCI to obtain these data. In the near 

future, EPA will provide further information and guidance on this effort. The pollinator 

studies that are anticipated to be required are listed in Table 1 below.
10

Table 1. Potential Pollinator Data Requirements

Test Guideline (GLN) 

Number

Study Type

850.3040** Field testing for pollinators 

Non–GLN*

(OECD 237)

Honey bee larvae acute oral toxicity

Non-GLN* Honey bee adult chronic oral toxicity

Non-GLN* Honey bee larvae chronic oral toxicity

Non-GLN** Semi-field testing for pollinators (tunnel or colony feeding studies)

Non-GLN** Residues in pollen and nectar/field residue analysis

*Tier 1 (laboratory-based studies)

**Tier 2 and 3 (Semi-field and full field colony-level studies). The need for a higher tier test for pollinators will be determined 

based upon lower-tiered tests and/or other lines of data and the need for a refined pollinator risk assessment. 

2. Ecological Incidents

A review of all available information in the following incident databases was completed in 

November 2014: Ecological Incident Information System (EIIS), Avian Monitoring Information 

System (AIMS), and OPP Aggregate Incident Data System (IDS). Based on a search of EIIS, 

the Agency has received 30 reports of adverse field effects to non-target plants linked to 

propoxycarbazone-sodium. A query of AIMS resulted in no records of incidents associated with 

propoxycarbazone-sodium. Based on a search of IDS, between 2005 and 2013, EPA received 

reports of 36 incidents involving propoxycarbazone-sodium, all of which were associated with 

plant damage. For additional discussion of the reported ecological incidents see Preliminary 

Environmental Fate and Ecological Risk Assessment for the Registration Review of 

Propoxycarbazone-sodium, March 3, 2015. 

3. Characterization of Ecological Risk

The preliminary risk assessment for propoxycarbazone-sodium identified some RQs that 

exceeded EPA’s LOC for non-target plant species. The Agency uses the LOC as an indicator of 

potential adverse effects to non-target organisms. LOC exceedances are only one line of 

evidence used by EPA to describe the risks posed by a pesticide to non-target organisms. This 

risk characterization section describes other lines of evidence for propoxycarbazone-sodium, 

puts the LOC exceedances into a broader context, and provides additional perspective on the 

exceedances.

Terrestrial Plants

The preliminary risk assessment for propoxycarbazone-sodium identified potential risks of

concerns for non-target terrestrial plants (monocots and dicots) for almost all modeled exposure 

scenarios (non-listed terrestrial plant RQs range from 0.81 – 5.8 following exposure at labeled

maximum application rates). Toxicity to terrestrial plant species is consistent with the herbicidal 
11

mode of action. The Agency’s principal concern is off-target spray drift resulting from aerial 

applications. The droplet size distribution (DSD) was modeled for both fine to medium and 

medium to coarse DSD categories for aerial spray applications. Potential effects distances are 

significantly reduced using medium to coarse droplet size. Accordingly, the propoxycarbazonesodium technical registrant has agreed to require the use of spray nozzles that limit product 

droplet size to coarse during applications. To further address concern of spray drift impact to 

non-target plants, the propoxycarbazone-sodium registrant has also agreed to various label 

changes designed to reduce off-target spray drift and extent of exposure to non-target plant 

exposure.

Listed Species

Although the Agency is not making a complete endangered species finding at this time and the 

risk conclusions described in this document pertain to non-listed species; the proposed label 

changes to address concern for and reduce spray drift impact to non-target (non-listed) terrestrial 

plants are also expected to reduce the extent of exposure and may reduce risk to the following 

listed taxa whose range and/or critical habitat co-occur with the use of propoxycarbazonesodium: terrestrial and semi-aquatic plants; terrestrial invertebrates; birds; terrestrial and aquaticphase amphibians; reptiles; mammals; freshwater and marine/estuarine fish and invertebrates.

EPA has not yet fully evaluated risks to listed species at this time. The Agency will complete its 

endangered species assessment and any necessary consultation with the Services for 

propoxycarbazone-sodium prior to completing the propoxycarbazone-sodium registration 

review. 

C. Benefits Assessment

Propoxycarbazone-sodium inhibits acetolactate synthase (ALS), and is classified by the Weed 

Science Society of America (WSSA) as a Group 2 herbicide. It is a selective herbicide and is 

absorbed by leaves and roots and then translocated. Propoxycarbazone-sodium is characterized 

by a low rate of use and its efficacy is not affected by low air temperatures. In evaluating 

potential risk mitigation for propoxycarbazone-sodium, EPA considered the risks, the benefits, 

and the use pattern of this compound. EPA believes that there is potential risk to non-target 

plants from the use of propoxycarbazone-sodium. However, these potential risks are outweighed 

by the benefits associated with use of this compound. The major agricultural use of 

propoxycarbazone-sodium is in wheat. It is applied post-emergence to the weeds through ground 

or aerial application equipment. Data from 2010-2014 indicate that it was applied on average to 

more than one million acres annually, approximately 2% of all wheat acres in the United States, 

with a higher percentage in certain regions such as Washington, which suggests that it is an 

important tool for controlling weeds regionally. Propoxycarbazone-sodium is one of the 

commonly used cheatgrass herbicides in winter wheat.

Alternatives to propoxycarbazone-sodium in winter wheat include other ALS herbicides as well 

as synthetic auxins (WSSA Group 4). Alternatives for spring wheat are other ALS herbicides, as 

well as synthetic auxin, and inhibitors of acetyl CoA carboxylase (ACCase) (WSSA Group 1), 
12

and photosystem II inhibitors (WSSA Group 6). Most of these alternatives have been used 

mainly post-emergence, like propoxycarbazone-sodium.

D. Endangered Species Assessment

In November 2013, the EPA, along with the Services and the USDA, released a summary of 

their joint Interim Approaches for assessing risks to endangered and threatened (listed) species 

from pesticides. The Interim Approaches were developed jointly by the agencies in response to 

the National Academy of Sciences’ (NAS) recommendations and reflect a common approach to 

risk assessment shared by the agencies as a way of addressing scientific differences between the 

EPA and the Services. The NAS report1 outlines recommendations on specific scientific and 

technical issues related to the development of pesticide risk assessments that EPA and the 

Services must conduct in connection with their obligations under the ESA and FIFRA. 

The joint Interim Approaches were released prior to a stakeholder workshop held on November 

15, 2013. In addition, the EPA presented the joint Interim Approaches at the December 2013 

Pesticide Program Dialogue Committee (PPDC) and State-FIFRA Issues Research and 

Evaluation Group (SFIREG) meetings. The agencies also held stakeholder workshops —in 

April and October 2014, and in April 2015 — allowing additional opportunities for stakeholders 

to comment on the Interim Approaches. Additional workshops are planned to enhance 

stakeholder involvement. As part of a phased, iterative process for developing the Interim 

Approaches, the agencies will also consider public comments on the Interim Approaches in 

connection with the development of upcoming Registration Review decisions. The details of the 

joint Interim Approaches are contained in the white paper Interim Approaches for National-Level 

Pesticide Endangered Species Act (ESA) Assessments Based on the Recommendations of the 

National Academy of Sciences April 2013 Report2

, dated November 1, 2013. 

Given that the agencies are continuing to develop and work toward implementation of the 

Interim Approaches to assess the potential risks of pesticides to listed species and their 

designated critical habitat, the ecological risk assessment supporting this Proposed Interim 

Decision for propoxycarbazone-sodium does not contain a complete ESA analysis that includes 

effects determinations for specific listed species or designated critical habitat. Although EPA 

has not yet completed effects determinations for specific species or habitats, for this preliminary 

assessment EPA’s evaluation assumed, for all taxa of non-target wildlife and plants, that listed 

species and designated critical habitats may be present in the vicinity of the application of 

propoxycarbazone-sodium. This assessment will allow EPA to focus its future evaluations on 

the types of species where the potential for effects exists once the scientific methods being 

developed by the agencies have been fully vetted. Once the agencies have fully developed and 

implemented the scientific methodology for evaluating risks for listed species and their 

designated critical habitats, these methods will be applied to subsequent analyses for 

propoxycarbazone-sodium as part of completing this registration review. 

 1 Assessing Risks to Endangered and Threatened Species from Pesticides. Available at 

http://www.nap.edu/catalog.php?record_id=18344 

2 Available at http://www2.epa.gov/endangered-species/assessing-pesticides-under-endangered-species-act#report 
13

E. Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of its most recent registration decision for propoxycarbazone-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), 

propoxycarbazone-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. A second list 

of chemicals identified for EDSP screening was published on June 14, 20133 and includes some 

pesticides scheduled for Registration Review and chemicals found in water. Propoxycarbazonesodium was not among the group of 58 pesticide active ingredients on the initial list nor is it on 

the second list of chemicals to be screened under the EDSP. Accordingly, as part of registration 

review, EPA will issue future EDSP orders/data call-ins for registration review chemicals, 

including propoxycarbazone-sodium. 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. 

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

chemicals.
14

In this proposed interim decision, EPA is making no human health or environmental safety 

findings associated with the EDSP screening of propoxycarbazone-sodium. Before completing 

this Registration Review, the Agency will make an EDSP FFDCA section 408(p) determination. 

IV. PROPOSED INTERIM REGISTRATION REVIEW DECISION

A. Risk Mitigation and Regulatory Rationale

As discussed in the Ecological Risk Assessment Section of this document, propoxycarbazonesodium poses a potential risk concern for non-target terrestrial plants exposed to off-target spray 

drift from aerial applications. In evaluating potential risk mitigation for propoxycarbazonesodium, EPA considered the risks, the benefits, and the use pattern of this compound. EPA 

believes that there is potential risk to non-target plants from the use of propoxycarbazonesodium. However, these potential risks are outweighed by the benefits associated with use of this 

compound. To address the risks to non-target plants, EPA is proposing the following risk 

mitigation measures.

1. Spray Drift Reduction

Current propoxycarbazone-sodium labels are inconsistent with respect to droplet size (a major 

factor influencing spray drift). Additionally, some labels designate boom height and wind speed 

while others do not. To address spray drift concerns, the propoxycarbazone-sodium technical 

registrant has agreed to undertake label language changes to achieve uniform spray drift 

parameters across all labels, including droplet size. EPA’s intention is to establish a baseline 

level of protection against spray drift that is consistent across all propoxycarbazone-sodium 

products registered for use in agricultural settings. 

These label changes are expected to reduce the extent of environmental exposure and risk to nontarget plants and animals. Although the Agency is not making a complete listed species safety

finding at this time, these label changes are also expected to reduce the extent of exposure and 

may reduce risk to listed species whose range and/or critical habitat co-occur with the use of 

propoxycarbazone-sodium. 

The Agency is proposing the following label restrictions for propoxycarbazone-sodium:

• Select nozzles and pressure that deliver coarser spray droplets as indicated in nozzle 

manufacturer’s catalogs and in accordance with ASABE Standard S-572.

• Applicators may spray only when wind speed is between 3 and 10 mph. 

• For aerial applications, the release height must be no higher than 10 feet from the top of 

the crop canopy, unless a greater application height is required for pilot safety.

• For aerial applications, the distance of the outer most nozzles on the boom must not 

exceed three-fourths of the length of the wingspan or rotor diameter. To further reduce 

drift, use one-half of the length of the wingspan or rotor diameter at the edge of a field.

• Applicators may not spray during temperature inversions.
15

• For ground applications, boom height must be no higher than 4 feet above the crop 

canopy.

The Agency is encouraging the development of pesticide drift reduction technologies (or DRTs; 

see http://www.epa.gov/reducing-pesticide-drift/about-drift-reduction-technology-program) that 

will help realize user, societal, and environmental benefits including:

• Reducing the loss of pesticide from the application site;

• Improving pest control;

• Slowing the advancement of herbicide-resistant weed populations;

• Reducing pesticide exposures to people, wildlife, and the environment; and

• Reducing risks of damage and liabilities from off-target deposition of drift.

Furthermore, EPA believes that the use of proven DRTs will provide users with a wider range of 

options for addressing drift concerns. Such DRTs could include specialized nozzles, spray

shields, and drift-reducing adjuvant chemicals. The Agency encourages users and producers of 

propoxycarbazone-sodium to consider, test, and use these types of innovations as part of the risk 

management plan for propoxycarbazone-sodium. DRTs are expected to be useful in mitigating 

the risks drift poses to non-target species, and particularly in addressing risks to listed species.

2. Herbicide Resistance Management

The development and spread of herbicide resistant weeds in agriculture is a widespread problem 

that has the potential to fundamentally change production practices in US agriculture. While 

herbicide resistant weeds have been known since the 1950s, the number of species and their 

geographical extent, has been increasing rapidly. Currently there are 249 weed species 

worldwide with confirmed herbicide resistance, especially since the turn of the century. In the 

United States there are 155 weed species with confirmed resistance to one or more herbicides.

Management of herbicide resistant weeds, both in mitigating established herbicide resistant 

weeds and in slowing or preventing the development of new herbicide resistant weeds, is a 

complex problem without a simple solution. Coordinated efforts of growers, agricultural 

extension, academic researcher, scientific societies, pesticide registrants, and state and federal 

agencies are required to address this problem.

The EPA, Office of Pesticide Programs (OPP) is proposing measures for the pesticide registrants 

to provide growers and users with detailed information and recommendations to slow the 

development and spread of herbicide resistant weeds. This is part of a more holistic, proactive 

approach recommended by crop consultants, commodity organizations, professional/scientific 

societies, researchers, and the registrants themselves. OPP’s approach is measured, based on the 

inherent risk of weed resistance developing for a given herbicide, considering the target weeds 

and the agronomic practices of the registered crops. Situations with the least concern for the 

development of herbicide resistant weeds will have the fewest resistance management elements 

and the situations with the highest concern will have additional resistance management elements. 
16

Implementation Timeline and Opportunities for Public Comment on Herbicide Resistance 

Approach

OPP is proposing to implement herbicide resistance measures for existing chemicals during 

registration review, and to implement herbicide resistance measures for new chemicals and new 

uses at the time of registration. In registration review, proposed herbicide resistance elements 

will be included in every herbicide proposed interim decision. Comments on these chemical 

specific measures are welcomed. The Agency will also soon issue a Pesticide Registration 

Notice (PRN) that will provide additional guidance to registrants. All stakeholders are 

encouraged to comment.

Public comments received on both the propoxycarbazone-sodium PID and the PRN will be 

considered prior to the final decision on this propoxycarbazone-sodium registration review.

Propoxycarbazone-sodium Specific Herbicide Resistance Measures

Propoxycarbazone-sodium acts to inhibit acetolactate synthase (ALS), a key enzyme in the 

biosynthesis of the branched-chain amino acids in plants. This herbicide is classified by the 

Weed Science Society of America as belonging to mechanism of action Group 2. This 

mechanism of action (MOA) has a number of confirmed resistant weeds with over 150 

confirmed cases of weed resistance worldwide and 48 cases of resistant weed species in the U.S. 

Of the 48 confirmed ALS resistant weeds in the US, approximately 15 have been identified and 

reported in wheat. Several target weeds in wheat have confirmed resistance to 

propoxycarbazone-sodium. 

The Group 2 herbicides are of the highest concern for weed resistance development because the

mechanism of action already has a large number of confirmed herbicide resistant weed species in 

the U.S., is used on large acreage crop, wheat, with many reported resistant weeds, and Group 2 

has seven commercialized herbicide resistant crops. Proposed herbicide resistance management 

elements for propoxycarbazone-sodium include:

On the label

1. List Mechanism of Action (MOA) WSSA Group 2.

2. List seasonal and annual maximum number of applications and rates for all crops.

3. List best management practices for Herbicide Resistance (as appropriate to crop).

4. State that user should scout before and after application.

5. List the definition of likely resistance on label.

6. State that user should report lack of performance to registrant or their representative. 

7. List confirmed resistant weeds in a separate table and list effective or recommended rates 

for these weeds with the table.

8. For products containing multiple MOA, identify the weeds controlled by each herbicide.

Reporting, Education, and Stewardship
17

9. Registrant should report new cases of likely and confirmed resistance to EPA and users 

yearly. This will be in addition to any adverse effects reporting.

10. For sites/crops of high concern registrant should provide growers with:

• Resistance Management Plan

• Remedial Action Plan

• Educational materials on herbicide resistance management.

B. Tolerance Amendments

EPA has determined that there are no expected adverse human health effects from use of 

propoxycarbazone-sodium. However, the Agency will pursue the following changes to the 

propoxycarbazone-sodium tolerances listed in 40 CFR Section 180.650:

• The tolerances for cattle (meat byproducts), goat (meat byproducts), horse (meat 

byproducts), and sheep (meat byproducts) will be changed from 0.3 ppm to 0.30 ppm to 

reflect the correct number of significant figures, in accordance with current policy.

• Update the tolerance expression in accordance with current policy as recommended in 

Section 2.2.3 of the Propoxycarbazone-sodium. Human Health Assessment Scoping 

Document and Preliminary Human Health Risk Assessment in Support of Registration 

Review.

C. Proposed Interim Registration Review Decision

In accordance with 40 CFR Sections 155.56 and 155.58, the Agency is issuing this Proposed 

Interim Registration Review Decision. Except for the EDSP, ESA and pollinator components of 

this case, the Agency has made the following Proposed Interim Registration Review Decision: 

(1) no additional data are required at this time; and (2) changes to the affected registrations or 

their labeling are needed at this time. 

In this proposed interim registration review decision, EPA is making no human health or 

environmental safety findings associated with the EDSP screening of propoxycarbazone-sodium, 

nor is it making a complete endangered species finding or a complete assessment of effects to 

pollinators. Although the Agency is not making a complete endangered species finding at this 

time, the proposed mitigation described in this document is expected to reduce the extent of 

environmental exposure and may reduce risk to listed species whose range and/or critical habitat 

co-occur with the use of propoxycarbazone-sodium. The Agency’s final registration review 

decision for propoxycarbazone-sodium will be dependent upon the result of the Agency’s ESA 

assessment and any necessary consultation with the Services, an EDSP FFDCA section 408(p) 

determination, and an assessment of non-target exposure to pollinators (bees).

D. Data Requirements

No additional data are required as part of this proposed interim registration review decision. EPA 

will request the propoxycarbazone-sodium registrant to submit pollinator data as a separate 

action.
18

V. NEXT STEPS AND TIMELINE 

A. Interim Registration Review Decision

In accordance with 40 CFR Sections 155.56 and 155.58, the Agency is issuing this Proposed 

Interim Registration Review Decision, and posting it in the propoxycarbazone-sodium 

registration review docket (EPA-HQ-OPP-2015-0095) for a 60-day comment period. If there are 

no significant comments or additional information submitted to the docket during the comment 

period that leads the Agency to change its proposed decision, EPA will issue an Interim 

Registration Review Decision for propoxycarbazone-sodium.

B. Implementation of Mitigation Measures 

Registrants are to submit amended labels that include the label changes summarized in Appendix 

B to the Agency for approval within 60 days following issuance of the Interim Registration 

Review Decision in final form. A summary of the proposed mitigation measures are described in 

Appendices A and B. 
19

Appendix A: Summary of Proposed Actions Taken for Propoxycarbazone-sodium

Appendix B: Propoxycarbazone-sodium label table

Summary of Proposed Labeling Changes for Propoxycarbazone-sodium

Description Proposed Labeling Language for FPE Products Placement on Label

SPRAY DRIFT

Spray Drift 

Language

• Select nozzles and pressure that deliver coarse

(VMD 326-400) spray droplets as indicated in 

nozzle manufacturer’s catalogs and in 

accordance with ASABE Standard S-572.

• Applicators may spray only when wind speed is 

between 3 and 10 mph.

• For aerial applications, the maximum release 

height must be no higher than 10 feet from the 

top of the crop canopy, unless a greater 

application height is required for pilot safety.

• For aerial applications, the distance of the outer 

most nozzles on the boom must not exceed 

three-fourths of the length of the wingspan or 

rotor diameter. To further reduce drift, use 

one-half of the length of the wingspan or rotor 

diameter at the edge of a field.

• Applicators may not spray during temperature 

inversions.

• For ground applications, boom height must be 

no higher than 4 feet above the crop canopy.

Directions for Use

Registration Review Case#: 7264

PC Code: 122019

Chemical Type: herbicide

Chemical Family: Sulfonylaminocarbonyltriazolinone

Mechanism of Action: WSSA Group 2

Affected 

Population(s)

Source of 

Exposure

Route of 

Exposure

Duration of 

Exposure

Risk(s) of 

Concern

Proposed 

Action(s) Taken

• Terrestrial 

Plants 

(monocots 

and dicots)

• Aerial 

Application

• Foliar and 

root 

absorption

• Acute • Acute 

toxicity

• Require 

spray drift 

reduction 

language.

• Require 

herbicide 

resistance 

management 

language on 

label.
20

Summary of Proposed Labeling Changes for Propoxycarbazone-sodium

Description Proposed Labeling Language for FPE Products Placement on Label

HERBICIDE RESISTANCE MANAGEMENT- Products Labeled for Agricultural Use

Herbicide 

Mechanism of Action “Group 2 HERBICIDE”

Front Panel, upper right 

quadrant, surrounded by a 

black (or suitable color) 

rectangle

Weed Resistance 

Management

• Listing of herbicide mechanism of action 

(MOA), and/or WSSA herbicide group 

number, at the top of the first page of each 

product label.

• List seasonal and annual maximum number of 

applications and pounds.

• Resistance management language from PR

Notice 2001-5 and/or Best Management 

Practices (appropriate to crop) from Weed 

Science Society of America (WSSA) & 

Herbicide Resistance Action Committee 

(HRAC), and/or HRAC proposed guidelines 

for herbicide labels.

• Users should scout before and after application.

• Include the definition of likely resistance.

• List confirmed resistant weeds in separate table 

and list effective or recommended rates for 

these weeds with the table.

• For combination products with multiple 

MOAs, list which herbicide is controlling 

which weed and minimum recommended rate.

Directions for Use, prior to 

directions for specific crops 

under the heading “WEED 

RESISTANCE 

MANAGEMENT”