### Docket Number EPA-HQ-OPP-2009-0387 www.regulations.gov



# Maleic Hydrazide

Proposed Interim Registration Review Decision Case Number 0381

March 2015

Approved by:

## ~~~,.,'):> Richard P. Keigwin, Jr. Director
Pesticide Re-evaluation Division

Date: S- 1 

### 7- olOtS-

### Table ofContents



## Contents

I. INTRODUCTION

...................................................................................................................3
A. Public Comments

....................................................................................................................4
II. USE AND USAGE

..................................................................................................................5
A. Agricultural Use

................................... . . .. .....................................................5

B. Non-agricultural Use

.......................................................................................5 

### C. Usage

..........................................................................................................5
D. Benefits

.......................................................................................................6
III. SCIENTIFIC ASSESSMENTS

...............................................................................................6
A. Human Health

...................................................... ...................................................................6
B. Ecological

..............................................................................................................................8
C. Endangered Species Assessment

.......................................................................................... 12
D. Endocrine Disruptor Screening Program

.............................................................................. 13
IV. PROPOSED INTERIM REGISTRATION REVIEW DECISION

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

............................................................................ 14 

### B. Proposed Interim Registration Review Decision

................................................................ 15
V. NEXT STEPS AND TIMELINE

............................................................................................ 15
A. Interim Registration Review Decision

.................................................................................. 15
B. Proposed Data Requirements

.............................................................................................. 16
C. Implementation ofMitigation Measures

................... .......................................................... 16 Appendix A: Summary ofRisk and Proposed Mitigation for Maleic Hydrazide Appendix B: Registration Review Proposed DataNeeds for Maleic Hydrazide Appendix C: Maleic Hydrazide Label Table

2

### I. INTRODUCTION

This document is the Environmental Protection Agency's (EPA orthe agency) Proposed Interim Registration Review Decision for maleic hydrazide, Case #03 81, which is being issued pursuant to 40 CFR sections 155.56 and 155.58. A registration review decision is the agency's detennination ofwhether a pesticide meets, or does not meet, the standard for registration in the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). The agency may issue, whenit detennines 

### itto be appropriate, an Interim Registration Review Decision before completing a registration review. Among other things, the Interim Registration Review Decision may require

new risk mitigation measures, impose interim risk mitigation measures, identify data or information required to complete the review, and include schedules for submitting the required data, conducting the new risk assessment and completing the registration review. For further information on maleic hydrazide, additional documents can be found in EP A's public docket (EPA-HQ-OPP-2009-0387) at www.regulations.gov. FIFRA, as amended by the Food Quality Protection Act (FQPA) of 1996, mandated the continuous review ofexisting pesticides. All pesticides distributed or sold in the United States generally must be registered by the EPA based on scientific data showing thatthey 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 meetthe statutory standard ofno 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. Infonnation on this program is provided at www.epa.gove/oppsrrdl/registration review/.
In 2006, the agency implemented the registration reviewprogram 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.
Maleic hydrazide is a systemic growth retardant with the majority ofend use products formulated using the potassium salt ofmaleic hydrazide. Products containing maleic hydrazide

are registered for use as a plant growth regulator and herbicide, that when sprayed on plants, is absorbed and moves internally where it blocks cell division. Products containing maleic hydra.Zide are registered for use on tobacco, potatoes, onions, non-bearing citrus, residential turf, utility and highway rights-of-way, airports, industrial land, lawns, recreational areas, ornamental/shade trees and ornamental plants. The first product containing maleic hydrazide was registered in 1975 and a Reregistration Eligibility Decision (RED) was issued for maleic hydrazide in June 1994. Pursuant to 40 CFR section 155.50, EPA formally initiated registration review for maleic hydrazide (case 0381) in September 2009. The following highlights significant events that have occurred during the registration review ofmaleic hydrazide and can be found in EPA's public docket, EPA-HQ-OPP-2009-0387, which may be accessed at

www.regulations.gov:

• September 23, 2009

- Publication of

### Maleic Hydrazide SummaryDocument for a 60-day public commentperiod. The 

### Summary Document includedthe 

### Preliminary Work Plan

. (PWP) and was accompanied by the 

### Health Effects Division Scoping Document andthe 

### Registration Review Preliminary Problem Formulation for the Ecological Risk Assessment of Maleic Hydrazide. 

### 3• February 19, 2010

- Final Work Plan (FWP) for maleic hydrazide was issued. One public comment was received during the 60-day commentperiod for the maleic hydrazide PWP. The comment did not change the data and risk assessment needs or the timeline for the maleic hydrazide registration review, so no modifications to the PWP were made.

• August 24, 2010 - A Generic Data Call-In for Registration Review (GDCI 051501-856)

was issued for maleic hydrazide.

• July 

### l, 2014

- The agency published the PreliminaryEcological RiskAssessment for the Registration Review of Maleic Hydrazide and the Maleic Hydrazide, and its Potassium Salt: Qualitative RiskAssessment for Registration Review andScreen of the Hydrazine Impurity for a 60-day public comment period. One comment was received, which is summarized below along with the agency response.

• March 2015

- The agency is now publishing the Maleic Hydrazide ProposedInterim Registration Review Decision onregulation.gov under docket number EPA-HQ-OPP2009-0387.



### A. Public Comments on the Preliminary RiskAssessments
One comment was submitted to the agency during 

### the 60 day public comment period for the Maleic Hydrazide Preliminary EcologicalRiskAssessment and Maleic Hydrazide, and its Potassium Salt: Qualitative RiskAssessment for Registration Review andScreen of the Hydrazine Impurity. The comment received was from the Center for Biological Diversity (CBD) which described the agency's responsibilities under the Endangered Species Act (ESA). The full comment is located in the docket, EPA-HQ-OPP- 2009-0387, accessible at www.regulations.gov.


### Comment Submitted by the Center for Biological Diversity in 

### EPA-HQ-OPP-2009-0387- 0018
Comment: The CBD comments focus on the EPA's independent duty under the Endangered Species Act (ESA) to consult with the U.S. Fish and Wildlife Service and the National Marine Fisheries Service (the Services) on the registration review ofmaleic hydrazide. The CBD comments mention various aspects ofthe risk assessment process, including use ofthe best available data to develop endangered species risk assessments, and evaluation ofeffects on endangered and threatened species and their designated critical habitat. CBD also expresses
concern regarding the rigor ofthe agency's preliminary determinations regarding the effects of maleic hydrazide on endangered and threatened (listed) species and their designated critical habitat for the maleic hydrazide registration review.

Response: EPA has reviewed the comments from CBD on the registration review preliminary risk assessments for maleic hydrazide and plans to address many ofthe concerns raised by CBD

as part ofthe implementation plan for assessing the risks ofpesticides to listed species based on the recommendations ofthe April 2013 National Academy ofSciences (NAS) report. EPA will address concerns specific to m.aleic hydrazide in connection with the development ofits registration review decision for maleic hydrazide. See the section entitled "Endangered Species Assessment" for more information.



### 4

### II. USE AND USAGE
Maleic hydrazide is a systemic growth retardant with the majority ofend use products formulated using the potassium salt ofmaleic hydrazide. Products containing maleic hydrazide

are registered as plant growth regulators (sprout inhibitor) and herbicides whose mode ofactivity is as a uracil antimetabolite. When sprayed onplants, it is absorbed and moves internally where it blocks cell division. Products containing rnaleic hydrazide are registered for use on tobacco, potatoes, onions, non-bearing citrus, residential turf, utility and highway rights-of-way, airports, industrial land, lawns, recreational areas, ornamental/shade trees and ornamental plants. Formulations include an emulsifiable concentrate and soluble concentrate/liquid and solid. Maleic hydrazide is applied by aircraft or ground spray equipment.



### A. Agricultural Use Maleic hydrazide is used to prevent sucker development on flue-cured, burley, dark, Maryland and cigar (Pennsylvania and Wisconsin) tobacco. Under normal growing conditions maleic hydrazide will control the growth ofnew suckers for about six weeks after application. Maleic hydrazide is also used on potatoes to help reduce the number ofvolunteer potatoes, and to control the sprouting ofpotatoes in storage. Maleic hydrazide has also been shown to reduce shrinkage ofonions in storage.



### B. Non-agricultural Use Maleic hydrazide is used to control the growth ofperennial grasses on commercial and residential turf. Maleic hydrazide can slow grass growth in hard-to mow commercial 

### turf locations, such as areas along highways, airport property, military installations, Federal, state and municipal properties, industrial areas, golfcourse roughs and similar areas. Perennial grasses controlled by maleic hydrazide include: bluegrasses, fescues, bromegrass, orchard grass, quackgrass, perennial rye, ryegrass and bahiagrass. On golfcourse fairways, maleic hydrazide

can reduce Poa (annual bluegrass) and inhibit the growth ofbermudagrass, enabling ryegrass or other grasses to produce a good stand. On home lawns (turf), maleic hydrazide can be used as a band or edge treatment to slow grass growth in areas where it is difficult to trim mechanically. On ornamental trees and shrubs, maleic hydrazide canbe used to inhibit the growth ofHahn and Algerian 

### Ivy. On fallow land, maleic hydrazide can be used to control Silverleafnightshade, a perennial weed that over-winters and may compete 

### with subsequent crops and cultivations.



### C. 

### Usage Based onthe 2012 Screening Level Usage Analysis (SLUA) most ofthe maleic hydrazide used in the U.S. is applied to tobacco (80%), followed by potato (18%). In 2012 an estimated 600,000 lb ofactive ingredient (a.i.) was applied to tobacco, with an average percent crop treated (PCT) of65% (max 80%). Next was potato with an estimated 200,000 lb a.i. applied annually with an average PCT of 10% (max 15%), then 30,000 lb a.i. for onion (10% avg PCT), and <500 lb a.i. for shallot. No information is available on non-agricultural usage ofmaleic hydrazide.



### 5

### D. Benefits Maleic hydrazide is the only systemic treatment (i.e., absorbed by leaves and translocated through the plant) available which controls suckers in tobacco'. Restriction ofsucker growth in tobacco contributes to higher yields, better quality leaf, and more efficient use ofharvesting equipment'. Chemical sucker control (such as with maleic hydrazide) may also result in reduced production cost by reducing cultural practices otherwise done by hand1• 

### Maleic hydrazide use on potatoes contributes to control ofsprouting, which helps reduce any unwanted cropping, and decreases the number ofundersized potatoes in the field at harvest. For potatoes and onions, maleic hydrazide is also effective at controlling sprout growth in storage, providing an extended dormancy break2•



## III. SCIENTIFIC ASSESSMENTS

A. 

### Human Health
There are no dietary, residential, occupational, or aggregate risks ofconcern for maleic hydrazide. The agency reviewed the toxicological database for maleic hydrazide and did not identify toxicity endpoints for maleic hydrazide. As a result, a quantitative human health risk assessment was not necessary to conclude with reasonable certainty that exposures from the currently registered uses ofmaleic hydrazide do not pose a significant human health risk.A summary of the agency's human health risk assessment is presented below. For detailed discussions of all aspects ofthe human health risk assessment, see the document Maleic Hydrazide, and its Potassium Salt: Qualitative RiskAssessment for Registration Review and Screen of the Hydrazine Impurity, 

### dated June 18, 2014, available in the public docket EPAHQ-OPP-2009-0387, which can be accessed at www

.regulations.gov.



### 1. Risk Conclusions DietaryAssessment


### While exposure to maleic hydrazide exists from food and drinking water, based on a qualitative assessment, no dietary risk is expected to result from registered uses ofmaleic hydrazide.

ResidentialAssessment


### While exposure to maleic hydrazide exists from residential use (i.e., golfcourse and spot/perimeter treatment), based on a qualitative assessment, no residential risk is expected to result from registered uses ofmaleic hydrazide. AggregateAssessment


### Since the agency does not expect risk for dietary and/or residential exposure, no aggregate risk is expected to result from registered uses ofmaleic hydrazide.

1 Moore, Michael J. Topping and ChemicalSucker Control Programs for Georgia. 2 Comin, Donald. Inhibiting Sprouting of Potatoes and Onions in Storage in Ohio. 

### 6

### Cumulative Assessment
Unlike other pesticides for which EPA 

### has followed a cumulative risk approach based on
a common mechanism oftoxicity, EPA has not made a common mechanism oftoxicity finding

as to maleic hydrazide and any other substances, and maleic hydrazide does not appear to produce a toxic metabolite produced by other substances. For information regarding EPA's efforts to determine which chemicals have a common mechanism oftoxicity and to evaluate the cumulative effects ofsuch chemicals, see the policy statements released by EPA's Office of Pesticide Programs concerning common mechanism determinations and procedures for cumulating effects from substances found to have a common mechanism on EPA's website at http://www.epa.gov/pesticides/cumulative/. OccupationalAssessment
While occupational exposure to maleic hydrazide is expected, based on a qualitative assessment, no occupational risk is expected from the registered uses ofmaleic hydrazide. Hydrazine
While the Agency did not identify toxicity endpoints for maleic hydrazide per se, the technical grade active ingredient maleic hydrazide contains the contaminant hydrazine, which 

### has been associated with known cancer effects. In 1982, the agency established a 15 ppm upper limit for hydrazine in technical products that contain maleic hydrazide to protect against potential cancer risk. During registration review, the agency reviewed its information on hydrazine, establishing that current technical products that contain maleic hydrazide do not contain hydrazine in excess of 15 ppm, and conducted a screening level aggregate cancer assessment ofhydrazine at the 15 ppm limit. Based upon this re-assessment ofhydrazine, the agency confirmed that the current upper limit of 15 ppm in technical products poses no risk

concern. For more discussion ofhydrazine please see the document, Maleic Hydrazide. and its Potassium Salt: Qualitative RiskAssessment/orRegistration Review andScreen of the Hydrazine Impurity, dated June 18, 2014, available in the public docket EPA-HQ-OPP-2009- 0387, which can be accessed at www.regulations.gov.



### 2. Human Incidents In 2009 the agency conducted a search ofavailable adverse effects information to identify any adverse human health incidents attributable to maleic hydrazide. The agency reviewed the National Office ofPesticide Programs (OPP) Incident Data System (IDS), for the years 2002 through 2009 and found no human health incidents attributable to maleic hydrazide. The full review ofincident reports can be found in the Updated Review of Maleic Hydrazide Incidents, located in the public docket under EPA-HQ-OPP-2009-0387, which can be accessed at www.regulations.gov. Based upon the lack ofincidents identified in the 2009 search, no update search was conducted.



### 3. Food Tolerances
Tolerances for residues ofmaleic hydrazide on food are established in 40 CFR 

### §180.175. The agency has determined that, given 

### its low toxicity and there being no toxicity endpoints identified for maleic hydrazide, that the current tolerances for maleic hydrzide may be changed

7to exemptions from the requirement for a tolerances. Ifthese exemptions are not sought, then additional tolerances for residues ofmaleic hydrazide in livestock commodities will need to be established. For more information on tolerance harmonization review for maleic hydrazide, please see, Maleic Hydrazide, andits Potassium Salt: Qualitative RiskAssessment for Registration Review andScreen of the Hydrazine Impurity.



### B. Ecological
A summary ofthe agency's ecological risk assessment is presented below. The agency used the most up-to-date science policies and risk assessment methodologies to prepare a quantitative ecological risk assessment in support ofthe registration review ofmaleic hydrazide. For a detailed discussion ofecological fate and effects for maleic hydrazide see Preliminary Ecological RiskAssessment for the Registration Review of Ma/eic Hydrazide dated June 18, 2014, available in the public docket EPA-HQ-OPP-2009-0387, which can be accessed at http:/ /www.regulations.gov/.
The agency also completed a screening-level endangered and threatened (listed) species assessment for maleic hydrazide. The agency is currently working with its federal counterparts 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 maleic hydrazide. As such, only screeninglevel risks to non-listed species are described herein, risks to listed species will not be characterized.

1. 

### Environmental Fate
For the ecological risk assessment, maleic hydrazideper se has been identified as the only residue ofconcern. The major degradate ofmaleic hydrazide is C02. Other degradates of maleic hydrazide were identified in small amounts, and also degrade to C02

. Maleic hydrazide is considered fairly non-persistent in the environment, and is expected to be mobile due to its low adsorption to soils. Due to its mobility and persistence in anaerobic conditions, maleic hydrazide products are required to contain surface water advisory language on their labels.



### 2. Risk Conclusions
Inthe preliminary ecological risk assessment, a use rate of 13 lb a.i./acre was calculated for the fallow/idle land use ofmaleic hydrazide, and a use rate of9.2 lb a.i./acre was calculated for the ornamental/shade tree use ofmaleic hydrazide. However, during the risk management phase, the agency recalculated these application rates, and identified that the correct rate, for both the fallow/idle land, and ornamental/shade tree uses ,is 9.0 lb a.i./acre. For many taxa, the agency evaluated potential risk at 9.2 lb a.i./acre. Since there would likely be very little difference between RQs based upon 9.2 lb a.i./acre and RQs based upon 9.0 lb a.i./acre, the agency decided to base its risk management considerations upon RQs calculated at the 9.2 lb a.i./acre rate.
TerrestrialAssessment

8Mammals Toxicity data with mammals indicated no acute mortality or sublethal effects up to the highest dose tested. Since the estimated environmental concentrations (EECs) are greater than the highest dose tested, the agency used the highest dose tested 

### (i.e., the non-definitive endpoint) to compare to the EEC and report a highly conservative risk quotient (RQ). Using the nondefinitive endpoint and EECs (estimated from 9.2 lb a.i./acre) acute mammalian RQs ranged from below levels ofconcern to 0.19, where the listed LOC = 0.1 and the non-listed LOC = 0.5.

Chronic LOC exceedances for mammals were identified for uses with a maximum application rate of6.1 lb a.i./acre or greater, which include tobacco, golfcourse turf, ornamental shade trees and fallow/idle land. Chronic RQs ranged from below the LOC to 1.92, exceeding the LOC of 1.0 (applicable to both listed and non-listed mammalian species).

Birds
Birds are considered surrogates for terrestrial phase amphibians and reptiles. 

### Inthe available acute toxicity data for maleic hydrazide, no mortality or sublethal effects were seenup to the highest dose tested. Since the estimated environmental concentrations (EECs) are greater than the highest dose tested, the agency used the highest dose tested 

### (i.e., the non-definitive endpoint) to compare to the EEC and report a highly conservative risk quotient (RQ). Using the non-definitive endpoints, acute LOC exceedances were identified birds, where the maximum application rate is greater than 4.6 lb a.i./acre, which include ornamental woody shrubs, tobacco, golfcourse turf, ornamental shade trees and fallow/idle land. Acute avian dose-based RQs exceed the LOC, ranging from below the acute LOC to 1.30. Dietary-based RQs are below LOCs for all size classes.
No chronic toxicity data for birds 

### was available to evaluate chronic risk to birds. As a result, chronic risk to birds is uncertain.

Terrestrial Invertebrates

Acute toxicity data with the honey bee (considered surrogates for terrestrial invertebrates)

was also non-definitive, where the highest dose tested in the acute toxicity test (designed to indicate an LDso value) only resulted in 3.2% mortality. Based on the non-definitive endpoint, acute RQs ranged from below the LOC to 0.68, where the interim non-listed terrestrial invertebrate LOC = 0.4, and the interim listed terrestrial invertebrate LOC 

### = 0.05. The LOC is exceeded for uses with maximum application rates of6.1 lb a.i./acre or greater, which include tobacco, golfcourse turf, ornamental shade trees and fallow/idle land.

No chronic terrestrial invertebrate data was available, therefore, due to a lack ofsufficient data, risk to terrestrial invertebrates is uncertain.

Terrestrial Plants

- dry and semi-aquatic

For terrestrial plants, LOC exceedances (where the LOC 

## = 1) were identified at all application rates for maleic hydrazide uses. RQ estimates presented in the ecological Preliminary Risk Assessment (in Table 17) represent potential risk at the edge ofthe field either from run-offor from spray drift, and are based upon an application rate of 13 lb a.i./acre. The estimated RQs range from below the LOC to 18.82. At 9.2 lb a.i./acre RQs would be lower but 9would continue to exceed the LOC for listed and non-listed dry monocots; listed dry dicots; all semi-aquatic monocots and dicots, and listed monocots from aerial spray drift. For all uses, risks exceed the LOC for semi-aquatic plants; RQs range from belowthe LOC to 13.49. At the lower application rate of6.1 lb a.i./acre (tobacco) risks no longer exceed the LOC for dry dicots.


### AquaticAssessment
Predicted EECs are lower than any ofthe available ecotoxicity endpoints for fish, aquatic invertebrates, or aquatic plants

. Therefore, estimated RQs are below all LOCs (both non-listed LOCs and listed LOCs) for these tax.a.



### 3. Ecological Incidents
The Ecological Incident Information System (EIIS), Avian Incident Monitoring System (AIMS), and aggregate incident databases were searched for reports on March 11, 2014, and no adverse incidents attributed to maleic hydrazide were identified for the period between 1995 and 2014. A more detailed discussion ofthe search can be found in 

### Preliminary Ecological Risk Assessment/or the Registration Review of Maleic Hydrazide.



### 4. Risk Characterization Ecological
The actual maximum application rate for products containing maleic hydrazide is 9.0 lb a.i./acre. Due to a miscalculation, RQ estimates based on 13 lb a.i./acre are included in the ecological risk assessment. While the agency did not assess ecological risk based upon 9.0 lb a.i./acre, the agency did estimated RQs based on 9.2 lb a.i./acre. Differences betweenRQs based

on 9.2 lb a.i./acre and RQs based on 9.0 lb a.i./acre would be negligible, and therefore the agency will base itsjudgement ofLOC exceedances, its risk characterization, and its proposed risk management on the 9.2 lb a.i./acre application rate. Basedupon the 9.2 lb a

.i./acre rate, the agency estimated RQs for several tax.a that exceed LOCs, see Table 1 below.



### Table 1. Summary ofHighest RQs for Maleic Hydrazide
Taxa 

### Duration LOC 

### HighestRQs
Mammals Chronic 1.0 1.92
Birds Acute 0

.5 1.30
Terrestrial Acute 0.4 0.68 Invertebrates
Terrestrial Plants Acute 1.0 2.45 (Dry) non-listed
Terrestrial Plants Acute 1.0 13.49 (semi-aquatic) nonlisted

10Terrestrial Plants Acute 1.0 3.42 (Dry) listed
Terrestrial Plants Acute 1.0 18.82 (semi-aquatic) listed

The highest RQ for acute risk to mammals, representing the most conservative exposure scenario, is below the agency's LOC. However, some chronic risks to mammals exceed the LOC. The highest chronic RQ for mammals is 1.92 (LOC= 1.0) for small and medium sized mammals. In estimating this chronic RQ, the agency employed a no observed adverse effect level (NOAEL) of 10,000 mg/kg diet (based upon 8.5% body weight loss seen at 30,000 mg/kg diet). The agency notes that while this effect is considered statistically significant, its biological significance is equivocal, and it is uncertain whether 8.5% body weight loss would affect fitness ofan organism. 

### Ifthe 30,000 mg/kg diet was used as a NOAEL, (based upon decreased body weight ofoffspring at 50,000 mg/kg diet), then the maximum RQ would be 0.90, and no longer exceed the LOC (1.0) for all size classes ofnon-listed and listed mammals. 

### In addition, the EECs used to calculate these RQs are estimated by the Kenaga model, which relies onupper-bound values (90th percentile residue exposure). Ifmean Kenaga values are used instead, to be more representative 

### ofexpected exposure, chronic mammal risk (already belowthe LOC) is further reduced.
For birds, the highest acute dose-based RQ for risk to birds is 1.83. Inestimating the acute RQs the agency employed the most conservative (lowest) acute non-definitive LDso of 2,000 mg/kg, were no lethality or sublethal effects were seen. Other acute ecotoxicity studies, with higher test doses, are also in the database that showed a slight or no effects. Including studies with doses up to 2150 mg/kg diet, 4640 mg/kg diet, and 10,000 mg/kg diet. Ifan endpoint of4640 mg/kg diet (the highest treatment level showing only slight body weight effects) is used to calculate an acute RQ, instead of2,000 mg/kg diet, the RQ for 

### small birds feeding on short grass, the most conservative exposure scenario, is 0.56, which is very near the agency LOC for non-listed birds (0.5). In addition, the EEC concentrations used to calculate these RQs are estimated with upperbound (90th percent) exposure values. Ifmean exposure values are used to estimate exposure, to be more representative ofexpected exposure, acute avian risk is further reduced to below the LOC.
No chronic data were available to estimate chronic risk to birds, resulting in uncertainty regarding potential risk. Based on chronic mammal data, which does not directly relate to chronic risk to birds, there could be a potential for risks which are near or over the agency LOC. The agency needs chronic avian toxicity data before determining potential chronic risk to this taxa. For terrestrial invertebrates, the acute risk is estimated to be 0.68, which marginally exceeds the agency LOC of0.4. In estimating this RQ, the agency employed an endpoint based

on an acute contact study with honey bees, where only 3.2 

### % mortality was observed at the highest tested dose. No other data with the honey bee are available to characterize the potential hazard ofmaleic hydrazide to honey bees. The agency also reviewed open literature data with predatory mites and parasitic wasps that showed potential effects at approximately 4.5 lbs. a.i./acre. Therefore, due to the lack ofdata, because estimated risk likely exceeds the agency 11

### LOC, and without both acute (oral) and chronic data, the agency cannot preclude risk to terrestrial invertebrates. The agency needs more data, specifically on pollinators, before determining potential risk to this taxa.
As a plant growth regulator and herbicide, risks to terrestrial plants represent the highest risk values for maleic hydrazide. RQs for terrestrial and semi-aquatic dicots and semi-aquatic monocots at the edge-of-the-field exceed the agency's LOC. Estimated RQs indicate that semiaquatic plants are more sensitive than dry 

### plants and that the application method (ground vs. aerial) has only a slight effect onthe estimated RQs. The highest non-listed terrestrial plant RQ is for semi-aquatic monocots at 13.49. Spray drift and application method are not major contributors to risk, while runoffis likely the greatest contributor to risk.



### C. Endangered Species Assessment
Consistent with EPA's responsibility under the Endangered Species Act (ESA), the Agency will evaluate risks to federally listed threatened and endangered (listed) species from registered uses ofpesticides in accordance with the Joint Interim Approaches developed to implement the recommendations ofthe April 2013 National Academy ofSciences (NAS) report3

, AssessingRisks to Endangeredand ThreatenedSpecies from Pesticides. 

### The NAS report 2

### outlines recommendations on specific scientific andtechnical issues related to the development ofpesticide risk assessments that EPA and the Services must conduct in connection with their obligations under the ESA and FIFRA. EPA will address concerns specific to maleic hydrazide in connection with the development ofits final registration review decision for maleic hydrazide.

In November 2013, EPA, the U.S. Fish and Wildlife Service, National Marine Fisheries Services (the Services), and the U.S. Department ofAgriculture released a white paper containing a summary oftheirjoint Interim Approaches for assessing risks to listed species from pesticides. These Interim Approaches were developedjointly by the agencies in response to the NAS recommendations, and reflect a common approach to risk assessment shared by the agencies as a way ofaddressing scientific differences between the EPA and the Services. Details ofthejoint Interim Approaches are contained in the November 1, 2013 white paper,,, Interim Approaches for National-Level Pesticide EndangeredSpeciesActAssessments Basedon the Recommendations of the NationalAcademy o.fSciencesApril2013 Report. 4



### Given that the agencies are continuing to develop and work toward implementation ofthe Interim Approaches to assess the potential risks ofpesticides to listed species and their designated critical habitat, the ecological risk assessment supporting this Proposed Interim Registration Review Decision for maleic hydrazide does not contain a complete ESA analysis, including effects determinations for specific listed species or designated critical habitat. While the agencies continue to develop a common method for ESA analysis, the preliminary risk assessment for the registration review ofmaleic hydrazide describes the level ofESA analysis completed for this particular registration review case. This assessment will allow EPA to focus its future evaluations on the types ofspecies where the potential for effects exists. once the

3 http://www.nap.edu/catalog.php?record id= 18344

4 http://www.epa.gov/espp/2013/nas.html 

### 12scientific methods being developed by the agencies have been fully vetted. Once the agencies have fully developed and implemented the scientific methods necessary to complete risk assessments for listed species and their designated critical habitats, these methods will be applied to subsequent analyses ofmaleic hydrazide as part ofcompleting this registration review.

D. 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 ofcarcinogenicity, 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 andreproductive effects in different taxonomic groups. As part ofits most recent registration decision for maleic hydrazide, EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. As required by FFDCA section 408(p ), maleic hydrazide is subject to the endocrine screening part ofthe 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 ofa battery of 11 screening assays to identify the potential ofa 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 ofthe EDSP where EPA will determine which, ifany, ofthe 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 of67 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, 2013 5 and includes some pesticides scheduled for Registration Review and chemicals found in water. Neither ofthese lists should be construed as a list ofknown or likely endocrine disruptors. For further information on the status ofthe EDSP, the policies and procedures, the lists ofchemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our website. 6

In this proposed interim decision, EPA is making no human health or environmental safety findings associated with the EDSP screening ofmaleic hydrazide. Before completing this Registration Review, the agency will make an EDSP FFDCA section 408(p) determination.

5 See http://www.regulations.gov/#!documentDetail:D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of chemicals.
6 http://www.epa.gov/endo/ 

### 13

### IV. PROPOSED INTERIM REGISTRATION REVIEW DECISION
A. Risk Mitigation and Regulatory Rationale
Under FIFRA, when considering whether a pesticide poses unreasonable adverse ecological effects from its use, the agency considers both risks and benefits. As discussed in Section III. ofthis document, the agency identified LOC exceedances for several tax.a including birds (surrogate for terrestrial-phase amphibians and reptiles), mammals, and terrestrial plants (monocot and dicot). Due to a lack ofdata, the agency is not able to make a determination regarding potential risk to terrestrial invertebrates or regarding potential chronic risk to birds. The agency also provided information to further characterize the potential ecological risks from maleic hydrazide. 

### In Section II. ofthis document, the agency briefly discusses the use and benefits ofmaleic hydrazide which indicate rnaleic hydrazide is an important tool in the production oftobacco, onions, and potatoes. However, little information is available indicating maleic hydrazide benefits from use on fallow/idle land, ornamental trees and shrubs, or turf

. The acute RQs to birds and chronic RQs to mammals have been characterized in the

same way, using alternative endpoints that result in RQs that do not exceed LOCs. Therefore, when the estimated RQs for birds and mammals are viewed in the context ofrisk characterizations, the agency believes that acute risks to birds and chronic risks to mammals are low or below the LOC, and therefore neither additional mitigation nor additional data are believed to be needed

.for these scenarios.
A lack ofdata precludes the agency from making a determination with respect to the potential chronic effect to birds. Basedon low chronic risk exhibited by maleic hydrazide to mammals, the agency reasons that chronic riskto birds is low, and therefore does not propose additional mitigation at this time. However, the agency proposes to require chronic avian toxicity data, identified below, in order to better inform the potential chronic risk ofmaleic hydrazide to this taxa. (See also, Appendix B: Maleic Hydrazide Proposed DataNeeds)

• Avian reproduction (Guideline 850.2300)
While a lack ofdata precludes the agency from making a determination with respect to potential risks to terrestrial invertebrates, the available information (i.e., low acute toxicity) indicate that risk is likely low, and therefore the agency is not proposing additional mitigation for this scenario at this time. However, the agency proposes to require pollinator data (nonguideline studies), identified below, 

### in order to better inform the potential risk ofmaleic hydrazide to terrestrial invertebrates. (See also, Appendix B: Maleic Hydrazide Proposed Data needs)

• Acute oral toxicity to adult honey bees

• Acute oral toxicity to larval honey bees

• Chronic toxicity to adult bees

• Chronic oral toxicity to larval honey bees

• Field trail ofresidues in pollen and nectar

• Semi-field testing for pollinator

14

### The agency determined that certain LOC exceedances exist for terrestrial plants for all application scenarios ofmaleic hydrazide (i.e

., at all registered application rates)

. The agency also notes that the primary benefits ofmaleic hydrazide are to tobacco production, potato and onion production (with maximum application rates of6.1 lb a.i./acre, 4.3 lb a.i./acre and 2.9 lb a.i./acre respectively). However, little benefits information is available for uses such as fallow/idle land, ornamentals, or non-agricultural turf(with application rates of9.0 lb a.i./acre 8.7 lb a.i./acre and 8 lb a.i./acre respectively). In the absence ofbenefits information on the maleic hydrazide uses with higher application rates, the agency proposes to bring the benefits into balance with the potential risks by lowering the maximum annual application rate to 6.1 lb a.i./acre (same as the tobacco use rate) for maleic hydrazide use on: idle land, fallow land, CRP land, ornamentals and/or shade trees and shrubs, ornamental lawns and 

### turf, airports, golfcourse 

### turf, right-of-ways, nonagricultural areas, uncultivated soils, and urban areas (also listed in Appendix C). Lowering the application rate for these uses would reduce all estimated plantRQs, and would specifically reduce RQs for dry dicots to below the LOC, and reduce all RQs from spray drift beyond the edge-of-the-field to belowthe LOC. Even with these changes slight LOC exceedances are still expected for risk to 

### dry and semi-aquatic monocots. The agency is not proposing to require additional data for this scenario. Finally, the agency notes that current product labels are missing or contain certain information that is unclear or inconsistent regarding the maximum number ofapplications allowed per year. The agency proposes to require registrants ofmaleic hydrazide products 

### to rectify their labels to specify a maximum ofI application per year with the exception oftobacco which will be allowed a second application in case ofrain within 6 hours after application of maleic hydrazide (see Appendix C: Maleic Hydrazide Label Table), and non-bearing citrus which allows up to 2 applications per year.



### B. 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 and ESA components of this case, the agency has made the following Proposed Interim Registration Review Decision: (1) reduce maximum application rates to 6.1 lb a.i./acre ofmaleic hydrazide on certain sites, identified in Appendix C, to reduce potential risk to terrestrial plants; (2) to better assess potential exposure and effects to honey bees and birds, the agency proposes requiring additional data, identified in Appendix B; (3) change maleic hydrazide labels, as identified in Appendix C, specifying the maximum number ofapplications annually to clarify product labels.
In this proposed interim registration review decision, EPA is making no human health or environmental safety findings associated with the EDSP screening ofmaleic hydrazide, nor is it making a complete endangered species finding. The agency's final registration review decision for maleic hydrazide will depend upon boththe result ofan ESA Section 7 consultation with the Services, and an EDSP FFDCA section 408(p) determination.



### V. NEXT STEPS AND TIMELINE
A. Interim Registration Review Decision

15In accordance with 40 CFR Sections 155.56 and 155.58, the agency is issuing this Proposed Interim Registration Review Decision, and placing it in the maleic hydrazide registration review docket (EPA-HQ-OPP- 2009-0387) for public comment for 60 days. A Federal RegisterNotice will announce the availability ofthis Proposed Interim Registration Review Decision for maleic hydrazide and initiate a 60-day comment period. 

### Ifthere are no significant comments or additional information submitted to the docket during the comment period that leads the agency to change its decision, EPA will issue an Interim Registration Review Decision for maleic hydrazide (case 03 81 ).

B. Proposed Data Requirements
The agency proposes to require additional data, identified in Appendix B, to better assess potential risks. A Data Call-In Notice will be issued following the issuance ofthe Interim Registration Review Decision.



### C. Implementation ofMitigation Measures
Once the Interim Registration Review Decision is issued in final form, registrants affected bythe required label changes will be required to submit amended labels that include the label changes summarized 

### in Appendix C to the agency for approval within 60 days following issuance ofthe Interim Registration Review Decision in 

### final form. A summary ofthe mitigation measures are described 

### in Appendix A.

16AppendixA:SummaryofRisksandProposedMitigationforMaleicHydrazideRegistrationReviewCase#:0381PCCode:051501ChemicalType:HerbicideIPlantGrowthRegulatorChemicalFamily:NIAModeofAction:UracilantimetaboliteAffectedPopulation(s)SourceofExposureRouteofExposureDurationofRisk(s)ofConcernMitigationMeasuresCommentExposureTerrestrial(monocot)andSpraydriftandNotapplicablePossibleeffectstooff-site!ReducemaximumNoinformationissemi-aquatic(monocotandrunoffnon-targetplantssingleandannualavailabledescribingdicot)plantsand!applicationrateto6.1thebenefitsofhigherlba.i./acreforallusesapplicationratesforitishigherorfallow/idleland,turf,tnotspecified.landornamentals.AppendixB:RegistrationReviewProposedDataNeedsforMaleicHydrazideStudyTitleGuideline/Referenee1.AvianReproduction(mallard)GuidelineNumber850.23002.AcuteoraltoxicitytoadulthoneybeesNon-guideline,OECDTG2133.AcuteoraltoxicitytolarvalhoneybeesNon-guideline,OECDTG2374.ChronictoxicitytoadultbeesNon-Guideline5.ChronicoraltoxicitytolarvalhoneybeesNon-guideline6.FieldtrailofresiduesinpollenandnectarNon-guideline7.Semi-fieldtestingforpollinatorNon-guideline,OECDGuidance752AppendixC:MaleicHydrazideLabelTableDescriptionAmendedLabelingLanguageforMaleicHydrazideUseProductsPlacementonLabelEndUseProductsSpecifymaximumSpecifyamaximumofoneapplicationperyear.Exceptionfortobaccowherere-applicationmaybemadecaseofrainDirectionsforUsenumberofapplicationswithin6hoursafterapplicationofmaleichydrazideproducts,andnon-bearingcitrustreeswhereasecondapplication(annual)maybemadebasedonseasonaltemperaturevariations.SetmaximumannualForalluseswherethemaximumapplicationrateisnotspecifiedorgreaterthan6.llba.i./acre,includingidleland,DirectionsforUseapplicationratefallow,land,CRPland,ornamentaland/orshadetreesandshrubs,ornamentallawnsandturf,airports,golfcourseturf,right-of-ways,nonagriculturalareas,uncultivatedsoils,andurbanareas:Specifyamaximumannualapplicationrateof6.1lba.i./acre.