### Docket Number EPA

- HQ

-OPP

-2009

-0387 www
.regulations.gov



# Maleic Hydrazide
Interim Registration Review Decision Case Number 0381

Approve d by :



### D ate: 

# September 2015**~ _..)** **Ku-c ~**  

# :()J R ichard P

. Keigwin, Jr. Director Pestici de R e-evaluation Division

### I. 

### INTRODUCTION

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

### Inte rim 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. regul ati o n s.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/o pp srrd 1 /re gi s tration rev iew/

. 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 Rere gi stration E ligibility Deci s ion (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. reg ul ati o n s.gov :

• September 23 , 2009

- Publication of

### Mal e ic Hydrazide Summar y Document for a 60-day public comment period. The 

### Summar y Document included the 

### Preliminar y Work Plan 2

### (PWP) and was accompanied by the 

### Hea lth Effects Division Scoping Document and the 

### Registration Review Preliminary Problem Formulationfor th e Ecological Risk Assessm ent of Maleic H ydraz ide.
• 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 hydraz ide PWP

. The comment did not change the data and risk assessment needs or the timeline for th e maleic hydrazide registration review , so no modifications to the PWP were made

. • August 24, 2010-A Generic Data Call-In for Registration Review (G DCI 051501-856) was issued for maleic hydrazide.
• July 1 , 2014

- The agency published the 

### Preliminary Ecological Risk Assessme nt /or the Regis tration Rev iew of Maleic H ydraz id e and the 

### Maleic H ydrazide, and it s Potassium Salt: Qualitative Risk Assessment for Registration Review and Screen of th e H yd razine Impu r ity for a 60-day public comment period. One comment was received , whic h is summarized in the Proposed Interim Decision

. • March 25 , 2015

- The agency is sued the 

### Maleic H ydrazide Propo sed In terim Registration Review Decis ion

. One comment was recei ve d from the Center for Biolo gical 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 H ydraz id e Inte rim Decision in docket number EPA-HQ -OPP- 2009 -0 387 , which can be accessed at www
.regulations

. gov


### A. Changes from the Proposed Interim Decision
Pollinator data requirements , proposed in the 

### Maleic H y drazide 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 Registrati on Re v iew D ecision for details)

. In its document, 

### Maleic Hydrazide, and its Potassium Sa lt : Qualitative Risk Assessment for Registration R ev iew and Screen of the H y draz in e Impurit y , the agency determined that , give n 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 re view of maleic hydrazide , the agency will propose an exemption from tolerances for maleic hydrazide.


### II. USE AND USAGE
Maleic hydraz ide 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 i s as a uracil antimetabolite

. When sprayed on plants , it is absorbed and mo ves internall y where it blocks cell division.
Products containing maleic hydrazide are registered for use on tobacc o, potatoe s , onions , non-bearing citrus, golf course turf, utility and highway right s -of-way, airports , indu strial lan d , 

### 3lawns , 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 s uck er 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-ag ricultural 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 Moor e , Mic hael J. Topping and Chemical Su c ker Contro l Pro gra ms fo r Ge o rg ia

. 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 O nions in St o rage in O

hi o . 

### 5as 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.


### H

ydrazine
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 H

ydrazine Impurity, dated June 18, 2014 , availab le in the public docket EPA

- HQ-OPP-2009- 0387 , which can be accessed at www.regulations

. gov.
2. H um an Health In cide n ts
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 

### U pdated Rev iew of Maleic H yd razid e Incid ents, 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. Foo d To le ran ces 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 -0 387 , 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). Us ing 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 fa llow/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 7for 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 Inv ertebrat es
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 (desig ned to indicate an LDs o 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 app lication 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 Pre liminary 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 , risk s 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. A qu atic Assess ment
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 . E co log ical Incid e nts
The Eco logical Incident Information System (EIIS) , Avian Incident Monitoring System (A IMS ), 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 Reg istration Review of Maleic Hydrazide

. IV. Ri s k C haracter iz ation
A
. Eco logica l Ri s k
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 th e agency did not assess eco lo gical risk based upon 9.0 lb a.i ./acre , the agency did estimated RQ s based on 9

.2 lb a.i ./acre
. Differences between RQs ba sed 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 Tab le 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 (se mi-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 LD so 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 9these RQs are estimated with upper bound (90 111 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 age ncy 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. 

### E ndan ge red S pec ies Assess ment
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 recommendation s of the April 2013 ational Academy of Sciences (NAS) report 3

, 

### Assessing Risks to Endangered and Threatened Speciesfrom Pesticides. The AS report 2outlines 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 , E PA , 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 Assessment s Based on th e 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
. Endocrin e Dis ruptor S creenin g Pro g ram
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 , incl uding 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 eco logical 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 rele vant 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 Pro gram (EDSP).
EPA has developed the EDSP to determine whether certain substance s (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 identi fy 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.go v/ espp /2 013 / na s .htm l 11where 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 , 2013 5 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 E DSP screening of maleic hydrazide

. Before completing this Registration Re v ie w , the agency will make an EDSP FFDCA section 408(p) determination

. V. INTE RI M REG ISTRAT IO N REV IEW D EC IS IO N
A. R is k M itigatio n a nd Regul atory Rati o na le
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 includin g 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
m a leic 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 wa y, 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
s c enano s.
The agency determined that some LOC exceedances exist for terrestrial plants for all applic ation scenarios of maleic hydrazide (i

. e., at all registered application rates). The agenc y 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 S ee http ://www.regulations.gov/# 'documentDe tail;D = EPA- HQ

- OPPT-2009-0477-0074 for th e final s ec o nd li s t 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 hydraz ide , EPA did not identif y the need for any additional studies to evaluate potential effects on pollinators. However , since the issuance of the June 2014 

### Guidancefor Ass essing Pesticid e Risks to Be e 5

, 

### 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 E PA determines that additional pollinator exposure and effects data are necessary to help make a fipal registration review decision , EPA intends to is s ue 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 0 6 19 14.pdf


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



### Tabl e 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 ora l toxicity (OECD 213) Non-Guideline* Honey bee larvae acute oral toxicity (OECD 237)

on-GuideIi 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)

*Tie r 1 (Laboratory -b ased s tudie s) **Tier 2 a nd 3 (Sem i-field and full fi e ld colony -l evel s tudie s) The need for a hi g her tier tes t for pollinators will be determined based up on low e r-ti e red te s t s a nd/ or other line s of d ata a nd the need for a refined pollin ator ri s k assess ment. C. 

### Inte rim Re g is tration Rev iew Deci s ion

In accordance with 40 CFR Sections 155.56 and 155.58 , the agency is issuing this Interim Regi stration Review Decision. Exc ept for the E DSP and ESA components of this case , the agency ha s 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

.

14VI. 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 E DSP FFDCA section 408(p) , complete pollinator and ESA determinations have been made.

15AppendixA:SummaryofRisksandMitigationforMaleicHydrazideRegistrationReviewCase#:0381PCCode:OS150IChemicalType:HerbicideIPlantGrowthRegulatorChemicalFamily:NIAModeofAction:UracilantimetaboliteAffectedPopulation(s)SourceofExposureRouteofExposureDurationofRisk(s)ofConcernMitigationMeasuresCommentExposureTerrestrial(monocot)andSpraydriftand!NotapplicableAcutePossibleeffectstooff-siteReducemaximumINoinformation issemi-aquatic(monocotandrunoffnon-targetplantssingleandannualavailabledescribingdicot)plantsandapplicationrateto6.1benefitsofhigherlba.i./acreforallusesapplicationratesforwhereitishigherorfallow/idleland,turf,notspecified.andornamentals.AppendixB:RegistrationReviewDataNeedsforMaleicHydrazideIStudyTitleIGuideline/Reference1.IAvianReproduction(mallard)IGuidelineNumber850.2300AppendixC:MaleicHydrazideLabelTableDescriptionAmendedLabelingLanguageforMaleicHydrazideUseProductsPlacementonLabelEndUseProductsSpecifymaximumWiththeexceptionofuseontobaccoandnon-bearingcitrustrees,allusesformaleichydrazidemustspecifyaDirectionsforUsenumberofapplicationsmaximumofoneapplicationperyear.(annual)Fortobaccore-applicationofmaleichydrazidemaybemadeincaseofrainwithin6hoursafterapplicationofmaleichydrazideproducts.Fornon-bearingcitrustreesasecondapplicationmaybemadebasedonseasonaltemperaturevariations.SetmaximumannualProductlabelsmustspecifythatthemaximumannualapplicationratemustnotexceed6.1lbs/acre,withtheexceptionDirectionsforUseapplicationrateoftobaccoandnon-bearingcitrustreeswheremorethanoneapplicationperyearmaybepermitted.