2 

### TABLE OF CONTENTS

Page #

I. Preliminary Work Plan (PWP) 3

II. Fact Sheet 7

III. Ecological Risk Assessment Problem Formulation 10

IV. Human Health Effects Scoping Document 27

V. Glossary of Terms and Abbreviations 333 I. Preliminary Work Plan

Introduction: The Food Quality Protection Act of 1996 manda ted a new program: registration review. All pesticides distributed or sold in the United States generally must be registered by EPA, based on scientific data showing that they will not cause unreasonable risks to human health, workers, or the environment wh en used as directed on product labeling. The new registration review progr am is intended to make sure that, as the ability to assess risk evolves and as policies and practices cha nge, all registered pesticides continue to meet the statutory standard of no unreasonabl e adverse effects. Changes in science, public policy, and pesticide use practices will occur over time. Through the new registration review program, th e Agency periodically reevaluate s pesticides to make sure that as change occurs, products in the mark etplace can be used safely. Information on this program is provided at: http:// www.epa.gov/oppsrrd1/regist ration_review/.

The Agency has begun to implement the new Registration Review program, and plans to review each registered pesticide every 15 year s to determine whether it continues to meet the FIFRA standard for registration. The public phase of registration review begins when the initial docket is opened for each case. The docket is the Agency’s opportunity to state clearly what it knows about the pesticide and wh at additional risk analyses and data or

information it believes are needed to make a registration review decision.

Anticipated Risk Assessment and Data Needs: The Agency anticipates conducting a comp rehensive ecological risk assessment, including an endangered speci es assessment for paclobutrazol. For human health assessments, the Agency anticipates that o ccupational and residential risk assessments may be needed for some uses.

Ecological Risk:

• While there are summaries of available effects and environmental data, there are no risk assessments available for paclobutr azol. Please refer to the Ecological

Risk Assessment Problem Formulati on, for a detailed discussion of the anticipated risk assessment needs.

• Based on preliminary screening-level risk estimates using Structure Activity Relationship parameters for structurally similar compounds, extrapolated toxicity endpoints indicate that risk quotients may exceed the Agency’s level of concern using conservative exposure assumptions for birds, amphibians, and fish. It should be noted that these risk quotie nts have a high uncertainty level.

• In order to complete a comprehensive risk assessment for paclobutrazol, the Agency anticipates requiring additional toxicity data for plants and chronic toxicity data for birds an d fish, as listed below.

• (GLN 850.1400) Fish early life stage.

• (GLNs 850.4320, 850.4320) Seedling emergence and vegetative vigor.

• (GLN 850.2300) Avian reproduction.4 Human Health Risk:

• Paclobutrazol has no food use registrations; therefore, a dietary (food only) risk assessment is not required. Additionall y, no toxicity endpoint was identified for an acute dietary assessment. However, paclobutrazol has a turf use which could lead to exposure through drinking water. The Agency anticipates needing a groundwater and surface water exposure assessment analysis and a chronic drinking water risk assessment. No a dditional data are needed to conduct the drinking water assessment.

• Occupational risk assessments may be needed for uses on turf, outdoor ornamentals, greenhouse ornamentals, bulb soak treatments, and seed treatments; however, no additional data are needed to complete these assessments. The scenarios for the occupationa l assessments would include short- and intermediateterm dermal and inhalation scenarios.

• Paclobutrazol can currently be used on residential turf which requires residential

risk assessments for short- and interm ediate-term dermal and inhalation and children’s incidental oral exposures. No additional data are needed for this assessment. The only technical regist rant with residential lawn uses has requested that the Agency cancel this re sidential use. The Agency intends to publish the receipt of this request in th e Federal Register and to take public comment as required under FIFRA 6(f). If this use for residential turf is removed from all paclobutrazol labels, no chil dren’s assessment will be required.

Timeline: EPA has created the following estimated time line for the completion of the paclobutrazol registration review. The Agency may conduct the residential or o ccupational assessment for turf, outdoor ornamentals, greenhouse orna mentals, bulb soak treatments, and seed treatments and residential assessments for turf much earlier in the process, allowing mitigation (if necessary) to occur well before the 5.5 years elapse.5 Activities Estimated

Month/Year Phase 1: Opening the docket Open Public Comment Period for Pa clobutrazol Docket March 2007

Close Public Comment Period June 2007 Phase 2: Case Development
Develop Final Work Plan (FWP) Aug. 2007

Issue DCI June 2008 Data Submission May 2010 Open Public Comment Period for Preliminary Risk Assessments Sept. 2011

Close Public Comment Period N ov 2011
Phase 3: Registration Review Decision Open Public Comment Period for Proposed Reg. Review Decision Feb 2012 Close Public Comment Period April 2012 Final Decision and Begin Post-Decision Follow-up Aug. 2012 Total (years) 5.5

Guidance for Commenters: The public is invited to comme nt on EPA’s preliminary regi stration review work plan and rationale. The Agency will carefully consider all comments as well as any additional information or data provided prior to issuing a final work plan for the paclobutrazol case.

Through the registration review process, th e Agency intends to solicit information on trade irritants and, to the extent feasible, take steps toward fa cilitating irritant resolution.

Growers and other stakeholders are asked to comment on any trade irritant issues resulting from lack of Maximum Residue Li mits (MRLs) or disparities between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible regarding the nature of the concern. There ar e no U.S. tolerances for paclobutrazol, nor are there Codex MRLs; so trade irritants are not e xpected for paclobutrazol.

Stakeholders are also specifically asked to pr ovide information and da ta that will assist the Agency in refining the ecological risk assessment, including any species-specific effects determinations. The Agency is interested in the following information:

1. confirmation on the following label information

a. sites of application

b. formulations

c. application methods and equipment

d. maximum application rates in units related to mass per unit area of

treatment zone6 e. frequency of application, applicati on intervals, and maximum number of applications per season

f. geographic limitations on use

2. use or potential use distri bution (e.g., acreage and geogr aphical distribution of relevant crops)

3. use history

4. median and 90 th percentile reported use rates (l bs ai/acre) from usage data – national, state, and county

5. application timing (date of first applica tion and application intervals) by crop – national, state, and county

6. sub-county crop location data

7. usage/use information for non-agricultural uses (e.g., forestry, residential, rightsof-way)

8. directly acquired county-level usage da ta (not derived from state level data)

a. maximum reported use rate (lbs a i/acre) from usage data – county

b. percent crop treated – county

c. median and 90 th percentile number of applications – county

d. total pounds per year – county

e. the year the pesticide was last us ed in the county/sub-county area

f. the years in which the pesticide was applied in the county/sub-county area

9. typical interval (days)

10. state or local use restrictions

11. ecological incidents (non-target plant dama ge and avian, fish, reptilian, amphibian and mammalian mortalities) not already reported to the Agency

12. monitoring data

13. data on the residues of paclobutrazol in above gr ound portions of vegetation following tree injection, root zone injection of basal dr ench, and soil drench uses.

Additionally, paclobutrazol is no t identified as a cause of im pairment for any waterbodies listed as impaired under sect ion 303(d) of the Clean Water Act, based on information provided at http://oaspub.epa.gov/tmdl/w aters_list.impairments?p_impid=3

. However, the Agency invites submission of other existi ng water quality data fo r these chemicals. To the extent possible, data elements iden tified in Appendix A of the “OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessmen t and Management Process” should be provided (reference: http://www.epa.gov/ oppfead1/cb/ppdc/2006/ november06/session1- sop.pdf ), in order to ensure they can be us ed quantitatively or qua litatively in pesticide

risk assessments.

Next Steps: After the comment period closes, the Agency will prepare a Final Work Plan for this pesticide.7 II. FACT SHEET

Background Information :

• Paclobutrazol registration review case number: 7002

• Paclobutrazol PC Code: 125601 CAS#:76738-62-0

• Technical registrants: Syngenta Crop Protection, Chemtura USA Corporation, Fine Agricultural Chemicals Limited, and Zhejiang Tide CropScience Co. Ltd.

• First registered in 1985; therefore it was not subject to reregistration.

• No food uses or tolerances.

• Special Review and Reregistration Divi sion Chemical Review Manager (CRM): Nathan Mottl: mottl.nathan@epa.gov

• Registration Division Product Contacts: Tony Kish: Kish.Tony@epa.gov John Bazuin: Bazuin.John@epa.gov

• 28 total active products are registered; 5 manufacturing use products, 19 end-use products, and 4 experimental use permits.

• Paclobutrazol is sold in several different formulations includ ing wettable powder, soluble concentrates, granular fertil izer, and emulsifiable concentrate

formulations.

• Paclobutrazol can be applie d through drop and push spreader and a variety of spray equipment on grass; chemigati on, foliar spray, dren ch, bulb soak in greenhouses; basal drench, soil inco rporation, and tr ee injection

Use & Usage Information: (For additional details on label rates and allowed uses, please refer to the BEAD Appendix A doc ument in the pacl obutrazol docket.)

• Paclobutrazol is a plant growth regula tor that slows vegetative growth by inhibiting gibberilin biosynthesis creating more compact plants.

• Paclobutrazol can be used as a tree inject ion, soil incorporation, and basal drench to reduce above ground vegeta tive growth (reduces term inal growth and pruning volume) of deciduous trees and pine trees for power line and u tility rights of way. It is most effective when applied to the soil near the base of the tree.

• Paclobutrazol can be used on ornamental pl ants (flowers, seedlings, etc.) grown in containers in nurseries, greenhouses, shade houses and interior landscapes.

• Paclobutrazol is used on turf (e.g., reside ntial, commercial, ornamental, and golf course applications) and can be combined with fertilizers. It can act as a nonselective, post-emergent he rbicide for control of a nnual grasses and broadleaf

weeds. It is used to reduce lawn mowing and to increase turf density.

• California use data indicate appr oximately 11,000 pounds used annually in California with rights of way as the predominant use).

• National usage data is not available.8 Ecological Risk Assessment Status : In order to meet current standards, new eco logical risk assessments are needed for all registered outdoor uses. However a preliminar y screening level assessm ent indicates that

• Risks are unlikely to exceed the Agency’s LOC for listed and non-listed species include: acute risks to birds, mammals, fi sh, amphibians, aquatic invertebrates and

chronic risks to mammals , aquatic invertebrate.

• Risks are likely to exceed the Agency’s LOC fo r listed and non-listed species include: chronic risk to birds, fish, and amphibians.

• Risks to listed and non-listed plants have not been assessed, but may be expected to exceed the Agency’s level of concern based on the chemical’s known

mechanism of action.

Human Health Risk Assessment Status:

Please refer to Section IV of this documen t, Human Health Effects Scoping Document, for a detailed discussion of the anticipated risk assessment needs for human health. A summary follows:

Dietary (Food and Water):

• No tolerances since it has no food uses.

• Current turf use requires a drinking water assessment which has not been previously completed.

Residential:

• No risk assessments have been conducted for paclobutrazol use on residential turf. However, the only known technical registrant with this use has recently requested voluntary cancellation of the residential tu rf use which would preclude the need for assessing risk from this use scenario.

Occupational :

• No occupational risk assessments have been conducted for paclobutrazol.

• Occupational assessments will be required during registration review for use on turf, outdoor ornamentals, greenhouse ornamentals and bulb soak treatments.

• The Agency anticipates need ing to assess short- and intermediate-term dermal and

inhalation scenarios.

Tolerances:

• No MRLs for paclobutrazol have been established or proposed by Codex for any agricultural commodities.

• There are no Canadian or Me xican MRLs for paclobutrazol.

• No U.S. tolerances are listed.

Data Call-In Status:

• A DCI has not been issu ed for paclobutrazol.9 Labels : A list of registration numbers may be found in the paclobutrazol docket and the labels

can then be obtained from the Pesticid e Product Label System (PPLS) website: http://oaspub.epa.gov/pestlabl/ppls.home

.10 III. 

### Ecological Risk Assessment Problem Formulation



## R EGISTRATION 

## R EVIEW



## E COLOGICAL 

## R ISK 

## A SSESSMENT



## P ROBLEM 

## F ORMULATION FOR 

## :

PACLOBUTRAZOL

( α R

, β R )- rel

- β -[(4-chlorophenyl)methyl]- α -(1,1-dimethylethyl)-1 H

1,2,4-triazole-1-ethanol

P REPARED B Y :

Ed Odenkirchen, Senior Biologist Thuy Nguyen, RAPL

Environmental Risk Branch 1

Environmental Fate and Effects Division Office of Pesticide Programs

A PPROVED B Y :

Nancy Andrews, Chief

Environmental Risk Branch

Environmental Fate and Effects Division Office of Pesticide Programs11 

### S TRESSOR 

### S OURCE AND 

### D ISTRIBUTION

The source of the stressor considered in this document is paclobutr azol. Paclobutrazol, ( α

R

, β R )- rel

- β -[(4-chlorophenyl)methyl]- α -(1,1-dimethylethyl)-1 H -1,2,4-triazole-1- ethanol, is a plant growth regul ator used to modify the physi cal structure of vegetation. According to BEAD data for paclobutrazol use Updated Appendix A submitted to EFED on January 19, 2007, this compound is currently registered for use on golf course turf, ornamental potted plants, trees, shrubs, and vines.

Paclobutrazol is a cell elongati on and internode extension in hibitor that retards plant growth by inhibition of gibbere llin biosynthesis. The compound is expected to be systemically transported through the plant vi a the xylem. It is important to note that current screening risk assessment processes for wildlife exposure via treated vegetation do not address systemic pesticides. Additiona l risk assessment characterization is needed to discuss soil to plant transf er. The purpose of paclobutrazo l use is to produce compact plants with denser vegetative growth. On turf , the material also reduces the frequency of required mowing.



### I NTEGRATION OF 

### A VAILABLE 

### I NFORMATION

While there are summaries of available effect s and environmental fate data, there are no risk assessments available in the docket. This document utilizes screening estimates of exposure and chemical analog data to investig ate the significance of exposure and effects, data gaps on future risk assessment conclusi ons and to identify where there may be data generation opportunities that have important implications of confidence in risk

assessment conclusions.



### E COLOGICAL 

### E FFECTS

Available Toxicity Studies

The following table summarizes the available acute and chronic toxicity data available for paclobutrazol and includes da ta within OPP records as well as the web-based reported of public holdings of the ECOTOX database:

Test Species Effects Endpoint Effects value Mallard duck LD50 >7913 mg/kg-bw Mallard duck LC50 >5,000 mg.kg-diet Bobwhite quail LC50 >20,000 mg.kg-diet Rat LD50 1,336 mg/kg-bw Rat Reproduction NOEL, NOEC 2.5 mg.kg-bw, 50 mg/kg-diet Bluegill sunfish LC50 23.6 mg/L12 Rainbow trout LC50 27.8 mg/L Daphnia magna LC50 33.2 mg/L Daphnia magna LC50 16 mg/L (a.i. based on tested formulation) Limnodrilus hoffmeisteri (tubificid worm) LC50 35.5 mg/L Pseudokirchneriella subcapitata (green alga) EC50 41.5 mg/L Bufo bofo (toad ) LC50 11 mg/L

Beauveria bassian a (fungus) LOEL 500 mg/L

There are no chronic toxicity da ta available for birds, fish, or aquatic invertebrates. To

address the lack of data for chronic effect s in these taxa, the Agency consulted the database for chemical analogs and identifie d tebuconazole and c yproconazole as having

similar structures:

Tebuconazole 128997

Cyproconazole 128993

The Agency then consulted past risk assessments for these two analogs and compared within species acute and chronic endpoints for birds, fish, and aquati c invertebrates. The following table summarizes these findings. Th e acute to chronic ratios (ACRs) these data provide, while within species, are not lik ely always the product of endpoints derived within a single lab (i.e. paired studies) and so they include some increased variation from inter-laboratory sources. As a result, these ACRs do appear to be on the higher side of commonly encountered ratios.13 Within Species Comparisons of Acute and Chronic Endpoints for Chemical Analogs

Chemical Taxa Acute Endpoint Chronic Endpoint Acute/chronic

Ratio
Rainbow trout 4400 ug/L 12 ug/L 367 Sheepshead

minnow 5900 ug/L 21.9 ug/L 269

Daphnia 4000 ug/L 120 ug/L 33 tebuconazole

Bobwhite quail >5000 mg/kgdiet 156 mg/kg-diet >32

Rainbow trout 19000 ug/L 150 ug/L 127 Daphnia 26000 ug/L 290 ug/L 90 Bobwhite quail 816 mg/kg-diet 50 mg/kg-diet 16 cyproconazole

Mallard duck 1197 mg/kgdiet 10 mg/kg-diet 120

There is little information to assess the m echanism of toxic action differences between these analogs and paclobutr azol. The analogs selected for the paclobutrazol problem formulation are triazole fungicides. They ha ve a primary activity shared with all the DeMethylation Inhibitor (DMI) fungicides in that they act through modification of the CYP51 family of cytrochromes. The CYP51 re ference pertains to th e lanosterol 14-alpha demethylase that is key in making cholesterol fr om lanosterol. In other words the triazole fungicides act on the sterol biosynthesis pa thway, thereby disrupting cell membranes. This enzyme is evolutionarily conserved in pl ants, fungi and animals, and bacteria. This is the only P450 to be so highly conserved and it may have been the ancestor to all eukaryotic P450s. As such, chemical imp act on sterol biosynthesis has potential implications for reproduction and devel opment in higher organisms through possible effects on steroidal hormone synthesis in addition to cellular effects..

The question is whether paclobutrazol is bi ochemically similar. Paclobutrazol is a

triazole which inhibits sterol as well as giberellin bios ynthesis so it also has some fugicidal activity (against mildews and rusts). The inhibition of sterol synthesis is likely

similar to the other triazole s. Therefore, effects on hi gher organisms (e.g., development and reproduction) as mediated by sterol products is likely similar to that of the fungicidal analogs used in the problem formulation.

The analogs are fungicides and while pacl obutrazol is not labeled as a fungicide,

available data summarized above shows that paclobutrazol can produce effects in at least one fungal species. Moreover, with aqua tic organisms, the acute values for cyproconazole for trout and daphnids (19,000 and 26,000 ug/L) are on the order of those for paclobutrazol (27,000 and 33,000 ug/L). For terrestrial wildlife, the tebuconazole quail LD50 (>5000 mg/kg-diet as a limit test) ca nnot be said to be radically different from the paclobutrazol endpoint (>20,000 mg/kg-di et). With this limited information and assuming that structural analogs may exhibi t similar, though not exact, toxicological properties, EFED selected the largest and sma llest acute to chronic ratios (ACRs) for fish, aquatic invertebrates, and bird s and then applied them to available paclobutrazol acute endpoints to conservatively estimate a chroni c endpoint range for each un-tested taxa. The following table presents these results.14 Taxa Measured Acute Endpoint Acute:Chronic Ratio Esti mated Chronic Endpoint

Fish 23.6 mg/L 127 to 367 0.06 to 0.19 mg/L Aquatic phase amphibian 11 mg/L 127 to 367 0.03 to 0.09 mg/L*

Aquatic invertebrate 33.2 mg/L 33 to 90 0.37 to 1 mg/L Bird >5000 mg/kg-diet 16 to 120 >41.7 to > 312 mg/kg-diet
*high uncertainty concerning this extrapolation because it extends to another vertebrate taxonomic group

It should be noted that the measured effects va lues for the analogs are not used to directly predict a chronic endpoint for p aclobutrazol. Rather, it is the relationships between the measured acute and chronic endpoints (ACRs) fo r these analogs that are used to estimate chronic endpoints from known acute paclobutra zol endpoints. Because these ACRs may be conservative (see above discussion), the resulting estimated chronic endpoints for paclobutrazol may also be conservative. Howeve r, the ACRs employed are not as great as an ACR for paclobutrazol in mammals, wher e the relationship betw een the rat LD50 and the rat reproduction NOEL is greater than 500.

The range of estimated toxicity values for paclobutrazol can be used to preliminarily determine the potential impact of reducing chronic effects endpoint uncertainty on conclusions generated by the ecological risk assessment. In addition, where available, information on toxicity to estuarine/marine organisms for analogs can be used to extrapolate values for paclobutrazo l in future risk assessments.

In terms of direct effects to terrestrial plants, both dico ts and monocots are known to be sensitive to paclobutrazol based on the targ et uses on turf (monocot) and ornamentals (dicot). The mechanism of action may be exp ected to product altera tions in the growth characteristics of exposed non-plants. However, the lack of terrestrial plant effects data precluded a quantitative assessment of th e magnitude of potential effects and the geographical extent of those eff ects, especially as they relate to analyses for effects on federally listed threatened or endangered spec ies. Because some uses (e.g. turf) involve both spray and granular applica tions of paclobutrazol, exposur es to non-target plants may occur via spray drift and surface runoff. These exposure routes suggest that both vegetative vigor and seedling emergence e ndpoints may be applicable to a risk assessment for paclobutrazol. Therefore, Tier 1 non-target plant toxicity testing with both monocot and dicot plants would provide an initial set of effects endpoints to quantify risk estimates relevant to expected paclobutrazol e ffects, patterns of use, and mechanisms of application.

Incident Reports

The Agency has no incident reports in the Ec ological Incident Information System (EIIS)

for adverse effects to fish or wildlife that were attributed to paclobutrazol use.

.



### E XPOSURE 

### C HARACTERISTICS15 In general terms, paclobutrazol can be char acterized as an environmentally stable compound with a moderate potential for m obility in soil and water environments.

Paclobutrazol is relatively stable in ster ile aqueous solutions with 94.9- 95, 94.2-95.6, and 96-6-98.8 percent of triazo le ring labeled compound present after 30 days in pH 4, 7 and 9 solutions, respectively (no MRID).

The compound did not undergo appreciable phot olysis in water when exposed to 1.94- 2.50 W/m2 at 420 nm in pH7 buffer. By da y 10 of the exposure, 96.6-98.8 percent of paclobutrazol was still present (no MRID). Similar results were observed for paclobutrazol photolysis on soil, with 87.4 perc ent of the compound still present on loam soil irradiated for 105.4 hours by xenon arc lamp (MRID 40685002).

Triazole- and methine-labeled pa clobutrazol degraded with a half life of more than one year in loam soil incubated at 20 o C with 40 percent moisture holding capacity. By the end of an entire incubation year, 54 percen t of triazole-labeled and 50.4 percent of methane labeled parent were not degraded (MRID 40685003).

Both triazole- and methine-labeled paclobutrazo l degraded with a half life of more than one year in flooded loam and silt loam soils incubated at 20 o C. At 1 year post treatment 72.4 percent of triazole-labeled and 60.5 percent of methine- labeled parent were still present (MRID 40685003).

Batch equilibrium testing indicated that pa clobutrazol has the capacity to be mobile on some conditions. Testing was conducted in nine soils ranging in texture from sand to silt

loam. Values for K ads ranged from 1.3 to 23.0 ml/g. Adsorption increased with an increase in soil organic matter content a nd a decrease in soil pH. Values for K des ranged from 1.87 to 27.97 following the first desorp tion step and from 2.66 to 33.95 following the second desorption step (MRID 40685005).

Soil column leaching experiments involving ag ed (9 week) residues of methine-labeled paclobutrazol determined that the compound was relatively immobile in 30 cm columns of sand, sandy loam, loamy sand, and clay loam soils leached with 66 cm of calcium

chloride solution over 9 weeks. In cont rast, aged residues of triazole-labeled paclobutrazol determined that the compound to be of low mob ility in 30 cm columns of sand and sandy loam soils, and mobile in loamy sand and clay loam soils. In all cases, the majority (58.6 – 90.7 percent of the applied) of the aged residue did not leach out of the upper 10 cm of the treat ed soil columns (MRID 40685004).

Further analysis of the unde rlying data is warranted to determine the soil factors influencing paclobutrazol sorption and mobility in soils. In particular, additional analysis of the existing dataset used to establish the role of organic carbon on adsorption in soils and sediment would have implications for surface water exposure modeling as well as determining whether sediment biot a impacts need to be evaluated.16 Paclobutrazol is unlikely to vola tilize to any signif icant extent owing to a low estimated vapor pressure on the order of 10 -6 mm Hg at 20 o C. However, the log K

ow of 3.2 indicates a potential for this chemical to bi oaccumulate in fish. A bioaccumulation in fish study, which was only conducted for 14 days , showed BCF factors of 20x for edible tissues (day 3), 248x for non edible tissues (day 3), and 44x for whole fish (day 10).

The only degradate of paclobutrazol is it s ketone analog, (2RS)-1-(4-chlorophenyl)-4,4- dimethyl-2-(1,2,4-triazol-1-yl)-p entan-3-one, detected in the aerobic soil metabolism study at approximately 18% of total applied a nd at less than 10% in other soil studies.

Paclobutrazol residues were persistent and mobile in terrestrial field dissipation studies in California, West Virginia, Florida, North Carolina, Illinois, and Mississippi (Supplemental MRID 00155854, 40685007, 40685009, 40685010, 40685011, 4068512, and 40685006; and Pearson, 1985 no MRID). Paclobutrazol residues include paclobutrazol and its ketone metabolite. Half -lives of paclobutrazo l residues ranged from 450-950 days for orchard soils in California, We st Virginia, Florida and 25 weeks to 36 weeks in agricultural soils in Mississippi, North Carolina, and Illinois. Although, it was characterized as moderately mobile by la boratory studies, no signi ficant movement of paclobutrazol was detected in the agricultural so ils. In the orchard studies, paclobutrazol residues (parent plus degradate) were detected at 10% or less of total applied, in soil depth of 48 inches in the California study, 24 inches in West Virginia study, and 48 inches in the Florida study. Note that thes e depths are the maximum depths sampled at each study. The paclobutrazol ketone metabolite was predominately detected in the subsurface soil layers, also at insignificant levels.

Based on laboratory and field studies, paclobutrazol has th e potential to contaminate ground water via leaching and su rface water through mainly r unoff. Using the highest rates from the current registered uses (4 ground applications of 0.75 lb ai/A per application), SCI-GROW modeling estimated 4 ppb of parent residues in ground water,

while PRZM/EXAMS estimated acute and ch ronic concentrati ons of 40 and 20 ppb, respectively, in surface water.



### C HARACTERISTICS OF 

### E COSYSTEMS 

### P OTENTIALLY AT 

### R ISK

For paclobutrazol and pesticides in general, the ecosystems at greatest risk are those in close proximity to the use areas. For existing re gistrations of this pesticide, these areas of potential concern for non-target organism effects would include golf courses, plant nurseries, urban landscape areas, residential landscapes, road right s of way, and water bodies directly adjacent to tr eated areas that may receive chemical residues via drift

and/or runoff.

For golf course turf uses paclobutrazol is app lied either as a spray or in granular form from a drop spreader at rates ranging from 0.1 to 0.75 pounds of active ingredient per acre. Mapping the locations of all golf cour ses is beyond the scope of this document. However, based on proprietary usage data, the spatial extent of potential treatment sites17 could extend to tens of thousands of acres for this use alone. There is insufficient

information available to establish locations of use but it is exp ected that potential candidate sites for paclobut razol use extend to most areas of the United States.

Additional information on the amount and geographical distribution of paclobutrazol used on golf courses would assist the Agency in defining the geogra phical scope of this

use.

Tree applications involve urban environments, utility rights of way, residential areas, and other non-crop areas. The compound may be a pplied as a basal dr ench in a trench surrounding the tree trunk-soil intersection, soil injection to a depth of 3 to 6 inches around the base of the tree, or direct injecti on into the tree trunk. Application rates for basal and soil injection range from 1 to 4 g of active ingredient per inch of tree basal area and is tree species dependant. It is presumed th at trunk injection is similar. As is the case for golf courses, mapping the locations of ur ban environments, rights of way, residential areas, and other non-crop areas is beyond the scope of this document. The Agency’s Biological Evaluation and Assessment Divisi on cannot, with available information, assess the mass of use per acre for this use scen ario; therefore the spatial extent of the use

site cannot be defined at this time. However it is expected that potential candidate sites for paclobutrazol use extends to most areas of the United States. Additional information on the amount and geographical distribution of paclobutrazol applied to these use sites would assist the Agency in defining the geographical scope of this use.

For potted ornamental uses the pesticide is a pplied as an indoor or outdoor foliar spray, bulb soak, and indoor soil drench. Labeling does not present applicati on in terms of rates per unit area for these uses. Drenches to pots (EPA registration no. 10182266) range from 0.063 mg active ingredient for 4 inch pot s to 5 mg active ingredient for 12 inch pots. All other applications to potted plants by drench or foliar appl ication are as ppm in application water. The Agency’s existi ng exposure models, both for terrestrial and aquatic organisms rely on application rates expressed in terms of mass per unit area of treatment. The labels for the foliar spray and soil drench methods are not expressed in

these terms. Additional information on the a pplication practices employed for these uses, specifically information that would allow for a conversion of labeled applications rates to units employed in Agency exposure models w ould all for a quantitative assessment of exposure to non target aquatic and terrestrial organisms.

The water column is expected to be the predominant compartment for exposure to paclobutrazol in aquatic systems. Owing to th e use patterns describe d, it is possible that both freshwater and estuarine/marine syst ems may be exposed. Depending on additional analysis of sediment adsorption poten tial through reevaluation of organic carbon influences on available soil adsorption, expos ure to sediment organisms for a persistent compound like paclobutrazol may also be cons idered in future risk assessments.18 

### A SSESSMENT 

### E NDPOINTS

Assessment endpoints are defined as “explicit expressions of the ac tual environmental value that is to be protected.” Defining an assessment endpoint involves two steps: 1) identifying the valued attributes of the envir onment that are considered to be at risk; and 2) operationally defining the assessment endpoint in terms of an ecolo gical entity (i.e., a community of fish and aquatic invertebrate s) and its attributes (i.e., survival and reproduction). Therefore, selection of th e assessment endpoints is based on valued entities (i.e., ecological recep tors), the ecosystems potential ly at risk, the migration pathways of pesticides, and the routes by which ecological receptors are exposed to pesticide-related contamination. The selecti on of clearly defined assessment endpoints is important because they provide direction a nd boundaries in the ri sk assessment for addressing risk management issues of c oncern. Changes to assessment endpoints are typically estimated from the available toxicity studies, which are used as the measures of effects to characterize potentia l ecological risks associated w ith exposure to a pesticide, such as paclobutrazol.

To estimate exposure concentra tions, the ecological risk as sessment considers a single application at the maximum application rate to fields that have vul nerable soils. The most sensitive toxicity endpoints are used from surrogate test species to estimate

treatment-related direct eff ects on acute mortality and chr onic reproductive, growth and survival assessment endpoints. Toxicity te sts are intended to determine effects of pesticide exposure on birds, mammals, fish, te rrestrial and aquatic invertebrates, and plants. These tests include short-term acu te, sub-acute, and repr oduction studies and are typically arranged in a hierarchical or tiered system that progresse s from basic laboratory tests to applied field studies. The toxicity st udies are used to evaluate the potential of a pesticide to cause adverse effects, to determ ine whether further tes ting is required, and to determine the need for precautionary label st atements to minimize the potential adverse effects to non-target animals and plants.

In terms of direct effects to terrestrial plants, both di cots and monocots are assumed sensitive to paclobutrazol, ba sed on the turf (monocot) and tree (dicot) target uses. The mechanism of action may be expected to al ter the growth characteristics of exposed plants. Because there are spray and granul ar applications possible under some use scenarios, exposures for non-target plants ma y involve exposure to both runoff and spray drift. The Agency commonly uses different effects endpoints (v egetative vigor and seedling emergence) for assessing risks to non- target plants from these different exposure

routes.



### C ONCEPTUAL 

### M ODEL

In order for a chemical to pose an ecologica l risk, it must reach ecological receptors in biologically significant concen trations. An exposure pathway is the means by which a pesticide moves in the environment from a source to an ecological receptor. For an ecological exposure pathway to be complete, it must have a source, a release mechanism,19 an environmental transport medium, a point of exposure for ecologi cal receptors, and a feasible route of exposure.

The conceptual model ( Figure 1 ) depicts the potential path ways for ecological risk associated with paclobutrazol use. The c onceptual model provide s an overview of the expected exposure routes fo r organisms within the pacl obutrazol action area. For terrestrial organisms, the ma jor route of exposure considered is the dietary route; consumption of food items such as plant l eaves or insects that have paclobutrazol residues as a result of spraying, drift, and translocation from soil or plant injection through xylem flow. It is important to note that since current scr eening risk assessment processes for wildlife exposur e via treated vegetation do not address systemic pesticides,

additional risk assessment characterization is needed to discuss interplant, and soil to plant transfer. Simplifying first approxima tions of paclobutrazol exposure to wildlife from tree injection, soil drench, root area inje ction, etc. could expl ore pesticide residues

either as a uniform translocation to a ll above ground biomass, or translocation concentrating the material in fruits, seeds, leaves of vegetation could be employed to establish coexposure to herbi vorous wildlife. The Agency would be interested in any available residue monitoring in above ground portions of treated ve getation (particular

trees and shrubs. This information woul d be important to refinement of first approximations of residues in browse for wildlife.

For aquatic animal species, the major routes of exposure are considered to be via the respiratory surface (gills) or the integument.

Direct contact and/or root uptake is the major route of exposure for terrestrial and wetland (riparian) plants, while aquatic plan ts may be exposed via direct uptake and adsorption. Estimated exposure concentrations for all organisms are obtained through the use of several Agency exposure models.20 F IGURE 1. E COLOGICAL CONCEPTUAL DIAGRAM FOR P ACLOBUTRAZOL21 R ISK H YPOTHESIS

Based on an examination of the physical/chemi cal properties of paclobutrazol, the fate and disposition in the environment, and m ode of application, a conceptual model was developed that represents the possible rela tionships between the stressor, ecological receptors, and the assessment endpoints.

The hypotheses for testing by risk assessmen t methods for each existing and proposed paclobutrazol use is “paclobutrazol, used in accordance with the label, produces adverse effects on individual survival , growth, or reproduction in terrestrial vertebrates,
terrestrial invertebrates, terre strial plants, aquatic vertebrat es, aquatic invertebrates, or aquatic plants.”



### A NALYSIS 

### P LAN 

### O PTIONS

In Registration Review, pesticide ecological risk assessments will follow the Agency’s Guidelines for Ecological Risk Assessment, will be in compliance with the paper titled “Overview of the Ecological Risk Assessm ent Process in the Office of Pesticide Programs, U.S. Environmental Protection Ag ency” (“Overview Document”) (January 2004), and will be done in accordance with Se ction 7 of the Endangered Species Act.

Most paclobutrazol exposure scenarios associ ated with terrestrial wildlife and aquatic organisms are covered by existing Agency risk assessment methods. However, as

indicated earlier in this documen t, direct injection of paclobut razol to trees, soil injection in the root zone of vegetati on, soil drench applications of the pesticide involve xylem translocation of the pesticide throughout th e plant. For these uses, the Agency will incorporate in the risk characterization and exploration of different assumptions of the mass of pesticide in edible portions of tr eated plants. Any available information on above ground plant residues of paclobutr azol following these us es would allow the Agency an opportunity to consider refi nement to these exposure assumptions.

There are no ecological risk assessments available for cu rrent and proposed uses of paclobutrazol. Therefore, to evaluate th e adequacy of existin g data sets, EFED conducted some comparisons of upper-bound ex posure estimates with available and estimated effects endpoints.

To look at first approximations of up per bound aquatic exposure EFED conducted PRZM/EXAMS modeling for the turf use. Turf was selected for upper bound estimates of exposure because it likely represents the highe st and most frequent applications of the pesticide. The following were results for th is modeling (all in units of mg/L), assuming 4 applications per year of 0.75 lb ai/A pe r application and 28 day interval between application:22 Peak 96 hr 21day 60day 90day

PA Turf: 0.113 0.113 0.113 0.113 0.113

FL Turf: 0.176 0.176 0.176 0.176 0.176

A comparison of exposure estimates with fi sh, aquatic phase amphibian, and aquatic

invertebrate effects was made to determine the possible ranges of aquatic risk concerns and to evaluate how the range of potential e ffects extrapolations could influence risk assessment conclusions. The following table summarizes these preliminary risk

assessment results and shows that unc ertainties surrounding chronic effects extrapolations do influence the risk conclusi ons for fish and aquatic phase amphibians.

Preliminary Risk Quotients for Turf Use Site and Measured and Estimated Aquatic Organism Effects Endpoints

Use Site Taxa (endpoints mg/L)* Peak EEC (mg/l) Chronic EEC (mg/L) Acute RQ Chronic RQ

Fish (acute:23.6) (chronic:0.06 to 0.19) 0.113 0.113 0.004 0.59 to 1.88*

Amphibian (acute: 11) (chronic 0.03 to 0.09) 0.113 0.113 0.010 1.26** to

3.77** PA turf

Invert (acute:33.2) (chronic: 0.37 to 1) 0.113 0.113 0.003 0.113 to 0.31

FL turf Fish (acute:23.6) (chronic:0.06 to 0.19) 0.176 0.176 0.007 0.92 to 2.93**

Amphibian (acute: 11) (chronic 0.03 to 0.09) 0.176 0.176 0.016 1.96** to

5.87**

Invert (acute:33.2) (chronic: 0.37 to 1) 0.176 0.176 0.005 0.18 to 0.48

* chronic endpoint reflects the range in estimates from the range of available ACR values **RQ exceeds the Agency chronic LOC

Preliminary risk estimates can also be ma de using measured and extrapolated avian effects values to determine if endpoint extr apolation uncertainties can potentially affect risk conclusions. Using a turf applicati on rate of 0.75 lb ai/acre, the acute and extrapolated effects endpoint discussed in this document, and the Agency’s T-TEX terrestrial wildlife risk assessment model the following preliminary risk results are possible. The reader should note that this set of calculatins involves only a single application of paclobutrazol. The available la bels suggest that multiple applications are possible, and depending on the application interval and residue dissipation rates, paclobutrazoll exposures may be higher for multiple applications than depicted in the table. Therefore risk quotients may also be hi gher. The results show that two sources of uncertainty in effects endpoint extrapolation may influence the risk conclusions. First extrapolation from a non-defi nitive acute effects endpoint (i.e., a “greater than” LD50)23 results in non-definitive ch ronic endpoints, which result in risk quotients with upper bounds but no lower bounds. Second, the range of possible ACR values results in a range in chronic endpoints that when used in th e risk assessment mode l, result in risk conclusions that range above a nd below Agency concern levels . Therefore, uncertainties associated with chronic endpoi nt extrapolations can influe nce in ultimate avian risk

conclusions. In addition information relative to the dissipation of paclobitrazol from turf may also influence exposure modeling for multi ple application scenarios for thepesticide.

Preliminary Avian Risk Quotients for Tu rf Use Site and Measured and Estimated Effects Endpoints

Wildlife food item EEC (mg/kgdiet) Acute Endpoint (mg/kg-diet) Chronic Endpoint (mg/kg-diet)* Acute RQ*** Chronic RQ***

Short Grass 180.00 <0.1 <0.58 to

<4.32**

Tall Grass 82.50 <0.1 <0.26 to

<1.98** Broadleaf plants/small

Insects 101.25 <0.1 <0.32 to

<2.43** Fruits/pods/seeds/large

insects 11.25 >5000 >41.7 to >312

<0.1 <0.04 to

<0.27
* chronic endpoint reflects the range in estimates from the range of available ACR values **RQ exceeds the Agency chronic LOC *** The RQ values presented in this table refer to exposures from a single application of paclobutrazol. Multiple applications are possible under the label and, depending upon the dissipation of the compound from wildlife dietary items, residues may reach levels higher than depicted here and RQ values may be higher.

The Agency wishes to better understand 1) wh ich environmental and product specific the results of the comparison between upper bound exposure estimates and measured and estimated aquatic organism effects endpoint s suggest a potential for chronic effects concerns. Because all the aquatic organi sm chronic effects endpoints are estimated values, there is considerable uncertainty a ssociated with risk estimates based on these endpoints. The ranges of the preliminary risk quotients for chronic e ither bracket or are very close to the screening leve l chronic level of concern (RQ > 1). The generation and incorporation of actual measured endpoint for chronic effects in future aquatic organism

risk assessments could have substantial in fluence in the risk assessment conclusions.

If future ecological risk assessments c ontinue to indicate that paclobutrazol may potentially impact, either direct ly or indirectly, listed spec ies or critical habitat, and therefore does not support a “not likely to adversely affect” determination, further refinements to both assessment of expos ure and evaluation of more taxonomically specific effects endpoints will likely be conducted. This will involve determining whether use of paclobutrazol “may affect” a pa rticular listed species, and if so, whether it is “likely to adversely affect” the species, or in the case of critical habitat, whether use of the pesticide may destroy or adversely modify any principle constituent elements for the critical habitat, and if so, whether the exp ected impacts are “likely to adversely affect” the critical habitat. The first step in th e process is to improve the exposure estimates based on refining the geographic proximity of paclobutrazol use and the listed species24 and/or critical habitat. If there is no geographic proxi mity, this information would support a determination that paclobutrazol use will have no effect on the species or

critical habitat. If after c onducting the first step of this analysis the Agency determines that geographic proximity exists, both potenti al direct effects and any potential indirect effects of the pesticide use will be examine d. This process is consistent with the Agency's Overview Document. The Agency w ill consult as necessary with the U.S. Fish and Wildlife Service and National Marine Fisheries Service (Services), consistent with the Services' regulations.

If the screening level risk assessment identifies potential concerns for indirect effects on listed species for those organisms dependent upo n terrestrial plants, the next step for EPA

and the Services would be to identify which listed species and critical habitat are potentially implicated. Analytically, the identif ication of such species and critical habitat

can occur in either of two wa ys. First, the agencies could determine whether the action area overlaps critical habitat or the occupied range of any listed species. If so, EPA would examine whether paclobutrazol pot ential impacts on non-endangered species would affect the listed species indirectly or directly affect a constituent element of the critical habitat. Alternatively, the agencies could determine which listed species depend on biological resources, or have constituent elements that fall into, the taxa that may be directly or indirectly impact ed by paclobutrazol. Then EPA would determine whether the use of paclobutrazol overlaps the critical habi tat or the occupied ra nge of those listed species.

A NTICIPATED D ATA N EEDS

The Agency does not foresee requiring any additi onal environmental fate studies listed in

40 CFR Part 158 prior to conducting the planned assessments.

In contrast the Agency notes the absence of av ailable data for terrestrial plants. In light of the complete absence of definitive terrestria l plant effects endpoints, Tier 1 terrestrial plant toxicity testing (guide line 122-1) with dicots and monocots and for emergence and vigor endpoints would allow the Agency to determine if non-target plant effects are possible. However, the mechanism of action of paclobutrazol suggests that Tier 1 plant testing would likely show at l east a 25% effect in one or mo re plant species which would trigger Tier 2 testing to esta blish more definitive effects e ndpoints. Therefore, a move directly to Tier 2 (guideli ne 123-1), bypassing Tier 1 test ing, would reduce resource expenditures and plant tests would supply effects endpoints nece ssary for quantitative assessment of plants risks for those uses (e.g. turf) where paclobutrazol may run off or drift to areas with non-target pl ant cover. The Tier 2 plant te sting would be of potentially high value for assessing risks to non-target plants for over the top applications of paclobutrazol and would have important utilit y for assessing the potential for indirect effects to federally listed thre atened and endangered species.

In addition, preliminary risk estimates for a quatic organisms indicat e that extrapolation efforts to populate missing chronic endpoints for fish are very uncertain and that these

uncertainties can influence the risk conclusions . Fish early life stag e testing would be of25 potentially high value in addr essing the effects uncertainties that limit the potential

confidence of assessment chronic risks to fish. Reproduction effects endpoints in

terrestrial vertebrates have lead to risk c oncerns in terrestrial wildlife for chemical analogs, and the uncertainties surrounding avia n reproduction endpoint extrapolations for paclobutrazol are large and play an important role in uncertainti es associated with preliminary risk conclusions. Again, avian reproduction testing w ould be of potentially high value in addressing the effects uncertain ties that limit the pot ential confidence of

assessment chronic risks to birds. C onsidering the uncertainties surrounding risk

conclusions associated with the use of extra polated chronic effects endpoints in fish and birds, performance of fish early life st age (guideline 72-4) and avian reproduction (guideline 71-4) studies would be of potentially high value because endpoints established from this testing would allow for less uncer tain effects endpoints than achievable with current analog extrapolations. These more de finitive endpoints woul d, in turn, allow for

a clearer set of risk conclusions for paclobutrazol for thes e taxonomic groups.

While the Agency will conduct a search of the open literature to en sure that all best available science is utilized, it is anticipate d that such a search, based on a preliminary review of the on-line holdings of ECOTOX, will not produce additional effects data for terrestrial plants, aquatic orga nisms, or birds. Agency uses the ECOTOX database as its mechanism for searching the open literatur e for ecological effects information. ECOTOX integrates three previously i ndependent databases - AQUIRE, PHYTOTOX, and TERRETOX - into a system which includes toxicity data derived predominately from the peer-reviewed literature, for aquatic life, terrestrial plants, and terrestrial wildlife, respectively.

A NTICIPATED R ISK A SSESSMENT N EEDS

As stated previously, there are no drinki ng water and ecological risk assessments

available in the docket for the current uses of this chemical. These assessments are needed for the Registration Review process and will be performed in accordance with the Agency’s Guidelines for Ecological Risk Asse ssment (“Overview of the Ecological Risk

Assessment Process in the Office of Pesticid es Programs, U.S. Environmental Protection Agency”, January 2004) and with the S ection 7 of the Endangered Species Act.

O THER I NFORMATION N EEDS

There is specific information that will assist the Agency in refini ng the ecological risk assessment, including any species-specific effects determinations. The Agency is very much interested in obtaining the following information:

1. confirmation on the following label information

a. sites of application

b. formulations

c. application methods and equipment

d. maximum application rates in units related to mass per unit area of

treatment zone26 e. frequency of application, applicati on intervals, and maximum number of applications per season

f. geographic limitations on use.

2. use or potential use distri bution (e.g., acreage and geogr aphical distribution of relevant crops)

3. use history

4. median and 90 th percentile reported use rates (l bs ai/acre) from usage data – national, state, and county

5. application timing (date of first applica tion and application intervals) by crop – national, state, and county

6. sub-county crop location data

7. usage/use information for non-agricultural uses (e.g., forestry, residential, rightsof-way)

8. directly acquired county-level usage da ta (not derived from state level data)

g. maximum reported use rate (lbs a i/acre) from usage data – county

h. percent crop treated – county

i. median and 90 th percentile number of applications – county j. total pounds per year – county

k. the year the pesticide was last us ed in the county/sub-county area

l. the years in which the pesticide was applied in the county/sub-county area

9. typical interval (days)

10. state or local use restrictions

11. ecological incidents (non-target plant dama ge and avian, fish, reptilian, amphibian and mammalian mortalities) not already reported to the Agency

12. monitoring data

13. data on the residues of paclobutrazol in above gr ound portions of vegetation following tree injection, root zone injection of basal dr ench, and soil drench uses.

The analysis plan will be re visited and may be revised de pending upon the data available in the open literature and the information s ubmitted by the public in response to the opening of the Registration Review docket.27 IV. 

### Human Health Effects Scoping Document

UNITED STATES ENVIRONMEN TAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

OFFICE OF PREVENTION, PESTICIDES

AND TOXIC SUBSTANCES

MEMORANDUM

DATE: 13 March 2007

SUBJECT: Paclobutrazol: Registration Review Scopi ng Document for Human Health Assessments; PC Code: 125601; DP Number: DP335538

REVIEWER: Elissa Reaves, Ph.D ., Risk Assessor/Toxicologist Charles Smith, Occupational/Residential Exposure Reregistration Branch 2 Health Effects Division (7509P)

THROUGH: William Hazel, Ph.D., Chief Reregistration Branch 2 Health Effects Division (7509P)

TO: Nathan Mottl/Susan Lewis Reregistration Branch 1 Special Review and Reregi stration Division (7508P)

Attached is the human health scoping documen t to support the regist ration review of the plant growth regulator paclobutrazol.28 HED Preliminary Work Plan for the Registration Review of Paclobutrazol (PC Code 125601)

Introduction

The HED Paclobutrazol Registration Review Team has evaluated the status of the human health assessments for the plant growth regulat or paclobutrazol to determine the scope of work necessary to support registration review. The team looked at the hazard and exposure databases for paclobutrazol and atte mpted to determine whether changes in science policy or deficien cies in the databases materially affected the overall risk picture. The current supported uses for paclobutr azol include turf, outdoor ornamentals, greenhouse ornamentals and bulb soaks. Re sidential uses incl ude use on turf. Paclobutrazol was first registered in 1985; th erefore a Reregistrati on Eligibility Decision (RED) has never been performed. Although a dietary point of departure was identified previously, there are currently no food uses for paclobutrazol and therefore a dietary assessment is not required. In addition, the occupational and re sidential uses of paclobutrazol have never been assessed.

The primary sources for the status update we re the most recent RfD/Peer Review reports (September, 1986; March, 1994) and an OPPI N bibliography search for any newly submitted data. No new toxicity data have been submitted to the Agency since the RfD/Peer Report of June 1994. Route specific inhalation data are cu rrently not available for the occupational inhalation scenarios. A comprehensive search of the open literature was not done primarily because a screening Go ogle search and a Science Direct search indicated very little information was available that pertained to unavailable toxicity data (inhalation, cancer) for paclobut razol. A comprehensive listing of the documents considered is presented in Section 9 of this document. The purpose of this screen is to

determine whether sufficient data are availa ble to support registra tion review. The HED

Risk Assessment team includes El issa Reaves and Charles Smith.

Paclobutrazol is currently registered for use on turf. Therefore, there are no tolerances for paclobutrazol on any commodities.

Section 1. Chemical Identity

Table 1.1 Chemical Identity

Common Name Paclobutrazol IUPAC name (2 RS, 3 RS )-1-(4-chlorophenyl)-4,4-dimethyl-2-(1 H-1,2,4-triazol1-yl)pentan-3-ol CAS name (a R ,ß R )- rel -ß-[(4-chlorophenyl)methyl ]-a-(1,1-dimethylethyl)-

1 H -1,2,4-triazole-1-ethanol

PC Code 125601 CAS registry

number 76738-62-0

Registration Review

Case No. 700229 Chemical Structure

H 3 C C C OH

H H 3 C CH 3

C H CH 2 CL

N N

N

Section 2. Toxicology

A human health assessment has not been perf ormed for paclobutrazol. However, the

RfD/Peer Review Committee evaluated the ex isting toxicology data in 1994 (Memo, G. Ghali, 6/21/94). The RfD Committee concl uded there was no evidence, based on the available data, to suggest that paclobutr azol was associated with developmental or reproductive effects. Pesticid al uses of paclobutrazol do not involve use on food and, therefore, are not subject to the Food Quality Protection Act (FQPA) (1996). The risk

assessment team has reevaluated the toxic ity endpoints for the occupational and residential scenarios and current policies on se lecting endpoints and uncertainty factors.

The HED team believes that there are reliable data to assess occupational and residential risk of paclobutrazol for the process of registration review.

The toxicity database for paclobutrazol is ade quate for the purpose of registration review. A short-term inhalation study is not available to assess occupa tional and reside ntial risk. As such, an oral guideline toxi city study and endpoint will likely be used to estimate risk from inhalation exposure. In addition, an acceptable/guideline cancer study is not

available. The current cancer studies ar e not acceptable since the highest dose was insufficient to adequately eval uate carcinogenicity. However, these cancer studies are considered adequate for the purposes of regist ration review. No toxi city studies have been received by the Agency since the Rf D/Peer Review Committee Report of June

1994.

Table 2.1 includes the toxicity endpoints established from the 1994 RfD Peer Review Committee Report.

Table 2.1 Summary of Toxicological Point of Depa rtures and Endpoints for Paclobutrazol from the RfD/Peer Review Committee Report (1994)

Exposure/

Scenario Point of Departure Uncertainty

Factors Level of

Concern for

Risk

Assessment Study and Toxicological Effects

Acute Dietary All populations No endpoints identified from the available developmental toxicity studies (rat and rabbit) appropriate for an acute diet ary assessment for paclobutrazol.30 Table 2.1 Summary of Toxicological Point of Depa rtures and Endpoints for Paclobutrazol from the RfD/Peer Review Committee Report (1994)

Chronic Dietary All Populations A chronic dietary assessment is not required due to the lack of food uses with paclobutrazol.

Dermal ShortTerm (1-30 days)

Dermal

Intermediate-Term (1-6 months) NOAEL =

10 mg/kg/day

24.5% absorption UF A =10x

UF H =10x Occupational

LOC for MOE

= 100 21-Day Dermal- Rabbit Irritation LOAEL = 100 mg/kg/day, irritation appeared 2 ndweek, doserelated effects included hyperkeratosis, acanthosis, inflammation of superficial dermal.

Dermal LongTerm (>6 months) Long-term dermal exposure is not expected based on the use pattern for paclobutrazol.

Inhalation ShortTerm (1-30 days)

Inhalation

Intermediate-term (1-6 months) Oral

NOAEL =

2.5 mg/kg/day

100% absorption UF A =10x

UF H =10x Occupational

LOC for MOE

= 100 2-Gen Reproduction-Rat LOAEL= 12.5 mg/kg/day, based on ↑ liver weights and fatty changes in

parental females; ↑ incidence of chromodacryorrhea and thickened eyelids, dental malocclusion, liver mottling or accentuation of lobular structure, liver en largement, pallor

and discoloration in male and female pups.

Inhalation Longterm (>6 months) Long-term inhalation exposure is not expected based on the use pattern for paclobutrazol.

Cancer (oral, dermal, inhalation) Classification: Group D The RfD Committee noted that new carcinogeni city studies may be required if the current use pattern changes (i.e. food uses or uses which are in the high exposure category and require carcinogenic ity data) (RfD Report,1994).

1 Explanation of Abbreviations: Point of Departure (PoD) = A data point or an estimated point that is derived from observed dose-response data and used to ma rk the beginning of extrapolation to determine risk associated with lower environmentally relevant hum an exposures. NOAEL = no observed adverse e ffect level. LOA EL = lowest observed

adverse effect level. UF = uncertainty factor. UF A = extrapolation from animal to human (interspecies). UF H = potential variation in se nsitivity among members of the human population (int raspecies). MOE = margin of exposure.

LOC = level of concern.

Section 3. Current Dietary Assessments

In 1994 the RfD Committee consid ered critical endpoints appr opriate for the acute and chronic dietary assessments of paclobutrazol. There were no pertinent effects from the available developmental toxicity studies to establish an acute RfD. The 2-generation reproductive rat study was appropriate for use in the chronic RfD. However, due to the

lack of a tolerance and status as a non-food use, a dietary assessment is currently not required. A dietary assessment will be required if tolerances are requested at a later date.

Drinking water risks have never been asse ssed. The current turf use necessitates a screening level groundwater and surface wate r analysis. The HED paclobutrazol team believes that drinking water risks should be ev aluated to ensure the turf use is acceptable31 at current use rates. Available developmenta l studies indicate no a ppropriate endpoint for use in the acute dietary assessment. Th e 2-generation reproduction rat study, however, would provide a chronic endpoint fo r a screening water analysis.

Section 4. Aggregate and Cumulative Exposure

Paclobutrazol has no food registrations and is therefore not subj ect to FQPA which requires the Agency to consider aggregate a nd cumulative exposures. However, there is the potential for dietary exposur es from drinking water as a result of its use on turf as well as non-occupational (i.e., residential)expos ures from this use. These assessments should be conducted and the aggregate exposur es considered. In addition, EPA has not yet determined whether paclobutrazol has a common mechanism with other compounds, consequently a cumulative assessment will not be performed.

Section 5. Occupational/Residential Exposure

Neither an occupational nor a residentia l assessment has been performed for paclobutrazol. For both a residential and occupational assessment, a 21-day dermal toxicity study is available; however, a 28-day inhalation stud y is not. An oral endpoint from the 2-generation reproduction study with 100% absorption factor may be used in

lieu of inhalation data. For a residential assessment, there are sufficient toxicity data to evaluate incidental oral exposures. Occ upational assessments will be required during registration review for use on turf, outdoor ornamentals, greenhouse ornamentals and bulb soak treatments. Based on currently s upported uses, short- and intermediate-term dermal and inhalation scenarios will be requi red for registration review. A residential assessment will be required for the turf use fo r short- and intermediate-term dermal and

inhalation and children’s in cidental oral exposures.

Section 6. Incident Reports

Based upon a review available data bases (O PP Incident Data System, Poison Control Centers, and NIOSH SENSOR ) from 1992-2005, there were almost no reports of ill effects from exposure to paclobutra zol (M. Hawkins, D335541, 02/27/2007).

Section 7. Anticipated Data Needs

HED does not believe additional data ar e needed for registration review.

Section 8. Tolerances

There are no tolerances for paclobutrazol.

Section 9. Overall Conclusions32 HED does not believe that new data are re quired for registration review. There is currently adequate information to support o ccupational and residential assessments of paclobutrazol. A screening level drinki ng water assessment will be conducted.

Section 10. Reference Memoranda

The memoranda listed in Table 9.1 were consider ed in the development of this document.

Table 9.1. HED Memoranda Relevant to Registration Review

Author Barcode Date Title

Pam Hurley TXR

013485 4/11/94 Toxicology Endpoint Selection Document

George

Ghali TXR

011081 6/23/94 RfD/Peer Report of Paclobutrazol33 V. GLOSSARY of TERMS and ABBREVIATIONS

ai Active Ingredient AR Anticipated Residue CFR Code of Federal Regulations cPAD Chronic Population Adjusted Dose

CSF Confidential Statement of Formula CSFII USDA Continuing Surveys for Food Intake by Individuals

DCI Data Call-In DEEM Dietary Exposure Evaluation Model DFR Dislodgeable Foliar Residue DNT Developmental Neurotoxicity DWLOC Drinking Water Level of Comparison

EC Emulsifiable Concentrate Formulation EDWC Estimated Drinking Water Concentration

EEC Estimated Environmental Concentration EPA Environmental Protection Agency

EUP End-Use Product FDA Food and Drug Administration FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FFDCA Federal Food, Drug, and Cosmetic Act FQPA Food Quality Protection Act FOB Functional Observation Battery GENEEC Tier I Surface Water Computer Model

IR Index Reservoir

LC 50 Median Lethal Concentration. A statistically derived concentration of a substance that can be expected to cause death in 50% of test animals. It is usually expressed as the weight of substance per weight or volume of water, air or feed, e.g., mg/l, mg/kg or ppm.

LD 50 Median Lethal Dose. A statistically deri ved single dose that can be expected to

cause death in 50% of the test animals when administered by the route indicated (oral, dermal, inhalation). It is expressed as a weight of substance per unit weight of animal, e.g., mg/kg.

LOC Level of Concern

LOAEL Lowest Observed Adverse Effect Level μg/g Micrograms Per Gram μg/L Micrograms Per Liter mg/kg/day Milligram Per Kilogram Per Day mg/L Milligrams Per Liter MOE Margin of Exposure

MRID Master Record Identifi cation (number). EPA's system of recording and tracking

submitted studies. MUP Manufacturing-Use Product NA Not Applicable NAWQA USGS National Ambient Water Quality Assessment NPDES National Pollutant Discharge Elimination System NR Not Required

NOAEL No Observed Adverse Effect Level OPP EPA Office of Pesticide Programs OPPTS EPA Office of Prevention, Pesticides and Toxic Substances PAD Population Adjusted Dose PCA Percent Crop Area PDP USDA Pesticide Data Program PHED Pesticide Handler's Exposure Data34 PHI Preharvest Interval ppb Parts Per Billion PPE Personal Protective Equipment ppm Parts Per Million PRZM/EXAMS Tier II Surface Water Computer Model Q 1 * The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer

Risk Model RAC Raw Agriculture Commodity RED Reregistration Eligibility Decision REI Restricted Entry Interval

RfD Reference Dose RQ Risk Quotient SCI-GROW Tier I Ground Water Computer Model SAP Science Advisory Panel SF Safety Factor SLN Special Local Need (Registra tions Under Section 24©) of FIFRA) TGAI Technical Grade Active Ingredient USDA United States Department of Agriculture UF Uncertainty Factor

WPS Worker Protection Standard