### 1 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION 

### UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON

, D.C. 20460

January 28, 2015

PC Code: 128819 MEMORANDUM DP Barcode: 422524

SUBJECT: EFED Registration Review Problem Formulation for Forchlorfenuron

FROM: Christina Wendel, Biologist Greg Orrick, Environmental Scientist Environmental Risk Branch 2 Environmental Fate and Effects Division (7507P)

REVIEWED Ronald D. Parker, Senior Environmental Engineer BY: Donna Reed Judkins, Ph.D., Biologist Environmental Risk Branch 2 Environmental Fate and Effects Division (7507P)

THROUGH: Brian Anderson, Branch Chief Environmental Risk Branch 2 Environmental Fate a nd Effects Division (7507P)

TO: Wilhelmena Livingston, Chemical Review Manager Kevin Costello, Acting Branch Chief Risk Management and Implementation Branch 4 Pesticide Re-evalua tion Division (7508P)

### 2 

## Table	of	Contents

1. Executive summary ............................................................................................................. .... 3 2. Introduction .................................................................................................................. ........... 4

a. Mode of Action ................................................................................................................ .... 4 3. Use Characterization .......................................................................................................... ..... 4 4. Conclusions from Previous Risk Assessments ....................................................................... 5

a. Ecological Risk Assessment ................................................................................................ 5 b. Drinking Water Exposure Assessments ............................................................................... 7

c. Clean Water Act Programs .................................................................................................. 7 5. Environmental Fate and Transport.......................................................................................... 7

a. Transformation Products ...................................................................................................... 9 6. Receptors...................................................................................................................... ......... 10

a. Effects to Aquatic Organisms ............................................................................................ 11 b. Effects to Terrestrial Organisms ........................................................................................ 11

c. Ecological Incidents .......................................................................................................... . 13 7. Exposure Pathways of Concern ............................................................................................ 13 8. Analysis Plan ................................................................................................................. ....... 14

a. Stressors of Concern .......................................................................................................... 14 b. Measures of Exposure ........................................................................................................ 1 4

c. Measures of Effect ............................................................................................................ . 15 d. Endangered Species Assessments ...................................................................................... 15

e. Endocrine Disruptor Screening Program ........................................................................... 15 9. Preliminary Identification of Data Gaps ............................................................................... 15

a. Environmental Fate ............................................................................................................ 15 b. Effects ....................................................................................................................... ......... 16 10. References .................................................................................................................... ...... 24

a. Submitted Environmenta l Fate Studies .............................................................................. 25 b. Submitted Ecological Toxicity Studies .............................................................................. 26 APPENDIX A. Forchlorfenuron Ecotoxicity Data ....................................................................... 28 APPENDIX B. SIP & STIR Inputs and Outputs .......................................................................... 32

### 3 

## 1. Executive summary

The Environmental Fate and Effects Division (E FED) has completed the preliminary problem formulation for the ecological risk, environmenta l fate, endangered species, and drinking water assessments to be conducted as part of the re gistration review of fo rchlorfenuron. The problem formulation describes the methods planned to be used during the completion of drinking water and ecological risk assessments in support of regi stration review and provi des an overview of the environmental fate, ecological eff ects, potential risks associated with the use, and uncertainties unique to the risk assessment of forchlorfenuron. This document al so identifies additional studies that would be beneficial to the condu ct of an ecological risk assessment.

Three ecological risk assessments have been conducted for forc hlorfenuron FIFRA §3 actions: a new chemical assessment in 2004 (DP 301774) and new use assessments in 2008 (DP 341868+) and in 2013 (DP 406985). The assessments conclude d that proposed uses of forchlorfenuron do not result in level-of-concern (LOC) exceedances fo r aquatic or terrestrial organisms. However, past risk assessments noted uncertainties in chroni c risks to birds and aquatic organisms based on lack of chronic data, and risks to bees are uncerta in in the absence of data. Previous conclusions remain unchanged; however, based on the cu rrent toxicity and exposure profile of forchlorfenuron, EFED believes that chronic effects to birds or a quatic animals are unlikely to be of concern. An updated, full ecological risk asse ssment is not needed for registration review, although EFED recommends that additional data be requested to allow for a more comprehensive evaluation of potentia l effects to honey bees and se diment dwelling invertebrates. EFED will evaluate those data when they are submitted and will work with the Pesticide Reevaluation Division (PRD) to address any ri sks of concern identified by those data.

The following are the needed data and ma jor uncertainties for forchlorfenuron:

Data Needs

 Environmental Fate Data

o None (due to no currently identified risk LOC exceedances; however, if the requested data identif y a risk concern, then additional environmental fate studies may be needed to further characterize the magnitude and duration of the risk)

 Ecotoxicity Data

o OECD TG 213 and Non-guide line special studies: H oney bee adult acute and chronic oral t oxicity studies

o OECD TG 237 and Non-guide line special studies: H oneybee larval acute and chronic oral t oxicity studies

o Special study OECD TG 75 and OSC PP 850.3040: Semi-field testing for pollinators and Field testing for pollinator s (both studies that are conditionally required based on the results of the Tier I – laboratory based studies listed above; if needed these additional field studies w ill be discussed pending the results of the acute and chronic adult and larval or al toxicity studies to honey bees)

o OSCPP 850.1760 or 850.1770: Whole Sediment Chronic Life-cycle Freshwater invertebrate toxicity testing

### 4 o Avian reproduction study (OSCPP 850.2300) (c urrently in revi ew –the review will be finalized prior to issuance/publication of the DCI – status update forthcoming)

o OSCPP 850.4150: Terrestrial plant, Tier II vegetative vigor data with the TEP is still an uncertainty, as the current available vegetative vigor study did not test the active ingredient, forchlorfenuron, at the highest application rate.

Some data gaps are not identified as data needs at this time (see Section 9 for details) due to the low risks of forchlorfenuron uses in the United States. If a risk of concern is identified in the future, data needs for risk assessment may also change.


## 2. Introduction

Forchlorfenuron is a plant growth regulator that was firs t registered in 2005. It is registered for use on blueberries, bushberries (b lack currants, red currants, elderberries, gooseberries, and lingonberries), kiwifruit, and grap es, with applications pending for use on figs, sweet cherries, plums including prunes, pears, almonds, and pistach ios. Forchlorfenuron was recently assessed in 2013 (USEPA, 2013).



## a. Mode of Action

Forchlorfenuron is a phenylurea, cytokinin plant growth regulator. The compound acts synergistically with natural auxi ns to promote plant cell division and lateral growth, resulting in improved fruit size, fruit set, cluster weight, cold st orage, and/or resistance to splitting from rain in a variety of fruits and nuts (USEPA, 2008). Th e mode of action in non-target organisms is unknown.


## 3. Use Characterization

Three end-use formulations containing forchlorfe nuron are currently registered for use in the United States (EPA Reg. No. 71049-1, 71049-3, and 71049-4). Table 1 lists the maximum use patterns for the labeled use sites. There ar e no ambiguous label directions that require clarification for exposure assessment.

Table 1. Forchlorfenuron Use Patterns

Uses Max. Single App. Rate (lbs a.i./A) Max. Annual App. Rate (lbs a.i./A) App. Interval (d) Application Type
Almonds, sweet cherries, figs, pears, pistachios, plums/prunes 0.022 0.022 n/a

Ground/air-blast Blueberries 0.022 A 0.044 B 14 Black currants, red currants, elderberries, gooseberries, lingonberries ( i.e. , bushberries) 0.0044 0.0088 B 14
Grapes 0.022 0.022 B n/a
Kiwifruit 0.018 0.018 B n/a

A This rate is used to delay harvest. Otherwise, th e maximum single application rate is 0.0044 lbs a.i./A.

B The labeled application rate is limited per crop cycle or per season. These crops have only one crop cycle or

growing season per year (USEPA, 2007; USDA, 2000). Ther efore, these rate limits were used as annual rate limits.

### 5 A Screening Level Usage Analysis conducte d by the Agency indicates that annual forchlorfenuron usage from 2004 to 2012 was a pproximately 1,000 pounds on table grapes and less than 500 pounds each on rais in grapes, kiwifruit, and bl ueberries (USEPA, 2014). The treated fraction of crops was reported to be <1-25% on average, with a maximum of 50% on kiwifruit (USEPA, 2014).


## 4. Conclusions from Previous Risk Assessments

a. Ecological Risk Assessment

Three ecological risk assessments have been conducted for forc hlorfenuron FIFRA §3 actions: a new chemical assessment in 2004 (DP 301774) and new use assessments in 2008 (DP 341868+) and in 2013 (DP 406985). These assessments concl uded that proposed uses of forchlorfenuron do not result in LOC exceedances for federally en dangered and threatened (listed) and non-listed aquatic or terrestrial organisms. However, chronic risks to birds (also a surrogate for terrestrialphase amphibians and reptiles) and risks to honey bees are uncertain in the absence of data. It is also unclear how stimulative growth effects to terrestrial and aquatic plants could directly impact listed terrestrial and aquatic plant species, or indi rectly impact species that rely on plants for shelter or sustenance. Therefore, due to this un certainty, direct effects to listed plants and potential indirect risks to all listed species that depend on plants for food or shelter cannot be ruled out. Chronic risk to aquatic animals is un certain in the absence of data, but unlikely to exceed concern levels based on toxicity estimate s using acute-to-chronic ratios. A summary of LOC exceedances is listed in Table 2

. Figure 1 and Table 3 summarize the potential risks and the supporting evidence.

Table 2. LOC Exceedances for Recently Assessed Uses

Effect Taxonomic Group

Birds Mammals Terrestrial Plants Terrestrial Inverts Fish Aquatic Inverts Aquatic Plants
Direct Effect LOC Exceedance √ A

-- -- B

-- -- -- -- B

Indirect Effect Potential C √ √ √ √ √ √ √

A Uncertain chronic risks to bi rds (surrogates for te rrestrial-phase amphibians and reptiles)

B Stimulative growth effects observed in both terrestrial and aquatic plant species, direct risks to listed plants cannot be dismissed.

C Indirect risks to all listed species cannot be ruled out due to uncertainties of stimulative growth effects on both terrestrial and aquatic plant species.

### 6 Figure 1. Graphic Summary of Potential Risks of Recently Assessed Uses

Table 3. Evidence of Risk to Taxonomic Groups from Forchlorfenuron Uses
Predominant Evidence of Negligible Risk Predominant Evidence of Risk

Mammals: No toxicity observed in acute studies. Chronic RQs <1.0.

Limited Evidence of Negligible Risk Limited Evidence of Risk

Fish & Aquatic Invertebrates: No toxicity was observed in acute studies with multiple species. Chronic risk is unlikely to exceed concern levels; toxicity would have to be 15,000 to 27,000 times greater than acute toxicity to trigger risk concerns. Terrestrial & Aquatic Plants: Observed stimulative growth effects could direc tly impact terrestrial and aquatic plants. However, the relationship between the stimulative effect and survival and reproduction of plant species or animals that depe nd on them for food or shelter is uncertain.

Birds: No toxicity was ob served in acute studies. Preliminary review of chronic toxicity data are available; chronic effects were observed at all test concentrations. In addition, drinking water was found to be an exposure pathway of potential concern on a chronic basis, based on the Screening Imbibition Program (SIP).

Terrestrial Invertebrates: Risk is presumed in the absence of acute and chronic or al toxicity data for adults and larvae. Forchlorfenuron is systemic in plants so exposure via pollen and nectar is possible.

### 7 

## b. Drinking Water Exposure Assessments

Three drinking water exposure assessments have been conducted for forchlorfenuron FIFRA §3 actions: a new chemical assessment in 2004 (DP 301774) and new use assessments in 2008 (DP 341630) and in 2013 (DP 407227). Maximum screeni ng exposure estimates for forchlorfenuron (which is the only residue of concern) were 0.60 μg/L (1-in-10-year peak) and 0.21 μg/L (1-in10-year annual mean) for surface water and 8.8 μg /L (1-in-10-year peak) and 7.3 μg/L (1-in-10- year annual mean) for ground water.


## c. Clean Water Act Programs

The Clean Water Act requires the Agency to publish water quality criteria that accurately reflect the latest scientific knowledge on the kind and ex tent of all identifiabl e effects on health and welfare that might be expected from the presen ce of pollutants in any body of water, including ground water. While these recommended crit eria do not, in themselves, impose any requirements, states and authorized tribes can us e them to develop water quality standards. An Aquatic Life Ambient Water Quality Crite ria document has not been published for forchlorfenuron (see url: http://www.epa.gov/waterscience/criteria/ ).

The Office of Pesticide Programs (OPP) publishes a quatic life benchmarks for freshwater species based on toxicity values for the most sensitive species from the most recent risk assessments. However, aquatic life benchmarks have not b een published for forchl orfenuron (see url: http://www.epa.gov/oppefed1/ecorisk_ders/a quatic_life_benchmark.htm#benchmarks ). Any data submitted or otherwise located as part of the re gistration review process may be used to update aquatic life benchmar ks if applicable.

Forchlorfenuron is not identifie d as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Water Act, based on information provided at http://iaspub.epa.gov/tmdl_waters10/attains_ nation_cy.cause_detail_303d?p_cause_group_id=88 5 . No Total Maximum Daily Load (TMDL) criter ia have been developed for forchlorfenuron, based on information provided at http://iaspub.epa.gov/tmdl_waters10/attains_ nation.tmdl_pollutant_de tail?p_pollutant_group_id =885&p_pollutant_group_name=PESTICIDES

.


## 5. Environmental Fate and Transport

The available environmental fate da ta for forchlorfenuron are listed in Table 4 . In summary, the compound persists in the environment, has mode rate to slight mobility in soil, does not appreciably volatilize, is hydrophilic, and, therefore, does not apprec iably bioconcentrate in fish. Sorption to soil correlates with soil clay content (r 2 

### =0.97) and with soil organic carbon (r 2 

### =0.70), with the coefficient of variation (CV) for K FOC 

### (0.61) less than that for K F 

### (1.0). Major degradates other than carbon di oxide have not been found. Fi eld data are not available.

Forchlorfenuron may infiltrate to ground water in some soils and may move to surface water bodies via spray drift and/or runoff of dissolved and/or sorbed residues.

### 8 Table 4. Chemical Properties and Environmen tal Fate Parameters of Forchlorfenuron

Parameter Value Source Selected Physical/Chemical Parameters Molecular mass (molecular formula) 247.69 g/mol (C 12 H 10 ClN 3 O) (Calculated) Vapor pressure (25 °C) 3.5 x 10 -10 torr MRID 44359508 Aqueous solubility (20-21  C) 39 mg/L MRID 44359509 Henry’s Law Constant (25 °C) 2.9 x10 -12 atm-m 3 /mol (Calculated) Octanol-to-water partition coefficient (K OW ); log K O W (20  C) 1600; 3.20 MRID 44359512

Dissociation constants (pKa, pKb) 2.5, 12.2 MRID 44394603

Persistence

Hydrolysis half-life (25  C) No substantial degradation (pH 5, 7, and 9) MRID 44394604

Aqueous photolysis half-life (25  C) No substantial degradation MRID 44394605

Aerobic soil metabolism half-life (25°C) 577 d MRID 44359515/ 45840119

Anaerobic soil metabolism half-life (25  C) 234 d MRID 44359514/ 45840118 Mobility Freundlich soil-water partition coefficients (K F ); Freundlich organic carbon-normalized coefficients (K FOC ) 2.13, 5.79, 17.2, 39.8 L/kg; 852, 1430, 1,450, 3,320 L/kg OC MRID 44359516/ 45840121

Field Dissipation
Field data were not submitted.

Fish Bioconcentration Fish bioconcentration factors (steady-state, total residues); depuration rate Not quantified 1 (edible), 16 (inedible), 7.2 (whole fish); >88% in 3 days MRID 44359524/ 45840120

1 A BCF for fillet tissue was not quan tified because residues were not present above the LOQ (75 μg/kg).9a. Transformation ProductsMajor degradates of forchlorfenuron other than carbon dioxide havenot been found. Chemical namesand structures of forchlorfenuronand carbon dioxide are inTable 5.Table 5. Forchlorfenuron and Its Environmental Transformation ProductsCode Name/SynonymChemical NameChemical StructureStudy TypeMRIDMaximum%AR (time)Final %AR(study length)PARENTForchlorfenuronN-(2-chloro-4-pyridinyl)-N’-phenylureaCAS No.:68157-60-8Formula:C12H10ClN3OMW:247.68 g/molSMILES:C1=CC(=CC=C1)NC(=O)NC2=CC(=NC=C2)ClTRANSFORMATION PRODUCTSUnextractedresiduesNot applicableNot applicableAerobic soil44359515/4584011924%(365 d)24%(365 d)Anaerobic soil44359514/4584011831%(90 d)31%(90 d)Carbon dioxideCarbon dioxideFormula:CO2MW:44.1 g/molOOAerobic soil44359515/458401199.9% (365 d) 9.9% (365 d)Anaerobic soil44359514/458401181.5% (90 d) 1.5% (90 d)

### 10 

## 6. Receptors

The toxicity endpoints that will be used in risk assessment for aquatic and terrestrial organisms exposed to forchlorfenuron are presented in Table 6 and Table 7 below. A complete list of the ecotoxicity data available for forchlorfenuron can be found in Appendix A

. Forchlorfenuron is moderately toxic to freshwat er fish and invertebrates; however, no effects were observed in the aquatic vascular or non-vascul ar plant toxicity studie s. Forchlorfenuron is practically non-toxic to birds and mammals on an acute exposure basis. The acute mammalian toxicity study used in previous risk assessm ents was reclassified as unacceptable by HED; however, there was another acute oral mamma lian study available using an end-use product (0.86% a.i.) that was classified as acceptable. The change in e ndpoint from the previously used endpoint to the new endpoint shoul d not change any risk conclusi ons for mammals (the previous endpoint LD 50 

### = 4889 mg/kg and the new endpoint LD 50 

### >5050 mg/kg). Toxicity to terrestrial invertebrates has only been assessed for adu lt honey bees via an acu te contact exposure.

No chronic toxicity data for forchlorfenuron are available for fish or aquatic or terrestrial invertebrates. The chronic bird toxicity data wi th Bobwhite quail was recently submitted to the agency and is undergoing review. Based on an initi al review of the data, there are indications of significant effects on 14-day survivor weight observe d in all test concentrat ions (7-9%), resulting in a NOAEC of <170 mg a.i./kg-diet. There were, however, no other treatment related effects of forchlorfenuron on survival, abnor mal behavior or reproductive e ndpoints. Although the effects indicate a NOAEC of less than the lowest te st concentration, the NOAEC is likely being approached given the diminished magnitude of the effect observed at the lowest test concentration. It is reasonable to consider this LOAEC value from the submitted avian reproduction study to be sufficient. The chronic NOAEC for birds (a surrogate for reptiles and terrestrial-phase amphibians) would need to be approximately 30-fold lower than the LOAEC value (170 mg a.i./kg-diet) to result in LOC exceedances. The mammalian 2-generation reproduction study indicated effects to mammal s based on decreased food consumption in F 0 

### & F 1 

### males, clinical signs of toxi city and lower body weight in F 1 

### males & females, and growth retardation in F 1 

### & F 2 

### pups.

There were no significant effect s in reduction of growth obser ved for aquatic plant species exposed to forchlorfenuron at the treatment levels tested; however, there were stimulative, growth effects that were observe d for both vascular and non-vascul ar aquatic plant species that were tested. The most substantial stimulative e ffect was observed in the freshwater green algal study ( Pseudokirchneriella subcapitata ), after 96 hours of exposure to 16 μ g a.i./L of forchlorfenuron a 43% increase in growth (cell density) was observed (MRID 46753502).

There were no ≥ 25% effects in reduction that were observe d for terrestrial plant species exposed to forchlorfenuron at the treatment rates tested ( i.e., 0.055 lbs a.i./A (seedling emergence, MRID 45840111) or 0.022 lbs a.i./A (vegetative vigor, MRID 46753505)), although a reduction of 20% in dry weight was observed in cucumber in th e vegetative vigor study. However, stimulative growth effects were observed for so me terrestrial plant species that were tested, in both terrestrial plant toxicity studies. A 46% increase in shoot weight was observed in ryegrass in the seedling emergence study (MRID 45840111), and a 36% increase in shoot weight in turnip was observed

### 11 in the vegetative vigor study. The measured concen trations in the vegetative vigor study (based on spray solution recoveries) were 30.3% - 32.2% of nominal, whic h indicates that the study has not tested the active ingredient at the highest a pplication rate. Based on the available data, there is uncertainty of risk to terrestrial pl ants at the maximum application rate.


## a. Effects to Aquatic Organisms

Table 6. Summary of the Most Sensitive Endp oints from Aquatic Toxicity Studies for Forchlorfenuron 1

Taxonomic Group Study Type Surrogate Species Toxicity Value (mg a.i./L) Acute Toxicity Classification MRID (Study Classification) Freshwater fish & Aquatic-phase amphibians Acute Bluegill ( Lepomis macrochirus )/ (TGAI, 100% a.i.) 96-h LC 50 = 8.8 Moderately toxic 44359519 (Acceptable)

Freshwater invertebrates Acute Waterflea ( Daphnia magna) (TGAI, 100% a.i.) 96-h EC 50 = 5.3 Moderately toxic 44359520 (Acceptable)

Aquatic plants 2 Vascular Duckweed ( Lemna gibba ) (EP, 0.86% a.i.) 7-d EC 50 > 0.90 7-d NOAEC = 0.90 Stimulated growth of 4% 2 45840110 (Acceptable)

Nonvascular Marine diatom ( Skeletonema costatum ) (TGAI, 98.2% a.i.) 96-h EC 50 > 0.016 NOAEC = 0.016 No significant effects 46753501 (Acceptable)

Freshwater green algae ( Pseudokirchneriella subcapitata ) (TGAI, 98.2 % a.i.) 96-h EC 50 > 0.016 NOAEC = 0.016 No significant effects, but cell

density had stimulated growth of 43% 2 46753502 (Acceptable)

1 No chronic freshwater toxi city data and no estuarine/marine acut e or chronic toxicity are available for forchlorfenuron.

2 No significant effects in reduction were observed for aquatic plant species exposed to forchlorfenuron at the treatment levels tested. However, there were stimulativ e, positive growth effects that were observed for some aquatic plant species that were tested. Stimulative growth was observed in the following aquatic non-vascular plants: the green algae ( Pseudokirchneriella subcapitata ; +43% growth ), the freshwater diatom ( Navicula pelliculosa ; +4% growth), and stimulative growth was also ob served in the vascular aquatic plant duckweed ( L. gibba ; +4% growth). 

## b. Effects to Terrestrial Organisms

Table 7. Summary of the Most Sensitive Endp oints from Terrestrial Toxicity Studies for Forchlorfenuron

Taxonomic Group Study Type Species Toxicity Value (Endpoints) Acute Toxicity Classification MRID (Study Classification) Birds, Reptiles, &Terrestrialphase amphibians Acute Bobwhite quail ( Colinus virginianus ) (TGAI, 100% a.i.) LD 50 > 2250 mg a.i./kgbw 1 Practically nontoxic 44359523 (Acceptable)

Sub-acute dietary Bobwhite quail LC 50 > 5620 mg a.i./kgdiet 1 Practically nontoxic 44359521 (Acceptable)

### 12 Taxonomic Group Study Type Species Toxicity Value (Endpoints) Acute Toxicity Classification MRID (Study Classification)

Repro Bobwhite quail NOAEC/LOAEC<170/170 mg a.i./kgdiet 2 NA 49350901 (IN REVIEW)

Mammals Acute oral Laboratory rat ( Rattus norvegicus ) (EP, 0.86% a.i.) LD 50 > 5,050 mg/kgbw (M&F) 3 Practically nontoxic; Toxicity

category IV 45794401 (Acceptable)

Chronic 2-gen. Laboratory rat (TGAI, 98.5% a.i.) NOAEC/LOAEC = 150/2000 ppm (9/115 mg/kg/day) 4 NA 44394616 (Acceptable)

Acute inhal. Laboratory rat (EP, 0.86% a.i.) LC 50 > 2.14 mg/L (M&F) 5 Toxicity category IV 45794403 (Acceptable)

Terrestrial invertebrates Acute
contact Honey bee ( Apis mellifera ) (TGAI, 98.5% a.i.) LD 50 >25 ug a.i./bee 6 Practically nontoxic 44359525 (Acceptable)

Terrestrial plants 7 Seedling Emergence Monocot and Dicot species EC 25 > 0.055 lbs a.i./A NOAEC = 0.055 lbs a.i./A NA 45840111 (Acceptable)
Vegetative Vigor (monocot) Oat ( Avena sativa ) EC 25 > 0.0067 lbs a.i./A NOAEC = 0.0067 lbs a.i./A NA 46753505 (Supplemental)
Vegetative Vigor (dicot) Cucumber ( Cucumis sativa ) EC 25 > 0.0071 lbs a.i./A NOAEC < 0.0071 lbs a.i./A 8 NA 46753505 (Supplemental)
NA: Not Applicable

1 No mortality

2 Significant (7-9%) dose-dependent reductions in 14-d survivor weight in all treatment levels when compared to the negative control.

3 No mortality was observed; the only clinical sign was diarrhea in males on the day of dosing.

4 Endpoints affected included: de creased food consumption in F 0 & F 1 M; clinical signs of toxicity & lower BW in F 1 M & F and growth retardation in F 1 & F 2 pups); Concentrations tested: 0, 150, 2000, and 7500 ppm, Premating doses for the adult F 0 males were 11, 144, and 544 mg/kg/day and for the F 0 females were 13, 169, and 701 mg/kg/day, respectively. Premating doses for the adult F 1 males were 13, 168, and 829 mg/kg/day and for the F 1 females were 15, 202, and 926 mg/kg/day, respectively.
5 No mortality was observed; Clinical signs included activity decrease and p iloerection in both sexes on the day of dosing only.

6 There were two (2) mortalities (4%) in the negative control and 25 μ g a.i./bee (measured) test concentrations; and one (1) mortality (2%) in the solvent control at 48 hours. Imm obility and lethargy were noted in a few instances, but this was largely the case in the two control groups.

7 No significant effects in reduction were observed for terrestri al plant species exposed to forchlorfenuron at the treatment rate tested, i.e ., 0.055 lbs a.i./A (seedling emerge nce, MRID 45840111) or 0.022 lbs a.i./A (vegetative vigor, MRID 46753505). However, there were stimulative, positive growth e ffects that were obse rved for some terrestrial plant species that were tested. For the seedling emergence study, these stimulative effects were obse rved in cabbage (+11% shoot length), corn (+9% shoot weight), oat (+13% shoo t weight), onion (+8% shoot weight), perennial ryegrasses (+4% shoot length and +46% shoot weight ), and turnips (+3% shoot length); and for the vegetative vigor study, these stimulative effects were observed in corn (+4% shoot length and +8% dry weight), oat (+2% shoot length), onion (+1% shoot length and +6% dry weight), ryegrass (+4% shoot length and +15% dry weight), cabbage (+2% dry weight), lettuce (+19% shoot length dry weight), soybean (+6% dry weight), and turnips (+36% dry weight) . For the vegetative vigor study, the measured concentrations were 30.3-32.2% of nominal, which was supposed to be set at the maximum application rate of 0.022 lbs a.i./A. However, the study does provide some information on potential toxic effects to plants; but the study did not test forchlorfenuron at the highest application rate.

8 Endpoints affected: None, but there was a 20% reduction in dry weight in cucumber.

### 13 

## c. Ecological Incidents

The ecological incident information system (EIIS ) is an OPP database that houses ecological incidents that have been reporte d to the Agency. When available, EIIS includes date and location of an incident, type and magnitude of effects obs erved in various species, use(s) of pesticides known or suspected of contributing to the incident, and results of any chemical residue analysis or other analyses conducted dur ing incident investigation. E IIS incidents are categorized according to the certainty that the incident resulted from pesticide exposure. The Avian Monitoring System (AIMS) is a database admini stered by the American Bird Conservancy that contains publicly available data on reported avian incidents invol ving pesticides. Many of the incidents listed in this database are also in the EIIS. The Aggregate Incident Reports database is an Agency database that may contain minor wildlife and plant incidents for chemicals.

As of November 24, 2014, there were no ecological incidents reported in EIIS or AIMS for forchlorfenuron. There were also no minor incidents reported in the Aggregate Incident Reports database for forchlorfenuron. However, an abse nce of incident reports does not necessarily equate to an absence of incidents give n the nature of incident reporting. 

## 7. Exposure Pathways of Concern

The environmental fate properties and use patterns of forchlorfenuron indicate that direct spray, spray drift, and runoff represent potential transport mechanisms to aquatic and terrestrial organisms. The conceptual model will consider forchlorfenuron as the residue of concern.

Drinking water and inhalation e xposure pathways were screen ed using the SIP (Screening Imbibition Program, version 1.0) and STIR (Scr eening Tool for Inhalation Risk, version 1.0) screening methods. Only one potential route of exposure (drinking water to birds on a chronic basis) was found to be an exposure pathway of potential concern ( Table 8 ). Although, SIP suggests that exposure to contam inated drinking water could lead to LOC exceedances, a number of factors affect the likelihood that exposures will result in adverse effect s, including pesticide concentrations in the contaminated puddles (SIP assumes the pesticid e is present at the solubility limit) and duration of exposure relative to the duration of exposure n eeded to cause adverse effects. Refinements of these parameters are currently not available. A number of speciesspecific parameters, including water content of di et, size, and behavioral parameters will also influence the potential exposure levels that ma y occur from contaminated puddles. Although SIP was designed as a conservative screen, it ma y over- or under-estimate potential individual exposures based on varying behavi ors of individual birds. The other screening methods found no other potential exposure routes of concer n (outputs for each model are located in Appendix B ). SIP and STIR are described in detail at: http://www.epa.gov/oppefed1/ models/terrestrial/index.htm

.

### 14 Table 8. SIP Avian Results

Parameter Acute Chronic Upper bound exposure (mg/kg-bw) 32 32 Adjusted toxicity value (mg/kg-bw) 1621 18 Ratio of exposure to acute toxicity 0.020 1.7

Conclusion* Drinking water exposure alone is NOT a potential concern for birds Exposure through drinking water alone is a potential concern for birds 

## 8. Analysis Plan

Three ecological risk assessments have been conducted for forc hlorfenuron FIFRA §3 actions: a new chemical assessment in 2004 (DP 301774) and new use assessments in 2008 (DP 341868+) and in 2013 (DP 406985). The assessments conclude d that proposed uses of forchlorfenuron do not result in level-of-concern (LOC) exceedances fo r aquatic or terrestrial organisms. However, chronic risks to birds (a surrogate for terrestria l-phase amphibians and reptiles) and risks to bees are uncertain in the absence of data. These conclusions remain unchanged and an updated, full ecological risk assessment is not needed fo r registration review. EFED recommends that additional data be requested to allow for a more comprehensive evaluation of potential effects to honey bees. EFED will evaluate those data when they are submitted and will work with PRD to address any risks of concer n identified by those data.



## a. Stressors of Concern

i. Ecological Risk Assessment

Forchlorfenuron is the only residue of concer n for terrestrial and aquatic organisms in the ecological risk assessment for forchlorfenuron. Ma jor degradates of forchlorfenuron other than carbon dioxide have not been found.

ii. Drinking Water

Forchlorfenuron is the only residue of concer n for the forchlorfenuron drinking water exposure assessment in support of human health dietary risk assessment, due to a lack of observed organic degradates. The results of the recent 2013 dri nking water exposure assessment (DP 407227) will be used for registration review unless an update is warranted due to ne w data or assessment methodologies.


## b. Measures of Exposure

Past assessments of forchlorfenuron EFED have used standard available models to evaluate potential exposures to aquatic and te rrestrial organisms as described at http://www.epa.gov/oppefed1/models/water/index.htm and http://www.epa.gov/pesticides/science/models_db.htm . GENEEC or the Surface Water Concentration Calculator (SWCC) are currently th e models that are typically used to estimate

### 15 aquatic exposure. T-REX, Bee-RE X, and TerrPlant are currently the models that are typically used to estimate terrestrial exposure. i. Available Monitoring Data

The Agency is not aware of monitoring c onducted by federal and state agencies for forchlorfenuron, as of September 8, 2014. Monitori ng will be considered in the assessment to the extent that data on forc hlorfenuron are available.



## c. Measures of Effect

Toxicity data presented in Section 6 of this probl em formulation would be used to calculate risk quotients. Any additional information submitted by the registrant or found in the open literature prior to conduct of the risk a ssessment would also be considere d. The open literature studies are identified using EPA’s ECOTOXicology database (ECOTOX) (USEPA, 2007a), which employs a literature search engine for lo cating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. The evaluation of both sources of data can also provide insigh t into the direct and indirect effects of pesticides on biotic communities from loss of species that are sensitive to the chemicals and from changes in structure and functional characteristics of the affected communities.


## d. Endangered Species Assessments

Consistent with the Agency’s responsibility under the Endangered Species Act (ESA), the Agency would evaluate risks to federally listed, threatened and/or endangered (listed) species from registered uses of pesticides in regist ration review. The process for evaluating potential risks to listed species is further described at http://www.epa.gov/oppfead1/enda nger/litstatus/riskasses.htm

. 

## e. Endocrine Disruptor Screening Program

Forchlorfenuron was not included in the first gr oup of 67 chemicals issued an order to conduct Tier 1 EDSP testing and is not on the second li st of chemicals for Tier 1 screening. For additional information the EDSP program, visit http://www.epa.gov/endo/

. 

## 9. Preliminary Identification of Data Gaps

a. Environmental Fate

Table 9 identifies environmental fate studies by MR ID that offer data for each guideline requirement, as well as study classi fications and whether or not furt her data are needed in order to support risk assessment. Additio nal environmental fate studies and analytical methods are not needed at this time; however, if the requested ecotoxicity data identify a risk concern, then additional environmental fate studies and anal ytical methods may be needed to further characterize the magnitude and duration of the risk.

### 16 Table 9. Submitted Environmental Fa te Data for Forchlorfenuron

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Sufficient for risk assessment? Current Additional Data Need

835.2120 Hydrolysis 4439 4604 Acceptable Yes None 835.2240 Aqueous photolysis 44394605 Supplemental Yes None
835.2410 Soil photolysis (None) (Not applicable) Yes None: forchlorfenuron is not expected to photolyze

835.4100 Aerobic soil metabolism 44359515/ 45840119 Acceptable Yes N one: a study of three additional soils is not needed due to the limited risks

835.4200 Anaerobic soil metabolism 44359514/ 45840118 Acceptable Yes None

835.4300 Aerobic aquatic metabolism (None) (Not applicable) Yes None: a study is not needed due to the limited risks

835.4400 Anaerobic aquatic metabolism (None) (Not applicable) Yes None: a study is not needed due to the limited risks

835.1230 835.1240 Adsorption/ desorption and leaching 44359516/ 45840121 Acceptable Yes None

835.6100 Terrestrial field dissipation (None) (Not applicable) Yes None: a study is not needed due to the limited risks

850.1730 Fish bioconcentration 44359524/ 45840120 Acceptable Yes None

850.6100 Analytical method in soil (None) (Not applicable)

Yes* *Analytical methods are not needed to address low risks. However, if the requested ecotoxicity data identify a risk concern, then an analytical method will be needed for the relevant environmental matrix. Analytical method in water (None) (Not applicable)



## b. Effects

Table 10 and Table 11 identify ecological effects studies by MRID that offer data for each guideline requirement, as well as study classifica tions and whether further data are needed in order to support risk assessment. The rationale for additional non-guideli ne data requested is presented below the tables.

### 17 Table 10. Submitted Aquatic Ecological Ef fects Data for Forchlorfenuron

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Sufficient for risk assessment? Current Additi onal Data Need

850.1010 Freshwater invertebrate acute toxicity 44359520 Acceptable Yes None

850.1025 850.1035 850.1045 850.1055 Saltwater invertebrate acute toxicity (None) (Not applicable) Yes An acute study with an estuarine/marine invertebrate species would allow for a more comprehensive evaluation of potential risks; however, freshwater data will be used as a surrogate in the absence of data. The margin of safety from use of freshwater invertebrate data as a surrogate is such that EFED is confident in the risk conclusions for saltwater invertebrates.

850.1075 Freshwater fish acute toxicity 44359518 Acceptable Yes None 44359519 Acceptable

850.1075 Saltwater fish acute toxicity (None) (Not applicable) Yes An acute study with an estuarine/marine fish species would be useful; however, freshwater data will be used as a surrogate in the absence of data. The margin of safety from use of freshwater fish data as a surrogate is such that EFED is confident in the risk conclusions for saltwater fish.

850.1300 Freshwater invertebrate life cycle (None) (Not applicable) Yes
None. Chronic effects to fish and aquatic invertebrates are unlikely because chronic NOAEC’s would need to be approximately 3 to 4 orders of magnitude lower than acute LC50s to result in chronic risk concern. Tier 1 EECs from past assessments were less than 1 ug/L, and acute LC50s are approximately 5,000 ug/L to 9,000 ug/L. 850.1350 Saltwater invertebrates life cycle (None) (Not applicable) Yes

850.1400 Freshwater fish early-life stage (None) (Not applicable) Yes

850.1400 Saltwater fish early-life stage (None) (Not applicable) Yes

850.1500 Fish life cycle (N one) (Not applicable) Yes

### 18 OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Sufficient for risk assessment? Current Additi onal Data Need

Either 850.1760 Or 850.1770 Whole sediment (chronic) Life cycle freshwater invertebrate (None) (Not applicable) No Yes, Forchlorfenuron has the potential to partition to the sediment (log Kow of 3.2; MRID 44359512 and remain for an extended amount of time (aerobic soil metabolism is 577d; MRID 44359515/ 45840119). One freshwater invertebrate chronic sediment toxicity study would allow us to characterize any potential difference in toxicity to invertebrates exposed via water column vs. sediment.

850.1780 Whole sediment Chronic (Life cycle) estuarine/marine invertebrate (None) (Not applicable) Yes Although based on the fact that forchlorfenuron has the potential to partition to the sediment and remain for an extended amount of time; however, at this time estuarine/marine sediment toxicity data is not being requested, it may be requested at a later date. Freshwater data will be used as a surrogate in the absence of data.

850.4400 Aquatic plant Toxicity Test using Lemna spp. 45840110 Acceptable Yes None

850.4500 Algal toxicity 46753501 Acceptable Yes None; (Marine diatom; Skeletonema costatum )

46753502 Acceptable Yes None; (Freshwater green alga; Pseudokirchneriella subcapitata )

46753503 Acceptable Yes None; (Freshwater diatom; Navicula pelliculosa )

850.4550 Cyanobacteria 46753504 Acceptable Yes None; (Freshwater blue-green alga; Anabaena flos-aquae )

### 19 Table 11. Submitted Terrestrial Ecological Effects Data for Forchlorfenuron

OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Sufficient for risk assessment? Current Additional Data Need

850.2100 Avian oral toxicity 44359523 Acceptable Yes Yes – a second acute oral species is needed to fulfill guideline requirements - passerine or upland game species. However, Tier 1 EECs from past assessments ranged from approximately 5-11 mg/kg, and acute LD50 was >2250 mg/kg-bwand acute LC50 was >5620 mg/kgdiet. The passerine LC50 would have to be 6 orders of magnitude lower than the other avian species to result in an acute listed species LOC exceedance of 0.1. Therefore, based on this, there is a margin of safety given the lack of acute effects to other birds and additional data would not likely add significantly to the risk assessment. 850.2200 Avian dietary toxicity 44359521 Acceptable Yes None 44359522 Acceptable

850.2300 Avian reproduction 49350901 In Review In Review Currently in review, at this time; however, the review will be finalized prior to publication of the DCI. A status update is forthcoming

870.1100 Mammalian acute oral 45794401 Acceptable Yes None

870.1300 Mammalian acute inhalation 45794403 Acceptable Yes None

870. Mammalian 2- generation Reproduction 44394616 Acceptable Yes None

850.3020 Honey bee adult
acute contact toxicity 44359525 Acceptable Yes None

Special study OECD 213 Honey bee adult acute oral toxicity (None) (Not applicable) No An acute oral toxicity study with the adult honey bee is needed.

Special Study Honey bee adult chronic toxicity (None) (Not applicable) No A chronic oral toxicity study with the adult honey bee is needed.

Special study OECD 237 Honey bee larvae acute oral toxicity (None) (Not applicable) No An acute oral toxicity study with the honey bee larvae is needed.

Special Study Honey bee larvae chronic toxicity (None) (Not applicable) No A repeat dose toxicity study with honey bee larvae is needed.

### 20 OCSPP Guideline Data Requirement Submitted Studies (MRID) Study Classifications Sufficient for risk assessment? Current Additional Data Need

Special Study Field trial of residues in pollen and nectar (None) (Not applicable) No A field trial measuring the residues of forchlorfenuron in pollen and nectar is needed

850.3030 Honey bee residue on foliage (None) (Not applicable) Yes None. Acute contact LD 50 >25 μg/bee; study is not triggered, LD 50 is not < 0.11 μg/bee. Special Study OECD 75 Semi-field testing for pollinators (None) (Not applicable) Maybe Need for this study depends on the results of the Tier I studies that are needed.

850.3040 Field testing for pollinators (None) (Not applicable) Maybe Need for this study depends on the results of the Tier I studies that are needed.

850.4100 Seedling Emergence 45840111 Acceptable Yes None

850.4150 Vegetative Vigor 46753505 Supplemental No Additional data is still needed. Measured concentrations (were based on spray solution recoveries) that were 30.3% - 32.2% of nominal. Therefore, based on this the study did not test at the highest application rate. Uncertainty of risk at maximum application rate.



### Honeybee Toxicity

Although forchlorfenuron is categor ized as practically non-toxic to adult honeybees on contact exposure basis, and by extension, to other beneficial terrestr ial invertebrates on an acute exposure basis, there is consider able uncertainty regarding the potential effects of the compound on honeybee larval development and survival as well as potential for chronic effects. Therefore, additional data on pollinators are needed to fu lly characterize the ri sk associated with forchlorfenuron use to all developmental stages of honeybees, as sensitiv ity may vary according to life-stage and length of exposure (adult vs. la rval and acute vs. chronic, respectively). Additional information is needed, but uncertainty associat ed with risks to hone y bees need to be evaluated with more data to different life stages. Open literature data is needed to help better characterize some uncertainties regarding potential effects to bees and othe r non-target terrestrial invertebrates. In addition, highe r tier effects toxicity tests ( i.e., semi-field and/or field studies – Tier II and Tier III, respectivel y) may be needed, based on the results of the larval and chronic adult toxicity studies. Higher tier studies are recommended if the ra tio of the EEC and larval or adult bee acute LD50> 0.4 or the ratio of the EEC and the chronic NOAEC> 1 . Incident data and/or compelling open literature studies can also be used to support the need for higher tier studies. Should the screening level risk assessment identify that there are risk concerns to bees, mitigation measures may need to be considered or the registrant may need to conduct Tier II or Tier III effects studies ( e.g. OECD Guideline 75 and/or 850.3040 guideline studies) that reduce uncertainty by characterizing forchlorfenur on’s effects at the whole-colony level 1



### .

1 http://www2.epa.gov/pollinator-protection/pollinator-risk-assessment-guidance

.

### 21 Study Title: Honey Bee Adult Acute Oral Toxicity Test; Guideline Number: Special Study – OECD 213; Test Substance: Forchlorfenuron – TGAI Rationale for Requiring the Data No data are available with which to assess the toxi city of forchlorfenuron to honey bees on an acute oral exposure basis. Based on the registered use patte rns, terrestrial invertebrates have the potential to be exposed by contacting and consum ing forchlorfenuron residues. Therefore, the acute oral toxicity test is needed for EFED’s current screening-level pr ocess for assessing potential effects to terrestrial invertebrates.
The Agency finalized its framewo rk to assess risk to pollinators (USEPA, 2014). EPA now requires these studies for all use sites where potential exposur e to pollinators may occur. Registrants may request a waiver of the studies if use practices signifi cantly restrict exposure of the pesticide to bees.
The Agency does not have a guideline for the acute oral honey bee study; however, the OECD 213 guideline may be useful in protocol development. Practical Utility of the Data How will the data be used and how could the data impact the Agency’s future decisionmaking? Data will be used to assess hazard and characterize ri sk to non-target listed and non-listed terrestrial invertebrate species. See Guidance for Assessi ng Pesticide Risks to Bees (USEPA, 2014) for additional details.
If future endangered species risk assessments are performed without these data, the Agency would have to assume that forchlorfenuron "may affect " endangered terrestrial insects directly (and endangered species from other taxa indirectly), and u se of forchlorfenuron might need to be restricted in areas where endangered species could be exposed. The lack of these data will limit the flexibility the Agency and registrants have in coming into compliance with the Endangered Species Act and could result in use restrictions for forchlorfe nuron which are unnecessarily severe. In addition, the lack of these data may result in an uncertain assu med risk and potential mitig ation of forchlorfenuron formulations under FIFRA.

### 22 Study Title: Honey Bee Adult Chronic Oral Toxicity Study; Guideline Number: Special Study – Non-guideline; Test Substance: Forchlorfenuron – TGAI Rationale for Requiring the Data No data have been submitted on the chronic toxicity of forchlorfenuron to adult honey bees. A study is needed to determine the chronic toxicity of the compound to adult honey bees, including mortality and sub-lethal effects. This study is part of EFED’s current screening-level process for determining potential effects to terrestrial invertebrates. Ther efore, a non-guideline honeybee larval toxicity study is recommended. Although EPA has not developed a guideline for this study and OECD has yet to finalize test guidance for chronic studies, efforts are currently underway to develop standardized guidelines for assessing effects from chronic (10-day) exposures to adult bees in the laboratory. The registrant should submit a proposed protocol for re view and approval by EFED prior to initiation of the study.
The Agency finalized its framewo rk to assess risk to pollinators (USEPA, 2014). EPA now requires this study for all use sites where potential expos ure to pollinators may occur. Registrants may request a waiver of the study if use practices signifi cantly restrict exposure of the pesticide to bees. Practical Utility of the Data How will the data be used and how could the data impact the Agency’s future decisionmaking?
The 10-day toxicity study with young adult bees provides no-observed adverse effect level (NOAEL) and lowest-observed adverse effect level (LOAEL) for assessing chronic effects. Data obtained from this study will be used in estimating chronic risk to individual adult bees. Risk estimates based on these data will be considered along with other lines of evidence to determine whether higher-tier studies are needed at the whole colony level.
These data are needed for the registration review risk assessment and for future endangered species assessments. The data would allow the Agency be tter characterize the potential for risk to insects (including beneficial pollinators) from the use of forchlorfenuron. This data may help the Agency determine whether any mitigations are needed. If the registration review a nd any future endangered species risk assessments are performed without these data, the Agency would have to assume that forchlorfenuron "may affect" insects, including b ees and beneficial pollinators, directly (and endangered species from other taxa indirectly), and uses of forchlorfenuron might need to be restricted in areas where pollinators could be exposed.

### 23 Study Title: Honey Bee Acute and Chronic Larvae Oral Toxicity Study; Guideline Number: Special Study – OECD 237 and Non-Guideline; Test Substance: Forchlorfenuron – TGAI Rationale for Requiring the Data No data have been submitted on the toxicity of forc hlorfenuron to honey bee larvae. Larval toxicity study are needed to determine the toxicity of the compound to developing brood ( i.e ., larvae and pupae), including mortality and adult emergence. This study is part of EFED’s current screeninglevel process for determining potential effects to terrestrial invertebrates. Although EPA has not developed a guideline for this study, the 21-day larv al toxicity study currently under development by OECD provides both acute and chronic oral toxicity data on developing b ee brood and (when this guidance is finalized) may be used to satisfy the re quirement for both acute and chronic oral toxicity to honey bee larvae. Registrants are at liberty th ough to submit a separate acute (single dose) larval toxicity study following OECD TG 237 as well as the 21-day repeat dose chronic toxicity study. For the chronic toxicity study though, since no guide line is available, it is recommended that the registrant should submit a proposed protocol for re view and approval by EFED prior to initiation of the study.
The Agency finalized its framewo rk to assess risk to pollinators (USEPA, 2014). EPA now requires these studies for all use sites where potential exposur e to pollinators may occur. Registrants may request a waiver of the studies if use practices signifi cantly restrict exposure of the pesticide to bees. Practical Utility of the Data How will the data be used and how could the data impact the Agency’s future decisionmaking?
The 21-day larval toxicity study under development by OECD provides both acute and chronic toxicity data on developing bee brood and will yield a median lethal dose (LD 50 ) for assessing acute toxicity during the early part of the study as well as a 21-day no-observe d adverse effect level (NOAEL) and lowest-observed adverse effect level (LOAEL) for assessing chronic effects. Effects on survival and development (adult bee emergence) from repeat exposures to the active ingredient will be used in estimating chronic risk to individual brood. Risk estimates based on these data will be considered along with other lines of evidence to de termine whether higher-tier studies are needed at the whole colony level.
Data will be used to assess risk to non-target listed and non-listed terrestrial invertebrate species. This study would allow the Agency to refine the screening-level hazard assessment for beneficial terrestrial invertebrates. The effects data will be used to determine the potential for adverse effects on beneficial terrestrial invertebrates through direct effects on larval bees. See Guidance for Assessing Pesticide Risks to Bees (USEPA, 2014) for additional details. These data are needed for the registration review risk assessment and for future endangered species assessments. The data would allow the Agency be tter characterize the potential for risk to insects (including beneficial pollinators) from the use of forchlorfenuron. This data may help the Agency determine whether any mitigations are needed. If the registration review a nd any future endangered species risk assessments are performed without these data, the Agency would have to assume that forchlorfenuron "may affect" insects, including b ees and beneficial pollinators, directly (and endangered species from other taxa indirectly), and uses of forchlorfenuron might need to be restricted in areas where pollinators could be exposed.

### 24 

## 10. References

U.S. Department of Agriculture (USDA). 2000. Crop Profile for Kiwi in Ca lifornia. NSF Center for Integrated Pest Management (host). U.S. Department of Agriculture, National Institute of Food and Agriculture. January, 2000. http://www.ipmcenters.org/cropprofiles/index.cfm

United States Environmental Protection Agency (USEPA). 2004. Overview of the Ecological Risk Assessment Process in th e Office of Pesticide Programs . U.S. Environmental Protection Agency, Office of Pesticide Pr ograms, Environmental Fate and Effects Division. Available at http://www.epa.gov/espp/consultation/ecorisk-overview.pdf

USEPA. 2007. Kaul, M. 2007. Maximu m Number of Crop Cycles pe r Year in California for Methomyl Use Sites. U.S. Environmental Protection Agency, Office of Prevention, Pesticides, and Toxic Substances, Biol ogical and Economic Analysis Division. Memorandum to M. Panger, Environmenta l Fate and Effects Division. Feb. 28, 2007.

USEPA. 2007 a . ECOTOXicology Database. Office of Research and Development National Health and Environmental Effects Research Laboratory’s (NHEERL’s) Mid-Continent Ecology Division (MED). http://cfpub.epa.gov/ecotox/

USEPA. 2008. Borges, S., Wm. J. Shaughnessy, a nd D. Spatz. Ecological Risk Assessment for the Section 5 Experimental Use Permit for Forchlorfenuron on Almond, Cherry, Fig, Pear, Pistachio, and Plum/Prune, and the Section 3 Proposed New Use of Forchlorfenuron on the Bushberry Subgroup 13H. DP barcode 341868+. U.S. Environmental Protection Agency, Office of Pe sticide Programs, Environmental Fate and Effects Division. Memorandum to th e Registration Division. Feb. 15, 2008.

USEPA. 2013. Wendel, C. and G. Orrick. Forchl orfenuron: Ecological Risk Assessment for the Section 3 Proposed New Uses on Almonds, Swee t Cherries, Figs, Pear s, Pistachios, and Plums Including Prunes. DP barcode 406985. U. S. Environmental Protection Agency, Office of Chemical Safety and Pollution Pr evention, Environmenta l Fate and Effects Division. Memorandum to the Re gistration Division. Apr. 24, 2013.

USEPA. 2014. Screening Level Usage Analysis (SLUA): Forchlorfenuron. U.S.Environmental Protection Agency, Office of Chemical Safe ty and Pollution Prevention, Biological and Economic Analysis Division. May 20, 2014.

USEPA. 2014 a . Guidance for Assessing Pesticide Risks to Bees. U.S. Environmental Protection Agency, Office of Pesticide Programs; Heal th Canada Pest Management Regulatory Agency; and California Department of Pe sticide Regulation. Jun. 23, 2014. Available at http://www2.epa.gov/pollinator-protectio n/pollinator-risk-assessment-guidance

.

### 25 

## a. Submitted Environmental Fate Studies

MRID Citation Reference
44359508 Harteveld, J. (1992) The Vapor Pressure of SKW 20010: Lab Project Number: 132191310. Unpublished study prepared by Prins Maurits Laboratory TNO. 15 p.
44359509 Treur, J. (1991) Determination of th e Water Solubility of SKW 20010: Lab Project Number: 056622. Unpublished study prepared by RCC Notox B.V. 19 p.
44359512 Treur, J. (1991) Determination of the Partition Coefficient (N-octanol/water) of SKW 20010: Lab Project Number: 056644. Unpublishe d study prepared by RCC Notox B.V. 22
p. 44359514 Schmidt, J. (1992) Anaerobic Soil Me tabolism of (carbon 14)-Forchlorfenuron: Lab Project Number: 38176: N-162-2. Unpublished study prepared by ABC Laboratories, Inc. 674 p.
44359515 Schmidt, J. (1992) Aerobic Soil Metabolism of (carbon 14)-Forchlorfenuron: (Final Report): Lab Project Number: 38175. Unpublished study prepared by ABC Laboratories, Inc. 885 p.
44359516 Dykes, J. (1989) Soil Adsorption/Desorption with (carbon 14)-Forchlorfenuron: Lab Project Number: 38173: N-163-1. Unpublished study prepared by ABC Laboratories, Inc. 360 p.
44359524 Burgess, D. (1990) Uptake, Depuration and Bioconcentration of (carbon 14)-SKW 20010 by Bluegill Sunfish (Lepomis macrochi rus): Lab Project Number: 38137: 7701. Unpublished study prepared by ABC Laboratories, Inc. 327 p.
44394603 Rozek, A. (1985) Determination of the Dissociation Constant, pka of CN-11-3183 (KT30): Lab Project Number: 411975. Unpublished st udy prepared by Velsicol Chemical Lab. 10 p.
44394604 Fostiak, W. (1986) Aqueous Hydrolysis of CN-11-3183 (KT-30): Lab Project Number: 411978. Unpublished study prepared by Sandoz Crop Protection Corp. 12 p.
44394605 Dykes, J. (1990) Determination of the P hotolysis Rate of Forchlorfenuron: Lab Project Number: 38174. Unpublished study prepared by ABC Labs., Inc. 387 p.
45840118 Siemer, S. (2002) Addendum to An aerobic Soil Metabolism of (Carbon 14)- Forchlorfenuron: Lab Project Number: 02- 38176: 38176: 38175. Unpublished study prepared by Seimer and Associates, Inc. 172 p.
45840119 Siemer, S. (2002) Addendum to Aerobic Soil Metabolism of (Carbon 14)-Forchlorfenuron: Lab Project Number: 02-38175: 38175: 38173. U npublished study prepared by Seimer and Associates, Inc. 187 p.
45840120 Siemer, S. (2002) Addendum to Uptake, Depuration and Bioconcentration of (Carbon 14)- SKW 20010 by Bluegill Sunfish (Lepomis mach rochirus): Lab Project Number: 02-38137: 38137: 38173. Unpublished study prepared by Siemer and Associates, Inc. 74 p.
45840121 Siemer, S. (2002) Addendum to Soil Adsorption/Desorption with (Carbon 14)- Forchlorfenuron: Lab Project Number: 02- 38173: 38173: 38175. Unpublished study prepared by Siemer and Associates, Inc. 49 p.

### 26 

## b. Submitted Ecological Toxicity Studies

MRID Citation Reference

44359523 Grimes, J.; Jaber, M. (1989) SKW 20010--An Acute Oral Toxicity Study with the Bobwhite: (Final Report): Lab Project Nu mber: 248-103: 89-0032 WILTR. Unpublished study prepared by Wildlife International Ltd. 25 p.

44359521 Grimes, J.; Jaber, M. (1989) A Dietary LC50 Study with the Bobwhite: (SKW 20010): (Final Report): Lab Project Number: 248 -101: 89-0032: 89-0032 WILTL. Unpublished study prepared by Wildlife International Ltd. 26 p.
44359522 Grimes, J.; Jaber, M. (1989) A Dietary LC50 Study with the Mallard: (SKW 20010): (Final Report): Lab Project Number: 248-102: 89-0032 WILTR. Unpublished study prepared by Wildlife International Ltd. 26 p.
44359518 Bowman, J. (1990) Acute Toxicity of SKW 20010 to Rainbow Trout ( Oncorhynchus mykiss ): Lab Project Number: 37721: 7601-SEP: Unpublished study prepared by ABC Laboratories, Inc. 180 p.
44359519 Bowman, J. (1990) Acute Toxicity of SKW 20010 to Bluegill ( Lepomis macrochirus ): Lab Project Number: 37720: 7601-SEP. Unpublished st udy prepared by ABC Laboratories, Inc. 179 p.
44359520 Forbis, A. (1989) Acute Toxicity of SKW 20010 to Daphnia magna : Lab Project Number: 37722: 7806-SEP. Unpublished study prepar ed by ABC Laboratories, Inc. 158 p.
45794401 Kuhn, J. (2001) Acute Oral Toxicity Study in Rats: KT-30: Final Report: Lab Project Number: 6243-01. Unpublished study prepar ed by Stillmeadow, Inc. 10 p. {OPPTS 870.1100

45794403 Carter, L. (2001) Acute Inhalation Toxicity St udy in Rats: KT-30: Final Report: Lab Project Number: 6245-01. Unpublished study prepar ed by Stillmeadow, Inc. 20 p. {OPPTS 870.1300}

44394616 Nemec, M. (1997) Dietary Two-Generation Reproduction Study of SKW20010 in Rats: Final Report: Lab Project Number: WIL-171002: WIL-171002B: WIL-171002A. Unpublished study prepared by WI L Research Labs., Inc. 2573 p.

45840111 Teixeira, D. (2002) ABG-3207--Determination of Effects on Seedling Emergence of Ten Plant Species: Lab Project Number: 13774.6100: 014123.IT-1. Unpublished study prepared by Springborn Laboratories, In c. 130 p. {OPPTS 850.4100, 850.4225}
45840110 Hoberg, J. (2002) ABG-3207--Toxicity to Duckweed, Lemna gibba: Lab Project Number: 13774.6101: 014123.IT-2: 990106. Unpublished study prepared by Springborn Smithers Laboratories. 49 p. {OPPTS 850.4400}
44359525 Hoxter, K.; Bernard, W.; Smith, G. (1993) SKW 20010: An Acute Contact Toxicity Study with the Honey Bee: Final Report: Lab Project Number: 248-106A: 079212. Unpublished study prepared by Wildlife International Ltd. 36 p
46753505 Teixeira, D. (2005) CPPU - Determinati on of Effects on Vegetative Vigor of Ten Plant Species. Project Number: 13774/6107, 044123/1A/5, METH/171. Unpublished study prepared by Springborn Smithers Laboratories and Morse Laboratories, Inc. 124 p.

### 27 MRID Citation Reference
46753501 Hoberg, J. (2005) CPPU - Acute Toxicity to the Marine Diatom, Skeletonema costatum

. Project Number: 13774/6105, 044123/1A/1, METHH/171. Unpublished study prepared by Springborn Smithers Laboratories and Morse Laboratories, Inc. 51 p.
46753502 Hoberg, J. (2005) CPPU - Acute Toxicity to the Freshwater Green Alga, Pseudokirchneriella subcapitata . Project Number: 13774/6104, 044123/1A/2, METH/171. Unpublished study prepared by Springborn Smithers Laboratories and Morse Laboratories, Inc. 51 p.
46753503 Hoberg, J. (2005) CPPU - Acute Toxicity to the Freshwater Diatom ( Navicula pelliculosa ). Project Number: 13774/6103, 044123/1A/3, METH/171. Unpublished study prepared by Springborn Smithers Laboratories and KIM-C1, LLC and Morse Laboratories, Inc. 51 p.
46753504 Hoberg, J. (2005) CPPU - Acute Toxi city to the Freshwater Blue-Green Alga, Anabaena flosaquae . Project Number: 13774/6106, 044123/1A/4, METH/171. Unpublished study prepared by Springborn Smithers Laboratories and Morse Laboratories, Inc. 51 p.
49350901 Frey LT, Martin KH, Beavers JB, Jaber M. 2014. Forchlorfenuron: A Reproduction Study with the Northern Bobwhite. Unpublished study performed by Wildlife International, Ltd., Easton, Maryland. 180 p.

### 28 

## APPENDIX A. Forchlor fenuron Ecotoxicity Data Toxicity to Terrestrial Animals
Avian Toxicity Table A-1. Acute Oral Toxicity of Forchlorfenuron to Birds
Species % ai LD 50 (mg a.i./kg-bw) Toxicity Category MRID Author, Year Study Classification Northern bobwhite quail (Colinus virginianus) 100 > 2250 1 Practically non-toxic 44359523 Grimes and Jaber, 1989 Acceptable

1 No mortality of toxicity occurred at the highest concentration tested


### Table A-2. Subacute Dietary Toxicity of Forchlorfenuron to Birds
Species % ai LC 50 (ppm a.i.) Toxicity Category MRID Author, Year Study Classification Northern bobwhite quail (Colinus virginianus) 100 >5620 1 Practically non-toxic 44359521 Grimes and Jaber, 1989 Acceptable

Mallard duck (Anas platyrhynchos) 100 >5620 2 Practically non-toxic 44359522 Grimes and Jaber, 1989 Acceptable

1 One control bird out of fifty died on the first day of te sting. The mortality was attributed to physical injuries

2 No mortality.


### Table A-3. Avian Reproduction Toxicity of Forchlorfenuron to Birds
Species % ai NOAEC/LOAEC (ppm a.i.) Endpoints MRID Author, Year Study Classification Northern bobwhite quail (Colinus virginianus) 96.95 <170/170 1 14-d survivor weight 49350901 Frey, et al . 2014 In Review

1 Significant (7-9%) dose-dependent reductions in 14-d survivor weight in all treatment levels when compared to the negative control


### Mammalian Toxicity Table A-4. Mammalian Toxicity of Forchlorfenuron

Species % ai Test Type Toxicity Value Most Sensitive Endpoints MRID No. Author, Year (Study Classification)
Laboratory rat ( Rattus norvegicus ) 0.86 Acute Oral LD 50 >5,50 1 mg a.i./kg-bw None 45794401 Kuhn, 2001 (Acceptable)

Laboratory rat 0.86 Acute Inhal. LC 50 > 2.14 mg/L 1 None 45794403 Carter, 2001 (Acceptable)

Laboratory rat 98.5 2-gen
repro. NOAEC/LOAEC = 150/2000 ppm (11/144 mg/kg/day) Decreased food consumption in F0 & F1 M; clinical signs of toxicity & lower BW in F1M & F and growth retardation in F1 & F2 pups 44394616 Nemec, 1997 (Acceptable)

1 Male and female; No mortality was observed; the only c linical sign was diarrhea in males on the day of dosing

2 Male and female; No mortality was observed; Clinical signs included activity decrease and piloerection in both sexes on the day of dosing only.

3 Concentrations tested: 0, 150, 2000, and 7500 ppm, Premating doses for the adult F 0 males were 11, 144, and 544 mg/kg/day and for the F 0 females were 13, 169, and 701 mg/kg/day, respectively. Premating doses for the adult F 1 males were 13, 168, and 829 mg/kg/day and for the F 1 females were 15, 202, and 926 mg/kg/day, respectively.

### 29 Terrestrial Invertebrate Toxicity

Table A-5. Terrestrial Invertebrate Acut e Contact Toxicity of Forchlorfenuron

Species % ai LD 50 (μg a.i./bee) Toxicity Category MRID No. Author, Year Study Classification Honey bee (Apis mellifera) 98.5 LD 50 >25 1 Practically non-toxic 44359525 Hoxter et. al., 1993 Acceptable

1 Sporadic mortalities noted were not believed to be treatment-related.



### Toxicity to Terrestrial Plants
No significant effects in reduction were observed for terrestrial plant species exposed to forchlorfenuron at the treatment rates tested, i.e ., 0.055 lbs a.i./A (seedling emergence, MRID 45840111) or 0.022 lbs a.i./A (vegetative vigor, MRID 46753505). However, there were stimulative, positive growth effects that were observed for some te rrestrial plant species that were tested (Table A-6 & A-7).


### Table A-6. Summary of Effects of Fo rchlorfenuron on Vegetative Vigor 1

Species EC25 (lb a.i./acre) NOAEC (lb a.i./acre) Most Sensitive Endpoint MRID (Study Classification) Oat ( Avena sativa )/ Monocot >0.0067 0.0067 No reductions, but a 2% stimulative growth in shoot length

46753505 Teixeira (2005) (Supplemental) Corn ( Zea mays )/Monocot >0.0067 0.0067 No reductions, but a 4% stimulative growth in shoot length and 8% in dry weight

Onion ( Allium cepa )/Monocot >0.0067 0.0067 No reductions, but a 1% stimulative growth in shoot length and 6% in dry weight
Ryegrass ( Lolium perenne )/Monocot >0.0067 0.0067 No reductions, but a 4% stimulative growth in shoot length and 15% in dry weight Cucumber ( Cucumis sativa )/Dicot >0.0071 <0.0071 None, but there was a 20% reduction in dry weight Cabbage ( Brassica oleracea ) Dicot >0.0067 0.0067 No reductions, but a 2% stimulative growth in shoot length

Lettuce ( Latuca sativa )/Dicot >0.0067 0.0067 No reductions, but a 19% stimulative growth in shoot length and dry weight Soybean ( Glycine max )/Dicot >0.0069 0.0069 No reductions, but a 6% stimulative growth in dry weight Tomato ( Solanum lycopersicum )/ Dicot >0.0067 0.0067 None, but there was a 16% reduction in dry weight
Turnip ( Brassica rapa )/Dicot >0.0067 0.0067 No reductions, but a 36% stimulative growth in dry weight

1 Stimulative effects were observed in corn (+4% shoot length and +8% dry weight), oat (+2% shoot length), onion (+1% shoot length and +6% dry weight), ryegrass (+4% shoot length and +15% dry weight), cabbage (+2% dry weight), lettuce (+19% shoot length & dry weight), soybean (+6% dry weight), and turnips (+36% dry weight) . Vegetative vigor study measured concentrations were 30.3-32.2% of nominal, which was supposed to be set at the maximum application rate of 0.022 lbs a.i./A.

### 30 The study does provide some information on potential toxic effects to plants; however, the study has not tested the active ingredient, forchlorfenuron, at the highest application rate.


### Table A-7. Summary of Effects of Fo rchlorfenuron on Seedling Emergence 1
Species EC 25 (lb a.i./acre) NOAEC (lb a.i./acre) Most Sensitive Endpoint MRID (Study Classification)

Monocot and Dicot species >0.055 0.055 No reductions, but stimulative effects in growth were observed for most species (both

monocot and dicot species) 1 45840111 Teixeira (2002)

(Acceptable)

1 Stimulative effects were observed in cabbage (+11% shoot length), corn (+9% shoot weight), oat (+13% shoot weight), onion (+8% shoot weight), perennial ryegrasses (+4% shoot length and +46% shoot weight ), and turnips (+3% shoot length).



### Toxicity to Aquatic Animals
Aquatic Vertebrate Toxicity

Table A-8. Freshwater Fish Acute Toxicity of Forchlorfenuron
Species % ai 96-hour LC 50 (ppm a.i.) Toxicity Category MRID No. Author, Year Study Classification Rainbow trout, ( Oncorhynchus mykiss ) 100 9.2 Moderately toxic 44359518 Bowman, 1990 Acceptable
Bluegill sunfish, ( Lepomis macrochirus ) 100 8.3 Moderately toxic 44359519 Bowman, 1990 Acceptable



### Freshwater Fish Chronic Toxicity No fish early-life stage or fish life cycl e studies are availabl e for forchlorfenuron.

Estuarine/Marine Fish Toxicity No estuarine/marine fish toxicity st udies are available for forchlorfenuron.

Aquatic Invertebrate Toxicity

Table A-9. Acute Toxicity of Forchlor fenuron to Freshwater Invertebrates

Species % ai 48-hour LC 50 (ppm a.i.) Toxicity Category MRID No. Author, Year Study Classification

Waterflea ( Daphnia magna ) 100 5.3 1 Moderately toxic 44359520 Forbis, 1989 Acceptable



### Freshwater Aquatic Inverteb rates Chronic Toxicity No chronic freshwater aquatic invertebrate studies are av ailable for forchlorfenuron.

Estuarine/Marine Aquatic Invertebrates Toxicity No estuarine/marine aquatic i nvertebrate toxicity studies ar e available for forchlorfenuron.

### 31 Aquatic Plant Toxicity

Table A-10. Toxicity of Forchlo rfenuron to Aquatic Plants

Species % ai 96 hr EC 50 (mg a.i./L) EC 05 or NOAEC (mg a.i./L) MRID No. Author (Year) Study Classification

Duckweed ( Lemna gibba ) 0.86 > 0.90 1 0.90 1 45840110 Hoberg (2002) Acceptable 3

Marine diatom ( Skeletonema costatum ) 98.2 > 0.016 2 0.016 2 46753501 Hoberg (2005) Acceptable 3
Green algae ( Pseudokirchneriella subcapitata ) 98.2 > 0.016 2 0.016 2 46753502 Hoberg (2005) Acceptable 3

Freshwater diatom ( Navicula pelliculosa ) 98.2 > 0.017 2 0.017 2 46753503 Hoberg (2005) Acceptable 3
Blue-green cyanobacteria ( Anabaena flos-aquae ) 98.2 > 0.017 2 0.017 2 46753504 Hoberg (2005) Acceptable 3

1 Based on frond numbers and growth rate; no significant effects were seen.

2 Based on cell density; no significant effects were seen.

3 No significant effects in reduction were observed for aquatic plant species exposed to forchlorfenuron at the treatment levels tested. However, there were stimulative, positive growth effects that were obse rved for some aquatic plant species that were tested. Stimulative growth was observed in the following aquatic non-vascular plants: the green algae ( Pseudokirchneriella subcapitata ; +43% growth ), the freshwater diatom ( Navicula pelliculosa ; +4% growth), and stimulative growth was also observed in the vascular aquatic plant duckweed ( L. gibba ; +4% growth).

### 32 

## APPENDIX B. SIP & STIR Inputs and Outputs

SIP Inputs/Outputs Table 1. Inputs Parameter Value Chemical name Forchlorfenuron Solubility (in water at 25 o C; mg/L) 39

Mammalian LD 50 (mg/kg-bw) 5050 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species Mammalian NOAEL (mg/kg-bw) 9 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species

Avian LD 50 (mg/kg-bw) 2250 Avian test species northern bobwhite quail Body weight (g) of "other" avian species Mineau scaling factor 1.15 Mallard NOAEC (mg/kg-diet) 0 Bobwhite quail NOAEC (mg/kg-diet) 170 NOAEC (mg/kg-diet) for other bird species Body weight (g) of other avian species NOAEC (mg/kg-diet) for 2nd other bird species Body weight (g) of 2nd other avian species

Table 2. Mammalian Results Parameter Acute Chronic Upper bound exposure (mg/kg-bw) 6.7080 6.7080 Adjusted toxicity value (mg/kg-bw) 3884.2609 6.9224 Ratio of exposure to toxicity 0.0017 0.9690

Conclusion* Drinking water exposure alone is NOT a potential

concern for mammals Drinking water exposure alone is NOT a potential

concern for mammals

Table 3. Avian Results Parameter Acute Chronic Upper bound exposure (mg/kg-bw) 31.5900 31.5900 Adjusted toxicity value (mg/kg-bw) 1620.9664 18.0707 Ratio of exposure to acute toxicity 0.0195 1.7481

Conclusion* Drinking water exposure alone is NOT a potential concern for birds Exposure through drinking water alone is a potential concern for birds

*Conclusion is for drinking water exposure alone. This does not combine all routes of exposure. Therefore, when aggregated with other routes ( i.e ., diet, inhalation, dermal), pesticide exposure through drinking water may contribute to a total exposure that has potential for effects to non-target animals.

### 33 STIR Inputs/Outputs 

## Input

Application and Chemical Information
Enter Chemical Name Forchlorfenuron Enter Chemical Use Blueberries Is the Application a Spray? (enter y or n) y If Spray What Type (enter ground or air) air Enter Chemical Molecular Weight (g/mole) 247.69 Enter Chemical Vapor Pressure (mmHg) 3.50E-10 Enter Application Rate (lb a.i./acre) 0.022

Toxicity Properties

Bird Enter Lowest Bird Oral LD 50 (mg/kg bw) 2250 Enter Mineau Scaling Factor 1.15 Enter Tested Bird Weight (kg) 0.178 Mammal Enter Lowest Rat Oral LD 50 (mg/kg bw) 5050 Enter Lowest Rat Inhalation LC 50 (mg/L) 2.14 Duration of Rat Inhalation Study (hrs) 4 Enter Rat Weight (kg) 0.35


## Output Results Avian (0.020 kg ) Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 4.67E-06 Maximum 1-hour Vapor Inhalation Dose (mg/kg) 5.86E-07 Adjusted Inhalation LD 50 5.32E+00 Ratio of Vapor Dose to Adjusted Inhalation LD 50 1.10E-07 Exposure not Likely Significant Maximum Post-treatment Spray Inhalation Dose (mg/kg) 2.11E-03 Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD 50 3.98E-04 Exposure not Likely Significant

Results Mammalian (0.015 kg ) Maximum Vapor Concentration in Air at Saturation (mg/m 3 ) 4.67E-06 Maximum 1-hour Vapor Inhalation Dose (mg/kg) 7.37E-07 Adjusted Inhalation LD 50 1.27E+02 Ratio of Vapor Dose to Adjusted Inhalation LD 50 5.79E-09 Exposure not Likely Significant Maximum Post-treatment Spray Inhalation Dose (mg/kg) 2.66E-03 Ratio of Droplet Inhalation Dose to Adjusted Inhalation LD 50 2.09E-05 Exposure not Likely Significant **NOTE**: When entering values, pre s in order to update linked cells.