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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 33 
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I. Preliminary Work Plan 

Introduction:

The Food Quality Protection Act of 1996 mandated 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 when used as directed on product labeling. 

The new registration review program is intended to make sure that, as the ability to assess 

risk evolves and as policies and practices change, all registered pesticides continue to 

meet the statutory standard of no unreasonable adverse effects. Changes in science, 

public policy, and pesticide use practices will occur over time. Through the new 

registration review program, the Agency periodically reevaluates pesticides to make sure 

that as change occurs, products in the marketplace can be used safely. Information on 

this program is provided at: http://www.epa.gov/oppsrrd1/registration_review/. 

The Agency has begun to implement the new Registration Review program, and plans to

review each registered pesticide every 15 years 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 what 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 comprehensive ecological risk assessment, 

including an endangered species assessment for paclobutrazol. For human health 

assessments, the Agency anticipates that occupational 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 paclobutrazol. Please refer to the Ecological 

Risk Assessment Problem Formulation, 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 quotients 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 and 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. Additionally, 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 additional 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 occupational 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 intermediate-term dermal and inhalation and 

children’s incidental oral exposures. No additional data are needed for this 

assessment. The only technical registrant with residential lawn uses has 

requested that the Agency cancel this residential use. The Agency intends to 

publish the receipt of this request in the 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 children’s assessment will be required.

 

Timeline:

EPA has created the following estimated timeline for the completion of the paclobutrazol 

registration review. The Agency may conduct the residential or occupational assessment 

for turf, outdoor ornamentals, greenhouse ornamentals, 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 Paclobutrazol 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 Nov 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 comment on EPA’s preliminary registration 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, the Agency intends to solicit information on 

trade irritants and, to the extent feasible, take steps toward facilitating irritant resolution. 

Growers and other stakeholders are asked to comment on any trade irritant issues 

resulting from lack of Maximum Residue Limits (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 are no U.S. tolerances for paclobutrazol, nor 

are there Codex MRLs; so trade irritants are not expected for paclobutrazol. 

Stakeholders are also specifically asked to provide information and data 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 zone 
6

e. frequency of application, application intervals, and maximum number of 

applications per season 

f. geographic limitations on use 

2. use or potential use distribution (e.g., acreage and geographical distribution of 

relevant crops) 

3. use history 

4. median and 90th percentile reported use rates (lbs ai/acre) from usage data – 

national, state, and county 

5. application timing (date of first application 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 data (not derived from state level data) 

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

b. percent crop treated – county 

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

d. total pounds per year – county 

e. the year the pesticide was last used 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 damage 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 ground portions of vegetation 

following tree injection, root zone injection of basal drench, and soil drench uses. 

Additionally, paclobutrazol is not identified as a cause of impairment for any waterbodies 

listed as impaired under section 303(d) of the Clean Water Act, based on information 

provided at http://oaspub.epa.gov/tmdl/waters_list.impairments?p_impid=3. However, 

the Agency invites submission of other existing water quality data for these chemicals. 

To the extent possible, data elements identified 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 Assessment 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 used quantitatively or qualitatively 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 Division 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 including wettable powder, 

soluble concentrates, granular fertilizer, and emulsifiable concentrate 

formulations. 

• Paclobutrazol can be applied through drop and push spreader and a variety of 

spray equipment on grass; chemigation, foliar spray, drench, bulb soak in 

greenhouses; basal drench, soil incorporation, and tree injection 

Use & Usage Information: (For additional details on label rates and allowed uses, 

please refer to the BEAD Appendix A document in the paclobutrazol docket.)

• Paclobutrazol is a plant growth regulator that slows vegetative growth by 

inhibiting gibberilin biosynthesis creating more compact plants. 

• Paclobutrazol can be used as a tree injection, soil incorporation, and basal drench 

to reduce above ground vegetative growth (reduces terminal growth and pruning 

volume) of deciduous trees and pine trees for power line and utility rights of way. 

It is most effective when applied to the soil near the base of the tree. 

• Paclobutrazol can be used on ornamental plants (flowers, seedlings, etc.) grown in 

containers in nurseries, greenhouses, shade houses and interior landscapes. 

• Paclobutrazol is used on turf (e.g., residential, commercial, ornamental, and golf 

course applications) and can be combined with fertilizers. It can act as a nonselective, post-emergent herbicide for control of annual grasses and broadleaf 

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

• California use data indicate approximately 11,000 pounds used annually in 

California with rights of way as the predominant use). 

• National usage data is not available. 
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Ecological Risk Assessment Status: 

In order to meet current standards, new ecological risk assessments are needed for all 

registered outdoor uses. However a preliminary screening level assessment indicates that 

• Risks are unlikely to exceed the Agency’s LOC for listed and non-listed species 

include: acute risks to birds, mammals, fish, amphibians, aquatic invertebrates and 

chronic risks to mammals, aquatic invertebrate. 

• Risks are likely to exceed the Agency’s LOC for 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 document, 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 turf 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 needing 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 Mexican MRLs for paclobutrazol. 

• No U.S. tolerances are listed. 

Data Call-In Status:

• A DCI has not been issued 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 Pesticide Product Label System (PPLS) website: 

http://oaspub.epa.gov/pestlabl/ppls.home. 
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III. Ecological Risk Assessment Problem Formulation

REGISTRATION REVIEW

ECOLOGICAL RISK ASSESSMENT

PROBLEM FORMULATION FOR:

PACLOBUTRAZOL

(αR,βR)-rel-β-[(4-chlorophenyl)methyl]-α-(1,1-dimethylethyl)-1H1,2,4-triazole-1-ethanol 

PREPARED BY: 

Ed Odenkirchen, Senior Biologist 

Thuy Nguyen, RAPL 

Environmental Risk Branch 1 

Environmental Fate and Effects Division 

Office of Pesticide Programs 

APPROVED BY: 

Nancy Andrews, Chief 

Environmental Risk Branch 

Environmental Fate and Effects Division 

Office of Pesticide Programs 
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STRESSOR SOURCE AND DISTRIBUTION

The source of the stressor considered in this document is paclobutrazol. Paclobutrazol, 

(αR,βR)-rel-β-[(4-chlorophenyl)methyl]-α-(1,1-dimethylethyl)-1H-1,2,4-triazole-1-

ethanol, is a plant growth regulator used to modify the physical 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 elongation and internode extension inhibitor that retards plant 

growth by inhibition of gibberellin biosynthesis. The compound is expected to be 

systemically transported through the plant via the xylem. It is important to note that 

current screening risk assessment processes for wildlife exposure via treated vegetation 

do not address systemic pesticides. Additional risk assessment characterization is needed 

to discuss soil to plant transfer. The purpose of paclobutrazol use is to produce compact 

plants with denser vegetative growth. On turf, the material also reduces the frequency of 

required mowing. 

 

INTEGRATION OF AVAILABLE INFORMATION

While there are summaries of available effects 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 investigate the significance of exposure and effects, 

data gaps on future risk assessment conclusions and to identify where there may be data 

generation opportunities that have important implications of confidence in risk 

assessment conclusions. 

ECOLOGICAL EFFECTS

Available Toxicity Studies 

The following table summarizes the available acute and chronic toxicity data available 

for paclobutrazol and includes data 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/L 
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 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 data available for birds, fish, or aquatic invertebrates. To 

address the lack of data for chronic effects in these taxa, the Agency consulted the 

database for chemical analogs and identified tebuconazole and cyproconazole 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 aquatic invertebrates. The 

following table summarizes these findings. The acute to chronic ratios (ACRs) these data 

provide, while within species, are not likely 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. 
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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 mechanism of toxic action differences between 

these analogs and paclobutrazol. The analogs selected for the paclobutrazol problem 

formulation are triazole fungicides. They have 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 reference pertains to the lanosterol 14-alpha 

demethylase that is key in making cholesterol from lanosterol. In other words the triazole 

fungicides act on the sterol biosynthesis pathway, thereby disrupting cell membranes. 

This enzyme is evolutionarily conserved in plants, 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 impact on sterol biosynthesis has potential 

implications for reproduction and development in higher organisms through possible 

effects on steroidal hormone synthesis in addition to cellular effects.. 

The question is whether paclobutrazol is biochemically similar. Paclobutrazol is a 

triazole which inhibits sterol as well as giberellin biosynthesis so it also has some 

fugicidal activity (against mildews and rusts). The inhibition of sterol synthesis is likely 

similar to the other triazoles. Therefore, effects on higher 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 paclobutrazol is not labeled as a fungicide, 

available data summarized above shows that paclobutrazol can produce effects in at least 

one fungal species. Moreover, with aquatic 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) cannot be said to be radically different 

from the paclobutrazol endpoint (>20,000 mg/kg-diet). With this limited information and 

assuming that structural analogs may exhibit similar, though not exact, toxicological 

properties, EFED selected the largest and smallest acute to chronic ratios (ACRs) for fish, 

aquatic invertebrates, and birds and then applied them to available paclobutrazol acute 

endpoints to conservatively estimate a chronic endpoint range for each un-tested taxa. 

The following table presents these results. 
14

Taxa Measured Acute 

Endpoint 

Acute:Chronic Ratio Estimated 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 values for the analogs are not used to directly 

predict a chronic endpoint for paclobutrazol. Rather, it is the relationships between the 

measured acute and chronic endpoints (ACRs) for these analogs that are used to estimate 

chronic endpoints from known acute paclobutrazol endpoints. Because these ACRs may 

be conservative (see above discussion), the resulting estimated chronic endpoints for 

paclobutrazol may also be conservative. However, the ACRs employed are not as great as 

an ACR for paclobutrazol in mammals, where the relationship between 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 paclobutrazol in future risk assessments. 

In terms of direct effects to terrestrial plants, both dicots and monocots are known to be 

sensitive to paclobutrazol based on the target uses on turf (monocot) and ornamentals 

(dicot). The mechanism of action may be expected to product alterations in the growth 

characteristics of exposed non-plants. However, the lack of terrestrial plant effects data 

precluded a quantitative assessment of the magnitude of potential effects and the 

geographical extent of those effects, especially as they relate to analyses for effects on 

federally listed threatened or endangered species. Because some uses (e.g. turf) involve 

both spray and granular applications of paclobutrazol, exposures to non-target plants may 

occur via spray drift and surface runoff. These exposure routes suggest that both 

vegetative vigor and seedling emergence endpoints 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 effects, patterns of use, and 

mechanisms of application.

Incident Reports 

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

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

. 

EXPOSURE CHARACTERISTICS
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In general terms, paclobutrazol can be characterized as an environmentally stable 

compound with a moderate potential for mobility in soil and water environments. 

Paclobutrazol is relatively stable in sterile aqueous solutions with 94.9- 95, 94.2-95.6, 

and 96-6-98.8 percent of triazole ring labeled compound present after 30 days in pH 4, 7 

and 9 solutions, respectively (no MRID). 

The compound did not undergo appreciable photolysis in water when exposed to 1.94-

2.50 W/m2 at 420 nm in pH7 buffer. By day 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 percent of the compound still present on loam 

soil irradiated for 105.4 hours by xenon arc lamp (MRID 40685002). 

Triazole- and methine-labeled paclobutrazol degraded with a half life of more than one 

year in loam soil incubated at 20oC with 40 percent moisture holding capacity. By the 

end of an entire incubation year, 54 percent of triazole-labeled and 50.4 percent of 

methane labeled parent were not degraded (MRID 40685003). 

Both triazole- and methine-labeled paclobutrazol degraded with a half life of more than 

one year in flooded loam and silt loam soils incubated at 20oC. 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 paclobutrazol 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 Kads ranged from 1.3 to 23.0 ml/g. Adsorption increased with an 

increase in soil organic matter content and a decrease in soil pH. Values for Kdes ranged 

from 1.87 to 27.97 following the first desorption step and from 2.66 to 33.95 following 

the second desorption step (MRID 40685005). 

Soil column leaching experiments involving aged (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 contrast, aged residues of triazole-labeled 

paclobutrazol determined that the compound to be of low mobility 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 treated soil columns (MRID 40685004). 

Further analysis of the underlying 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 biota impacts need to be evaluated. 
16

Paclobutrazol is unlikely to volatilize to any significant extent owing to a low estimated 

vapor pressure on the order of 10-6 mm Hg at 20oC. However, the log Kow of 3.2 

indicates a potential for this chemical to bioaccumulate 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 its ketone analog, (2RS)-1-(4-chlorophenyl)-4,4-

dimethyl-2-(1,2,4-triazol-1-yl)-pentan-3-one, detected in the aerobic soil metabolism 

study at approximately 18% of total applied and 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 paclobutrazol residues ranged from 

450-950 days for orchard soils in California, West 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 laboratory studies, no significant movement of 

paclobutrazol was detected in the agricultural soils. 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 these 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 the potential to contaminate 

ground water via leaching and surface water through mainly runoff. 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 chronic concentrations of 40 and 20 ppb, 

respectively, in surface water. 

 

CHARACTERISTICS OF ECOSYSTEMS POTENTIALLY AT RISK

For paclobutrazol and pesticides in general, the ecosystems at greatest risk are those in 

close proximity to the use areas. For existing registrations 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 rights of way, and water 

bodies directly adjacent to treated areas that may receive chemical residues via drift 

and/or runoff. 

For golf course turf uses paclobutrazol is applied 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 courses is beyond the scope of this document. 

However, based on proprietary usage data, the spatial extent of potential treatment sites 
17

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 expected that potential 

candidate sites for paclobutrazol 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 geographical scope of this 

use. 

Tree applications involve urban environments, utility rights of way, residential areas, and 

other non-crop areas. The compound may be applied as a basal drench 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 injection 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 that trunk injection is similar. As is the case 

for golf courses, mapping the locations of urban 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 Division cannot, with available information, 

assess the mass of use per acre for this use scenario; 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 applied as an indoor or outdoor foliar spray, 

bulb soak, and indoor soil drench. Labeling does not present application 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 pots to 5 mg active ingredient for 12 inch 

pots. All other applications to potted plants by drench or foliar application are as ppm in 

application water. The Agency’s existing 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 application practices employed for these uses, 

specifically information that would allow for a conversion of labeled applications rates to 

units employed in Agency exposure models would 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 the use patterns described, it is possible that 

both freshwater and estuarine/marine systems may be exposed. Depending on additional 

analysis of sediment adsorption potential through reevaluation of organic carbon 

influences on available soil adsorption, exposure to sediment organisms for a persistent 

compound like paclobutrazol may also be considered in future risk assessments. 
18

ASSESSMENT ENDPOINTS

Assessment endpoints are defined as “explicit expressions of the actual environmental 

value that is to be protected.” Defining an assessment endpoint involves two steps: 1) 

identifying the valued attributes of the environment that are considered to be at risk; and 

2) operationally defining the assessment endpoint in terms of an ecological entity (i.e., a 

community of fish and aquatic invertebrates) and its attributes (i.e., survival and 

reproduction). Therefore, selection of the assessment endpoints is based on valued 

entities (i.e., ecological receptors), the ecosystems potentially at risk, the migration 

pathways of pesticides, and the routes by which ecological receptors are exposed to 

pesticide-related contamination. The selection of clearly defined assessment endpoints is 

important because they provide direction and boundaries in the risk assessment for 

addressing risk management issues of concern. Changes to assessment endpoints are 

typically estimated from the available toxicity studies, which are used as the measures of 

effects to characterize potential ecological risks associated with exposure to a pesticide, 

such as paclobutrazol. 

To estimate exposure concentrations, the ecological risk assessment considers a single 

application at the maximum application rate to fields that have vulnerable soils. The 

most sensitive toxicity endpoints are used from surrogate test species to estimate 

treatment-related direct effects on acute mortality and chronic reproductive, growth and 

survival assessment endpoints. Toxicity tests are intended to determine effects of 

pesticide exposure on birds, mammals, fish, terrestrial and aquatic invertebrates, and 

plants. These tests include short-term acute, sub-acute, and reproduction studies and are 

typically arranged in a hierarchical or tiered system that progresses from basic laboratory 

tests to applied field studies. The toxicity studies are used to evaluate the potential of a 

pesticide to cause adverse effects, to determine whether further testing is required, and to 

determine the need for precautionary label statements to minimize the potential adverse 

effects to non-target animals and plants. 

In terms of direct effects to terrestrial plants, both dicots and monocots are assumed 

sensitive to paclobutrazol, based on the turf (monocot) and tree (dicot) target uses. The 

mechanism of action may be expected to alter the growth characteristics of exposed 

plants. Because there are spray and granular applications possible under some use 

scenarios, exposures for non-target plants may involve exposure to both runoff and spray 

drift. The Agency commonly uses different effects endpoints (vegetative vigor and 

seedling emergence) for assessing risks to non-target plants from these different exposure 

routes. 

CONCEPTUAL MODEL

In order for a chemical to pose an ecological risk, it must reach ecological receptors in 

biologically significant concentrations. 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 ecological receptors, and a 

feasible route of exposure. 

The conceptual model (Figure 1) depicts the potential pathways for ecological risk 

associated with paclobutrazol use. The conceptual model provides an overview of the 

expected exposure routes for organisms within the paclobutrazol action area. For 

terrestrial organisms, the major route of exposure considered is the dietary route; 

consumption of food items such as plant leaves 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 screening risk assessment 

processes for wildlife exposure via treated vegetation do not address systemic pesticides, 

additional risk assessment characterization is needed to discuss interplant, and soil to 

plant transfer. Simplifying first approximations of paclobutrazol exposure to wildlife 

from tree injection, soil drench, root area injection, etc. could explore pesticide residues 

either as a uniform translocation to all above ground biomass, or translocation 

concentrating the material in fruits, seeds, leaves of vegetation could be employed to 

establish coexposure to herbivorous wildlife. The Agency would be interested in any 

available residue monitoring in above ground portions of treated vegetation (particular 

trees and shrubs. This information would 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 plants 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

FIGURE 1. ECOLOGICAL CONCEPTUAL DIAGRAM FOR PACLOBUTRAZOL
21

RISK HYPOTHESIS

Based on an examination of the physical/chemical properties of paclobutrazol, the fate 

and disposition in the environment, and mode of application, a conceptual model was 

developed that represents the possible relationships between the stressor, ecological 

receptors, and the assessment endpoints. 

The hypotheses for testing by risk assessment 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, terrestrial plants, aquatic vertebrates, aquatic invertebrates, or 

aquatic plants.” 

ANALYSIS PLAN OPTIONS

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 Assessment Process in the Office of Pesticide 

Programs, U.S. Environmental Protection Agency” (“Overview Document”) (January 

2004), and will be done in accordance with Section 7 of the Endangered Species Act. 

Most paclobutrazol exposure scenarios associated with terrestrial wildlife and aquatic 

organisms are covered by existing Agency risk assessment methods. However, as 

indicated earlier in this document, direct injection of paclobutrazol to trees, soil injection 

in the root zone of vegetation, soil drench applications of the pesticide involve xylem 

translocation of the pesticide throughout the 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 treated plants. Any available information on 

above ground plant residues of paclobutrazol following these uses would allow the 

Agency an opportunity to consider refinement to these exposure assumptions. 

There are no ecological risk assessments available for current and proposed uses of 

paclobutrazol. Therefore, to evaluate the adequacy of existing data sets, EFED 

conducted some comparisons of upper-bound exposure estimates with available and 

estimated effects endpoints. 

To look at first approximations of upper 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 highest and most frequent applications of the 

pesticide. The following were results for this modeling (all in units of mg/L), assuming 

4 applications per year of 0.75 lb ai/A per 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 fish, 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 effects extrapolations could influence risk 

assessment conclusions. The following table summarizes these preliminary risk 

assessment results and shows that uncertainties surrounding chronic effects 

extrapolations do influence the risk conclusions 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 made using measured and extrapolated avian 

effects values to determine if endpoint extrapolation uncertainties can potentially affect 

risk conclusions. Using a turf application 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 labels 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 higher. The results show that two sources of 

uncertainty in effects endpoint extrapolation may influence the risk conclusions. First 

extrapolation from a non-definitive acute effects endpoint (i.e., a “greater than” LD50) 
23

results in non-definitive chronic 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 the risk assessment model, result in risk 

conclusions that range above and below Agency concern levels. Therefore, uncertainties 

associated with chronic endpoint extrapolations can influence in ultimate avian risk 

conclusions. In addition information relative to the dissipation of paclobitrazol from turf 

may also influence exposure modeling for multiple application scenarios for thepesticide. 

Preliminary Avian Risk Quotients for Turf 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) which environmental and product specific the 

results of the comparison between upper bound exposure estimates and measured and 

estimated aquatic organism effects endpoints suggest a potential for chronic effects 

concerns. Because all the aquatic organism chronic effects endpoints are estimated 

values, there is considerable uncertainty associated with risk estimates based on these 

endpoints. The ranges of the preliminary risk quotients for chronic either bracket or are 

very close to the screening level 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 influence in the risk assessment conclusions. 

If future ecological risk assessments continue to indicate that paclobutrazol may 

potentially impact, either directly or indirectly, listed species or critical habitat, and 

therefore does not support a “not likely to adversely affect” determination, further 

refinements to both assessment of exposure and evaluation of more taxonomically 

specific effects endpoints will likely be conducted. This will involve determining 

whether use of paclobutrazol “may affect” a particular 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 expected impacts are “likely to adversely affect” 

the critical habitat. The first step in the process is to improve the exposure estimates 

based on refining the geographic proximity of paclobutrazol use and the listed species 
24

and/or critical habitat. If there is no geographic proximity, this information would 

support a determination that paclobutrazol use will have no effect on the species or 

critical habitat. If after conducting the first step of this analysis the Agency determines 

that geographic proximity exists, both potential direct effects and any potential indirect 

effects of the pesticide use will be examined. This process is consistent with the 

Agency's Overview Document. The Agency will 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 upon 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 identification of such species and critical habitat 

can occur in either of two ways. 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 potential 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 impacted by paclobutrazol. Then EPA would determine whether the 

use of paclobutrazol overlaps the critical habitat or the occupied range of those listed 

species. 

ANTICIPATED DATA NEEDS

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

40 CFR Part 158 prior to conducting the planned assessments. 

In contrast the Agency notes the absence of available data for terrestrial plants. In light 

of the complete absence of definitive terrestrial plant effects endpoints, Tier 1 terrestrial 

plant toxicity testing (guideline 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 least a 25% effect in one or more plant species which would 

trigger Tier 2 testing to establish more definitive effects endpoints. Therefore, a move 

directly to Tier 2 (guideline 123-1), bypassing Tier 1 testing, would reduce resource 

expenditures and plant tests would supply effects endpoints necessary for quantitative 

assessment of plants risks for those uses (e.g. turf) where paclobutrazol may run off or 

drift to areas with non-target plant cover. The Tier 2 plant testing would be of potentially 

high value for assessing risks to non-target plants for over the top applications of 

paclobutrazol and would have important utility for assessing the potential for indirect 

effects to federally listed threatened and endangered species. 

In addition, preliminary risk estimates for aquatic organisms indicate 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 stage testing would be of 
25

potentially high value in addressing the effects uncertainties that limit the potential 

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

terrestrial vertebrates have lead to risk concerns in terrestrial wildlife for chemical 

analogs, and the uncertainties surrounding avian reproduction endpoint extrapolations for 

paclobutrazol are large and play an important role in uncertainties associated with 

preliminary risk conclusions. Again, avian reproduction testing would be of potentially 

high value in addressing the effects uncertainties that limit the potential confidence of 

assessment chronic risks to birds. Considering the uncertainties surrounding risk 

conclusions associated with the use of extrapolated chronic effects endpoints in fish and 

birds, performance of fish early life stage (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 uncertain effects endpoints than achievable with 

current analog extrapolations. These more definitive endpoints would, in turn, allow for 

a clearer set of risk conclusions for paclobutrazol for these taxonomic groups. 

While the Agency will conduct a search of the open literature to ensure that all best 

available science is utilized, it is anticipated 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 organisms, or birds. Agency uses the ECOTOX database as its 

mechanism for searching the open literature for ecological effects information. 

ECOTOX integrates three previously independent 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. 

ANTICIPATED RISK ASSESSMENT NEEDS

As stated previously, there are no drinking 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 Assessment (“Overview of the Ecological Risk 

Assessment Process in the Office of Pesticides Programs, U.S. Environmental Protection 

Agency”, January 2004) and with the Section 7 of the Endangered Species Act. 

OTHER INFORMATION NEEDS

There is specific information that will assist the Agency in refining 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 zone 
26

e. frequency of application, application intervals, and maximum number of 

applications per season 

f. geographic limitations on use. 

2. use or potential use distribution (e.g., acreage and geographical distribution of 

relevant crops) 

3. use history 

4. median and 90th percentile reported use rates (lbs ai/acre) from usage data – 

national, state, and county 

5. application timing (date of first application 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 data (not derived from state level data) 

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

h. percent crop treated – county 

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

j. total pounds per year – county 

k. the year the pesticide was last used 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 damage 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 ground portions of vegetation 

following tree injection, root zone injection of basal drench, and soil drench uses. 

The analysis plan will be revisited and may be revised depending upon the data available 

in the open literature and the information submitted by the public in response to the 

opening of the Registration Review docket. 

 
27

IV. Human Health Effects Scoping Document

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

OFFICE OF 

PREVENTION, PESTICIDES 

AND TOXIC SUBSTANCES 

MEMORANDUM

DATE: 13 March 2007 

SUBJECT: Paclobutrazol: Registration Review Scoping 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 Reregistration Division (7508P) 

Attached is the human health scoping document to support the registration 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 regulator paclobutrazol to determine the scope of 

work necessary to support registration review. The team looked at the hazard and 

exposure databases for paclobutrazol and attempted to determine whether changes in 

science policy or deficiencies in the databases materially affected the overall risk picture. 

The current supported uses for paclobutrazol include turf, outdoor ornamentals, 

greenhouse ornamentals and bulb soaks. Residential uses include use on turf. 

Paclobutrazol was first registered in 1985; therefore a Reregistration 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 residential uses of 

paclobutrazol have never been assessed. 

The primary sources for the status update were the most recent RfD/Peer Review reports 

(September, 1986; March, 1994) and an OPPIN 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 currently not available 

for the occupational inhalation scenarios. A comprehensive search of the open literature 

was not done primarily because a screening Google search and a Science Direct search 

indicated very little information was available that pertained to unavailable toxicity data 

(inhalation, cancer) for paclobutrazol. 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 available to support registration review. The HED 

Risk Assessment team includes Elissa 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 (2RS,3RS)-1-(4-chlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol1-yl)pentan-3-ol 

CAS name (aR,ßR)-rel-ß-[(4-chlorophenyl)methyl]-a-(1,1-dimethylethyl)-

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

PC Code 125601 

CAS registry 

number 

76738-62-0 

Registration Review 

Case No. 

7002 
29

Chemical Structure 

H3C

C C

OH

H3C H

CH3

H C CH2

CL

N N

N

Section 2. Toxicology 

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

RfD/Peer Review Committee evaluated the existing toxicology data in 1994 (Memo, G. 

Ghali, 6/21/94). The RfD Committee concluded there was no evidence, based on the 

available data, to suggest that paclobutrazol was associated with developmental or 

reproductive effects. Pesticidal 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 toxicity endpoints for the occupational and 

residential scenarios and current policies on selecting 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 adequate for the purpose of registration review. 

A short-term inhalation study is not available to assess occupational and residential risk. 

As such, an oral guideline toxicity 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 are not acceptable since the highest dose was 

insufficient to adequately evaluate carcinogenicity. However, these cancer studies are 

considered adequate for the purposes of registration review. No toxicity studies have 

been received by the Agency since the RfD/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 Departures 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 dietary assessment for paclobutrazol. 
30

Table 2.1 Summary of Toxicological Point of Departures 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 

UFA=10x 

UFH=10x 

Occupational 

LOC for MOE 

= 100 

21-Day Dermal- Rabbit 

Irritation LOAEL = 100 mg/kg/day, 

irritation appeared 2nd week, 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 

UFA=10x 

UFH=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 enlargement, 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 carcinogenicity 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 carcinogenicity 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 mark the beginning of extrapolation to determine risk associated with lower 

environmentally relevant human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed 

adverse effect level. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = 

potential variation in sensitivity among members of the human population (intraspecies). MOE = margin of exposure. 

LOC = level of concern. 

Section 3. Current Dietary Assessments 

In 1994 the RfD Committee considered critical endpoints appropriate 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 assessed. The current turf use necessitates a 

screening level groundwater and surface water analysis. The HED paclobutrazol team 

believes that drinking water risks should be evaluated to ensure the turf use is acceptable 
31

at current use rates. Available developmental studies indicate no appropriate endpoint for 

use in the acute dietary assessment. The 2-generation reproduction rat study, however, 

would provide a chronic endpoint for a screening water analysis. 

Section 4. Aggregate and Cumulative Exposure 

Paclobutrazol has no food registrations and is therefore not subject to FQPA which 

requires the Agency to consider aggregate and cumulative exposures. However, there is 

the potential for dietary exposures from drinking water as a result of its use on turf as 

well as non-occupational (i.e., residential)exposures from this use. These assessments 

should be conducted and the aggregate exposures 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 residential 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 study 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. Occupational assessments will be required during 

registration review for use on turf, outdoor ornamentals, greenhouse ornamentals and 

bulb soak treatments. Based on currently supported uses, short- and intermediate-term 

dermal and inhalation scenarios will be required for registration review. A residential 

assessment will be required for the turf use for short- and intermediate-term dermal and 

inhalation and children’s incidental oral exposures. 

Section 6. Incident Reports 

Based upon a review available data bases (OPP Incident Data System, Poison Control 

Centers, and NIOSH SENSOR) from 1992-2005, there were almost no reports of ill 

effects from exposure to paclobutrazol (M. Hawkins, D335541, 02/27/2007). 

Section 7. Anticipated Data Needs 

HED does not believe additional data are needed for registration review. 

Section 8. Tolerances 

There are no tolerances for paclobutrazol. 

Section 9. Overall Conclusions 
32

HED does not believe that new data are required for registration review. There is 

currently adequate information to support occupational and residential assessments of 

paclobutrazol. A screening level drinking water assessment will be conducted. 

Section 10. Reference Memoranda 

The memoranda listed in Table 9.1 were considered 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 Paclobutrazol 
33

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 

LC50 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. 

LD50 Median Lethal Dose. A statistically derived 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 Identification (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 Data 
34

PHI Preharvest Interval 

ppb Parts Per Billion 

PPE Personal Protective Equipment 

ppm Parts Per Million 

PRZM/EXAMS Tier II Surface Water Computer Model 

Q1* 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 (Registrations Under Section 24©) of FIFRA) 

TGAI Technical Grade Active Ingredient 

USDA United States Department of Agriculture 

UF Uncertainty Factor 

WPS Worker Protection Standard