Docket Number EPA-HQ-OPP-2009-0387 

www.regulations.gov 

Maleic Hydrazide 

Interim Registration Review Decision 

Case Number 0381 

Approved by: 

Date: 

September 2015 

~ _..) Ku-c ~ :()J 

Richard P. Keigwin, Jr. 

Director 

Pesticide Re-evaluation Division 
I. INTRODUCTION 

This document is the Environmental Protection Agency's (EPA or the agency) Interim 

Registration Review Decision for maleic hydrazide and maleic hydrazide potassium salt (maleic 

hydrazide ), PC codes 051501 and 051503 , and is being issued pursuant to 40 CFR Sections 

155.56 and 155.58. A registration review decision is the agency's determination whether a 

pesticide meets, or does not meet, the standard for registration in the Federal Insecticide, 

Fungicide, and Rodenticide Act (FIFRA). The agency may issue, when it determines it to be 

appropriate, an interim registration review decision before completing a registration review. 

Among other things, the interim registration review decision may 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 EPA'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. ln 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. Through the registration review program, the agency periodically re-evaluates 

pesticides to make sure that as these changes occur, products in the marketplace can continue to 

be used safely. Information on this program is provided at 

www.epa. gov/oppsrrd 1 /registration review/. 

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 

hydrazide are registered for use on tobacco, potatoes, onions, non-bearing citrus, golf course 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 all relevant 

documents 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 

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(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. 

• 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 1, 2014 - The agency published the Preliminary Ecological Risk Assessment/or 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 in the Proposed Interim Decision. 

• March 25, 2015 - The agency issued the Maleic Hydrazide Proposed Interim 

Registration Review Decision. One comment was received from the Center for Biological 

Diversity, commenting on the agency's requirement to consult with the U.S. Fish and 

Wildlife Service (FWS) and National Marine Fisheries Service (NMFS) prior to 

completing registration review. 

• September 2015- The agency is now publishing the Maleic Hydrazide Interim Decision 

in docket number EPA-HQ-OPP-2009-0387, which can be accessed at 

www.regulations.gov 

A. Changes from the Proposed Interim Decision 

Pollinator data requirements, proposed in the Maleic Hydrazide Proposed Interim 

Decision, are no longer being required for maleic hydrazide. Instead, the agency plans to review 

all active ingredients whose dockets opened prior to June 2014, to determine whether additional 

pollinator data are needed (see Section V. Interim Registration Review Decision for details). 

In its document, Maleic Hydrazide, and its Potassium Salt: Qualitative Risk Assessment 

for Registration Review and Screen of the Hydrazine Impurity , the agency determined that, given 

its low toxicity and lack of human health toxicity endpoints identified for maleic hydrazide, the 

current tolerances for maleic hydrazide under 40 CFR may be changed to exemptions. As part of 

the registration review of maleic hydrazide, the agency will propose an exemption from 

tolerances for maleic hydrazide. 

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 maleic hydrazide are registered for use on tobacco, potatoes, onions, 

non-bearing citrus, golf course turf, utility and highway rights-of-way, airports, industrial land, 

3 
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 

whose growth is controlled by maleic hydrazide include: bluegrasses, fescues, bromegrass, 

orchard grass, quackgrass, perennial rye, ryegrass and bahiagrass. On golf course fairways, 

maleic hydrazide can reduce Paa annua (annual bluegrass) and inhibit the growth of 

bermudagrass, enabling ryegrass or other desirable 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), available in the docket, 

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 nonagricultural usage of maleic hydrazide. 

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 1

• Restriction of sucker growth in 

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

equipment 1

• Chemical sucker control (such as with maleic hydrazide) may also result in reduced 

i Moore , Michael J. Topping and Chemical Su c ker Contro l Programs fo r Geo rgia . 

4 
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/or Registration Review and 

Screen of the Hydrazine Impurity, dated June 18, 20 14, available in the public docket EPAHQ-OPP-2009-0387, which can be accessed at www.regulations.gov. 

1. Human Health Risk Summary 

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. 

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 

2 Comin, Donald. Inhibiting Sprouting of Potatoes and Onions in St orage in 

Ohio . 

5 
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, and established that current technical products that contain maleic hydrazide do not 

contain hydrazine in excess of 15 ppm. The agency 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 for 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 Health 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 

Currently, tolerances for residues of maleic hydrazide on food are established under 40 

CFR § 180.415, and have been reviewed during this registration review. The agency will make 

revisions to 40 CFR § 180.415, by initiating the process to exempt maleic hydrazide from 

tolerances. For more information on tolerance review for maleic hydrazide, please see section 

IV, A. , below, or the section entitled, "International Harmonization/Tolerance Considerations", 

6 
in the agency's document, Registration Review Preliminary Human Health Risk Assessment.for 

Maleic hydrazide. 

B. Ecological Risk Summary 

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. 

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

Preliminary Ecological Risk Assessment.for the Registration Review of Maleic Hydrazide dated 

June 18, 2014, available in the public docket EPA-HQ-OPP-2009-0387, which can be accessed 

at http://www.regulations.gov/. 

1. Terrestrial Assessment 

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 for 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 

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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 

The honey bee is considered the surrogate for terrestrial invertebrates. Toxicity data with 

the honey bee 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 data, risk to terrestrial invertebrates is 

uncertain. 

Terrestrial Plants 

For terrestrial plants, LOC exceedances (LOC=l) 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 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. 

2. 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 taxa. 

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 Preliminaty Ecological Risk 

Assessment.for the Registration Review of Maleic Hydrazide. 

IV. Risk Characterization 

A. Ecological Risk 

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 

8 
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 risk mitigation 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 taxa that exceed LOCs, see Table 1 below. 

Table 1. Summary of LOC Exceedances for Maleic Hydrazide at 9.2 lb a.i./acre 

Taxa Duration LOC Highest RQs 

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 

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 of 2,000 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 

9 
these RQs are estimated with upper bound (90111 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 of maleic 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 

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. 

B. 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 ational Academy of Sciences (NAS) 

report3

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

3 http: //www.nap.edu/ catalog.php?record id=l8344 

10 
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 of Sciences 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 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 of ESA 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 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. 

C. 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, deve lopmental 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 l 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 

4 http: //www.epa.gov/ espp/2 013 / na s .html 

11 
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 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. 

V. 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 taxa 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 presented information which further characterizes 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 maleic 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 were 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 were viewed in the context of risk characterizations, the 

agency determined that acute risks to birds and chronic risks to mammals were low or below the 

LOC, and therefore neither additional mitigation nor additional data were needed for these 

scenanos. 

The agency determined that some LOC exceedances exist for terrestrial plants for all 

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

also noted that the primary benefit of maleic hydrazide use is in tobacco, 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). While little benefits information was available for uses such as fallow/idle land, 

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/ 

12 
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). Due to the absence of evidence of sufficient benefits from uses with 

higher application rates, the agency will 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 maximum 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 reduces all estimated plant RQs, specifically reduces RQs for 

dry dicots to below the LOC, and reduces 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 requiring additional data for this scenario. 

Finally, the agency notes that current maleic hydrazide product labels are missing or 

contain certain information that is unclear or inconsistent regarding the maximum number of 

applications allowed per year. As part of this interim decision, the registrants of maleic hydrazide 

products will amend their labels to specify a maximum of 1 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 nonbearing citrus which allows up to 2 applications per year. 

B. Data Requirements 

A lack of data precluded the agency from estimating an RQ for chronic effects of maleic 

hydrazide to birds. However, based on low chronic risk exhibited by maleic hydrazide to 

mammals, the agency reasons that chronic risk to birds is probably low, and therefore risk 

mitigation is not being pursued for this scenario at this time. The agency will require chronic 

avian toxicity data, identified below, in order to understand potential chronic effects of maleic 

hydrazide to this taxa (See Appendix B: Registration Review Data Needs for Maleic Hydrazide). 

• Avian reproduction (Guideline 850.2300) 

Pollinator Studies and Assessment 

When initially scoping the registration review for maleic hydrazide, EPA did not identify 

the need for any additional studies to evaluate potential effects on pollinators. However, since the 

issuance of the June 2014 Guidance for Assessing Pesticide Risks to Bee5

, EPA has begun to 

require these data where applicable. EPA is currently determining whether additional pollinator 

data are needed for active ingredients in registration review whose dockets opened prior to June 

2014. For those active ingredients where EPA determines that additional pollinator exposure and 

effects data are necessary to help make a fipal registration review decision, EPA intends to issue 

a DCI to obtain these data. In the near future, EPA will provide further information and guidance 

on this effort. The pollinator studies that could be required are included in Table 2 below. At a 

5 http: //www2.epa . gov/ sites/ production/ files/ 2014 -

06 / documents/ pollinator risk assessment guidance 06 19 14.pdf 

13 
later date, the Agency will require data it believes are needed to help inform the pollinator risk 

assessment. 

Table 2. Potential Pollinator Data Requirements 

Guideline# Study 

850.3020* Acute contact toxicity study with adult honey bees 

850.3030* Honey bee toxicity of residues on foliage 

850.3040** Field testing for pollinators 

Non-Guideline* Honey bee adult acute oral toxicity 

(OECD 213) 

Non-Guideline* Honey bee larvae acute oral toxicity 

(OECD 237) 

on-Guide Ii ne* Honey bee adult chronic oral toxicity 

Non-Guideline* Honey bee larvae chronic oral toxicity 

onResidues in pollen and nectar/field residue analysis Guideline** 

NonSemi-field testing for pollinators (tunnel or colony feeding Guideline** 

(OECD 75) studies) 

*Tier 1 (Laboratory-based studies) 

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

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

C. Interim Registration Review Decision 

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

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

the agency has made the following Interim Registration Review Decision: 

risk. 

( 1) There are no human health risk concerns based on the current use patterns of maleic 

hydrazide; and, 

(2) Data, identified in Appendix B, are required to determine chronic risk to birds; and, 

(3) Label changes, identified in Appendix C, are needed to reduce potential ecological 

In this 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. 

14 
VI. NEXT STEPS AND TIMELINE 

A. Implementation of Mitigation Measures 

Following the issuance of this Interim Decision, registrants are required to submit 

amended labels that include the changes described in Appendix C to the agency for approval 

within 60 days. 

B. Tolerance Amendments 

Following issuance of this Interim Decision, the agency will propose a rule, with a public 

comment period of sixty (60) days, to establish an exemption from tolerances for maleic 

hydrazide under 40 CFR. After reviewing any timely comments received the agency may 

establish an exemption for tolerances for maleic hydrazide in a final rule, which will be 

published in the Federal Register. 

C. Final Registration Review Decision 

A final decision on the maleic hydrazide registration review case will occur after EDSP 

FFDCA section 408(p), complete pollinator and ESA determinations have been made. 

15 
Appendix A: Summary of Risks and Mitigation for Maleic Hydrazide 

Registration Review Case#: 0381 

PC Code:OS 150 I 

Chemica l Type: Herbicide I Plant Growth Regulator 

Chemica l Family: NIA 

Mode of Action: Uraci l antimetabolite 

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

Exposure 

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

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

dicot) plants and application rate 

lb a.i./acre for a

where it is hi ghe

not specified. 
Appendix B: Registration Review Data Needs for Maleic Hydrazide 

I Study Title I Guideline/Reference 

1. I Avian Reproduction (mallard) I Guideline Number 850.2300 
Appendix C: Maleic Hydrazide Label Table 

Description Amended Labeling Language for Maleic Hydrazide Use Products 

End Use Products 

Specify maximum With the exception of use on tobacco and non-bearing citrus trees, all uses for maleic hydrazide must specify a 

number of applications maximum of one application per year. 

(annua l) For tobacco re-app lication of maleic hydrazide may be made in case ofrain within 6 hours after application of m

hydrazide products. 

For non-bearing citrus trees a second application may be made based on seasonal temperature variations. 

Set maximum annual Product labels must specify that the maximum an nual application rate must not exceed 6.1 lbs/acre, with the exc

app li cation rate of tobacco and non-bearing citrus trees where more than one app li cation per yea r may be permitted.