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 of Contents 

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 Pro gram .............................................................................. 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 of Mitigation Measures ................... .......................................................... 16 

Appendix A: Summary of Risk and Proposed Mitigation for Maleic Hydrazide 

Appendix B: Registration Review Proposed Data Needs for Maleic Hydrazide 

Appendix C: Maleic Hydrazide Label Table 

2 
I. INTRODUCTION 

This document is the Environmental Protection Agency's (EPA or the 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 of whether a pesticide meets, or does not meet, the standard for registration in the 

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). The agency may issue, when it 

detennines it to 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 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. Infonnation on this program is 

provided at www.epa.gove/oppsrrd l/registration review/. 

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. 

Maleic hydrazide is a systemic growth retardant with the majority of end use products 

formulated using the potassium salt of maleic 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 of maleic 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 Summary Document for a 60-day 

public comment period. The Summary Document included the Preliminary Work Plan . 

(PWP) and was accompanied by the Health Effects Division Scoping Document and the 

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 comment period 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 Preliminary Ecological Risk Assessment for the 

Registration Review of Maleic Hydrazide and the Maleic Hydrazide, and its Potassium 

Salt: Qualitative Risk Assessment for Registration Review and Screen 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 Proposed Interim 

Registration Review Decision on regulation.gov under docket number EPA-HQ-OPP2009-0387. 

A. Public Comments on the Preliminary Risk Assessments 

One comment was submitted to the agency during the 60 day public comment period for 

the Maleic Hydrazide Preliminary Ecological Risk Assessment and Maleic Hydrazide, and its 

Potassium Salt: Qualitative Risk Assessment for Registration Review and Screen 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 of maleic hydrazide. The CBD 

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

available data to develop endangered species risk assessments, and evaluation of effects on 

endangered and threatened species and their designated critical habitat. CBD also expresses 

concern regarding the rigor of the 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 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 m.aleic hydrazide in connection with the development of its 

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 of end use products 

formulated using the potassium salt of maleic hydrazide. Products containing maleic hydrazide 

are registered as plant growth regulators (sprout inhibitor) and herbicides whose mode of activity 

is as a uracil antimetabolite. When sprayed on plants, 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 of new suckers for about six weeks after application. 

Maleic hydrazide is also used on potatoes to help reduce the number of volunteer potatoes, and 

to control the sprouting of potatoes in storage. Maleic hydrazide has also been shown to reduce 

shrinkage of onions in storage. 

B. Non-agricultural Use 

Maleic hydrazide is used to control the growth of perennial 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, golf course roughs and similar areas. Perennial grasses 

controlled by maleic hydrazide include: bluegrasses, fescues, bromegrass, orchard grass, 

quackgrass, perennial rye, ryegrass and bahiagrass. On golf course 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 can be used to inhibit the growth of Hahn and 

Algerian Ivy. On fallow land, maleic hydrazide can be used to control Silverleaf nightshade, a 

perennial weed that over-winters and may compete with subsequent crops and cultivations. 

C. Usage 

Based on the 2012 Screening Level Usage Analysis (SLUA) most of the maleic 

hydrazide used in the U.S. is applied to tobacco (80%), followed by potato (18%). In 2012 an 

estimated 600,000 lb of active ingredient (a.i.) was applied to tobacco, with an average percent 

crop treated (PCT) of 65% (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 of maleic 

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 of sucker growth in 

tobacco contributes to higher yields, better quality leaf, and more efficient use of harvesting 

equipment'. Chemical sucker control (such as with maleic hydrazide) may also result in reduced 

production cost by reducing cultural practices otherwise done by hand 1

• Maleic hydrazide use on 

potatoes contributes to control of sprouting, which helps reduce any unwanted cropping, and 

decreases the number of undersized 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 of concern 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 of maleic 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 of the human health risk assessment, see the document Maleic 

Hydrazide, and its Potassium Salt: Qualitative Risk Assessment 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 

Dietary Assessment 

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 of maleic 

hydrazide. 

Residential Assessment 

While exposure to maleic hydrazide exists from residential use (i.e., golf course and 

spot/perimeter treatment), based on a qualitative assessment, no residential risk is expected to 

result from registered uses of maleic hydrazide. 

Aggregate Assessment 

Since the agency does not expect risk for dietary and/or residential exposure, no 

aggregate risk is expected to result from registered uses of maleic hydrazide. 

1 Moore, Michael J. Topping and Chemical Sucker 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 of toxicity, EPA has not made a common mechanism of toxicity 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 of toxicity and to evaluate the 

cumulative effects of such 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/. 

Occupational Assessment 

While occupational exposure to maleic hydrazide is expected, based on a qualitative 

assessment, no occupational risk is expected from the registered uses of maleic 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 of hydrazine at the 15 ppm limit. Based upon this re-assessment of hydrazine, the 

agency confirmed that the current upper limit of 15 ppm in technical products poses no risk 

concern. For more discussion of hydrazine please see the document, Maleic Hydrazide. and its 

Potassium Salt: Qualitative Risk Assessment/or Registration Review and Screen 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 of available adverse effects information to 

identify any adverse human health incidents attributable to maleic hydrazide. The agency 

reviewed the National Office of Pesticide 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 of incident 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 of incidents identified in the 2009 search, no 

update search was conducted. 

3. Food Tolerances 

Tolerances for residues of maleic 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 

7 
to exemptions from the requirement for a tolerances. If these exemptions are not sought, then 

additional tolerances for residues of maleic hydrazide in livestock commodities will need to be 

established. For more information on tolerance harmonization review for maleic hydrazide, 

please see, Maleic Hydrazide, and its Potassium Salt: Qualitative Risk Assessment for 

Registration Review and Screen of the Hydrazine Impurity. 

B. Ecological 

A summary of the 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 of the registration review of maleic hydrazide. 

For a detailed discussion of ecological fate and effects for maleic hydrazide see Preliminary 

Ecological Risk Assessment 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 hydrazide per se has been identified as the 

only residue of concern. The major degradate of maleic 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 

In the preliminary ecological risk assessment, a use rate of 13 lb a.i./acre was calculated 

for the fallow/idle land use of maleic hydrazide, and a use rate of 9 .2 lb a.i./acre was calculated 

for the ornamental/shade tree use of maleic 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. 

Terrestrial Assessment 

8 
Mammals 

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 of concern 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 of 6.1 lb a.i./acre or greater, which include tobacco, golf course 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. In the 

available acute toxicity data for maleic hydrazide, no mortality or sublethal effects were seen 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 

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, 

golf course 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 of 6.1 lb a.i./acre or greater, which include 

tobacco, golf course turf, ornamental shade trees and fallow/idle land. 

No chronic terrestrial invertebrate data was available, therefore, due to a lack of sufficient 

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 of the field either 

from run-off or 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 

9 
would 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 below the LOC to 13.49. At the lower 

application rate of 6.1 lb a.i./acre (tobacco) risks no longer exceed the LOC for dry dicots. 

Aquatic Assessment 

Predicted EECs are lower than any of the 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 of the 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 between RQs 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 its judgement of LOC exceedances, its risk characterization, and its proposed risk 

management on the 9.2 lb a.i./acre application rate. Based upon 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 of Highest 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 

10 
Terrestrial 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 

of an organism. If the 30,000 mg/kg diet was used as a NOAEL, (based upon decreased body 

weight of offspring 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 of non-listed and listed mammals. In addition, the EECs 

used to calculate these RQs are estimated by the Kenaga model, which relies on upper-bound 

values (90th percentile residue exposure). If mean Kenaga values are used instead, to be more 

representative of expected exposure, chronic mammal risk (already below the LOC) is further 

reduced. 

For birds, the highest acute dose-based RQ for risk to birds is 1.83. In estimating 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. If an 

endpoint of 4640 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 upper bound (90th percent) exposure values. If mean exposure 

values are used to estimate exposure, to be more representative of expected 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 

tax a. 

For terrestrial invertebrates, the acute risk is estimated to be 0.68, which marginally 

exceeds the agency LOC of 0.4. 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 of data, 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 on the 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 runoff is 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 of pesticides in accordance with the Joint Interim Approaches developed to 

implement the recommendations of the April 2013 National Academy of Sciences (NAS) 

report3

, Assessing Risks to Endangered and Threatened Species from Pesticides. The NAS 

report 2

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. EPA will address concerns specific to maleic 

hydrazide in connection with the development of its 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 of Agriculture released a white paper 

containing a summary of their joint Interim Approaches for assessing risks to listed species from 

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

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. Details 

of the joint Interim Approaches are contained in the November 1, 2013 white paper,,, Interim 

Approaches for National-Level Pesticide Endangered Species Act Assessments Based on the 

Recommendations of the National Academy o.fSciences April 2013 Report. 4 

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 

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 of maleic 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 of species 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 

12 
scientific 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 of maleic hydrazide as part of completing 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 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 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 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, 20135 and includes some 

pesticides scheduled for Registration Review and chemicals found in water. Neither of these 

lists should be construed as a list of known or likely endocrine disruptors. 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.6 

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

safety findings associated with the EDSP screening of maleic 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. of this 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 of data, 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. of this document, the agency briefly discusses the use and 

benefits of maleic hydrazide which indicate rnaleic hydrazide is an important tool in the 

production of tobacco, 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 of risk 

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 of data precludes the agency from making a determination with respect to the 

potential chronic effect to birds. Based on low chronic risk exhibited by maleic hydrazide to 

mammals, the agency reasons that chronic risk to 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 of maleic 

hydrazide to this taxa. (See also, Appendix B: Maleic Hydrazide Proposed Data Needs) 

• Avian reproduction (Guideline 850.2300) 

While a lack of data 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 of maleic 

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 of residues 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 of maleic hydrazide (i.e., at all registered application rates). The agency 

also notes that the primary benefits of maleic hydrazide are to tobacco production, potato and 

onion production (with maximum application rates of 6.1 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 of 9.0 lb a.i./acre 

8.7 lb a.i./acre and 8 lb a.i./acre respectively). In the absence of benefits 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, golf course 

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 plant RQs, 

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 below the 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 of applications 

allowed per year. The agency proposes to require registrants of maleic hydrazide products to 

rectify their labels to specify a maximum of I application per year with the exception of tobacco 

which will be allowed a second application in case of rain 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 of maleic 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 of applications 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 of maleic hydrazide, nor is it 

making a complete endangered species finding. The agency's final registration review decision 

for maleic hydrazide will depend upon both the result of an ESA Section 7 consultation with the 

Services, and an EDSP FF DC A section 408(p) determination. 

V. NEXT STEPS AND TIMELINE 

A. Interim Registration Review Decision 

15 
In 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 Register Notice will announce the availability of this Proposed Interim Registration 

Review Decision for maleic hydrazide and initiate 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 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 of the Interim 

Registration Review Decision. 

C. Implementation of Mitigation Measures 

Once the Interim Registration Review Decision is issued in final form, registrants 

affected by the 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 of the Interim Registration Review Decision in final form. A summary of the 

mitigation measures are described in Appendix A. 

16 
Appendix A: Summary of Risks and Proposed Mitigation for Maleic Hydraz

Registration Review Case#: 03 81 

PC Code:051501 

Chemical Type: Herbicide I Plant Growth Regulator 

Chemical Family: NIA 

Mode of Action: Uracil antimetabolite 

Affected Population(s) Source of Exposure Route of Exposure Duration of Risk(s) of Concern Mitigation Me

Exposure 

Terrestrial (monocot) and Spray drift and Not applicable Possible effects to off-site !Reduce maxim

semi-aquatic (monocot and runoff non-target plants single and annu

dicot) plants and !application rate 

lb a.i./acre for 

it is high

tnot specified. 
Appendix B: Registration Review Proposed Data Needs for Maleic Hydrazid

Study Title Guideline/Ref ere nee 

1. Avian Reproduction (mallard) Guideline Number 850.2300 

2. Acute oral toxicity to adult honey bees Non-guideline, OECD TG 213 

3. Acute oral toxicity to larval honey bees Non-guideline, OECD TG 237 

4. Chronic toxicity to adult bees Non-Guideline 

5. Chronic oral toxicity to larval honey bees Non-guideline 

6. Field trail of residues in pollen and nectar Non-guideline 

7. Semi-field testing for pollinator Non-guideline, OECD Guidance 75 
Appendix C: Maleic Hydrazide Label Table 

Description Amended Labeling Language for Maleic Hydrazide Use Products 

End Use Products 

Specify maximum Specify a maximum of one application per year. Exception for tobacco where re-application may be made case 

number of applications within 6 hours after application of maleic hydrazide products, and non-bearing citrus trees where a second appli

(annual) may be made based on seasonal temperature variations. 

Set maximum annual For all uses where the maximum application rate is not specified or greater than 6. l lb a.i./acre, including idle la

application rate fallow, land, CRP land, ornamental and/or shade trees and shrubs, ornamental lawns and turf, airports, golf cour

right-of-ways, nonagricultural areas, uncultivated soils, and urban areas: Specify a maximum annual application 

6.1 lb a.i./acre.